Imaging system for fluorescence assays

• US 6,556,299 B1
• Filed: 02/15/2000
• Issued: 04/29/2003
• Est. Priority Date: 07/10/1996
• Status: Expired due to Term

• Current Assignee: PerkinElmer Singapore Pte Ltd. (Revvity, Inc.)
• Original Assignee: Packard Instrument Co., Inc. (Revvity, Inc.)
• Inventors: Neale, William Wray, Rushbrooke, John Gordon, Hooper, Claire Elizabeth
• Primary Examiner(s): Evans, F. L.
• Application Number:
  US09/214,919
• Time in Patent Office: 1,169 Days
• Field of Search: 356/417, 250/458.1, 250/459.1, 250/461.1, 250/461.2
• US Class Current: 356/417
• CPC Class Codes: G01N 2021/6484 Optical fibres
• 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 imaging system for fluorescence assays includes a fiber optic coupling plate (20, 24, 26) for transmitting radiation emitted by a sample (18) towards a camera. This is combined with an interference filter (22) so as to enable highly sensitive transmission of radiation to the camera, according to wavelength. The interference filter may be combined with a fiber optic coupling plate in which sample sites or wells of an array are viewed by separate fiber optic bundles, each bundle transmitting emitted light from a one sample or well to a discrete region of the field of view of the camera.

Claims

1. An imaging system for conveying light produced by fluorescence within each of a plurality of sites in a multi-site sample, to a photodetector, wherein fluorescence occurring at one wavelength is distinguished from that occurring at another wavelength by the use of an interference filter, and in which:

1) the photodetector is a two dimensional CCD array camera with an input faceplate;

2) a plurality of optical fibre bundles each having a cross sectional area commensurate with that of each site are located with the bundle ends adjacent the said sites, each bundle communicating with one of the sites;

3) a plate is provided, adapted to register the ends of the bundles relative to one another and to the sites; and

4) an angle collimating device is positioned between the other ends of the bundles and the camera faceplate to reduce the transmission of skew rays to the camera.

2. An imaging system as claimed in claim 1, in which the angle collimating device comprises a fibre optic device in which each of the optical fibre forming the device has a numerical aperture the value of which is sufficiently low as to reduce the transmission of skew rays incident thereon.

3. An imaging system as claimed in claim 2, in which the angle collimating device is incorporated into the fibre optic camera faceplate.

4. An imaging system as claimed in claim 1, in which each fibre optic bundle is divided into two sub-bundles and the sub-bundles are grouped to form two light paths so that fluorescence from the sites is conveyed along the two different paths to two different interference filters and bundles of optical fibre convey light transmitted by the filters to two different regions of the camera faceplate.

5. An imaging system as claimed in claim 1, in which a fibre optic taper is located between the output ends of the bundles and the filter, in which the larger end of the taper faces the filter.

6. An imaging system as claimed in claim 1, wherein air gaps exist between the filter and each adjoining optical element to permit the filter to be removed and replaced by another.

7. An imaging system as claimed in claim 5, including a converging lens located between the filter and the camera faceplate.

8. An imaging system as claimed in claim 5, including an array of fibre optic bundles located between the filter and the camera faceplate, with air gaps between the opposed faces of the optical elements.

9. An imaging system as claimed in claim 1, in which an interference filter is located between the said other ends of the bundles and the camera faceplate.

10. An imaging system for conveying light produced by fluorescence within each of plurality of sites in a multi-site sample, to the input of a photodetector, wherein fluorescence occurring at one wavelength is distinguished from that occurring at another wavelength by the use of interference filter, and in which:

1) the photodetector is a two dimensional CCD array camera;

2) a plurality of optical fibre bundles each having a cross-sectional area commensurate with that of each site are located with the input ends adjacent the said sites, each bundle communicating with one of the sites; and

3) each of the fibre bundles is divided into two sub-bundles of fibre which convey light from each of the sites to each of two different wavelength interference filters or two different wavelength selective regions of a single interference filter, to select between different wavelengths.

11. An imaging system for a fluorescence array comprising fibre optic coupling means for transmitting fluorescence emissions from sites in a plural site sample towards a photodetector in combination with interference filter means for selecting fluorescence for transmission to the photodetector according to wavelength, and in which:

1) the photodetector is a two dimensional CCD array camera onto which light from a plurality of different sites can be directed simultaneously to occupy different parts of the array; and

2) the fibre optic coupling means provides N different paths from each of the sites to N different interference filters, each selecting a different one of N different wavelengths, for onward transmission to the CCD camera.

12. An imaging system for conveying light produced by fluorescence within each of a plurality of sites in a multi-site sample to a photodetector, wherein fluorescence occurring at one wavelength is distinguished from that occurring at another wavelength by the use of an interference filter, and in which:

1) the photodetector is a two dimensional CCD array camera;

2) a plurality of optical fibre bundles each having a cross-sectional area commensurate with that of each site are located with the bundle ends adjacent the said plurality of sites, each bundle communicating with one of the sites; and

3) the output ends of the fibre bundles are located adjacent an interference filter and are arranged differently from the arrangement of the input ends of the bundles adjacent the sample site.

13. An imaging system as claimed in claim 12, including optical means which reduce the numerical aperture at the output of the fibre bundles as seen by the interference filter.

14. An imaging system as claimed in claim 13, in which the optical means comprises a mini-lens or gradient index lens at the end of each fibre bundle.

15. An imaging system as claimed in claim 13, in which the optical means comprises an optical fibre taper.

16. An imaging system as claimed in claim 13, wherein an angle collimating plate is located in the light path between the sample and the camera faceplate to reduce the transmission of skew rays to the camera.