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EP-4740007-A1 - ORGANIC ELECTROCHEMICAL SENSOR WITH MUTUALIZED ELECTRODES AND METHOD FOR MEASURING

EP4740007A1EP 4740007 A1EP4740007 A1EP 4740007A1EP-4740007-A1

Abstract

The invention relates to an organic electrochemical sensor for the detection of analytes in a physiological sample, the sensor comprising at least two organic electrochemical transistors.

Inventors

  • ROHTLAID, Katlin
  • PREIRA, Pascal
  • ARRUABARRENA, Jean-Francois
  • MARTY, ALAIN
  • KANAAN, Joanne
  • SHIRINSKAYA, Anna

Assignees

  • Omini

Dates

Publication Date
20260513
Application Date
20240705

Claims (20)

  1. 1. An organic electrochemical sensor for the detection of analytes in a physiological sample, the sensor comprising: at least two sets of electrodes, each set of electrodes comprising a source (Si, S2, S3, S4) electrode and a drain (Di, D2, D3, D4) electrode, the source and drain electrodes of each set being connected by an organic conductive channel (Ci, C2, C3, C4) and at least two gates (Gi, G2, G3, G4), wherein at least one channel (Ci) and at least one gate (Gi) are unfunctionalized; wherein the channels (C2, C3, C4) and gates (G2, G3, G4) satisfy at least two of the following three conditions: i. at least one channel (C2, C3, C4) or at least one gate (G2, G3, G4) comprises a selective ion recognition layer, preferably a selective alkali ion recognition layer; ii. at least one channel (C2, C3, C4) or at least one gate (G2, G3, G4) comprises a faradaic recognition layer allowing recognition of a specific analyte by the reduction or oxidation of said analyte at said channel or said gate; iii. at least one channel (C2, C3, C4) or at least one gate (G2, G3, G4) comprises an affinity recognition layer allowing a recognition of a biomolecule in the sample by affinity; wherein any set of electrodes, the channel (Ci, C2, C3, C4) connected to said set of electrodes and any gate (Gi, G2, G3, G4) form an organic electrochemical transistor.
  2. 2. The organic electrochemical sensor according to claim 1, wherein for each organic electrochemical transistor, at least one of the channel or the gate forming said organic electrochemical transistor is unfunctionalized.
  3. 3. The organic electrochemical sensor according to claim 1 or 2, wherein the channels (C2, C3, C4) and gates (G2, G3, G4) satisfy said three conditions.
  4. 4. The organic electrochemical sensor according to any one of claims 1 to 3, wherein the faradaic recognition layer is an enzymatic recognition layer allowing recognition of the specific analyte by enzymatic reaction with the sample, preferably the enzymatic recognition layer is configured to detect creatinine.
  5. 5. The organic electrochemical sensor according to claim 4, wherein the enzymatic recognition layer is configured to perform a multi-enzyme cascade reaction.
  6. 6. The organic electrochemical sensor according to claim 5, further comprising a gate (G4) configured for the direct detection of creatine.
  7. 7. The organic electrochemical sensor according to claim 5, wherein the enzymatic recognition layer for the detection of creatinine comprises creatininase or creatinine amidinohydrolase.
  8. 8. The organic electrochemical sensor according to any one of claims 1 to 7, wherein the affinity recognition layer comprises at least one of the following: specific antibodies, aptamers, nanobodies or molecularly imprinted polymers, preferably the affinity recognition layer is configured to detect NT-pro-BNP.
  9. 9. The organic electrochemical sensor according to any one of claims 1 to 8, wherein at least one channel (C2, C3, C4) comprises an ion recognition layer being configured to detect Potassium ion.
  10. 10. The organic electrochemical sensor according to any one of claims 1 to 9, wherein at least one channel (C2, C3, C4) comprises an ion recognition layer being configured to detect Sodium ion.
  11. 11. The organic electrochemical sensor according to any one of claims 1 to 10, wherein at least two drain (D2, D3) electrodes are mutualized so that each drain electrode of the mutualized drain electrodes is used by two of the organic electrochemical transistors and/or at least two source (Si, S2, S3, S4) electrodes are mutualized so that each source electrode of the mutualized source electrodes is used by two of the organic electrochemical transistors.
  12. 12. The organic electrochemical sensor according to claim 4, comprising one channel (C2) comprising a selective Potassium ion recognition layer; one gate (G2) comprising an enzymatic recognition layer configured to detect creatinine; one unfunctionalized channel (Ci); one unfunctionalized gate (Gi).
  13. 13. The organic electrochemical sensor according to any one of claims 1 to 12, wherein the sensor comprises at least three gates (Gi, G2, G3, G4).
  14. 14. The organic electrochemical sensor according to claim 13, comprising one channel (C2) comprising a selective Potassium ion recognition layer; one gate (G2) comprising a faradaic recognition layer wherein the faradaic recognition layer is an enzymatic recognition layer allowing recognition of the specific analyte by enzymatic reaction with the sample, the enzymatic recognition layer being configured to detect creatinine; one gate (G3) comprising an affinity recognition layer configured to detect NT- pro-BNP; one unfunctionalized channel (Ci); one unfunctionalized gate (Gi).
  15. 15. The organic electrochemical sensor according to claim 13, comprising one channel (C2) comprising a selective Potassium ion recognition layer; one channel (C3) comprising a selective Sodium ion recognition layer; one gate (G2) comprising a faradaic recognition layer wherein the faradaic recognition layer is an enzymatic recognition layer allowing recognition of the specific analyte by enzymatic reaction with the sample, the enzymatic recognition layer being configured to detect creatinine; one gate (G3) comprising an affinity recognition layer configured to detect NT- pro-BNP; one unfunctionalized channel (Ci); and one unfunctionalized gate (Gi).
  16. 16. The organic electrochemical sensor according to claim 15, wherein the sources (Si, S2, S3, S4) comprise one mutualized pair of sources so that each source of the mutualized pairs sources is used by two of the organic electrochemical transistors; and wherein the drains (Di, D2, D3, D4) comprise one mutualized pair of drains so that each drain of the mutualized pairs drains is used by two of the organic electrochemical transistors.
  17. 17. The organic electrochemical sensor according to claim 15 or 16, further comprising one gate comprising an enzymatic recognition layer configured to directly detect creatin.
  18. 18. The organic electrochemical sensor according to any one of claims 1 to 17, wherein the size of the organic electrochemical sensor is lower than 5 cm 2 .
  19. 19. Electronic device comprising an organic electrochemical sensor according to any one of claims 1 to 18.
  20. 20. A method for detecting analytes in a physiological sample, the method comprising the steps of: a. Providing the organic electrochemical sensor according to any one of claims 1 to 18, b. Disposing the sample on the at least two channels (Ci, C2, C3, C4) and the at least three gates (Gi, G2, G3, G4), c. For each organic electrochemical transistor comprising the enzymatic recognition layer or the affinity recognition layer: i. voltages are respectively applied to the unfunctionalized channel (Ci) and to the unfunctionalized gate (Gi); and to the unfunctionalized channel (Ci) and to the functionalized gate (G2, G3, G 4 ), ii. an output is then measured, the output being a change of a value of drain current. d. For each organic electrochemical transistor comprising the selective ion recognition layer: i. voltages are respectively applied to the unfunctionalized channel (Ci), to the unfunctionalized gate (Gi); and to the functionalized channel (C2, C3, C4) and to the unfunctionalized gate (Gi), ii. an output is then measured, the output being a difference of value of current between the two drain (Di, D2, D3, D4) electrodes.

Description

ORGANIC ELECTROCHEMICAL SENSOR WITH MUTUALIZED ELECTRODES AND METHOD FOR MEASURING FIELD OF INVENTION [0001] The present invention relates to an organic electrochemical sensor. BACKGROUND OF INVENTION [0002] Heart failure is a chronic life-threatening disease needing lifelong management with 30% of patients being readmitted within 30 days after discharge. For most patients, the goal of therapy and pharmaceuticals is to improve patients’ quality of life, slow down disease progression and avoid acute life-threatening events during which hospitalization becomes necessary. Optimizing pharmaceutical dosing is patient specific; it requires titration to balance therapeutic efficacy with minimal side effects. While efforts are being made to reduce hospitalizations and readmissions, these are focused on monitoring surrogate and late indicators of heart failure acute events such as weight and patient symptoms, as opposed to frequent blood testing which can provide an early indication that an adjustment to patient medication dosage is required. [0003] Chronic kidney disease and kidney failure are also major public health issues affecting millions of people worldwide. These conditions are characterized by the gradual loss of kidney function, preventing the kidneys from effectively filtering waste and excess fluid from the blood. If left untreated, the conditions can lead to end-stage renal disease (ESRD), requiring dialysis or kidney transplantation for survival. Prevention and management of kidney failure rely on awareness, early screening, and control of underlying risk factors. [0004] However, known detection method and device for these diseases are not satisfactory. [0005] Indeed, current blood testing exclusively relies on clinical chemistry in laboratories or point-of-care devices that can only be used in professional healthcare setups. There is currently no solution that provides for home monitoring of all the key blood biomarkers for assessing disease evolution in heart failure or kidney failure. The patient thus needs to go regularly to the hospital or the doctor’s office to be monitored which may be difficult and leads to a lack of proper monitoring. In the worst case, the patient is taken to the hospital because the symptoms are present which implies that it is too late to detect heart or kidney failure aggravation without or with small aftereffects. [0006] The same issue arises in many other chronic diseases. [0007] Organic electrochemical transistors (OECTs) have been recently developed. An OECT basically comprises a source electrode and a drain electrode connected by a channel and a gate electrode. By functionalizing the gate or the channel of the OECTs, it is possible to use them as biosensors, i.e. , it allows detection and quantification of analytes in a sample. However, known OECTs merely allow to detect only one analyte at a time. Therefore, several OECTs with different functionalization are needed to diagnose chronic diseases such as heart failure or kidney failure which leads to an increase of the manufacturing costs and a complex use for the patient. [0008] Thus, there is a need for a device suitable for the detection and measurement of a plurality analytes in a single sample with high sensibility and high sensitivity in order to monitor chronic diseases such as heart failure or kidney failure. The device needs to be simple in order to be used by a patient, as well as compact and requiring reduced manufacturing costs. [0009] A purpose of this invention is therefore to provide an organic electrochemical sensor solving one or some of the drawbacks of known devices, in particular for the measure and monitoring chronic diseases such as of heart failure or kidney failure analytes. The sensor comprises a plurality of source electrodes and drain electrodes connected by channels and a plurality of gate electrodes. Some of the channels and gates are functionalized so that different analytes can be measured in an unprepared physiological sample such as a single blood drop. SUMMARY [0010] To this aim, the invention relates to an organic electrochemical sensor for the detection of analytes in a physiological sample. [0011] The sensor comprises at least two sets of electrodes, each set of electrodes comprising a source (Si, S2, S3, S4) electrode and a drain (Di, D2, D3, D4) electrode, the source and drain electrodes of each set being connected by an organic conductive channel (Ci, C2, C3, C4) and at least two gates (Gi, G2, G3, G4), wherein at least one channel (Ci) and at least one gate (Gi) are unfunctionalized; wherein the channels (C2, C3, C4) and gates (G2, G3, G4) satisfy at least two of the following three conditions: i. at least one channel (C2, C3, C4) or at least one gate (G2, G3, G4) comprises a selective ion recognition layer, preferably a selective alkali ion recognition layer; ii. at least one channel (C2, C3, C4) or at least one gate (G2, G3, G4) comprises a faradaic recognition layer allowi