Ultrasensitive biochemical sensing platform

• US 20050224346A1
• Filed: 10/29/2004
• Published: 10/13/2005
• Est. Priority Date: 10/31/2003
• Status: Active Grant

• Current Assignee: Research Corporation of The University of Hawaii
• Original Assignee: James W. Holm-Kennedy
• Inventors: Holm-Kennedy, James W.
• Granted Patent: US 7,317,216 B2
• Time in Patent Office: Days
• US Class Current: 204/403.10
• 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 positive 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.

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.

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

11. The sensor of claim 10, wherein the sensitivity of the sensor is increased by applying a bias to the back gate or side gate.

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

13. The sensor of claim 12, wherein the recognition element is selected from the group consisting of antibodies, antibody fragments, oligonucleotides, DNA, RNA, aptamers, enzymes, cell fragments, receptors, bacteria, bacterial fragments, viruses, and viral fragments.

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

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

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

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

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

19. The array of claim 18 comprising two or more sensors for detecting multiple targets.

20. The array of claim 19, 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.

21. The array of claim 20, wherein the presence of the second target of interest provides confirmation of the presence of the first target of interest.

22. A method for identifying the presence of a charged target of interest in a sample comprising:

contacting the active region of a sensor with the sample, wherein the sensor comprises one or more recognition elements for the target of interest bound to the active region and wherein the active region overlies a buried conducting channel connecting a source and drain;

providing an electrode at a first distance from the active region;

measuring sensor output; and

identifying the presence of the target of interest where the sensor output indicates a change in conductance of the channel upon exposing the active region to the sample, wherein the electrode generates an electric field in the sample that increases target concentration in the vicinity of the active region.

23. The method of claim 22, wherein the electric filed does not terminate on the sensor.

24. The method of claim 22, wherein the sensor output is selected from the group consisting of conductance, voltage, current, capacitance and resistance.

25. The method of Clam 22, wherein the change in conductance is caused by binding of the target to the recognition element.

26. The method of claim 22, wherein the change in conduction is enhanced by contacting the bound target with a secondary charged particle.

27. The method of claim 26, wherein the secondary charged molecule is selected from the group consisting of an antibody, a bead, a nanoparticle, a nanotube, a nucleic acid and a peptide.

28. A sensor for detecting the presence of a charged target in a sample comprising a field effect transistor, wherein binding of the target of interest to a recognition element on an active region of the sensor increases or decreases conduction through a channel connecting a source region and a drain region and wherein the active region is surrounded by a conducting shield.

29. The sensor of claim 28, wherein the conducting shield is parallel to the substrate surface.

30. The sensor of claim 28, wherein the conducting shield defines an opening over the active region.

31. The sensor of claim 28, wherein the conducting shield is adjacent to the active region and extends away from the active region in all directions.

32. The sensor of claim 28, wherein the conducting shield comprises a conductive metal.

33. The sensor of claim 28, wherein the conducting shield comprises a conductive polymer.

34. The sensor of claim 28, wherein the conducting shield is biased.

35. The sensor of claim 28, wherein the channel is selected from the group consisting of a p conducting channel and an n conducting channel.

36. The sensor of claim 28, wherein the active region comprises a width and a length and the width to length ratio is at least 10:

1.

37. The sensor of claim 28, wherein the target is selected from the group consisting of toxins, insecticides, polypeptides, nucleic acids, pathogens, drugs, sugars organic compounds and inorganic compounds.

38. A sensor for detecting the presence of a target in a sample, the sensor comprising one or more recognition elements for the target associated with an active region and an electrode located at a first distance from the active region of the sensor, wherein the electrode is configured to increase target concentration in the vicinity of the active region.

39. The sensor of claim 38, wherein the electrode is a grid.

40. The sensor of claim 38, wherein the electrode is a cage.

41. The sensor of claim 40, wherein the cage surrounds the active region.

42. The sensor of claim 40, wherein the cage comprises a conducting mesh.

43. The sensor of claim 42, wherein the mesh is selected from the group consisting of a metal mesh, a conducting polymer mesh and a metal-coated mesh.

44. The sensor of claim 43, wherein the mesh is a stainless steel mesh.

45. The sensor of claim 38, wherein a second electrode is located at a second distance from the active region of the sensor.

46. The sensor of claim 45, wherein the second electrode is arranged in a grid.

47. The sensor of claim 45, wherein the second electrode is arranged as cage.

48. The sensor of claim 47, wherein the second electrode cage surrounds the active region.