Nanostructured microelectrodes and biosensing devices incorporating the same

• US 10,274,453 B2
• Filed: 09/13/2017
• Issued: 04/30/2019
• Est. Priority Date: 09/02/2008
• Status: Active Grant

• Current Assignee: The Governing Council of the University of Toronto (University of Toronto)
• Original Assignee: The Governing Council of the University of Toronto (University of Toronto)
• Inventors: Soleymani, Leyla, Fang, Zhichao, Kelley, Shana, Sargent, Edward, Taft, Bradford
• Primary Examiner(s): Ball, J. Christopher
• Application Number:
  US15/703,120
• Publication Number:
  US 20180003665A1
• Time in Patent Office: 594 Days
• CPC Class Codes: G01N 27/30 Electrodes, e.g. test electrodes; Half-cells G01N27/414 takes precedence
• CPC Class Codes: G01N 27/3272 Test elements therefor, i.e. disposable laminated substrates with electrodes, reagent and channels optical biosensors G01N33/52
• CPC Class Codes: G01N 27/3275 Sensing specific biomolecules, e.g. nucleic acid strands, based on an electrode surface reaction
• CPC Class Codes: G01N 27/3278 involving nanosized elements, e.g. nanogaps or nanoparticles nanopores G01N33/48721; magnetic beads G01N27/745
• CPC Class Codes: G01N 33/5438 Electrodes
• CPC Class Codes: Y10S 977/754 Dendrimer, i.e. serially branching or "tree-like" structure
• CPC Class Codes: Y10S 977/925 Bioelectrical

Abstract

Nanostructured microelectrodes and biosensing devices incorporating the same are disclosed herein.

Claims

1. A biosensing workstation comprising:

a cartridge holder for holding a biosensing cartridge, the biosensing cartridge including a sample chamber for containing a biological sample and a biosensing chamber containing a biosensing device, the biosensing device including;

a substrate;

an electrically conductive lead on the substrate;

an insulating layer covering the lead, the insulating layer having an aperture exposing a portion of the lead;

a nanostructured microelectrode, the microelectrode in electrical communication with the exposed portion of the lead, the microelectrode adapted to generate a charge in response to a biomolecular stimulus; and

a charge storage in electrical communication with the lead for storing charge from the microelectrode, the charge on the charge storage at the end of an integration period indicative of the biomolecular stimulus;

an instrument tip for accessing the biosensing cartridge;

a selection mechanism for selecting a biosensing process to be carried out;

a processor adapted to carry out the biosensing process using the biosensing cartridge and to determine results of the biosensing process from electronic signals generated from the biosensing cartridge; and

a display for displaying the results of the biosensing process.

2. The workstation of claim 1, wherein there is a plurality of cartridge holders for holding a plurality of biosensing cartridges.

3. The workstation of claim 1, wherein the instrument tip is disposable.

4. The workstation of claim 1, further comprising a bar code reader for uniquely identifying the biosensing cartridge.

5. The workstation of claim 1, further comprising a waste chamber for containing waste products from the biosensing process.

6. The workstation of claim 1, wherein the workstation is capable of wireless communication through a wireless network.

7. The biosensing workstation of claim 1, wherein the lead comprises a material selected from the group consisting of:

Au, Al, W, TiN, and polysilicon.

8. The biosensing workstation of claim 1, wherein the substrate comprises a material selected from the group consisting of:

silicon, silica, quartz, glass, sapphire, gallium arsenide, germanium, silicon carbide, indium compounds, selenium sulfide, ceramic, plastic, polycarbonate and other polymer or combinations of any of the above.

9. The biosensing workstation of claim 1, wherein the insulating layer is comprised of a material selected from the group consisting of:

silicon dioxide, silicon nitride, nitrogen doped silicon oxide, and parylene or combinations of any of the above.

10. The biosensing workstation of claim 1, wherein the aperture has an approximate diameter in the range of about 100 nm to about 10 μ

m.

11. The biosensing workstation of claim 1, wherein the biosensing device further comprises a display component for displaying the charge stored in the charge storage.

12. The biosensing workstation of claim 1, wherein the biosensing device further comprises a transistor.

13. The biosensing workstation of claim 12, wherein the transistor is a field-effect transistor (FET).

14. The biosensing workstation of claim 13, wherein the FET is selected from the group consisting of:

an n-type silicon channel and a p-type silicon channel.

15. The biosensing workstation of claim 14, wherein the bipolar transistor is selected from the group consisting of:

an n-p-n bipolar junction transistor, and a p-n-p bipolar junction transistor.

16. The biosensing workstation of claim 12, wherein the transistor is a bipolar transistor.

17. The biosensing workstation of claim 1, wherein the biosensing device comprises a plurality of leads, each having a respective microelectrode.

18. The biosensing workstation of claim 17, wherein the biosensing device comprises at least two different probe molecules provided on the microelectrodes.

19. The biosensing workstation of claim 1, wherein the microelectrodes are provided in an array, and each microelectrode is individually electronically accessible.

20. The biosensing workstation of claim 1, wherein the biosensing chamber is adapted to subdivide the biological sample through chemical, mechanical or vibrational means.

21. The biosensing workstation of claim 1, wherein the biosensing cartridge further comprises a purifying chamber for purifying or isolating the sample.

22. The biosensing workstation of claim 1, wherein the biosensing cartridge further comprises a lid having capsules, the capsules containing reagents for carrying out the biosensing process.

23. The biosensing workstation of claim 22, wherein one of the capsules is associated with the sample chamber, the capsule containing a lysis buffer reagent.

24. The workstation of claim 23, further comprising a bar code reader for uniquely identifying the biosensing cartridge.

25. The biosensing workstation of claim 1, wherein the biosensing cartridge is disposable.

26. A biosensing workstation comprising:

a cartridge holder for holding a biosensing cartridge, the biosensing cartridge including a sample chamber for containing a biological sample and a biosensing chamber containing a biosensing device, the biosensing device including;

a substrate;

an electrically conductive lead on the substrate;

an insulating layer covering the lead, the insulating layer having an aperture exposing a portion of the lead;

a nanostructured microelectrode, the microelectrode being in electrical communication with the exposed portion of the lead, the microelectrode being adapted to generate a charge in response to a biomolecular stimulus; and

a charge storage in electrical communication with the lead for storing charge from the microelectrode, the charge on the charge storage at the end of an integration period indicative of the biomolecular stimulus;

an instrument tip for accessing the biosensing cartridge;

a processor adapted to carry out a biosensing process using the biosensing cartridge and to determine results of the biosensing process from electronic signals generated from the biosensing cartridge; and

a display for displaying the results of the biosensing process.

27. The workstation of claim 26, wherein there is a plurality of cartridge holders for holding a plurality of biosensing cartridges.

28. The workstation of claim 26, wherein the instrument tip is disposable.

29. The workstation of claim 26, further comprising a waste chamber for containing waste products from the biosensing process.

30. The workstation of claim 26, wherein the workstation is capable of wireless communication through a wireless network.

31. The biosensing workstation of claim 26, wherein the lead comprises a material selected from the group consisting of:

Au, Al, W, TiN, and polysilicon.

32. The biosensing workstation of claim 26, wherein the substrate comprises a material selected from the group consisting of:

silicon, silica, quartz, glass, sapphire, gallium arsenide, germanium, silicon carbide, indium compounds, selenium sulfide, ceramic, plastic, polycarbonate and other polymer or combinations of any of the above.

33. The biosensing workstation of claim 26, wherein the insulating layer is comprised of a material selected from the group consisting of:

silicon dioxide, silicon nitride, nitrogen doped silicon oxide, and parylene or combinations of any of the above.

34. The biosensing workstation of claim 26, wherein the aperture has an approximate diameter in the range of about 100 nm to about 10 μ

m.

35. The biosensing workstation of claim 26, wherein the biosensing device further comprises a display component for displaying the charge stored in the charge storage.

36. The biosensing workstation of claim 26, wherein the biosensing device further comprises a transistor.

37. The biosensing workstation of claim 36, wherein the transistor is a field-effect transistor (FET).

38. The biosensing workstation of claim 37, wherein the FET is selected from the group consisting of:

an n-type silicon channel and a p-type silicon channel.

39. The biosensing workstation of claim 38, wherein the bipolar transistor is selected from the group consisting of:

an n-p-n bipolar junction transistor, and a p-n-p bipolar junction transistor.

40. The biosensing workstation of claim 36, wherein the transistor is a bipolar transistor.

41. The biosensing workstation of claim 26, wherein the biosensing device comprises a plurality of leads, each having a respective microelectrode.

42. The biosensing workstation of claim 41, wherein the biosensing device comprises at least two different probe molecules provided on the microelectrodes.

43. The biosensing workstation of claim 26, wherein the microelectrodes are provided in an array, and each microelectrode is individually electronically accessible.

44. The biosensing workstation of claim 26, wherein the biosensing chamber is adapted to subdivide the biological sample through chemical, mechanical or vibrational means.

45. The biosensing workstation of claim 26, wherein the biosensing cartridge further comprises a purifying chamber for purifying or isolating the sample.

46. The biosensing workstation of claim 26, wherein the biosensing cartridge further comprises a lid having capsules, the capsules containing reagents for carrying out the biosensing process.

47. The biosensing workstation of claim 46, wherein one of the capsules is associated with the sample chamber, the capsule containing a lysis buffer reagent.

48. The biosensing workstation of claim 26, wherein the biosensing cartridge is disposable.