Optical system for chemical and/or biochemical reactions

• US 9,089,828 B2
• Filed: 09/06/2013
• Issued: 07/28/2015
• Est. Priority Date: 01/08/2009
• Status: Active Grant

• Current Assignee: IT-IS International Limited (Novacyt SAS)
• Original Assignee: IT-IS International Limited (Novacyt SAS)
• Inventors: Howell, James Richard, Clark, Mark Quentin, Howell, Richard Alfred, Webster, Benjamin Masterman
• Primary Examiner(s): SIEFKE, SAMUEL P
• Application Number:
  US14/019,687
• Publication Number:
  US 20140005078A1
• Time in Patent Office: 690 Days
• Field of Search: 422/52
• US Class Current: 1/1
• CPC Class Codes: B01J 19/0046 Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays synthesis methods per se C40B50/00
• CPC Class Codes: G01N 21/253 for batch operation, i.e. multisample apparatus analytical automats G01N35/00
• CPC Class Codes: G01N 21/6452 Individual samples arranged in a regular 2D-array, e.g. multiwell plates
• CPC Class Codes: G01N 2201/0826 Fibre array at source, distributing
• CPC Class Codes: G01N 2201/0833 Fibre array at detector, resolving

Abstract

An apparatus for detecting light emanating from chemical or biochemical reactions occurring in at least one reaction vessel of a plurality of reaction vessels is disclosed. Each reaction vessel has a receptacle portion having an emitting area from which light can emanate. A plurality of light waveguides are arranged to guide light from apertures in a masking element to a light dispersing device for dispersing the light from each waveguide into a dispersed spectrum. A light detecting device detects specific spectra in the dispersed spectra of light substantially simultaneously In one embodiment, the light waveguides have a diameter that tapers from a first end substantially similar in diameter to the area of the top of the reaction vessel to a second end that is substantially smaller in diameter.

Claims

1. Apparatus for monitoring light emanating from an array of reaction vessels in which a chemical or biochemical reaction is occurring, said apparatus comprising:

an array of reaction vessels, each reaction vessel comprising a receptacle portion having an interior volume in which a chemical or biochemical reaction may occur and in which volume the light may be produced, the reaction vessel having an emitting area from which at least part of the produced light can emanate;

a light detecting device for detecting one or more wavebands of at least part of the light produced in the interior volumes of all of the reaction vessels where light is produced;

a first set of light waveguides comprising at least one light waveguide for each reaction vessel in the array of reaction vessels, each light waveguide arranged to guide at least part of the light produced in the interior volumes of a respective reaction vessels and emanating from the respective reaction vessel to the light detecting device, whereby at least a part of the produced light emanating from all of the reaction vessels where light is produced is detected substantially simultaneously by the light detecting device, each light waveguide having a first end arranged adjacent a corresponding emitting area of a respective reaction vessel, and a second end arranged for providing at least part of the light emanating from the respective reaction vessel to the light detecting device, wherein the first ends of the first set of light waveguides are arranged in an array arranged adjacent the array of reaction vessels;

at least one excitation light source for providing excitation light; and

a second set of further light waveguides for guiding excitation light from the at least one excitation light source to all of the reaction vessels substantially simultaneously, the second set of further light waveguides comprising at least one further light waveguide for each reaction vessel in the array of reaction vessels, each further light waveguide having a first end arranged adjacent a respective reaction vessel and a second end arranged for receiving at least part of the light from the at least one excitation light source.

2. Apparatus according to claim 1, further comprising a plurality of excitation light sources providing excitation light of the same or different spectra.

3. Apparatus according to claim 1, where the second end of each of the light waveguides of the first set is arranged adjacent a filter so as to limit the light reaching the light detecting device to a specific spectrum or waveband.

4. Apparatus according to claim 1, wherein the light detecting device comprises a light dispersing device for producing a dispersed spectrum from the light emanating from each of the plurality of reaction vessels on a plane, and one or more detectors for detecting specific spectra within each of the dispersed spectra.

5. Apparatus according to claim 1, wherein said first ends of the plurality of light waveguides are arranged in a plurality of apertures in a masking element arranged adjacent the emitting areas of the reaction vessels.

6. Apparatus according to claim 5, wherein the first end of each of the further light waveguides is arranged in a further aperture in the masking element adjacent each reaction vessel.

7. Apparatus according to claim 1, wherein the light waveguides of the first set taper in diameter from their first ends, which first ends have a diameter substantially similar to that of the respective emitting areas of the receptacle portions of the reaction vessels, whereby the second ends of the first set of light waveguides are substantially smaller in diameter than the first ends.

8. Apparatus according to claim 4, wherein the second ends are arranged so that the dispersed spectra on a plane of the light detecting device do not overlap, at least within the spectral range where there is significant light emitted from the reaction vessels and passed to the detector, and where the detector has significant sensitivity.

9. Apparatus according to claim 5, wherein the masking element is provided by a thermal mount in which the array of reaction vessels is mounted.

10. Apparatus according to claim 4, wherein the light dispersing device comprises a light splitting device for dispersing the light into different wavebands.

11. Apparatus according to claim 1, wherein the light emitting area of at least one reaction vessel is at a top of the receptacle portion of the reaction vessel.

12. Apparatus according to claim 1, wherein the light emitting area of at least one reaction vessel is at a side of the receptacle portion of the reaction vessel.

13. Apparatus according to claim 1, wherein the light emitting area of at least one reaction vessel is at a bottom of the receptacle portion of the reaction vessel.

14. Apparatus according to claim 1, wherein the light detecting device comprises a CCD or CMOS detector.

15. Apparatus according to claim 1, wherein the array of reaction vessels is contained within a multi-well plate.

16. Apparatus according to claim 15, further comprising a thermal cycler having a block heater for holding the multi-well plate.

17. Apparatus according to claim 4, wherein the specific spectrum is characteristic of a particular reagent or state of a particular reagent within a reaction vessel.

18. Apparatus according to claim 4, wherein the specific spectrum is derived from a single species of fluorophore, present in the reaction.

19. Apparatus according to claim 1, wherein the chemical or biochemical reaction is a polymerase chain reaction (PCR) conducted in the presence of at least one fluorophore, which may be one or more fluorophores taken from the group including:

fluorophores which intercalate with nucleic acid, such as intercalating dyes;

fluorophores which hybridize with nucleic acid, such as labeled hybridization probes;

fluorophores which are modified by the PCR process, such as labeled digestion probes;

fluorophores which provide for fluorescent energy transfer between them, such as fluorescent labeled probes; and

other fluorescent probes.

20. Apparatus according to claim 19, wherein the fluorophore is a fluorescent label attached to a first oligonucleotide probe which specifically hybridizes to a target nucleic acid sequence of the PCR and wherein the first oligonucleotide probe contains a second fluorophore, which is able to exchange fluorescent energy with said fluorescent label when present together on the probe, wherein a polymerase having 5′

-3′

exonuclease activity is utilized in the PCR so as to digest any first probe bound to target nucleic acid during an extension phase of the reaction.

21. Apparatus according to claim 1, wherein the second ends of the second set of further light waveguides are arranged within a smaller area than an area within which the first array of the first ends of the second set of further light waveguides are arranged.

22. Apparatus according to claim 5, wherein the masking element is heated.

23. Apparatus for monitoring light emanating from an array of reaction vessels in which a chemical or biochemical reaction is occurring, said apparatus comprising:

an array of reaction vessels, each reaction vessel comprising a receptacle portion having an interior volume in which a chemical or biochemical reaction may occur and in which volume the light may be produced, the reaction vessel having an emitting area from which at least part of the produced light can emanate;

a light detecting device for detecting one or more wavebands of at least part of the light produced in the interior volumes of all of the reaction vessels where light is produced;

a first set of light waveguides comprising at least one light waveguide for each reaction vessel in the array of reaction vessels, each light waveguide arranged to guide at least part of the light produced in the interior volume and emanating from the emitting area of a respective reaction vessel to the light detecting device, whereby at least part of the produced light emanating from all of the reaction vessels where light is produced is detected substantially simultaneously by the light detecting device, each light waveguide having a first end arranged adjacent a corresponding emitting area of a respective one of the reaction vessels, and a second end arranged for providing at least part of the light emanating from the respective reaction vessel to the light detecting device, wherein the first ends of the first set of light waveguides are arranged in an array arranged adjacent the array of reaction vessels;

at least one excitation light source for providing excitation light; and

a second set of further light waveguides for guiding at least part of the excitation light from the at least one excitation light source to all of the respective reaction vessels substantially simultaneously, the second set of further light waveguides comprising at least one further light waveguide for each reaction vessel in the array of reaction vessels, each further light waveguide having a first end arranged adjacent a respective reaction vessel and a second end arranged for receiving at least part of the light from the at least one excitation light source,

wherein the second ends of the first set of light waveguides are arranged within a smaller area than an area within which the array of the first ends of the first set of light waveguides are arranged.