Optoelectronic biochip

• US 20060197960A1
• Filed: 04/20/2005
• Published: 09/07/2006
• Est. Priority Date: 04/21/2004
• Status: Active Grant

• Current Assignee: Michael Bazylenko
• Original Assignee: Michael Bazylenko
• Inventors: Bazylenko, Michael
• Granted Patent: US 7,768,650 B2
• Time in Patent Office: Days
• US Class Current: 356/491
• CPC Class Codes: G01N 2021/7776 Index
• CPC Class Codes: G01N 2021/7786 Fluorescence
• CPC Class Codes: G01N 21/253 for batch operation, i.e. multisample apparatus analytical automats G01N35/00
• 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
• CPC Class Codes: G01N 21/7743 the reagent-coated grating coupling light in or out of the waveguide
• CPC Class Codes: Y10S 977/701 Integrated with dissimilar structures on a common substrate
• CPC Class Codes: Y10S 977/702 having biological material component
• CPC Class Codes: Y10S 977/707 having different types of nanoscale structures or devices on a common substrate
• CPC Class Codes: Y10S 977/712 formed from plural layers of nanosized material, e.g. stacked structures

Abstract

The present invention provides a biochip for testing biological substances comprising a plurality of binding sites, optical means for determining a specific binding event at each binding site, wherein the plurality of binding sites and the means for determining a specific binding event at each binding site are monolithically integrated into a single chip which is electrically powered and produces electrical signals in response to binding events at each binding site. The means for determining a specific binding event can include a micro-cavity light source formed in a semiconductor layer and a photodetector formed in the same semiconductor layer and further include a grating assisted vertical planar waveguide coupler for in-situ monitoring hybridisation dynamics at each binding site via associated changes in refractive index. The invention further provides a method of manufacturing a biochip containing light sources, photodetectors, binding sites and optical means for determining a specific binding event at each binding site wherein said light sources, photodetectors, binding sites and optical means for determining a specific binding event at each binding site are produced by processing a single planar substrate in a sequence of deposition, photolithography and etching steps.

Claims

1. A biochip for testing biological substances comprising a plurality of binding sites, optical means for determining a specific binding event at each binding site, wherein the plurality of binding sites and the means for determining a specific binding event at each binding site are monolithically integrated into a single chip which is electrically powered and produces electrical signals in response to binding events at each binding site.

2. A biochip in accordance with claim 1 wherein the means for determining a specific binding event comprise at least one light source and at least one photodetector associated with each binding site.

3. A biochip in accordance with claim 2 said biochip further comprising a first plurality of electrodes for individually controlling each light source and a second plurality of electrodes for individually controlling each photodetector.

4. A biochip in accordance with claim 2 wherein either or both the light sources and the photodetectors are implemented in a thin film semiconductor layer.

5. A biochip in accordance with claim 4 wherein the light sources and photodetectors are implemented in the same semiconductor thin film layer.

6. A biochip in accordance with claim 4 wherein the semiconductor thin film material comprises semiconductor polymer.

7. A biochip in accordance with claim 4 wherein the thin film light source is a microcavity light source.

8. A biochip in accordance with claim 7 wherein the microcavity light source is a vertical microcavity light source.

9. A biochip in accordance with claim 7 wherein the microcavity light source is a photonic band gap microcavity light source.

10. A biochip in accordance with claim 4 wherein the thin film photodetector is a microcavity photodetector.

11. A biochip in accordance with claim 10 wherein the microcavity photodetector is a vertical microcavity photodetector.

12. A biochip in accordance with claim 10 wherein the microcavity photodetector is a photonic band gap microcavity photodetector.

13. A biochip in accordance with claim 2 wherein the photodetectors are formed in a semiconductor substrate.

14. A biochip in accordance with claim 13 wherein the semiconductor substrate is made of silicon.

15. A biochip in accordance with any of the preceding claims wherein the means for determining a binding event at each binding site further comprise at least one planar optical waveguide, the evanescent field of light propagating in the waveguide interacting with the biological substance under test.

16. A biochip in accordance with claim 15 wherein the waveguide is made of inorganic material.

17. A biochip in accordance with claim 15 wherein the waveguide is made of organic material.

18. A biochip in accordance with claim 15 wherein the light is coupled in or decoupled from the waveguides by way of at least one diffraction grating located in or in the vicinity of the waveguide.

19. A biochip in accordance with claim 15 wherein the light is coupled in or decoupled from the waveguide by way of a tilted mirror located in or in the vicinity of the waveguide.

20. A biochip in accordance with any of the preceding claims wherein the means for determining a binding event at each site comprise means for determining a refractive index change associated with a binding event.

21. A biochip in accordance with claim 20 wherein the means for determining refractive index change comprise a first planar waveguide on surface of which the binding event occurs, a second planar waveguide located below the first waveguide and separated by coupling layer of lower refractive index than that of the two waveguides.

22. A biochip in accordance with claim 21 wherein the parameters of the two waveguides and the coupling layer are selected such that the amount of light coupled from the first waveguide into the second waveguide changes in response to a binding event occurring on the surface of the first waveguide.

23. A biochip in accordance with claim 20 wherein the means for determining refractive index change comprise a first planar waveguide on surface of which the binding event occurs, a grating formed in said waveguide, a second planar waveguide located below the first waveguide and separated by coupling layer of lower refractive index than that of the two waveguides.

24. A biochip in accordance with claim 23, wherein the parameters of grating, first and second waveguides and the coupling layer between them are selected such that the amount of light coupled from the first waveguide into the second waveguide changes in response to a binding event occurring on the surface of the first waveguide.

25. A biochip in accordance with any of the preceding claims wherein one light source is shared between a number of binding sites.

26. A biochip in accordance with any of the preceding claims wherein the means for determining a binding event further comprise a reference light paths provided at each each binding site for error correction.

27. A biochip in accordance with any of the preceding claims wherein the biochip comprises a further plurality of electrodes to control hybridization conditions at each binding site.

28. A biochip in accordance with claim 27 wherein the electrodes comprise resistive heater electrodes formed underneath idiviudal binding sites or groups of biding sites.

29. A biochip in accordance with any of the preceding claims, said biochip is formed on a silicon substrate said silicon substrate containing one or more transistors associated with each binding site for facilitating control of light sources, photodetectors or hybridization process at that binding site.

30. A biochip in accordance with any of the preceding claims, wherein one or more thin film transistors are associated with each binding site for facilitating control of light sources, photodetectors or hybridization at that binding site.

31. A biochip in accordance with claim 1 said biochip comprising a fluidic chamber attached to the plurality of binding sites for delivering the biological substance.

32. A method of manufacturing a biochip containing light sources, photodetectors, binding sites and optical means for determining a specific binding event at each binding site wherein said light sources, photodetectors, binding sites and optical means for determining a specific binding event at each binding site are produced by processing a single planar substrate in a sequence of deposition, photolithography and etching steps.

33. A method of manufacturing a biochip in accordance with claim 32, said method comprising steps of (i) forming a first plurality of electrodes that are optically non-transparent;

(ii) forming at least one semiconductor layer;

(iii) forming a second plurality of electrodes that are optically transparent;

(iv) forming at least one planar waveguide layer;

(v) forming means of in- and out-coupling for the waveguide layer; and

(vi) forming a plurality of binding sites on top on the surface of the waveguide layer.

34. A method of testing a biological substance comprising steps of disposing the substance over a plurality of binding sites, hybridization of the substance to the binding sites and detecting the sites at which the binding events occurred using optical means, said method further comprising the use of a single biochip which is electrically powered and produces electrical signals in response to binding events at each binding site.

35. A method in accordance with claim 34, wherein the biochip allows for in-situ monitoring and detection of binding events at each binding site during the hybridisation.

36. A method in accordance with claim 35 wherein in-situ monitoring and detection comprises generating an optical signal at each binding site and then receiving a corresponding electrical signal from each binding site that contains information about the interaction of the optical signal with the biological substance at each binding site.

37. A method in accordance with claim 36, wherein the information comprises the change in refractive index associated with a binding event.