There is a close juxtaposition of biologically-active molecules, cells and tissues with convential electronic systems for advanced applications in analytical science, electronic materials, device fabrication and neuronal prosthesis
Bioelectronics—an offshoot of biotechnology and electronics—finds applications in at least three areas of research and development: bio-sensors, molecular electronics, and neuronal interfaces. Some scientists, who include biochips and biocomputer in the area of carbon-based information technology, suggest that biological molecules might be incorporated within a self-structuring bio-informatic system which displays novel information-processing and pattern-recognition capabilities. However, these applications are still in the speculative stage, but technically feasible nevertheless. Scientists working in this field of organic electronics are of the view that this carbon-based technology will replace inorganic electronics in use now, just as semiconductors replaced vacuum tubes.
Biosensors
Of the three disciplines—biosensors, molecular electronics and neuronal interfaces (which collectively constitute bioelectronics)—the most mature is the burgeoning area of biosensors.
The term ‘biosensor’ is used to describe two different classes of analytical devices—those that measure biological analytes and those that exploit biological recognition as a part of the sensing mechanism. It is the latter concept which truly captures the spirit of bioelectronics.
A biosensor is an analytical device that converts the concentration of an analyte in an appropriate sample into an electrical signal by means of a biological-sensing element intimately connected to or integrated into a transducer. Biosensors differ from existing analytical technologies in several important respects. First, there is an intimate contact between the biological component—be it enzyme, sequence of enzymes, organelle whole cell, tissue slice, antibody, or other receptors or binding protein and the transducer. Second, most new-generation biosensors are functionally small in size, thereby permitting small sampling volumes with minimum interruptions of bodily functions following implantation, or, if used with process streams, following insertion in-line. Third, the biological material may be tailored to suit medical or industrial needs.
Biosensors are simple to use, single-step, reagentless devices which are inexpensive, disposable and fully competitive with conventional data-processing technology. Fig. 1 illustrates the general principle of biosensors. Intimate contact between biological and electrochemical systems is usually achieved by immobilisation of the biosensing system on the transducer surface by physical restraint behind a polymer membrane, or within gel matrix, by chemical crossing with a bifunctional agent, or by direct covalent attachment.
The biological system is responsible for specific recognition of the analyte and will subsequently respond with a concomitant change in a physiochemical parameter associated with the interaction. For instance, if the biological interaction results in a change in H, uptake or release of gases, ions, heat or electrons on a perturbation of an optical parameter proximal to the transducer, the biological signal may be converted into electrical signal prior to amplification, digitisation and presentation of the output in the desired format.
Transducer
There are physiochemcial devices that respond to the products of the binding on biocatalytic process. The choke of the most appropriate transducer configuration will be conditioned largely by the nature of the biocatalyst system, the secondary products to be monitored and the potential application of the final device. The ideal transducer should display a moderately fast response time, be amendable to facile fabrication and miniaturisation, be reliable and be able to compensate for adverse environmental effects such as temperature dependency and drift.
The potential of an ion-sensitive electrode is a logarithmic function of the ionic activity, with a 59.2ml charge in the electrode potential per tenfold change in concentration of a monovalent ion.
Photoactive P-nitrophenylazides, photosensitive polyvinylalcohol with pendent stilbazolium groups as a photo-cross linkable enterphnent matrix and piezoelectric ink-jet devices have all been used successfully to generate active, small-area enzyme membranes. For instance, it has been demonstrated that it is feasible to generate monolytinic multi-enzyme modified FET biosensors by using photolithographically-patterned, enzyme-loaded polyvinylalcohol films, and a triple-function silicon-on-sapphire array with an on-chip pseudo reference electrode for the measurement of urea, glucose and potassium ion. Thus, despite some unresolved problems, biosensors, based on integrated solidstate devices, display considerable potential for miniaturisation of multifunction configuration.
Ampreometric devices—also known as current-measuring devices—offer a wider scope of applications than potentiometric techniques and are dependent on analyte concentration, thereby according a normal dynamic range and normal response to error in measurement of current. A solidstate hydrogen peroxide (H2O2) sensor has been fabricated and used in a glucose sensor.
Fig. 2 displays a typical calibration curve for miniaturised amperometric glucose sensor. Thin-film microsensors of this type are promising devices for H2O2 detection since these are widely applicable and display good sensitivity.
Solution Conductance
An alternative measuring principle, which is also widely applicable to biological systems, is the exploitation of solution conductance. The development and operation of an accurate microelectronic conductance biosensor, which operates in a differential mode by monitoring the change in conductance occasioned by the catalytic action of enzymes, has also been described.
Other on-chip measurement principles are also exploited in the fabrication of biosensors. For instance, it has been demonstrated that two temperature-sensitive devices, each consisting of three Darlington-connected npn transistors and CMOS and constant current circuits, can be used for differential calourimetric determination of glucose concentrations.
The difference in steady-state output voltage of enzyme-modified sensor compared to unmodified (after addition of 2-100 millimoles glucose) was related to catalytically-induced temperature changes and, thus, glucose concentration.
Furthermore, miniature piezoelectric sensors like quartz crystal and surface acoustic wave devices can be used directly in aqueous solution as enzyme substrate of immunochemical sensor. Excellent reproducibilities, coating lifetimes, response time and sensitivity are obtained.
Potential for Technology
Clearly, biosensors have evolved into miniaturised disposable solidstate devices, having the theoretical capability to cointegrate the signal-processing and signal-conditioning circuitries directly on chip and, thereby, obviate the requirements for traditional external instrumentation. A multifunction chip, comprising an array of biologically-sensitised gases deposited on a monolithic silicon chip, could also incorporate sufficient signal-conditioning capability to integrate each sensor. This, in turn, assesses outputs, compares with calibration-channel and releases the information on concentration, date, batch code, expiration date and operations code. However, the obstacles that remain are formidable.
Molecular Electronics
‘Molecular electronics’ is the term coined to describe the exploitation of bio-molecules in the fabrication of electronic materials with novel electronic, optical or magnetic properties.In biology one finds many examples of organised structures on an intracellular, cellular or intercellular level, and at even the molecular level has an analogy with conventional electronic data-processing. Biological systems, in fact, perform all the functions of interest to modern electronic industry—sensing, input/output, memory, computations—as well as functions not yet achieved like rapid, complex pattern-recognition and learning. It is more likely that the self-assembly property of proteins will be exploited to form a template or matrix for proper assembly of complex architecture for conventional electronic components. In fact, the razor-sharp incisors of rodents, which make them one of the most destructive pests, have now played a dramatic role reversal. They may hold the key to incalculable benefits to humanity by speeding up computer revolution. A team of scientists, led by Dr Venkatesan Ranugopal Krishnan at Harvard University, claims to have demonstrated that protein derived from the enamel of a rodent’s tooth could be used to make computer chips a thousand times more powerful than those used today.
Though computer already functions at high speed, complex number-crunching tasks, such as detailed weather prediction, still take hours to complete. The human body, for instance, houses an amazing network of electronic circuitry that conducts information in a flash to various organs. Understanding the structure of microscopic protein material that resembles the task of semiconductors in a computer would help scientists solve the problem of miniaturisation. The stumbling block has been the inability to find a protein capable of sustaining the harsh atmosphere of a computer and correspond to a computer’s logical structure of commands. That is critical because computers operate in the binary system where paths through a microchip either open or shut when stimulated by an electrical impulse. The flip-flop action—at present taking a few billions of a second—determines the speed with which a computer will process information.
When Dr Krishnan’s team isolated a protein called amelogenin from rodents’ tooth enamel, they found that it could not only withstand the engineering required to make computer chips but also remained stable under working conditions.The team found that proteins could be used for reading and writing data using lasers and offered enormous amounts of memory. A chip made from amelogenin also increases processing speed. This is because of its capability to alternate between open and shut states in a few trillionths of a second—a 1000-fold improvement, offering tetrabytes instead of the currently-available gigabytes of memory. In short, amelogenin promises far more efficient and reliable protein-based chips than anything developed previously. Still, these biochips need more development before they are ready for commercial use. This can safely be estimated to take place at least two decades hence. However, a prototype of hybrid protein is planned to bring the bionic computer—a perennial fantasy of science fiction writers—a lot closer to reality.
In addition, biological analogies are likely to suggest the development of novel structures and algorithms to achieve functions not readily accomplished by computing devices of present-day design. In addition, the analysis- sensitive membranes of ion-sensitive electrodes have been integrated with monolithic solidstate FET technology to introduce a range of ion-selective and substrate-specific FETs. For instance, an FET sensitive to penicillin has been constructed which responded to penicillin concentration of up to 50-60 millimole in less than 30 seconds. It displayed a lifetime of approximately two months and permitted automatic compensation for temperature and ambient pH. However, the buffer capacity of the analyte was found to have a profound influence on the sensitivity and range and linear response.
Similar limitations are experienced with enzyme-modified FET devicessuch as those responsive to glucose, urea, acetylcholine, adenosinetri-phosphate (ATP) and lipid, with the complementary enzyme glucoseoxidase, uncase acetylcholinesterase, adenosinetriphosphatase (ATPase) and lipase respectively immobilised to pH-responsive Si3N4 or iridium oxide (I203) gate materials. A co-integrated, coulometric-feedback system may circumvent these limitations. The electrolysis of water at a noble-metal electrode, spatially positioned close to urea-sensitive FET, generates H+ which can be used to balance the uptake engendered by enzyme activity.
Neuronal Interfaces
Finally, bioelectronics incorporates the development of functional neuronal interfaces which permit contiguity among neuronal tissues and conventional solidstate and computing technology. This is done to achieve applications such as avral and visual prostheses, treatment of paralysis and even enhancement of memory and intelligence.
The term biochip is sometimes used to describe an implantable system that would enable the interconnection of nervous tissues with conventional computers. However, like the construction of bio-sensor, the fabrication of a functioning neuronal interface or artificial synapse will require the development of appropriate reversible chemical to electrical-transduction processes. The development at neuronal interface is likely to acquire greater knowledge about chemical mechanism which govern synaptic communication.
The subject of bioelectronics has moved from mere conjecture to an experimental stage but further research is necessary to bring a commercial class to this technology. However, this is a high-risk and a high-investment field. Nevertheless, it is one of the most fascinating and promising fields and, once developed to an extent, will make bioelectronic systems very cheap.
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