NANOBIOTECHNOLOGY-THE FUTURE REVOLUTION
The zeal to develop more miniaturized and sophisticated tools is ever increasing in today's modern world. This has led to the advent of new technologies such as nanotechnology, which deals with the creation and fabrication of materials at nano scale. For the past three decades, engineers have been seriously working on shrinking the dimensions of fabricated structures in order to enable faster and higher density electronic chips. These chips have the featured sizes of as small as 20 nm. On the other hand, for many years molecular biologists have been dealing with molecular and cellular dimensions ranging from several nanometers (DNA molecules, viruses) to several micrometers (cells) .With such a close relationship among the two disciplines it was believed that a combination of these disciplines would result in relatively a new class of multifunctional devices and systems for biological and chemical analysis characterized by better sensitivity and specificity. This amalgamation of engineering and molecular biology has resulted in the birth of Nanobiotechnology.
In this paper I would like to describe some of the applications of Nanotechnology in the area of biotechnology, followed by a brief emphasis on its current status and potential challenges.
Based on high specificity and sensitivity of biological reactions for detecting target analytes, biosensors are considered as useful research tools to discern genetic abnormalities and physiological diseases. Biosensors couple a biological recognition element with a physical transducer that translates the bio-recognition event into a measurable effect, such as electrical signal, an optical emission or a mechanical motion. Progress in nanotechnologies allows development of highly sensitive sensors with the addition advantages of miniaturization. These miniaturized biosensor provides on the target analysis based on microelectronics and related micro-electromechanical system (MEMS).
A new class of promising nanobio-sensor (microcantilever) to detect biomolecular interaction with great accuracy was designed . This new class of high sensitivity biosensors can perform local, high resolution and label-free molecular recognition measurement. Mechanisms of these biosensors are based on cantilever in atomic force microscopy (AFM). Basic mechanism of these sensors is the bending induced in the cantilever when a biomolecular interaction takes place on its surface. The nanomechanical motion is often coupled to an optical or piezo-resistive read-out system. As derived from standard AFM, optical read-out is one of the most common schemes for detecting the movement of microcantilevers. Laser deflection on the microcantilever is detected by sensitive photodetector. An alternative to optical read out is piezo-resistive read-out. The mechanism of this read-out is based on resistively changes on the cantilever as a result of surface stress change. For piezo-resistivity to be observable, the electrical conductivity along the thickness of the cantilever has to be asymmetric, which is often accomplished by differential doping of the material. The current scale of the cantilevers is in microns, but with the success in the nanotechnology, reduction in scale can provide the advantage of multiple detection in one device and local on-site detection.
In recent years, applications of gold nanoparticles have also been extended to the research of DNA functioning and detection of proteins involved in cancers. Examples of these diagnostic tools involved the use of gold particle particles bound to a DNA-probe . Gold nanoparticles are manufactured to contain a ligand with biomolecule, typically a specific sequence of DNA nucleotides. The DNA in question will bind to the gold particle if the DNA has the target sequence. The binding of these nanoparticles will result in an aggregation. Based on surface plasmon resonance of gold nanoparticles, an aggregation of gold particles will result in a color change. One of these researches is the Qdot™ by Invitrogen. The significance of this biomarker is its nanoscale size (comparable to protein) and the tuneability to produce different wave length.
Other theoretical development in nano-diagnostics also includes antibodies labelled with magnetic nanoparticles. Upon exposed to a magnetic field, these anibodies respond with a strong magnetic signal if they are reacting with certain substances. Furthermore, gold nanoshells linked to specific antibodies that target tumors could, when hit by infrared light, heat up to destroy growths selectively. Currently, different medium of nano materials such as nanotubes, nanoparticles, nanowires, and nanoporous materials are also examined for biocompatibility and subsequent detection .
The advantages of these nano-biosensors are mainly driven by their high-throughput and the ability to perform In Vivo analysis. These analyses are in real time and do not require labeling of the target. Economically, arrays of nanosenors can be fabricated in tens of thousands of units.
Development of synthetic polymer
Recently new and exciting opportunities for bionanofabrication have emerged in the fields of synthetic biology and recombinant protein engineering. Although bionanofabrication is still at its infancy, it has a wild scope of applications and promising future. The field of synthetic polymer can be ranged from genetic engineering, biomolecule fabrications to tissue engineering.
More recently, the research area of nanobiotechnology has been broadening to genetic engineering. Genetic materials can be characterized as repeating units of monomers in nanoscales. The possibility of modifying genes in nucleotide level is driven by the advance of the before mentioned nano-biosensor . DNA strands, which have complementary sticky-end overhangs, can be fabricated and self-assemble into a branched junction. These branched junctions can further self-assemble into DNA nanogrids owing to the orientation of the complementary sticky ends. Micropatterned DNA arrays have been proposed to be used as templates for high-throughput gene synthesis and protein expression. As compare to traditional Polymerase Chained Reaction (PCR), this process can have much higher production rate and thus provide a significant economical advantage.
Another group of material focused in nanofabrication is peptides . Peptides are short chains of nucleic acids which are fragment of proteins and can form biological entities such as antibodies. Researchers have shown various types of self-assembling peptide systems with capabilities to form twisted β-sheets, to undergo conformational changes, to bind to specific surfaces, and to construct nanotubes and nanovesicles. Each of these supramolecular formations is governed by the properties of the peptide units. The research in nanofabrication can be further extended to tissue engineering. Since the morphology and patterning of the tissue is determined by it microstructures, the researcher focused on various methods on controlling polymeric substrates and fabricate the materials into micro- and nanometric patterns.
Nanoscale Drug Delivery Devices
In addition to the potential improvements in the diagnostic field, nanotechnology offers advantages that allow a more targeted drug delivery and a more controllable release of a therapeutic compound. The aim of targeted drug delivery and a controlled release is to better manage drug pharmacokinetics, non-specific toxicity and biorecognition of systems. Cancer treatment often involves the administration of inhibitors to block overreaction or overproduction of cancer cells. A controlled and precise release of inhibitors is essential in preventing damage or side effects bring to surrounding or non-targeted cells. In nanoscale drug delivery, the inhibitor is suitably encapsulated, in nanoparticulate form, and then specifically target cancer cells based on the biomolecular interaction between the coating layer and the target. This specific targeting prevents premature degredation and size effects caused to surrounding cells. The use of nanoscale devices offers direct on site drug delivery and provide direct release, and thus increase patient acceptabilty .
The route of administration is another key for a therapeutic success. The focus of nanoscale delivery system is to cross a specific barrier, such as the blood-brain barrier, and to prevent degradation during the process. In general, gastrointestinal administration is noninvasive to the patient; however, the enzymatic digestion in the intestinal tract can cause degradation to the drug. Intravenous administration is direct and can be applied to unconscious patients; however, repeated administration is invasive and often cause discomfort to the patient. Pulmonary administration (by inhalation) can be a focus of these nanoscale delivery systems. This administration route is noninvasive and is relatively fast coupled with oxygen delivery system. Nanocarrier can be used to prevent degradation and facilitate the nasal or pulmonary crossover.
Nanobiotechnology is still at its early stages of development however, the development is multi-directional and fast-paced. Universities are forming nanotechnology centers and the number of papers and patent applications in the area is rising quickly. The nanotechnology ‘tool-box' is quickly being filled with nanotools, but realistically, some of these newly developed tools might not have viable applications and could end-up on the ‘technology shelf' in the future. The flurry of new nano-based sensors, for example, looks at first glance to be appealing, but in many cases, the techniques for preparing these sensors are complex; the sensor performance might not be superior to existing methods relying on micro-approaches (as opposed to nano-approaches). Nevertheless, there are definite benefits emerging from these developments. Nanobiotechnology is interdisciplinary and brings together life scientists and engineers. This, in turn, fuels further growth of ideas, which would not occur without these interdisciplinary interactions. Finally, many bets have been placed on the future importance of nanobiotechnology and nanobiotech start-ups, which constitute nearly 50% of the venture capital invested in nanotechnology.
Nanobiotechnology is here to stay! We expect that the current multi-directional and chaotic developments will gradually become more ordered and develop sharp focus as applications mature to produce useful and validated technologies. It is still not entirely clear whether nanobiotechnology will be the basis of the next technological revolution and, if this is indeed the case, what is a realistic timescale for this potentially industry-transforming event. There is little doubt that there is great optimism among scientists, politicians and policy makers who anticipate significant job creation associated with the growth of this new field .Nanobiotechnology will certainly provide opportunities for developing new materials and methods that will enhance our ability to develop faster, more reliable and more sensitive analytical systems. A gradual, rather than explosive incorporation of these new discoveries into molecular recognition is predicted. The progression of fabrication techniques driven by the semiconductor industry will allow realization of smaller and smaller structures, challenging researchers to provide new applications for those structures, which reach beyond electronic devices, for which they were initially made. QDs and gold nanoparticles are just two examples of this transfer of technology into molecular detection applications. Finally, future applications of nanobiotechnology include development of in vivo sensors. Nano-sized devices are envisaged that could be ingested or injected into the body, where they could act as reporters of in vivo concentrations of key analytes. These devices would have a capability for sensing and transmitting data to an external data capture system. The constant vigilance of these devices would provide a real-time, 24/7 scrutiny of the state of a person's health. The regulatory issues that will have to be addressed for such devices are as yet unknown; however, the basic technology that would underlie their development can already be discerned
I believe that the advance in nanotechnology has opened up various opportunities, especially in the area of biotechnology. In this paper, three areas of bioapplication of nanotechnology have been discussed. These included nanoscale biosensors, nano-syntheic polymers, and nanoscale drug delivery systems. However, there is still a huge gap between concepts and clinical realities.
The main challenge, as faced in other areas of nanotechnology application, is the material property change in reduced size. The reliability of the nanobiosensor lies on the understanding of material science in such a small scale. Also, in reduced scale, the quality control to manufacture consistent repeatable units is expensive and difficult. An explicit problem faced by the biological application is that the natural immune system can obstruct the nanodevices and nanopolymers if they are not well coated or disguised. Future research need to focus on stabilizing the nanomaterial in the In Vivo environment and also on inexpensive quality control.
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