The present disclosure relates to electrochemical sensors for measuring creatinine and creatine in a patient's blood. More particularly, the disclosure relates to compositions and methods for improving calibration accuracy of electrochemical sensors used for measuring creatinine and creatine.

The disclosure relates to electrochemical sensors for measuring creatinine and creatine in a patient's blood. More particularly, the disclosure relates to compositions and methods for improving measurement accuracy of electrochemical sensors used for measuring creatinine and creatine.

The invention includes method and materials designed to measure the material properties (e.g. thickness) of layers of material in a sensor using non-Faradaic EIS (Electrochemical Impedance Spectroscopy) methods. The methods are non-destructive, very sensitive and rapid. Typically in these methods, an AC voltage is applied to the desired material layer while the output current and therefore impedance is measured. This voltage can be applied in multiple frequencies in sweep mode in order to detect both the material and, for example, the thickness of the target material. In this way, EIS allows the characterization of properties of various layers of material disposed in devices such as electrochemical glucose sensors.

An apparatus for measuring a concentration of an analyte in a bio-sample using an electrochemical bio-sensor, includes a connector with a sample cell in which an oxidation/reduction enzyme and an electron transfer mediator are fixed and a working electrode and an counter electrode are provided; a digital-to-analog converter circuit configured to apply a constant DC voltage to start the oxidation/reduction reaction of the analyte, proceed with an electron transfer reaction, and apply a -step ladder-type perturbation potential for fluctuating a potential of the sample cell after applying the constant DC voltage; and a microcontroller configured to control the digital-to-analog converter circuit and directly obtain a concentration value of the analyte from a calibration equation using the -step ladder-type perturbation potential. The apparatus can improve measurement accuracy by effectively minimizing a matrix interference effect of a background material in a bio-sample, particularly an inaccuracy caused by a change in hematocrit.

In various embodiments a molecular circuit is disclosed. The circuit comprises a negative electrode, a positive electrode spaced apart from the negative electrode, and an enzyme molecule conductively attached to both the positive and negative electrodes to form a circuit having a conduction pathway through the enzyme. In various examples, the enzyme is a polymerase. The circuit may further comprise molecular arms used to wire the enzyme to the electrodes. In various embodiments, the circuit functions as a sensor, wherein electrical signals, such as changes to voltage, current, impedance, conductance, or resistance in the circuit, are measured as substrates interact with the enzyme.

The present application discloses a planar enzyme sensor for measuring the concentration of an analyte in a solution comprising a substrate of an electrically insulating material supporting an electrode layer of an electrically conductive material. The substrate and electrode layer have a plurality of layers disposed thereon which include an enzyme layer and a microporous outer layer covering the enzyme layer, wherein the outer layer comprises a continuous phase of a water-resistant polymer (e.g. a polyvinylacetate or an acrylate copolymer), a protein (e.g. an enzyme) embedded in the continuous phase, and possibly polytetrafluoroethylene particles. The enzyme and the polytetrafluoroethylene particles provide a controlled porosity to the outer membrane.

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.

Creatinine levels may be monitored as a measure of kidney function. Conventionally, blood and/or urine tests are used for this purpose. Analyte sensors capable of monitoring creatinine in vivo may comprise: a sensor tail comprising at least a first working electrode, a creatinine-responsive active area disposed upon a surface of the first working electrode, a first membrane that is permeable to creatinine and overcoats the creatinine-responsive active area, and an oxygen scavenger located upon the sensor tail in proximity to the creatinine-responsive active area. The creatinine-responsive active area comprises a first electron transfer agent, a first polymer, and an enzyme system comprising multiple enzymes, particularly creatinine amidohydrolase, creatine amidohydrolase, and sarcosine oxidase, that are capable of acting in concert to facilitate detection of creatinine. An oxidase enzyme may serve as the oxygen scavenger, particularly glucose oxidase when detecting creatinine in fluids also containing glucose.

A method of identifying a therapeutic compound for treating cancer in a human subject, the method including: providing a device that measures cell-substrate impedance; culturing cancer cells in the at least two wells, wherein the cancer cells are obtained from a human subject and have a receptor tyrosine kinase (RTK) pathway; adding to a first well a proposed therapeutic compound that affects an RTK pathway and an RTK stimulating factor for the RTK pathway to form a test well, and adding to another well the RTK stimulating factor to form a control well; continuously monitoring cell-substrate impedance of the at least two wells; and determining a difference in impedance or optionally in cell index between the test well and control well; and if significantly different, concluding the proposed therapeutic compound is therapeutically active in the RTK pathway within the cancer cells of the human subject.

The disclosure generally relates to a deoxyribonucleic acid (DNA) sequencing circuit having a controllable pore size and a lower membrane capacitance and noise floor relative to biological nanopore devices. For example, design principles used to fabricate a fin-shaped field effect transistor (FinFET) may be applied to form, on a first wafer, a nanopore that has a desired pore size in a silicon-based membrane. Electrodes and an interconnect embedded with an amplifier and analog-to-digital converter (ADC) may be formed on a separate second wafer, wherein the first wafer and the second wafer may then be bonded and further processed to form a sensing device that includes appropriate wells and pores to be used in a DNA sequencing circuit.