Signal enhancement mechanism for dual-gate ion sensitive field effect transistor in on-chip disease diagnostic platform
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.
1. A dual-gate ion-sensitive field effect transistor (ISFET) for analyzing a biological sample, the dual-gate 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 an electrolyte solution; and
wherein the dual-gate ISFET is configured to generate an electrical signal when the sensing layer reacts with an ion generated from an enzymatic reaction that occurs when an enzyme-modified detection mechanism detects a target analyte and an ion generated from a reaction between a product of the enzymatic reaction and a constituent of the electrolyte solution, the electrical signal indicating an ion concentration in the electrolyte solution that correlates with a presence or a quantity of target analytes in the biological sample.
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 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 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) for analyzing a biological sample, the dual-gate 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;
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:
an electrolyte solution that includes an iron-containing constituent that can react with a product of an enzymatic reaction that occurs when an enzyme-modified detection mechanism detects a target analyte; and
a sensing layer configured to 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 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 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 a biological sample using a dual-gate ion-sensitive field effect transistor (ISFET), the method comprising:
providing the biological sample to the dual-gate 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 opposite surfaces of a device substrate;
generating an enzymatic reaction when an enzyme-modified detection mechanism detects a target analyte, such that a first ion and a product are released into an electrolyte solution of the fluidic gate structure;
generating a reaction between the product of the enzymatic reaction and a constituent of the electrolyte solution, such that a second ion is released into the electrolyte solution of the fluidic gate structure; and
generating an electrical signal as a sensing layer of the fluidic gate structure reacts with the first ion and the second ion, wherein the electrical signal indicates an ion concentration in the electrolyte solution that correlates with a presence or a quantity of target analytes in the biological sample.
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 generating the electrical signal includes biasing the fluidic gate structure with a fluidic gate voltage, wherein the electrical signal is evaluated when the fluidic gate voltage reaches a threshold voltage.
20. The method of claim 15 , further comprising controlling a temperature of the device substrate to optimize generation of the generated enzymatic reaction and the generated reaction.