Wireless CMOS Biosensor

• US 20090298704A1
• Filed: 07/12/2006
• Published: 12/03/2009
• Est. Priority Date: 07/12/2005
• Status: Abandoned Application

• Current Assignee: Anwar M. Mekhail, Aytur Turgut, Paul Matsudaira
• Original Assignee: Anwar M. Mekhail, Aytur Turgut, Paul Matsudaira
• Inventors: Turgut, Aytur, Anwar, M. Mekhail, Matsudaira, Paul
• Application Number:
  US11/988,473
• Publication Number:
  US 20090298704A1
• Time in Patent Office: Days
• US Class Current: 506/9
• CPC Class Codes: A61B 5/0031 Implanted circuitry
• CPC Class Codes: A61B 5/0071 by measuring fluorescence emission
• CPC Class Codes: A61B 5/0084 for introduction into the body, e.g. by catheters A61B5/1459 takes precedence
• CPC Class Codes: B82Y 10/00 Nanotechnology for information processing, storage or transmission, e.g. quantum computing or single electron logic
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: G01N 21/6428 Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" in vivo A61B5/00; immunoassay G01N33/53
• CPC Class Codes: G01N 21/6454 using an integrated detector array
• CPC Class Codes: G01N 21/648 using evanescent coupling or surface plasmon coupling for the excitation of fluorescence

Abstract

System and methods for detection and measurement of interactions in microarrays or within a human body are described. The system includes a CMOS sensor which can be placed in a fluidic environment, and is capable of measuring DNA interactions and protein binding kinetics, as well as cellular interactions and signals within the body. The sensor can be placed in close proximity with the sample and eliminates the need for optics, and in some embodiments is a wireless device.

Claims

1. A system for measuring a biological sample, the system comprising:

a sensor which provides an electrical output;

an analog to digital converter in electrical communication with said sensor for converting said output into a digital signal, wherein at least said sensor and said analog to digital converter form a CMOS circuit; and

a processor for processing said digital signal.

2. The system of claim 1, wherein the sensor comprises a photodiode for converting photons obtained from interaction with the sample into electrons.

3. The system of claim 1, further comprising a wireless interface in communication with said sensor and said processor, said wireless interface configured to provide power to said sensor, and further configured to transmit and receive data from said processor.

4. The system of claim 3, wherein said wireless interface comprises an external antenna.

5. The system of claim 3, wherein said wireless interface comprises an integrated antenna, said integrated antenna integrated into a physical structure of said system.

6. The system of claim 1, wherein the sensor is integrated with an implantable device.

7. The system of claim 6, wherein said implantable device is a stent, and wherein said sensor is integrated with said stent.

8. The system of claim 6, wherein said implantable device is a drug delivery device, and said sensor is integrated with said drug delivery device.

9. The system of claim 1, wherein said sensor further comprises a flip-chip bonding scheme.

10. The system of claim 2, wherein said sensor further comprises multiple photodiodes arranged in a pixel array of photodiodes.

11. The system of claim 10, wherein said pixel array of photodiodes comprises a one-to-one correspondence with an array of the biological sample.

12. The system of claim 11, wherein a size of each pixel in said pixel array is less than 150 micrometers.

13. The system of claim 12, wherein a size of each pixel of said pixel array is approximately 120 micrometers×

120 micrometers.

14. The system of claim 10, wherein said sensor further comprises an outer layer substantially surrounding said pixel array, said outer layer providing a fluid barrier between electrical components of said sensor and the biological sample.

15. The system of claim 2, further comprising an evanescent illumination system said illumination system comprising a prism positioned beneath said sensor for introducing light, wherein said at least one photodiode is configured for receiving photons via said evanescent illumination system.

16. The system of claim 2, wherein said at least one photodiode is selected from the group consisting of an N-plus P-sub diode, an N-well P-sub diode, a P-plus N-well P-sub diode, and an N-plus P-well diode.

17. The system of claim 16, wherein all of said diodes are used.

18. The system of claim 10, wherein each pixel of said pixel array comprises a sensor photodiode and a reference photodiode.

19. The system of claim 18, wherein said reference photodiode is covered with metal.

20. The system of claim 18, wherein each pixel of said pixel array further comprises a first source follower, a second source follower, and a hold capacitor, and wherein said first source follower is for applying a sample and hold operation onto said hold capacitor for storage, said second source follower is for transmitting said stored hold operation to said processor.

21. The system of claim 1, further comprising a microarray of the biological sample, wherein said sensor is positionable in close proximity with said microarray.

22. The system of claim 21, further comprising multiple photodiodes arranged in a pixel array of photodiodes wherein a size of each pixel ranges from less than the size of a spot on the microarray to a maximum of the pitch between spots on the microarray.

23. The system of claim 21, wherein said microarray is selected from the group consisting of:

a protein array, a DNA array, an RNA array, a cellular array, an array including a virus, an array including a bacteria, and an array including small molecules.

24. The system of claim 1, wherein the biological sample is tagged with quantum dots, the system further comprising a UV illuminator, said obtained photons obtained from illumination of said quantum dots by said UV illuminator.

25. The system of claim 1, wherein said sensor is implantable in a human body.

26. The system of claim 25, wherein said obtained photons are obtained from optical signals in the body.

27. The system of claim 26, wherein said optical signals include cellular signals.

28. The system of claim 26, wherein said optical signals include signals from a biological marker.

29. The system of claim 25, wherein said obtained photons are obtained from an external dye marker.

30. The system of claim 3, further comprising a light source powered by said wireless interface.

31. The system of claim 14, wherein said outer layer is a biocompatible material.

32. A sensor for identifying an interaction in a microarray, the sensor comprising:

a pixel array of photodiodes, wherein a size of each pixel of said pixel array corresponds to said microarray; and

an outer layer substantially surrounding said pixel array, said outer layer providing a fluid barrier between electrical components of said sensor and said biological sample.

33. The sensor of claim 32, wherein a size of each pixel ranges from less than the size of a spot on the microarray to a maximum of the pitch between spots on the microarray.

34. The sensor of claim 32, wherein a size of each pixel is less than 150 micrometers.

35. The sensor of claim 34, wherein each pixel of said pixel array is approximately 120 micrometers×

120 micrometers in size.

36. The sensor of claim 32, wherein said sensor is implantable within a human body.

37. The sensor of claim 32, wherein said outer layer is a biocompatible material.

38. The sensor of claim 32, wherein said pixel array of photodiodes comprises at least one photodiode selected from the group consisting of an N-plus P-sub diode, an N-well P-sub diode, and a P-plus N-well P-sub diode.

39. The system of claim 38, wherein all of said diodes are used.

40. The sensor of claim 32, wherein each pixel of said pixel array comprises a sensor photodiode and a reference photodiode.

41. The sensor of claim 40, wherein said reference photodiode is covered with metal.

42. The sensor of claim 32, further comprising an analog/digital converter in electrical communication with said photodiodes.

43. The sensor of claim 42, wherein each pixel of said pixel array further comprises a first source follower, a second source follower, and a hold capacitor, and wherein said first source follower is for applying a sample and hold operation onto said hold capacitor for storage, said second source follower is for transmitting said stored hold operation to said processor.

44. The sensor of claim 42, wherein said photodiodes and at least said analog/digital converter form a CMOS circuit on said sensor.

45. A method for measuring a sample, comprising:

providing a wireless CMOS biosensor comprising a pixel array of photodiodes;

providing a biological sample;

tagging said biological sample with a fluorescent label;

placing said biosensor proximal to said biological sample;

illuminating said biosensor and said biological sample, wherein said illuminating causes said tagged biological sample to emit photons;

converting said photons into an electrical signal using said CMOS biosensor; and

wirelessly receiving said electrical signal, said electrical signal being representative of an amount of said tagged biological sample.

46. The method of claim 45, wherein said sample is a biological sample.

47. The method of claim 46, wherein said biological sample is a DNA sample.

48. The method of claim 46, wherein said biological sample is a protein sample.

49. The method of claim 45, wherein said placing said biosensor proximal to said biological sample comprises placing said biosensor in solution.

50. The method of claim 45, wherein said placing said biosensor proximal to said biological sample comprises placing said biosensor in contact with said biological sample.

51. The method of claim 45, wherein said placing said biosensor proximal to said biological sample comprises providing said biological sample as a microarray, and placing said biosensor within a distance which is several times a spot size of the microarray.

52. The method of claim 45, wherein said tagging comprises tagging with quantum dots.

53. The method of claim 45, wherein said illuminating comprises evanescently illuminating.