Apparatus for assaying fluorophores in a biological sample

• US 7,221,449 B2
• Filed: 06/28/2004
• Issued: 05/22/2007
• Est. Priority Date: 06/28/2004
• Status: Expired due to Fees

• Current Assignee: Applied Biosystems LLC (Thermo Fisher Scientific Incorporated)
• Original Assignee: Applera Corporation (Thermo Fisher Scientific Incorporated)
• Inventors: Boege, Steven J.
• Primary Examiner(s): Toatley, Jr.; Gregory J.
• Assistant Examiner(s): Akanbi; Isiaka O.
• Application Number:
  US10/879,374
• Publication Number:
  US 20050286047A1
• Time in Patent Office: 1,058 Days
• Field of Search: 356300-334
• US Class Current: 356/317
• CPC Class Codes: G01J 3/02 Details
• CPC Class Codes: G01J 3/0208 using focussing or collimating elements, e.g. lenses or mirrors; performing aberration correction
• CPC Class Codes: G01J 3/18 using diffraction elements, e.g. grating gratings per se G02B
• CPC Class Codes: G01J 3/4406 Fluorescence spectrometry
• CPC Class Codes: G01N 2021/6478 Special lenses
• CPC Class Codes: G01N 21/645 Specially adapted constructive features of fluorimeters
• CPC Class Codes: G02B 19/0023 at least one surface having optical power
• CPC Class Codes: G02B 19/0028 refractive and reflective surfaces, e.g. non-imaging catadioptric systems
• CPC Class Codes: G02B 19/0047 for use with a light source G02B19/009, G02B19/0095 take precedence; details of lighting devices in general F21V; non-semiconductor lasers having optical devices external to the laser cavity H01S3/005

Abstract

An optical device adapted to detect fluorescence from a biological sample. The optical device includes an optical relay to collect fluorescence emitted by the fluorophores and to direct the collected fluorescence towards a detector.

Claims

1. An optical device for fluorescence detection from biological samples, the device comprising:

a detector;

an optical relay optically coupled to the detector, the optical relay comprising;

a convex reflector;

a first concave reflector; and

a second concave reflector, wherein the second concave reflector comprises a first filter that reflects fluorescence emitted by fluorophores and that transmits an excitation light; and

an excitation light source disposed such that the excitation light optically couples through the second concave reflector of the optical relay.

2. The optical device of claim 1, further comprising a first optical element to concentrate the excitation light on the second concave reflector.

3. The optical device of claim 1, further comprising a second optical element disposed to reflect the excitation light and fluorescence emitted by fluorophores.

4. The optical device of claim 1, further comprising a second optical relay optically coupled to the optical relay and the detector, the second optical relay comprising:

a second convex reflector;

a third concave reflector; and

a fourth concave reflector.

5. The optical device of claim 4, wherein the second convex reflector comprises a diffraction grating.

6. The optical device of claim 4, wherein the third and fourth concave reflectors are concave mirrors.

7. The optical device of claim 4, further comprising a second filter disposed to transmit fluorescence emitted by fluorophores and to reflect the excitation light.

8. The optical device of claim 4, wherein at least one of the first optical relay and the second optical relay comprises an Offner relay.

9. The optical device of claim 1, wherein the excitation light comprises a slit backlit by a lamp.

10. The optical device of claim 1, further comprising a light pipe to increase irradiance of collimated light to a region.

11. The optical device of claim 1, further comprising a mixing rod to increase uniformity of the excitation light.

12. An optical device for fluorescence detection from biological samples, the device comprising:

a excitation light source;

a detector; and

an optical relay optically coupled to the excitation light source and the detector, the optical relay comprising;

a concave reflector, and

a convex reflector, wherein the convex reflector comprises a diffraction grating.

13. The optical device of claim 12, wherein the concave reflector comprises a first mirror and a second mirror.

14. The optical device of claim 12, further comprising a first filter disposed to transmit an excitation light from the excitation light source and to reflect fluorescence emitted by fluorophores.

15. The optical device of claim 12, further comprising a second filter disposed to reflect an excitation light from the excitation light source and to transmit fluorescence emitted by fluorophores.

16. The optical device of claim 12, wherein the excitation light source comprises a slit, wherein the slit is backlit by a lamp.

17. The optical device of claim 12, further comprising a light pipe to increase irradiance of collimated excitation light to a region.

18. The optical device of claim 12, further comprising a mixing rod to increase uniformity of the excitation light.

19. The optical device of claim 12, further comprising a second optical relay optically coupled to the optical relay and the detector, wherein the second optical relay comprises:

a second convex reflector; and

a second concave reflector.

20. The optical device of claim 19, wherein the second concave reflector comprises a first mirror and a second mirror.

21. The optical device of claim 19, wherein at least one of the first optical relay and the second optical relays comprises an Offner relay.

22. An optical device for fluorescence detection from biological samples, the device comprising:

an excitation light source;

a detector;

an optical relay optically coupled to the excitation light source and the detector, the optical relay comprising;

a convex reflector,

a first concave reflector, and

a second concave reflector; and

a lens disposed to vary a collection angle of the optical device, wherein the lens transmits fluorescence emitted by fluorophores and reflects an excitation light from the excitation light source.

23. The optical device of claim 22, wherein the lens comprises an aplanat disposed adjacent to the first concave reflector.

24. The optical device of claim 22, further comprising a filter disposed to transmit an excitation light from the excitation light source and reflect fluorescence emitted by fluorophores.

27. The optical device of claim 22, further comprising at least one of a light pipe to increase irradiance of the collimated excitation light and a mixing rod to increase uniformity of the excitation light.

28. The optical device of claim 22, wherein at least one of the first optical relay and the second optical relay comprises an Offner relay.

25. An optical device for fluorescence detection from biological samples, the device comprising:

an excitation light source;

a detector;

an optical relay, comprising

a convex reflector,

a first concave reflector, and

a second concave reflector; and

a lens disposed to vary a collection angle of the optical device

a second optical relay, wherein the second optical relay comprises;

a further convex reflector; and

a further concave reflector, wherein the further convex reflector includes a diffraction grating.

26. The optical device of claim 25, wherein the further concave reflector comprises a first mirror and a second mirror.

29. An optical device for fluorescence detection from biological samples, the device comprising:

an excitation light source disposed to excite fluorophores to emit fluorescence;

a detector;

a first Schwarzschild telescope disposed to collect fluorescence emitted by fluorophores;

a wavelength separation system disposed to reject the excitation light and transmit fluorescence collected by the first Schwarzschild telescope; and

a focusing system disposed to focus fluorescence transmitted by the wavelength separation system onto the detector.

30. The optical system of claim 29, wherein the focusing system comprises a second Schwarzschild telescope.

31. The optical system of claim 30, wherein at least one of the first Schwarzschild telescope and the second Schwarzschild telescope comprises a concave reflector comprising an aperture.

32. The optical system of claim 29, wherein the focusing system comprises at least one of a refractive, reflective, or catadioptric optical system.

33. The optical system of claim 32, wherein the wavelength separation system comprises a diffraction grating.

34. The optical system of claim 32, wherein the wavelength separation system comprises a dispersive prism.

35. The optical system of claim 32, wherein the wavelength separation system comprises at least one of a shortpass filter, a longpass filter, and a bandpass filter.

36. The optical system of claim 35, wherein the filter is disposed to provide the rejected excitation light to the first Schwarzschild telescope for focusing on the sample.

37. The optical system of claim 29, further comprising an optical element disposed to direct light from a convex mirror of the first Schwarzschild telescope to a limiting aperture of the focusing system.

38. The optical system of claim 29, wherein the first Schwarzschild telescope is unobstructed.

39. The optical system of claim 29, wherein the focusing system is a Wadsworth spectrograph.