Bioanalytical instrumentation using a light source subsystem

• US 8,728,399 B2
• Filed: 06/01/2012
• Issued: 05/20/2014
• Est. Priority Date: 05/22/2006
• Status: Active Grant

• Current Assignee: Lumencor, Inc.
• Original Assignee: Lumencor, Inc.
• Inventors: Jaffe, Claudia B., Jaffe, Steven M., Jones, Michieal L.
• Primary Examiner(s): BROWN, MELANIE YU
• Application Number:
  US13/486,399
• Publication Number:
  US 20120252704A1
• Time in Patent Office: 718 Days
• Field of Search: 422/82.08, 422/50, 422/82.05, 435/283.1, 435/287.1, 435/287.2, 435/288.7
• US Class Current: 422/82.08
• CPC Class Codes: G01J 3/10 Arrangements of light sources specially adapted for spectrometry or colorimetry
• CPC Class Codes: G01N 2021/6419 Excitation at two or more wavelengths
• CPC Class Codes: G01N 2021/6469 Cavity, e.g. ellipsoid
• CPC Class Codes: G01N 2021/6484 Optical fibres
• CPC Class Codes: G01N 21/253 for batch operation, i.e. multisample apparatus analytical automats G01N35/00
• CPC Class Codes: G01N 21/255 Details, e.g. use of specially adapted sources, lighting or optical systems
• CPC Class Codes: G01N 21/4788 Diffraction for sizing particles G01N15/0205
• CPC Class Codes: G01N 21/51 inside a container, e.g. in an ampoule G01N21/53 takes precedence
• CPC Class Codes: G01N 21/53 within a flowing fluid, e.g. smoke
• CPC Class Codes: G01N 21/6452 Individual samples arranged in a regular 2D-array, e.g. multiwell plates
• CPC Class Codes: G01N 2201/06193 Secundary in-situ sources, e.g. fluorescent particles

Abstract

The invention relates to a light source for irradiating molecules present in a detection volume with one or more selected wavelengths of light and directing the fluorescence, absorbance, transmittance, scattering onto one or more detectors. Molecular interactions with the light allow for the identification and quantitation of participating chemical moieties in reactions utilizing physical or chemical tags, most typically fluorescent and chromophore labels. The invention can also use the light source to separately and simultaneously irradiate a plurality of capillaries or other flow confining structures with one or more selected wavelengths of light and separately and simultaneously detect fluorescence produced within the capillaries or other flow confining structures. In various embodiments, the flow confining structures can allow separation or transportation of molecules and include capillary, micro bore and milli bore flow systems. The capillaries are used to separate molecules that are chemically tagged with appropriate fluorescent or chromophore groups.

Claims

1. An illumination system for illuminating a plurality of separate detection volumes simultaneously, the illumination system comprising:

a light pipe in the form of a length of tube, rod, or fiber having a first end and a second end,

an excitation source which provides excitation light wherein the excitation source is optically coupled to the light pipe to provide excitation light along the length of the tube, rod, or fiber, and

a luminescent material in the light pipe which absorbs the excitation light and, in response generates and emits luminescent light by spontaneous emission through the first end of the tube, rod, or fiber, wherein the luminescent light emitted from the light pipe is of sufficient power to illuminate said plurality of separate detection volumes simultaneously;

a mirror coupled to the second end of the tube, rod, or fiber to reflect luminescence toward the first end of the tube, rod, or fiber, and

coupling optics including an optical receiving element and a plurality of optical distribution elements,

wherein said optical receiving element receives said luminescent light emitted from the light pipe and transmits said luminescent light to all of said plurality of optical distribution elements simultaneously, and

wherein each of said plurality of optical distribution elements receives said luminescent light and transmits said luminescent light to a separate one of said plurality of separate detection volumes,

whereby all of said plurality of separate detection volumes are illuminated simultaneously with said luminescent light emitted from said light pipe.

2. The illumination system of claim 1, adapted for illuminating at least four separate detection volumes simultaneously, wherein:

the luminescent light emitted from the light pipe is of sufficient power to illuminate said at least four separate detection volumes simultaneously; and

wherein the coupling optics are adapted to direct the luminescent light emitted by the light pipe to said at least four separate detection volumes simultaneously.

3. The illumination system of claim 1, adapted for illuminating at least twelve separate detection volumes simultaneously, wherein:

the luminescent light emitted from the light pipe is of sufficient power to illuminate said at least twelve separate detection volumes simultaneously; and

wherein the coupling optics are adapted to direct the luminescent light emitted by the light pipe to said at least twelve separate detection volumes simultaneously.

4. The illumination system of claim 1, adapted for illuminating 96 separate detection volumes of a microtiter plate simultaneously, wherein:

the luminescent light emitted from the light pipe is of sufficient power to illuminate said 96 separate detection volumes simultaneously; and

wherein the coupling optics are adapted to direct the luminescent light emitted by the light pipe to said 96 separate detection volumes of a microtiter plate simultaneously.

5. The illumination system of claim 1, wherein the excitation source comprises an LED light source optically coupled to the light pipe.

6. The illumination system of claim 1, wherein the excitation source comprises a linear array of LEDs optically coupled to the light pipe.

7. The illumination system of claim 1, wherein the coupling optics include an optical filter.

8. The illumination system of claim 1, further comprising a driver circuit which modulates the excitation source at a modulation rate of at least one MHz in order to modulate the luminescence emitted by the light pipe.

9. The illumination system of claim 1, wherein the luminescent material comprises a rare earth doped crystalline material.

10. The illumination system of claim 1, further comprising a bioanalytical tool connected to the coupling optics such the coupling optics transmit the luminescence to the bioanalytical tool, wherein the bioanalytical tool is a bioanalytical tool selected from the group consisting of:

microarray scanners;

microtiter plate readers;

DNA sequencers;

PCR instruments;

Q-PCR instruments;

microscopes;

flow cytometry instruments;

lab-on-a-chip devices;

diagnostic medical devices; and

therapeutic medical devices.

11. An illumination system for illuminating a plurality of separate detection volumes simultaneously, the illumination system comprising:

a light pipe in the form of a length of tube, rod, or fiber having a first end and a second end,

an array of LEDs which provides excitation light wherein the array of LEDs is optically coupled to the light pipe to provide excitation light along the length of the tube, rod, or fiber, and

a luminescent material in the light pipe which absorbs the excitation light and, in response generates and emits luminescent light through the first end of the tube, rod, or fiber, wherein the luminescent light emitted from the light pipe is of sufficient power to illuminate said plurality of separate detection volumes simultaneously;

a mirror coupled to the second end of the tube, rod, or fiber to reflect luminescent light toward the first end of the tube, rod, or fiber, and

coupling optics including an optical receiving element and a plurality of optical distribution elements,

wherein said optical receiving element receives said luminescent light emitted from the light pipe and transmits said luminescent light to all of said plurality of optical distribution elements simultaneously, and

wherein each of said plurality of optical distribution elements receives said luminescent light and transmits said luminescent light to a separate one of said plurality of separate detection volumes,

whereby all of said plurality of separate detection volumes are illuminated simultaneously with said luminescent light emitted from said light pipe.

12. The illumination system of claim 11, adapted for illuminating at least four separate detection volumes simultaneously, wherein:

the luminescent light emitted from the light pipe is of sufficient power to illuminate said at least four separate detection volumes simultaneously; and

wherein the coupling optics are adapted to direct the luminescent light emitted by the light pipe to said at least four separate detection volumes simultaneously

the excitation light has a shorter wavelength than the luminescence.

13. The illumination system of claim 11, adapted for illuminating at least seven separate detection volumes simultaneously, wherein:

the luminescent light emitted from the light pipe is of sufficient power to illuminate said at least seven separate detection volumes simultaneously; and

wherein the coupling optics are adapted to direct the luminescent light emitted by the light pipe to said at least seven separate detection volumes simultaneously.

14. The illumination system of claim 11, adapted for illuminating at least twelve separate detection volumes simultaneously, wherein:

the luminescent light emitted from the light pipe is of sufficient power to illuminate said at least twelve separate detection volumes simultaneously; and

wherein the coupling optics are adapted to direct the luminescent light emitted by the light pipe to said at least twelve separate detection volumes simultaneously.

15. The illumination system of claim 14, wherein the coupling optics include an optical filter.

16. The illumination system of claim 14, wherein the luminescent material comprises a rare earth doped crystalline material.

17. The illumination system of claim 14, wherein the luminescent material comprises a rare earth doped YAG.

18. The illumination system of claim 14, wherein the illumination system simultaneously or sequentially generates light at a plurality of wavelengths.

19. The illumination system of claim 14, further comprising a driver circuit which modulates the array of LEDs at a modulation rate of at least one MHz in order to modulate the luminescence emitted by the light pipe.

20. The illumination system of claim 14, further comprising a bioanalytical tool connected to the coupling optics such the coupling optics transmit the luminescence to the bioanalytical tool, wherein the bioanalytical tool is a bioanalytical tool selected from the group consisting of:

microarray scanners;

microtiter plate readers;

DNA sequencers;

PCR instruments;

Q-PCR instruments;

microscopes;

flow cytometry instruments;

lab-on-a-chip devices;

diagnostic medical devices; and

therapeutic medical devices.

21. A bioanalytical system comprising:

a bioanalytical tool selected from the group consisting of;

microarray scanners;

microtiter plate readers;

DNA sequencers;

PCR instruments;

Q-PCR instruments;

microscopes;

flow cytometry instruments;

lab-on-a-chip devices;

diagnostic medical devices; and

therapeutic medical devices, the bioanalytical tool defining a plurality of separate detection volumes;

a light pipe in the form of a length of tube, rod, or fiber having a first end and a second end,

an array of LEDs which provides excitation light wherein the array of LEDs is optically coupled to the light pipe to provide excitation light along the length of the tube, rod, or fiber, and a luminescent material in the light pipe which absorbs the excitation light and, in response generates and emits luminescent light through the first end of the tube, rod, or fiber wherein the luminescent light emitted from the light pipe is of sufficient power to illuminate said plurality of separate detection volumes simultaneously; and

coupling optics including an optical receiving element and a plurality of optical distribution elements,

wherein said optical receiving element receives said luminescent light emitted from the light pipe and transmits said luminescent light to all of said plurality of optical distribution elements simultaneously, and

wherein each of said plurality of optical distribution elements receives said luminescent light and transmits said luminescent light to a separate one of said plurality of separate detection volumes,

whereby all of said plurality of separate detection volumes are illuminated simultaneously with said luminescent light emitted from said light pipe.

22. The bioanalytical system of claim 21, wherein:

said bioanalytical tool defines at least four separate detection volumes;

the luminescent light emitted from the light pipe is of sufficient power to illuminate said at least four separate detection volumes simultaneously; and

wherein the coupling optics are adapted to direct the luminescent light emitted by the light pipe to said at least four separate detection volumes simultaneously.

23. The bioanalytical system of claim 21, wherein:

said bioanalytical tool defines at least 96 separate detection volumes;

the luminescent light emitted from the light pipe is of sufficient power to illuminate said at least 96 separate detection volumes simultaneously; and

wherein the coupling optics are adapted to direct the luminescent light emitted by the light pipe to said at least 96 separate detection volumes simultaneously.

24. The bioanalytical system of claim 21, wherein:

said bioanalytical tool defines at least seven separate detection volumes;

the luminescent light emitted from the light pipe is of sufficient power to illuminate said at least seven separate detection volumes simultaneously; and

wherein the coupling optics are adapted to direct the luminescent light emitted by the light pipe to said at least seven separate detection volumes simultaneously.

25. The bioanalytical system of claim 24, wherein the coupling optics include an optical filter.

26. The bioanalytical system of claim 24, wherein the luminescent material comprises a rare earth doped crystalline material.

27. The bioanalytical system of claim 24, wherein the luminescent material comprises a rare earth doped YAG.

28. The bioanalytical system of claim 24, wherein the light pipe simultaneously or sequentially generates light at a plurality of wavelengths.

29. The bioanalytical system of claim 24, further comprising a driver circuit which modulates the array of LEDs at a modulation rate of at least one MHz in order to modulate the luminescence emitted by the light pipe.

30. The bioanalytical system of claim 24, wherein the array of LEDs is a linear array of LEDs.