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US-12616400-B2 - Sensor array systems for reaction measurement by electronic gate

US12616400B2US 12616400 B2US12616400 B2US 12616400B2US-12616400-B2

Abstract

The present invention is directed to devices for measuring reactions between a recognition element and a biological fluid (biomarker) to determine user well-being. The present invention features a sensor for analyzing a plurality of features of a reaction between an enzyme and a biomarker to measure a user's health. The sensor may comprise a substrate with an enzyme source and a drain. The enzyme source may comprise an enzyme path leading to a substrate surface to direct the enzyme to react with the biomarker to become a post-reaction mixture. The drain may comprise a drain path. The post-reaction mixture may travel from the substrate surface through the drain path to the drain. The sensor may further comprise an electronic gate disposed above the surface of the substrate for measuring the plurality of features. The sensor may be wearable on a skin surface of the user.

Inventors

  • Erin L. Ratcliff
  • Jonathan Harris
  • Songyan Yu

Assignees

  • ARIZONA BOARD OF REGENTS ON BEHALF OF THE UNIVERSITY OF ARIZONA

Dates

Publication Date
20260505
Application Date
20230505

Claims (20)

  1. 1 . A sensor for analyzing one or more features of a reaction between a first reactant and a second reactant, the sensor comprising: a. a substrate, the substrate comprising: i. a reactant source fluidly connected to a reactant path leading to a surface ( 250 ) of the substrate, wherein the first reactant contained in the reactant source travels through the reactant path to the surface to react with the second reactant to become a post-reaction mixture on the surface of the substrate, ii. a drain fluidly connected to a drain path, wherein the post-reaction mixture travels from the surface of the substrate through the drain path to the drain; and b. an electronic gate in fluid communication with the post-reaction mixture for measuring the one or more features of the reaction between the first reactant and the second reactant; wherein the one or more features are selected from a group consisting of a rate constant of the reaction, a concentration of the first reactant in the post-reaction mixture, a concentration of the second reactant in the post-reaction mixture, and an amount of energy produced by the reaction.
  2. 2 . The sensor of claim 1 , wherein analyzing the one or more features allows the sensor to measure physiological parameters of fluids produced by an animal.
  3. 3 . The sensor of claim 1 further comprising a pump for directing the first reactant from the reactant source through the reactant path to the surface of the substrate.
  4. 4 . The sensor of claim 1 , wherein the reactant path comprises a plurality of capillaries, wherein the first reactant is directed through the reactant path by a wicking action.
  5. 5 . The sensor of claim 1 , wherein the sensor is communicatively coupled to a computing device.
  6. 6 . The sensor of claim 5 , wherein the computing device implements a machine learning algorithm for analyzing the one or more features.
  7. 7 . The sensor of claim 1 , wherein the sensor is communicatively coupled to one or more additional sensors disposed in different locations to act as an array of sensors.
  8. 8 . The sensor of claim 7 , wherein the array of sensors are capable of measuring one or more array features selected from a group consisting of spatial distribution, distribution of rate constants, and a variety of analytes.
  9. 9 . The sensor of claim 1 further comprising an attachment component allowing the sensor to attach to a surface or tissue.
  10. 10 . The sensor of claim 1 further comprising an interacting channel comprising a first control gate electrode and a first solid-state analyte disposed in a first biofluid for providing a charge transfer to the electronic gate.
  11. 11 . A method for analyzing one or more features of a reaction between a first reactant and a second reactant, the method comprising: a. providing a sensor, wherein the sensor comprises: i. a substrate, the substrate comprising: A. a reactant source fluidly connected to a reactant path leading to a surface of the substrate, wherein the first reactant contained in the reactant source travels through the reactant path to the surface to react with the second reactant to become a post-reaction mixture on the surface of the substrate, B. a drain fluidly connected to a drain path, wherein the post-reaction mixture travels from the surface of the substrate through the drain path to the drain; and ii. an electronic gate in fluid communication with the post-reaction mixture for measuring the one or more features of the reaction between the first reactant and the second reactant; wherein the one or more features are selected from a group consisting of a rate constant of the reaction, a concentration of the first reactant in the post-reaction mixture, a concentration of the second reactant in the post-reaction mixture, and an amount of energy produced by the reaction; b. applying the second reactant to the sensor; and c. analyzing, by a computing device, a readout from the electronic gate upon detecting the reaction between the first reactant and the second reactant.
  12. 12 . The method of claim 11 , wherein analyzing the one or more features allows the sensor to measure physiological parameters of a fluid produced by an animal.
  13. 13 . The method of claim 11 , wherein the sensor ( 100 ) further comprises a pump for directing the first reactant from the reactant source ( 300 ) through the reactant path to the surface ( 250 ) of the substrate ( 200 ).
  14. 14 . The method of claim 11 , wherein the reactant path comprises a plurality of capillaries, wherein the first reactant is directed through the reactant path by a wicking action.
  15. 15 . The method of claim 14 , wherein the plurality of capillaries comprises a plurality of microfluidic capillaries.
  16. 16 . The method of claim 11 , wherein the computing device implements a machine learning algorithm for analyzing the one or more features.
  17. 17 . The method of claim 11 , wherein the sensor is communicatively coupled to one or more additional sensors disposed in different locations to act as an array of sensors.
  18. 18 . The method of claim 17 , wherein the array of sensors are capable of measuring one or more array features selected from a group consisting of spatial distribution, distribution of rate constants, and a variety of analytes.
  19. 19 . The method of claim 11 , wherein the sensor further comprises an attachment component allowing the sensor to attach to a surface or tissue.
  20. 20 . The method of claim 11 , wherein the sensor wherein the surface or tissue is an animal surface, an animal tissue, a synthetic surface, or a natural surface.

Description

CROSS-REFERENCES TO RELATED APPLICATIONS This application is a Continuation-In-Part and claims benefit of PCT Application No. PCT/US2021/058336 filed Nov. 5, 2021, which claims benefit of U.S. Provisional Patent Application No. 63/110,211 filed Nov. 5, 2020, the specifications of which are incorporated herein in their entirety by reference. This application is also a Continuation-In-Part and claims benefit of PCT Application No. PCT/US2022/079168 filed Nov. 2, 2022, which claims benefit of U.S. Provisional Patent Application No. 63/276,400 filed Nov. 5, 2021, the specifications of which are incorporated herein in their entirety by reference. FIELD OF THE INVENTION The present invention is directed to methods, sensor systems, and devices for measuring reactions between a recognition element and a reactant such as but not limited to a biological fluid (biomarker). BACKGROUND OF THE INVENTION Organic electrochemical transistors (OECTs) have garnered considerable interest for sensing and bioelectronics applications, as the device architecture enables simple electrical readout, convenient fabrication, fast manufacturing on flexible substrates, and straightforward miniaturization for lab-on-a-chip applications with versatile geometries. Of particular note, OECTs exhibit a hybrid electrical-ionic conduction mechanism, where electrochemical doping/dedoping of the channel yields a significant modulation of conductivity at low operating voltages (<1 V). This effect enables very low levels of detection of biological materials through signal amplification. Given the exciting attributes of OECTs as sensors, several models have been developed to understand the operation of the OECT. One mode is the capacitive mode, whereby the gate electrode and channel are treated as capacitors in series. The device response is highly dependent on electrolyte potential, where capacitances of the semiconductor channel can change from 1-10 μF/cm2 (double-layer-like) to >103 μF/cm3 (volumetric) over 100 mV. A second mode, termed the faradaic mode, is achieved via electron transfer (i.e., redox reactions) at the gate electrode. This mode enables the majority of the electric field to drop across the polymer channel, yielding higher amplifications than in a non-faradaic (capacitive) mode. The present invention is directed to OECTs operated in the faradaic mode. For sensing applications including wearables, microfluidics, and/or implantable devices, one must balance size, target analyte concentration, biocompatibility, fabrication, and the cost of the net sensor design. Thus, a better performing OECT (higher transconductance) may not necessarily translate to higher sensitivity. For sensors, key advantages of the faradaic mode OECT are directly connected to ultralow level analyte detection, whereby reduction in device size may have the following advantages: opportunities to approach single-molecule/entity detection, inherently less power due to less current draw from smaller electrodes, enhanced mass transport effects, reduction in cost associated with bio-recognition elements and/or microfluidics, and translation to multiplexing and/or small fluid volumes (nL to fL). Demonstrations of faradaic mode OECT sensors to date are quantification of redox-active biomarkers H2O2, glucose, and dopamine. More recently, the introduction of redox probes/catalysis at OECT gate electrodes facilitates the detection of more complex biologically-relevant species. A similar approach combining redox-active molecules with chemically selective bio-recognition elements in a mixed monolayer at an electrode is gaining traction in electrochemical impedance-based sensing. The present invention describes how the redox behavior at the gate can be used to lower OECT operating power, specifically its onset voltage and maximum transconductance, with the outcome of combining redox moieties for high amplification in the faradaic mode with chemical selectivity of a surface-confined bio-recognition element. Since the electrochemical doping process of the polymer channel is coupled by the reaction at the gate in the faradaic mode, the effective density of states (DOS) overlaps between the two processes (as a function of electrolyte potential) plays a crucial role in determining OECT characteristics. The present invention describes implementing two common p-type polymers, poly(3-hexylthiophene) (P3HT) and poly[2-5-bis(3-dode-cylthiophen-2-yl)thieno[3,2-b ]thiophene)] (PBTTT-C12), and a set of representative redox molecules with varying redox potentials. Aligning the oxidation potential of the polymer with the reduction potential of the electrolyte oxidant, the gate voltage can be successfully minimized at maximum transconductance, toward realization of a self-driven or self-powered gate device. The present invention implements a Marcus—Gerischer perspective for electrochemical events at both the gate and semiconductor channel. This electrochemical perspective is selected as it enab