UGWU OKECHUKWU EMMANUEL
Abstract
Biosensors are of great significance because of their capability to resolve a potentially large number of analytical problems and challenges in very diverse areas such as defense, homeland security, agriculture and food safety, environmental monitoring, medicine, pharmacology, industry, etc. The expanding role of bio-sensing in society and a real-world environment has led to an exponential growth of the R&D efforts around the world. Such growth is driven by several factors including medical and health problems, such as a growing population with a high risk of diabetes and obesity, and the rising incidence of chronic diseases such as heart disease, stroke, cancer, chronic respiratory diseases, tuberculosis, etc.; significant problems with environmental monitoring; and of course serious challenges in security and military applications and agriculture/food safety. As the potential threat of bioterrorism increases, there is great need for a tool that can quickly, reliably and accurately detect contaminating bio-agents in the atmosphere. Biosensors can essentially serve as low-cost and highly efficient devices for this purpose in addition to being used in other day- to- day applications. A biosensor is a sensing device comprised of a combination of a specific biological element and a transducer.
CHAPTER ONE
Introduction
Biosensors are analytical devices incorporating a biological sensing element. They harness the exquisite sensitivity and specificity of biology in conjunction with physicochemical transducers to deliver complex bioanalytical measurements with simple, easy-to-use formats. Potential uses embrace virtually every conceivable analytical task, ranging from medical diagnostics through drug discovery, food safety, process control and environmental monitoring, to defense and security applications. The basic concept of the biosensor was first elucidated by Leyland C. Clark in 1962, in his seminal description of an “enzyme electrode”. Building on his earlier invention of the Clark oxygen electrode, he reasoned that electrochemical detection of oxygen or hydrogen peroxide could be used as the basis for broad range of bio-analytical instruments, by the incorporation of appropriate immobilized enzymes (J. Newman and Turner., 2005). The classic example was immobilized glucose oxidase (GOx), which converted a simple platinum electrode into a powerful analytical instrument for the detection of glucose in human samples from people with diabetes. Two decades later, optical transducers were harnessed in conjunction with antibodies to create real-time bio affinity monitors. These immunosensors laid the foundation for the second major evolutionary line of biosensing instrumentation. Both the enzyme electrode and the bio affinity sensors originally found utility in laboratory instruments, but advances in manufacturing coupled with mediated electrochemistry, launched the enzyme-based systems along a new and highly successful trajectory of home use, which was to lead to a turnover currently in excess of US$13 billion and engaged the full attention of the world's major diagnostics companies. Hence, electrochemistry has come to dominate distributed diagnostics, while optical techniques have found their niche principally in R&D. To complete the picture concerning transduction strategies, advances in acoustic resonance devices are certainly worthy of note, but both thermometric and magnetic transduction have failed to have any serious practical impact to date.
Growth in the field of biosensors has been phenomenal. Despite the vast numbers of papers published, the field of biosensors may be viewed as comprising essentially two broad categories of instrumentation: (a) sophisticated, high-throughput laboratory machines capable of rapid, accurate and convenient measurement of complex biological interactions and components; (b) easy-to-use, portable devices for use by non-specialists for decentralized, in situ or home analysis. The former are expensive and the latter are mass produced and inexpensive. With the emphasis on the research tools that demonstrate how the performance of biosensors evolved from the classical electrochemical to optical/visual, polymers, silica, glass, and nanomaterial to improve the detection limit, sensitivity, and selectivity. Interestingly, microbes and bioluminescence (Du et al., 2007) also contributed largely for label-based biosensors, while label-free biosensors involved usage of transistor or capacitor-based devices and nanomaterials. Biosensors provide a basis to understand technological improvement in the instrumentation involving sophisticated high-throughput machines for quantitative biologists and portable qualitative or semi-quantitative devices for non-specialists. Finally, current research trends, future challenges, and limitations in the field are highlighted. The present review is divided to various subsections describing two major technical strategies followed by various types of biosensor devices ranging from electrochemical, optical/ visual, polymers, silica, glass, and nanomaterials. These devices were developed for specific purposes and an overview of these will provide readers a comprehensive data on biosensor devices and their applications.
CHAPTER TWO
LITERATURE REVIEW
2.0 Biosensors
Biosensors are known as: immunosensors, optrodes, chemical canaries, resonant mirrors, glucometers, biochips, biocomputers, and so on. A commonly cited definition is: “a biosensor is a chemical sensing device in which a biologically derived recognition entity is coupled to a transducer, to allow the quantitative development of some complex biochemical parameter”, and also: “a biosensor is an analytical device incorporating a deliberate and intimate combination of a specific biological element (that creates a recognition event) and a physical element (that transduces the recognition event)”. The name “biosensor” signifies that the device is a combination of two parts: (i) a bio-element, and (ii) a sensor-element.
A specific “bio” element (say, enzyme) recognizes a specific analyte and the “sensor” element transduces the change in the biomolecule into an electrical signal. The bio element is very specific to the analyte to which it is sensitive. It does not recognize other analytes. Depending on the transducing mechanism used, the biosensors can be of many types such as:
Biosensors can have a variety of biomedical, industry, and military applications.
2.1 Basic Concepts
A biosensor consists of a bio-element and a sensor-element. The bio-element may be an enzyme, antibody, living cells, tissue, etc., and the sensing element may be electric current, electric potential, and so on. Different combinations of bio-elements and sensor-elements constitute several types of biosensors to suit a vast pool of applications.
The “bio” and the “sensor” elements can be coupled together in one of the four possible ways
In the membrane entrapment scheme, a semi permeable membrane separates the analyte and the bio-element, and the sensor is attached to the bio-element. The physical adsorption scheme is dependent on a combination of van der Waals forces, hydrophobic forces, hydrogen bonds, and ionic forces to attach the biomaterial to the surface of the sensor. The porous entrapment scheme is based on forming a porous encapsulation matrix around the biological material that helps in binding it to the sensor. In the case of the covalent bonding the sensor surface is treated as a reactive group to which the biological materials can bind.
The typically used bio-element, enzyme is a large protein molecule that acts as a catalyst in chemical reactions, but remains unchanged at the end of reaction.
An enzyme upon reaction with a substrate forms a complex molecule which under appropriate conditions forms the desirable product molecule releasing the enzyme at the end. The enzymes are extremely specific in their action: an enzyme X will change a specific substance A (not C) to another specific substance B (not D), this extremely specific action of the enzymes is the basis of biosensors.
2.2 TYPES OF BIOSENSORS
2.2.1 Resonant Biosensors
In this type of biosensor, an acoustic wave transducer is coupled with an antibody (bio-element).
When the analyte molecule (or antigen) gets attached to the membrane, the mass of the membrane changes. The resulting change in the mass subsequently changes the resonant frequency of the transducer. This frequency change is then measured.
2.2.2 Optical-detection Biosensors
The output transduced signal that is measured is light for this type of biosensor. The biosensor can be made based on optical diffraction or electro-chemiluminescence. In optical diffraction-based devices, a silicon wafer is coated with a protein via covalent bonds. The wafer is exposed to UV light through a photo-mask and the antibodies become inactive in the exposed regions. When the diced wafer chips are incubated in an analyte, antigen-antibody bindings are formed in the active regions, thus creating a diffraction grating. This grating produces a diffraction signal when illuminated with a light source such as laser. The resulting signal can be measured or can be further amplified before measuring for improved sensitivity.
2.2.3 Thermal-detection Biosensors
This type of biosensor is exploiting one of the fundamental properties of biological reactions, namely absorption or production of heat, which in turn changes the temperature of the medium in which the reaction takes place. They are constructed by combining immobilized enzyme molecules with temperature sensors. When the analyte comes in contact with the enzyme, the heat reaction of the enzyme is measured and is calibrated against the analyte concentration. The total heat produced or absorbed is proportional to the molar enthalpy and the total number of molecules in the reaction. The measurement of the temperature is typically accomplished via a thermistor, and such devices are known as enzyme thermistors. Their high sensitivity to thermal changes makes thermistors ideal for such applications. Unlike other transducers, thermal biosensors do not need frequent recalibration and are insensitive to the optical and electrochemical properties of the sample. Common applications of this type of biosensor include the detection of pesticides and pathogenic bacteria.
2.2.4 Ion-Sensitive Biosensors
These are semiconductor FETs having an ion-sensitive surface. The surface electrical potential changes when the ions and the semiconductor interact. This change in the potential can be subsequently measured. The Ion Sensitive Field Effect Transistor (ISFET) can be constructed by covering the sensor electrode with a polymer layer. This polymer layer is selectively permeable to analyte ions. The ions diffuse through the polymer layer and in turn cause a change in the FET surface potential. This type of biosensor is also called an ENFET (Enzyme Field Effect Transistor) and is primarily used for pH detection.
2.2.5 Electrochemical Biosensors
Electrochemical biosensors are mainly used for the detection of hybridized DNA, DNA-binding drugs, glucose concentration, etc. The underlying principle for this class of biosensors is that many chemical reactions produce or consume ions or electrons which in turn cause some change in the electrical properties of the solution which can be sensed out and used as measuring parameter. Electrochemical biosensors can be classified based on the measuring electrical parameters as:
2.2.5.1 Conductimetric
The measured parameter is the electrical conductance / resistance of the solution. When electrochemical reactions produce ions or electrons, the overall conductivity or resistivity of the solution changes. This change is measured and calibrated to a proper scale. Conductance measurements have relatively low sensitivity. The electric field is generated using a sinusoidal voltage (AC) which helps in minimizing undesirable effects such as Faradaic processes, double layer charging and concentration polarization.
2.2.5.2 Amperometry
This high sensitivity biosensor can detect electroactive species present in biological test samples.
Since the biological test samples may not be intrinsically electro-active, enzymes are needed to catalyze the production of radio-active species. In this case, the measured parameter is current.
2.2.5.3 Potentiometric
In this type of sensor, the measured parameter is oxidation or reduction potential of an electrochemical reaction. The working principle relies on the fact that when a ramp voltage is applied to an electrode in solution, a current flow occurs because of electrochemical reactions. The voltage at which these reactions occur indicates a particular reaction and particular species.
2.3 Characteristics of a biosensor
There are certain static and dynamic attributes that every biosensor possesses. The optimization of these properties is reflected on the performance of the biosensor.
Selectivity
Selectivity is perhaps the most important feature of a biosensor. Selectivity is the ability of a bioreceptor to detect a specific analyte in a sample containing other admixtures and contaminants. The best example of selectivity is depicted by the interaction of an antigen with the antibody. Classically, antibodies act as bioreceptors and are immobilized on the surface of the transducer. A solution (usually a buffer containing salts) containing the antigen is then exposed to the transducer where antibodies interact only with the antigens. To construct a biosensor, selectivity is the main consideration when choosing bioreceptors.
Reproducibility
Reproducibility is the ability of the biosensor to generate identical responses for a duplicated experimental set-up. The reproducibility is characterized by the precision and accuracy of the transducer and electronics in a biosensor. Precision is the ability of the sensor to provide alike results every time a sample is measured and accuracy indicates the sensor's capacity to provide a mean value close to the true value when a sample is measured more than once. Reproducible signals provide high reliability and robustness to the inference made on the response of a biosensor.
Stability
Stability is the degree of susceptibility to ambient disturbances in and around the biosensing system. These disturbances can cause a drift in the output signals of a biosensor under measurement. This can cause an error in the measured concentration and can affect the precision and accuracy of the biosensor. Stability is the most crucial feature in applications where a biosensor requires long incubation steps or continuous monitoring. The response of transducers and electronics can be temperature-sensitive, which may influence the stability of a biosensor. Therefore, appropriate tuning of electronics is required to ensure a stable response of the sensor. Another factor that can influence the stability is the affinity of the bioreceptor, which is the degree to which the analyte binds to the bioreceptor. Bioreceptors with high affinities encourage either strong electrostatic bonding or covalent linkage of the analyte that fortifies the stability of a biosensor. Another factor that affects the stability of a measurement is the degradation of the bioreceptor over a period of time.
Sensitivity
The minimum amount of analyte that can be detected by a biosensor defines its limit of detection (LOD) or sensitivity. In a number of medical and environmental monitoring applications, a biosensor is required to detect analyte concentration of as low as ng/ml or even fg/ml to confirm the presence of traces of analytes in a sample. For instance, a prostate-specific antigen (PSA) concentration of 4 ng/ml in blood is associated with prostate cancer for which doctors suggest biopsy tests. Hence, sensitivity is considered to be an important property of a biosensor.
Linearity
Linearity is the attribute that shows the accuracy of the measured response (for a set of measurements with different concentrations of analyte) to a straight line, mathematically represented as y=mc, where c is the concentration of the analyte, y is the output signal, and m is the sensitivity of the biosensor. Linearity of the biosensor can be associated with the resolution of the biosensor and range of analyte concentrations under test. The resolution of the biosensor is defined as the smallest change in the concentration of an analyte that is required to bring a change in the response of the biosensor. Depending on the application, a good resolution is required as most biosensor applications require not only analyte detection but also measurement of concentrations of analyte over a wide working range. Another term associated with linearity is linear range, which is defined as the range of analyte concentrations for which the biosensor response changes linearly with the concentration.
2.4 A BIOSENSOR TO MONITOR CELL MORPHOLOGY
Another type of biosensor can be used to monitor cell morphology in tissue culture environments. The sensing principle used is known as Electric Cell-substrate Impedance Sensing (ECIS). In this process, a small gold electrode is immersed in a tissue culture medium. When cells get attached and spread on the electrodes, the impedance measured across the electrode’s changes. This changing impedance can be used for understanding the cell behavior in the culture medium. The attachment and spreading behavior of the cells are important factors for this type of biosensor. Cancerous cells can usually grow and reproduce (mitosis) freely in a medium without being attached to any substrate/surface. Normal cells, on the other hand, need to be attached to a surface before they grow. After attachment the shape of the cells becomes flat and no longer remains spherical.
The principle of measurement is as follows: The cells are grown on gold electrodes. The electrodes are immersed in a tissue culture medium which works as electrolyte. A voltage is applied through a resistance and the magnitude and phase of the voltage are measured with a lock-in-amplifier.
Since the current is constant, the measured magnitude and phase can be assumed to be proportional to impedance (resistance and capacitance). After some time, it is found that the resistance and capacitance values fluctuate very often. This happens when cells are alive and moving. This type of biosensor has several advantages: It is less time consuming compared to conventional methods, it is possible to automate and quantify cell morphology measurements, and the fluctuating pattern can be used as signature for a cell.
2.5 DNA Detection
The category of biosensors used for DNA detection is also known as bio detectors. The objective is to isolate and measure the strength of single DNA–DNA or antibody–antigen bonds, which in turn helps in detecting and characterizing single molecules of DNA or antigen. In one method, multiple copies of the sample DNA are created using polymerase chain reaction (PCR). On the other hand, FABS (Force Amplified Biological Sensor), BARC (Bead Array Counter), and FDA (Force Differentiation Assay) biosensors can perform many such measurements in a single easy operation. In these cases, magnetic microbeads are used to pull on DNA–DNA or antibody–antigen bonds with a known force, and the strengths of the presumed bonds are tested by observing with a micromechanical sensor (FABS), or with a magneto resistive sensor (BARC) whether the beads detach from the surface. This kind of biosensor is extremely useful in the detection of Anthrax, Ricin, Botulinum and other pathogens. The FABS is needed for monitoring the concentration of various biological agents that may possibly be present in the environment. FABS is designed in such a way that it is fully automated, compact and rugged, and can be implemented remotely. The assay is also a rapid process as it may warn of some kind of potential threat to human health. FABS can detect various biologically active materials like toxins, proteins, viruses, and bacteria, in low concentrations.
2.6 Glucose monitoring
Commercially available glucose monitors rely on amperometry sensing of glucose by means of glucose oxidase, which oxidizes glucose producing hydrogen peroxide which is detected by the electrode. To overcome the limitation of amperometry sensors, a flurry of research is present into novel sensing methods, such as fluorescent glucose biosensors.
2.7 Interferometric reflectance imaging sensor
The interferometric reflectance imaging sensor (IRIS) is based on the principles of optical interference and consists of a silicon-silicon oxide substrate, standard optics, and low-powered coherent LEDs. When light is illuminated through a low magnification objective onto the layered silicon-silicon oxide substrate, an interferometric signature is produced (Ahn et al.)
Since initial publication, IRIS has been adapted to perform various functions. First, IRIS integrated a fluorescence imaging capability into the interferometric imaging instrument as a potential way to address fluorescence protein microarray variability. Briefly, the variation in fluorescence microarrays mainly derives from inconsistent protein immobilization on surfaces and may cause misdiagnoses in allergy microarrays. To correct from any variation in protein immobilization, data acquired in the fluorescence modality is then normalized by the data acquired in the label-free modality. IRIS has also been adapted to perform single nanoparticle counting by simply switching the low magnification objective used for label-free biomass quantification to a higher objective magnification. This modality enables size discrimination in complex human biological samples. Monroe et al. used IRIS to quantify protein levels spiked into human whole blood and serum and determined allergen sensitization in characterized human blood samples using zero sample processing. Other practical uses of this device include virus and pathogen detection.
2.8 Food analysis
There are several applications of biosensors in food analysis. In the food industry, optics coated with antibodies are commonly used to detect pathogens and food toxins. Commonly, the light system in these biosensors is fluorescence, since this type of optical measurement can greatly amplify the signal. A range of immuno- and ligand-binding assays for the detection and measurement of small molecules such as water-soluble vitamins and chemical contaminants (drug residues) such as sulfonamides and Beta-agonists have been developed for use on SPR based sensor systems, often adapted from existing ELISA or other immunological assay. These are in widespread use across the food industry.
2.9 DNA biosensors
In the future, DNA will find use as a versatile material from which scientists can craft biosensors. DNA biosensors can theoretically be used for medical diagnostics, forensic science, agriculture, or even environmental clean-up efforts. No external monitoring is needed for DNA-based sensing devices. This is a significant advantage. DNA biosensors are complicated mini-machines—consisting of sensing elements, micro lasers, and a signal generator. At the heart of DNA biosensor function is the fact that two strands of DNA stick to each other by virtue of chemical attractive forces. On such a sensor, only an exact fit—that is, two strands that match up at every nucleotide position—gives rise to a fluorescent signal (a glow) that is then transmitted to a signal generator.
2.10 Microbial biosensors
Using biological engineering researchers have created many microbial biosensors. An example is the arsenic biosensor. To detect arsenic they use the Ars operon.[94] Using bacteria, researchers can detect pollutants in samples.
2.11 Ozone biosensors
Because ozone filters out harmful ultraviolet radiation, the discovery of holes in the ozone layer of the earth's atmosphere has raised concern about how much ultraviolet light reaches the earth's surface. Of particular concern are the questions of how deeply into sea water ultraviolet radiation penetrates and how it affects marine organisms, especially plankton (floating microorganisms) and viruses that attack plankton. Plankton form the base of the marine food chains and are believed to affect our planet's temperature and weather by uptake of CO2 for photosynthesis.
Deneb Karentz, a researcher at the Laboratory of Radio-biology and Environmental Health (University of California, San Francisco) has devised a simple method for measuring ultraviolet penetration and intensity. Working in the Antarctic Ocean, she submerged to various depths thin plastic bags containing special strains of E. coli that are almost totally unable to repair ultraviolet radiation damage to their DNA. Bacterial death rates in these bags were compared with rates in unexposed control bags of the same organism. The bacterial "biosensors" revealed constant significant ultraviolet damage at depths of 10 m and frequently at 20 and 30 m. Karentz plans additional studies of how ultraviolet may affect seasonal plankton blooms (growth spurts) in the oceans.
2.12 Metastatic cancer cell biosensors
Metastasis is the spread of cancer from one part of the body to another via either the circulatory system or lymphatic system. Unlike radiology imaging tests (mammograms), which send forms of energy (x-rays, magnetic fields, etc.) through the body to only take interior pictures, biosensors have the potential to directly test the malignant power of the tumor. The combination of a biological and detector element allows for a small sample requirement, a compact design, rapid signals, rapid detection, high selectivity and high sensitivity for the analyte being studied. Compared to the usual radiology imaging tests biosensors have the advantage of not only finding out how far cancer has spread and checking if treatment is effective but also are cheaper, more efficient (in time, cost and productivity) ways to assess metastaticity in early stages of cancer.
2.13 EMERGING TECHNOLOGIES
Much has been written about glucose sensors due to their dominance in the field of biosensors, but this example should really be viewed largely a model that can be copied for hundreds and potentially thousands of alternative analytes. Admittedly, GOx has proved a remarkable useful, versatile and robust enzyme for incorporation into biosensors, but it has been superseded by alternative, engineered proteins based on quinoprotein glucose dehydrogenase in recent years. A wide range of other catalysts and affinity elements are now available to the biosensor technologist to create a diverse range of portable and lab-based instruments using electrochemical, optical or other transducer technologies. Genetic manipulation of catalytic proteins has created hybrid enzymes combining the best redox centres with protein shells exhibiting the greatest affinity and specificity for the desired metabolite. Meanwhile, the art of stabilisation has improved, using polyelectrolytes and sugars to stabilise dry reagents and yield long, stable shelf lives.
While electrochemical biosensors have made most impact in the form of enzyme electrodes, electrochemical immunoassay has delivered some remarkable results and a few minor commercial products.
The mainstay affinity element, the antibody, has likewise been modified to reduce excess baggage (antibody fragments) and improve selectivity (monoclonal antibodies). Moreover alternatives in the form of affibodies, peptides, aptamers and molecularly imprinted polymers have emerged as viable ways to construct affinity sensors.
Another non-immunoglobulin protein that can be used in sensors is the affibody, based for example, on the immunoglobulin binding B domain of protein A from the bacteria Staphylococcus aureus. Genetic engineering of this region results in an analogue known as the Z domain, further modification of which, via mutagenesis, leads to the production of a range of high affinity molecules that can be used as alternatives to antibodies in affinity sensors and assays.
Progressing from semi-synthetic to fully synthetic analogues of biological receptors could furnish a new generation of sensors that display the desired sensitivity and specificity of biosensors, but lack their consequential instability and, in some instances, irreproducibility. A variety of synthetic receptors have been explored for this purpose, but one of the most promising approaches is the use of molecularly-imprinted polymers.
Another relatively new imprinting approach that is particularly useful for electrochemical sensors uses electropolymerizing of a thin film of the recognition element directly on the sensor surface. The ability to precisely control the thickness of the layer and the fact that it is generated in situ, makes this an attractive alternative.
2.14 THE IMPACT OF NANOTECHNOLOGY
Reflecting on the last decade of biosensor development, one can clear see the impact of nanotechnology. One of the first new nanomaterials to impact on amperometry biosensors was the carbon nanotube (CNT), which was blended into a number of formulations to improve current densities and overall performance of enzyme electrodes and enzyme-labelled immunosensors.25 The most widely used nanomaterial in industry overall to date, however, is the silver nanoparticle. These have also been harnessed as a simple electrochemical label in a highly sensitive amperometry immunoassay intended for distributed diagnostics and as an inexpensive solution for immunoassays performed in developing countries. In this electrochemical sandwich immunoassay, silver nanoparticles are used as a robust label, which can be solubilized after the binding reaction has occurred, using thiocyanate, to form a silver chelate.
CHAPTER THREE
3.0 APPLICATION OF BIOSENSORS
Biosensors have a very wide range of applications that aim to improve the quality of life. This range covers their use for environmental monitoring, disease detection, food safety, defense, drug discovery and many more. One of the main applications of biosensors is the detection of biomolecules that are either indicators of a disease or targets of a drug. For example, electrochemical biosensing techniques can be used as clinical tools to detect protein cancer biomarkers. Biosensors can also be used as platforms for monitoring food traceability, quality, safety and nutritional value. These applications fall into the category of ‘single shot’ analysis tools, i.e. where cost-effective and disposable sensing platforms are required for the application. On the other hand, an application such as pollution monitoring requires a biosensor to function from a few hours to several days. Such biosensors can be termed ‘long-term monitoring’ analysis tools. Whether it is long-term monitoring or single shot analysis, biosensors find their use as technologically advanced devices both in resource-limited settings and sophisticated medical set-ups: e.g. with applications in drug discovery; for the detection of a number of chemical and biological agents that are considered to be toxic materials of defense interest; for use in artificial implantable devices such as pacemakers and other prosthetic devices; and sewage epidemiology
3.1 The role of biosensors in healthcare
Simple, easy-to-use measurement devices for a diverse range of biologically relevant analytes have an intuitive appeal as portable or pocket-sized analyzers, and this has driven the diverse range of applications. However, both historical precedent and a critical analysis of potential markets leads to an indisputable conclusion that healthcare is and will continue to be the most important area for the application of biosensors. The maintenance of health is one of the most laudable technological objectives challenging science and technology and diagnosis is an essential prerequisite for treatment and prevention of disease. Moreover, related applications of biosensors, such as the maintenance of food safety and environmental monitoring can be aligned with this central objective. The developing world has a desperate need for robust diagnostics that can be deployed in the field by both healthcare professionals and volunteers.
Glucose biosensors for diabetes have had the most profound effect on disease management to date, biosensors for other metabolites promise utility for other non-communicable diseases such as kidney disease, which is increasingly being recognized as an emerging problem in a rapidly ageing population. Multifarious affinity biosensors have been described to detect cardiac disease markers such as creatine kinase and troponin, while cancer markers and single cell cancer detection have attracted considerable recent literature. Last but by no means least, nucleic acid-based biosensors such as SNP detectors and gene chips, have played an increasingly significant role in personalized medicine. An example is the predetermination of the presence or absence of the KRAS genetic mutation, since its presence results in no benefit from Vectibix™, a monoclonal antibody-based therapy used for colorectal cancer. All this adds up to a prediction of a strong commercial future for biosensor technology.
3.2 CONCLUSION AND PERSPECTIVE
The enormous success of the glucose sensor serves as a model for future possibilities and should not overshadow the multifarious other applications that this versatile technology can address. Theranostics (companion diagnostics) offers an important new financial model to drive the development of biosensors, since the principal customer is not the patient, but the pharmaceutical company seeking to deliver an efficacious therapeutic. The impact of this freedom of patient access and mobility of data, enabled by information technology, is likely to stimulate demand for more analytical data and enable the patient or healthy subject to add data themselves, aided by a new range of over-the-counter biosensors. The expanding market generated by this boom in personal diagnostics will stimulate the development of new, inexpensive sensor platforms that can compete effectively to meet consumers' needs. Next generation diagnostics manufacturing is therefore targeting further integration to create complete sensing systems that can interface seamlessly with modern telecommunications. New technologies are likely to encompass all-printed systems capitalizing on the printed electronics revolution and systems with high compatibility with future mobile technology such as tablets and 4G phones. Emerging science, driving new sensors to deliver the molecular information that underpins all this, includes the development of semi-synthetic ligands that can deliver the exquisite sensitivity and specificity of biological systems without the inherent instability and redundancy associated with natural molecules. Currently aptamers, affibodies, peptide arrays and molecularly imprinted polymers are particularly promising research directions in this respect. Chances of success are enhanced by the potential utility of some of these materials for novel therapeutic, antimicrobial and drug release strategies, since these complimentary areas will drive investment in these approaches. New nanomaterials, conducting polymers and switchable systems offer exciting possibilities for hybrid devices.
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