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transducers biosensors sensors electronics

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These lecture notes cover different types of transducers, with a focus on electrochemical sensors. They discuss principles, methods, and examples of biosensors. The notes provide helpful background information on the topic of transducers and their diverse applications.

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Transducers General Definition: A device that converts variations in a physical quantity, such as pressure, temperature, brightness, etc, into an electrical signal, or vice versa In a biosensor: The transducer converts the biochemical interactions into measurable electric signals. Thermal...

Transducers General Definition: A device that converts variations in a physical quantity, such as pressure, temperature, brightness, etc, into an electrical signal, or vice versa In a biosensor: The transducer converts the biochemical interactions into measurable electric signals. Thermal : temperature, heat, heat flow, etc Mechanical : position, acceleration, force, pressure, etc Chemical : concentration, composition, reaction rate, etc Optical : intensity, wavelength, polarization, etc Magnetic : field intensity, flux, etc. Electrical : voltage, current, charge, etc Transducers Sensor and actuator are kinds of transducers Sensors: a device that converts a physical parameter to an electrical output. Actuators : a device that converts an electrical signal to a physical output. Electrochemical Biosensors Electrochemical reactions that take place at electrode-electrolyte interface are detected Three types: – Potentiometric – Amperometric – Conductometric Amperometric transduction The electrode potential is Typical electrochemical oxidase biosensor maintained at a constant level The product, H2O2, is oxidised at +650mV vs sufficient for oxidation or a Ag/AgCl reference electrode. reduction of the species of Thus, a potential of + 650mV is applied and interest the oxidation of H2O2 measured. The current that flows is This current is directly proportional to the proportional to the analyte concentration of glucose concentration  They are very prone to interferences from Amperometric enzyme exogenous oxygen. electrodes based on oxidases in combination with hydrogen peroxide indicating electrodes have become most common among biosensors. Amperometric transduction To increase the selectivity of the detecting electrode: Membranes Mediators Metallised electrodes Polymers Amperometric transduction Discriminative Membrane. Membranes are one of the essential components of a biosensor. They are used for (1) preventing fouling; (2) eliminating interference; (3) controlling the operating regime of the biosensor. Examples: Cellulose acetate (charge and size), Nafion (charge) Polycarbonate (size) The disadvantage of using membranes is, however, their effect on diffusion. Amperometric transduction Mediators Artificial electron acceptor molecules e- transfer shuttle: a low molecular weight redox couple which can transfer electrons from the active site of the enzyme to the surface of the electrode  electrical contact between them Amperometric transduction Metallised electrodes To create conditions in which the oxidation of enzymatically generated H2O2 can be achieved at a lower applied potential, by creating a highly catalytic surface. Metallization is achieved by electrodepositing the relevant noble metal on to a glassy carbon electrode using cyclic voltammetry. Most promising ones: platinum, palladium, rhodium and ruthenium. Amperometric transduction Polymers polymers could be used to prevent interfering species from reaching the electrode surface. Ex: polypyrrole. – A polypyrrole film has to be in the reduced state to become permeable for anions. If the film is oxidised, no anion can permeate. Noninvasive Alcohol Monitoring Using a Wearable Tattoo-Based Iontophoretic-Biosensing System, ACS Sens. 2016, 1, 8, 1011–1019 wearable tattoo-based alcohol biosensing system for noninvasive alcohol monitoring in induced sweat. The wearable prototype enables the transdermal delivery of the pilocarpine drug to induce sweat via iontophoresis and amperometric detection of ethanol in the generated sweat using the alcohol- oxidase enzyme and the Prussian Blue electrode transducer. The new skin-compliant biosensor displays a highly selective and sensitive response to ethanol. Alcohol iontophoretic-sensing tattoo device with integrated flexible electronics applied to a human patient (A); schematic diagram of constituents in the iontophoretic system (left) and processes involved in the amperometric sensing of ethanol (right) (B); scheme of the wireless operation for transdermal alcohol sensing (C); amperograms recorded before (a) and after (b) drinking alcohol beverage (D). BAC (blood alcohol concentration) recorded by a breath analyzer. Potential step to −0.2 V vs. Ag/AgCl. Potentiometric transduction A potentiometric biosensor monitors the potential (relative to a reference) under zero current conditions. The potential generated is directly proportional to the logarithm of the analyte concentration (E = Eo + RT/nF ln[analyte]). Ion-selective electrodes are used to determine changes in concentration of chosen ions, e.g., hydrogen ions  pH electrode Potentiometric transduction Ion Selective Electrode (ISE) Polymeric membrane electrodes are commercially available and routinely used for the selective detection of several ions such as K+, Na+, Ca2+, NH4+, H+, CO32- in complex biological matrices. Potentiometric transduction Ion Selective Electrode (ISE) Potentiometric transduction Ion Selective Electrode (ISE) Responsive over a wide concentration range Not affected by color or turbidity of sample Durable Rapid response time Real time measurements Low cost to purchase and operate Easy to use Potentiometric transduction Ion Selective Field Effect Transistors (ISFETs): miniature ISEs CMOS (Complementary metal–oxide–semiconductor) technology to fabricate integrated circuits, is generally used Miniaturized, solid state Potentiometric transduction ISE-based biosensors The two main ones are for urea and creatinine. These potentiometric enzyme electrodes are produced by entrapment of the enzymes urease and creatinase, on the surface of a cation sensitive (NH4+) ISE The kidneys maintain the blood creatinine in a normal range. Creatinine has been found to be a fairly reliable indicator of kidney function. Elevated creatinine level signifies impaired kidney function or kidney disease. Amplified potentiometric transduction of DNA hybridization using ion-loaded liposomes DOI: 10.1039/c0an00198h Amplified potentiometric transduction of DNA hybridization based on using liposome ‘nanocarriers’ loaded with the signaling ions is reported. The liposome-amplified potentiometric bioassay involved the duplex formation, followed by the capture of calcium- loaded liposomes, a surfactant- induced release and highly- sensitive measurements of the calcium signaling ions using a Ca2+ ion-selective electrode (ISE). The high loading yield of nearly one million signaling ions per liposome leads to sub-fmol DNA detection limits. Conductometric transduction Conductivity is a measurement of the ability of a solution to conduct an electric current. Instruments measure conductivity by placing two plates of conductive material with known area and distance apart in a sample. Then a voltage potential is applied and the resulting current is measured. This is a technique where the changes in ionic concentrations are measured. If the biocatalyst produces ionic products, or consumes ions, this is often a convenient and simple technique.  Example: Alkaline phosphatase inhibition based conductometricbiosensor for phosphate estimation in biological fluids In this study, a simple, novel, and cost-effective conductometric biosensor for the indirect determination of phosphate ions in aqueous solution has been demonstrated. The developed biosensor is based on the inhibition of the activity of alkaline phosphatase, immobilized on the glass internal surface. DOI: 10.1016/j.bios.2015.01.064 Optical Transducers Optical sensors rely on the optical transduction of the signal and comprise ultraviolet, visible and infrared spectrophotometry in transmission or reflectance modes. Absorption, refractive indices, fluorescence, phosphorescence, chemiluminescence, etc., can be used in monitoring Can be miniaturized by using different systems like optical fibres Protein detection- Western Blot (http://www.bio-rad.com/en-tr/applications-technologies/detection-methods) Mechanism of detection chemistries. In each method of western blot detection, a detectable signal is generated following binding of an antibody specific for the protein of interest. In colorimetric detection (A), the signal is a colored precipitate. In chemiluminescence (B), the reaction itself emits light. In fluorescence detection (C), the antibody is labeled with a fluorophore Optical Transducers a mass produced bioluminescent biosensor Optical Transducers miniaturization is possible in vivo measurements are possible diode arrays allow for multi-analyte detection signal is not prone to electromagnetic interference Ambient light is a strong interferent Fibres are expensive Optical Transducers Photonic crystals (PC) are periodic optical nanostructures that affect the motion of photons. If the periodicity and symmetry of the crystal and the dielectric constants of the materials used are chosen appropriately, the Photonic Crystal will selectively couple energy at particular wavelengths, while excluding others They can be fabricated for one, two, or three-D. PC biosensors have been applied to the detection of antibody–antigen and small molecule–protein interactions, as well as cell-based assays Optical Transducers-PC Ex: Biomolecular interaction detection system PCs utilized in this system are composed of an epoxy-cured polycarbonate diffraction grating that is coated with a thin layer of TiO2. Binding of macromolecules is monitored by shifts of nanometres in wavelength with a sensitivity < 1 pg/mm2 2-PC Zhongyu Cai et al, Anal. Chem. 2015 Shrinking or swelling: This alters the CCA (crystalline colloidal array) spacing, which shifts the diffracted wavelength and changes the diffracted color (a) 3-D crystalline colloidal arrays (CCA) self-assembled because of electrostatic repulsion between particles. The spacings are ∼200 nm, such that they diffract visible light. Polymerized CCA (PCCA) are formed by polymerizing a cross -linked hydrogel networks around CCA. The hydrogel is functionalized with a molecular recognition agent, which interacts with the analyte to actuate either shrinking or swelling. This alters the CCA spacing, which shifts the diffracted wavelength and changes the diffracted color. (b) 2-D 2-PC Zhongyu Cai et al, Anal. Chem. 2015 (a) Complex formation between glucose (in furanose form) and two boronates (b) Digital photograph of glucose sensing photonic crystal at different [glucose] Zhang and Wang, 2012 Optical Transducers Surface Plasmon Resonance (SPR) The SPR is an optical phenomenon due to a charge density oscillation at the interface of a metal and a dielectric, which have dielectric constants of opposite signs Kretschmann configuration: prisms coated with a thin film of metal, usually gold or silver (~55-nm thick), was used. A light wave passes through the high-refractive-index prism Above a certain incidence angle, all of the light is reflected. This phenomenon is called Total Internal Reflection (TIR) Optical Transducers Surface Plasmon Resonance (SPR) Label-free and sensitive analysis (in pg/mL) Calorimetric Based on measurement of the heat produced by the reaction and the amount of heat produced is correlated to the reactant concentration (ΔT = nΔH/cp) Enzyme-catalysed reactions  Considerable heat evolution (5- 100 kJ/mol). Thus, calorimetric transducers are universally applicable in enzyme sensors. Mass sensitive Quartz crystal microbalance (QCM) A piezoelectric quartz crystal that utilizes the Converse Piezoelectric Effect to determine mass changes as a result of frequency change of the crystal. When a mechanical stress was carried out to a piezoelectric material (e.g., quartz crystal), a voltage proportional to the stress was generated. In 1959, Sauerbrey proved that quartz crystal oscillation frequency depended on the mass change at the sensor surface, and he coined the term as quartz crystal microbalance Mass sensitive-QCM QCM's are piezoelectric devices fabricated of a thin plate of quartz, with gold electrodes affixed to each side of the plate. Mass accumulated on the surface lowers the crystal frequency, the amount being directly related to its mass (ng). Quantification could be done by Sauerbrey eqn – Δf0 – Resonant frequency (Hz) – Δf – Frequency change (Hz) – Δm – Mass change (g) – A – Piezoelectrically active crystal area (cm2) – rho – Density of quartz (2.648 g/cm3) –  – Shear modulus of quartz for AT-cut crystal (2.947x1011 g·cm-1·s-2) Mass sensitive-QCM Mass sensitive Cantilever- nanomechanical biosensors Cantilevers are an example of label free biosensors which offer a simple, rapid, reliable, minimal cost and low limit of analyte detection. Due to its label free detection principle and small size, this type of biosensor has applicable advantages The surface is coated with recognition elements and once specific binding occurs, the cantilever will bend

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