Biosensor

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A biosensor is a device for the detection of an analyte that combines a biological component with a physicochemical detector component.

It consists of 3 parts:

• the sensitive biological element (biological material (eg. tissue, microorganisms, organelles, cell receptors, enzymes, antibodies, nucleic acids, etc), a biologically derived material or biomimic) The sensitive elements can be created by biological engineering.
• the transducer in between (associates both components)
• the detector element (works in a physicochemical way; optical, piezoelectric electrochemical, thermometric, or magnetic.)

The most widespread example of a commercial biosensor is the blood glucose biosensor, which uses an enzyme to break blood glucose down. In doing so it transfers an electron to an electrode and this is converted into a measure of blood glucose concentration. The high market demand for such sensors has fueled development of associated sensor technologies.

Recently, arrays of many different detector molecules have been applied in so called electronic nose devices, where the pattern of response from the detectors is used to fingerprint a substance.

A canary in a cage, as used by miners to warn of gas could be considered a biosensor. Many of today's biosensor applications are similar, in that they use organisms which respond to toxic substances at a much lower level than us to warn us of their presence. Such devices can be used both in environmental monitoring and in water treatment facilities.

[edit] Principles of Detection

Piezoelectric biosensors and optical biosensors based on the phenomenon of surface plasmon resonance are both evanescent wave techniques. This utilises a property shown of gold and other materials; specifically that a thin layer of gold on a high refractive index glass surface can absorb laser light, producing electron waves (surface plasmons) on the gold surface. This occurs only at a specific angle and wavelength of incident light and is highly dependent on the surface of the gold, such that binding of a target analyte to a receptor on the gold surface produces a measurable signal.

Other optical biosensors are mainly based on changes in absorbance or fluorescence of an appropriate indicator compound.

Piezoelectric sensors utilise crystals which undergo a phase transformation when an electrical current is applied to them. An alternating current (A.C.) produces a standing wave in the crystal at a characteristic frequency. This frequency is highly dependent on the surface properties of the crystal, such that if a crystal is coated with a biological recognition element the binding of a (large) target analyte to a receptor will produce a change in the resonant frequency, which gives a binding signal.

Electrochemical biosensors are normally based on enzymatic catalysis of a reaction that produces ions. The sensor substrate contains three electrodes, a reference electrode, an active electrode and a sink electrode. A counter electrode may also be present as an ion source. The target analyte is involved in the reaction that takes place on the active electrode surface, and the ions produced create a potential which is subtracted from that of the reference electrode to give a signal. Another example of an electrochemical biosensor, which is contrary to the current understanding of their ability, are screenprinted, conducting polymer coated, open circuit potential biosensors based on immunoassays. These biosensors only have two electrodes and are extremely sensitive, robust and accurate. They enable the detection of analytes at levels previously only achievable by HPLC and LC/MS and without rigourous sample preparation. The signal is produced by electrochemical and physical changes in the conducting polymer layer due to changes occurring at the surface of the sensor such as; ionic strength, pH, hydration and redox due to the enzyme label turning over a substrate.

Surface plasmon resonance sensors operate using a sensor chip consisting of a plastic cassette supporting a glass plate, one side of which is coated with a microscopic layer of gold. This side contacts the optical detection apparatus of the instrument. The opposite side is then contacted with a microfluidic flow system. The contact with the flow system creates channels across which reagents can be passed in solution. This side of the glass sensor chip can be modified in a number of ways, to allow easy attachment of molecules of interest. Normally it is coated in carboxymethyl dextran or similar compound.

Light, at a fixed wavelength is reflected off the gold side of the chip, at the angle of total internal reflection and detected inside the instrument. This induces the evanescent wave to penetrate through the glass plate and someway into the liquid flowing over the surface.

The refractive index at the flow side of the chip surface has a direct influence on the behaviour of the light reflected off the gold side. Binding to the flow side of the chip has an effect on the refractive index and in this way biological interactions can be measured to a high degree of sensitivity.

Thermometric and magnetic based biosensors are rare.

[edit] Applications

There are many potential application of biosensors of various types. The main requirements for a biosensor approach to be valuable in terms of research and commercial applications are the identification of a target molecule, availability of a suitable biological recognition element, and the potential for disposable portable detection systems to be preferred to sensitive laboratory-based techniques in some situations. Some examples are given below:

• Glucose monitoring in diabetes patients <-- historical market driver
• Other medical health related targets
• Environmental applications e.g. the detection of Pesticides and river water contaminants
• Remote sensing of airborne bacteria e.g. in counter-bioterrorist activities
• Detection of pathogens
• Determining levels of toxic substances before and after bioremediation
• Detection and determining of organophosphate
• Routine analytical measurement of folic acid, biotin, vitamin B12 and pantothenic acid as an alternative to microbiological assay
• Determination of drug residues in food, such as antibiotics and growth promoters, particularly meat and honey.
• Drug discovery and evaluation of biological activity of new compounds.