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A biotransducer is the recognition-transduction component of a biosensor system. It consists of two intimately coupled parts; a bio-recognition layer and a physicochemical transducer, which acting together converts a biochemical signal to an electronic or optical signal. The bio-recognition layer typically contains an enzyme or another binding protein such as antibody. However, oligonucleotide sequences, sub-cellular fragments such as organelles (e.g. mitochondria) and receptor carrying fragments (e.g. cell wall), single whole cells, small numbers of cells on synthetic scaffolds, or thin slices of animal or plant tissues, may also comprise the bio-recognition layer. It gives the biosensor selectivity and specificity. The physicochemical transducer is typically in intimate and controlled contact with the recognition layer. As a result of the presence and biochemical action of the analyte (target of interest), a physico-chemical change is produced within the biorecognition layer that is measured by the physicochemical transducer producing a signal that is proportionate to the concentration of the analyte. [1] The physicochemical transducer may be electrochemical, optical, electronic, gravimetric, pyroelectric or piezoelectric. Based on the type of biotransducer, biosensors can be classified as shown to the right.
Electrochemical biosensors contain a biorecognition element that selectively reacts with the target analyte and produces an electrical signal that is proportional to the analyte concentration. In general, there are several approaches that can be used to detect electrochemical changes during a biorecognition event and these can be classified as follows: amperometric, potentiometric, impedance, and conductometric.
Amperometric transducers detect change in current as a result of electrochemical oxidation or reduction. Typically, the bioreceptor molecule is immobilized on the working electrode (commonly gold, carbon, or platinum). The potential between the working electrode and the reference electrode (usually Ag/AgCl) is fixed at a value and then current is measured with respect to time. The applied potential is the driving force for the electron transfer reaction. The current produced is a direct measure of the rate of electron transfer. The current reflects the reaction occurring between the bioreceptor molecule and analyte and is limited by the mass transport rate of the analyte to the electrode.
Potentiometric sensors measure a potential or charge accumulation of an electrochemical cell. The transducer typically comprises an ion selective electrode (ISE) and a reference electrode. The ISE features a membrane that selectively interacts with the charged ion of interest, causing the accumulation of a charge potential compared to the reference electrode. The reference electrode provides a constant half-cell potential that is unaffected by analyte concentration. A high impedance voltmeter is used to measure the electromotive force or potential between the two electrodes when zero or no significant current flows between them. The potentiometric response is governed by the Nernst equation in that the potential is proportional to the logarithm of the concentration of the analyte.
Electrochemical impedance spectroscopy (EIS) involves measuring resistive and capacitive changes caused by a biorecognition event. Typically, a small amplitude sinusoidal electrical stimulus is applied, causing current to flow through the biosensor. The frequency is varied over a range to obtain the impedance spectrum. The resistive and capacitive components of impedance are determined from in phase and out of phase current responses. Typically, a conventional three-electrode system is made specific to the analyte by immobilizing a biorecognition element to the surface. A voltage is applied and the current is measured. The interfacial impedance between the electrode and solution changes as a result of the analyte binding. An impedance analyzer can be used to control and apply the stimulus as well as measure the impedance changes.
Conductometric sensing involves measuring the change in conductive properties of the sample solution or a medium. The reaction between the biomolecule and analyte changes the ionic species concentration, leading to a change in the solution electrical conductivity or current flow. Two metal electrodes are separated at a certain distance and an AC potential is applied across the electrodes, causing a current flow between the electrodes. During a biorecognition event the ionic composition changes, using an ohmmeter the change in conductance can be measured.
Optical biotransducers, used in optical biosensors for signal transduction, use photons in order to collect information about analyte. [2] These are highly sensitive, highly specific, small in size and cost effective.
The detection mechanism of optical biotransducer depends upon the enzyme system that converts analyte into products which are either oxidized or reduced at the working electrode. [3]
Evanescent field detection principle is most commonly used in an optical biosensor system as the transduction principle . This principle is one of the most sensitive detection methods. It enables the detection of fluorophores exclusively in the close proximity of the optical fiber. [4]
Electronic biosensing offers significant advantages over optical, biochemical and biophysical methods, in terms of high sensitivity and new sensing mechanisms, high spatial resolution for localized detection, facile integration with standard wafer-scale semiconductor processing and label-free, real-time detection in a nondestructive manner [6].
Devices based on field-effect transistors (FETs) have attracted great attention because they can directly translate the interactions between target biological molecules and the FET surface into readable electrical signals. In a FET, current flows along the channel which is connected to the source and the drain. The channel conductance between the source and the drain is switched on and off by gate electrode that is capacitively coupled through a thin dielectric layer [6].
In FET-based biosensors, the channel is in direct contact with the environment, and this gives better control over the surface charge. This improves the sensitivity of surface FET-based biosensors as biological events occurring at the channel surface could result in the surface potential variation of the semiconductor channel and then modulate the channel conductance. In addition to ease of on-chip integration of device arrays and the cost-effective device fabrication, the surface ultrasensitivity of FET-based biosensors makes it an attractive alternative to existing biosensor technologies[6].
Gravimetric biosensors use the basic principle of a response to a change in mass. Most gravimetric biosensors use thin piezoelectric quartz crystals, either as resonating crystals (QCM), or as bulk/surface acoustic wave (SAW) devices. In the majority of these the mass response is inversely proportional to the crystal thickness. Thin polymer films are also used in which biomolecules can be added to the surface with known surface mass. Acoustic waves can be projected to the thin film to produce an oscillatory device, which then follows an equation that is nearly identical to the Sauerbrey equation used in the QCM method. [5] Biomolecules, such as proteins or antibodies can bind and its change in mass gives a measureable signal proportional to the presence of the target analyte in the sample.
Pyroelectric biosensors generate an electric current as a result of a temperature change. This differential induces a polarization in the substance, producing a dipole moment in the direction of the temperature gradient. The result is a net voltage across the material. This net voltage can be calculated by the following equation. [6]
where V = Voltage, ω = angular frequency of the modulated incident, P = pyroelectric coefficient, L = film thickness, ε = film dielectric constant, A = area of film, r = resistance of the film, C = capacitance of the film, τE = electrical time constant of the detector output.
Electrophysiology is the branch of physiology that studies the electrical properties of biological cells and tissues. It involves measurements of voltage changes or electric current or manipulations on a wide variety of scales from single ion channel proteins to whole organs like the heart. In neuroscience, it includes measurements of the electrical activity of neurons, and, in particular, action potential activity. Recordings of large-scale electric signals from the nervous system, such as electroencephalography, may also be referred to as electrophysiological recordings. They are useful for electrodiagnosis and monitoring.
In the broadest definition, a sensor is a device, module, machine, or subsystem whose purpose is to detect events or changes in its environment and send the information to other electronics, frequently a computer processor. A sensor is always used with other electronics.
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 with, binds with, or recognizes 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 connects 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. The readers are usually custom-designed and manufactured to suit the different working principles of biosensors.
Nanosensors are nanoscale devices that measure physical quantities and convert these to signals that can be detected and analyzed. There are several ways proposed today to make nanosensors; these include top-down lithography, bottom-up assembly, and molecular self-assembly. There are different types of nanosensors in the market and in development for various applications, most notably in defense, environmental, and healthcare industries. These sensors share the same basic workflow: a selective binding of an analyte, signal generation from the interaction of the nanosensor with the bio-element, and processing of the signal into useful metrics.
Cyclic voltammetry (CV) is a type of potentiodynamic electrochemical measurement. In a cyclic voltammetry experiment, the working electrode potential is ramped linearly versus time. Unlike in linear sweep voltammetry, after the set potential is reached in a CV experiment, the working electrode's potential is ramped in the opposite direction to return to the initial potential. These cycles of ramps in potential may be repeated as many times as needed. The current at the working electrode is plotted versus the applied voltage to give the cyclic voltammogram trace. Cyclic voltammetry is generally used to study the electrochemical properties of an analyte in solution or of a molecule that is adsorbed onto the electrode.
An ion-sensitive field-effect transistor (ISFET) is a field-effect transistor used for measuring ion concentrations in solution; when the ion concentration (such as H+, see pH scale) changes, the current through the transistor will change accordingly. Here, the solution is used as the gate electrode. A voltage between substrate and oxide surfaces arises due to an ion sheath. It is a special type of MOSFET (metal-oxide-semiconductor field-effect transistor), and shares the same basic structure, but with the metal gate replaced by an ion-sensitive membrane, electrolyte solution and reference electrode. Invented in 1970, the ISFET was the first biosensor FET (BioFET).
A potentiostat is the electronic hardware required to control a three electrode cell and run most electroanalytical experiments. A Bipotentiostat and polypotentiostat are potentiostats capable of controlling two working electrodes and more than two working electrodes, respectively.
Chronoamperometry is an electrochemical technique in which the potential of the working electrode is stepped and the resulting current from faradaic processes occurring at the electrode is monitored as a function of time. The functional relationship between current response and time is measured after applying single or double potential step to the working electrode of the electrochemical system. Limited information about the identity of the electrolyzed species can be obtained from the ratio of the peak oxidation current versus the peak reduction current. However, as with all pulsed techniques, chronoamperometry generates high charging currents, which decay exponentially with time as any RC circuit. The Faradaic current - which is due to electron transfer events and is most often the current component of interest - decays as described in the Cottrell equation. In most electrochemical cells this decay is much slower than the charging decay-cells with no supporting electrolyte are notable exceptions. Most commonly a three electrode system is used. Since the current is integrated over relatively longer time intervals, chronoamperometry gives a better signal to noise ratio in comparison to other amperometric techniques.
A ChemFET is a chemically-sensitive field-effect transistor, that is a field-effect transistor used as a sensor for measuring chemical concentrations in solution. When the target analyte concentration changes, the current through the transistor will change accordingly. Here, the analyte solution separates the source and gate electrodes. A concentration gradient between the solution and the gate electrode arises due to a semi-permeable membrane on the FET surface containing receptor moieties that preferentially bind the target analyte. This concentration gradient of charged analyte ions creates a chemical potential between the source and gate, which is in turn measured by the FET.
A potentiometric sensor is a type of chemical sensor that may be used to determine the analytical concentration of some components of the analyte gas or solution. These sensors measure the electrical potential of an electrode when no current is present.
Electroanalytical methods are a class of techniques in analytical chemistry which study an analyte by measuring the potential (volts) and/or current (amperes) in an electrochemical cell containing the analyte. These methods can be broken down into several categories depending on which aspects of the cell are controlled and which are measured. The three main categories are potentiometry, coulometry, and voltammetry.
Reflectometric interference spectroscopy (RIfS) is a physical method based on the interference of white light at thin films, which is used to investigate molecular interaction.
Amperometry in chemistry is detection of ions in a solution based on electric current or changes in electric current.
Biosensors and Bioelectronics is a peer-reviewed scientific journal published by Elsevier. It covers research on biosensors and bioelectronics. The journal was established in 1985 as Biosensors and obtained its current name in 1991. The journal was established by I. John Higgins, W. Geoff Potter and Anthony P.F. Turner, who became editor-in-chief, a position which he continues to hold today.
As with any material implanted in the body, it is important to minimize or eliminate foreign body response and maximize effectual integration. Neural implants have the potential to increase the quality of life for patients with such disabilities as Alzheimer's, Parkinson's, epilepsy, depression, and migraines. With the complexity of interfaces between a neural implant and brain tissue, adverse reactions such as fibrous tissue encapsulation that hinder the functionality, occur. Surface modifications to these implants can help improve the tissue-implant interface, increasing the lifetime and effectiveness of the implant.
A field-effect transistor-based biosensor, also known as a biosensor field-effect transistor, field-effect biosensor (FEB), or biosensor MOSFET, is a field-effect transistor that is gated by changes in the surface potential induced by the binding of molecules. When charged molecules, such as biomolecules, bind to the FET gate, which is usually a dielectric material, they can change the charge distribution of the underlying semiconductor material resulting in a change in conductance of the FET channel. A Bio-FET consists of two main compartments: one is the biological recognition element and the other is the field-effect transistor. The BioFET structure is largely based on the ion-sensitive field-effect transistor (ISFET), a type of metal-oxide-semiconductor field-effect transistor (MOSFET) where the metal gate is replaced by an ion-sensitive membrane, electrolyte solution and reference electrode.
Electrochemical stripping analysis is a set of analytical chemistry methods based on voltammetry or potentiometry that are used for quantitative determination of ions in solution. Stripping voltammetry have been employed for analysis of organic molecules as well as metal ions. Carbon paste, glassy carbon paste, and glassy carbon electrodes when modified are termed as chemically modified electrodes and have been employed for the analysis of organic and inorganic compounds.
An Electrochemical aptamer-based (E-AB) biosensor has the ability to generate an electrochemical signal in response to specific target binding in vivo The signal is measured by a change in Faradaic current passed through an electrode. E-AB sensors are advantageous over previously reported aptamer-based sensors, such as fluorescence generating aptamers, due to their ability to detect target binding in vivo with real-time measurements. An E-AB sensor is composed of a three-electrode cell: an interrogating electrode, a reference electrode, and a counter electrode. A signal is generated within the electrochemical cell then measured and analyzed by a potentiostat. There are several biochemical and electrochemical parameters to optimize signal gain for E-AB biosensors. The density packing of DNA or RNA aptamers, the ACV frequency administered by the potentiostat, and the chemistry of the SAM are all factors that determine signal gain as well as the signal to noise ratio of target binding. E-AB biosensors provide a promising mechanism for in-situ sensing and feedback-controlled drug administration.
Screen-printed electrodes (SPEs) are electrochemical measurement devices that are manufactured by printing different types of ink on plastic or ceramic substrates, allowing quick in-situ analysis with high reproducibility, sensitivity and accuracy. The composition of the different inks used in the manufacture of the electrode determines its selectivity and sensitivity. This fact allows the analyst to design the most optimal device according to its purpose.