Biosensor and method for analyzing analyte concentration in a liquid sample

• US 10,379,078 B2
• Filed: 10/02/2015
• Issued: 08/13/2019
• Est. Priority Date: 04/20/2015
• Status: Active Grant

• Current Assignee: National Tsing Hua University
• Original Assignee: National Tsing Hua University
• Inventors: Wang, Yu-Lin, Chyi, Jen-Inn, Chu, Chia-Ho, Sarangadharan, Indu
• Primary Examiner(s): Kaur, Gurpreet
• Application Number:
  US14/873,765
• Publication Number:
  US 20160305900A1
• Time in Patent Office: 1,411 Days
• CPC Class Codes: G01N 27/4145 specially adapted for biomolecules, e.g. gate electrode with immobilised receptors

Abstract

A biosensor includes a transistor and a reactive electrode. The transistor has a source, a drain and a gate surface disposed therebetween. The reactive electrode is spaced apart from the gate surface of the transistor, has a receptor immobilized thereon for specific binding with an analyte in a liquid sample, and is configured to contact the liquid sample together with the gate surface of the transistor.

Claims

1. A method for analyzing concentration of an analyte in a liquid sample, comprising:

applying the liquid sample to a biosensor, wherein the biosensor includes a transistor that has a drain, a source and a gate surface disposed between the drain and the source, and a reactive electrode spaced apart from the gate surface of the transistor, the reactive electrode having a receptor immobilized thereon for specific binding with the analyte in the liquid sample and being configured to, together with the gate surface of the transistor, contact the liquid sample;

applying a voltage pulse between the reactive electrode and the source of the transistor, the voltage pulse having a pulse width;

monitoring a response current, which is produced in response to the voltage pulse, within the pulse width from the biosensor;

performing arithmetic computational processing to divide entries of the response current by a maximum value of the response current;

performing integration computational processing on results of the arithmetic computational processing with respect to at least a certain period in the pulse width to obtain time constant; and

analyzing the time constant that is correlated to the concentration of the analyte in the liquid sample.

2. The method of claim 1, wherein the pulse width of the voltage pulse is not greater than 10⁻

3 second.

3. The method of claim 1, wherein the transistor is selected from the group consisting of a high electron mobility transistor (HEMT), a silicon-based transistor, a nanowire transistor, a graphene transistor, and a molybdenum disulfide (MoS₂)-included transistor.

4. The method of claim 1, wherein the reactive electrode has a surface layer that has the receptor immobilized thereon and that contains gold.

5. The method of claim 1, wherein the reactive electrode is disposed on top of and faces the gate surface of the transistor.

6. The method of claim 1, wherein the reactive electrode and the gate surface of the transistor are arranged in a coplanar manner.

7. The method of claim 1, further comprising steps of:

prior to the application of the liquid sample, applying a reference protein solution to the biosensor;

applying the voltage pulse between the reactive electrode and the source of the transistor after applying the reference protein solution;

monitoring a reference response current within the pulse width from the source of the biosensor; and

removing the reference protein solution.

8. The method of claim 5, further comprising a step of performing subtraction processing on the response current with respect to the pulse width by subtracting out the reference response current.