A biosensor is an analytical device for the detection of an analyte
An analyte, or component , is a substance or chemical constituent that is of interest in an analytical procedure. Grammatically, it is important to note that experiments always seek to measure properties of analytes—and that analytes themselves can never be measured. For instance, one cannot...

 that combines a biological component with a physicochemical detector component.

It consists of 3 parts:
  • the sensitive biological element (biological material (e.g. tissue, microorganisms, organelles, cell receptors, enzyme
    Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

    s, antibodies
    An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...

    , nucleic acid
    Nucleic acid
    Nucleic acids are biological molecules essential for life, and include DNA and RNA . Together with proteins, nucleic acids make up the most important macromolecules; each is found in abundance in all living things, where they function in encoding, transmitting and expressing genetic information...

    s, etc.), a biologically derived material or biomimic component that interacts (binds or recognises) the analyte under study. The biologically sensitive elements can also be created by biological engineering
    Biological engineering
    Biological engineering, biotechnological engineering or bioengineering is the application of concepts and methods of biology to solve problems in life sciences, using engineering's own analytical and synthetic methodologies and also its traditional...

  • the transducer or the detector element (works in a physicochemical way; optical, piezoelectric, electrochemical, etc.) that transforms the signal resulting from the interaction of the analyte with the biological element into another signal (i.e., transducers) that can be more easily measured and quantified;
  • biosensor reader device with the associated electronics or signal processors that are primarily responsible for the display of the results in a user-friendly way. This sometimes accounts for the most expensive part of the sensor device, however it is possible to generate a user friendly display that includes transducer and sensitive element(see Holographic Sensor
    Holographic sensor
    A holographic sensor is a device that comprises a hologram embedded in a smart material that detects certain molecules or metabolites. This detection is usually a chemical interaction that is transduced as a change in one of the properties of the holographic reflection , either refractive index or...

    ). The readers are usually custom-designed and manufactured to suit the different working principles of biosensors. Known manufacturers of biosensor electronic readers include PalmSens, Gwent Biotechnology Systems and Rapid Labs.

A common example of a commercial biosensor is the blood glucose biosensor, which uses the enzyme glucose oxidase
Glucose oxidase
The glucose oxidase enzyme is an oxido-reductase that catalyses the oxidation of glucose to hydrogen peroxide and D-glucono-δ-lactone. In cells, it aids in breaking the sugar down into its metabolites....

 to break blood glucose down. In doing so it first oxidizes glucose and uses two electrons to reduce the FAD (a component of the enzyme) to FADH2. This in turn is oxidized by the electrode (accepting two electrons from the electrode) in a number of steps. The resulting current is a measure of the concentration of glucose. In this case, the electrode is the transducer and the enzyme is the biologically active component.

Recently, arrays of many different detector molecules have been applied in so called electronic nose
Electronic nose
An electronic nose is a device intended to detect odors or flavors.Over the last decade, “electronic sensing” or “e-sensing” technologies have undergone important developments from a technical and commercial point of view...

 devices, where the pattern of response from the detectors is used to fingerprint a substance. . In the Wasp Hound odor-detector, the mechanical element is a video camera and the biological element is five parasitic wasps who have been conditioned to swarm in response to the presence of a specific chemical. Current commercial electronic noses, however, do not use biological elements.

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 concentrations than humans can detect to warn of the presence of the toxin. Such devices can be used in environmental monitoring, trace gas detection and in water treatment facilities.


Many optical biosensors based on the phenomenon of surface plasmon resonance
Surface plasmon resonance
The excitation of surface plasmons by light is denoted as a surface plasmon resonance for planar surfaces or localized surface plasmon resonance for nanometer-sized metallic structures....

 (SPR) are evanescent wave
Evanescent wave
An evanescent wave is a nearfield standing wave with an intensity that exhibits exponential decay with distance from the boundary at which the wave was formed. Evanescent waves are a general property of wave-equations, and can in principle occur in any context to which a wave-equation applies...

 techniques. This utilises a property of gold
Gold is a chemical element with the symbol Au and an atomic number of 79. Gold is a dense, soft, shiny, malleable and ductile metal. Pure gold has a bright yellow color and luster traditionally considered attractive, which it maintains without oxidizing in air or water. Chemically, gold is a...

 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.

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 of 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 some distance 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 with some sort of energy. The refractive index of the medium near the surface changes when biomolecules attach to the surface, and the SPR angle varies as a function of this change.

Other evanescent wave biosensors have been commercialised using waveguides where the propagation constant through the waveguide is changed by the absorption of molecules to the waveguide surface. One such example, Dual Polarisation Interferometry
Dual Polarisation Interferometry
Dual polarization interferometry is an analytical technique that can probe molecular scale layers adsorbed to the surface of a waveguide by using the evanescent wave of a laser beam confined to the waveguide...

 uses a buried waveguide as a reference against which the change in propagation constant is measured. Other configurations such as the Mach-Zehnder have reference arms lithographically defined on a substrate. Higher levels of integration can be achieved using resonator geometries where the resonant frequency of a ring resonator changes when molecules are absorbed.

Other optical biosensors are mainly based on changes in absorbance or fluorescence of an appropriate indicator compound and do not need a total internal reflection geometry. For example, a fully operational prototype device detecting casein in milk has been fabricated. The device is based on detecting changes in absorption of a gold layer. A widely used research tool, the micro-array, can also be considered a biosensor.

Nanobiosensors use a immobilized bioreceptor probe that is selective for target analyte molecules. Nanomaterials are exquisitely sensitive chemical and biological sensors. Nanoscale materials demonstrate unique properties. Their large surface area to volume ratio can achieve rapid and low cost reactions, using a variety of designs.

Biological biosensors often incorporate a genetically modified form of a native protein or enzyme. The protein is configured to detect a specific analyte and the ensuing signal is read by a detection instrument such as a fluorometer or luminometer. An example of a recently developed biosensor is one for detecting cytosol
The cytosol or intracellular fluid is the liquid found inside cells, that is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondrion into compartments....

ic concentration of the analyte cAMP (cyclic adenosine monophosphate), a second messenger involved in cellular signaling triggered by ligands interacting with receptors on the cell membrane. Similar systems have been created to study cellular responses to native ligands or xenobiotics (toxins or small molecule inhibitors). Such "assays" are commonly used in drug discovery development by pharmaceutical and biotechnology companies. Most cAMP assays in current use require lysis of the cells prior to measurement of cAMP. A live-cell biosensor for cAMP can be used in non-lysed cells with the additional advantage of multiple reads to study the kinetics of receptor response.


Electrochemical biosensors are normally based on enzymatic catalysis of a reaction that produces or consumes electrons (such enzymes are rightly called redox enzymes). The sensor substrate usually contains three electrode
An electrode is an electrical conductor used to make contact with a nonmetallic part of a circuit...

s; a reference electrode
Reference electrode
A reference electrode is an electrode which has a stable and well-known electrode potential. The high stability of the electrode potential is usually reached by employing a redox system with constant concentrations of each participants of the redox reaction.There are many ways reference...

, a working electrode and a counter electrode. The target analyte is involved in the reaction that takes place on the active electrode surface, and the reaction may cause either electron transfer across the double layer (producing a current) or can contribute to the double layer potential (producing a voltage). We can either measure the current (rate of flow of electrons is now proportional to the analyte concentration) at a fixed potential or the potential can be measured at zero current (this gives a logarithmic response). Note that potential of the working or active electrode is space charge sensitive and this is often used. Further, the label-free and direct electrical detection of small peptides and proteins is possible by their intrinsic charges using biofunctionalized ion-sensitive field-effect transistors.

Another example, the potentiometric biosensor, (potential produced at zero current) gives a logarithmic response with a high dynamic range. Such biosensors are usually often made by screen printing the electrode patterns on a plastic substrate, coated with a conducting polymer and then some protein (enzyme or antibody) is attached. They have only two electrodes and are extremely sensitive and robust. They enable the detection of analytes at levels previously only achievable by HPLC and LC/MS and without rigorous sample preparation. All biosensors usually involve minimal sample preparation as the biological sensing component is highly selective for the analyte concerned. 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 changes can be attributed to ionic strength, pH, hydration and redox reactions, the latter due to the enzyme label turning over a substrate ( Field effect transistors, in which the gate region has been modified with an enzyme or antibody, can also detect very low concentrations of various analytes as the binding of the analyte to the gate region of the FET cause a change in the drain-source current.

Ion Channel Switch

The use of ion channels has been shown to offer highly sensitive detection
of target biological molecules. By imbedding the ion channels in supported or tethered bilayer membranes
Model lipid bilayer
A model lipid bilayer is any bilayer assembled in vitro, as opposed to the bilayer of natural cell membranes or covering various sub-cellular structures like the nucleus. A model bilayer can be made with either synthetic or natural lipids. The simplest model systems contain only a single pure...

 (t-BLM) attached to a gold electrode, an electrical circuit is created. Capture molecules such as antibodies can be bound to the ion channel so that the binding of the target molecule controls the ion flow through the channel. This results in a measurable change in the electrical conduction which is proportional to the concentration of the target.

An Ion Channel Switch (ICS) biosensor can be created using gramicidin, a dimeric peptide channel, in a tethered bilayer membrane. One peptide of gramicidin, with attached antibody, is mobile and one is fixed. Breaking the dimer stops the ionic current through the membrane. The magnitude of the change in electrical signal is greatly increased by separating the membrane from the metal surface using a hydrophilic spacer.

Quantitative detection of an extensive class of target species, including proteins, bacteria, drug and toxins has been demonstrated using different membrane and capture configurations.


Piezoelectric sensors utilise crystals which undergo an elastic deformation when an electrical potential is applied to them. An alternating potential (A.C.) produces a standing wave in the crystal at a characteristic frequency. This frequency is highly dependent on the elastic 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 resonance frequency, which gives a binding signal. In a mode that uses surface acoustic waves (SAW), the sensitivity is greatly increased. This is a specialised application of the Quartz crystal microbalance
Quartz crystal microbalance
A quartz crystal microbalance measures a mass per unit area by measuring the change in frequency of a quartz crystal resonator. The resonance is disturbed by the addition or removal of a small mass due to oxide growth/decay or film deposition at the surface of the acoustic resonator...

 as a biosensor.

Thermometric and magnetic based biosensors are rare.


There are many potential applications 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
    Bioremediation is the use of microorganism metabolism to remove pollutants. Technologies can be generally classified as in situ or ex situ. In situ bioremediation involves treating the contaminated material at the site, while ex situ involves the removal of the contaminated material to be treated...

  • Detection and determining of organophosphate
    An organophosphate is the general name for esters of phosphoric acid. Phosphates are probably the most pervasive organophosphorus compounds. Many of the most important biochemicals are organophosphates, including DNA and RNA as well as many cofactors that are essential for life...

  • Routine analytical measurement of folic acid
    Folic acid
    Folic acid and folate , as well as pteroyl-L-glutamic acid, pteroyl-L-glutamate, and pteroylmonoglutamic acid are forms of the water-soluble vitamin B9...

    , biotin
    Biotin, also known as Vitamin H or Coenzyme R, is a water-soluble B-complex vitamin discovered by Bateman in 1916. It is composed of a ureido ring fused with a tetrahydrothiophene ring. A valeric acid substituent is attached to one of the carbon atoms of the tetrahydrothiophene ring...

    , vitamin B12
    Vitamin B12
    Vitamin B12, vitamin B12 or vitamin B-12, also called cobalamin, is a water-soluble vitamin with a key role in the normal functioning of the brain and nervous system, and for the formation of blood. It is one of the eight B vitamins...

     and pantothenic acid
    Pantothenic acid
    Pantothenic acid, also called pantothenate or vitamin B5 , is a water-soluble vitamin. For many animals, pantothenic acid is an essential nutrient. Animals require pantothenic acid to synthesize coenzyme-A , as well as to synthesize and metabolize proteins, carbohydrates, and fats.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.
  • Protein engineering in biosensors
  • Detection of toxic metabolites such as mycotoxin
    A mycotoxin is a toxic secondary metabolite produced by organisms of the fungus kingdom, commonly known as molds. The term ‘mycotoxin’ is usually reserved for the toxic chemical products produced by fungi that readily colonize crops...

  • Detection of molecules in human breath to locate and save trapped survivors during disasters.

Glucose monitoring

Commercially available gluocose monitors rely on amperometric sensing of glucose
Blood glucose monitoring
Blood glucose monitoring is a way of testing the concentration of glucose in the blood . Particularly important in the care of diabetes mellitus, a blood glucose test is performed by piercing the skin to draw blood, then applying the blood to a chemically active disposable 'test-strip'...

 by means of glucose oxidase
Glucose oxidase
The glucose oxidase enzyme is an oxido-reductase that catalyses the oxidation of glucose to hydrogen peroxide and D-glucono-δ-lactone. In cells, it aids in breaking the sugar down into its metabolites....

, which oxidises glucose producing hydrogen peroxide which is detected by the electrode. To overcome the limitation of ameperometric sensors, a flurry of research is present into novel sensing methods, such as fluorescent glucose biosensors.

Biosensors in food analysis

There are several applications of biosensors in food analysis. In food industry optic coated with antibodies are commonly used to detect pathogens and food toxins. The light system in these biosensors has been 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
Surface plasmon resonance
The excitation of surface plasmons by light is denoted as a surface plasmon resonance for planar surfaces or localized surface plasmon resonance for nanometer-sized metallic structures....

 based sensor systems, often adapted from existing ELISA
Enzyme-linked immunosorbent assay , is a popular format of a "wet-lab" type analytic biochemistry assay that uses one sub-type of heterogeneous, solid-phase enzyme immunoassay to detect the presence of a substance in a liquid sample."Wet lab" analytic biochemistry assays involves detection of an...

 or other immunological assay. These are in widespread use across the food industry.

Surface Attachment of the biological elements

An important part in a biosensor is to attach the biological elements (small molecules/protein/cells) to the surface of the sensor (be it metal, polymer or glass). The simplest way is to functionalize
Surface engineering
Surface engineering is the sub-discipline of materials science which deals with the surface of solid matter. It has applications to chemistry, mechanical engineering, and electrical engineering ....

 the surface in order to coat it with the biological elements. This can be done by polylysine, aminosilane, epoxysilane or nitrocellulose in the case of silicon chips/silica glass. Subsequently the bound biological agent may be for example fixed by Layer by layer
Layer by layer
Layer-by-Layer deposition is a thin film fabrication technique. The films are formed by depositing alternating layers of oppositely charged materials with wash steps in between. A simple representation can be made by defining two oppositely charged polyions as + and -, and defining the wash step...

 depositation of alternatively charged polymer coatings
Alternatively three dimensional lattices (hydrogel/xerogel) can be used to chemically or physically entrap these (where by chemically entraped it is meant that the biological element is kept in place by a strong bond, while physically they are kept in place being unable to pass through the pores of the gel matrix). The most commonly used hydrogel is sol-gel, a glassy silica generated by polymerization of silicate monomers (added as tetra alkyl orthosilicates, such as TMOS
Tetramethyl orthosilicate
Tetramethyl orthosilicate is the chemical compound with the formula Si4. This molecule consists of four methyl groups attached to the hypothetical anion SiO44-...

 or TEOS
Tetraethyl orthosilicate
Tetraethyl orthosilicate is the chemical compound with the formula Si4. Often abbreviated TEOS, this molecule consists of four ethyl groups attached to SiO44- ion, which is called orthosilicate. As an ion in solution, orthosilicate does not exist. Alternatively TEOS can be considered to be the...

) in the presence of the biological elements (along with other stabilizing polymers, such as PEG
Polyethylene glycol
Polyethylene glycol is a polyether compound with many applications from industrial manufacturing to medicine. It has also been known as polyethylene oxide or polyoxyethylene , depending on its molecular weight, and under the tradename Carbowax.-Available forms:PEG, PEO, or POE refers to an...

) in the case of physical entrapment.
Another group of hydrogels, which set under conditions suitable for cells or protein, are acrylate hydrogel, which polymerize upon radical initiation
Radical initiator
In chemistry, radical initiators are substances that can produce radical species under mild conditions and promote radical reactions . These substances generally possess weak bonds—bonds that have small bond dissociation energies. Radical initiators are utilized in industrial processes such...

. One type of radical initiator is a peroxide
A peroxide is a compound containing an oxygen–oxygen single bond or the peroxide anion .The O−O group is called the peroxide group or peroxo group. In contrast to oxide ions, the oxygen atoms in the peroxide ion have an oxidation state of −1.The simplest stable peroxide is hydrogen peroxide...

 radical, typically generated by combining a persulfate
Ammonium persulfate
Ammonium persulfate 2S2O8 is a strong oxidizing agent. It is very soluble in water; the dissolution of the salt in water is endothermic. It is a radical initiator. It is used to etch copper on printed circuit boards as an alternative to ferric chloride solution...

 with TEMED
Tetramethylethylenediamine is a chemical compound with the formula 2NCH2CH2N2. This species is derived from ethylenediamine by replacement of the four N-H groups with four N-methyl groups. Its odor is remarkably similar to that of fish.-As a reagent in organic and inorganic synthesis:TMEDA is...

 (Polyacrylamide gel are also commonly commonly used for protein electrophoresis
Protein electrophoresis
Protein electrophoresis is a method for analysing the proteins in a fluid or an extract. The electrophoresis may be performed with a small volume of sample in a number of alternative ways with or without a supporting medium: SDS polyacrylamide gel electrophoresis Protein electrophoresis is a method...

), alternatively light can be used in combination with a photoinitiator, such as DMPA (2,2-dimethoxy-2-phenylacetophenone
2,2-Dimethoxy-2-phenylacetophenone is a photoinitiator, which is used to initialise radical polymerisation e.g. in the preparation of acrylate polymers....

). Smart materials that mimic the biological components of a sensor can also be classified as biosensors using only the active or catalytic site or analogous configurations of a biomolecule.

See also

  • Bioactive paper
    Bioactive paper
    Bioactive paper has been developed at the biosensor stage level, which means it can detect pesticides but is not yet able to repel and deactivate toxins. However, its ability to detect potential hazards is still very beneficial to human health and safety....

  • DNA field-effect transistor
  • Surface plasmon resonance
    Surface plasmon resonance
    The excitation of surface plasmons by light is denoted as a surface plasmon resonance for planar surfaces or localized surface plasmon resonance for nanometer-sized metallic structures....

  • plasmon
    In physics, a plasmon is a quantum of plasma oscillation. The plasmon is a quasiparticle resulting from the quantization of plasma oscillations just as photons and phonons are quantizations of light and mechanical vibrations, respectively...

  • Dual Polarisation Interferometry
    Dual Polarisation Interferometry
    Dual polarization interferometry is an analytical technique that can probe molecular scale layers adsorbed to the surface of a waveguide by using the evanescent wave of a laser beam confined to the waveguide...

  • Biointerface
    A biointerface is the interface between a cell, a biological tissue or a biomaterial with another material. The motivation for biointerface science stems from the urgent need to increase the understanding of interactions between biomolecules and surfaces...

External links

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