Abstract: A method of forming a high-throughput, three-dimensional (3D) microelectrode array for in vitro electrophysiological applications includes 3D printing a well plate having a top face and bottom face. A plurality of culture well each includes a plurality of 3D printed, vertical microchannels and microtroughs communicating with the microchannels. The microtroughs and the microchannels are filled with a conductive paste to form self-isolated microelectrodes in each of the culture wells and conductive traces that communicate with the self-isolated microelectrodes.

Abstract: A measuring instrument is capable of suppressing a flow path from being clogged due to the precipitation of crystals from an internal solution or a calibration liquid even when kept in a waiting state. The measuring instrument includes a measuring electrode and a reference electrode and on the basis of the potential difference generated therebetween, measures a characteristic value of a sample. In order to accomplish the above object, the measuring instrument is adapted to be able to have two states, i.e., a measurement state of measuring the characteristic value of the sample and a waiting state of not performing measurement, and further include a refilling mechanism that refills the calibration liquid or the internal solution used in the reference electrode. In addition, the refilling mechanism is adapted to continuously or intermittently refill the calibration liquid or the internal solution in the waiting state.

Abstract: An eye-mountable device includes an electrochemical sensor embedded in a polymeric material configured for mounting to a surface of an eye. The electrochemical sensor includes a working electrode, a reference electrode, and a reagent that selectively reacts with an analyte to generate a sensor measurement related to a concentration of the analyte in a fluid to which the eye-mountable device is exposed. The working electrode can have at least one dimension less than 25 micrometers. The reference electrode can have an area at least five times greater than an area of the working electrode. A portion of the polymeric material can surround the working electrode and the reference electrode such that an electrical current conveyed between the working electrode and the reference electrode is passed through the at least partially surrounding portion of the transparent polymeric material.

Abstract: Electrophysiology culture plates are provided and are formed from a transparent microelectrode array (MEA) plate. The MEA plate comprises a substrate, a first layer and a first insulating layer. The substrate has a plurality of vias extending from an upper to a lower surface, each via being in electrical contact with each of a plurality of contact pads disposed on the lower surface. The first layer is disposed on the upper surface of the substrate and has a plurality of MEA arrays in in electrical communication with at least a first routing layer. Each MEA array comprises a plurality of reference electrodes and a plurality of microelectrodes and the first routing layer is in electrical communication with a select number of the plurality of vias. A first insulating layer is disposed on the first layer.

Abstract: Disclosed are methods and devices for biomolecular detection, comprising a nanopipette, exemplified as a hollow inert, non-biological structure with a conical tip opening of nanoscale dimensions, suitable for holding an electrolyte solution which may contain an analyte such as a protein biomolecule to be detected as it is passed through the tip opening. Biomolecules are detected by specific reaction withy peptide ligands chemically immobilized in the vicinity of the tip. Analytes which bind to the ligands cause a detectible change in ionic current. A sensitive detection circuit, using a feedback amplifier circuit, and alternating voltages is further disclosed. Detection of Il-10 at a concentration of 4ng/nl is also disclosed, as is detection of VEGF.

Abstract: Among others things, techniques, systems, and apparatus are disclosed for recording electrophysiological signals. In one aspect, a microelectrode sensing device includes a printed circuit board (PCB), a chip unit electrically connected to the PCB, and a cell culture chamber positioned over the chip unit and sealed to the PCB with the chip unit between the PCB and the cell culture chamber. The chip unit includes a substrate; a conductive layer positioned over the substrate that includes one or more recording electrodes; an insulation layer positioned over the conductive layer; another conductive layer positioned over the insulation layer that includes positioning electrodes; and another insulation layer positioned over the other conductive layer. The recording and positioning electrodes are electrically independent so as to independently receive a stimulus signal at each recording electrode and positioning electrode and independently detect a sensed signal at each recording electrode.

Abstract: An eye-mountable device includes an electrochemical sensor embedded in a polymeric material configured for mounting to a surface of an eye. The electrochemical sensor includes a working electrode and a reference electrode that reacts with an analyte to generate a sensor measurement related to a concentration of the analyte in a fluid to which the eye-mountable device is exposed. An example assembly process includes: forming a sacrificial layer on a working substrate; forming a first layer of a bio-compatible material on the sacrificial layer; providing an electronics module on the first layer of the bio-compatible material, forming a second layer of the bio-compatible material to cover the electronics module; and annealing the first and second layers of the bio-compatible material together to form an encapsulated structure having the electronics module fully encapsulated by the bio-compatible material.

Abstract: An eye-mountable device includes an electrochemical sensor embedded in a polymeric material configured for mounting to a surface of an eye. The electrochemical sensor includes a working electrode, a reference electrode, and a reagent that selectively reacts with an analyte to generate a sensor measurement related to a concentration of the analyte in a fluid to which the eye-mountable device is exposed. The working electrode can have a first side edge and a second side edge. The reference electrode can be situated such that at least a portion of the first and second side edges of the working electrode are adjacent respective sections of the reference electrode.

Abstract: An eye-mountable device includes an electrochemical sensor embedded in a polymeric material configured for mounting to a surface of an eye. The electrochemical sensor includes a working electrode and a reference electrode that reacts with an analyte to generate a sensor measurement related to a concentration of the analyte in a fluid to which the eye-mountable device is exposed. An example assembly process includes: forming a sacrificial layer on a working substrate; forming a first layer of a bio-compatible material on the sacrificial layer; providing an electronics module on the first layer of the bio-compatible material, forming a second layer of the bio-compatible material to cover the electronics module; and annealing the first and second layers of the bio-compatible material together to form an encapsulated structure having the electronics module fully encapsulated by the bio-compatible material.

Abstract: The present invention relates to a sensor used together with a detector to measure biomaterial, and to an apparatus using same. A sensor of the present invention comprises: a body portion with a three-dimensional shape, having a biomaterial introduction hole, and attachable and detachable to/from a detector; a sensor portion with a plurality of reaction electrodes formed on one surface thereof, and a plurality of transfer electrodes formed on the other surface thereof; and an analyzer reagent fixed above the reaction electrodes. The sensor portion, together with the body portion, forms a reaction chamber connected to the biomaterial introduction hole, and is attached to the body portion such that the reaction electrodes are oriented toward the reaction chamber. According to the present invention, attachment and detachment is easy, even for the elderly, and the contamination of the sensor can be minimized.

Abstract: An in vivo amperometric sensor is provided for measuring the concentration of an analyte in a body fluid. The sensor comprises a counter electrode and a working electrode, and the working electrode comprises a sensing layer which is generally water permeable and arranged on a support member adjacent to a contact pad. The sensing layer comprises an immobilized enzyme capable of acting catalytically in the presence of the analyte to cause an electrical signal. The sensing layer has an upper surface facing the body fluid and a lower surface facing away from the body fluid, and the immobilized enzyme is distributed within the sensing layer in such a way that the enzyme concentration in the middle between the upper and lower surfaces is at least as high as on the upper surface of the sensing layer.

Abstract: A small diameter flexible electrode designed for subcutaneous in vivo amperometric monitoring of glucose is described. The electrode is designed to allow “one-point” in vivo calibration, i.e., to have zero output current at zero glucose concentration, even in the presence of other electroreactive species of serum or blood. The electrode is preferably layered, with the layers serially deposited within a recess upon the tip of a polyamide insulated gold wire. A first glucose concentration-to-current transducing layer can be overcoated with an electrically insulating and glucose flux limiting layer (second layer) on which, optionally, an immobilized interference-eliminating horseradish peroxidase based film is deposited. An outer layer is preferably biocompatible.

Abstract: A small diameter flexible electrode designed for subcutaneous in vivo amperometric monitoring of glucose is described. The electrode is designed to allow “one-point” in vivo calibration, i.e., to have zero output current at zero glucose concentration, even in the presence of other electroreactive species of serum or blood. The electrode is preferably layered, with the layers serially deposited within a recess upon the tip of a polyamide insulated gold wire. A first glucose concentration-to-current transducing layer can be overcoated with an electrically insulating and glucose flux limiting layer (second layer) on which, optionally, an immobilized interference-eliminating horseradish peroxidase based film is deposited. An outer layer is preferably biocompatible.

Abstract: The present invention provides a class of sensors prepared from regions of conducting organic materials and conducting materials that show an increase sensitivity detection limit for amines. The present class of sensors have applications in the detection of spoiled food products and in testing for diseases, such as cholera and lung cancer, which have amines as biomarkers.

Abstract: A dynamic and noninvasive method of monitoring the adhesion and proliferation of biological cells through multimode operation (acoustic and optical) using a ZnO nanostructure-modified quartz crystal microbalance (ZnOnano-QCM) biosensor is disclosed.

Abstract: The chip includes electrodes on a substrate. The electrodes include a working electrode, a reference electrode, and a counter electrode. The reference electrode is constructed so as to not have an intrinsic potential. A self-assembly monolayer is positioned on the reference electrode. The self-assembly monolayer includes spacers and active probes. The active probes are configured to have a higher affinity for a capture probe than the spacers have for the capture probe.

Abstract: A sensor electrode for the detection of nucleotides in a biological sample is described. The sensitivity of the electrode is enhanced by the nanostructured sensor architecture that increases the available surface area of the electrode. The electrode detects nucleotides using standard electrochemical methods.

Abstract: A BUN (blood urea nitrogen) sensor containing immobilized carbonic anhydrase and immobilized urease for the in vitro detection of urea nitrogen in blood and biological samples with improved performance and precision characteristics.

Abstract: A process for the manufacture of small sensors with reproducible surfaces, including electrochemical sensors. One process includes forming channels in the surface of a substrate and disposing a conductive material in the channels to form an electrode. The conductive material can also be formed on the substrate by other impact and non-impact methods. In a preferred embodiment, the method includes cutting the substrate to form a sensor having a connector portion and a transcutaneous portion, the two portions having edges that define one continuous straight line.

Abstract: A method for determining a concentration of an analyte is disclosed. The method includes applying a potential excitation to a fluid sample containing an analyte and determining if a current decay curve associated with the fluid sample has entered an analyte depletion stage. The method also includes measuring a plurality of current values associated with the fluid sample during the analyte depletion stage and calculating an analyte concentration based on at least one of the plurality of current values.

Abstract: A high-sensitivity field effect transistor using as a channel ultrafine fiber elements such as carbon nanotube, and a biosensor using it. The field effect transistor comprises a substrate, a source electrode and a drain electrode arranged on the substrate, a channel for electrically connecting the source electrode with the drain electrode, and a gate electrode causing polarization due to the movement of free electrons in the substrate. For example, the substrate has a support substrate consisting of semiconductor or metal, a first insulating film formed on a first surface of the support substrate, and a second insulating film formed on a second surface of the support substrate, the source electrode, the drain electrode, and the channel arranged on the first insulating film, the gate electrode disposed on the second insulating film.

Abstract: Method and systems provide improved cell handling in microfluidic systems and devices using lateral cell trapping and methods of fabrication of the same that allow for selective low voltage electroporation and electrofusion.

Abstract: The invention provides an implantable membrane for regulating the transport of analytes therethrough that includes a matrix including a first polymer; and a second polymer dispersed throughout the matrix, wherein the second polymer forms a network of microdomains which when hydrated are not observable using photomicroscopy at 400× magnification or less. In one aspect, the homogeneous membrane of the present invention has hydrophilic domains dispersed substantially throughout a hydrophobic matrix to provide an optimum balance between oxygen and glucose transport to an electrochemical glucose sensor.

Abstract: The invention concerns an electrochemical cell which, either alone or together which a substrate onto which it is placed, is in the form of a receptacle. The electrochemical cell contains a working electrode and a counter electrode, the working electrode being in a wall of the receptacle. At least one of the electrodes has at least one dimension of less than 50 ?m. The electrochemical cell is principally intended for use as a micro-electrode suitable for screening water, blood, urine or other biological or non-biological fluids.

Abstract: The present invention provides a sensor, such as a biosensor, comprising at least one self-assembled monolayer (SAM) comprising analyte-sensitive groups, such as glucose-sensitive groups, attached to the surface of the outer wall of a carbon nanotube (CNT), such as a single-walled carbon nanotube (SWNT), by terminal groups, which bind to a thin layer of a metal or metal oxide, which has been deposited on the surface of the outer wall of the nanotube.

Abstract: A system apparatus (101) includes an integrated sensing and separation component (108) for the monitoring and analysis of clinical species present in biological fluids. In the preferred embodiment this is by use of a polyHIPE membrane (109) with a chemically active sol-gel (110), and a plurality of micro-electrode arrays adapted for selectively adjusting sensitivity.

Abstract: A sensor utilizing a non-leachable or diffusible redox mediator is described. The sensor includes a sample chamber to hold a sample in electrolytic contact with a working electrode, and in at least some instances, the sensor also contains a non-leachable or a diffusible second electron transfer agent. The sensor and/or the methods used produce a sensor signal in response to the analyte that can be distinguished from a background signal caused by the mediator. The invention can be used to determine the concentration of a biomolecule, such as glucose or lactate, in a biological fluid, such as blood or serum, using techniques such as coulometry, amperometry, and potentiometry. An enzyme capable of catalyzing the electrooxidation or electroreduction of the biomolecule is typically provided as a second electron transfer agent.

Abstract: A BUN (blood urea nitrogen) sensor containing immobilized carbonic anhydrase and immobilized urease for the in vitro detection of urea nitrogen in blood and biological samples with improved performance and precision characteristics.

Abstract: A bio-battery includes a biomolecular energy source, a first electrode and a second electrode. In some configurations, a bio-battery may also include a first cell containing the first electrode and the biomolecular energy source, and a second cell having a reducible substrate and the second electrode. The first cell can be in ionic communication with the second cell, for example by a proton exchange membrane. Various biomolecular energy sources can be used, including proton donor molecules or electrolytically oxidizable molecules. For example, the biomolecular energy source can be selected from the group consisting of Nicotinamide Adenine Dinucleotide (NADH), Nicotinamide Adenine Dinucleotide Phosphate (NADPH) and 5,10-Methylenetetrahydrofolate Reductase (FADH).

Abstract: A method and system for electrically wounding and/or monitoring cell activity in vitro. The invention comprises methods and systems for wounding and/or monitoring cells that place a cell culture on a well that has an exposed electrode. The cell culture can then be wounded and/or monitored using the electrode.

Abstract: The present invention is directed to devices and methods for carrying out and/or monitoring biological reactions in response to electrical stimuli. A programmable multiplexed active biologic array includes an array of electrodes coupled to sample-and-hold circuits. The programmable multiplexed active biologic array includes a digital interface that allows external control of the array using an external processor. The circuit may monitor, digitally control, and deliver electrical stimuli to the electrodes individually or in selected groups.

Abstract: A biosensor that is highly responsive and capable of rapid and highly sensitive quantification of a specific component contained in a sample is provided. The biosensor of this invention comprises: an electrically insulating base plate; an electrode system comprising a working electrode and a counter electrode disposed on the base plate; and a reagent system comprising an oxidoreductase which catalyzes the oxidation reaction of glucose, gluconolactonase and a buffer. The buffer is selected from the group consisting of phthalic acid and its salts, maleic acid and its salts, succinic acid and its salts, phospholic acid and its salts, acetic acid and its salts, boric acid and its salts, citric acid and its salts, glycine, tris(hydroxymethyl)aminomethane, piperazine-N,N?-bis(2-ethane sulfonic acid) and the like.

Abstract: A variety of elastomeric-based microfluidic devices and methods for using and manufacturing such devices are provided. Certain of the devices have arrays of reaction sites to facilitate high throughput analyses. Some devices also include reaction sites located at the end of blind channels at which reagents have been previously deposited during manufacture. The reagents become suspended once sample is introduced into the reaction site. The devices can be utilized with a variety of heating devices and thus can be used in a variety of analyses requiring temperature control, including thermocycling applications such as nucleic acid amplification reactions, genotyping and gene expression analyses.

Abstract: A multiple electrode includes a plurality of micro-electrodes provided on a substrate, and a wiring portion for providing an electrical signal to the micro-electrodes or extracting an electrical signal from the micro-electrodes. Each micro-electrode has porous conductive material on its surface, and the impedance of the micro-electrode is 50 k? or less. Preferably, the porous conductive material is gold, and formed by the passage of current at a current density of 1.0 to 5.0 A/dm2 for 10 to 360 sec. The multiple electrode may include micro-electrodes provided on a substrate in the form of a matrix, a lead line connected to the micro-electrodes, and an electrical junction connected to an end of the lead line.

Abstract: To measure or exert optically-induced forces on at least one particle in the focus of an optical cage, the following steps are taken: a) the focus is positioned in a microelectrode arrangement with a three-dimensional electrical field that has a field gradient which forms an electrical capture area, and the focus is at a distance from the capture are and b) the amplitude of the electrical field, the light power of the light beam forming the optical cage, and/or the distance of the capture area from the focus are varied to detect which varied field property moves the particle from the focus to the capture area or vice versa, or at least to temporarily move the particle into the capture area.

Abstract: A thick film electrochemical microsensor device for measuring or regulating chlorine and bromine in water, comprising a substrate to which is applied an optimum arrangement of at least two electrodes. The device is especially useful for measuring or regulating chlorine and bromine levels in swimming pool or spa water. A method of measuring or regulating ions of at least one of chlorine and bromine in water is also described, which comprises contacting the water with the microsensor of the present invention; measuring the current output of the microsensor; determining the level of at least one of chlorine and bromine indicated by the current output; and generating a signal.

Abstract: The present invention provides an apparatus and method for nucleotide or DNA sequencing by monitoring the molecular charge configuration as the DNA moves through a protein that is capable of transcribing the DNA. The apparatus and method provides a nanoscale electrometer that immobilizes the protein. The protein receives the DNA and transcribes the DNA. The nanoscale electrometer is a sensitive device that is capable of sensing and measuring the electronic charge that is released during the transcription process. The apparatus and method of the present invention further provides monitoring means that are attached to the nanoscale electrometer to monitor the electronic charge configuration as the DNA moves through the protein. Once the electronic charge configuration is established, a correlation is computed, using computing means, between the electronic charge configuration and a nucleotide signature of the DNA.

Abstract: An apparatus, compositions and related methods for sequencing a target nucleic acid are described. In certain embodiments, the apparatus is a microfluidic apparatus comprising an input chamber, microchannel, output chamber and a detection unit that is operatively connected to the microchannel. In preferred embodiments, the methods include hybridizing a target nucleic acid to one or more probe libraries, moving the hybridized target nucleic acid past the detector, and detecting bound probes. Probe libraries may comprise oligonucleotides or oligonucleotide analogs, preferably with each probe uniquely labeled. A linear order of labeled probes hybridized to the target nucleic acid can be detected and the target nucleic acid sequence deduced. In preferred embodiments, probe labels are detected by analysis of electron-induced fluorescence of probes labeled with conductive polymers.

Abstract: An electro-chemical analysis device and method for analyzing biomolecular samples, including a means for holding a sample on a substrate platform, a thermal sensor, a biosensor formed having a specific spatial resolution as related to the thermal sensor, and a means for providing radiation to the biomolecular sample. The means for holding the sample, the thermal sensor, the biosensor, and the means for providing radiation all three-dimensionally integrated with the substrate platform, thereby defining a compact biomolecular analysis device having a volume resolution of less than 50 micro liters. During operation, radiation is provided to the biomolecular sample to provide for a constant temperature at which hybridization of the biomolecules takes place. The temperature of the biomolecular sample is monitored and controlled by the integrated thermal sensor and the integrated heater. Once hybridization takes place, the change in electric condition (e.g.

Abstract: The invention concerns an apparatus (10) comprising essentially a support (11) wherein is placed a measuring card (12), a perfusion device (13), a thermostat (14), a measuring box (15) and a measurement management system (16). The measuring card (12) comprises an electrode array whereof one end emerges into the chamber and the other end is placed outside said chamber. The group of cells is placed in the chamber which is connected to the perfusion device (13). The support (11) comprises a connector (25) connecting the card (12) electrodes to the measurement management system (16) via the measuring box (15).

Abstract: Sensors and methods of making the same are disclosed. Sensors are microfabricated with multiple working electrodes and a single, common counter electrode. The multiple working electrodes can be fabricated in different geometrical configurations for advantageously analyzing multiple components simultaneously in the same microcell sensor. Furthermore, sensors according to certain embodiments of the invention include openings to allow photometric analysis along with electroanalytical methods.

Abstract: A cell analysis and sorting apparatus is capable of monitoring over time the behavior of each cell in a large population of cells. The cell analysis and sorting apparatus contains individually addressable cell locations. Each location is capable of capturing and holding a single cell, and selectively releasing that cell from that particular location. In one aspect of the invention, the cells are captured and held in wells, and released using vapor bubbles as a means of cell actuation. In another aspect of the invention, the cells are captured, held and released using electric field traps.

Abstract: This invention relates to the detection of molecular interactions between biological molecules. Specifically, the invention relates to electrical detection of interactions such as hybridization between nucleic acids or peptide antigen-antibody interaction using arrays of peptides or oligonucleotides. In particular, the invention relates to an apparatus and methods for detecting nucleic acid hybridization or peptide binding using electronic methods including AC impedance. In some embodiments, no electrochemical or other label moieties are used. In others, electrochemically active labels are used to detect reactions on hydrogel arrays, including genotyping reactions such as the single base extension reaction.

Abstract: Chemical sensors for detecting analytes in fluids comprising a plurality of alternating nonconductive regions (comprising a nonconductive material) and conductive regions (comprising a conductive material). In preferred embodiments, the conducting region comprises a nanoparticle. Variability in chemical sensitivity from sensor to sensor is provided by qualitatively or quantitatively varying the composition of the conductive and/or nonconductive regions. An electronic nose for detecting an analyte in a fluid may be constructed by using such arrays in conjunction with an electrical measuring device electrically connected to the conductive elements of each sensor.

Abstract: A biosensor for detecting and measuring analytes in an aqueous solution. The biosensor device has a sensor design based on modeling of the active-site chemistry of reactive molecules such as enzymes, antibodies and cellular receptors. The sensor design takes advantage of a synthetic polymer modeled after these reactive molecules to provide reversible, sensitive and reliable detection of analytes in the form of a versatile and economical device.

Abstract: The present invention relates to a process analyzer for analyzing composition of sample electrochemical deposition solutions, comprising at least one microelectrode having a radius of not more than about 5 &mgr;m. The process analyzer preferably comprises: (1) two or more independent analytical modules for analyzing fluid samples, (2) a primary manifold communicatively connected to the analytical modules for introducing fluid samples thereinto, and (3) a computational device communicatively associated with the analytical modules for colleting and processing analytical data therefrom, and therefore can be used to conduct automatic and simultaneous analysis of two or more sample solutions.

Abstract: An apparatus for automatically measuring minute membrane potential, based on a technique developed for controlling a membrane denaturation reaction without using a physical shearing force, for example, a method of causing the destruction of membrane at a limited portion of a living membrane by making a stimulus, such as light and a compound activated by the stimulus react with each other in a membrane, such as a living membrane, this method being applied to a minute electrode to facilitate the insertion thereof into a cell, which has been difficult in the use of a minute metal electrode, and enable membrane potential in a cell to be measured easily, the minute metal electrode enabling the integration thereof and the development of a neural interface in the barrier-free technology.

Abstract: This invention relates to a low impedance cell potential measuring electrode assembly typically having a number of microelectrodes on an insulating substrate and having a wall enclosing the region including the microelectrodes. The device is capable of measuring electrophysiological activities of a monitored sample using the microelectrodes while cultivating those cells or tissues in the in the region of the microelectrodes. The invention utilizes independent reference electrodes to lower the impedance of the overall system and to therefore lower the noise often inherent in the measured data. Optimally the microelectrodes are enclosed by a physical wall used for controlling the atmosphere around the monitored sample.

Abstract: An electrochemical biosensor test strip with four new features. The test strip includes an indentation for tactile feel as to the location of the strips sample application port. The sample application port leads to a capillary test chamber, which includes a test reagent. The wet reagent includes from about 0.2% by weight to about 2% by weight polyethylene oxide from about 100 kilodaltons to about 900 kilodaltons mean molecular weight, which makes the dried reagent more hydrophilic and sturdier to strip processing steps, such as mechanical punching, and to mechanical manipulation by the test strip user. The roof of the capillary test chamber includes a transparent or translucent window which operates as a “fill to here” line, thereby identifying when enough test sample (a liquid sample, such as blood) has been added to the test chamber to accurately perform a test. The test strip may further include a notch located at the sample application port. The notch reduces a phenomenon called “dose hesitation”.