Ultrasensitive biochemical sensing platform

• US 7,317,216 B2
• Filed: 10/29/2004
• Issued: 01/08/2008
• Est. Priority Date: 10/31/2003
• Status: Active Grant

• Current Assignee: Research Corporation of The University of Hawaii
• Original Assignee: University of Hawai'i
• Inventors: Holm-Kennedy, James W.
• Primary Examiner(s): Pert; Evan
• Assistant Examiner(s): TRAN, TAN N
• Application Number:
  US10/976,503
• Publication Number:
  US 20050224346A1
• Time in Patent Office: 1,166 Days
• Field of Search: 257/253, 257/414, 257/40, 435/7.9
• US Class Current: 257/253
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: G01N 33/54373 involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings

Abstract

An electronic sensor is provided for detecting the presence of one or more targets of interest in a sample. The sensor preferably comprises a special type of field effect transistor in which conductance is enhanced by target binding to recognition elements in the active region. An array of sensors may be formed to analyze a sample for multiple targets. The sensor may be used, for example, to detect the presence of pathogens, polypeptides, nucleic acids, toxins and other biochemical and chemical agents. The sensor is useful in a wide variety of applications including medical diagnostics, agriculture, public health, environmental monitoring and biomedical research.

Claims

1. A sensor for detecting the presence of a positively or negatively charged target in a sample comprising an active region of a field effect transistor (FET) overlying a buried conducting channel connecting a source region and a drain region, wherein the active region comprises multiple target recognition elements dispersed in a material matrix, and wherein the source and drain are p and the buried conducting channel is a p-channel or the source and drain are n and the buried conducting channel is an n-channel to provide an ohmic contact to a channel.

2. The sensor of claim 1, wherein the material matrix is a gel.

3. The sensor of claim 1, wherein the buried channel is a p-channel or an n-channel.

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

5. The sensor of claim 4, wherein the gate comprises a semiconducting material.

6. The sensor of claim 4, wherein the active region comprises a polysilicon gate.

7. The sensor of claim 4, wherein the gate comprises a conducting material.

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

9. The sensor of claim 1, wherein the gate dielectric layer is a silicon nitride layer of sufficient thickness to block unwanted sample effects including moisture.

10. The sensor of claim 9, wherein the silicon nitride layer is about 3000 Angstroms thick.

11. The sensor of claim 1, additionally comprising a back gate or side gate.

12. The sensor of claim 11, wherein the sensitivity of the sensor is increased by applying a bias to the back gate or side gate.

13. The sensor of claim 1, wherein the recognition element is selected from the group consisting of polypeptides, nucleic acids, inorganic molecules and organic molecules.

14. The sensor of claim 13, wherein the recognition element is selected from the group consisting of antibodies, nucleic acids, inorganic molecules and organic molecules.

15. The sensor of claim 1, wherein each of the recognition elements is specific for the same target.

16. The sensor of claim 1, wherein two or more recognition elements are specific for different targets.

17. The sensor of claim 16, wherein the number of each type of recognition element is such that the signal for binding of any of the targets is of approximately the same magnitude.

18. The sensor of claim 16, wherein the number of each type of recognition element is approximately equal and the recognition elements are readily saturated so that differences in the measured signal allow the identity of the present target or targets to be determined.

19. The sensor of claim 1, wherein the sensor operates in accumulation mode upon binding of a target.

20. The sensor of claim 1, wherein the sensor operates in depletion mode upon binding of a target.

21. An array comprising two or more of the sensor of claim 1.

22. The array of claim 21 comprising two or more sensors for detecting multiple targets.

23. The array of claim 22, comprising a first sensor for detecting the presence of a first target of interest and a second sensor for detecting the presence of a second target of interest.

24. The array of claim 23, wherein the presence of the second target of interest provides confirmation of the presence of the first target of interest.

25. The sensor of claim 1, further comprising secondary charged particles that contact bound targets to amplify their charge.

26. The sensor of claim 1, wherein the recognition elements further comprise orthogonal recognition elements.

27. The sensor of claim 1, wherein the density of the recognition elements is maximized to maximize sensor sensitivity.

28. The sensor of claim 1, wherein the active region is the minimum size necessary to produce a desired signal.

29. The sensor of claim 1, further comprising a protective material covering the area of the sensor outside of the active region to prevent unwanted interactions.

30. The sensor of claim 29, wherein the protective material is a biochemical layer that does not bind to components in the sample.

31. The sensor of claim 1, wherein targets are identified by chemical reaction with the gate material or a material deposited on the gate.

32. The sensor of claim 1, wherein the number of recognition elements is such that the production of any measurable signal corresponds to a particular concentration of a target in a sample.

33. The sensor of claim 1, further comprising linker molecules that attach recognition elements to the active region.

34. The sensor of claim 1, wherein the sensitivity of the sensor is tuned by channel doping.