# US 11,029,278 B2 · Ion sensor based on differential measurement, and production method

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- Number: US 11,029,278 B2
- Document ID: US11029278B2
- Status: Granted
- Kind: B2
- Application number: 16/530,574
- Filed: 2019-08-02
- Published: 2020-01-23
- Granted: 2021-06-08
- Earliest claimed: 2014-02-11
- Assignees: Consejo Superior De Investigaciones Cientificas (Csic)
- Applicants: Consejo Superior de Investigaciones Cientifícas (CSIC)
- Inventors: Antoni Baldi Coll; Carlos Dominguez Horna; Cecilia Jimenéz Jorquera; César Fernández Sánchez; Andreu Llobera Adan; Ángel Merlos Domingo; Alfredo Cadarso Busto; Isabel Burdallo Bautista; Ferrán Vera Gras
- Web page: https://patentgrep.com/patent/US11029278B2

## CPC

- G01N 27/414: Ion-sensitive or chemical field-effect transistors, i.e. ISFETS or CHEMFETS
- H10D 86/201: {the substrates comprising an insulating layer on a semiconductor body, e.g. SOI (H10D86/40 take precedence)}
- H10P 54/00: Cutting or separating of wafers, substrates or parts of devices
- H10W 74/131: {the semiconductor body being only partially enclosed}
- H10W 72/01515: {Forming coatings}
- H10W 72/075: {of bond wires}
- H10W 72/932: {Plan-view shape, i.e. in top view}
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)
- H10D: INORGANIC ELECTRIC SEMICONDUCTOR DEVICES
- H10P: GENERIC PROCESSES OR APPARATUS FOR THE MANUFACTURE OR TREATMENT OF DEVICES COVERED BY CLASS H10
- H10W: GENERIC PACKAGES, INTERCONNECTIONS, CONNECTORS OR OTHER CONSTRUCTIONAL DETAILS OF DEVICES COVERED BY CLASS H10

## Abstract

Ion sensor based on differential measurement comprising an ISFTET-REFET pair wherein the REFET is defined by a structure composed of an ISFET covered by a microreservoir where an internal reference solution is contained. The sensor comprises a first and a second ion-selective field effect transistor, an electrode, a substrate on the surface whereof are integrated the two transistors, connection tracks and the electrode and a structure adhered on the first ion-selective field effect transistor which creates a microreservoir on the gate of said first transistor, with the microreservoir having a microchannel which connects the microreservoir with the exterior and the microreservoir being filled with the reference solution.

## Claims

### Claim 1

A device comprising an ion sensor based on differential measurement, wherein the ion sensor comprises;
(i) a first ion-selective field effect transistor and a second ion-selective field effect transistor, electrically connected by connection tracks to an ion measurement system and each ion-selective field effect transistor having a gate;
(ii) an electrode arranged to be in contact with a solution to measure;
(iii) at least one chip on the surface whereof are integrated the ion-selective field effect transistors;
(iv) a structure adhered on the first ion-selective field effect transistor configured to create a microreservoir on the gate of only the first ion-selective field effect transistor the microreservoir being filled with a reference solution, wherein the first ion-selective field effect transistor is arranged to be in contact with the reference solution and the second ion-selective field effect transistor is in contact with a solution to measure;
(v) at least one microchannel having an outlet, the at least one microchannel connecting the microreservoir with the exterior of the structure, the at least one microchannel being filled with the reference solution;
(vi) a substrate whereon is integrated the at least one chip, the connection tracks and the electrode; and,
(vii) an encapsulating material which completely insulates the connection tracks and partially insulates the first and second ion-selective field effect transistors of the solution to measure, wherein the gates of the first and second ion-selective field effect transistors and the outlet of the microchannel are uncovered.

### Claim 2 (depends on 1)

The device according to claim 1, wherein the device further comprises a measurement receptacle, wherein the solution to measure is situated within the measurement receptacle.

### Claim 3 (depends on 1)

A method of ion measurement using the device of claim 1 comprising:
(i) introducing the ion sensor in a conditioning receptacle filled with a reference solution to fill the microreservoir with the reference solution;
(ii) removing the ion sensor from the conditioning receptacle;
(iii) rinsing the ion sensor;
(iv) immersing the ion sensor in a solution to measure situated within a measurement receptacle;
(v) measuring with the ion sensor at least one ion in the solution to measure;
(vi) cleaning the ion sensor;
(vii) re-inserting the ion sensor in the conditioning receptacle so that the microreservoir solution balances with the reference solution and returns to its original ion concentration.

### Claim 4 (depends on 3)

The method according to claim 3, wherein the solution to measure is selected from the group consisting of urine, a vaginal solution, and cell culture medium.

### Claim 5 (depends on 2)

A method of diagnosing a disease or condition in a subject comprising measuring at least one ion in a solution to measure obtained from the subject using the device of claim 2, wherein
(i) the device is a self-diagnostic device;
(ii) the at least one ion is H+;
(iii) the solution to measure is urine;
(iv) the disease is lithiasis or osteoporosis; and
wherein the method comprises
(a) calibrating the sensor by immersing the sensor in a conditioning receptacle filled with a reference solution; and,
(b) immersing the sensor in the solution to measure, wherein the solution to measure is situated within a measurement receptacle.