Bioanalytical instrumentation using a light source subsystem

• US 7,846,391 B2
• Filed: 05/21/2007
• Issued: 12/07/2010
• Est. Priority Date: 05/22/2006
• Status: Active Grant

• Current Assignee: Lumencor, Inc.
• Original Assignee: Lumencor, Inc.
• Inventors: Jaffe, Claudia B., Jones, Michieal L., Jaffe, Steven M.
• Primary Examiner(s): BROWN, MELANIE YU
• Application Number:
  US11/805,185
• Publication Number:
  US 20070281322A1
• Time in Patent Office: 1,296 Days
• Field of Search: 435/283.1, 435/287.1, 435/287.2, 435/288.7, 422/50, 422/82.05, 422/82.08
• 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 apparatus for analyzing one or more analyte comprising:

(a) one or more light pipes for use in generating luminescence, wherein each light pipe includes

an excitation source which provides excitation energy, and

a luminescent material which acts as a secondary absorber of the excitation energy, and wherein the luminescent material, when excited by the excitation source, generates and emits luminescence through an exit region of the light pipe;

(b) luminescence relay optics for directing the luminescence at one or more wavelengths, from the one or more light pipes, onto one or more analyte;

(c) emission relay optics for directing emitted light, from the one or more analyte as a reaction to the luminescence, onto one or more light detector; and

(d) one or more light detector which is used for detecting the presence of the one or more analyte, based on the emitted light.

2. The apparatus of claim 1, wherein the one or more analyte undergoes an electrochemical reaction prior to, during or after the luminescence.

3. The apparatus of claim 1, further comprising the step of identifying a characteristic of the one or more analyte based on the detection of the light emitted from the one or more analyte.

4. The apparatus of claim 1, further comprising a coupler for directing one or more flow of the one or more analyte into one or more detection volume, wherein the luminescence is directed onto the one or more detection volume and the light emitted by the one or more analyte is emitted from the one or more detection volume.

5. The apparatus of claim 4, wherein the luminescence is simultaneously and separately directed to the one or more detection volume.

6. The apparatus of claim 4, further comprising a coupling plate for separating the one or more analyte in the one or more flow while directing the one or more flow into the one or more detection volume.

7. The apparatus of claim 6, wherein the separation of the one or more analyte is temporal with respect to the duration of time of the one or more flow and the one or more analyte is detected at one or more elapsed time.

8. The apparatus of claim 7, further comprising identifying the one or more analyte based on detecting one or more of the characteristics selected from the group consisting of emitted light wavelength, difference in emitted light wavelength, emitted light intensity, difference in emitted light intensity, direction of emitted light, difference in direction of emitted light, temperature, temperature change, potential, potential change, number of molecules, change in number of molecules, time elapsed and change in elapsed time.

9. The apparatus of claim 1, wherein each of the one or more light pipes comprises a plurality of excitation sources whose combined energy is absorbed by the luminescent material as a secondary absorber, which in turn generates the light pipe'"'"'s radiated output or luminescence.

10. The apparatus of claim 1, wherein the excitation source provides optical and/or electronic excitation energy, and wherein if electronic excitation is used the excitation can be either voltage or current based.

11. The apparatus of claim 1, wherein the excitation source provides optical excitation energy in the form of radiation by photoluminescent, cathodoluminescent and/or electroluminescent sources, such as from an ultraviolet (UV) light source, light emitting diode (LED) source, or laser source.

12. The apparatus of claim 1, wherein the luminescent material which acts as a secondary absorber comprises one or more of a crystalline material, or doped crystalline, glass, or plastic material which includes one or more inorganic or organic luminescent dopants or co-dopants.

13. The apparatus of claim 1, wherein the luminescent material has a geometric cross section and length, such as a tube, rod, fiber, disk, slab, or other shape.

14. The apparatus of claim 1, wherein the one or more light pipe simultaneously or sequentially generates luminescence at a plurality of wavelengths, for direction by the luminescence relay optics onto the one or more analyte.

15. The apparatus of claim 1, wherein the one or more light pipe includes a luminescent material which is formed or constrained within the shape of a tube, rod, fiber, disk, slab, or other shape, and wherein the luminescent material is excited by an excitation source which is optically coupled to the light pipe and provides excitation energy in the form of radiation to the luminescent material, which then absorbs the radiation and emits luminescence through an end of the tube, rod, fiber, disk, slab, or other shape.

16. The apparatus of claim 1, wherein the excitation source is a light source, and wherein the luminescent material is wrapped around or otherwise optically coupled to the light source, so that it receives excitation energy along its length, and emits the luminescence through its end.

17. The apparatus of claim 1, wherein the excitation light source is an ultraviolet (UV) lamp, light-emitted diode (LED), laser, or other light-emitting source, and wherein the light output of which is used to excite the luminescent material in the light pipe.

18. The apparatus of claim 1, wherein the luminescent material, when excited by the excitation source, generates and emits luminescence by absorption and secondary spontaneous emission.

19. The apparatus of claim 1, wherein the one or more analyte present in a detection volume undergoes a reaction selected from the group consisting of a heterogeneous reaction and a homogeneous reaction.

20. The apparatus of claim 1, wherein the luminescence relay optics and emission relay optics are combine to reflect luminescence that has passed over the one or more analyte back to the detector.

21. The apparatus of claim 1, wherein a plurality of light pipes are connected in series.

22. The apparatus of claim 1, wherein a plurality of light pipes are connected in parallel.

23. The apparatus of claim 1, wherein the detection volume is selected from the group consisting of a well, micro-cuvette, a micro-titer plate, a micro-array chip, a capillary, a tube, a pore, a sensor, a fluidic chip and a detection volume of free flowing stream.

24. The apparatus of claim 1, wherein the emitted light is detected based on one or more properties of the light emitted selected from the group consisting of fluorescence, phosphorescence, absorbance, transmittance, scattering and luminescence.