Abstract: NADP-dependent oxidoreductase compositions, and electrodes, sensors and systems that include the same. Analyte sensors include an electrode having a sensing layer disposed thereon, the sensing layer comprising a polymer and an enzyme composition distributed therein. The enzyme composition includes nicotinamide adenine dinucleotide phosphate (NAD(P)+) or derivative thereof; an NAD(P)+-dependent dehydrogenase; an NAD(P)H oxidoreductase; and an electron transfer agent comprising a transition metal complex.

Abstract: Multiple enzymes may be present in one or more active areas of an electrochemical analyte sensor for detecting one or more different analytes. In particular, an analyte sensor may comprise a sensor tail configured for insertion into a tissue and one or more working electrodes having a glucose-responsive active area and an ethanol-responsive active area to detect glucose and ethanol in vivo.

Abstract: The present disclosure relates to a method of improving the sensitivity of sensing ketones that includes providing i) a ketone sensing electrode comprising a ketone-responsive enzyme and a redox mediator; and ii) a background sensing electrode comprising a redox mediator and no ketone-responsive enzyme and applying a potential less than +40 mV to provide a steady state. The ketone sensing electrode and background sensing electrode can be simultaneously or sequentially disconnected from the circuit to allow the charge to accumulate for a set period of time. After sufficient charge has been built up, both electrodes can be reconnected to the circuit. The ketone signal can be measured by subtracting a signal obtained from the background sensing electrode from a signal obtained from the ketone sensing electrode. The present disclosure further relates to a ketone sensor comprising a first sensing electrode that senses ketone and a second sensing electrode that senses the background.

Abstract: The present disclosure provides analyte sensors comprising a sensing layer disposed upon a surface of a first working electrode, wherein the sensing layer comprises an NAD(P)-dependent enzyme and a supply of NAD(P); and a multilayered membrane that overcoats at least a part of the sensing layer and is permeable to an analyte, wherein the membrane comprises at least one layer of negatively charged polymer. The present disclosure also provides methods of using such analyte sensors for detecting one or more analytes preset in a biological sample and methods of manufacturing the analyte sensors.

Abstract: The present disclosure provides analyte sensors comprising a first working electrode, a sensing layer disposed upon a surface of the first working electrode, and a highly permeable membrane that overcoats at least a part of the sensing layer and that is permeable to an analyte, wherein the highly permeable membrane comprises a copolymer of poly(N-vinylimidazole) and poly(N-isopropylacrylamide), and wherein the analyte sensor shows a sensitivity of at least 100 nA/mM to the analyte. The present disclosure also provides methods of using such analyte sensors for detecting one or more analytes preset in a biological sample and methods of manufacturing the analyte sensors.

Abstract: Multiple analytes may be dysregulated singularly or concurrently in certain physiological conditions and may be advantageously assayed together using analyte sensors capable of detecting multiple analytes. Certain analyte sensors capable of the detection of multiple analytes may include first and second working electrodes, analyte-responsive active areas disposed on each of the working electrodes, and reference and counter electrodes. Analyte sensors that include multiple working electrodes but do not include reference and counter electrodes can also be used in conjunction with another sensor that contains reference and counter electrodes, such that these electrodes are shared.

Abstract: Analyte sensor comprises an electrode layer having an elongate body comprising a proximal end and a distal end. The electrode layer includes a first active working electrode area, a second electrode portion, and at least one gap electrically separating the first active working electrode portion and the second electrode portion. The first active working electrode area comprises at least one sensing spot with at least one analyte responsive enzyme disposed thereupon. Additional analyte sensors disclosed.

Abstract: NADP-dependent oxidoreductase compositions, and electrodes, sensors and systems that include the same. Analyte sensors include an electrode having a sensing layer disposed thereon, the sensing layer comprising a polymer and an enzyme composition distributed therein. The enzyme composition includes nicotinamide adenine dinucleotide phosphate (NAD(P)+) or derivative thereof; an NAD(P)+-dependent dehydrogenase; an NAD(P)H oxidoreductase; and an electron transfer agent comprising a transition metal complex.

Abstract: An analyte sensor including an antiglycolytic agent or a precursor thereof and a chelating agent that stabilizes the antiglycolytic agent positioned proximate to the working electrode of the sensor. Also provided are systems and methods of using the electrochemical analyte sensors in analyte monitoring.

Abstract: A lactate-responsive enzyme may form the basis for lactate detection and quantification using an electrochemical analyte sensor. Various features may be incorporated within an analyte sensor containing a lactate-responsive enzyme, particularly lactate oxidase, to improve sensitivity and response stability of the analyte sensor. Such analyte sensors may comprise: a working electrode having an active area disposed thereon, and a mass transport limiting membrane overcoating at least the active area upon the working electrode. The active area comprises at least a polymer, an albumin, and a lactate-responsive enzyme that is covalently bonded to the polymer. The mass transport limiting membrane may comprise at least a crosslinked polyvinylpyridine homopolymer or copolymer. The analyte sensors may determine a lactate concentration in a biological fluid, particularly in vivo, which may be correlated to various physiological conditions.

Abstract: Multiple enzymes may be present in one or more active areas of an electrochemical analyte sensor for detecting one or more different analytes. In particular, an analyte sensor may comprise a sensor tail configured for insertion into a tissue and one or more working electrodes having a glucose-responsive active area and an ethanol-responsive active area to detect glucose and ethanol in vivo.

Abstract: The present disclosure relates to a creatinine sensor comprising a first working electrode, a creatinine sensing layer on the first working electrode comprising a redox mediator, creatinine amidohydrolase, creatine amidinohydrolase, and sarcosine oxidase, and a hydrophilic polyurethane membrane overcoating the creatinine sensing layer. The creatinine sensor can further comprise a background sensing electrode that does not detect creatinine.

Abstract: Analyte sensors responsive at low working electrode potentials may comprise an active area upon a surface of a working electrode, wherein the active area comprises a polymer, a redox mediator covalently bonded to the polymer, and at least one analyte-responsive enzyme covalently bonded to the polymer. A specific redox mediator responsive at low potential may have a structure of wherein G is a linking group covalently bonding the redox mediator to the polymer. A mass transport limiting membrane permeable to the analyte may overcoat the active area. In some sensor configurations, the mass transport limiting membrane may comprise a membrane polymer crosslinked with a branched crosslinker comprising three or more crosslinkable groups, such as polyethylene glycol tetraglycidyl ether.

Abstract: Methods and analyte sensors including at least a first working electrode having a first active area thereon, and performing a dip coating operation to deposit a bilayer membrane upon the first working electrode and the first active area. The bilayer may include an inner layer having a first membrane polymer and an outer layer having a second membrane polymer, the first membrane polymer and the second membrane polymer differing from one another. The dip coating operation may comprise one or more first dips in a first membrane formulation to form the inner layer of the bilayer membrane and one or more second dips in a second membrane formulation to form the outer layer of the bilayer membrane upon the inner layer.

Abstract: Multiple enzymes may be present in the active area(s) of an electrochemical sensor to facilitate analysis of one or more analytes. The multiple enzymes may function independently to detect several analytes or in concert to detect a single analyte. One sensor configuration includes a first active area and a second active area, where the first active area has an oxidation-reduction potential that is sufficiently separated from the oxidation-reduction potential of the second active area to allow independent signal production. Some sensor configurations may have an active area overcoated with a multi-component membrane containing two or more different membrane polymers. Sensor configurations having multiple enzymes capable of interacting in concert include those in which a first enzyme converts an analyte into a first product and a second enzyme converts the first product into a second product, thereby generating a signal at a working electrode that is proportional to the analyte concentration.

Abstract: The present invention provides systems, devices and methods for in vivo monitoring of an analyte level. In particular, the present invention relates to improved sensors for use in in vivo monitoring of an analyte level.

Abstract: The present disclosure provides an analyte sensor comprising a working electrode, a sensing layer disposed on at least a portion of the working electrode, and a hydrophilic polyurethane membrane overcoating at least the sensing layer, wherein the hydrophilic polyurethane is aliphatic, aromatic, or both aliphatic and aromatic. The hydrophilic polyurethane membrane limits the transport of mass to the sensing layer without the need to be crosslinked. With such membrane, the analyte sensor can provide consistent analyte measurements over a temperature range of about 22-42° C. The present disclosure is further related to a method of forming an analyte sensor comprising providing a working electrode, disposing a sensing layer on at least a portion of the working electrode, and coating at least the sensing layer with a hydrophilic polyurethane membrane, wherein the hydrophilic polyurethane is aliphatic, aromatic, or both aliphatic and aromatic.

Abstract: A lactate-responsive enzyme may form the basis for lactate detection and quantification using an electrochemical analyte sensor. Various features may be incorporated within an analyte sensor containing a lactate-responsive enzyme, particularly lactate oxidase, to improve sensitivity and response stability of the analyte sensor. Such analyte sensors may comprise: a working electrode having an active area disposed thereon, and a mass transport limiting membrane overcoating at least the active area upon the working electrode. The active area comprises at least a polymer, an albumin, and a lactate-responsive enzyme that is covalently bonded to the polymer. The mass transport limiting membrane may comprise at least a crosslinked polyvinylpyridine homopolymer or copolymer. The analyte sensors may determine a lactate concentration in a biological fluid, particularly in vivo, which may be correlated to various physiological conditions.

Abstract: The present disclosure relates to sensing composition comprising a pyruvate-responsive enzyme and thiamine pyrophosphate (TPP). In particular, the sensing composition can comprise a pyruvate-responsive enzyme (e.g., pyruvate oxidase), TPP, optionally flavin adenine dinucleotide (FAD), a stabilizing agent (e.g., an albumin), and a redox mediator. The sensing composition forms a sensing layer on a working electrode to form a sensing electrode. The sensing electrode, along with a circuit, can form part of a system for sensing pyruvate. The present disclosure is further related to a method for sensing pyruvate, which includes accumulating charge derived from pyruvate reacting with the sensing composition for a set period of time and then measuring a signal from the accumulated charge.

Abstract: The present disclosure provides analyte sensors including one or more NAD(P)-dependent enzymes and an internal supply of NAD(P) for the detection of an analyte. The present disclosure further provides methods of using such analyte sensors for detecting one or more analytes present in a biological sample of a subject, and methods of manufacturing said analyte sensors.