New Tool for Next-Generation Cancer Treatments using Nanodiamonds
A research team at Northwestern University has demonstrated a tool that can precisely deliver tiny doses of drug-carrying nanomaterials to individual cells.
The tool, called the Nanofountain Probe, functions in two different ways: in one mode, the probe acts like a fountain pen, wherein drug-coated nanodiamonds serve as the ink, allowing researchers to create devices by "writing" with it. The second mode functions as a single-cell syringe, permitting direct injection of biomolecules or chemicals into individual cells.
The research was led by Horacio Espinosa, professor of mechanical engineering, and Dean Ho, assistant professor of mechanical and biomedical engineering, both at the McCormick School of Engineering and Applied Science at Northwestern. Their results were recently published online in the scientific journal Small.
The probe could be used both as a research tool in the development of next-generation cancer treatments and as a nanomanufacturing tool to build the implantable drug delivery devices that will apply these treatments. The potential of nanomaterials to revolutionize drug delivery is emergent in early trials, which show their ability to moderate the release of highly toxic chemotherapy drugs and other therapeutics. This provides a platform for drug-delivery schemes with reduced side effects and improved targeting.
“This is an exciting development that complements our previous demonstrations of direct patterning of DNA, proteins and nanoparticles,” says Espinosa.
Using the Nanofountain Probe, the group injected tiny doses of nanodiamonds into both healthy and cancerous cells. This technique will help cancer researchers investigate the efficacy of new drug-nanomaterial systems as they become available.
The group also used the same Nanofountain Probes to pattern dot arrays of drug-coated nanodiamonds directly on glass substrates. The production of these dot arrays, with dots that can be made smaller than 100 nanometers in diameter, provides the proof of concept by which to manufacture devices that will deliver these nanomaterials within the body.
The work addresses two major challenges in the development and clinical application of nanomaterial-mediated drug-delivery schemes: dosage control and high spatial resolution.
In fundamental research and development, biologists are typically constrained to studying the effects of a drug on an entire cell population because it is difficult to deliver them to a single cell. To address this issue, the team used the Nanofountain Probe to target and inject single cells with a dose of nanodiamonds.
“This allows us to deliver a precise dose to one cell and observe its response relative to its neighbors,” Ho says. “This will allow us to investigate the ultimate efficacy of novel treatment strategies via a spectrum of internalization mechanisms.”
Beyond the broad research focused on developing these drug-delivery schemes, manufacturing devices to execute the delivery will require the ability to precisely place doses of drug-coated nanomaterials. Ho and colleagues previously developed a polymer patch that could be used to deliver chemotherapy drugs locally to sites where cancerous tumors have been removed. This patch is embedded with a layer of drug-coated nanodiamonds, which moderate the release of the drug. The patch is capable of controlled and sustained low levels of release over a period of months, reducing the need for chemotherapy following the removal of a tumor.
“An attractive enhancement will be to use the Nanofountain Probe to replace the continuous drug-nanodiamond films currently used in these devices with patterned arrays composed of multiple drugs,” Ho says. “This allows high-fidelity spatial tuning of dosing in intelligent devices for comprehensive treatment.”
“One of the most significant aspects of this work is the Nanofountain Probe’s ability to deliver nanomaterials coated with a broad range of drugs and other biological agents,” Espinosa says. “The injection technique is currently being explored for delivery of a wide variety of bio-agents, including DNA, viruses and other therapeutically relevant materials.”
Nanodiamonds have also proven effective in seeding the growth of diamond thin films. These diamond films have exciting applications in next-generation nanoelectronics. Here again, the ability to pattern nanodiamonds with sub-100-nanometer resolution provides inroads to realizing these devices on a mass scale. The resolution in nanodiamond patterning demonstrated by the Nanofountain Probe represents an improvement of three orders of magnitude over other reported direct-write schemes of nanodiamond patterning.
The work was supported by the National Science Foundation, the National Institutes of Health, the V Foundation for Cancer Research and the Wallace H. Coulter Foundation.
In addition to Espinosa and Ho, other authors of the paper, entitled “Nanofountain Probe-based High-resolution Patterning and Single-cell Injection of Functionalized Nanodiamonds,” are Owen Loh, Robert Lam, Mark Chen, Nicolaie Moldovan and Houjin Huang of Northwestern University.
>http://www.nanotechwire.com/news.asp?nid=7939
Monday, June 15, 2009
Drug Delivery
NanoVentures Australia
Unveils Novel Pulmonary Drug Delivery Technology
NVA’s predecessor, Nanotechnology Victoria Ltd (”NanoVic”) invested nearly $500,000 with Monash University’s Micro NanoPhysics Research Laboratory to develop and demonstrate a novel mechanism for generation of liquid aerosol drugs. The proprietary SAW (Surface Acoustic Wave) generated mechanism allows fluids to be atomised as precisely controlled droplets, making them ideal for a new generation of inhaler devices. These inhalers are likely to be very low cost, as they require very few moving parts.
Further, the SAW technology means that drugs like insulin can be delivered in fluid droplet form from an inhaler. Previous attempts to deliver insulin from an inhaler have used dry powders, which are more difficult to control, and may cause new issues for certain groups of patients.
Last month, NVA and Monash University filed for the protection of new intellectual property around their proprietary pulmonary drug delivery device. The parties hold the Australian provisional patent application 2009902063 Microfluidics apparatus for the atomisation of a liquid. In particular the team has demonstrated in vitro results with maintenance of insulin structure and function after aerosolisation, and over 70% delivery to the lungs using the test protein insulin.
There has been growing interest in the potential for the systematic delivery of drugs and therapeutic agents (e.g. peptides and proteins) via inhalation. Pulmonary drug delivery is an attractive option compared to oral administration or other invasive delivery techniques, and is particularly suited to a number of frequent-application drugs. The surface acoustic atomisation technology developed by Monash University provides for the controlled generation of aerosol particles, and is ideal for drug delivery to the deep regions of the lungs.
NVA has exclusive rights to the exploitation of the technology for potential applications in the administration of insulin and erythropoietin, as well as for the treatment of Cystic Fibrosis and Multiple Sclerosis.
The delivery device R&D program, led by Associate Professor James Friend at the Monash University Micro NanoPhysics Research Laboratory, commenced in January 2007 and is due for completion in October 2009. Dr Friend is internationally known for his leadership in the application of nanotechnology to medical devices.
NVA commercialises nanotechnologies developed by Nanotechnology Victoria Ltd (”NanoVic”), the Victorian Government funded nanotechnology accelerator which operated from 2002 to 2009. NVA has a portfolio of other technologies being positioned for commercial development, in medical therapeutics, diagnostics, advanced materials and water analysis and purification. NVA commercialises nanotechnologies developed by Nanotechnology Victoria Ltd (”NanoVic”), the Victorian Government funded nanotechnology accelerator which operated from 2002 to 2009.
>http://www.nanotechwire.com/news.asp?nid=8000
Unveils Novel Pulmonary Drug Delivery Technology
NVA’s predecessor, Nanotechnology Victoria Ltd (”NanoVic”) invested nearly $500,000 with Monash University’s Micro NanoPhysics Research Laboratory to develop and demonstrate a novel mechanism for generation of liquid aerosol drugs. The proprietary SAW (Surface Acoustic Wave) generated mechanism allows fluids to be atomised as precisely controlled droplets, making them ideal for a new generation of inhaler devices. These inhalers are likely to be very low cost, as they require very few moving parts.
Further, the SAW technology means that drugs like insulin can be delivered in fluid droplet form from an inhaler. Previous attempts to deliver insulin from an inhaler have used dry powders, which are more difficult to control, and may cause new issues for certain groups of patients.
Last month, NVA and Monash University filed for the protection of new intellectual property around their proprietary pulmonary drug delivery device. The parties hold the Australian provisional patent application 2009902063 Microfluidics apparatus for the atomisation of a liquid. In particular the team has demonstrated in vitro results with maintenance of insulin structure and function after aerosolisation, and over 70% delivery to the lungs using the test protein insulin.
There has been growing interest in the potential for the systematic delivery of drugs and therapeutic agents (e.g. peptides and proteins) via inhalation. Pulmonary drug delivery is an attractive option compared to oral administration or other invasive delivery techniques, and is particularly suited to a number of frequent-application drugs. The surface acoustic atomisation technology developed by Monash University provides for the controlled generation of aerosol particles, and is ideal for drug delivery to the deep regions of the lungs.
NVA has exclusive rights to the exploitation of the technology for potential applications in the administration of insulin and erythropoietin, as well as for the treatment of Cystic Fibrosis and Multiple Sclerosis.
The delivery device R&D program, led by Associate Professor James Friend at the Monash University Micro NanoPhysics Research Laboratory, commenced in January 2007 and is due for completion in October 2009. Dr Friend is internationally known for his leadership in the application of nanotechnology to medical devices.
NVA commercialises nanotechnologies developed by Nanotechnology Victoria Ltd (”NanoVic”), the Victorian Government funded nanotechnology accelerator which operated from 2002 to 2009. NVA has a portfolio of other technologies being positioned for commercial development, in medical therapeutics, diagnostics, advanced materials and water analysis and purification. NVA commercialises nanotechnologies developed by Nanotechnology Victoria Ltd (”NanoVic”), the Victorian Government funded nanotechnology accelerator which operated from 2002 to 2009.
>http://www.nanotechwire.com/news.asp?nid=8000
Nanotechnology
UB Scientists Develop Novel Nanotechnology
Method to Stimulate Growth of New Neurons in Adult Brain
University at Buffalo researchers have identified a new mechanism that plays a central role in adult brain stem cell development and prompts brain stem cells to differentiate into neurons.
Their discovery, known as Integrative FGFR1 Signaling (INFS), has fundamentally challenged the prevailing ideas of how signals are processed in cells during neuronal development.
The INFS mechanism is considered capable of repopulating degenerated brain areas, raising possibilities for new treatments for Parkinson’s disease, Alzheimer’s disease and other neurodegenerative disorders, and may be a promising anti-cancer therapy.
Michal Stachowiak, Ph.D., director of the Molecular and Structural Neurobiology and Gene Therapy Program at UB, lead the research team that discovered INFS.
Results of the research appear in a recent issue of Integrative Biology at http://xlink.rsc.org/?doi=B902617G.
The approach uses gene engineering and nanoparticles for gene delivery to activate the INFS mechanism directly and promote neuronal development. The INFS-targeting gene can prompt these stem cells to differentiate into neurons.
Stachowiak, UB associate professor of pathology and anatomical sciences in the UB School of Medicine and Biomedical Sciences, said the research team set out to see if it is possible to generate a wave of new neurons from stem cells and direct them to the affected areas using a mouse model.
“In this way, targeting the INFS potentially could be used to cure certain brain diseases, particularly in the case of a stroke or injuries that happen as a single episode and are not continuously attacking the brain,” he said.
“This study provides proof of concept for a novel approach to the treatment of neuronal loss by means of therapeutic gene transfer. This is a particularly attractive alternative to viral-mediated gene transfer.
“The health risks associated with using viruses to carry genes in this type of gene transfer have led to the search for safer means of gene delivery,” noted Stachowiak. “Nanotechnology offers an unprecedented advantage in enhancing the efficacy of non-viral gene delivery.”
Stachowiak and his wife, Ewa K. Stachowiak, Ph.D., research assistant professor of pathology and anatomical sciences, along with their postdoctoral fellows and graduate students, have spent more than 15 years studying the mechanisms controlling natural neurogenesis, the creation of new neurons.
Brain injuries, stroke and progressive chronic diseases such as Parkinson’s or Alzheimer’s disease result in an extensive loss of neurons, accompanied by functional deterioration in the affected brain tissue. Such neurodegenerative diseases are a major health concern, given the rising aging population worldwide.
In addition, neurodevelopmental disorders, such as autism and schizophrenia, diminish the production of neurons and disrupt the brain’s cellular structure.
“Manipulation of pre-existing adult stem cells to repopulate diseased areas of the brain holds the key towards the treatment of these neurodegenerative and, possibly, neurodevelopmental disorders,” said Michal Stachowiak.
“However, after birth, the ability of the brain’s stem cells to form the necessary new neurons normally is greatly diminished, and the mechanisms controlling natural neurogenesis are not well understood.”
The neurogenic potential of targeting INFS was described initially in cultured stem cells in vitro by the Stachowiak team. Following these initial studies, together with a team of UB chemists that included Indrajit Roy, Ph.D., Dhruba Bharali, Ph.D., and Paras N. Prasad, Ph.D., Stachowiak’s group investigated the use of organically modified silica nanoparticles as gene delivery vehicles into the stem cells of the brain in vivo.
Prasad is executive director of the UB Institute for Lasers, Photonics and Biophotonics and SUNY Distinguished Professor in the departments of Chemistry, Physics, Electrical Engineering and Medicine. Roy is an assistant research professor in the institute; Bharali was a research associate.
Injae Shin, Ph.D., an expert in genetics at Yonsei University, Seoul, Korea, in an online article on the Chemical Biology Web site, called the work “exciting.” He noted that it has the potential to treat neurological diseases, but pointed out the need for further development of gene delivery methods for the treatment of neuronal loss.
Stachowiak and colleagues currently are working on such approaches.
“Targeting the INFS mechanisms by small molecules could potentially replace the need for gene transfers and create a classical drug therapy for the neuronal loss,” said Ewa Stachowiak. “Now that we know the mechanism, we can search effectively for the means to control it.”
>http://www.nanotechwire.com/news.asp?nid=7956
Method to Stimulate Growth of New Neurons in Adult Brain
University at Buffalo researchers have identified a new mechanism that plays a central role in adult brain stem cell development and prompts brain stem cells to differentiate into neurons.
Their discovery, known as Integrative FGFR1 Signaling (INFS), has fundamentally challenged the prevailing ideas of how signals are processed in cells during neuronal development.
The INFS mechanism is considered capable of repopulating degenerated brain areas, raising possibilities for new treatments for Parkinson’s disease, Alzheimer’s disease and other neurodegenerative disorders, and may be a promising anti-cancer therapy.
Michal Stachowiak, Ph.D., director of the Molecular and Structural Neurobiology and Gene Therapy Program at UB, lead the research team that discovered INFS.
Results of the research appear in a recent issue of Integrative Biology at http://xlink.rsc.org/?doi=B902617G.
The approach uses gene engineering and nanoparticles for gene delivery to activate the INFS mechanism directly and promote neuronal development. The INFS-targeting gene can prompt these stem cells to differentiate into neurons.
Stachowiak, UB associate professor of pathology and anatomical sciences in the UB School of Medicine and Biomedical Sciences, said the research team set out to see if it is possible to generate a wave of new neurons from stem cells and direct them to the affected areas using a mouse model.
“In this way, targeting the INFS potentially could be used to cure certain brain diseases, particularly in the case of a stroke or injuries that happen as a single episode and are not continuously attacking the brain,” he said.
“This study provides proof of concept for a novel approach to the treatment of neuronal loss by means of therapeutic gene transfer. This is a particularly attractive alternative to viral-mediated gene transfer.
“The health risks associated with using viruses to carry genes in this type of gene transfer have led to the search for safer means of gene delivery,” noted Stachowiak. “Nanotechnology offers an unprecedented advantage in enhancing the efficacy of non-viral gene delivery.”
Stachowiak and his wife, Ewa K. Stachowiak, Ph.D., research assistant professor of pathology and anatomical sciences, along with their postdoctoral fellows and graduate students, have spent more than 15 years studying the mechanisms controlling natural neurogenesis, the creation of new neurons.
Brain injuries, stroke and progressive chronic diseases such as Parkinson’s or Alzheimer’s disease result in an extensive loss of neurons, accompanied by functional deterioration in the affected brain tissue. Such neurodegenerative diseases are a major health concern, given the rising aging population worldwide.
In addition, neurodevelopmental disorders, such as autism and schizophrenia, diminish the production of neurons and disrupt the brain’s cellular structure.
“Manipulation of pre-existing adult stem cells to repopulate diseased areas of the brain holds the key towards the treatment of these neurodegenerative and, possibly, neurodevelopmental disorders,” said Michal Stachowiak.
“However, after birth, the ability of the brain’s stem cells to form the necessary new neurons normally is greatly diminished, and the mechanisms controlling natural neurogenesis are not well understood.”
The neurogenic potential of targeting INFS was described initially in cultured stem cells in vitro by the Stachowiak team. Following these initial studies, together with a team of UB chemists that included Indrajit Roy, Ph.D., Dhruba Bharali, Ph.D., and Paras N. Prasad, Ph.D., Stachowiak’s group investigated the use of organically modified silica nanoparticles as gene delivery vehicles into the stem cells of the brain in vivo.
Prasad is executive director of the UB Institute for Lasers, Photonics and Biophotonics and SUNY Distinguished Professor in the departments of Chemistry, Physics, Electrical Engineering and Medicine. Roy is an assistant research professor in the institute; Bharali was a research associate.
Injae Shin, Ph.D., an expert in genetics at Yonsei University, Seoul, Korea, in an online article on the Chemical Biology Web site, called the work “exciting.” He noted that it has the potential to treat neurological diseases, but pointed out the need for further development of gene delivery methods for the treatment of neuronal loss.
Stachowiak and colleagues currently are working on such approaches.
“Targeting the INFS mechanisms by small molecules could potentially replace the need for gene transfers and create a classical drug therapy for the neuronal loss,” said Ewa Stachowiak. “Now that we know the mechanism, we can search effectively for the means to control it.”
>http://www.nanotechwire.com/news.asp?nid=7956
Capsules encapsulated
Drug Deliver With Nanotechnology:
Capsules Encapsulated
When cells cannot carry out the tasks required of them by our bodies, the result is disease. Nanobiotechnology researchers are looking for ways to allow synthetic systems take over simple cellular activities when they are absent from the cell. This requires transport systems that can encapsulate medications and other substances and release them in a controlled fashion at the right moment.
The transporter must be able to interact with the surroundings in order to receive the signal to unload its cargo. A team led by Frank Caruso at the University of Melbourne has now developed a microcontainer that can hold thousands of individual "carrier units"—a "capsosome". These are polymer capsules in which liposomes have been embedded to form subcompartments.
Currently, the primary type of nanotransporter used for drugs is the capsule: Polymer capsules form stable containers that are semipermeable, which allows for communication with the surrounding medium. However, these are not suitable for the transport of small molecules because they can escape. Liposomes are good at protecting small drug molecules; however, they are often unstable and impermeable to substances from the environment. The Australian researchers have now combined the advantages of both systems in their capsosomes.
Capsosomes are produced by several steps. First, a layer of polymer is deposited onto small silica spheres. This polymer contains building blocks modified with cholesterol. Liposomes that have been loaded with an enzyme can be securely anchored to the cholesterol units and thus attached to the polymer film. Subsequently, more polymer layers are added and then cross-linked by disulfide bridges into a gel by means of a specially developed, very gentle cross-linking reaction. In the final step, the silica core is etched away without damaging the sensitive cargo.
Experiments with an enzyme as model cargo demonstrated that the liposomes remain intact and the cargo does not escape. Addition of a detergent releases the enzyme in a functional state. By means of the enzymatic reaction, which causes a color change of the solution, it was possible to determine the number of liposome compartments to be about 8000 per polymer capsule.
"Because the capsosomes are biodegradable and nontoxic", says Brigitte Staedler, a senior researcher in the group, "they would also be suitable for use as resorbable synthetic cell organelles and for the transport of drugs." In addition, the scientists are planning to encapsulate liposomes filled with different enzymes together and to equip them with specific "receivers" which would allow the individual cargo to be released in a targeted fashion. This would make it possible to use enzymatic reaction cascades for catalytic reaction processes.
Frank Caruso. A Microreactor with Thousands of Subcompartments: Enzyme-Loaded Liposomes within Polymer Capsules. Angewandte Chemie International
Edition, 2009, 48, No. 24, 4359-4362 DOI: 10.1002/anie.200900386
>http://www.nanotechwire.com/news.asp?nid=7944
Capsules Encapsulated
When cells cannot carry out the tasks required of them by our bodies, the result is disease. Nanobiotechnology researchers are looking for ways to allow synthetic systems take over simple cellular activities when they are absent from the cell. This requires transport systems that can encapsulate medications and other substances and release them in a controlled fashion at the right moment.
The transporter must be able to interact with the surroundings in order to receive the signal to unload its cargo. A team led by Frank Caruso at the University of Melbourne has now developed a microcontainer that can hold thousands of individual "carrier units"—a "capsosome". These are polymer capsules in which liposomes have been embedded to form subcompartments.
Currently, the primary type of nanotransporter used for drugs is the capsule: Polymer capsules form stable containers that are semipermeable, which allows for communication with the surrounding medium. However, these are not suitable for the transport of small molecules because they can escape. Liposomes are good at protecting small drug molecules; however, they are often unstable and impermeable to substances from the environment. The Australian researchers have now combined the advantages of both systems in their capsosomes.
Capsosomes are produced by several steps. First, a layer of polymer is deposited onto small silica spheres. This polymer contains building blocks modified with cholesterol. Liposomes that have been loaded with an enzyme can be securely anchored to the cholesterol units and thus attached to the polymer film. Subsequently, more polymer layers are added and then cross-linked by disulfide bridges into a gel by means of a specially developed, very gentle cross-linking reaction. In the final step, the silica core is etched away without damaging the sensitive cargo.
Experiments with an enzyme as model cargo demonstrated that the liposomes remain intact and the cargo does not escape. Addition of a detergent releases the enzyme in a functional state. By means of the enzymatic reaction, which causes a color change of the solution, it was possible to determine the number of liposome compartments to be about 8000 per polymer capsule.
"Because the capsosomes are biodegradable and nontoxic", says Brigitte Staedler, a senior researcher in the group, "they would also be suitable for use as resorbable synthetic cell organelles and for the transport of drugs." In addition, the scientists are planning to encapsulate liposomes filled with different enzymes together and to equip them with specific "receivers" which would allow the individual cargo to be released in a targeted fashion. This would make it possible to use enzymatic reaction cascades for catalytic reaction processes.
Frank Caruso. A Microreactor with Thousands of Subcompartments: Enzyme-Loaded Liposomes within Polymer Capsules. Angewandte Chemie International
Edition, 2009, 48, No. 24, 4359-4362 DOI: 10.1002/anie.200900386
>http://www.nanotechwire.com/news.asp?nid=7944
Dead or alive
Nanotechnology technique tells the difference
(Nanowerk Spotlight)
A major concern in microbiology is to determine whether a bacterium is dead or alive. This crucial question has major consequences in food industry, water supply or health care. While culture-based tests can determine whether bacteria can proliferate and form colonies, these tests are time-consuming and work poorly with certain slow-growing or non-culturable bacteria. They are not suitable for applications where real-time results are needed, e.g. in industrial manufacturing or food processing. A team of scientists in France has now discovered that living and dead cells can be discriminated with a nanotechnology technique on the basis of their cell wall nanomechanical properties. This finding is totally new and has been made possible thanks to an interdisciplinary approach which mixes physics, biology and chemistry. This work is a key stone in the understanding of bacterial cell wall behavior. "We have developed a method to probe the mechanical properties of living and dead bacteria via atomic force microscope (AFM) indentation experimentations," Aline Cerf tells Nanowerk. ". Indeed, we provide a new way to probe bacterial cell viability based on cell wall nanomechanical properties, independently from cell ability to grow on a medium or to be penetrated by a fluorescent dye." Cerf, a PhD student in the NanoBioSystems group at LAAS-CNRS, is first author of a recent paper in Langmuir ("Nanomechanical Properties of Dead or Alive Single-Patterned Bacteria") where she and collaborators from LAAS-CNRS describe their findings. "We wanted to explore the modifications that could occur in the nanomechanical properties of a single E. coli bacterium, while it is alive and while it is dead," says Etienne Dague, a researcher in the NanoBioSystems group. "To reach this goal, it has been of first importance to immobilize the living bacteria in an aqueous environment to avoid any cell wall modifications due to a drying step." Thus, in developing a technique to probe the mechanical properties of bacteria via AFM indentation experiments, the French team also came up with an immobilization method for bacteria that doesn't require a chemical fixation.
The researchers set up a fast and simple procedure – based on a conventional microcontact printing and a simple incubation technique to generate functionalized patterns so as to induce local bacteria deposition – that allowed them to produce reliable chemical patterns exhibiting different surface properties to induce selective adsorption of individual bacteria in liquid media at registered positions. "We have evidenced a selective adsorption of bacteria on these local chemical patterns, producing highly ordered arrays of single living bacteria with a success rate close to 100%," says Cerf. The team then used this controlled immobilization method to study the mechanical properties of dead or alive bacterial cell in aqueous environment. Using force spectroscopy before and after heating , they measured the Young moduli of the same cell. The cells with a damaged membrane (after heating) present a Young modulus twice as high (6.1 ? 1.5 MPa versus 3.0 ? 0.6 MPa) as that of healthy bacteria. At the same time it has been impossible to evidence a difference between the AFM images of the living and the dead cell. "We have shown that we are capable of engineering large areas with patterns of single bacteria and this will be of major interest for future applications," says Dague. "Indeed, thanks to a periodic arrangement of cells, the process consisting in measuring the nanomechanical properties of cells could possibly be automated and a tool to count live or dead bacteria could be designed."
The researchers set up a fast and simple procedure – based on a conventional microcontact printing and a simple incubation technique to generate functionalized patterns so as to induce local bacteria deposition – that allowed them to produce reliable chemical patterns exhibiting different surface properties to induce selective adsorption of individual bacteria in liquid media at registered positions. "We have evidenced a selective adsorption of bacteria on these local chemical patterns, producing highly ordered arrays of single living bacteria with a success rate close to 100%," says Cerf. The team then used this controlled immobilization method to study the mechanical properties of dead or alive bacterial cell in aqueous environment. Using force spectroscopy before and after heating , they measured the Young moduli of the same cell. The cells with a damaged membrane (after heating) present a Young modulus twice as high (6.1 ? 1.5 MPa versus 3.0 ? 0.6 MPa) as that of healthy bacteria. At the same time it has been impossible to evidence a difference between the AFM images of the living and the dead cell. "We have shown that we are capable of engineering large areas with patterns of single bacteria and this will be of major interest for future applications," says Dague. "Indeed, thanks to a periodic arrangement of cells, the process consisting in measuring the nanomechanical properties of cells could possibly be automated and a tool to count live or dead bacteria could be designed."
By Michael Berger. Copyright 2009 Nanowerk LLC >http://www.nanowerk.com/spotlight/spotid=10816.php
Virus Battery
MIT researchers make virus battery
WASHINGTON, April 2 (Xinhua)
For the first time, MIT researchers have shown they can genetically engineer viruses to build both the positively and negatively charged ends of a lithium-ion battery, according to a study released on Thursday in the online edition of journal Science.
The new virus-produced batteries have the same energy capacity and power performance as state-of-the-art rechargeable batteries being considered to power plug-in hybrid cars, and they could also be used to power a range of personal electronic devices, said Angela Belcher, the MIT materials scientist who led the research team.
The new batteries could be manufactured with a cheap and environmentally benign process: The synthesis takes place at and below room temperature and requires no harmful organic solvents, and the materials that go into the battery are non-toxic.
In a traditional lithium-ion battery, lithium ions flow between a negatively charged anode, usually graphite, and the positively charged cathode, usually cobalt oxide or lithium iron phosphate. Three years ago, an MIT team led by Belcher reported that it had engineered viruses that could build an anode by coating themselves with cobalt oxide and gold and self-assembling to form a nanowire.
In the latest work, the team focused on building a highly powerful cathode to pair up with the anode, said Belcher, the Germeshausen Professor of Materials Science and Engineering and Biological Engineering in MIT. Cathodes are more difficult to build than anodes because they must be highly conducting to be a fast electrode. However, most candidate materials for cathodes are highly insulating (non-conductive).
To achieve that, the researchers, including MIT Professor Gerbrand Ceder of materials science and Associate Professor Michael Strano of chemical engineering, genetically engineered viruses that first coat themselves with iron phosphate, then grab hold of carbon nanotubes to create a network of highly conductive material.
Because the viruses recognize and bind specifically to certain materials (carbon nanotubes in this case), each iron phosphate nanowire can be electrically "wired" to conducting carbon nanotubenetworks. Electrons can travel along the carbon nanotube networks, percolating throughout the electrodes to the iron phosphate and transferring energy in a very short time.
The viruses are a common bacteriophage, which infect bacteria but are harmless to humans.
The team found that incorporating carbon nanotubes increases the cathode's conductivity without adding too much weight to the battery. In lab tests, batteries with the new cathode material could be charged and discharged at least 100 times without losing any capacitance. That is fewer charge cycles than currently available lithium-ion batteries, but "we expect them to be able to go much longer," Belcher said.
The prototype is packaged as a typical coin cell battery, but the technology allows for the assembly of very lightweight, flexible and conformable batteries that can take the shape of their container.
Last week, MIT President Susan Hockfield took the prototype battery to a press briefing at the White House where she and U.S. President Barack Obama spoke about the need for federal funding to advance new clean-energy technologies.
Now that the researchers have demonstrated they can wire virus batteries at the nanoscale, they intend to pursue even better batteries using materials with higher voltage and capacitance, such as manganese phosphate and nickel phosphate, said Belcher. Once that next generation is ready, the technology could go into commercial production, she said.
source: > www.chinaview.cn
Editor: Mu Xuequan
WASHINGTON, April 2 (Xinhua)
For the first time, MIT researchers have shown they can genetically engineer viruses to build both the positively and negatively charged ends of a lithium-ion battery, according to a study released on Thursday in the online edition of journal Science.
The new virus-produced batteries have the same energy capacity and power performance as state-of-the-art rechargeable batteries being considered to power plug-in hybrid cars, and they could also be used to power a range of personal electronic devices, said Angela Belcher, the MIT materials scientist who led the research team.
The new batteries could be manufactured with a cheap and environmentally benign process: The synthesis takes place at and below room temperature and requires no harmful organic solvents, and the materials that go into the battery are non-toxic.
In a traditional lithium-ion battery, lithium ions flow between a negatively charged anode, usually graphite, and the positively charged cathode, usually cobalt oxide or lithium iron phosphate. Three years ago, an MIT team led by Belcher reported that it had engineered viruses that could build an anode by coating themselves with cobalt oxide and gold and self-assembling to form a nanowire.
In the latest work, the team focused on building a highly powerful cathode to pair up with the anode, said Belcher, the Germeshausen Professor of Materials Science and Engineering and Biological Engineering in MIT. Cathodes are more difficult to build than anodes because they must be highly conducting to be a fast electrode. However, most candidate materials for cathodes are highly insulating (non-conductive).
To achieve that, the researchers, including MIT Professor Gerbrand Ceder of materials science and Associate Professor Michael Strano of chemical engineering, genetically engineered viruses that first coat themselves with iron phosphate, then grab hold of carbon nanotubes to create a network of highly conductive material.
Because the viruses recognize and bind specifically to certain materials (carbon nanotubes in this case), each iron phosphate nanowire can be electrically "wired" to conducting carbon nanotubenetworks. Electrons can travel along the carbon nanotube networks, percolating throughout the electrodes to the iron phosphate and transferring energy in a very short time.
The viruses are a common bacteriophage, which infect bacteria but are harmless to humans.
The team found that incorporating carbon nanotubes increases the cathode's conductivity without adding too much weight to the battery. In lab tests, batteries with the new cathode material could be charged and discharged at least 100 times without losing any capacitance. That is fewer charge cycles than currently available lithium-ion batteries, but "we expect them to be able to go much longer," Belcher said.
The prototype is packaged as a typical coin cell battery, but the technology allows for the assembly of very lightweight, flexible and conformable batteries that can take the shape of their container.
Last week, MIT President Susan Hockfield took the prototype battery to a press briefing at the White House where she and U.S. President Barack Obama spoke about the need for federal funding to advance new clean-energy technologies.
Now that the researchers have demonstrated they can wire virus batteries at the nanoscale, they intend to pursue even better batteries using materials with higher voltage and capacitance, such as manganese phosphate and nickel phosphate, said Belcher. Once that next generation is ready, the technology could go into commercial production, she said.
source: > www.chinaview.cn
Editor: Mu Xuequan
Thursday, June 11, 2009
Breath analyzer
Nanotechnology breath analyzer for kidney failure
(Nanowerk Spotlight)
High blood pressure and diabetes, increasingly common signs of the unhealthy lifestyle in most Western societies, often are the cause for chronic kidney disease (or chronic renal disease; CKD). CKD is a long-standing, progressive deterioration of renal function. In its end-stage, the disease is a debilitating medical condition of chronic kidney failure which requires intensive and costly treatments through dialysis or even transplantation. Initially, as renal tissue loses function, there are few abnormalities because the remaining tissue increases its performance. Diagnosis of CKD is mostly based on laboratory testing of renal function such as plasma levels of creatinine and urea, sometimes followed by renal biopsy. Imaging techniques are also applied to detect changes in size, texture, and position of the kidneys. These measurements are performed using ultrasound and are suitable only in patients suffering from progressive renal failure. Presently, renal biopsy remains the most definitive test to specifically diagnose chronic and acute renal failure. This method is invasive and thus comprises the risk of infections and bleeding among other possible complications. "So far, blood tests and urinalysis are the golden standard to identify a decline in kidney filtration, wherein high levels of creatinine and blood urea nitrogen usually reflect renal dysfunction – however, these tests tend to be highly inaccurate and may remain within the normal range even while 65-75% of kidney function is lost." Hossam Haick, senior lecturer in the Faculty of Chemical Engineering and the Russell Berrie Nanotechnology Institute at Technion-Israel Institute of Technology, tells Nanowerk. "Given the difficulties in separating healthy renal function from dysfunction, it is perhaps not too surprising that precise biochemical or clinical criteria for diagnosis of acute renal failure have been elusive. Therefore, there is an unmet need for a noninvasive method for detection of renal failure of various etiologies. Furthermore, the challenge remains to diagnose renal disorders with sufficient sensitivity and specificity to provide a large-scale screening technique, feasible for clinical practice, for people at increased risk of developing renal dysfunction." Haick, Zaid Abassi and coworkers from Technion used an experimental model of end stage renal disease (ESRD) in rats to identify by advanced, yet simple nanotechnology-based approach to discriminate between exhaled breath of healthy states and of ESRD states. The team reported their findings in the April 27, 2009 online edition of ACS Nano ("Sniffing Chronic Renal Failure in Rat Model by an Array of Random Networks of Single-Walled Carbon Nanotubes"). In their work, Haick and his team used gas chromatography/ mass spectroscopy in conjugation with solid phase microextraction of healthy and ESRD breath, collected directly from the trachea of the rats, to identify 15 common volatile organic compounds (VOCs) in all samples of healthy and ESRD states and 27 VOCs that appear in diseased rats but not in healthy states.
Online breath analysis via an array of chemiresistive random network of single walled carbon nanotubes (SWCNTs) coated with organic materials showed excellent discrimination between the various breath states. Furthermore, the analysis shows the adequacy of using representative simulated VOCs to imitate the breath of healthy and ESRD states and, therefore, to train the sensors’ array the pertinent breath signatures. "Using SWCNT networks circumvents the requirement of position and structural control (as is the case in devices based on individual SWCNT) because the devices display the averaged usual properties of many randomly distributed SWCNTs," says Haick. "An additional feature of SWCNT networks is that they can be processed into devices of arbitrary size using conventional microfabrication technology." An important implication of these findings, besides the detection of diseases directly related to the respiratory, cardiovascular, and renal systems, is the fact that VOCs are mainly blood borne and the concentration of biologically relevant substances in exhaled breath closely reflects that in the arterial system. Therefore, breath is predestined for monitoring different processes in the body.
Apart from the odor impression of chronic kidney failure, much about the biochemical processes and the formation of marker substances is already known. Haick notes that analysis of the various breath samples by an array of chemiresistive random network of SWCNTs showed excellent discrimination between the various breath states, while revealing significantly enhanced discriminations at lower humidity levels in the breath. "Furthermore, we show that it is enough to use selected number of simulated VOCs to 'train' the sensors’ array system to discriminate between the electronic patterns of healthy states and chronic failure states," says Haick. "Experiments to distinguish less severe kidney failure (e.g., 35-70% reduction in kidney function) and to distinguish chronic kidney failure from other disease (or patho-physiological) states that have a potential to produce a distorted profile of breath VOCs (e.g., liver failure, systemic infection, pneumonia, heart failure, etc.) are underway and will be published soon." The excellent discrimination between the various breath states obtained in this study provides expectations for future capabilities for diagnosis, detection, and screening various stages of kidney disease, especially in the early stages of the disease, where it is possible to control blood pressure, fat, glucose and protein intake to slow the progression. In terms of the devices, the challenges could be summarized in how to bring the sensing technology to a level that it will be very simple to use, lightweight, low-power, and able to detect diseases in noninvasive way (i.e., via breath samples) in real time.
By Michael Berger.
Nanowerk LLC
(Nanowerk Spotlight)
High blood pressure and diabetes, increasingly common signs of the unhealthy lifestyle in most Western societies, often are the cause for chronic kidney disease (or chronic renal disease; CKD). CKD is a long-standing, progressive deterioration of renal function. In its end-stage, the disease is a debilitating medical condition of chronic kidney failure which requires intensive and costly treatments through dialysis or even transplantation. Initially, as renal tissue loses function, there are few abnormalities because the remaining tissue increases its performance. Diagnosis of CKD is mostly based on laboratory testing of renal function such as plasma levels of creatinine and urea, sometimes followed by renal biopsy. Imaging techniques are also applied to detect changes in size, texture, and position of the kidneys. These measurements are performed using ultrasound and are suitable only in patients suffering from progressive renal failure. Presently, renal biopsy remains the most definitive test to specifically diagnose chronic and acute renal failure. This method is invasive and thus comprises the risk of infections and bleeding among other possible complications. "So far, blood tests and urinalysis are the golden standard to identify a decline in kidney filtration, wherein high levels of creatinine and blood urea nitrogen usually reflect renal dysfunction – however, these tests tend to be highly inaccurate and may remain within the normal range even while 65-75% of kidney function is lost." Hossam Haick, senior lecturer in the Faculty of Chemical Engineering and the Russell Berrie Nanotechnology Institute at Technion-Israel Institute of Technology, tells Nanowerk. "Given the difficulties in separating healthy renal function from dysfunction, it is perhaps not too surprising that precise biochemical or clinical criteria for diagnosis of acute renal failure have been elusive. Therefore, there is an unmet need for a noninvasive method for detection of renal failure of various etiologies. Furthermore, the challenge remains to diagnose renal disorders with sufficient sensitivity and specificity to provide a large-scale screening technique, feasible for clinical practice, for people at increased risk of developing renal dysfunction." Haick, Zaid Abassi and coworkers from Technion used an experimental model of end stage renal disease (ESRD) in rats to identify by advanced, yet simple nanotechnology-based approach to discriminate between exhaled breath of healthy states and of ESRD states. The team reported their findings in the April 27, 2009 online edition of ACS Nano ("Sniffing Chronic Renal Failure in Rat Model by an Array of Random Networks of Single-Walled Carbon Nanotubes"). In their work, Haick and his team used gas chromatography/ mass spectroscopy in conjugation with solid phase microextraction of healthy and ESRD breath, collected directly from the trachea of the rats, to identify 15 common volatile organic compounds (VOCs) in all samples of healthy and ESRD states and 27 VOCs that appear in diseased rats but not in healthy states.
Online breath analysis via an array of chemiresistive random network of single walled carbon nanotubes (SWCNTs) coated with organic materials showed excellent discrimination between the various breath states. Furthermore, the analysis shows the adequacy of using representative simulated VOCs to imitate the breath of healthy and ESRD states and, therefore, to train the sensors’ array the pertinent breath signatures. "Using SWCNT networks circumvents the requirement of position and structural control (as is the case in devices based on individual SWCNT) because the devices display the averaged usual properties of many randomly distributed SWCNTs," says Haick. "An additional feature of SWCNT networks is that they can be processed into devices of arbitrary size using conventional microfabrication technology." An important implication of these findings, besides the detection of diseases directly related to the respiratory, cardiovascular, and renal systems, is the fact that VOCs are mainly blood borne and the concentration of biologically relevant substances in exhaled breath closely reflects that in the arterial system. Therefore, breath is predestined for monitoring different processes in the body.
Apart from the odor impression of chronic kidney failure, much about the biochemical processes and the formation of marker substances is already known. Haick notes that analysis of the various breath samples by an array of chemiresistive random network of SWCNTs showed excellent discrimination between the various breath states, while revealing significantly enhanced discriminations at lower humidity levels in the breath. "Furthermore, we show that it is enough to use selected number of simulated VOCs to 'train' the sensors’ array system to discriminate between the electronic patterns of healthy states and chronic failure states," says Haick. "Experiments to distinguish less severe kidney failure (e.g., 35-70% reduction in kidney function) and to distinguish chronic kidney failure from other disease (or patho-physiological) states that have a potential to produce a distorted profile of breath VOCs (e.g., liver failure, systemic infection, pneumonia, heart failure, etc.) are underway and will be published soon." The excellent discrimination between the various breath states obtained in this study provides expectations for future capabilities for diagnosis, detection, and screening various stages of kidney disease, especially in the early stages of the disease, where it is possible to control blood pressure, fat, glucose and protein intake to slow the progression. In terms of the devices, the challenges could be summarized in how to bring the sensing technology to a level that it will be very simple to use, lightweight, low-power, and able to detect diseases in noninvasive way (i.e., via breath samples) in real time.
By Michael Berger.
Nanowerk LLC
Biosensing
Nanoparticle Libraries for Biosensing Over the past couple of years, researchers have developed a number of standardized techniques for attaching an antibody or protein to the surface of a nanoparticle in order to create a targeted drug delivery vehicle or imaging agent. This approach works well when trying to target a known cancer biomarker, but the fact is that today, researchers have only a few such markers to choose from, and many types of cancers do not express those few known markers.
In an attempt to overcome this limitation, a team of researchers at the Massachusetts General Hospital has taken a different approach, creating a large library of nanoparticles, each with a different small molecule decorating its surface. They then screen this library to see if any of the nanoparticles will bind to any number of cancer cells while ignoring healthy cells.
Reporting its work in the journal Bioconjugate Chemistry, a team led by Ralph Weissleder, M.D., and Lee Josephson, Ph.D., describes the methods they use for attaching a variety of small organic molecules to the surface of a magnetic and fluorescent nanoparticle. The researchers chose to use small molecules of “nonbiological origin” with an eye on keeping costs and regulatory burdens low should any of these nanoparticles prove clinically useful.
The researchers also worked out a method to ensure that each chemical preparation went as planned. This latter step is critically important in order to distinguish between modified nanoparticles that have no biological activity and those that have no activity because the expected chemical modifications never occurred in the first place. Finally, in order to automate the screening process, the researchers also developed two techniques for “printing” the resulting libraries of modified nanoparticles onto glass slides or for adding each member of the library to the tiny indentations on a standard 96-well assay plate used in a wide variety of screening technologies.
In a demonstration experiment, the investigators prepared a 96-well plate in which each well contained macrophages, a type of immune system cell that has a propensity to engulf nanoparticles. They then added individual members of the library to each well and identified modified nanoparticles that were not taken very effectively by macrophages (see illustration). The macrophage-avoiding nanoparticles may be able to more effectively deliver drugs to tumors since more of them may be able to reach their target rather than be eliminated from the body by macrophages.
This work, which was funded by the National Cancer Institute, is detailed in a paper titled, “Development of nanoparticle libraries for biosensing.” This paper was published online in advance of print publication.
An abstract is available at the journal’s website.
Source>http://www.nanotechwire.com/news.asp?nid=2838
In an attempt to overcome this limitation, a team of researchers at the Massachusetts General Hospital has taken a different approach, creating a large library of nanoparticles, each with a different small molecule decorating its surface. They then screen this library to see if any of the nanoparticles will bind to any number of cancer cells while ignoring healthy cells.
Reporting its work in the journal Bioconjugate Chemistry, a team led by Ralph Weissleder, M.D., and Lee Josephson, Ph.D., describes the methods they use for attaching a variety of small organic molecules to the surface of a magnetic and fluorescent nanoparticle. The researchers chose to use small molecules of “nonbiological origin” with an eye on keeping costs and regulatory burdens low should any of these nanoparticles prove clinically useful.
The researchers also worked out a method to ensure that each chemical preparation went as planned. This latter step is critically important in order to distinguish between modified nanoparticles that have no biological activity and those that have no activity because the expected chemical modifications never occurred in the first place. Finally, in order to automate the screening process, the researchers also developed two techniques for “printing” the resulting libraries of modified nanoparticles onto glass slides or for adding each member of the library to the tiny indentations on a standard 96-well assay plate used in a wide variety of screening technologies.
In a demonstration experiment, the investigators prepared a 96-well plate in which each well contained macrophages, a type of immune system cell that has a propensity to engulf nanoparticles. They then added individual members of the library to each well and identified modified nanoparticles that were not taken very effectively by macrophages (see illustration). The macrophage-avoiding nanoparticles may be able to more effectively deliver drugs to tumors since more of them may be able to reach their target rather than be eliminated from the body by macrophages.
This work, which was funded by the National Cancer Institute, is detailed in a paper titled, “Development of nanoparticle libraries for biosensing.” This paper was published online in advance of print publication.
An abstract is available at the journal’s website.
Source>http://www.nanotechwire.com/news.asp?nid=2838
Nanoparticle
Combining Two Drugs in One Nanoparticle Overcomes Multidrug Resistance
Cancer cells, like bacteria, can develop resistance to drug therapy. In fact, research suggests strongly that multidrug-resistant cancer cells that remain alive after chemotherapy are responsible for the reappearance of tumors and the poor prognosis for patients whose cancer recurs. One new approach that shows promise in overcoming such multidrug resistance is to combine two different anticancer agents in one nanoscale construct, providing a one-two punch that can prove lethal to such resistant cells. This work appears in the journal Molecular Pharmaceutics.
Mansoor Amiji, Ph.D., principal investigator of the National Cancer Institute-funded Nanotherapeutic Strategy for Multidrug Resistant Tumors Platform Partnership at Northeastern University, and postdoctoral fellow Srinivas Ganta, Ph.D., created a nanoemulsion entrapping both paclitaxel and curcumin. The former compound is a widely used anticancer agent, whereas the latter comes from the spice tumeric and has been shown to inhibit several cancer-related processes.
The investigators prepared their nanoformulation by mixing the two drugs with flaxseed oil, the emulsifier lecithin from egg yolks, and the biocompatible polymer polyethylene glycol. To help track this nanoformulation, the investigators also added a fluorescent dye to the mixture. Ultrasonification for 10 minutes produced stable, nanosize droplets that were readily taken up by tumor cells grown in culture. In addition, the nanoformulation had significant anticancer activity that surpassed that of either of the two drugs administered together or separately, particularly in multidrug-resistant cells. Biochemical assays showed that the curcumin component inhibited P-glycoprotein, which tumor cells use to excrete anticancer agents and protect themselves from the effects of those agents. Both drugs also had the effect of triggering apoptosis in the treated cells.
This work, which was detailed in the paper “Coadministration of paclitaxel and curcumin in nanoemulsion formulations to overcome multidrug resistance in tumor cells,” was supported by the NCI Alliance for Nanotechnology in Cancer, a comprehensive initiative designed to accelerate the application of nanotechnology to the prevention, diagnosis, and treatment of cancer.
An abstract is available at the journal’s Web site.
>http://www.nanotechwire.com/news.asp?nid=7861
Cancer cells, like bacteria, can develop resistance to drug therapy. In fact, research suggests strongly that multidrug-resistant cancer cells that remain alive after chemotherapy are responsible for the reappearance of tumors and the poor prognosis for patients whose cancer recurs. One new approach that shows promise in overcoming such multidrug resistance is to combine two different anticancer agents in one nanoscale construct, providing a one-two punch that can prove lethal to such resistant cells. This work appears in the journal Molecular Pharmaceutics.
Mansoor Amiji, Ph.D., principal investigator of the National Cancer Institute-funded Nanotherapeutic Strategy for Multidrug Resistant Tumors Platform Partnership at Northeastern University, and postdoctoral fellow Srinivas Ganta, Ph.D., created a nanoemulsion entrapping both paclitaxel and curcumin. The former compound is a widely used anticancer agent, whereas the latter comes from the spice tumeric and has been shown to inhibit several cancer-related processes.
The investigators prepared their nanoformulation by mixing the two drugs with flaxseed oil, the emulsifier lecithin from egg yolks, and the biocompatible polymer polyethylene glycol. To help track this nanoformulation, the investigators also added a fluorescent dye to the mixture. Ultrasonification for 10 minutes produced stable, nanosize droplets that were readily taken up by tumor cells grown in culture. In addition, the nanoformulation had significant anticancer activity that surpassed that of either of the two drugs administered together or separately, particularly in multidrug-resistant cells. Biochemical assays showed that the curcumin component inhibited P-glycoprotein, which tumor cells use to excrete anticancer agents and protect themselves from the effects of those agents. Both drugs also had the effect of triggering apoptosis in the treated cells.
This work, which was detailed in the paper “Coadministration of paclitaxel and curcumin in nanoemulsion formulations to overcome multidrug resistance in tumor cells,” was supported by the NCI Alliance for Nanotechnology in Cancer, a comprehensive initiative designed to accelerate the application of nanotechnology to the prevention, diagnosis, and treatment of cancer.
An abstract is available at the journal’s Web site.
>http://www.nanotechwire.com/news.asp?nid=7861
Dead or alive
Nanotechnology technique tells the difference
(From Nanowerk Spotlight)
A major concern in microbiology is to determine whether a bacterium is dead or alive. This crucial question has major consequences in food industry, water supply or health care. While culture-based tests can determine whether bacteria can proliferate and form colonies, these tests are time-consuming and work poorly with certain slow-growing or non-culturable bacteria. They are not suitable for applications where real-time results are needed, e.g. in industrial manufacturing or food processing. A team of scientists in France has now discovered that living and dead cells can be discriminated with a nanotechnology technique on the basis of their cell wall nanomechanical properties. This finding is totally new and has been made possible thanks to an interdisciplinary approach which mixes physics, biology and chemistry. This work is a key stone in the understanding of bacterial cell wall behavior. "We have developed a method to probe the mechanical properties of living and dead bacteria via atomic force microscope (AFM) indentation experimentations," Aline Cerf tells Nanowerk. ". Indeed, we provide a new way to probe bacterial cell viability based on cell wall nanomechanical properties, independently from cell ability to grow on a medium or to be penetrated by a fluorescent dye." Cerf, a PhD student in the NanoBioSystems group at LAAS-CNRS, is first author of a recent paper in Langmuir ("Nanomechanical Properties of Dead or Alive Single-Patterned Bacteria") where she and collaborators from LAAS-CNRS describe their findings. "We wanted to explore the modifications that could occur in the nanomechanical properties of a single E. coli bacterium, while it is alive and while it is dead," says Etienne Dague, a researcher in the NanoBioSystems group. "To reach this goal, it has been of first importance to immobilize the living bacteria in an aqueous environment to avoid any cell wall modifications due to a drying step." Thus, in developing a technique to probe the mechanical properties of bacteria via AFM indentation experiments, the French team also came up with an immobilization method for bacteria that doesn't require a chemical fixation.
The researchers set up a fast and simple procedure – based on a conventional microcontact printing and a simple incubation technique to generate functionalized patterns so as to induce local bacteria deposition – that allowed them to produce reliable chemical patterns exhibiting different surface properties to induce selective adsorption of individual bacteria in liquid media at registered positions. "We have evidenced a selective adsorption of bacteria on these local chemical patterns, producing highly ordered arrays of single living bacteria with a success rate close to 100%," says Cerf. The team then used this controlled immobilization method to study the mechanical properties of dead or alive bacterial cell in aqueous environment. Using force spectroscopy before and after heating , they measured the Young moduli of the same cell. The cells with a damaged membrane (after heating) present a Young modulus twice as high (6.1 ? 1.5 MPa versus 3.0 ? 0.6 MPa) as that of healthy bacteria. At the same time it has been impossible to evidence a difference between the AFM images of the living and the dead cell. "We have shown that we are capable of engineering large areas with patterns of single bacteria and this will be of major interest for future applications," says Dague. "Indeed, thanks to a periodic arrangement of cells, the process consisting in measuring the nanomechanical properties of cells could possibly be automated and a tool to count live or dead bacteria could be designed."
By Michael Berger.
Nanowerk LLC >http://www.nanowerk.com/spotlight/spotid=10816.php
(From Nanowerk Spotlight)
A major concern in microbiology is to determine whether a bacterium is dead or alive. This crucial question has major consequences in food industry, water supply or health care. While culture-based tests can determine whether bacteria can proliferate and form colonies, these tests are time-consuming and work poorly with certain slow-growing or non-culturable bacteria. They are not suitable for applications where real-time results are needed, e.g. in industrial manufacturing or food processing. A team of scientists in France has now discovered that living and dead cells can be discriminated with a nanotechnology technique on the basis of their cell wall nanomechanical properties. This finding is totally new and has been made possible thanks to an interdisciplinary approach which mixes physics, biology and chemistry. This work is a key stone in the understanding of bacterial cell wall behavior. "We have developed a method to probe the mechanical properties of living and dead bacteria via atomic force microscope (AFM) indentation experimentations," Aline Cerf tells Nanowerk. ". Indeed, we provide a new way to probe bacterial cell viability based on cell wall nanomechanical properties, independently from cell ability to grow on a medium or to be penetrated by a fluorescent dye." Cerf, a PhD student in the NanoBioSystems group at LAAS-CNRS, is first author of a recent paper in Langmuir ("Nanomechanical Properties of Dead or Alive Single-Patterned Bacteria") where she and collaborators from LAAS-CNRS describe their findings. "We wanted to explore the modifications that could occur in the nanomechanical properties of a single E. coli bacterium, while it is alive and while it is dead," says Etienne Dague, a researcher in the NanoBioSystems group. "To reach this goal, it has been of first importance to immobilize the living bacteria in an aqueous environment to avoid any cell wall modifications due to a drying step." Thus, in developing a technique to probe the mechanical properties of bacteria via AFM indentation experiments, the French team also came up with an immobilization method for bacteria that doesn't require a chemical fixation.
The researchers set up a fast and simple procedure – based on a conventional microcontact printing and a simple incubation technique to generate functionalized patterns so as to induce local bacteria deposition – that allowed them to produce reliable chemical patterns exhibiting different surface properties to induce selective adsorption of individual bacteria in liquid media at registered positions. "We have evidenced a selective adsorption of bacteria on these local chemical patterns, producing highly ordered arrays of single living bacteria with a success rate close to 100%," says Cerf. The team then used this controlled immobilization method to study the mechanical properties of dead or alive bacterial cell in aqueous environment. Using force spectroscopy before and after heating , they measured the Young moduli of the same cell. The cells with a damaged membrane (after heating) present a Young modulus twice as high (6.1 ? 1.5 MPa versus 3.0 ? 0.6 MPa) as that of healthy bacteria. At the same time it has been impossible to evidence a difference between the AFM images of the living and the dead cell. "We have shown that we are capable of engineering large areas with patterns of single bacteria and this will be of major interest for future applications," says Dague. "Indeed, thanks to a periodic arrangement of cells, the process consisting in measuring the nanomechanical properties of cells could possibly be automated and a tool to count live or dead bacteria could be designed."
By Michael Berger.
Nanowerk LLC >http://www.nanowerk.com/spotlight/spotid=10816.php
NanoMission
Nanomedicine Vesicle
Nanocomputers will be needed to guide these machines. These computers will direct machines to examine, take apart, and rebuild damaged molecular structures. Repair machines will be able to repair whole cells by working structure by structure. Then by working cell by cell and tissue by tissue, whole organs can be repaired. Finally, by working organ by organ, health is restored to the body. Cells damaged to the point of inactivity can be repaired because of the ability of molecular machines to build cells from scratch. Therefore, cell repair machines will free medicine from reliance on self repair. A new wave of technology and medicine is being created and its impact on the world is going to be monumental. From the possible applications such as drug delivery and in vivo imaging to the potential machines of the future, advancements in nanomedicine are being made every day. It will not be long for the 10 billion dollar industry to explode into a 100 billion or 1 trillion dollar industry, and drug delivery, in vivo imaging and therapy is just the beginning.
Source:>Wilkepedia
Nanocomputers will be needed to guide these machines. These computers will direct machines to examine, take apart, and rebuild damaged molecular structures. Repair machines will be able to repair whole cells by working structure by structure. Then by working cell by cell and tissue by tissue, whole organs can be repaired. Finally, by working organ by organ, health is restored to the body. Cells damaged to the point of inactivity can be repaired because of the ability of molecular machines to build cells from scratch. Therefore, cell repair machines will free medicine from reliance on self repair. A new wave of technology and medicine is being created and its impact on the world is going to be monumental. From the possible applications such as drug delivery and in vivo imaging to the potential machines of the future, advancements in nanomedicine are being made every day. It will not be long for the 10 billion dollar industry to explode into a 100 billion or 1 trillion dollar industry, and drug delivery, in vivo imaging and therapy is just the beginning.
Source:>Wilkepedia
Future Medicine
The photonic nanomedicine revolution:
Let the human side of nanotechnology emerge
Naomi J Halas
Department of Electrical & Computer Engineering & the Laboratory for Nanophotonics,
Rice University, 6100 Main St., Houston, TX 77005-1892, USA. halas@rice.edu
Nanoparticle-based photothermal ablation is showing extraordinary promise as an unusually effective and potentially revolutionary cancer therapy. This approach uses light at near-infrared wavelengths that pass through tissue, in combination with gold-based nanoparticles specifically engineered to absorb that light and convert it to heat. The light-absorbing nanoparticles serve as highly localized heat sources that destroy cells in their immediate vicinity by hyperthermia [4]. This method has been shown to be highly effective in extensive animal studies, with tumor remission rates above 90%. Extensive toxicity studies have been performed on nanoshells, the nanoparticles most utilized to date in these studies, and this is being followed by similar studies on other types of noble metal nanoparticles that are also promising candidates for this therapeutic modality. The US FDA has recently granted approval for initial human trials of this therapy for head and neck cancer. Given the extraordinary promise of these potentially revolutionary therapeutic nanodevices and their impending availability, research into nanoparticle-based therapeutics is beginning to move into the next critical phase: the development of nanoparticle-assisted therapeutic practices specifically for clinical use.
One of the most extraordinary aspects of nanoparticle-assisted photothermal therapy for tumor remission is that it is drug free: cell death is induced by the localized heat generated when the nanoparticles absorb near-infrared light. This is an exceedingly important aspect: with heat as the source of cell death, this approach is independent of the specifics of the immune systems of various animals on which it may be tested. This also means that with this therapeutic approach, the nanoparticles can be classified as a device, rather than a drug. They are nanoscale lenses, delivering highly focused light to cancer cells or within tumors much like a lens that captures sunlight delivers enough heat to a leaf to enable it to burst into flames. However, in the case of nanoparticle-based photothermal therapy, the heat required to induce cell death is only approximately 15–20? above physiological temperatures. Because the nanoparticles are devices and not drugs, operating only on heat and light and not interacting chemically with living systems, this therapy, and other variants of this approach, may be available for patients and practitioners in just a few years.
For cancer, this nanoparticle-based strategy will ultimately allow the clinician to remove localized tumors with a simple, minimally invasive, nonsurgical procedure performed, for example, with a portable laser in an outpatient clinic instead of a surgical suite. This could fundamentally revolutionize the treatment of virtually all soft-tissue cancers, transforming this feared, life-threatening disease to an actively managed illness that can be treated and contained prophylactically.
While early detection and treatment of localized, noninvasive tumors is ideal, in reality it is not the typical diagnostic scenario. In any given year, invasive carcinoma diagnoses far outnumber the diagnosed cases of localized cancer. While nanoparticle-based photothermal therapy appears to be highly promising for the removal of localized tumors, an important and immediate challenge is to develop strategies to address more advanced stages of cancer with this powerful new modality. The proliferation of cancer to the lymph nodes directly adjacent to the primary tumor is a key diagnostic for cancer clinicians, and determines the course of treatment. In conventional surgery, these adjacent lymph nodes are typically removed along with the primary tumor. Recent advances in the development of strongly enhanced fluorescent markers for deep-tissue imaging may make resolution at the limit of a few cells possible. Targeted imaging of cancer in lymph nodes, to quantify the proliferation of cancer beyond carcinoma in situ, could be combined with photothermal destruction of targeted cancer cells using nanoparticle-based probes. This would provide a method for removing the cancer cells in the lymph nodes while preserving, largely intact, the lymphatic system of the cancer patient. As markers become available this general approach should be extendable to additional strategies for the treatment of metastatic disease.
The centers of solid tumors are frequently observed to be largely necrotic, resulting from prolonged hypoxia: insufficient availability of oxygen and glucose to meet the metabolic demands of the malignant cells. Because of the decreased blood flow in these tumor regions, they are inaccessible by, and therefore highly resistant to, conventional chemotherapies. One possible scenario for the progression of cancer to its latter, highly fatal stages is that cells surviving in these inaccessible hypoxic regions may themselves be the source of subsequent local recurrence and distant metastasis. One of the body’s responses to the presence of a malignant neoplasm is to recruit peripheral blood monocytes into the tumor, which then differentiate into macrophages. These cells have been shown to promote metastatic disease. One potentially promising scenario is to induce uptake of nanoshells into monocytes, which are then recruited into the hypoxic regions of tumors: the presence of the nanoshells would then permit photothermal destruction of the necrotic region. This type of approach may provide a critical new strategy for thwarting tumor metastasis.
An exciting new use of nanoparticle-assisted photothermal therapy is in delivery methods for gene therapy. It is widely recognized that gene-based therapies hold extraordinary therapeutic promise for cancer: many genetic markers have been discovered, and numerous DNA-based therapeutics have been proposed for the targeting of pathogenic genes for various cancers. Genetic vaccines have also been suggested for certain forms of cancer now believed to have a hereditary basis, such as the 42–57% of prostate cancer cases that correlate with inherited genetic factors. However, while the discovery of gene targets and the development of gene-based therapies at the molecular level has been pursued aggressively for more than 15 years, the transition of these therapies from the research laboratory to the clinic is at a virtual impasse and fraught with severe challenges. Unprotected gene therapy drugs (DNA- or RNA-based) introduced into the bloodstream are rapidly broken down, preventing their diffusion to the region of disease. Viruses, the initial carrier of choice in most gene therapy research, present a variety of potential problems to the patient – toxicity, immune and inflammatory responses, and gene control and targeting issues. The first clinical gene therapy studies utilizing a viral delivery vector resulted in patient death, and had to be terminated in their initial stage. There is a clear critical need for nonviral delivery vectors for gene therapy for this field to advance towards its many clinical applications. Nanoparticle–biomolecule light-actuated complexes are being developed and tested with clinically relevant genetic markers. For example, by combining gold nanoparticles with specific oligonucleotides, the nanoparticle complex can serve as a nonviral gene-delivery vector, where incident light can trigger the release of the nucleotide once the complex has been taken up by cells. Initial release data in cell culture studies show that this approach has outstanding promise for gene delivery. Light-triggered nucleotide release from these nanoparticle–molecule complexes makes them particularly well suited for the localized administration of gene therapy drugs into the tissue or organ of interest.
In conclusion, nanoparticle-assisted, photothermal therapeutic strategies have the capability of providing revolutionary tools in many battles against human disease, with the clear potential for highly effective therapy for cancer and other diseases. Moreover, this approach is unparalleled in its level of noninvasiveness and in its low, essentially nonexistent toxicity. The long-term impact of the development of these new treatment methods will be to change the way we treat cancer. This approach may also provide effective new strategies for treatments of other, lesser known and less-studied diseases such as autoimmune disorders, where few or no treatment options currently exist. In addition to increased efficacy, an extraordinary advantage of nanoparticle-assisted photothermal therapy is that essentially no, or minimal, side effects are expected. Replacing current chemotherapy treatments, with their high level of systemic toxicity and deleterious side effects, with this benign therapeutic approach will greatly increase the quality of life for cancer patients and their families.
Financial & competing interests disclosure The author is the inventor of nanoshells and pioneered nanoparticle-based photothermal therapies along with her collaborators at Rice University (TX, USA), J West and R Drezek. She is the co-founder of Nanospectra Biosciences, Inc. (http://www.nanospectra.com/), a Houston-based company dedicated to the translation of this therapeutic approach into clinical practice. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Source >http://www.futuremedicine.com/doi/full/10.2217/nnm.09.26
Let the human side of nanotechnology emerge
Naomi J Halas
Department of Electrical & Computer Engineering & the Laboratory for Nanophotonics,
Rice University, 6100 Main St., Houston, TX 77005-1892, USA. halas@rice.edu
Nanoparticle-based photothermal ablation is showing extraordinary promise as an unusually effective and potentially revolutionary cancer therapy. This approach uses light at near-infrared wavelengths that pass through tissue, in combination with gold-based nanoparticles specifically engineered to absorb that light and convert it to heat. The light-absorbing nanoparticles serve as highly localized heat sources that destroy cells in their immediate vicinity by hyperthermia [4]. This method has been shown to be highly effective in extensive animal studies, with tumor remission rates above 90%. Extensive toxicity studies have been performed on nanoshells, the nanoparticles most utilized to date in these studies, and this is being followed by similar studies on other types of noble metal nanoparticles that are also promising candidates for this therapeutic modality. The US FDA has recently granted approval for initial human trials of this therapy for head and neck cancer. Given the extraordinary promise of these potentially revolutionary therapeutic nanodevices and their impending availability, research into nanoparticle-based therapeutics is beginning to move into the next critical phase: the development of nanoparticle-assisted therapeutic practices specifically for clinical use.
One of the most extraordinary aspects of nanoparticle-assisted photothermal therapy for tumor remission is that it is drug free: cell death is induced by the localized heat generated when the nanoparticles absorb near-infrared light. This is an exceedingly important aspect: with heat as the source of cell death, this approach is independent of the specifics of the immune systems of various animals on which it may be tested. This also means that with this therapeutic approach, the nanoparticles can be classified as a device, rather than a drug. They are nanoscale lenses, delivering highly focused light to cancer cells or within tumors much like a lens that captures sunlight delivers enough heat to a leaf to enable it to burst into flames. However, in the case of nanoparticle-based photothermal therapy, the heat required to induce cell death is only approximately 15–20? above physiological temperatures. Because the nanoparticles are devices and not drugs, operating only on heat and light and not interacting chemically with living systems, this therapy, and other variants of this approach, may be available for patients and practitioners in just a few years.
For cancer, this nanoparticle-based strategy will ultimately allow the clinician to remove localized tumors with a simple, minimally invasive, nonsurgical procedure performed, for example, with a portable laser in an outpatient clinic instead of a surgical suite. This could fundamentally revolutionize the treatment of virtually all soft-tissue cancers, transforming this feared, life-threatening disease to an actively managed illness that can be treated and contained prophylactically.
While early detection and treatment of localized, noninvasive tumors is ideal, in reality it is not the typical diagnostic scenario. In any given year, invasive carcinoma diagnoses far outnumber the diagnosed cases of localized cancer. While nanoparticle-based photothermal therapy appears to be highly promising for the removal of localized tumors, an important and immediate challenge is to develop strategies to address more advanced stages of cancer with this powerful new modality. The proliferation of cancer to the lymph nodes directly adjacent to the primary tumor is a key diagnostic for cancer clinicians, and determines the course of treatment. In conventional surgery, these adjacent lymph nodes are typically removed along with the primary tumor. Recent advances in the development of strongly enhanced fluorescent markers for deep-tissue imaging may make resolution at the limit of a few cells possible. Targeted imaging of cancer in lymph nodes, to quantify the proliferation of cancer beyond carcinoma in situ, could be combined with photothermal destruction of targeted cancer cells using nanoparticle-based probes. This would provide a method for removing the cancer cells in the lymph nodes while preserving, largely intact, the lymphatic system of the cancer patient. As markers become available this general approach should be extendable to additional strategies for the treatment of metastatic disease.
The centers of solid tumors are frequently observed to be largely necrotic, resulting from prolonged hypoxia: insufficient availability of oxygen and glucose to meet the metabolic demands of the malignant cells. Because of the decreased blood flow in these tumor regions, they are inaccessible by, and therefore highly resistant to, conventional chemotherapies. One possible scenario for the progression of cancer to its latter, highly fatal stages is that cells surviving in these inaccessible hypoxic regions may themselves be the source of subsequent local recurrence and distant metastasis. One of the body’s responses to the presence of a malignant neoplasm is to recruit peripheral blood monocytes into the tumor, which then differentiate into macrophages. These cells have been shown to promote metastatic disease. One potentially promising scenario is to induce uptake of nanoshells into monocytes, which are then recruited into the hypoxic regions of tumors: the presence of the nanoshells would then permit photothermal destruction of the necrotic region. This type of approach may provide a critical new strategy for thwarting tumor metastasis.
An exciting new use of nanoparticle-assisted photothermal therapy is in delivery methods for gene therapy. It is widely recognized that gene-based therapies hold extraordinary therapeutic promise for cancer: many genetic markers have been discovered, and numerous DNA-based therapeutics have been proposed for the targeting of pathogenic genes for various cancers. Genetic vaccines have also been suggested for certain forms of cancer now believed to have a hereditary basis, such as the 42–57% of prostate cancer cases that correlate with inherited genetic factors. However, while the discovery of gene targets and the development of gene-based therapies at the molecular level has been pursued aggressively for more than 15 years, the transition of these therapies from the research laboratory to the clinic is at a virtual impasse and fraught with severe challenges. Unprotected gene therapy drugs (DNA- or RNA-based) introduced into the bloodstream are rapidly broken down, preventing their diffusion to the region of disease. Viruses, the initial carrier of choice in most gene therapy research, present a variety of potential problems to the patient – toxicity, immune and inflammatory responses, and gene control and targeting issues. The first clinical gene therapy studies utilizing a viral delivery vector resulted in patient death, and had to be terminated in their initial stage. There is a clear critical need for nonviral delivery vectors for gene therapy for this field to advance towards its many clinical applications. Nanoparticle–biomolecule light-actuated complexes are being developed and tested with clinically relevant genetic markers. For example, by combining gold nanoparticles with specific oligonucleotides, the nanoparticle complex can serve as a nonviral gene-delivery vector, where incident light can trigger the release of the nucleotide once the complex has been taken up by cells. Initial release data in cell culture studies show that this approach has outstanding promise for gene delivery. Light-triggered nucleotide release from these nanoparticle–molecule complexes makes them particularly well suited for the localized administration of gene therapy drugs into the tissue or organ of interest.
In conclusion, nanoparticle-assisted, photothermal therapeutic strategies have the capability of providing revolutionary tools in many battles against human disease, with the clear potential for highly effective therapy for cancer and other diseases. Moreover, this approach is unparalleled in its level of noninvasiveness and in its low, essentially nonexistent toxicity. The long-term impact of the development of these new treatment methods will be to change the way we treat cancer. This approach may also provide effective new strategies for treatments of other, lesser known and less-studied diseases such as autoimmune disorders, where few or no treatment options currently exist. In addition to increased efficacy, an extraordinary advantage of nanoparticle-assisted photothermal therapy is that essentially no, or minimal, side effects are expected. Replacing current chemotherapy treatments, with their high level of systemic toxicity and deleterious side effects, with this benign therapeutic approach will greatly increase the quality of life for cancer patients and their families.
Financial & competing interests disclosure The author is the inventor of nanoshells and pioneered nanoparticle-based photothermal therapies along with her collaborators at Rice University (TX, USA), J West and R Drezek. She is the co-founder of Nanospectra Biosciences, Inc. (http://www.nanospectra.com/), a Houston-based company dedicated to the translation of this therapeutic approach into clinical practice. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Source >http://www.futuremedicine.com/doi/full/10.2217/nnm.09.26
Wednesday, June 10, 2009
Biomedical devices
The devices considered in this section fall into the category of nanobiotechnology, also known as nanomedicine, defined as the application of nanotechnology to human health.One of the most attractive candidate tasks for a radically new approach is the sequencing ofthe human genome. The growing fund of medical experience concerning individual patients’responses to pharmaceutical drugs is revealing significant differences between individuals, whichin many cases might be due to differences in DNA sequence. Despite the tremendousboost to the technology of DNA sequencing that came from the international project to sequencethe (putatively prototypical) human genome, the basic methods applied were the conventionalbiochemical ones; the vast increase in throughput was achieved through massive parallelizationand automation.
The four different DNA “bases” (or nucleotides, symbolized as A,C,G,T) differ not only in the chemical nature, but also in their physical nature, most significantly as regards size and shape.One of the early motivations for developing the atomic force microscope was the hope that thesephysical differences could be revealed by rapidly scanning a single strand of DNA. Although theresolution, at least in the presence of liquid water, has so far proved to be inadequate, alternativeapproaches with the same end in view are being intensively investigated. The favoured schemeis to pass the DNA strand through a nanopore while measuring ionic conductance (of theelectrolyte solution in which the DNA is dissolved), either along or across the pore, with theresolution of a single base. The different nucleotides can be thus distinguished, but it is difficultto capture the DNA and drive it through the pore.
The flagship nanomedical system (rather than device) is the “nanobot”, an autonomous robotenvisaged to be about the size of a bacterium (i.e., about one micrometre in diameter), andcontaining many nanodevices (an energy source, a means of propulsion, an information pro-cessor, environmental sensors, and so forth). When engineering such devices it is importantto note the environment in which they must operate: viscous (highly dissipative), dominatedby friction and fluctuations (Brownian motion), and in which inertia plays a negligible role.This is in contrast to the familiar macroscopic mechanisms that follow Newton’s laws: for thenanobot, force is not given by the product of mass and acceleration, but by the product of thecoefficient of friction and its velocity, together with superimposed random fluctuations. Anyself-propelling nanobot is therefore likely to resemble a motile bacterium rather than a deviceequipped with nanoscale oars or paddles.
Source: Jeremy Rameden," Nanotechnology " 2009
The four different DNA “bases” (or nucleotides, symbolized as A,C,G,T) differ not only in the chemical nature, but also in their physical nature, most significantly as regards size and shape.One of the early motivations for developing the atomic force microscope was the hope that thesephysical differences could be revealed by rapidly scanning a single strand of DNA. Although theresolution, at least in the presence of liquid water, has so far proved to be inadequate, alternativeapproaches with the same end in view are being intensively investigated. The favoured schemeis to pass the DNA strand through a nanopore while measuring ionic conductance (of theelectrolyte solution in which the DNA is dissolved), either along or across the pore, with theresolution of a single base. The different nucleotides can be thus distinguished, but it is difficultto capture the DNA and drive it through the pore.
The flagship nanomedical system (rather than device) is the “nanobot”, an autonomous robotenvisaged to be about the size of a bacterium (i.e., about one micrometre in diameter), andcontaining many nanodevices (an energy source, a means of propulsion, an information pro-cessor, environmental sensors, and so forth). When engineering such devices it is importantto note the environment in which they must operate: viscous (highly dissipative), dominatedby friction and fluctuations (Brownian motion), and in which inertia plays a negligible role.This is in contrast to the familiar macroscopic mechanisms that follow Newton’s laws: for thenanobot, force is not given by the product of mass and acceleration, but by the product of thecoefficient of friction and its velocity, together with superimposed random fluctuations. Anyself-propelling nanobot is therefore likely to resemble a motile bacterium rather than a deviceequipped with nanoscale oars or paddles.
Source: Jeremy Rameden," Nanotechnology " 2009
Trends in Biomedical Nanotechnology(1)
Trends in Biomedical Nanotechnology Programs Worldwide
By Mark Morrison and Ineke Malsch
An overview of trends in nanotechnology research programs for biomedical applications in the United States, leading European countries, and Japan. We focus on technologies for applications inside the body, including drug delivery technologies for pharmaceuticals, and new materials and technologies for prostheses and implants. We also include technologies for applications outside the body including diagnostics and high throughput screening of drug compounds. We cover the main application areas in pharmaceuticals and medical devices — areas where governments expect nanotechnology to make important contributions. We also outline the currently operational national and European Union (EU) policies and programs intended to stimulate the development of biomedical nanotechnology in the U.S., Europe, and Japan.
Several applications of nanotechnology are already available in the market. Lipid spheres (liposomes) with diameters of 100 nm are available for carrying anticancer drugs inside the body. Some anti-fungal foot sprays contain nanoscale zinc oxide particles to reduce clogging.
Nanotechnology is producing short-term impacts in the areas of:
Medical diagnostic tools and sensors
Drug delivery
Catalysts (many applications in chemistry and pharmaceuticals)
Alloys (e.g., steel and materials used in prosthetics) Improved and body-friendly implants
Biosensors and chemical sensors
Bioanalysis tools Bioseparation technologies Medical imaging
Filters
Most current applications utilize nanopowder qualities instead of other properties present at the nanoscale. The next stage of applications of nanotechnology will allow products to exhibit more unusual properties as product creation is approached from the bottom up. This is considered a measure of the development of nanotechnology. Long-term product and application perspectives of nanotechnology with high future market potentials include:
Perfect selective sensors for the control of environment, food, and body functions Pharmaceuticals that have long-term dosable capabilities and can be taken orally Replacements for human tissues and organs
Economical or reusable diagnostic chips for preventive medical surveys
It is estimated that more than 300 companies in Europe are involved in nano- technology as their primary areas of business, and many more companies, particu- larly larger organizations, are pursuing some activities in the field. Large organiza- tions currently exploring the possibilities of nanotechnology with near-term applications in drug delivery are Biosante, Akzo Nobel, Ciba, Eli Lilly, and Merck.
Source:Biomedical nanotechnology / edited by Neelina H. Malsch
Tuesday, June 9, 2009
Lab on a chip
Lab on a chip mimics brain chemistry
February 12th, 2008 Johns Hopkins researchers from the Whiting School of Engineering and the School of Medicine have devised a micro-scale tool – a lab on achip – designed to mimic the chemical complexities of the brain. The system should help scientists better understand how nerve cells in the brain work together to form the nervous system.
AmpliChip CYP450 Test – www.AmpliChip.us
Roche Diagnostics US Official Site FDA cleared CYP450 Test
A report on the work appears as the cover story in the February 2008 issue of the British journal Lab on a Chip. ”The chip we’ve developed will make xperiments on nerve cells more simple to conduct and to control,” says Andre Levchenko, Ph.D., associate professor of biomedical engineering at the Johns Hopkins Whiting School of Engineering and faculty affiliate of the Institute for NanoBioTechnology. Nerve cells decide which direction to grow by sensing both the chemical cues flowing through their environment as well as those attached to the surfaces that surround them. The chip, which is made of a plastic-like substance and covered with a glass lid, features a system of channels and wells that allow researchers to control the flow of specific chemical cocktails around single nerve cells.
“It is difficult to establish ideal experimental conditions to study how neurons react to growth signals because so much is happening at once that sorting out nerve cell connections is hard, but the chip, designed by experts in both brain chemistry and engineering, offers a sophisticated way to sort things out,” says Guo-li Ming,
M.D.,Ph.D., associate professor of neurology at the Johns Hopkins School of Medicine and Institute for Cell Engineering.
In experiments with their chip, the researchers put single nerve cells, or rons,onto the chip then introduced specific growth signals (in the form of hemicals).They found that the growing neurons turned and grew toward higher concentrations of certain chemical cues attached to the chip’s surfaces, as well as to signaling molecules free-flowing in solution.
When researchers subjected the neurons to conflicting signals (both surface bound and cues in solution), they found that the cells turned randomly, suggesting that cells do not choose one signal over the other. This,according to Levchenko,supports the prevailing theory that one cue can elicit different responses depending on
a cell’s surroundings. “The ability to combine several different stimuli in the chip resembles a more realistic environment that nerve cells will encounter in the living animal,” Ming says.This in turn will make future studies on the role of neuronal cells in development and regeneration more accurate and complete.
Source: Johns Hopkins Medical Institutions
New Drug Delivery Technique
New Drug Delivery Technique Avoids NeedlesBy Sarah Graham
Hypodermic needles are the stuff of nightmares for many people, but they represent a common method for administering a variety of drugs. Patients who fear a needle prick, however, may soon have an alternative, painless way to receive medication. A new technique described today in the journal BMC Medicine uses a stream of gas to help deliver drugs through the skin with what subjects describe as the sensation of a gentle stream of air.
James Weaver of the Massachusetts Institute of Technology and his colleagues developed the novel procedure, which is known as microscission. It uses minuscule inert crystals of aluminum oxide to remove the rough outer layer of skin and create tiny holes, known as microconduits and measuring less than a quarter of a millimeter in diameter, through which medication can move. A jet of flowing gas then takes the crystals and the loosened skin away. After creating four microconduits on the inner arm of volunteers, the team applied a pad soaked in the anesthetic lidocaine. Within two minutes, the drug had worked and the subjects reported no feeling in the region.
The size and depth of the microconduits is determined by holes punched in a polymer mask laid on top of the skin. The team reports that "the onset of anesthesia takes longer in microconduits deep enough to yield blood than in shallower, nonblood producing microconduits." But deep microconduits do have some advantages. Patients suffering from diabetes, for example, often have to jab a finger to test their blood sugar; microscission could represent a less painful alternative, the team suggests.
Source>http://www.scientificamerican.com/
Hypodermic needles are the stuff of nightmares for many people, but they represent a common method for administering a variety of drugs. Patients who fear a needle prick, however, may soon have an alternative, painless way to receive medication. A new technique described today in the journal BMC Medicine uses a stream of gas to help deliver drugs through the skin with what subjects describe as the sensation of a gentle stream of air.
James Weaver of the Massachusetts Institute of Technology and his colleagues developed the novel procedure, which is known as microscission. It uses minuscule inert crystals of aluminum oxide to remove the rough outer layer of skin and create tiny holes, known as microconduits and measuring less than a quarter of a millimeter in diameter, through which medication can move. A jet of flowing gas then takes the crystals and the loosened skin away. After creating four microconduits on the inner arm of volunteers, the team applied a pad soaked in the anesthetic lidocaine. Within two minutes, the drug had worked and the subjects reported no feeling in the region.
The size and depth of the microconduits is determined by holes punched in a polymer mask laid on top of the skin. The team reports that "the onset of anesthesia takes longer in microconduits deep enough to yield blood than in shallower, nonblood producing microconduits." But deep microconduits do have some advantages. Patients suffering from diabetes, for example, often have to jab a finger to test their blood sugar; microscission could represent a less painful alternative, the team suggests.
Source>http://www.scientificamerican.com/
Nanoparticles Home in on Brain Cancer
Nanoparticles Home in on Brain Cancer
By Nikhil Swaminathan
November 17, 2006
Call them laser-guided smart bombs for brain tumors. Researchers at the University of Michigan announced the testing of a drug delivery system that involves drug-toting nanoparticles and a guiding peptide to target cancerous cells in the brain. Their study finds that via this method more of the drug can be delivered to a tumor's general vicinity. They report their findings in the November 15 issue of Clinical Cancer Research.
The researchers used a pharmaceutical called Photofrin, which is photodynamic, meaning it is activated by a laser after it has entered the bloodstream. As its primary side effect, the drug renders patients photosensitive, and they must remain out of bright sunlight and even unshaded lamps for up to 30 days after receiving treatment. Despite this major drawback, Photofrin is used in the treatment of esophageal, bladder and skin cancers. But their novel delivery system, which relies on the intravenous delivery of 40-nanometer-wide particles to carry the drug, may actually avoid much of the photosensitivity, because less Photofrin circulates in the bloodstream thanks to a peptide called F3. A sequence of 31 amino acids broken off of the protein HMGN2 (high mobility group protein 2), F3 has the ability to penetrate cell membranes. "This peptide acts as a "zip code" in that it enables the binding of the nanoparticles only to blood vessels within the tumor and not normal blood vessels," says Alnawaz Rehemtulla, a radiologist and environmental health scientist who co-authored the study. F3 can detect the expression of a protein called nucleolin, which is a marker on the surface of tumor cells.
Another problem the researchers avoided was having to deliver their medicine in such a way that it could cross the blood-brain barrier, which keeps many substances from entering the brain from the bloodstream. Typical chemotherapies must penetrate this shield to treat tumors. In this case, however, the nontoxic polyacrylamide particles didn't have to cross over via the bloodstream. "The nanoparticles do not need to cross the blood-brain barrier as they were specifically designed to target the blood vessel cells within the tumor," explains radiologist Brian Ross, one of the study's authors. "The treatment should be thought of as an antivascular treatment thereby shutting off the tumor blood flow resulting in the death of the tumor cells through starvation of oxygen and energy sources."
To test the delivery method, researchers divided 34 rats--all who received injections of cancerous cells into their brains--into different groups. Those that received no treatment or got only the laser fared poorly, dying on average within 8.5 days. Those that got Photofrin either intravenously or encapsulated in nanoparticles had a median survival time of 13 days. The group that got F3 with the Photofrin-carrying nanoparticles came through the best: they lived for, on average, 33 days; three of the five in this grouping lived for 60 days, and two of those three appeared tumor-free after six months. By using iron oxide as a contrast agent--to more easily detect where the nanoparticles ended up via MRI--the group determined that twice as much drug with the F3 peptide attached reached the tumor site--10 percent of the total amount administered--compared with when nontargeted nanoparticles were injected.
Ross says that based on the success of the study, the team is investigating if this delivery technology will work for nonphotodynamic therapies. Rehemtulla adds that if other FDA-approved chemotherapeutic agents reach their targets as successfully as Photofrin did, "then we will have developed a way to make cancer drugs more 'tumor-specific,' because they will only get into tumor vasculature and not normal vasculature. This will spare patients from normal tissue toxicity that is commonly associated with almost all chemotherapy."
Source>http://www.scientificamerican.com/article.cfm?id=nanoparticles-home-in-on
By Nikhil Swaminathan
November 17, 2006
Call them laser-guided smart bombs for brain tumors. Researchers at the University of Michigan announced the testing of a drug delivery system that involves drug-toting nanoparticles and a guiding peptide to target cancerous cells in the brain. Their study finds that via this method more of the drug can be delivered to a tumor's general vicinity. They report their findings in the November 15 issue of Clinical Cancer Research.
The researchers used a pharmaceutical called Photofrin, which is photodynamic, meaning it is activated by a laser after it has entered the bloodstream. As its primary side effect, the drug renders patients photosensitive, and they must remain out of bright sunlight and even unshaded lamps for up to 30 days after receiving treatment. Despite this major drawback, Photofrin is used in the treatment of esophageal, bladder and skin cancers. But their novel delivery system, which relies on the intravenous delivery of 40-nanometer-wide particles to carry the drug, may actually avoid much of the photosensitivity, because less Photofrin circulates in the bloodstream thanks to a peptide called F3. A sequence of 31 amino acids broken off of the protein HMGN2 (high mobility group protein 2), F3 has the ability to penetrate cell membranes. "This peptide acts as a "zip code" in that it enables the binding of the nanoparticles only to blood vessels within the tumor and not normal blood vessels," says Alnawaz Rehemtulla, a radiologist and environmental health scientist who co-authored the study. F3 can detect the expression of a protein called nucleolin, which is a marker on the surface of tumor cells.
Another problem the researchers avoided was having to deliver their medicine in such a way that it could cross the blood-brain barrier, which keeps many substances from entering the brain from the bloodstream. Typical chemotherapies must penetrate this shield to treat tumors. In this case, however, the nontoxic polyacrylamide particles didn't have to cross over via the bloodstream. "The nanoparticles do not need to cross the blood-brain barrier as they were specifically designed to target the blood vessel cells within the tumor," explains radiologist Brian Ross, one of the study's authors. "The treatment should be thought of as an antivascular treatment thereby shutting off the tumor blood flow resulting in the death of the tumor cells through starvation of oxygen and energy sources."
To test the delivery method, researchers divided 34 rats--all who received injections of cancerous cells into their brains--into different groups. Those that received no treatment or got only the laser fared poorly, dying on average within 8.5 days. Those that got Photofrin either intravenously or encapsulated in nanoparticles had a median survival time of 13 days. The group that got F3 with the Photofrin-carrying nanoparticles came through the best: they lived for, on average, 33 days; three of the five in this grouping lived for 60 days, and two of those three appeared tumor-free after six months. By using iron oxide as a contrast agent--to more easily detect where the nanoparticles ended up via MRI--the group determined that twice as much drug with the F3 peptide attached reached the tumor site--10 percent of the total amount administered--compared with when nontargeted nanoparticles were injected.
Ross says that based on the success of the study, the team is investigating if this delivery technology will work for nonphotodynamic therapies. Rehemtulla adds that if other FDA-approved chemotherapeutic agents reach their targets as successfully as Photofrin did, "then we will have developed a way to make cancer drugs more 'tumor-specific,' because they will only get into tumor vasculature and not normal vasculature. This will spare patients from normal tissue toxicity that is commonly associated with almost all chemotherapy."
Source>http://www.scientificamerican.com/article.cfm?id=nanoparticles-home-in-on
Ultrasonic Nanotechnology
Revolutionary Ultrasonic Nanotechnology
May Allow Scientists To See Inside Patient’s Individual Cells
ScienceDaily (June 3, 2009)
—> Revolutionary ultrasonic nanotechnology that could allow scientists to see inside a patient’s individual cells to help diagnose serious illnesses is being developed by researchers at The University of Nottingham.
The technology would be tiny enough to allow scientists to see inside and image individual cells in the human body, which would further our understanding of the structure and function of cells and could help to detect abnormalities to diagnose serious illnesses such as some cancers.
The work by the Ultrasonics Group in the Division of Electrical Systems and Optics has been deemed so potentially innovative it has recently been awarded a £850,000 five-year Platform Grant by the Engineering and Physical Sciences Research Council (EPSRC).
Ultrasound refers to sound waves that are at a frequency too high to be detected by the human ear, typically 20 kHz and above. Medical ultrasound uses an electrical transducer the size of a matchbox to produce sound waves at much higher frequencies, typically around 100-1000 times higher to probe bodies.
The Nottingham researchers are aiming to produce a miniaturised version of this technology, with transducers so tiny that you could fit 500 across the width of one human hair which would produce sound waves at frequencies a thousand times higher again, in the GHz range.
Dr Matt Clark of the Ultrasonics Group, said: “By examining the mechanical properties inside a cell there is a huge amount that we can learn about its structure and the way it functions. But it’s very much a leap into the unknown as this has never been achieved before.
“One of the reasons for this is that it presents an enormous technical challenge. To produce nano-ultrasonics you have to produce a nano-transducers, which essentially means taking a device that is currently the size of a matchbox and scaling it down to the nanoscale. How do you attach a wire to something so small?
“Our answer to some of these challenges is to create a device that works optically — using pulses of laser light to produce ultrasound rather than an electrical current. This allows us to talk to these tiny devices.”
The new technology may also allow scientists to see objects even smaller than optical microscopes and be so sensitive they may be able to measure single molecules.
In addition to medical applications, the new technology would have important uses as a testing facility for industry to assess the integrity and quality of materials and to detect tiny defects which could have an impact on performance or safety.
Ultrasonics is currently used in applications such as testing landing gear components in the aero industry for cracks and damage which may not be immediately visible or may develop with use.
The group is also looking at developing new inspection techniques for inspecting engineering metamaterials — advanced composites that are currently impossible to inspect with ultrasound. These materials offer huge performance advantages allowing radical new engineering but can't be widely used because of the difficulty of inspection.
Dr Clark added: “We are also applying our technology to nanoengineering because we have to match the enormous growth in nanotechnology with techniques to inspect the nanoworld. As products and their components become ever tinier, the testing facilities for those also need to be scaled down accordingly.
In NEMS (nanoelectromechanical) and MEMS (microelectromechanical) based machines there is an increasing demand for testing facilities which offer the same capabilities as those for real-world sized devices.
Source:University of Nottingham (2009, June 3).
Revolutionary Ultrasonic Nanotechnology
May Allow Scientists To See Inside Patient’s Individual Cells.
ScienceDaily. Retrieved June 11, 2009,
from >http://www.sciencedaily.com /releases/2009/06/090602134943.htm
May Allow Scientists To See Inside Patient’s Individual Cells
ScienceDaily (June 3, 2009)
—> Revolutionary ultrasonic nanotechnology that could allow scientists to see inside a patient’s individual cells to help diagnose serious illnesses is being developed by researchers at The University of Nottingham.
The technology would be tiny enough to allow scientists to see inside and image individual cells in the human body, which would further our understanding of the structure and function of cells and could help to detect abnormalities to diagnose serious illnesses such as some cancers.
The work by the Ultrasonics Group in the Division of Electrical Systems and Optics has been deemed so potentially innovative it has recently been awarded a £850,000 five-year Platform Grant by the Engineering and Physical Sciences Research Council (EPSRC).
Ultrasound refers to sound waves that are at a frequency too high to be detected by the human ear, typically 20 kHz and above. Medical ultrasound uses an electrical transducer the size of a matchbox to produce sound waves at much higher frequencies, typically around 100-1000 times higher to probe bodies.
The Nottingham researchers are aiming to produce a miniaturised version of this technology, with transducers so tiny that you could fit 500 across the width of one human hair which would produce sound waves at frequencies a thousand times higher again, in the GHz range.
Dr Matt Clark of the Ultrasonics Group, said: “By examining the mechanical properties inside a cell there is a huge amount that we can learn about its structure and the way it functions. But it’s very much a leap into the unknown as this has never been achieved before.
“One of the reasons for this is that it presents an enormous technical challenge. To produce nano-ultrasonics you have to produce a nano-transducers, which essentially means taking a device that is currently the size of a matchbox and scaling it down to the nanoscale. How do you attach a wire to something so small?
“Our answer to some of these challenges is to create a device that works optically — using pulses of laser light to produce ultrasound rather than an electrical current. This allows us to talk to these tiny devices.”
The new technology may also allow scientists to see objects even smaller than optical microscopes and be so sensitive they may be able to measure single molecules.
In addition to medical applications, the new technology would have important uses as a testing facility for industry to assess the integrity and quality of materials and to detect tiny defects which could have an impact on performance or safety.
Ultrasonics is currently used in applications such as testing landing gear components in the aero industry for cracks and damage which may not be immediately visible or may develop with use.
The group is also looking at developing new inspection techniques for inspecting engineering metamaterials — advanced composites that are currently impossible to inspect with ultrasound. These materials offer huge performance advantages allowing radical new engineering but can't be widely used because of the difficulty of inspection.
Dr Clark added: “We are also applying our technology to nanoengineering because we have to match the enormous growth in nanotechnology with techniques to inspect the nanoworld. As products and their components become ever tinier, the testing facilities for those also need to be scaled down accordingly.
In NEMS (nanoelectromechanical) and MEMS (microelectromechanical) based machines there is an increasing demand for testing facilities which offer the same capabilities as those for real-world sized devices.
Source:University of Nottingham (2009, June 3).
Revolutionary Ultrasonic Nanotechnology
May Allow Scientists To See Inside Patient’s Individual Cells.
ScienceDaily. Retrieved June 11, 2009,
from >http://www.sciencedaily.com /releases/2009/06/090602134943.htm
Capsules Encapsulated
Drug Deliver With Nanotechnology:
Capsules Encapsulated
ScienceDaily (May 20, 2009)
—> When cells cannot carry out the tasks required of them by our bodies, the result is disease. Nanobiotechnology researchers are looking for ways to allow synthetic systems take over simple cellular activities when they are absent from the cell. This requires transport systems that can encapsulate medications and other substances and release them in a controlled fashion at the right moment.
The transporter must be able to interact with the surroundings in order to receive the signal to unload its cargo. A team led by Frank Caruso at the University of Melbourne has now developed a microcontainer that can hold thousands of individual "carrier units"—a "capsosome". These are polymer capsules in which liposomes have been embedded to form subcompartments.
Currently, the primary type of nanotransporter used for drugs is the capsule: Polymer capsules form stable containers that are semipermeable, which allows for communication with the surrounding medium. However, these are not suitable for the transport of small molecules because they can escape. Liposomes are good at protecting small drug molecules; however, they are often unstable and impermeable to substances from the environment. The Australian researchers have now combined the advantages of both systems in their capsosomes.
Capsosomes are produced by several steps. First, a layer of polymer is deposited onto small silica spheres. This polymer contains building blocks modified with cholesterol. Liposomes that have been loaded with an enzyme can be securely anchored to the cholesterol units and thus attached to the polymer film. Subsequently, more polymer layers are added and then cross-linked by disulfide bridges into a gel by means of a specially developed, very gentle cross-linking reaction. In the final step, the silica core is etched away without damaging the sensitive cargo.
Experiments with an enzyme as model cargo demonstrated that the liposomes remain intact and the cargo does not escape. Addition of a detergent releases the enzyme in a functional state. By means of the enzymatic reaction, which causes a color change of the solution, it was possible to determine the number of liposome compartments to be about 8000 per polymer capsule.
"Because the capsosomes are biodegradable and nontoxic", says Brigitte Staedler, a senior researcher in the group, "they would also be suitable for use as resorbable synthetic cell organelles and for the transport of drugs." In addition, the scientists are planning to encapsulate liposomes filled with different enzymes together and to equip them with specific "receivers" which would allow the individual cargo to be released in a targeted fashion. This would make it possible to use enzymatic reaction cascades for catalytic reaction processes.
Source:Wiley-Blackwell (2009, May 20).
Drug Deliver With Nanotechnology:
Capsules Encapsulated.
ScienceDaily. Retrieved June 11, 2009,
from> http://www.sciencedaily.com/ /releases/2009/05/090519134717.htm
Capsules Encapsulated
ScienceDaily (May 20, 2009)
—> When cells cannot carry out the tasks required of them by our bodies, the result is disease. Nanobiotechnology researchers are looking for ways to allow synthetic systems take over simple cellular activities when they are absent from the cell. This requires transport systems that can encapsulate medications and other substances and release them in a controlled fashion at the right moment.
The transporter must be able to interact with the surroundings in order to receive the signal to unload its cargo. A team led by Frank Caruso at the University of Melbourne has now developed a microcontainer that can hold thousands of individual "carrier units"—a "capsosome". These are polymer capsules in which liposomes have been embedded to form subcompartments.
Currently, the primary type of nanotransporter used for drugs is the capsule: Polymer capsules form stable containers that are semipermeable, which allows for communication with the surrounding medium. However, these are not suitable for the transport of small molecules because they can escape. Liposomes are good at protecting small drug molecules; however, they are often unstable and impermeable to substances from the environment. The Australian researchers have now combined the advantages of both systems in their capsosomes.
Capsosomes are produced by several steps. First, a layer of polymer is deposited onto small silica spheres. This polymer contains building blocks modified with cholesterol. Liposomes that have been loaded with an enzyme can be securely anchored to the cholesterol units and thus attached to the polymer film. Subsequently, more polymer layers are added and then cross-linked by disulfide bridges into a gel by means of a specially developed, very gentle cross-linking reaction. In the final step, the silica core is etched away without damaging the sensitive cargo.
Experiments with an enzyme as model cargo demonstrated that the liposomes remain intact and the cargo does not escape. Addition of a detergent releases the enzyme in a functional state. By means of the enzymatic reaction, which causes a color change of the solution, it was possible to determine the number of liposome compartments to be about 8000 per polymer capsule.
"Because the capsosomes are biodegradable and nontoxic", says Brigitte Staedler, a senior researcher in the group, "they would also be suitable for use as resorbable synthetic cell organelles and for the transport of drugs." In addition, the scientists are planning to encapsulate liposomes filled with different enzymes together and to equip them with specific "receivers" which would allow the individual cargo to be released in a targeted fashion. This would make it possible to use enzymatic reaction cascades for catalytic reaction processes.
Source:Wiley-Blackwell (2009, May 20).
Drug Deliver With Nanotechnology:
Capsules Encapsulated.
ScienceDaily. Retrieved June 11, 2009,
from> http://www.sciencedaily.com/ /releases/2009/05/090519134717.htm
Drug Delivery Systems
Drug Delivery SystemsMarkets and Applications for Nanotechnology Derived Drug Delivery SystemsBackgroundThe most promising aspect of pharmaceuticals and medicine as it relates to nanotechnology is currently drug delivery. In the words of LaVan and Langer: ‘It is likely that the pharmaceutical industry will transition from a paradigm of drug discovery by screening compounds to the purposeful engineering of targeted molecules.’
Reasons Why the Drug Delivery Market is Rapidly Expanding At present, there are 30 main drug delivery products on the market. The total annual income for all of these is approximately US$33 billion with an annual growth of 15% (based on global product revenue). Two major drivers are primarily responsible for this increase in the market. First, present advances in diagnostic technology appear to be outpacing advances in new therapeutic agents. Highly detailed information from a patient is becoming available, thus promoting much more specific use of pharmaceuticals. Second, the acceptance of new drug formulations is expensive and slow, taking up to 15 years to obtain accreditation of new drug formulas with no guarantee of success.
How Drug Companies are Reacting to this Expansion In response, some companies are trying to hurry the long clinical phase required in Western medicine. However, powerful incentives remain to investigate new techniques that can more effectively deliver or target existing drugs (Saxl, 2000). In addition, many of these new tools will have foundation in current techniques: a targeted molecule may simply add spatial or temporal resolution to an existing assay. Thus, although many potential applications are envisaged, the actual near future products are not much more than better research tools or aids to diagnosis. These are summarised in the following three tables.
More details see >> AZoNanotechnology Article
Reasons Why the Drug Delivery Market is Rapidly Expanding At present, there are 30 main drug delivery products on the market. The total annual income for all of these is approximately US$33 billion with an annual growth of 15% (based on global product revenue). Two major drivers are primarily responsible for this increase in the market. First, present advances in diagnostic technology appear to be outpacing advances in new therapeutic agents. Highly detailed information from a patient is becoming available, thus promoting much more specific use of pharmaceuticals. Second, the acceptance of new drug formulations is expensive and slow, taking up to 15 years to obtain accreditation of new drug formulas with no guarantee of success.
How Drug Companies are Reacting to this Expansion In response, some companies are trying to hurry the long clinical phase required in Western medicine. However, powerful incentives remain to investigate new techniques that can more effectively deliver or target existing drugs (Saxl, 2000). In addition, many of these new tools will have foundation in current techniques: a targeted molecule may simply add spatial or temporal resolution to an existing assay. Thus, although many potential applications are envisaged, the actual near future products are not much more than better research tools or aids to diagnosis. These are summarised in the following three tables.
More details see >> AZoNanotechnology Article
Monday, June 8, 2009
Age of Convergence
Nanomedicine is the medical application of nanotechnology. It covers areas such as nanoparticle drug delivery and possible future applications of molecular nanotechnology (MNT) and nanovaccinology. Current problems for nanomedicine involve understanding the issues related to toxicity and environmental impact of nanoscale materials Nanomedicine research is directly funded, with the US National Institutes of Health in 2005 funding a five-year plan to set up four nanomedicine centers. In April 2006, the journal Nature Materials estimated that 130 nanotech-based drugs and delivery systems were being developed worldwide
In the near future, advancement in nanomedicine will deliver a valuable set of research tools and clinically helpful devices. The National Nanotechnology Initiative expects new commercial applications in the pharmaceutical industry that will include advanced drug delivery systems, new therapies, and in vivo imaging. The most important innovations are taking place in drug delivery which involves developing nanoscale particles or molecules to improve bioavailability. Bioavailability refers to the presence of drug molecules where they are needed in the body and where they will do the most good. Drug delivery focuses on maximizing bioavailability both at specific places in the body and over a period of time. Over 65 billion dollars is wasted every year because of poor bioavailability. In vivo imaging is another area where tools and devices are being developed. Using nanoparticle contrast agents, images such as ultrasound and MRI have a favorable distribution and improved contrast. The new therapies and surgeries that are being developed might be effective in treating illnesses and diseases such as cancer. Finally, a shift from the possible to the potential will be made when nanorobots such as neuro-electronic interfaces and cell repair machines are discussed. Drug delivery systems, lipid- or polymer-based nanoparticles, can be designed to improve the pharmacological and therapeutic properties of drugs. The strength of drug delivery systems is their ability to alter the pharmacokinetics and biodistribution of the drug. Nanoparticles have unusual properties that can be used to improve drug delivery. Where larger particles would have been cleared from the body, cells take up these nanoparticles because of their size. Complex drug delivery mechanisms are being developed, including the ability to get drugs through cell walls and into cells. Efficiency is important because many diseases depend upon processes within the cell and can only be impeded by drugs that make their way into the cell. Triggered response is one way for drug molecules to be used more efficiently. Drugs are placed in the body and only activate on encountering a particular signal. For example, a drug with poor solubility will be replaced by a drug delivery system where both hydrophilic and hydrophobic environments exist, improving the solubility. Also, a drug may cause tissue damage, but with drug delivery, regulated drug release can eliminate the problem. If a drug is cleared too quickly from the body, this could force a patient to use high doses, but with drug delivery systems clearance can be reduced by altering the pharmacokinetics of the drug. Poor biodistribution is a problem that can affect normal tissues through widespread distribution, but the particulates from drug delivery systems lower the volume of distribution and reduce the effect on non-target tissue. Potential nanodrugs will work by very specific and well-understood mechanisms, one of the major impacts of nanotechnology and nanoscience will be in leading development of completely new drugs with more useful behavior and less side effects.
In the near future, advancement in nanomedicine will deliver a valuable set of research tools and clinically helpful devices. The National Nanotechnology Initiative expects new commercial applications in the pharmaceutical industry that will include advanced drug delivery systems, new therapies, and in vivo imaging. The most important innovations are taking place in drug delivery which involves developing nanoscale particles or molecules to improve bioavailability. Bioavailability refers to the presence of drug molecules where they are needed in the body and where they will do the most good. Drug delivery focuses on maximizing bioavailability both at specific places in the body and over a period of time. Over 65 billion dollars is wasted every year because of poor bioavailability. In vivo imaging is another area where tools and devices are being developed. Using nanoparticle contrast agents, images such as ultrasound and MRI have a favorable distribution and improved contrast. The new therapies and surgeries that are being developed might be effective in treating illnesses and diseases such as cancer. Finally, a shift from the possible to the potential will be made when nanorobots such as neuro-electronic interfaces and cell repair machines are discussed. Drug delivery systems, lipid- or polymer-based nanoparticles, can be designed to improve the pharmacological and therapeutic properties of drugs. The strength of drug delivery systems is their ability to alter the pharmacokinetics and biodistribution of the drug. Nanoparticles have unusual properties that can be used to improve drug delivery. Where larger particles would have been cleared from the body, cells take up these nanoparticles because of their size. Complex drug delivery mechanisms are being developed, including the ability to get drugs through cell walls and into cells. Efficiency is important because many diseases depend upon processes within the cell and can only be impeded by drugs that make their way into the cell. Triggered response is one way for drug molecules to be used more efficiently. Drugs are placed in the body and only activate on encountering a particular signal. For example, a drug with poor solubility will be replaced by a drug delivery system where both hydrophilic and hydrophobic environments exist, improving the solubility. Also, a drug may cause tissue damage, but with drug delivery, regulated drug release can eliminate the problem. If a drug is cleared too quickly from the body, this could force a patient to use high doses, but with drug delivery systems clearance can be reduced by altering the pharmacokinetics of the drug. Poor biodistribution is a problem that can affect normal tissues through widespread distribution, but the particulates from drug delivery systems lower the volume of distribution and reduce the effect on non-target tissue. Potential nanodrugs will work by very specific and well-understood mechanisms, one of the major impacts of nanotechnology and nanoscience will be in leading development of completely new drugs with more useful behavior and less side effects.
Biomarker
Biomarker discovery is the process by which biomarkers are discovered. It is a medical term. Many commonly used blood tests in medicine are biomarkers. The way that these tests have been found can be seen as biomarker discovery. However, their identification has mostly been a one-at-a time approach. Many of these well-known tests have been identified based on clear biological insight, from physiology or biochemistry. This means that only a few markers at a time have been considered. One example of this way of biomarker discovery is the use of injections of inulin for measuring kidney function. From this, one discovered a naturally occurring molecule, creatinine, that enabled the same measurements to be made easily without injections. This can be seen as a serial process.
The recent interest in biomarker discovery is because new molecular biologic techniques promise to find relevant markers rapidly, without detailed insight into mechanisms of disease. By screening many possible biomolecules at a time, a parallel approach can be tried. Genomics and proteomics are some technologies that are used in this process. Significant technical difficulties remain. There is considerable interest in biomarker discovery from the pharmaceutical industry. Blood test or other biomarkers could serve as intermediate markers of disease in clinical trials, and also be possible drug targets.
Source:>http://bioinformations.info/nano-bioengineering.html
Friday, June 5, 2009
Your doctor's on your Web cam
The new house call: Your doctor's at the door, er, on your Web cam
Too busy to go to the doctor? Unfortunately, it's the rare one who makes house calls these days. But how about the next best thing? The Hawaii Medical Service Association (HMSA) next week is set to begin offering doctor consults via Web cam, an emerging form of telemedicine.
The association (the state's Blue Cross Blue Shield insurance provider) will offer the 10-minute Internet visits through American Well, a Boston-based company that provides video conferencing and electronic medical record-keeping to doctors and patients, the New York Times reports today. HMSA is its first customer, the Times says. “It’s a better iteration on, ‘Take two aspirin and call me in the morning,’” Robert Sussman, a family practice doctor on Oahu, tells the newspaper. “We can’t lay on the hands, but we can lay on the eyes and get a better feel" than from a simple phone consult.
Telemedicine – by Internet or phone – is touted as a convenience for folks who don’t want to wait days for a doctor’s appointment, who don’t live near a physician, and who are willing to pay out of pocket for the perk of a visit on their own schedule. The cost is a $10 co-pay for HMSA members and $45 for non-members. Proponents say doctors can take care of about half of medical problems without a face-to-face workup.
While some traditional doctors consult with regular patients by phone or email, many don’t, says Jay Parkinson, a primary-care doctor who runs the telemedicine business Hello Health in Brooklyn, N.Y. “Doctors don’t get paid for communications – only office visits and procedures,” Parkinson tells ScientificAmerican.com. “Nowadays doctors see so many patients – 30, 40, 50 patients a day. When the day is over, they can’t sit down and answer 50 emails for free.”
Hello Health's fees are based on the length and type of visit: $100-to-$200 for an office visit versus $50-to-$100 for video, instant message and phone visits. (If the latter leads to an office visit or house call, that charge is applied to the cost of the in-person exam.) A similar service, Doctokr in Vienna, Va., a suburb of Washington, D.C., also provides scaled fees for phone, office and house consults. Both businesses require patients to be seen at least once in person.
Internet-based medicine is still in its infancy, Parkinson says, and whether it’s ideally practiced via Web cam or by text-based instant messaging or email is an open question. Just 16 percent of Internet users have used a Web cam, according to a 2005 report by the Pew Internet & American Life Project.
Whatever its form, telemedicine is really best suited for relatively minor problems, Parkinson says, and to determine whether further medical attention or lab tests are needed to check out, say, swollen lymph nodes or whether a sore throat may be strep. “We target someone who communicates and transacts online, and that’s everyone under 65 these days,” he says. But, a doctor really needs "to have a [previous] relationship with someone. Otherwise, it’s sort of reckless.”
Source>Scientific American
Too busy to go to the doctor? Unfortunately, it's the rare one who makes house calls these days. But how about the next best thing? The Hawaii Medical Service Association (HMSA) next week is set to begin offering doctor consults via Web cam, an emerging form of telemedicine.
The association (the state's Blue Cross Blue Shield insurance provider) will offer the 10-minute Internet visits through American Well, a Boston-based company that provides video conferencing and electronic medical record-keeping to doctors and patients, the New York Times reports today. HMSA is its first customer, the Times says. “It’s a better iteration on, ‘Take two aspirin and call me in the morning,’” Robert Sussman, a family practice doctor on Oahu, tells the newspaper. “We can’t lay on the hands, but we can lay on the eyes and get a better feel" than from a simple phone consult.
Telemedicine – by Internet or phone – is touted as a convenience for folks who don’t want to wait days for a doctor’s appointment, who don’t live near a physician, and who are willing to pay out of pocket for the perk of a visit on their own schedule. The cost is a $10 co-pay for HMSA members and $45 for non-members. Proponents say doctors can take care of about half of medical problems without a face-to-face workup.
While some traditional doctors consult with regular patients by phone or email, many don’t, says Jay Parkinson, a primary-care doctor who runs the telemedicine business Hello Health in Brooklyn, N.Y. “Doctors don’t get paid for communications – only office visits and procedures,” Parkinson tells ScientificAmerican.com. “Nowadays doctors see so many patients – 30, 40, 50 patients a day. When the day is over, they can’t sit down and answer 50 emails for free.”
Hello Health's fees are based on the length and type of visit: $100-to-$200 for an office visit versus $50-to-$100 for video, instant message and phone visits. (If the latter leads to an office visit or house call, that charge is applied to the cost of the in-person exam.) A similar service, Doctokr in Vienna, Va., a suburb of Washington, D.C., also provides scaled fees for phone, office and house consults. Both businesses require patients to be seen at least once in person.
Internet-based medicine is still in its infancy, Parkinson says, and whether it’s ideally practiced via Web cam or by text-based instant messaging or email is an open question. Just 16 percent of Internet users have used a Web cam, according to a 2005 report by the Pew Internet & American Life Project.
Whatever its form, telemedicine is really best suited for relatively minor problems, Parkinson says, and to determine whether further medical attention or lab tests are needed to check out, say, swollen lymph nodes or whether a sore throat may be strep. “We target someone who communicates and transacts online, and that’s everyone under 65 these days,” he says. But, a doctor really needs "to have a [previous] relationship with someone. Otherwise, it’s sort of reckless.”
Source>Scientific American
Who Needs a Doctor
When There's a Robot in the House, er, Hospital? [Slide Show]A Florida trauma center tests the use of a mobile robot to deliver telemedicine
By Larry Greenemeier
Scientificamerican:December 4, 2008
Telemedicine has caught on over the past several years as an effective way to bring patients and specialists together via the magic of video conferencing. Unfortunately, most telemedicine setups require the patient to be in a room equipped with a computer, camera, microphone and monitor, so that specialists can remotely assess his or her condition. Could robots be the answer, providing both patient care and a view for specialists checking in from afar?
The William Lehman Injury Research Center (WLIRC) in Miami for a year has been experimenting with a budding type of telemedicine that uses a robot to let videoconferencing go mobile, allowing a specialist working from a remote location to see a patient (and for the patient to see the physician) from the moment he or she checks in for surgery through recovery.
A typical scenario would unfold as such: A patient is brought to the Ryder Trauma Center at the University of Miami's Jackson Memorial Hospital (where the WLIRC doctors work) by ambulance or helicopter. While the patient is en route, the trauma center checks to see if there is a specialist on site who can treat the patient's specific injuries. If there are none available and the specialist on call is unable to make it to Ryder in time, staff at the center wheel out the RP-7, made by InTouch Technologies, Inc., a Santa Barbara, Calif., medical robotics technology company. Once a specialist is located, he or she uses a laptop or PC to remotely connect via wireless broadband with the robot. After the connection is made, the specialist is able to control the robot's movement, possibly even meeting the patient at the door. From there, the specialist can autonomously drive the robot to operating rooms, intensive care units and patients' bedsides so he or she can monitor those patients as well as instruct nurses and residents.
View a slideshow of the RP-7 in action
The WLIRC doctors and physicians from the U.S. Army's Trauma Training Center (working at the Ryder Trauma Center) have been testing the RP-7, to see if the above scenario is realistic. The 200-pound, (90.7-kilogram) 67-inch- (1.7-meter-) tall metal medical man glides along on three spherical balls (rather than wheels) at a top speed of four miles (6.4 kilometers) per hour. As the Army's Web site points out, it "looks vaguely like one of the Daleks [robots] from Doctor Who with a view screen mounted on top."
Ryder is the only "level 1" trauma center in Miami–Dade County, which makes it difficult to find specialists to weigh in on all cases, particularly within the critical first 60 minutes after an injury, says Jeffrey Augenstein, WLIRC's director and the RP-7 project's principal investigator. "There is a shortage of trauma specialists in this country," he says. "You need to have a plan B to bring expertise from the outside to the point of care, where decisions often involve life and death."
Source>http://www.scientificamerican.com/article.cfm?id=robot-telemedicine
By Larry Greenemeier
Scientificamerican:December 4, 2008
Telemedicine has caught on over the past several years as an effective way to bring patients and specialists together via the magic of video conferencing. Unfortunately, most telemedicine setups require the patient to be in a room equipped with a computer, camera, microphone and monitor, so that specialists can remotely assess his or her condition. Could robots be the answer, providing both patient care and a view for specialists checking in from afar?
The William Lehman Injury Research Center (WLIRC) in Miami for a year has been experimenting with a budding type of telemedicine that uses a robot to let videoconferencing go mobile, allowing a specialist working from a remote location to see a patient (and for the patient to see the physician) from the moment he or she checks in for surgery through recovery.
A typical scenario would unfold as such: A patient is brought to the Ryder Trauma Center at the University of Miami's Jackson Memorial Hospital (where the WLIRC doctors work) by ambulance or helicopter. While the patient is en route, the trauma center checks to see if there is a specialist on site who can treat the patient's specific injuries. If there are none available and the specialist on call is unable to make it to Ryder in time, staff at the center wheel out the RP-7, made by InTouch Technologies, Inc., a Santa Barbara, Calif., medical robotics technology company. Once a specialist is located, he or she uses a laptop or PC to remotely connect via wireless broadband with the robot. After the connection is made, the specialist is able to control the robot's movement, possibly even meeting the patient at the door. From there, the specialist can autonomously drive the robot to operating rooms, intensive care units and patients' bedsides so he or she can monitor those patients as well as instruct nurses and residents.
View a slideshow of the RP-7 in action
The WLIRC doctors and physicians from the U.S. Army's Trauma Training Center (working at the Ryder Trauma Center) have been testing the RP-7, to see if the above scenario is realistic. The 200-pound, (90.7-kilogram) 67-inch- (1.7-meter-) tall metal medical man glides along on three spherical balls (rather than wheels) at a top speed of four miles (6.4 kilometers) per hour. As the Army's Web site points out, it "looks vaguely like one of the Daleks [robots] from Doctor Who with a view screen mounted on top."
Ryder is the only "level 1" trauma center in Miami–Dade County, which makes it difficult to find specialists to weigh in on all cases, particularly within the critical first 60 minutes after an injury, says Jeffrey Augenstein, WLIRC's director and the RP-7 project's principal investigator. "There is a shortage of trauma specialists in this country," he says. "You need to have a plan B to bring expertise from the outside to the point of care, where decisions often involve life and death."
Source>http://www.scientificamerican.com/article.cfm?id=robot-telemedicine
Brain Rerouting signal
Skip the Robotics: Paralyzed Limbs Come to Life
with New Connection to Brain
Rerouting signal from neuron to muscle allows the brain to move deadened limbs
By Sharon Guynup
From the February 2009
Scientific American
Scientists have forged a promising avenue in the quest to restore mobility to patients paralyzed by disease or injury. Researchers at the University of Washington devised a way to reroute signals from the brain’s motor cortex to trigger hand movement directly.
For the past decade researchers have focused on “listening to” and decoding the specific brain signals that trigger muscle movement, using a wall of computers running complex algorithms to translate that brain activity into instructions for moving a computer cursor or a robotic arm or leg.
The new approach simplifies the process. Engineers and neuroscientists restored use of a monkey’s immobilized limb by replacing the lost biological connection. “Rather than decoding intention, we’ve just established a connection and encouraged the monkey to learn how to act on it,” says Chet Moritz, a neurophysiologist, who pioneered the work with fellow Washington professor Eberhard Fetz.
They trained macaques to play a simple video game using a joystick. Then they ran a wire from a single neuron in the animals’ motor cortex to a desktop computer. The electrical impulse from that cell was amplified by the computer and transmitted along another wire to one of the primates’ arm muscles, which had been temporarily anesthetized.
Within minutes, the monkeys learned to control wrist movements with their thoughts, moving the joystick left or right to match targets on a computer screen.
The surprise, Moritz says, was that any neuron within that general region of the brain could learn to stimulate wrist muscles—regardless of whether the neuron was originally involved in that specific movement.
“Monkeys can rapidly learn to change neuron activity, in this case to generate movement, much like humans can change heart rate activity with biofeedback,” Fetz explains. This control necessitated conscious attention; making such movements subconsciously would require repetitive training, much like learning a sport.
The long-term goal is to develop a miniaturized, implantable neuroprosthetic device that would enable paralyzed patients to move their own paralyzed limbs. Fetz has already taken the next step, developing a cell phone–size neurochip that can be linked to a microprocessor, small enough for monkeys to carry implanted in their head.
Many hurdles remain. It is difficult to record from the same neuron for a long period. Within days or weeks, scar tissue walls off electrodes, interrupting transmission. Guiding electrodes to new locations with tiny motors might mitigate that problem. Providing a decades-long power supply is also a challenge. Biocompatibility is another issue; fully implanting such a system under the skin presents a huge infection risk. And crucial questions exist: Can this model be scaled up to stimulate multiple neurons that trigger multiple muscles? How flexible is the brain in reassigning new functions to neurons?
The team hopes to restore arm movements in the near term—and ultimately to restore paraplegics’ ability to walk. But clinical trials remain perhaps a decade away.
Source>http://www.scientificamerican.com/article.cfm?id=robotics-provide-hope
with New Connection to Brain
Rerouting signal from neuron to muscle allows the brain to move deadened limbs
By Sharon Guynup
From the February 2009
Scientific American
Scientists have forged a promising avenue in the quest to restore mobility to patients paralyzed by disease or injury. Researchers at the University of Washington devised a way to reroute signals from the brain’s motor cortex to trigger hand movement directly.
For the past decade researchers have focused on “listening to” and decoding the specific brain signals that trigger muscle movement, using a wall of computers running complex algorithms to translate that brain activity into instructions for moving a computer cursor or a robotic arm or leg.
The new approach simplifies the process. Engineers and neuroscientists restored use of a monkey’s immobilized limb by replacing the lost biological connection. “Rather than decoding intention, we’ve just established a connection and encouraged the monkey to learn how to act on it,” says Chet Moritz, a neurophysiologist, who pioneered the work with fellow Washington professor Eberhard Fetz.
They trained macaques to play a simple video game using a joystick. Then they ran a wire from a single neuron in the animals’ motor cortex to a desktop computer. The electrical impulse from that cell was amplified by the computer and transmitted along another wire to one of the primates’ arm muscles, which had been temporarily anesthetized.
Within minutes, the monkeys learned to control wrist movements with their thoughts, moving the joystick left or right to match targets on a computer screen.
The surprise, Moritz says, was that any neuron within that general region of the brain could learn to stimulate wrist muscles—regardless of whether the neuron was originally involved in that specific movement.
“Monkeys can rapidly learn to change neuron activity, in this case to generate movement, much like humans can change heart rate activity with biofeedback,” Fetz explains. This control necessitated conscious attention; making such movements subconsciously would require repetitive training, much like learning a sport.
The long-term goal is to develop a miniaturized, implantable neuroprosthetic device that would enable paralyzed patients to move their own paralyzed limbs. Fetz has already taken the next step, developing a cell phone–size neurochip that can be linked to a microprocessor, small enough for monkeys to carry implanted in their head.
Many hurdles remain. It is difficult to record from the same neuron for a long period. Within days or weeks, scar tissue walls off electrodes, interrupting transmission. Guiding electrodes to new locations with tiny motors might mitigate that problem. Providing a decades-long power supply is also a challenge. Biocompatibility is another issue; fully implanting such a system under the skin presents a huge infection risk. And crucial questions exist: Can this model be scaled up to stimulate multiple neurons that trigger multiple muscles? How flexible is the brain in reassigning new functions to neurons?
The team hopes to restore arm movements in the near term—and ultimately to restore paraplegics’ ability to walk. But clinical trials remain perhaps a decade away.
Source>http://www.scientificamerican.com/article.cfm?id=robotics-provide-hope
artificial Heart valve
April 25, 2009
Artificial Valves That Lend Hearts a Helping Hand
For the past five decades, artificial heart-valve designs have evolved to successfully replace natural valves, which often begin to leak or harden over time
By Amber Dance
The heart relies on four valves that act as one-way gates, controlling blood flow out of each of the heart's four chambers. The mitral valve between the two left chambers of the heart has two leaflets, or cusps; the tricuspid, pulmonary and aortic valves each have three. The leaflets swing open and shut like saloon doors with every beat, maintaining a steady blood supply. (A person's heart generally beats 80 million times a year and five to six billion times over the course of a normal lifetime, according to Irvine, Calif.–based valve producer Edwards Lifesciences.)
> Slide Show: Artificial heart valve improvements over the past 50 years
As comedian and actor Robin Williams, 57, and 83-year-old former first lady Barbara Bush found out recently, in many cases, the valves don't last a lifetime; some become leaky. Called a regurgitating valve, this allows pumped blood to wash back into the heart. Others pick up calcium from the blood, eventually becoming hardened, restricting blood flow (a condition known as stenosis). When the body does not receive enough blood, a person can experience symptoms such as shortness of breath. Aortic and mitral valves most commonly require treatment. Once symptoms such as lightheadedness and blackouts arise, a person with an untreated faulty aortic valve has a 50 percent chance of dying within six months, says Eugene Grossi, a professor of cardiothoracic surgery at New York University School of Medicine and director of cardiac surgery research.That means that for thousands of Americans, an artificial heart valve fashioned from tissue-thin flaps is all that stands between health and heart failure. About 140,000 Americans go under the knife for valve replacement or repair every year, according to Toronto-based Millennium Research Group, a firm that tracks the medical device, pharmaceutical and biotechnology industries.Doctors have developed several stand-ins for the natural tissue that can regulate blood flow without missing a beat. "Heart valves are the one device that when you get it in and it's successful, you add 10 or 15 years to their life," says Donald Bobo, vice president for heart valve therapy at Edwards Lifesciences. Edwards—along with Saint Jude Medical in Saint Paul, Minn., and Minneapolis-based Medtronic, Inc.—is a top provider of artificial valves worldwide, Bobo says. Sorin Group in Milan, Italy, also has a share in the global heart valve therapy market, estimated to be worth $1.6 billion in 2008, according to Edwards market estimates.Valve technology took off in 1958 when engineer and Edwards founder Miles "Lowell" Edwards applied his experience designing hydraulic debarking methods for the lumber industry and a fuel-injection system for World War II aircraft to the medical arena. Working with cardiothoracic surgeon Albert Starr, the two developed a valve that Starr could use in his ailing patients. Surgeons implanted the Starr-Edwards artificial valve, designed in Edward's backyard workshop, for the first time in 1960. Although that first patient died shortly after receiving the device, the second survived for 10 more years before dying from a fall off a ladder.People tried dozens of different designs in the ensuing decades, says Ajit Yoganathan, a biomedical engineer who studies valves at the Georgia Institute of Technology in Atlanta. "Most of them were developed in someone's garage or someone's basement." The technology has evolved from a caged-ball design into valves with artificial flaps, pig valves processed for human use, and hand-sewn biologic valves made from cow tissue."All of these valves have analogues in hydraulics, pipelines, aviation, automobiles," Bobo says. But the human body presents special challenges. "Blood ends up being a pretty different environment compared to oil or gas," he adds. The lipids in blood can destroy synthetic materials; tissue valves are subject to the same wear and tear and calcification that natural valves are."There is still room for improvement," such as better materials, Yoganathan says. He would also like to see small valves available to children with congenital heart defects. The next development likely to hit the U.S. market is valves that can be implanted without open heart surgery.
Source:>http://www.scientificamerican.com/article.cfm?id=artificial-heart-valves
Artificial Valves That Lend Hearts a Helping Hand
For the past five decades, artificial heart-valve designs have evolved to successfully replace natural valves, which often begin to leak or harden over time
By Amber Dance
The heart relies on four valves that act as one-way gates, controlling blood flow out of each of the heart's four chambers. The mitral valve between the two left chambers of the heart has two leaflets, or cusps; the tricuspid, pulmonary and aortic valves each have three. The leaflets swing open and shut like saloon doors with every beat, maintaining a steady blood supply. (A person's heart generally beats 80 million times a year and five to six billion times over the course of a normal lifetime, according to Irvine, Calif.–based valve producer Edwards Lifesciences.)
> Slide Show: Artificial heart valve improvements over the past 50 years
As comedian and actor Robin Williams, 57, and 83-year-old former first lady Barbara Bush found out recently, in many cases, the valves don't last a lifetime; some become leaky. Called a regurgitating valve, this allows pumped blood to wash back into the heart. Others pick up calcium from the blood, eventually becoming hardened, restricting blood flow (a condition known as stenosis). When the body does not receive enough blood, a person can experience symptoms such as shortness of breath. Aortic and mitral valves most commonly require treatment. Once symptoms such as lightheadedness and blackouts arise, a person with an untreated faulty aortic valve has a 50 percent chance of dying within six months, says Eugene Grossi, a professor of cardiothoracic surgery at New York University School of Medicine and director of cardiac surgery research.That means that for thousands of Americans, an artificial heart valve fashioned from tissue-thin flaps is all that stands between health and heart failure. About 140,000 Americans go under the knife for valve replacement or repair every year, according to Toronto-based Millennium Research Group, a firm that tracks the medical device, pharmaceutical and biotechnology industries.Doctors have developed several stand-ins for the natural tissue that can regulate blood flow without missing a beat. "Heart valves are the one device that when you get it in and it's successful, you add 10 or 15 years to their life," says Donald Bobo, vice president for heart valve therapy at Edwards Lifesciences. Edwards—along with Saint Jude Medical in Saint Paul, Minn., and Minneapolis-based Medtronic, Inc.—is a top provider of artificial valves worldwide, Bobo says. Sorin Group in Milan, Italy, also has a share in the global heart valve therapy market, estimated to be worth $1.6 billion in 2008, according to Edwards market estimates.Valve technology took off in 1958 when engineer and Edwards founder Miles "Lowell" Edwards applied his experience designing hydraulic debarking methods for the lumber industry and a fuel-injection system for World War II aircraft to the medical arena. Working with cardiothoracic surgeon Albert Starr, the two developed a valve that Starr could use in his ailing patients. Surgeons implanted the Starr-Edwards artificial valve, designed in Edward's backyard workshop, for the first time in 1960. Although that first patient died shortly after receiving the device, the second survived for 10 more years before dying from a fall off a ladder.People tried dozens of different designs in the ensuing decades, says Ajit Yoganathan, a biomedical engineer who studies valves at the Georgia Institute of Technology in Atlanta. "Most of them were developed in someone's garage or someone's basement." The technology has evolved from a caged-ball design into valves with artificial flaps, pig valves processed for human use, and hand-sewn biologic valves made from cow tissue."All of these valves have analogues in hydraulics, pipelines, aviation, automobiles," Bobo says. But the human body presents special challenges. "Blood ends up being a pretty different environment compared to oil or gas," he adds. The lipids in blood can destroy synthetic materials; tissue valves are subject to the same wear and tear and calcification that natural valves are."There is still room for improvement," such as better materials, Yoganathan says. He would also like to see small valves available to children with congenital heart defects. The next development likely to hit the U.S. market is valves that can be implanted without open heart surgery.
Source:>http://www.scientificamerican.com/article.cfm?id=artificial-heart-valves
Nanoparticles Home in on Brain Cancer
Nanoparticles Home in on Brain Cancer
By Nikhil Swaminathan
November 17, 2006
Call them laser-guided smart bombs for brain tumors. Researchers at the University of Michigan announced the testing of a drug delivery system that involves drug-toting nanoparticles and a guiding peptide to target cancerous cells in the brain. Their study finds that via this method more of the drug can be delivered to a tumor's general vicinity. They report their findings in the November 15 issue of Clinical Cancer Research.
The researchers used a pharmaceutical called Photofrin, which is photodynamic, meaning it is activated by a laser after it has entered the bloodstream. As its primary side effect, the drug renders patients photosensitive, and they must remain out of bright sunlight and even unshaded lamps for up to 30 days after receiving treatment. Despite this major drawback, Photofrin is used in the treatment of esophageal, bladder and skin cancers. But their novel delivery system, which relies on the intravenous delivery of 40-nanometer-wide particles to carry the drug, may actually avoid much of the photosensitivity, because less Photofrin circulates in the bloodstream thanks to a peptide called F3. A sequence of 31 amino acids broken off of the protein HMGN2 (high mobility group protein 2), F3 has the ability to penetrate cell membranes. "This peptide acts as a "zip code" in that it enables the binding of the nanoparticles only to blood vessels within the tumor and not normal blood vessels," says Alnawaz Rehemtulla, a radiologist and environmental health scientist who co-authored the study. F3 can detect the expression of a protein called nucleolin, which is a marker on the surface of tumor cells.
Another problem the researchers avoided was having to deliver their medicine in such a way that it could cross the blood-brain barrier, which keeps many substances from entering the brain from the bloodstream. Typical chemotherapies must penetrate this shield to treat tumors. In this case, however, the nontoxic polyacrylamide particles didn't have to cross over via the bloodstream. "The nanoparticles do not need to cross the blood-brain barrier as they were specifically designed to target the blood vessel cells within the tumor," explains radiologist Brian Ross, one of the study's authors. "The treatment should be thought of as an antivascular treatment thereby shutting off the tumor blood flow resulting in the death of the tumor cells through starvation of oxygen and energy sources."
To test the delivery method, researchers divided 34 rats--all who received injections of cancerous cells into their brains--into different groups. Those that received no treatment or got only the laser fared poorly, dying on average within 8.5 days. Those that got Photofrin either intravenously or encapsulated in nanoparticles had a median survival time of 13 days. The group that got F3 with the Photofrin-carrying nanoparticles came through the best: they lived for, on average, 33 days; three of the five in this grouping lived for 60 days, and two of those three appeared tumor-free after six months. By using iron oxide as a contrast agent--to more easily detect where the nanoparticles ended up via MRI--the group determined that twice as much drug with the F3 peptide attached reached the tumor site--10 percent of the total amount administered--compared with when nontargeted nanoparticles were injected.
Ross says that based on the success of the study, the team is investigating if this delivery technology will work for nonphotodynamic therapies. Rehemtulla adds that if other FDA-approved chemotherapeutic agents reach their targets as successfully as Photofrin did, "then we will have developed a way to make cancer drugs more 'tumor-specific,' because they will only get into tumor vasculature and not normal vasculature. This will spare patients from normal tissue toxicity that is commonly associated with almost all chemotherapy."
Source>http://www.scientificamerican.com/article.cfm?id=nanoparticles-home-in-on
By Nikhil Swaminathan
November 17, 2006
Call them laser-guided smart bombs for brain tumors. Researchers at the University of Michigan announced the testing of a drug delivery system that involves drug-toting nanoparticles and a guiding peptide to target cancerous cells in the brain. Their study finds that via this method more of the drug can be delivered to a tumor's general vicinity. They report their findings in the November 15 issue of Clinical Cancer Research.
The researchers used a pharmaceutical called Photofrin, which is photodynamic, meaning it is activated by a laser after it has entered the bloodstream. As its primary side effect, the drug renders patients photosensitive, and they must remain out of bright sunlight and even unshaded lamps for up to 30 days after receiving treatment. Despite this major drawback, Photofrin is used in the treatment of esophageal, bladder and skin cancers. But their novel delivery system, which relies on the intravenous delivery of 40-nanometer-wide particles to carry the drug, may actually avoid much of the photosensitivity, because less Photofrin circulates in the bloodstream thanks to a peptide called F3. A sequence of 31 amino acids broken off of the protein HMGN2 (high mobility group protein 2), F3 has the ability to penetrate cell membranes. "This peptide acts as a "zip code" in that it enables the binding of the nanoparticles only to blood vessels within the tumor and not normal blood vessels," says Alnawaz Rehemtulla, a radiologist and environmental health scientist who co-authored the study. F3 can detect the expression of a protein called nucleolin, which is a marker on the surface of tumor cells.
Another problem the researchers avoided was having to deliver their medicine in such a way that it could cross the blood-brain barrier, which keeps many substances from entering the brain from the bloodstream. Typical chemotherapies must penetrate this shield to treat tumors. In this case, however, the nontoxic polyacrylamide particles didn't have to cross over via the bloodstream. "The nanoparticles do not need to cross the blood-brain barrier as they were specifically designed to target the blood vessel cells within the tumor," explains radiologist Brian Ross, one of the study's authors. "The treatment should be thought of as an antivascular treatment thereby shutting off the tumor blood flow resulting in the death of the tumor cells through starvation of oxygen and energy sources."
To test the delivery method, researchers divided 34 rats--all who received injections of cancerous cells into their brains--into different groups. Those that received no treatment or got only the laser fared poorly, dying on average within 8.5 days. Those that got Photofrin either intravenously or encapsulated in nanoparticles had a median survival time of 13 days. The group that got F3 with the Photofrin-carrying nanoparticles came through the best: they lived for, on average, 33 days; three of the five in this grouping lived for 60 days, and two of those three appeared tumor-free after six months. By using iron oxide as a contrast agent--to more easily detect where the nanoparticles ended up via MRI--the group determined that twice as much drug with the F3 peptide attached reached the tumor site--10 percent of the total amount administered--compared with when nontargeted nanoparticles were injected.
Ross says that based on the success of the study, the team is investigating if this delivery technology will work for nonphotodynamic therapies. Rehemtulla adds that if other FDA-approved chemotherapeutic agents reach their targets as successfully as Photofrin did, "then we will have developed a way to make cancer drugs more 'tumor-specific,' because they will only get into tumor vasculature and not normal vasculature. This will spare patients from normal tissue toxicity that is commonly associated with almost all chemotherapy."
Source>http://www.scientificamerican.com/article.cfm?id=nanoparticles-home-in-on
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