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Biosensor
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===Electrochemical=== Electrochemical biosensors, based on enzymes, work through the enzymatic catalysis of reactions that directly or indirectly produce or consume electrons (such enzymes are rightly called [[Oxidoreductase|redox enzymes]]). The sensor design usually consists of three [[electrode]]s; a [[reference electrode]], a working electrode, and a counter electrode. The target analyte is involved in the reaction that takes place on the surface of the active working electrode, and the reaction may cause either electron transfer across the [[Double_layer_(surface_science)|double layer]] (producing a current) or can contribute to the double layer potential (producing a voltage). The current (rate of flow of electrons is now proportional to the analyte concentration) can be measured at a fixed potential or the potential can be measured at zero current (this gives a logarithmic response). Note that potential of the working electrode is space charge sensitive and this is often used. Additionally, the label-free and direct electrical detection of small peptides and proteins is possible by their intrinsic charges using [[Bio-FET|biofunctionalized]] [[ISFET|ion-sensitive]] [[field-effect transistors]].<ref>{{cite journal | last1 = Lud | first1 = S.Q. | last2 = Nikolaides | first2 = M.G. | last3 = Haase | first3 = I. | last4 = Fischer | first4 = M. | last5 = Bausch | first5 = A.R. | year = 2006 | title = Field Effect of Screened Charges: Electrical Detection of Peptides and Proteins by a Thin Film Resistor | journal = ChemPhysChem | volume = 7 | issue = 2| pages = 379–384 | doi = 10.1002/cphc.200500484 | pmid = 16404758 }}</ref> Another example, the potentiometric biosensor, (potential produced at zero current) gives a logarithmic response with a high dynamic range. Such biosensors are 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.<ref>{{Cite web | url=http://www.universalsensors.co.uk/ |archive-url = https://web.archive.org/web/20141218190512/http://universalsensors.co.uk/|archive-date = 18 December 2014|title = Multivitamine Kaufberatung: So finden Sie das beste Präparat}}</ref> Field effect transistors, in which the [[metal gate|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. Impedance spectroscopy based biosensor development has been gaining traction nowadays and many such devices / developments are found in the academia and industry. One such device, based on a 4-electrode electrochemical cell, using a nanoporous alumina membrane, has been shown to detect low concentrations of human alpha thrombin in presence of high background of serum albumin.<ref>{{Cite journal |doi = 10.1016/j.bios.2018.10.010|pmid = 30396022|pmc = 6383723|title = Label free thrombin detection in presence of high concentration of albumin using an aptamer-functionalized nanoporous membrane|journal = Biosensors and Bioelectronics|volume = 126|pages = 88–95|year = 2019|last1 = Gosai|first1 = Agnivo|last2 = Hau Yeah|first2 = Brendan Shin|last3 = Nilsen-Hamilton|first3 = Marit|last4 = Shrotriya|first4 = Pranav}}</ref> Also interdigitated electrodes have been used for impedance biosensors.<ref>{{cite journal |last1=Sanguino |first1= P.|last2 = Monteiro |first2=T.|last3= Bhattacharyya |first3=S.R.|last4= Dias |first4=C.J.|last5= Igreja |first5=R.|last6= Franco |first6=R. |title = ZnO nanorods as immobilization layers for Interdigitated Capacitive Immunosensors |journal = Sensors and Actuators B-Chemical |volume = 204 |pages = 211–217 |year = 2014|doi= 10.1016/j.snb.2014.06.141|bibcode= 2014SeAcB.204..211S}}</ref>
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