Molecular detection chip including mosfet , molecular detection device employing the chip, and molecular detection method using the device

• US 20030102510A1
• Filed: 09/25/2002
• Published: 06/05/2003
• Est. Priority Date: 04/23/2001
• Status: Active Grant

• Current Assignee: Samsung Electronics Co. Ltd.
• Original Assignee: Samsung Electronics Co. Ltd.
• Inventors: Park, Chin-Sung, Lim, Geun-Bae, Kim, Sun-Hee, Cho, Yoon-Kyoung
• Granted Patent: US 7,235,389 B2
• Time in Patent Office: Days
• US Class Current: 257/368
• CPC Class Codes: B01J 2219/00497 Features relating to the solid phase supports
• CPC Class Codes: B01J 2219/00511 Walls of reactor vessels
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• CPC Class Codes: B01J 2219/00653 the compounds being bound to electrodes embedded in or on the solid supports
• CPC Class Codes: B01J 2219/00657 One-dimensional arrays
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00677 Ex-situ synthesis followed by deposition on the substrate
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: B01J 2219/00725 Peptides
• CPC Class Codes: B01J 2219/00729 Peptide nucleic acids [PNA]
• CPC Class Codes: B01J 2219/00731 Saccharides
• CPC Class Codes: B01J 2219/00743 Cells
• CPC Class Codes: B01L 3/5027 by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• CPC Class Codes: B82Y 15/00 Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: C12Q 1/6837 using probe arrays or probe chips C12Q1/6874 takes precedence
• CPC Class Codes: C12Q 2565/607 being a sensor, e.g. electrode
• CPC Class Codes: G01N 27/4145 specially adapted for biomolecules, e.g. gate electrode with immobilised receptors
• CPC Class Codes: G01N 33/54373 involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
• CPC Class Codes: G01N 33/5438 : Electrodes

Abstract

A molecular detection chip including a metal oxide silicon-field effect transistor (MOSFET) on sidewalls of a micro-fluid channel and a molecular detection device including the molecular detection chip are provided. A molecular detection method, particularly, qualification methods for the immobilization of molecular probes and the binding of a target sample to the molecular probes, using the molecular detection device, and a nucleic acid mutation assay device and method are also provided. The formation of the MOSFET on the sidewalls of the micro-fluid channel makes easier to highly integrate a molecular detection chip. In addition, immobilization of probes directly on the surface of a gate electrode ensures the molecular detection chip to check for the immobilization of probes and coupling of a target molecule to the probes in situ.

Claims

1. A molecular detection chip comprising:

a semiconductor substrate;

a micro-fluid channel serving as a flow path of a molecular sample and formed in the semiconductor substrate, and

a metal oxide silicon field-effect transistor (MOSFET) on sidewalls of the micro-fluid channel.

2. The molecular detection chip of claim 1, wherein a gate electrode of the MOSFET is formed of a thin gold (Au) layer.

3. The molecular detection chip of claim 2, wherein thiol-substituted probes are immobilized as self-assembled monolayers on the surface of the gate electrode.

4. The molecular detection chip of claim 1, wherein the molecular sample comprises nucleic acids, proteins, enzyme substrates, adjuvants, or oligosaccharides.

5. The molecular detection chip of claim 4, wherein the nucleic acids comprise single-stranded deoxyribonucleic acids (DNAs), single-stranded ribonucleic acids (RNAs), or single-stranded peptide nucleic acids (PNAs).

6. The molecular detection chip of claim 4, wherein the proteins comprise agonists to cell membrane receptors, antagonists to cell membrane receptors, toxins, virus epitopes, hormones, peptides, enzymes, or monoclonal antibodies.

11. The molecular detection device of claim 10, wherein the metal oxide silicon-field effect transistor sensor is implemented with the molecular detection chip of any of claims 1 through 6.

16. The nucleic acid mutation assay device of claim 15, wherein the metal oxide silicon-field effect transistor sensor is implemented with the molecular detection chip of any of claims 1 through 6.

7. A method for fabricating a molecular detection chip, the method comprising:

forming an oxide layer on the surface of a semiconductor substrate;

forming a micro-fluid channel having at least one convex corner by etching the surface of the semiconductor substrate;

forming an impurity diffusion region by doping the sidewalls of the micro-fluid channels with impurity ions;

defining a channel region of a metal oxide silicon-field effect transistor (MOSFET) by etching a portion of the impurity diffusion region formed on the sidewalls of the micro-fluid channel using an etching solution;

forming an oxide layer on the channel region; and

forming a gate electrode on the channel region using gold (Au).

8. The method of claim 7, wherein defining the channel region is performed by selectively etching the impurity diffusion region along the at least one convex corner.

9. The method of claim 7, wherein, in defining the channel region, an etch stop point is determined by measuring current level variations with application of reverse bias voltage to the semiconductor substrate.

10. A molecular detection device comprising:

a substrate;

a molecular-sample loading unit formed on the surface of the substrate;

at least one micro-fluid channel having one end connected to the molecular-sample loading unit and serving as a flow path for a molecular sample; and

a metal oxide silicon-field effect transistor (MOSFET) sensor connected to the other end of the micro-fluid channel and on which a molecular probe is immobilized.

12. A quantification method of the immobilization of molecular probes, the method comprising:

providing the molecular probes into the molecular-sample loading unit of the molecular detection device of claim 10 or 11;

immobilizing the molecular probes on the surface of a gate electrode of the metal oxide silicon-field effect transistor sensor by allowing the molecular probes to move along the micro-fluid channel; and

measuring current-voltage characteristics of the gate electrode.

13. A quantification method of the binding of molecular probes and a target molecular sample, the method comprising:

(a) providing the molecular probes into the molecular-sample loading unit of the molecular detection device of claim 10 or 11;

(b) immobilizing the molecular probes on the surface of a gate electrode of the metal oxide silicon-field effect transistor sensor by allowing the molecular probes to move along the micro-fluid channel;

(c) measuring current-voltage characteristics of the gate electrode;

(d) providing the target molecular sample into the molecular-sample loading unit

(e) binding the target molecular sample to the molecular probes immobilized on the surface of the gate electrode of the metal oxide silicon-field effect transistor sensor by allowing the target molecular sample to move along the micro-fluid channel; and

(f) measuring current-voltage characteristics of the gate electrode and comparing the result of the measurement with the current-voltage characteristics measured in step (c).

14. The quantification method of claim 13, wherein hybridization of a probe nucleic acid to a target nucleic acid is quantitatively measured.

15. A nucleic acid mutation assay device comprising:

a substrate;

a sample loading unit formed on the surface of the substrate;

a micro-fluid channel directly connected to the sample loading unit to serve as a sample flow path; and

at least one thermal control and detection unit formed in the micro-fluid channel and including a metal oxide silicon-field effect transistor (MOSFET) sensor for nucleic acid immobilization, a heater, and a thermal sensor.

17. The nucleic acid mutation assay device of claim 15, wherein the heater and the thermal sensor are located adjacent to the metal oxide silicon-field effect transistor sensor and control a temperature which is significant to the nucleic acid immobilized on the metal oxide silicon-field effect transistor sensor, and the metal oxide silicon-field effect transistor sensor detects denaturated or renaturated double-stranded nucleic acid at the melting point T_m of the immobilized nucleic acid.

18. A method for assaying nucleic acid mutation, the method comprising:

immobilizing single-stranded nucleic acid probes on the surface of a gate electrode of a metal oxide silicon-field effect transistor (MOSFET) sensor;

injecting a target nucleic acid responsive to the immobilized single-stranded nucleic acid probes into a sample loading unit and moving the target nucleic acid to the metal oxide silicon-field effect transistor sensor along a micro-fluid channel;

hybridizing the target nucleic acid to the single-stranded nucleic acid probes immobilized on the metal oxide silicon-field effect transistor sensor;

gradually raising a temperature to separate the double-stranded nucleic acid which are hybridized, into two single strands; and

measuring current-voltage characteristics of the gate electrode of the metal oxide silicon-field effect transistor sensor.

20. The method of claim 18 or 19, wherein single nucleotide polymorphism of nucleic acid is detected.

19. A method for assaying nucleic acid mutation, the method comprising.

immobilizing single-stranded nucleic acid probes on the surface of a gate electrode of a metal oxide silicon-field effect transistor (MOSFET) sensor;

injecting a target nucleic acid responsive to the immobilized single-stranded nucleic acid probes into a sample loading unit and moving the target nucleic acid to the metal oxide silicon-field effect transistor sensor along a micro-fluid channel;

keeping a temperature at which hybridization of the target nucleic acid to the single-stranded nucleic acid probes does not occur;

gradually dropping the temperature to renaturate single-stranded nucleic acids into double-stranded nucleic acids which are hybridized; and

measuring current-voltage characteristics of the gate electrode of the metal oxide silicon-field effect transistor sensor.