Recent advances in Bio-medical

February 17, 2010

10 Promising Biomedical Advances in Human Embryonic Stem Cell Research

Filed under: Uncategorized — bmeforum @ 7:53 am

Since the isolation of human embryonic stem cells, or hESCs, in 1998 (see the timeline: A Brief History of Stem Cell Research), scientists around the country have made significant strides laying the groundwork for clinical treatments. In January, the FDA approved the first clinical trial for a potential therapy, a treatment for spinal cord injuries. And today, President Obama lifted the Bush administration’s restrictions on on federal funding of research involving human embryonic stem cells.

The path from discovery to cure is long, as researchers like stem cell pioneer and Science Progress adviser John Gearhart point out. But with access to federal competitive grant money for responsible, ethical research projects, scientists can continue the work that will help us fully understand human development and fulfill the promise of regenerative medicine. With today’s change in policy, that can happen here in the United States. As we look forward a bright future of scientific discovery, here’s a glance back at some major advances in human embryonic stem cell research around the world over the past few years:

January 20th, 2009: Researchers produced massive volumes of “universal donor” type O-negative blood from human embryonic stem cells, potentially making blood donation a thing of the past.

December 5th, 2008: Harvard scientists created spinal motor neurons from hESCs, and were able to replicate the ALS, or Lou Gehrig’s disease, process in a Petri dish.

September 8th, 2008: Neural cells derived from hESCs showed effectiveness at reducing the clinical systems of multiple sclerosis in animals.

March 15th, 2008: Scientists developed a way to convert human embryonic stem cells into dopamine-producing nerve cells, holding great promise for therapy for Parkinson’s disease.

February 21st, 2008: Scientists at Novocell, Inc. created insulin-producing islet cells from human embryonic stem cells that effectively controlled insulin levels in diabetic mice.

January 31st, 2008: Scientists coaxed hESCs into functional hepatocytes (liver cells) that may be used for treatment of liver diseases.

September 21st, 2006: Vision was improved in rats suffering from a disease similar to age-related macular degeneration with the injection of human embryonic stem cells into the retina.

July 14th, 2006: UCLA Aids Institute researchers used hESCs to create lines of mature T-cells that could fight viruses like HIV, which destroys certain types of T-cells.

October 12th, 2005: Scientists used hESCs to create cancer-killing cells.

September 24th, 2004: Scientists in Israel derived fully functional cardiomyocytes (heart cells) from human embryonic stem cells, paving the way for hESC-derived pacemakers and heart tissue repair.

For more on a responsible and ethical stem cell research policy, see the Center for American Progress report, “A Life Sciences Crucible.”

BY: NIVEDITA, 11307023, 3rd YEAR….

USE OF MICROPROCESSOR IN PROSTHESIS

Filed under: Uncategorized — bmeforum @ 7:50 am

In recent years, the use of vacuum technology in which the prosthesis is attached to limb using a suction-like method has allowed amputees to remain active, even competing in sporting events.

Prosthetics are available for almost every body part and for just about every condition. Amputees benefit greatly from prosthetic limbs, which help them to regain the ability to walk or use their hands. Women who have had a mastectomy can benefit from prosthetic breasts in the form of implants. People with bad hips or knees can have these replaced with prosthetic alternatives and enable them to get up and moving again. Even prosthetic heart valves are available.

Microprocessors, powered by electronic and computer technology, are nothing new to the field of prosthetics. What is fairly new, however, is the use of the technology in the lower extremities.

Prosthesis improve the life of the human being. Prosthetics help people regain control over their lives and the ability to do things for themselves. They can walk around without assistance and tie their own shoelaces. Regaining control over your life is the most often cited reason of how a prosthetic can improve the life of an amputee.

Some of the latest improvements in artificial limb prosthesis technology is the myoelectric hand, a device fitted with a computer chip that can sense when you give a brain command to grasp something. Even though a person may have lost a hand, he or she can still tie a shoelace using this prosthesis. With the aid of computer technology and digital imaging, prosthetics are fitting better, lasting longer and providing a more natural look and feel to amputees.

The C-Leg and Ossur’s power knee and Propio foot are some examples of the latest and greatest technology in prosthetics.
With microprocessor technology, electrodes are placed over the socket of the limb and the patient is trained that when they flex certain muscles, it sends a signal to the motor to do a specific motion. So the electrode picks that signal up and that, for example, causes the hand to open or close.
The technology has made impressive strides in knee technology. Whereas the traditional prosthetic knee uses a hydraulic cylinder that has to be adjusted for more or less resistance, a knee using microprocessor technology is more fluid and acts more like an anatomical knee, he said. One of things that this allows a patient to do that they couldn’t do before is walk foot over foot downstairs. Before, you would have to lock the prosthetic knee and basically drag that leg down the stairs. Even going down a hill, you would have to lock the knee in place and kind of drag the leg. So what it’s really done is allowed people to walk more naturally.

Likewise, new technology in foot prosthesis uses carbon fiber for better flexibility when moving from one gate to the next. In some cases, a prosthetic foot is able to take a reading from a non-amputated foot so that the two feet will always be in proper alignment.

In recent years, the use of vacuum technology in which the prosthesis is attached to limb using a suction-like method has allowed amputees to remain active, even competing in sporting events.

By:

TANUSHREE

!!307055

recent advance in accelerator mass spectrometry

Filed under: Uncategorized — bmeforum @ 7:49 am

The use of radioisotopes has a long history in biomedical science, and the technique of accelerator mass spectrometry (AMS), an extremely sensitive nuclear physics technique for detection of very low-abundant, stable and long-lived isotopes, has now revolutionized high-sensitivity isotope detection in biomedical research, because it allows the direct determination of the amount of isotope in a sample rather than measuring its decay, and thus the quantitative analysis of the fate of the radiolabeled probes under the given conditions. Since AMS was first used in the early 90’s for the analysis of biological samples containing enriched 14C for toxicology and cancer research, the biomedical applications of AMS to date range from in vitro to in vivo studies, including the studies of 1) toxicant and drug metabolism, 2) neuroscience, 3) pharmacokinetics, and 4) nutrition and metabolism of endogenous molecules such as vitamins. In addition, a new drug development concept that relies on the ultrasensitivity of AMS, known as human microdosing, is being used to obtain early human metabolism information of candidate drugs. These various aspects of AMS are reviewed and a perspective on future applications of AMS to biomedical research is provided

MERGING OF BIOMEDICAL WITH OPTICS:

Filed under: Uncategorized — bmeforum @ 7:48 am

The rapid growth in laser and photonic technology has resulted in new tools being proposed
and developed for use in the medical and biological sciences. Specifically, a discipline known
as biomedical optics has emerged which is providing a broad variety of optical techniques
and instruments for diagnostic, therapeutic and basic science applications. New laser sources,
detectors and measurement techniques are yielding powerful new methods for the study of
diseases on all scales, from single molecules, to specific tissues and whole organs. For example,
novel laser microscopes permit spectroscopic and force measurements to be performed on
single protein molecules; new optical devices provide information on molecular dynamics
and structure to perform ‘optical biopsy’ non-invasively and almost instantaneously; and
optical coherence tomography and diffuse optical tomography allow visualization of specific
tissues and organs. Using genetic promoters to derive luciferase expression, bioluminescence
methods can generate molecular light switches, which serve as functional indicator lights
reporting cellular conditions and responses in living animals. This technique could allow
rapid assessment of and response to the effects of anti-tumour drugs, antibiotics, or antiviral
drugs.

by

Shreya Chandrasekhar

The Future Prospects of Microbial Cellulose in Biomedical Applications

Filed under: Uncategorized — bmeforum @ 7:47 am

The Future Prospects of Microbial Cellulose in Biomedical Applications

Microbial cellulose has proven to be a remarkably versatile biomaterial and can be used in wide variety of applied scientific endeavors, such as paper products, electronics, acoustics, and biomedical devices. In fact, biomedical devices recently have gained a significant amount of attention because of an increased interest in tissue-engineered products for both wound care and the regeneration of damaged or diseased organs. Due to its unique nanostructure and properties, microbial cellulose is a natural candidate for numerous medical and tissue-engineered applications.
For example, a microbial cellulose membrane has been successfully used as a wound-healing device for severely damaged skin and as a small-diameter blood vessel replacement. The nonwoven ribbons of microbial cellulose microfibrils closely resemble the structure of native extracellullar matrices, suggesting that it could function as a scaffold for the production of many tissue-engineered constructs.
In addition, microbial cellulose membranes, having a unique nanostructure, could have many other uses in wound healing and regenerative medicine, such as guided tissue regeneration (GTR), periodontal treatments, or as a replacement for dura mater (a membrane that surrounds brain tissue). In effect, microbial cellulose could function as a scaffold material for the regeneration of a wide variety of tissues, showing that it could eventually become an excellent platform technology for medicine. If microbial cellulose can be successfully mass produced, it will eventually become a vital biomaterial and will be used in the creation of a wide variety of medical devices and consumer products.
Rapid progress has been made in recent years in the field of biomedical materials, which utilize both natural and synthetic polymers and which can be used in a variety of applications, including wound closure, drug delivery systems, novel vascular grafts, or scaffolds for in vitro or in vivo tissue engineering. Several microbially derived polysaccharides (i.e., hyaluronic acid, dextran, alginate, scleroglucan) have interesting physical and biological properties and are particularly useful in various biomedical applications. Microbial cellulose (MC), a polysaccharide synthesized in abundance by Acetobacter xylinum, has already been used quite successfully in wound-healing applications, proving that it could become a high-value product in the field of biotechnology.
Traditional plant-originated cellulose and cellulose-based materials, usually in the form of woven cotton gauze dressings, have been used in medical applications for many years and are mainly utilized to stop bleeding. Even though this conventional dressing is not ideal, its use continues to be widespread. These cotton gauzes, consisting of an oxidized form of regenerated plant cellulose, were developed by Frantz during World War II, and have been successfully used as a hemostatic agent as well as an adhesion barrier. Another product, a plant cellulose sponge, has an established clinical application in wound-healing research as a component which stimulates granulation tissue in the wound bed after injury. In addition, several studies described the implantation of regenerated cellulose hydrogels and revealed their biocompatibility with connective tissue formation and long-term stability. Other in vitro studies showed that regenerated cellulose hydrogels promote bone cell attachment and proliferation and are very promising materials for orthopedic applications.

Although chemically identical to plant cellulose, the cellulose synthesized by Acetobacter is characterized by a unique fibrillar nanostructure which determines its extraordinary physical and mechanical properties, characteristics which are quite promising for modern medicine and biomedical research. In this review, the structural features of microbial cellulose and its properties are discussed in relation to the current and future status of its application in medicine.

One of the main requirements of any biomedical material is that it must be biocompatible, which is the ability to remain in contact with living tissue without causing any toxic or allergic side effects. A material composed of porous plant cellulose has been shown to be biocompatible with bone tissue and hepatocytes. Research conducted on an implanted cellulose sponge showed that it can be regarded as a slowly degradable material.9 As mentioned by the same authors, this material can be considered nondegradable if used as a temporary wound coverage for a short period of time. Unlike plant-originated cellulose, microbial cellulose is free of lignin and hemicelluloses. However, microbial cellulose is treated with strong bases in order to completely remove bacterial cells embedded in the polymer net. There are several in vivo biocompatibility studies that used MC on animal models.

For example, Kolodziejczyk and Pomorski implanted pieces of microbial cellulose (1 cm in diameter) into subcutaneous pockets on rabbits and periodically examined them after 1 and 3 weeks.The implants did not cause any macroscopic inflammatory responses, and histological observations showed only a small number of giant cells and a thin layer of fibroblasts at the interface between the cellulose and the tissue. Positive results were also obtained by Oster et al. in an in vitro study using mouse fibroblasts cells. A specific in vivo biocompatibility study of microbial cellulose has also been conducted by Klemm et al., who implanted cellulose in the form of a hollow tube as an interposition segment of the carotid arteries of rats. In a recent, very systematic study by Helenius et al., pieces of microbial cellulose were implanted into rats. Those implants evaluated after 1, 4, and 12 weeks showed no macroscopic or histologic signs of inflammation and no presence of giant cells. Also, according to the authors, no chronic inflammatory responses were observed throughout the course of the studies. Instead, they observed the formation of new blood vessels around and inside the implanted cellulose. Interestingly, the authors also noticed that cells, mostly fibroblasts, were able to significantly penetrate the more porous bottom side of a microbial cellulose membrane. The newly formed tissue, integrated with MC, contained fibroblasts and newly synthesized collagen.

Microbial Cellulose as a Scaffold For In Vitro Tissue Engineering
The difficulties encountered in repairing or replacing severely damaged skin may be resolved through a process called tissue engineering. This very promising technique involves the in vitro construction of a scaffold material, which successfully mimics the extracellular matrix of normal tissues. Cells of the desired tissue are seeded onto the scaffold which coaxes them to develop into the proper three-dimensional structure. This in vitro tissue construct can then be implanted into the affected area of the body, either as a replacement tissue or even as a replacement organ. Thus, tissue engineering could be very effective in replacing severely burned skin or in repairing chronic, nonhealing wounds, such as ulcers.
One of the key aspects of tissue engineering involves the creation of the scaffold, the three-dimensional matrix which enables the cells to develop into a fully functional tissue construct. Some scientists have proposed that the scaffold material must be biodegradable so that as the seeded cells proliferate, they will secrete their own extracellular molecules, thereby replacing the implanted material. However, this requirement is problematic due to the fact that the temporary scaffold can often degrade faster than the cells can replace it. Therefore, the solution to this problem may entail the need for a permanent scaffold material which is biocompatible, porous, and which contains the mechanical properties required for normal tissue function. Preliminary studies indicate that microbial cellulose could actually function as this ideal scaffold material for tissue engineering. If cellulose is to be used for tissue engineering, it must be biocompatible. Fortunately, studies have shown that cellulose is not harmful when it is used either as an implanted material or as a substrate for cell cultures. For instance, a study by Watanabe et al. investigated the biocompatibility of microbial cellulose by using it to produce cell cultures.87 They found that an unaltered MC membrane was not an effective substrate for cell culture or tissue engineering because the cells did not adhere to the MC surface and therefore did not proliferate. However, when the membranes were soaked in serum and electrolytic solutions such as sodium hydroxide, the cells were able to adhere and proliferate, indicating that MC membranes can function as a cell culture substrate and can be used in tissue engineering when infused with the proper substances. The authors also showed that proteins which function as adhesion factors for cells were successfully adsorbed by the MC membranes and that the high permeability of the membranes helped to diffuse the necessary nutrients, growth factors, and other products to the growing cell mass. These results are promising because they indicate that a skin tissue-engineered construct can be created with a cellulose membrane that is seeded with fibroblasts and/or keratinocytes. This construct can be created as a monolayer of cells which can then be placed directly on to the wound bed in order to provide immediate cover for the wound and to initiate the regeneration of skin tissue. Currently, in vitro and in vivo studies are in progress in order to test the efficacy of such a construct

Microbial cellulose is proving to be a very versatile material. It can be used in a wide variety of biomedical applications, from topical wound dressings to the durable scaffolds required for tissue engineering. Many scientists are already trying to develop novel biomaterials from synthetic polymers. These new materials could be used in many biomedical and biotechnological applications, such as tissue engineering, drug delivery, wound dressings, and medical implants. However, many of these synthetic polymers have their drawbacks. For instance, they often do not possess the correct mechanical properties and are usually not biocompatible.

Initial studies indicate that microbial cellulose is a better candidate for tissue engineering since it is both durable and biocompatible. In fact, microbial cellulose is a particularly interesting material for the development of many different biomedical devices. In some case, such as wound healing and organ replacement, a number of clinical studies have been performed showing its effectiveness in these areas. However, much interdisciplinary research is needed in order to bring microbial cellulose products to successful commercialization.

For example, a wide variety of mammalian cells need to be seeded onto MC membranes in order to assess their viability and proliferation. A number of clinical studies will be necessary to prove its usefulness and functionality. If microbial cellulose proves to be effective in wound repair and tissue engineering, then it will have to be produced on an industrial scale. Due to its simple fermentation process, large-scale microbial cellulose production appears to be quite feasible; however, specific engineering details need to elaborated. Also, more biochemical and genetic investigations need to be conducted in order to fully understand and improve the cellulose production process within Acetobacter.

PRIYA SHALINI KANAGARAJAH
11307031

February 16, 2010

Nanoplatforms for treating cancer and drug delivery

Filed under: Uncategorized — bmeforum @ 6:34 am

Nanotechnology is the design and assembly of submicroscopic devices called nanoparticles, which are 1-100 nanometers in diameter. Nanomedicine is the application of nanotechnology for the diagnosis and treatment of human disease. Disease-specific receptors on the surface of cells provide useful targets for nanoparticles. Because nanoparticles can be engineered from components that 1) recognize disease at the cellular level, 2) are visible on imaging studies, and 3) deliver therapeutic compounds, nanotechnology is well-suited for the diagnosis and treatment of a variety of diseases. Nanotechnology will enable earlier detection and treatment of diseases that are best treated in their initial stages, such as cancer. Advances in nanotechnology will also spur the discovery of new methods for delivery of therapeutic compounds, including genes and proteins, to diseased tissue. A myriad of nanostructured drugs with effective site-targeting can be developed by combining a diverse selection of targeting, diagnostic, and therapeutic components. Incorporating immune target specificity with nanostructures introduces a new type of treatment modality, nano-immunochemotherapy, for patients with cancer. In this review, we will discuss the development and potential applications of nanoscale platforms in medical diagnosis and treatment. To impact the care of patients with neurological diseases, advances in nanotechnology will require accelerated translation to the fields of brain mapping, CNS imaging, and nanoneurosurgery. Advances in nanoplatform, nano-imaging, and nano-drug delivery will drive the future development of nanomedicine, personalized medicine, and targeted therapy. We believe that the formation of a Science, Technology, Medicine Law-healthcare policy (STML) hub/Center, which encourages collaboration amongst universities, medical centers, US government, industry, patient advocacy groups, charitable foundations and philanthropists, could significantly facilitate such advancements and contribute to the translation of nanotechnology across medical disciplines.
J.LAHARI
11307017

CARDIOVASCULAR IMPLANTS

Filed under: Uncategorized — bmeforum @ 6:31 am

Cardiovascular and other medical implants fabricated from low-modulus Ti–Nb–Zr alloys to provide enhanced biocompatibility and hemocompatibility. The cardiovascular implants may be surface hardened by oxygen or nitrogen diffusion or by coating with a tightly adherent, hard, wear-resistant, hemocompatible ceramic coating. The cardiovascular implants include heart valves, total artificial heart implants, ventricular assist devices, vascular grafts, stents, electrical signal carrying devices such as pacemaker and neurological leads, defibrillator leads, and the like. It is contemplated that the Ti–Nb–Zr alloy can be substituted as a fabrication material for any cardiovascular implant that either comes into contact with blood thereby demanding high levels of hemocompatibility, or that is subject to microfretting, corrosion, or other wear and so that a low modulus metal with a corrosion-resistant, hardened surface would be desirable.
BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention relates to a range of cardiovascular and other implants fabricated of metallic alloys of enhanced hemocompatibility that can optionally be surface hardened to provide resistance to wear, or cold-worked or cold-drawn to reduce elastic modulus, if necessary. More specifically, the invention is of synthetic heart valves, ventricular assist devices, total artificial hearts, stents, grafts, pacers, pacemaker leads and other electrical leads and sensors, defibrillators, guide wires and catheters, and percutaneous devices fabricated of Ti–Nb–Zr alloys.

2. Description of the Related Art

Cardiovascular implants have unique blood biocompatibility requirements to ensure that the device is not rejected (as in the case of natural tissue materials for heart valves and grafts for heart transplants) or that adverse thrombogenic (clotting) or hemodynamic (blood flow) responses are avoided.

Cardiovascular implants, such as heart valves, can be fabricated from natural tissue. These bioprostheses can be affected by gradual calcification leading to the eventual stiffening and tearing of the implant.

Non-bioprosthetic implants are fabricated from materials such as pyrolytic carbon-coated graphite, pyrolytic carbon-coated titanium, stainless steel, cobalt-chrome alloys, cobalt-nickel alloys, alumina coated with polypropylene and poly-4-fluoroethylene.

For synthetic mechanical cardiovascular devices, properties such as the surface finish, flow characteristics, surface structure, charge, wear, and mechanical integrity all play a role in the ultimate success of the device. For example, typical materials used for balls and discs for heart valves include nylon, silicone, hollow titanium, TEFLON™, polyacetal, graphite, and pyrolytic carbon. Artificial hearts and ventricular assist devices are fabricated from various combinations of stainless steel, cobalt alloy, titanium, Ti-6A1-4V alloy, carbon fiber reinforced composites, polyurethanes, BIOLON™ (DuPont), HEMOTHANE™ (Sarns/3M), DACRON™, polysulfone, and other thermoplastics. Pacers, defibrillators, leads, and other similar cardiovascular implants are made of Ni–Co–Cr alloy, Co–Cr–Mo alloy, titanium, and Ti-6A1-4V alloy, stainless steel, and various biocompatible polymers. Stents and vascular grafts are often made of DACRON™ stainless steel or other polymers. Catheters and guide wires are constructed from Co–Ni or stainless steel wire with surrounding polymer walls.

One of the most significant problems encountered in heart valves, artificial hearts, assist devices, pacers, leads, stents, and other cardiovascular implants is the formation of blood clots (thrombogenesis). Protein coatings are sometimes employed to reduce the risk of blood clot formation. Heparin is also used as an anti-thrombogenic coating.

It has been found that stagnant flow regions in the devices or non-optimal materials contribute to the formation of blood clots. These stagnant regions can be minimized by optimizing surface smoothness and minimizing abrupt changes in the size of the cross section through which the blood flows or minimizing other flow interference aspects. While materials selection for synthetic heart valves, and cardiovascular implants generally, is therefore dictated by a requirement for blood compatibility to avoid the formation of blood clots (thrombus), cardiovascular implants must also be designed to optimize blood flow and wear resistance.

Even beyond the limitations on materials imposed by the requirements of blood biocompatibility and limitations to designs imposed by the need to optimize blood flow, there is a need for durable designs since it is highly desirable to avoid the risk of a second surgical procedure to implant cardiovascular devices. Further, a catastrophic failure of an implanted device will almost certainly result in the death of the patient.

The most popular current heart valve designs include the St. Jude medical tilting disc double cusp (bi-leaf) valve. This valve includes a circular ring-like pyrolytic carbon valve housing or frame and a flow control element which includes pyrolytic carbon half-discs or leaves that pivot inside the housing to open and close the valve. The two leaves have a low profile and open to 85° from the horizontal axis.

Another popular heart valve is the Medtronic-Hall Valve wherein the flow control element is a single tilting disc made of carbon coated with pyrolytic carbon which pivots over a central strut inside a solid titanium ring-like housing. A third, less popular design, is the Omniscience valve which has a single pyrolytic disc as a flow control element inside a titanium housing. Finally, the Starr-Edwards ball and cage valves have a silastic ball riding inside a cobalt-chrome alloy cage. The cage is affixed to one side of a ring-like body for attachment to the heart tissue. More recent designs include trileaflet designs and concave bileaflet designs to improve blood flow.

From the point of view of durability, heart valves made of low-thrombogenic pyrolyte carbon could fail from disc or pivot joint wear or fracture related to uneven pyrolytic carbon coating, fracture of the hall cage, disc impingement, strut wear, disc wear, hinge failure, and weld failure. A more recent heart valve, the Baruah Bileaflet is similar to the St. Jude design but opens to 80° and is made of zirconium metal. The valve has worked well over its approximately two-year history with roughly 200 implants to date in India. This performance can be partly attributed to the lower elastic modulus of zirconium (about 90 GPa) and the resultant lower contact stress severity factor (Cc of about 0.28×10 -7 m) when the disc contacts the frame. In contrast, pyrolytic constructions produce contact stress severity factors of about 0.54×10 -7 m.

Although zirconium has worked well to date and can reduce contact stress severity, zirconium metal is relatively soft and sensitive to fretting wear. This is partly due to hard, loosely attached, naturally-present passive oxide surface films (several nanometers in thickness) which can initiate microabrasion and wear of the softer underlying metal. However, this naturally present zirconium oxide passive film is thrombogenically compatible with blood and the design is acceptable from a hemodynamic standpoint. Therefore, while the zirconium bileaflet valve appears to meet at least two of the major requirements for cardiac valve implants, namely blood compatibility and design for minimum stagnant flow regions, the use of soft zirconium metal leads to a relatively high rate of fretting wear and leads to the expectation that the valve may be less durable than one produced from materials less susceptible to fretting wear. Titanium and titanium alloys present a similar limitation, and Co–Cr–Mo, stainless steel, and Co–Ni alloys have much greater elastic modulus.

There exists a need for a metallic cardiac valve implant that is biocompatible, compatible with blood in that it does not induce blood clotting and does not form a calcified scale, that is designed to minimize stagnant flow areas where blood clotting can be initiated, that has a low elastic modulus for lower contact stress severity factors to ensure resistance to wear from impact, and that has a surface that is also resistant to microabrasion thereby enhancing durability.

Heart diseases, many of which cannot be cured by conventional surgery or drug therapy, continue to be a leading cause of death. For the seriously ill patient, heart replacement is often one of the few viable options available.

K.N.L.ANUSHA
11307021

NANOWORMS IN TREATING CANCER

Filed under: Uncategorized — bmeforum @ 6:22 am

Scientists in United States have developed nanometer-sized “nanoworms” that can cruise through the bloodstream without significant interference from the body’s immune defense system and like tiny anti-cancer missiles act on tumors.
Using nanoworms, doctors should eventually be able to target and reveal the location of developing tumors that are too small to detect by conventional methods. Carrying payloads targeted to specific features on tumors, these microscopic vehicles could also one day provide the means to more effectively deliver toxic anti-cancer drugs to these tumors in high concentrations without negatively impacting other parts of the body.
Most nanoparticles are recognized by the body’s protective mechanisms, which capture and remove them from the bloodstream within a few minutes. “The reason these worms work so well is due to a combination of their shape and to a polymer coating on their surfaces that allows the nanoworms to evade these natural elimination processes. As a result, our nanoworms can circulate in the body of a mouse for many hours.”
When attached to drugs, these nanoworms could offer physicians the ability to increase the efficacy of drugs by allowing them to deliver them directly to the tumors. “They could decrease the side effects of toxic anti-cancer drugs by limiting their exposure of normal tissues and provide a better diagnosis of tumors and abnormal lymph nodes.”
The scientists constructed their nanoworms from spherical iron oxide nanoparticles that join together, like segments of an earthworm, to produce tiny gummy worm-like structures about 30 nanometers long—or about 3 million times smaller than an earthworm. Their iron-oxide composition allows the nanoworms to show up brightly in diagnostic devices, specifically the MRI, or magnetic resonance imaging, machines that are used to find tumors.
The iron oxide used in the nanoworms has a property of superparamagnetism, which makes them show up very brightly in MRI. “The magnetism of the individual iron oxide segments, typically eight per nanoworm, combine to provide a much larger signal than can be observed if the segments are separated. This translates to a better ability to see smaller tumors, hopefully enabling physicians to make their diagnosis of cancer at earlier stages of development.”
In addition to the polymer coating, which is derived from the biopolymer dextran, the scientists coated their nanoworms with a tumor-specific targeting molecule, a peptide called F3, developed in the laboratory of Burnham Institute for Medical Research at UC Santa Barbara. This peptide allows the nanoworms to target and home in on tumors.
Because of its elongated shape, the nanoworm can carry many F3 molecules that can simultaneously bind to the tumor surface. “And this cooperative effect significantly improves the ability of the nanoworm to attach to a tumor.”
The scientists were able to verify in their experiments that their nanoworms homed in on tumor sites by injecting them into the bloodstream of mice with tumors and following the aggregation of the nanoworms on the tumors. They found that the nanoworms, unlike the spherical nanoparticles of similar size that were shuttled out of the blood by the immune system, remained in the bloodstream for hours.
“This is an important property because the longer these nanoworms can stay in the bloodstream, the more chances they have to hit their targets, the tumors .It was the motivating force behind the discovery when it was found by accident that the gummy worm aggregates of nanoparticles stayed for hours in the bloodstream despite their relatively large size.
The researchers are now working on developing ways to attach drugs to the nanoworms and chemically treating their exteriors with specific chemical “zip codes,” that will allow them to be delivered to specific tumors, organs and other sites in the body.
Amulya Pendyala
11307025

February 15, 2010

Multipurpose Digital X-Ray Image Detectors

Filed under: Uncategorized — bmeforum @ 5:59 pm

A multipurpose X-ray image detector is able to work in dynamic (roentgenoscopy) and static (roentgenogra
phy) modes.
During the XX century the X-ray detectors for roentgenoscopy and roentgenography were developed independently. Only at the end of the XX century was there a trend toward their integration. The demand for multipurpose X-ray detectors is due to the transition to digital technology in TV apparatuses, surgical apparatuses, angiographs, and systems for intervention X-ray examination. These apparatuses provide both roentgenoscopy and roentgenography.
In the 1980s digital X-ray apparatuses with digital memory and apparatuses with image intensifiers were developed. This provided digital roentgenography. This class of multipurpose detectors is presently used in most X-ray apparatuses.
Short Xray pulses are used to reduce the radiation load of the patient and the unsharpness of the X-ray image. The pulse repetition frequency can be varied.Herrman and coworkers studied the dependence of pulse repetition frequency on the mobility of the organ to be examined.
Herrman and coworkers demonstrated that in case of phlebography 23 frames per sec were sufficient. This
pulse repetition frequency provides monitoring of contrast substance mobility. The pulse repetition frequency
48 frames per sec is sufficient for monitoring of barium swallow motion along the esophagus. Renal angiography and angiography of the iliac artery required pulse repetition frequency 36 frames per sec. Catheter positionmonitoring, fistulography, and puncture control required pulse repetition frequency of 3 frames per sec.
The results of pulse roentgenoscopy using video monitoring X-ray diagnostic systems containing image
intensifiers URI1.0M or URI4.0M (NIPK Electron,Ltd.) are consistent with results reported in.
Radiation dose in case of pulse roentgenoscopy was reported in at different pulse repetition frequency as
percentage of radiation dose in case of continuous roentgenoscopy.
X-Rayelectronic converters (XEC) are multipurpose detectors with limited working field. They are not
used in diagnosis of largesize organs. Nudelman demon strated that XEC could be used for digital Xray diagnosis. This diagnosis was shown to be economically feasible.It should be noted that XEC was developed forroentgenoscopy (time, 5 min). The main goal of this examination is to provide minimal radiation load (2-4 μR/frame). Large brightness in the XEC screen is provided by high coefficient of X-ray photon conversion .The allowable X-ray radiation dose for roentgenography is 1 mR (500 times larger).XEC of large dynamic range is able to provide both roentgenoscopy and roentgenography.

Richa Raina
11307037

IMPACT OF NANOTECHNOLOGY

Filed under: Uncategorized — bmeforum @ 1:07 pm

Abstract
Two of 21st century’s most promising technologies are biotechnology and nanotechnology.

This science of nanoscale structures deals with the creation, investigation and utilisation of systems that are 1000 times smaller than the components currently used in the field of microelectronics. Biotechnology deals with metabolic process with microoraganisms. Convergence of these two technologies results in growth of nanobiotechnology. This interdisciplinary combination can create many innovative tools.

The biomedical applications of nanotechnology are the direct products of such convergences.

However, the challenges facing scientists and engineers working in the field of nanotechnology are quite enormous and extraordinarily complex in nature.

Utility of nanotechnology to biomedical sciences imply creation of materials and devices designed to interact with the body at sub-cellular scales with a high degree of specificity. This could be potentially translated into targeted cellular and tissue-specific clinical applications aimed at maximal therapeutic effects with very limited adverse-effects.

Nanotechnology in biomedical sciences presents many revolutionary opportunities in the fight against all kinds of cancer, cardiac and neurodegenerative disorders, infection and other diseases.

This article presents an overview of some of the applications of nanotechnology in biomedical sciences.

Background
Nanotechnology is a new area of science that involves working with materials and devices that are at the nanoscale level. A nanometre is billionth of a meter. That is, about 1/80,000 of the diameter of a human hair, or ten times the diameter of a hydrogen atom. It manipulates the chemical and physical properties of a substance on molecular level. Nanotechnology alters the way we think, it blurs the boundaries between physics, chemistry and biology, the elimination of these boundaries will pose many challenges and new directions for the organisation of education and research.

Richard Feynman’s speech called ‘There is plenty of room at the bottom’ in 1959 emphasised this concept – If our small minds, for some convenience, divide this universe into parts, physics, biology, geology, astronomy, psychology and so on – Remember that nature does not know it [1].

Nanobiotechnology is the unification of biotechnology and nanotechnology. This hybrid discipline can also mean making atomic-scale machines by imitating or incorporating biological systems at the molecular level, or building tiny tools to study or change natural structure properties atom by atom. Nanobiotechnology can have a combination of the classical micro-technology with a molecular biological approach. Biotechnology uses the knowledge and techniques of biology to manipulate molecular, genetic, and cellular processes to develop products and services, and is used in diverse fields from medicine to agriculture. Convergence, is an activity or trend that occurs based on common materials and capabilities-in this case the discipline that enables convergence is nanotechnology. The potential opportunities offered by this interface is truly outstanding; the overlap of biotech, nanotech and information technology is bringing to fruition many important applications in life sciences.

This technology is expected to create innovations and play a vital role in various biomedical applications (fig. 1), not only in drug delivery and gene therapy, but also in molecular imaging, biomarkers and biosensors. Target-specific drug therapy and methods for early diagnosis of pathologies are the priority research areas where nanotechnology would play a prominent role [2].

Figure1. Schematic illustration of nanotechnology revolutionising biomedical sciences.

The National Institutes of Health Bioengineering Consortium (BECON) held a symposium in 2000 entitled “Nanoscience and Technology: Shaping Biomedical Research″[3]. Eight areas of nanoscience and nanotechnology were addressed at the conference and believed to be the most pertinent to research in biomedicine. These areas included synthesis and use of nanostructures, applications of nanotechnology to therapy, biomimetic and biologic nanostructures, electronic-biology interface, devices for early detection of disease, tools for the study of single molecules, nanotechnology and tissue engineering.

The aim of BECON was to enhance communication between biomedical scientists and engineers who bring different aspects of their skills and knowledge to bear on these problems and to make the biomedical community more aware of the emerging developments in the field of nanotechnology. The deliberations of the conference are now widely reinforced by day-to-day experience, increasing ability to manipulate individual molecules at a nanoscale and to combine biomolecules with other nanoscale structures. This ability provides the opportunity for untold new therapeutic and diagnostic applications by enabling the building of novel structures from the bottom up [4].

In the foreseeable future, the most important clinical application of nanotechnology will probably be in pharmaceutical development. These applications take advantage of the unique properties of nanoparticles as drugs or constituents of drugs or are designed for new strategies to controlled release, drug targeting, and salvage of drugs with low bioavailability [5-7].

Nanoscale polymer capsules can be designed to break down and release drugs at controlled rates, to allow differential release in certain environments, such as an acid medium, and to promote uptake in tumours versus normal tissues [8]. A lot of research is now focused on creating novel polymers and exploring specific drug-polymer combinations. Nanocapsules can be synthesized directly from monomers or by means of nanodeposition of preformed polymers [9]. Nanocapsules have also been formulated from albumin and liposomes. Implantable drug delivery systems that are being developed will make use of nanopores to control drug release.

One of the key issues in bio-availability is cell transfection in DNA gene therapy. Current methods have significant limitations, including the risk of inadvertent transmission of disease by viral vectors. This has led researchers to explore polymer-DNA complexes and liposome-DNA complexes for gene delivery [10]. It has also been shown that compacted DNA in the form of nanoparticles can be used to transfect postmitotic cells [11].

Despite the risk and limitations, viral vectors are an efficient biomimetic approach to drug targeting and delivery. The tat peptide from human immunodeficiency virus (HIV) and other viral proteins are being attached to DNA, proteins, and other materials for uptake into cells. These nano-assemblies mimic the action of the fusion proteins that make viral transfection efficient [12, 13]. Nanotechnology has also enabled the development of biochips and has a role in green manufacturing (e. g biocompatibility and biocomplexity areas). Other applications include the design of sensors for astronauts, soldiers, biofluids (for handling DNA and other molecules), in vitro fertilization of live stock, nanofiltration, bioprocessing ‘by design’ and traceability of genetically modified food (Table 1).

Exploratory areas for nanotechnology will include research into the condition and/or repair of the brain and other areas for regaining cognition. It might also find application in designing pharmaceuticals as a function of patient genotypes and in applying chemicals to stimulate production as a function of plant genotypes. The synthesis of more effective and biodegradable chemicals for agriculture and the production of implantable detectors could be aided by nanotechnology with minimal quantities of blood. Employing this technology it should also be possible to develop methods that use saliva instead of blood for the detection of illnesses or that can perform complete blood testing within a short period of time. Broader issues include economic molecular medicine, sustainable agriculture, conservation of biocomplexity, and enabling emerging technologies.

Richard E. Smalley, winner of the 1996 Nobel Prize in Chemistry announced in his congressional testimony to the U.S. government about the increasing awareness in the scientific and technical community of our entry into a new golden age. Burgeoning interest in the medical applications of nanotechnology has led to the emergence of a new discipline known as nanomedicine [14]. On a wider scope, nanomedicine is the process of diagnosing, treating, preventing disease and traumatic injury, of relieving pain, and of preserving and enhancing human health, using molecular tools and molecular knowledge of the human body. The purpose of this review is to throw more light on the recent advances and impact of nanotechnology on biomedical sciences.

Recent Developments
Medical diagnosis with appropriate and effective delivery of pharmaceuticals are the medical areas where nanosize particles have found practical applications. However, there are many other interesting proposals for the use of nanomechanical tools in the fields of medical research and clinical practice. Such nanotools are awaiting construction, and presently are more like a fantasy. Nevertheless, they might be quite useful, and become a reality in the near future [41].

Nanodevices in medical sciences could function to replace defective or improperly functioning cells, such as the respirocyte proposed by Freitas [42]. This man-made red blood cell is theoretically capable of providing oxygen more effectively than an erythrocyte. It could replace defective natural red cells in blood circulation. Primary applications of respirocytes may involve transfusable blood substitution, partial treatment of anaemia, prenatal/neonatal problems, and lung disorders.

It has been reported that nanomachines could administer drugs within a patient’s body. Such nanoconstructions could deliver drugs to peculiar sites making treatment more accurate and precise [43]. Similar machines with specific ‘weapons’ could be used to remove obstacles in the circulatory system or in the identification and killing of tumour cells.

The other vital application of nanotechnology in relation to medical research and diagnostics are nanorobots. Nanorobots, operating in the human body, could monitor levels of different compounds and record the information in the internal memory. They could be rapidly used in the examination of a given tissue, surveying its biochemical, biomechanical, and histometrical features in greater detail. Just as biotechnology extends the range and efficacy of treatment options available from nanomaterials, the advent of molecular nanotechnology will again expand enormously the effectiveness, comfort and speed of future medical treatments while at the same time significantly reducing their risk, cost, and invasiveness.

Biotechnology permits tailor-made production and biopharmaceuticals and biotechnological drugs, many of which require special formulation technologies to overcome drug-associated problems. Such major challenges to solve include the following: poor solubility, limited chemical stability in vitro and in vivo after administration (i.e. short half-life), poor bioavailability and potentially strong side-effects requiring drug enrichment at the site of action (targeting) [44]. Nanoparticulate carriers have been developed as one solution to overcome such delivery problems, i.e. drug nanocrystals, solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC) and lipid-drug conjugate (LDC) nanoparticles [44]. The carriers as reported by Muller and colleagues are suitable to solve delivery problems with biotech drugs of different solubility. Targeting with these carriers can be realised by a very simple approach, the differential protein adsorption (PathFinder® technology). This technology proved to be efficient enough to accumulate sufficiently high amounts of drugs in the brain to reach therapeutic levels and also fulfill the major requirement to be pursued by a pharmaceutical company.

Quantum Dot with nanodots of a specific colour are believed to be flexible and could offer a cheap and easy way to screen a blood sample for the presence of a number of different viruses at the same time. It could also give physicians a fast diagnosis tool to detect, say, the presence of a particular set of proteins that strongly indicates the onset of myocardial infarction. On the research front, the ability to simultaneously tag multiple biomolecules both on and inside cells could allow scientists to watch the complex cellular changes and events associated with disease, providing valuable clues for the development of future pharmaceuticals and therapeutics (Quantum Dot Corporation) [45].

The National Heart, Lung, and Blood Institute (NHLBI) plans to foster the application of nanotechnology to HLBS (Heart, Lung, Blood and Sleep) research and disorders. A request for information (RFI) was developed, with advice from scientists and physicians with interests in nanotechnology, to canvas the broader scientific community on approaches to developing and applying nanotechnology to HLBS disorders. A working Group comprising scientists, engineers, and physicians with expertise across nanotechnology, nanoscience, and HLBS medicine met on February 28th, 2003, using the RFI responses as the starting point for discussions. The Working Group was entrusted with assessing the field of nanotechnology and suggesting ways for research. The Working Group cautioned against overly rigid or restrictive definition of nanotechnology, emphasizing the continuum of scale from the nanoscale to the microscale. The Group also identified areas of opportunity and challenges to further development associated with the application of nanoscience and nanotechnology to improved diagnosis, treatment, and prevention of HLBS disorders. It as well developed prioritized recommendations to facilitate the application of nanotechnology to biological questions and improved patient care [46].

The RESIST Group at the Welsh School of Pharmacy at Cardiff University and others have looked at how molecularly imprinted polymers could be medically useful in clinical applications such as controlled drug release, drug monitoring devices, and biological and antibody receptor mimics. Histamine and ephedrine molecularly imprinted polymers (MIPs) were studied as potential biological receptor mimics whilst a propanolol MIP was investigated for its use as a rate attenuating selective excipient in a transdermal controlled device [47].

The first artificial voltage-gated molecular nanosieve was fabricated by Charles R. Martin and colleagues [48] at Colorado State University in 1995. Martin’s membrane contains an array of cylindrical gold nanotubules with inside diameters as small as 1.6nm. When the tubules are positively charged, positive ions are excluded and only negative ions are transported through the membrane. When the membrane receives a negative voltage, only positive ions can pass. Similar nanodevices may combine voltage gating with pore size, shape, and charge constraints to achieve precise control of ion transport with significant molecular specificity. An exquisitely sensitive ion channel switch biosensor was built by an Australian research group [49].

The year 2003 could be termed a very special year for biomedical research because we celebrated the completion of the sequencing of the entire human genome which coincided with the 50th anniversary of the discovery of the DNA double helix structure by Watson and Crick. In biomedical imaging, we also witnessed the awarding of the Nobel Prize in Medicine and Physiology to two pioneers in Magnetic Resonance Imaging, Professor Paul Lauterbur and Sir Peter Mansfield. These landmark events helped to highlight the impact of the rapid development in many diverse disciplines to biomedical research. The leverage and tremendous advances in electronics and information technology has been brought about by biomedical imaging research [50]. The opportunities and challenges in future biomedical research lie in the incorporation of knowledge gained from molecular biology with chemistry, physics, engineering, information technology, and nanotechnology to understand the ambiguity and complexity of life and come up with new diagnostic and therapeutic methods.

Calcium phosphate nanoparticles present a unique class of non-viral vectors, which can serve as efficient and alternative DNA carriers for targeted delivery of genes. The design and synthesis of ultra-low size, highly monodispersed DNA doped calcium phosphate nanoparticles of size around 80nm in diameter has been reported [51]. The DNA encapsulated inside the nanoparticle is protected from the external DNase environment and could be used safely to transfer the encapsulated DNA under in vitro and in vivo conditions.

The application of a combination of nanomedicine with biophotonics for optically tracking the cellular pathways of gene delivery and the resulting transfection by using nanoparticles as a non-viral vector has been demonstrated recently [52]. Gene delivery is an area of considerable current interest; genetic materials (DNA, RNA, and oligonucleotides) have been used as molecular medicine and are delivered to specific cell types to either inhibit some undesirable gene expression or express therapeutic proteins.

Nano-DNA Technology
The discovery of the polymerase chain reaction (PCR) [53, 54] paved the way to a new era of biological research. The impact can be felt not only in the field of molecular biology, but also in other allied fields of science. Novel classes of semi-synthetic DNA-protein conjugates, self-assembled oligomeric networks consisting of streptavidin and double-stranded DNA, which can be converted into well-defined supramolecular nanocircles have been developed [55, 56].

The DNA-streptavidin conjugates are applicable as modular building blocks for the production of new immunological reagents for the ultrasensitive trace analysis of proteins and other antigens by means of immuno-PCR methodology [57-59]. Immuno-PCR is a combination of the specificity of an antibody-based immuno-assay with the exponential power of the amplification of PCR, hence resulting in a 1000-fold degree of sensitivity as compared with standard ELISA (Enzyme-linked immunosorbent assay) methods.

Self-assembled DNA-streptavidin conjugates have also been applied in the field of nanotechnology. For example, the conjugates are used as model systems for ion-switchable nanoparticle networks, as nanometre-scale ‘soft material’ calibration standards for scanning probe microscopy [60, 61], or as programmed building blocks for the rational construction of complex biomolecular architecture, which may be used as templates for the growth of nanometre-scale inorganic devices [62, 63]. Covalent conjugates of single-stranded DNA and streptavidin are used as biomolecular adapters for the immobilization of biotinylated macromolecules at solid substrates through nucleic acid hybridization. This ‘DNA-directed immobilization’ allows for reversible and site-selective functionalization of solid substrates with metal and semiconductor nanoparticles or, vice versa, for the DNA directed functionalization of gold nanoparticles with proteins, such as immunoglobulins and enzymes. The fabrication of functional biometallic nanostructures from gold nanoparticles and antibodies are applied as diagnostic tools in bioanalytics [64].

Nanobiotechnology in High-Throughput Single Nucleotide Polymorphism Analysis
Following the publication of a map of variation in the human genome sequence containing over two million single nucleotide polymorphisms (SNPs) (The International SNP Map Working Group, 2001), the next challenge is the development of the technologies to use this information in a cost-effective manner. Genotyping methods have to be improved in order to increase throughput by at least two orders of magnitude to enable pharmaceutical, biotechnological and academic research to uncover associations between genetic variants and diseases, with consequent potential for the development of novel diagnostics and therapies. New approaches to DNA extraction and amplification have curtailed the times required for these processes to seconds. Microfluidic devices enable polymorphism detection through very rapid fragment separation using capillary electrophoresis and high-performance liquid chromatography, together with mixing and transport of reagents and biomolecules in integrated systems [65]. The basic objectives in the development of a DNA extraction and purification system that will be compatible with high-throughput SNP genotyping requirements are:

· Release of the DNA from the cells into solution without either enzymatic (i.e. endonucleases) or mechanical (shearing) breakdown of the DNA;
· Removal of cellular debris (e.g. proteins) that may hamper DNA amplification or hybridization assays;
· High-throughput and economical DNA sample preparation with simplified protocols that reduce the number of procedures involved;
· Avoidance of hazardous chemical requirements as much as possible to minimize handling and disposal costs;
· Consistency of both quality and quantity of DNA yield among samples so that quantification is unnecessary, and subsequent amplification and/or hybridization can be to a high degree of reproducibility;
· A highly efficient process, to ensure enough supply for the enormous number of assays anticipated; and
· An interface that will enable direct loading of conventionally sampled biopsies on to the system [65].
The potential for nanotechnology to contribute to rapid high-throughput SNP analysis is most evident with smart biochip platforms. The development of an electronically addressable microarray platform as described by Heller L. et al 2000 [66] has given rise to Nanogen Inc. (San Diego, California, USA). The challenge of providing one or more technology platforms capable of SNP screening throughput of the order of 107 genotypes per day will need to be achieved, to allow significant associations between genes and diseases to be established. Additionally, the technology platform(s) will also need to deliver economies of scale, such that the cost per genotype will be less than 0.01$ for the magnitude of screening necessary to be feasible. From the rapidly developing field of nanotechnology, novel tools and processes have been introduced with the potential to provide the capabilities required [67-69].

Differences of SNPs occurring in close proximity to each other on the genome is normally correlated due to linkage during the process of replication, and the extent of this correlation is termed linkage disequilibrium. Where a significant association occurs between the genetic variation observed at specific SNPs and the presence of a disease, susceptible genes can be identified. The statistical estimations needed to eliminate false-positive results were reviewed by McCarthy and Hilfiker (2000) [70]. They suggest a linear increase in sample size is necessary for every order of magnitude increase in the number of markers tested. Hence, positive identification of a susceptible gene from a screening programme including 1 Million SNPs would require a minimum sample size of 1000 (i.e. a minimum of 109 SNPs have to be screened).

Nanoparticles as Biomarkers
Nanoparticles can be used for both quantitative and qualitative in vitro detection of tumour cells. They enhance the detection process by concentrating and protecting a marker from degradation, in order to render the analysis more sensitive. For instance, streptavidin-coated fluorescent polystyrene nanospheres Fluospheres® (green fluorescence) and TransFluospheres® (red fluorescence) were applied in single colour flow cytometry to detect the epidermal growth factor receptor (EGFR) on A431 cells (human epidermoid carcinoma cells) [71]. The results have shown that the fluorescent nanospheres provided a sensitivity of 25 times more than that of the conjugate streptavidin-fluorescein.

New tools can now be developed, designed at the intersection of proteomics and nanotechnology, whereby nanoharvesting agents can be instilled into the circulation (e.g. derivatized gold particles) or into the blood collection devices to act as ″molecular mops″ that soak up and amplify the bound and complexed biomarkers that exist [72-74]. These nanoparticles, with their bound diagnostic cargo, can be directly queried via mass spectrometry to reveal the low molecular weight and enriched biomarker signatures. Ultimately, utility of any approach for detecting disease is assessed on its clinical impact to patient outcome and disease-free survival [75]. What is urgently required in the study of diseases in general, is the development of biomarkers that can detect curable diseases earlier, and not detecting advanced disease better.

Contrast agents have been loaded onto nanoparticles for tumour diagnosis purposes. The physico-chemical features (particle size, surface charge, surface coating, stability) of the nanoparticles allow the redirection and the concentration of the marker at the specific site of interest. Labelled colloidal particles could be used as radiodiagnostic agents. On the other hand, some non-labelled colloidal systems are already in use and some are still being tested as contrast agents in related diagnosis procedures such as computed tomography and NMR imaging.

To date, a study of radionucleide use in diagnostic imaging with nanoparticles for cancer detection is yet to be published. However, as conventional colloidal particles can be cells of organs like the liver, the spleen, the lungs and the bone marrow and as long-circulating nanoparticles can have a compartmental localization in the blood circulation or the lymphatic system- all these organs being potential sites for tumour development, these colloidal systems could potentially improve tumour diagnosis.

In the future, nanoparticles that are engineered with specific binding affinities can be resuspended into the collected body fluids, or perhaps even injected directly into the circulation. The nanoparticles, together with the bound molecules, could be directly captured on engineered filters and directly questioned by ultra high-resolution mass spectrometry (e. g. Fourier Transform Ion Cyclotron Resonance).

Nanotechnology in Measurements of Dissolved Oxygen
Oxygen is one of the major metabolites in aerobic systems, and the measurement of dissolved oxygen is of vital importance in medical, industrial, and environmental applications. Recent interest in the methods for measuring dissolved oxygen concentration has been focused mainly on optical sensors, due to their advantages over conventional amperometric electrodes in that they are faster, do not consume oxygen, and are not easily poisoned [76, 77].

Optical PEBBLE (probes encapsulated by biologically localized embedding) nanosensors have been developed for dissolved oxygen using organically modified silicate (ormosil) nanoparticles as a matrix. The ormosil nanoparticles are prepared through a sol-gel-based process, which includes the formation of core particles with phenyltrimethoxysilane as a precursor followed by the formation of a coating layer with methyltrimethoxysilane as a precursor [78]. The highly permeable structure and the hydrophobic nature of the ormosil nanoparticles, as well as their small size, result in an excellent overall quenching response to dissolved oxygen and a linear response over the whole range, from 0 -100% oxygen-saturated water. This PEBBLE sensor has a higher sensitivity and a broader linearity as well as longer excitation and emission wavelengths, resulting in reduced background noise for cellular measurement. The PEBBLE sensors are excellent in terms of their reversibility and stability to leaching and long-term storage. A real-time monitoring of changes in the dissolved oxygen due to cell respiration in a closed chamber was made by gene gun delivered PEBBLE. This sensor is now being applied for simultaneous intracellular measurements of oxygen and glucose [78].

Application of Nanotechnology to P450 Enzymes
Cytochromes P450 are highly relevant to the bio-analytical area [79]. They form a large family of enzymes present in all tissues essential to the metabolism of most drugs in use today, playing a vital role in the drug development and discovery process. They act as catalysts for the insertion of one of the two atoms of an oxygen molecule into a variety of substrates (R) with quite broad regioselectivity, leading to concomitant reduction of the other oxygen atom to water as shown in the equation below [29].

Several methods have been reported in the literature for the screening of substrate turnover by P450s in a high throughput format [80-83]. However, they all fall short of being limited to testing the activity of P450 enzymes through the detection of the conversion of a specific marker substrate, but Tsotsou et al 2002 [84] have been able to develop a method called the alkali method, which can detect the turnover of any NAD(P)H or NAD(P)+ dependent enzyme. The progress on these research fronts and their combinations provide a powerful platform for future applications of these enzymes, with particular reference to protein array technology.

Application of Nanotechnology to Tissue Engineering
Tissue engineering is based on the creation of new tissues in vitro followed by surgical placement in the body or the stimulation of normal repair in situ using bioartificial constructs or implants of living cells introduced in or near the area of damage. Though it is mainly concerned with using human material, either from the patient themselves (autologous) or from other human sources (allogeneic), material from other mammalian sources have also been applied in humans (xenogeneic).

The involvement of microelectronics or nanotechnology in creating a truly bioartificial tissue or organ that can take the place of one that is terminally diseased, such as an eye, ear, heart, or joint has been envisaged. Implantable prosthetic devices and nanoscaffolds for use in the growing of artificial organs are goals of nanotechnology researchers. Nanoengineering of hydroxyapatite for bone replacement is reasonably advanced [85, 86].

In the future, we could imagine a world where medical nanodevices are routinely implanted or even injected into the bloodstream to monitor wellness and to automatically participate in the repair of systems that deviate from established norms. These nanobots could be personalized by tailoring them to patient genotype and phenotype to optimize intervention at the earliest stage in the course of disease expression [4].

Growth of New Organs
Nanoscale building of cells can be accomplished by their programmed replication. The signals are transmitted back and forth with the instruction for the desired size and shape form the construction site. When complete instructions are finished, the organs can be grown according to the prerequisite specifications.

These organs could have the necessary DNA encoded to be compatible with the required human body immunological status. This can enhance integration of artificial structures with living tissues, presenting a more appropriate interface to biological systems. With the advantage in absence of immune reaction unlike today’s donor organ transplantation. In the years to come this can accomplish a Quantum leap in the management of organ failure disorders.

Figure 2. Graphical representation of the nanoscale construction and growth of new organs.

Molecular Imaging
New imaging approaches using genetically encoded fluorescent and bioluminescent reporters (i.e., illuminated or glowing identification tags) are offering revealing insights to the living body as never observed before. Information provided by these reporters can be used to enhance our understanding of human biology and the development of therapeutic approaches for many diseases, including cancer, infection, neurodegenerative and cardiovascular disease.

In addition to progresses so far made with molecular agents, industry leaders are also showcasing rapidly evolving imaging technologies that allow scientists to view organisms at the molecular level (Table 2).

Latest products in Molecular Imaging and associated producing Companies

Product Name

Company(ies)

SPECT/CT hybrid imaging systems
Philips Medical Systems/Siemens Medical Solutions

GFAP-luc (glial fibrillary acid protein)
Xenon

Ultrasound bubbles
Schering AG

NeuroSpec™ (radiodiagnostic agent)
Tyco Healthcare/Mallinckrodt Inc.

eXplore Locus Ultra (Volumetric CT system)
GE Medical system
Definity® or Sonolysis™ (nanosurgery)
ImaRx
· SPECT/CT hybrid systems capture both functional information on molecular and cellular processes (growth and activity) and anatomical detail (size and shape) of a targeted molecular structure more quickly, efficiently and clearly than standard imaging devices. The images obtained from these systems can assist with the rapid identification of tumours, analysis of appropriate treatment, delivery of targeted therapy to precisely destroy target cells, and follow up to assess treatment effectiveness.
· Xenon presented its newer light producing transgenic animal models (GFAP-luc) during the Society for Molecular Imaging’s 3rd Annual Meeting. This model may prove to be an important model for tracking damage and repair in chronic neurological conditions such as post-ischemic stroke or Parkinson’s disease.
· An ultrasound contrast agent is made of tiny “microbubbles″ that scatter light and allow the clinician to see which part of the heart muscle is poorly functioning. The sensitivity and flexibility of ultrasound makes it the most sensitive method of imaging microbubbles because it deliberately disrupts the pattern and produces a very strong and highly characteristic transient effect. For example,
· Definity® otherwise known as Sonolysis™ are gas-filled microbubbles for novel therapeutic applications. For dissolving vascular thrombosis, microbubbles are administered intravenously to a patient or injected locally into a specific vascular structure such as a vascular graft. Ultrasound is applied externally (or can be applied internally via catheter) over the area of the blood clot to provide localized, targeted action. As the microbubbles perfuse the clot, they act as micromechanical devices where ultrasound pulses the bubbles and blows up the bubbles in the ultrasound field, leading to blood clot dissolution. Sonolysis nanosurgery is locally targeted nanoinvasive therapy for treatment of vascular thrombosis. Compared with alternative therapies for treating thrombosis, sonolysis affords the potential merits of being less invasive than mechanical thrombectomy and faster than conventional drug therapy with less risk of bleeding.
· NeutroSpec™ is a radiodiagnostic agent which labels white blood cells and myeloid precursors without the need for removal and re-injection of blood into patients. This new product is for patients with equivocal signs of appendicitis who are five-years-old and up. NeutroSpec also facilitates the visualization of images generated via gamma camera allowing physicians to quickly and easily locate the sites of infection thereby eliminating time delays and/or risks normally affiliated with alternative white blood cell labelling processes.
· eXplore Locus Ultra is a first-class volumetric CT system capable of quantitating physiological measurements and elaborate anatomy of tissues, tumours and organ perfusion. The Locus Ultra also performs image acquisition at the rate of a sub-second, enabling dynamic imaging.
Summary
The multidisciplinary field of nanotechnology’s application for discovering new molecules and manipulating those available naturally could be dazzling in its potential to improve health care. The spin-offs of nanobiotechnology could be utilised across all the countries of the world.

In the future, we could imagine a world where medical nanodevices are routinely implanted or even injected into the bloodstream to monitor health and to automatically participate in the repair of systems that deviate from the normal pattern. The continued advancement in the field of biomedical nanotechnology is the establishment and collaboration of research groups in complementary fields. Such collaborations have to be maintained not only on specialty field level, but internationally as well. The successful development and implementation of international collaborations fosters a global perspective on research and brings together the benefits to mankind in general. However, nanotechnology in medicine faces enormous technical hurdles in that long delays and numerous failures are inevitable. Likewise, it should not be taken for granted the dangers and negative consequences of nanobiotechnology when applied in warfare, in the hands of terrorists and disasters associated with its application in energy generation when and wherever it strikes or the risks associated with nanoparticles in blood circulation. It should be appreciated that nanotechnology is not in itself a single emerging scientific discipline but rather a meeting point of traditional sciences like chemistry, physics, biology and materials science to bring together the required collective knowledge and expertise required for the development of these novel technologies.

BY N.KRUPA.
11307015

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