Biosensor

A biosensor is an analytical device, used for the detection of a chemical substance, that combines a biological component with a physicochemical detector. The sensitive biological element, e.g. tissue, microorganisms, organelles, cell receptors, enzymes, antibodies, nucleic acids, etc., is a biologically derived material or biomimetic component that interacts, binds, or recognizes with the analyte under study. The biologically sensitive elements can also be created by biological engineering.The transducer or the detector element, which transforms one signal into another one, works in a physicochemical way: optical, piezoelectric, electrochemical,electrochemiluminescence etc., resulting from the interaction of the analyte with the biological element, to easily measure and quantify.The 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 (holographic sensor). The readers are usually custom-designed and manufactured to suit the different working principles of biosensors. A biosensor is an analytical device, used for the detection of a chemical substance, that combines a biological component with a physicochemical detector. The sensitive biological element, e.g. tissue, microorganisms, organelles, cell receptors, enzymes, antibodies, nucleic acids, etc., is a biologically derived material or biomimetic component that interacts, binds, or recognizes with the analyte under study. The biologically sensitive elements can also be created by biological engineering.The transducer or the detector element, which transforms one signal into another one, works in a physicochemical way: optical, piezoelectric, electrochemical,electrochemiluminescence etc., resulting from the interaction of the analyte with the biological element, to easily measure and quantify.The 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 (holographic sensor). The readers are usually custom-designed and manufactured to suit the different working principles of biosensors. A biosensor typically consists of a bio-recognition site, biotransducer component, and electronic system which includes a signal amplifier, processor, and display. Transducers and electronics can be combined, e.g., in CMOS-based microsensor systems. The recognition component, often called a bioreceptor, uses biomolecules from organisms or receptors modeled after biological systems to interact with the analyte of interest. This interaction is measured by the biotransducer which outputs a measurable signal proportional to the presence of the target analyte in the sample. The general aim of the design of a biosensor is to enable quick, convenient testing at the point of concern or care where the sample was procured. In a biosensor, the bioreceptor is designed to interact with the specific analyte of interest to produce an effect measurable by the transducer. High selectivity for the analyte among a matrix of other chemical or biological components is a key requirement of the bioreceptor. While the type of biomolecule used can vary widely, biosensors can be classified according to common types of bioreceptor interactions involving: antibody/antigen, enzymes/ligands, nucleic acids/DNA, cellular structures/cells, or biomimetic materials. An immunosensor utilizes the very specific binding affinity of antibodies for a specific compound or antigen. The specific nature of the antibody-antigen interaction is analogous to a lock and key fit in that the antigen will only bind to the antibody if it has the correct conformation. Binding events result in a physicochemical change that in combination with a tracer, such as a fluorescent molecules, enzymes, or radioisotopes, can generate a signal. There are limitations with using antibodies in sensors: 1.The antibody binding capacity is strongly dependent on assay conditions (e.g. pH and temperature) and 2. The antibody-antigen interaction is generally irreversible. However, it has been shown that binding can be disrupted by chaotropic reagents, organic solvents, or even ultrasonic radiation. The use of antibodies as the bio-recognition component of biosensors has several drawbacks. They have high molecular weights and limited stability, contain essential disulfide bonds and are expensive to produce. In one approach to overcome these limitations, recombinant binding fragments (Fab, Fv or scFv) or domains (VH, VHH) of antibodies have been engineered. In another approach, small protein scaffolds with favorable biophysical properties have been engineered to generate artificial families of Antigen Binding Proteins (AgBP), capable of specific binding to different target proteins while retaining the favorable properties of the parent molecule. The elements of the family that specifically bind to a given target antigen, are often selected in vitro by display techniques: phage display, ribosome display, yeast display or mRNA display. The artificial binding proteins are much smaller than antibodies (usually less than 100 amino-acid residues), have a strong stability, lack disulfide bonds and can be expressed in high yield in reducing cellular environments like the bacterial cytoplasm, contrary to antibodies and their derivatives. They are thus especially suitable to create biosensors. The specific binding capabilities and catalytic activity of enzymes make them popular bioreceptors. Analyte recognition is enabled through several possible mechanisms: 1) the enzyme converting the analyte into a product that is sensor-detectable, 2) detecting enzyme inhibition or activation by the analyte, or 3) monitoring modification of enzyme properties resulting from interaction with the analyte. The main reasons for the common use of enzymes in biosensors are: 1) ability to catalyze a large number of reactions; 2) potential to detect a group of analytes (substrates, products, inhibitors, and modulators of the catalytic activity); and 3) suitability with several different transduction methods for detecting the analyte. Notably, since enzymes are not consumed in reactions, the biosensor can easily be used continuously. The catalytic activity of enzymes also allows lower limits of detection compared to common binding techniques. However, the sensor's lifetime is limited by the stability of the enzyme. Antibodies have a high binding constant in excess of 10^8 L/mol, which stands for a nearly irreversible association once the antigen-antibody couple has formed. For certain analyte molecules like glucose affinity binding proteins exist that bind their ligand with a high specificity like an antibody, but with a much smaller binding constant on the order of 10^2 to 10^4 L/mol. The association between analyte and receptor then is of reversible nature and next to the couple between both also their free molecules occur in a measurable concentration. In case of glucose, for instance, concanavalin A may function as affinity receptor exhibiting a binding constant of 4x10^2 L/mol. The use of affinity binding receptors for purposes of biosensing has been proposed by Schultz and Sims in 1979 and was subsequently configured into a fluorescent assay for measuring glucose in the relevant physiological range between 4.4 and 6.1 mmol/L. The sensor principle has the advantage that it does not consume the analyte in a chemical reaction as occurs in enzymatic assays. Biosensors that employ nucleic acid interactions can be referred to as genosensors. The recognition process is based on the principle of complementary base pairing, adenine:thymine and cytosine:guanine in DNA. If the target nucleic acid sequence is known, complementary sequences can be synthesized, labeled, and then immobilized on the sensor. The hybridization probes can then base pair with the target sequences, generating an optical signal. The favored transduction principle employed in this type of sensor has been optical detection. It has been proposed that properly optimized integrated optical resonators can be exploited for detecting epigenetic modifications (e.g. DNA methylation, histone post-translational modifications) in body fluids from patients affected by cancer or other diseases. Photonic biosensors with ultra-sensitivity are nowadays being developed at a research level to easily detect cancerous cells within the patient's urine. Different research projects aim to develop new portable devices that uses cheap, environmentally friendly, disposable cartridges that require only simple handling with no need of further processing, washing, or manipulation by expert technicians.