Waveguide grating structure and optical measurement arrangement

• US 8,503,833 B2
• Filed: 10/09/2009
• Issued: 08/06/2013
• Est. Priority Date: 08/09/2000
• Status: Expired due to Term

• Current Assignee: Artificial Sensing Instruments ASI AG
• Original Assignee: Artificial Sensing Instruments ASI AG
• Inventors: Tiefenthaler, Kurt
• Primary Examiner(s): Lepisto, Ryan
• Assistant Examiner(s): Chiem, Erin
• Application Number:
  US12/576,740
• Publication Number:
  US 20100026323A1
• Time in Patent Office: 1,397 Days
• Field of Search: 385 12- 13, 250/282, 356/128
• US Class Current: 385/12
• CPC Class Codes: G01N 2021/6463 Optics
• CPC Class Codes: G01N 21/648 using evanescent coupling or surface plasmon coupling for the excitation of fluorescence
• CPC Class Codes: G01N 21/6486 Measuring fluorescence of biological material, e.g. DNA, RNA, cells G01N21/6428 takes precedence
• CPC Class Codes: G01N 21/7743 the reagent-coated grating coupling light in or out of the waveguide
• CPC Class Codes: G01N 2201/08 Optical fibres; light guides
• CPC Class Codes: G01N 33/54373 involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
• CPC Class Codes: G02B 2006/12107 Grating
• CPC Class Codes: G02B 6/124 Geodesic lenses or integrated gratings
• CPC Class Codes: G02B 6/32 having lens focusing means positioned between opposed fibre ends with lens being an integral part of the single fibre end G02B6/262
• CPC Class Codes: Y10S 385/901 Illuminating or display apparatus

Abstract

The present invention describes (bio)chemo-functional waveguide grating structures consisting of at least one (bio)chemo-functional waveguide grating structure unit or at least one (bio)chemo-functional sensor location with beam guidance permitting light beam separation, as well as detection methods for parallel analysis which are marking-free or based on marking.

Claims

1. A sensor for studying cell behaviour, the sensor comprising:

a substrate;

a waveguide grating structure on the substrate

with the waveguide grating structure comprising a plurality of waveguide grating structure units or sensor locations;

wherein at least one of said waveguide grating structure units or sensor locations comprises at least one sensing pad with a modified surface of the waveguide grating structure;

the sensor further comprising;

a chemofunctional layer in physical contact with said modified surface, the chemofunctional layer comprising at least one living cell, the chemofunctional layer covering at least partially said at least one waveguide grating structure unit or sensor location;

wherein the at least one living cell is a living human cell or a living animal cell or a living plant cell; and

a liquid sample in physical contact with the chemofunctional layer,

the chemofunctional layer being thereby in physical contact with the modified surface and with the sample;

wherein the waveguide grating structure has waveguiding properties and comprises at least one grating, and the waveguide grating structure emits at least one light field when an incident light field at least partially illuminates the waveguide grating structure, thereby being capable of producing a signal indicative of a reaction or a behaviour of the at least one living cell due to a contact with the sample.

2. The sensor of claim 1, wherein the modified surface is a surface modified in that it is at least partially covered by one of:

a silane layer, a polymer layer, a lipid layer, a lipid layer with ion channels, a monolayer, and a bilayer.

3. The sensor of claim 1, wherein the waveguide grating structure comprises at least partially a monomolecular layer or self-assembled monolayer.

4. The sensor of claim 1, wherein the waveguide grating structure or at least one of the waveguide grating structure units or sensor locations comprises a waveguide grating.

5. The sensor of claim 4, wherein the waveguide grating is covered at least partially by a cell or by cells.

6. The sensor of claim 1, wherein the waveguide grating structure or at least one of the waveguide grating structure units or sensor locations comprises at least two waveguide gratings with an optional waveguide structure region between the two waveguide gratings.

7. The sensor of claim 6, wherein the waveguide grating structure or at least one of the waveguide grating structure units or sensor locations includes a waveguide structure region between the two waveguide gratings and is covered by a cell or cells at least partially in said waveguide structure region between the two waveguide gratings.

8. The sensor of claim 1, wherein the waveguide grating structure or at least one of the waveguide grating structure units or sensor locations comprises at least one signal sensing pad covered at least partially by a cell or cells and at least one reference sensing pad.

9. The sensor of claim 8, wherein the reference sensing pad comprises a cell or cells covering, at least partially, the waveguide grating structure or at least one of the waveguide grating structure units or sensor locations.

10. The sensor of claim 8, wherein the reference sensing pad comprises a modified surface or biocompatible surface or shielding layer covering at least partially the waveguide grating structure or at least one of the waveguide grating structure units or sensor locations.

11. The sensor of claim 8, wherein the reference sensing pad comprises at least one chemofunctional or biochemofunctional substance covering at least partially the waveguide grating structure or at least one of the waveguide grating structure units or sensor locations.

12. The sensor of claim 11, wherein the reference sensing pad is capable of supressing non-specific binding.

13. The sensor of claim 1, further comprising a tunable light source capable of generating the incident light field.

14. The sensor of claim 1, further comprising a broadband light source capable of generating the incident light field.

15. The sensor of claim 1, further comprising a monochromatic light source capable of generating the incident light field.

16. The sensor of claim 1, being equipped for measuring at least of one:

resonant wavelengths, resonant wavelength changes, resonant angles, resonant angle changes, resonant light distributions, and resonant light distribution changes.

17. The sensor of claim 1, being equipped for measuring at least one of:

incoupling angles, incoupling angle changes, outcoupling angles, outcoupling angle changes, effective refractive indices, and effective refractive index changes.

18. The sensor of claim 1, further comprising at least one liquid holder or sample accommodating device, wherein the at least one liquid holder or sample accommodating device is affixed onto the waveguide grating structure or wherein the waveguide grating structure is inserted into the at least one liquid holder or sample accommodating device.

19. The sensor of claim 18, wherein the liquid holder or sample accommodating device comprises at least one well or at least one flow-through cuvette or at least one capillary cuvette or at least one lab-on-chip.

20. The sensor of claim 18, wherein the liquid holders or sample accommodating devices are arranged in a one-dimensional or two-dimensional array like manner or circular ring like manner.

21. The sensor of claim 20, wherein the liquid holders or sample accommodating devices are formed by a well plate.

22. The sensor of claim 21, wherein the well plate comprises 24 wells or 48 wells or 96 wells or 384 wells or 1536 wells.

23. The sensor of claim 20, wherein the arrangement comprises 24 wells or 48 wells or 96 wells or 384 wells or 1536 wells.

24. The sensor of claim 18, wherein the liquid holder or sample accommodating device is at least partially made of scatter radiation absorbing material.

25. The sensor of claim 1, wherein the waveguide grating structure comprises at least two layers and wherein a grating is located at least at the interface between the two layers.

26. The sensor of claim 1, wherein a grating is located at an interface between the substrate and a waveguiding film.

27. The sensor of claim 1, wherein the substrate is a plastic or glass substrate, and wherein an inorganic layer is arranged between a waveguiding film and the substrate.

28. The sensor of claim 1, further comprising least one tempering device.

29. The sensor of claim 28, wherein the tempering device is associated with a temperature control.

30. The sensor of claim 1, wherein the waveguide grating structure comprises a waveguide structure comprising a layer of high refractive index.

31. The sensor of claim 1, wherein the waveguide grating structure units or sensor locations are arranged in a one-dimensional or two-dimensional array-like manner or circular ring like manner.

32. The sensor of claim 1, wherein the sample does not comprise any living cells.

33. The sensor of claim 1, further comprising a liquid holder or sample accommodating device, the liquid holder or sample accommodating device being dark.

34. The sensor of claim 33, wherein the liquid holder or sample accommodating device is black.

35. The sensor of claim 33, wherein the liquid holder or sample accommodating device comprises a cover plate.

36. The sensor of claim 1, further comprising a liquid holder or sample accommodating device, the liquid holder or sample accommodating device comprising a cover plate.

37. A sensor comprising:

a substrate,

a waveguide grating structure on the substrate,

the waveguide grating structure comprising a plurality of waveguide grating structure units or sensor locations;

wherein at least one of said waveguide grating structure units or sensor locations comprises at least one sensing pad with a modified surface of the waveguide grating structure;

the sensor further comprising

a chemofunctional layer in physical contact with said modified surface, the chemofunctional layer comprising at least one living cell, the chemofunctional layer covering at least partially said at least one waveguide grating structure unit or sensor location;

a liquid sample in physical contact with the chemofunctional layer,

the chemofunctional layer being thereby in physical contact with the modified surface and with the sample;

wherein the at least one living cell is a living human cell or a living animal cell or a living plant cell; and

wherein the waveguide grating structure has waveguiding properties and comprises at least one grating, wherein fluorescent or luminescent markers are present and fluorescence or luminescence excitation occurs when an incident light field at least partially illuminates the waveguide grating structure.

38. The sensor of claim 37, wherein the substrate is a plastic or glass substrate and wherein an inorganic layer is arranged between a waveguiding film and the substrate.

39. A sensor for studying the cell behavior, the sensor comprising:

a substrate;

a waveguide grating structure on said substrate;

the waveguide grating structure comprising a plurality of waveguide grating structure units or sensor locations,

wherein at least one of said waveguide grating structure units or sensor locations comprises at least one signal sensing pad with a modified surface of the waveguide grating structure, the sensor further comprising a chemofunctional layer in physical contact with the modified surface, the chemofunctional layer comprising at least one living cell and covering at least partially said at least one waveguide grating structure unit or sensor location;

the signal sensing pad having a signal sensing pad liquid holder or sample accommodating device for bringing the at least one living cell into physical contact with a liquid sample, whereby the chemofunctional layer is in physical contact with the modified surface and with the sample;

wherein the at least one living cell is a living human cell or a living animal cell or a living plant cell;

wherein said at least one waveguide grating structure unit or sensor location further comprises a reference sensing pad, said reference sensing pad having a reference sensing pad liquid holder or sample accommodating device separate from the signal sensing pad liquid holder or sample accommodating device; and

wherein the waveguide grating structure has waveguiding properties and comprises at least one grating, and the waveguide grating structure emits at least one light field when an incident light field at least partially illuminates the waveguide grating structure, thereby being capable of producing a signal indicative of a reaction or a behavior of the at least one living cell due to a contact with the sample.

40. The sensor according to claim 39, wherein the signal sensing pad comprises a modified surface, said living cell or living cells contacting said modified surface.

41. The sensor of claim 39, wherein the reference sensing pad comprises at least one living human cell or animal cell or plant cell.

42. The sensor of claim 41, wherein the signal sensing pad and the reference sensing pad comprise a modified surface, said at least one living cell contacting said modified surfaces.

43. The sensor of claim 42, wherein the modified surface of the signal sensing pad is the same as the modified surface of the reference sensing pad.

44. The sensor of claim 41, wherein the at least one living cell of the signal sensing pad is the same as the at least one living cell of the reference sensing pad.