Ultrasensitive biochemical sensor

• US 20050014178A1
• Filed: 05/24/2004
• Published: 01/20/2005
• Est. Priority Date: 05/22/2003
• Status: Active Grant

• Current Assignee: University of Hawai'i
• Original Assignee: University of Hawai'i
• Inventors: Holm-Kennedy, James W.
• Granted Patent: US 7,291,496 B2
• Time in Patent Office: Days
• US Class Current: 435/6
• 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: Y10S 436/806 Electrical property or magnetic property

Abstract

An electronic sensor is provided for detecting the presence of one or more analytes of interest in a sample. The sensor preferably comprises a field effect transistor in which conductance is enhanced by analyte binding to receptors in the active region. An array of sensors may be formed to analyze a sample for multiple analytes.

Claims

1. A sensor for detecting the presence of an analyte in a sample comprising a receptor for the analyte of interest bound to the active region of a field effect transistor (FET), wherein the active region overlies a p conducting channel connecting a source region and a drain region.

2. The sensor of claim 1, wherein the active region comprises a polysilicon gate.

3. The sensor of claim 1, wherein the active region comprises a gate dielectric layer.

4. The sensor of claim 1, wherein the gate dielectric layer is a silicon nitride layer.

5. The sensor of claim 1, wherein the receptor is bound to the silicon nitride layer.

6. The sensor of claim 1, additionally comprising a back gate.

7. The sensor of claim 7, wherein the sensitivity of the sensor is increased by applying a bias to the back gate.

8. The sensor of claim 7, wherein the receptor is selected from the group consisting of antibodies, antibody fragments, peptides, oligonucleotides, DNA, RNA, aptamers, and organic molecules.

9. The sensor of claim 1, comprising two or more receptors specific for the same analyte.

10. The sensor of claim 1, comprising two or more receptors specific for different analytes.

11. The sensor of claim 1, wherein the sensor operates in enhancement mode upon binding of a negatively charged analyte.

12. The sensor of claim 1, wherein the receptor is bound to the active region via a linker molecule.

13. A method for identifying the presence of an analyte of interest in a sample comprising:

contacting the active region of a sensor with the sample, wherein the sensor comprises one or more receptors for the analyte of interest bound to the active region and wherein the active region overlies a p conducting channel connecting a source and drain;

measuring sensor output; and

identifying the presence of the analyte of interest where the sensor output indicates a change in conductance of the channel upon exposing the active region to the sample.

14. The method of claim 13, wherein the sensor output is selected from the group consisting of conductance, voltage and resistance.

15. The method of Clam 13, wherein the change in conductance is caused by binding of the analyte to the receptor.

16. The method of claim 15, wherein the analyte is negatively charged.

17. The method of claim 15, wherein binding of the analyte of interest enhances conductance between the source and drain

18. The method of claim 13, wherein the change in conduction is enhanced by contacting the bound analyte with a secondary charged molecule.

19. The method of claim 18, wherein the secondary charged molecule is an antibody.

20. The method of claim 18, wherein the secondary charged molecule is a bead.

21. A sensor for detecting the presence of an analyte in a sample comprising a field effect transistor operating in enhancement mode, wherein binding of the analyte of interest to a receptor on the active region of the sensor increases conduction through a channel connecting a source region and a drain region.

22. The sensor of claim 21, wherein the channel is a p conducting channel.

23. The sensor of claim 22, wherein the analyte is negatively charged.

24. The sensor of claim 21, wherein the channel is an n−

conducting channel.

25. The sensor of claim 24, wherein the analyte is positively charged.

26. The sensor of claim 21, wherein conduction is increased by enhancement of a conducting inversion layer in the channel.

27. The sensor of claim 21, wherein the analyte is selected from the group consisting of toxins, insecticides, polypeptides, nucleic acids, pathogens and drugs.

28. An array comprising two or more sensors for detecting the presence of an analyte in a sample, each sensor comprising a receptor for a particular analyte of interest bound to the active region of a field effect transistor (FET), wherein the active region overlies a p conducting channel connecting a source region and a drain region.

29. The array of claim 28, comprising two or more sensors for detecting multiple toxins.

30. The array of claim 28, comprising two or more sensors for detecting multiple disease markers.

31. The array of claim 28, wherein at least two sensors comprise receptors that are specific for the same analyte.

32. The array of claim 28, comprising a first sensor for detecting the presence of a first analyte of interest and a second sensor for detecting the presence of a second analyte of interest.

33. The array of claim 32, wherein the presence of the second analyte of interest provides confirmation of the first analyte of interest.

34. The array of claim 28, comprising at least two orthogonal receptors.