Signal enhancement mechanism for dual-gate ion sensitive field effect transistor in on-chip disease diagnostic platform

Patent metadata

Field	Value
Publication number	US-9958443-B2
Application number	US-201715581673-A
Country	US
Kind code	B2
Filing date	Apr 28, 2017
Priority date	Oct 31, 2011
Publication date	May 1, 2018
Grant date	May 1, 2018

Abstract

Dual-gate ion-sensitive field effect transistors (ISFETs) for disease diagnostics are disclosed herein. An exemplary dual-gate ISFET includes a gate structure and a fluidic gate structure disposed over opposite surfaces of a device substrate. The gate structure is disposed over a channel region defined between a source region and a drain region in the device substrate. The fluidic gate structure includes a sensing well that is disposed over the channel region. The sensing well includes a sensing layer and an electrolyte solution. The electrolyte solution includes a constituent that can react with a product of an enzymatic reaction that occurs when an enzyme-modified detection mechanism detects an analyte. The sensing layer can react with a first ion generated from the enzymatic reaction and a second ion generated from a reaction between the product of the enzymatic reaction and the constituent, such that the dual-gate ISFET generates an enhanced electrical signal.

First claim

What is claimed is:

1. A dual-gate ion-sensitive field effect transistor (ISFET) comprising:
a device substrate having a first surface and a second surface, the first surface opposite the second surface;
a gate structure disposed over the first surface between a source region and a drain region in the device substrate, wherein a channel region is defined in the device substrate between the source region and the drain region;
a fluidic gate structure disposed over the second surface, wherein the fluidic gate structure includes a sensing well disposed over the channel region, the sensing well including a sensing layer; and
wherein the dual-gate ISFET is configured to generate an electrical signal when the sensing layer reacts with a first ion generated from an enzymatic reaction that occurs when an enzyme-modified detection mechanism detects a target analyte and a second ion generated from a reaction between a product of the enzymatic reaction and a constituent of an electrolyte solution.

2. The dual-gate ISFET of claim 1 , wherein the product is hydrogen peroxide.

3. The dual-gate ISFET of claim 1 , wherein the constituent is ferrous sulfate.

4. The dual-gate ISFET of claim 1 , wherein the enzyme-modified detection mechanism includes glucose oxidase enzyme (GO x ).

5. The dual-gate ISFET of claim 1 , wherein the enzyme-modified detection mechanism includes an enzyme immobilized on the sensing layer, wherein the enzyme generates the first ion and the product when the enzyme detects the target analyte.

6. The dual-gate ISFET of claim 1 , wherein the enzyme-modified detection mechanism includes:
a capture antibody for capturing the target analyte, wherein the capture antibody is immobilized on the sensing layer; and
a detection antibody conjugated with an enzyme, wherein the enzyme generates the first ion and the product upon the detection antibody binding with the target analyte.

7. The dual-gate ISFET of claim 1 , wherein the sensing layer includes a high-k dielectric material.

8. The dual-gate ISFET of claim 1 , further comprising:
a temperature sensor configured to measure a temperature of the device substrate; and
a heater configured to heat the device substrate.

9. The dual-gate ISFET of claim 1 , further comprising a reference electrode for biasing the fluid gate structure.

10. A dual-gate ion-sensitive field effect transistor (ISFET) comprising:
a device substrate having a first surface and a second surface, the first surface opposite the second surface;
a gate structure disposed over the first surface, the gate structure including:
a gate dielectric layer, and
a gate electrode layer disposed between a source region and a drain region in the device substrate, wherein a channel region is defined in the device substrate between the source region and the drain region; and

a fluidic gate structure disposed over the second surface, wherein the fluidic gate structure includes a sensing well disposed over the channel region, the sensing well including:
a sensing layer configured to react with a first ion generated from an enzymatic reaction that occurs when an enzyme-modified detection mechanism detects a target analyte and a second ion generated from a reaction between a product of the enzymatic reaction and an iron-containing constituent, such that the dual-gate ISFET generates an electrical signal.

11. The dual-gate ISFET of claim 10 , wherein:
the target analyte is glucose;
the enzyme-modified detection mechanism includes glucose oxidase enzyme (GO x ); and
the iron-containing constituent is ferrous sulfate (FeSO 4 ).

12. The dual-gate ISFET of claim 10 , wherein the enzyme-modified detection mechanism includes an enzyme immobilized on the sensing layer, wherein the enzyme generates the first ion and the product when the enzyme reacts with the target analyte.

13. The dual-gate ISFET of claim 12 , wherein the product is hydrogen peroxide.

14. The dual-gate ISFET of claim 10 , wherein the sensing layer includes a high-k dielectric material, and the gate electrode layer includes polysilicon.

15. A method for analyzing using a dual-gate ion-sensitive field effect transistor (ISFET) wherein the dual-gate ISFET includes a fluidic gate structure and a gate structure, wherein the fluidic gate structure and the gate structure are disposed over the opposite surfaces of a device substrate, the method comprising:
generating electrical characteristic data based on an an electrical signal generated from a sensing layer of the fluidic gate structure reacting with:
a first ion generated from an enzymatic reaction when an enzyme-modified detection mechanism detects a target analyte, and
second ion generated when a product of the enzymatic reaction reacts with a constitutent of an electrolyte solution; and determining a presence or a quantity of target analytes based on the electrical characteristic data.

16. The method of claim 15 , wherein:
the target analyte is glucose; and
the enzyme-modified detection mechanism includes glucose oxidase enzyme, such that the first ion is generated by an enzymatic reaction between glucose and glucose oxidase enzyme.

17. The method of claim 16 , wherein:
the constituent is ferrous sulfate; and
the enzymatic reaction between glucose and glucose oxidase enzyme produces hydrogen peroxide, such that the second ion is generated by a reaction between the hydrogen peroxide and the ferrous sulfate.

18. The method of claim 16 , wherein the constituent is an iron-containing constituent, and the product is hydrogen peroxide.

19. The method of claim 15 , wherein the generating the electrical characteristic data includes generating a current-voltage (I-V) curve by biasing the fluidic gate structure with a fluidic gate voltage.

20. The method of claim 19 , wherein the determining the presence or the quantity of target analytes based on the electrical characteristic data includes evaluating a drain-to-source current when the fluidic gate voltage reaches a threshold voltage.

Assignees

• Taiwan Semiconductor Mfg Co Ltd

Inventors

• Lin Ching-Hui
• Cheng Chun-Ren
• Huang Shih-Fen
• Chang Yi-Hsien

Classifications

• C12Q1/006

  for glucose · CPC title

• H01L29/66484

  Electricity · mapped topic

• G01N27/4145 Primary

  specially adapted for biomolecules, e.g. gate electrode with immobilised receptors · CPC title

• H01L51/0093

  Electricity · mapped topic

• H01L29/7831

  Electricity · mapped topic