Sensitive light detection system

• US 5,315,375 A
• Filed: 02/11/1992
• Issued: 05/24/1994
• Est. Priority Date: 02/11/1992
• Status: Expired due to Term

• Current Assignee: Acrogen, Inc.
• Original Assignee: Acrogen, Inc.
• Inventors: Allen, Fritz S.
• Primary Examiner(s): McGraw, Vincent P.
• Assistant Examiner(s): HANTIS, KAREN
• Application Number:
  US07/833,926
• Time in Patent Office: 833 Days
• Field of Search: 356/318, 356/417, 250/458.1, 250/459.1, 250/461.1, 250/461.2
• US Class Current: 356/417
• CPC Class Codes: G01J 3/0216 using light concentrators or collectors or condensers
• CPC Class Codes: G01N 2021/6463 Optics
• CPC Class Codes: G01N 21/645 Specially adapted constructive features of fluorimeters
• CPC Class Codes: G01N 21/6456 Spatial resolved fluorescence measurements; Imaging

Abstract

Apparatus and method for using the apparatus are provided, where the apparatus provides for a light beam of variable area in a narrow wavelength band, where the size of the beam incident on a sample and relative movement of the sample and light irradiation and collection means is carefully controlled, so as to vary the site of interrogation. A discrete element collector system is used to efficiently collect the emitted light from the sample and direct it to a focusing lens, filter pack and photodetector for collection of the light and transmitting signals to electronic circuitry for analysis.

Claims

1. An improved sensitivity light collection system capable of detecting luminescence from emitters in biological assay media comprising a sample resulting in a very low signal level, said light detection system comprising:

means for collecting emitted light from said assay media comprising a discrete element collector system, said system having a first discrete element collector catadioptric lens proximal to said sample having a small focal length and a low f number in the range of about 0.05-2 for collecting and collimating emitted light; and

a second lens in light receiving relationship with said first discrete element collector separated by from about 0.1 to 50 cm from said first discrete element collector and distal from said sample having a greater focal length and a larger f number in the range of about 1-10 for focusing said collimated emitted light collected by said first discrete element collector; and

photodetecting means for detecting light transmitted by said discrete element collector system.

2. A light detection system according to claim 1, including an irradiation source for directing a beam onto said sample, wherein said beam passes through a hole in said discrete element collector system.

3. A light detection system according to claim 1, wherein said first discrete element collector has an f-number in the range of about 0.075-1 and said second lens has an f-number of greater than about 1.

4. A light detection system according to claim 1, wherein said second discrete element collector lens is a Fresnel lens.

5. A light detection system for detecting light transmitted from a surface at a very low signal level as a result of light irradiation, said light detection system comprising:

means for providing a beam of light for irradiating a surface or volume with a beam of defined wave length range;

means for collecting emitted light from said surface or volume comprising a discrete element collector system, said system having a first discrete element collector catadioptric lens proximal to said sample having a small focal length and a low f number in the range of about 0.075-1 for collection and collimating emitted light; and

a second lens in light receiving relationship with said first discrete element collector lens seperated by from about 0.1 to 5 cm from said first discrete element collector and distal from said sample having a greater focal length and a larger f number in the range of about 1-10 for focusing said collimated emitted light collected by said first discrete element collector lens, wherein said beam irradiates said surface without interacting with said discrete element collector system; and

photodetecting means for detecting light transmitted by said discrete element collector system.

6. A light detection system according to claim 5, wherein said beam passes through a hole in said discrete element collector system.

7. A light detection system according to claim 5, wherein said light source is a laser having a wavelength in the range of about 350 to 700 nm.

8. An emitted light detection system for detecting an analyte in a sample, said decision system comprising:

a sample support;

means for providing a beam of light for irradiating a sample on said sample support with a beam of defined wave length range;

means for controlling the area of said beam impinging on said sample;

means for moving said sample support and beam relative to one another;

means for collecting emitted light from said sample comprising a discrete element collector system, said system having a first discrete element collector catadioptric lens proximal to said sample having a small focal length and a low f number in the range of about 0.075-1 for collecting and collimating said emitted light; and

a second lens in light receiving relationship to said first discrete element collector lens separately by from about 0.1 to 5 cm from said first discrete element collector and distal from said sample having a greater focal length and a larger f number in the range of about 1-10 for focusing said emitted light collimated by said first discrete element collector lens;

means for filtering emitted light to isolate enough sample emission from excitation wavelength;

photodetecting means for detecting light transmitted by said discrete element collector system; and

means connected to said photodetecting means for relating a signal from said photodetecting means to the presence of analyte in said sample.

9. A device according to claim 8, wherein said light source is a laser having a wave length in the range of about 350 to 700 nm.

10. A device according to claim 8, wherein said sample support is at least partially transparent;

and further comprising;

a reflector below said sample support for transmitting light to said discrete element collector system.

11. A device according to claim 8, wherein said device further comprises a movable stage supporting said sample support.

12. A device according to claim 8, wherein said beam area controlling means includes means for varying the beam size.

13. An emitted light detection system for detecting an analyte in a sample, said detection system comprising:

a sample support on a movable stage;

a laser light source for irradiating a sample on said sample support with a beam of defined wavelength range;

means for controlling the area of said beam impinging on said sample;

means for moving said sample support and beam relative to one another;

means for collecting emitted light from said sample comprising a discrete element collector system, said system having a first discrete element collector catadioptric lens proximal to said sample having a small focal length and a low f number in the range of about 0.075-1 for collecting and collimating said emitted light; and

a second lens in light receiving relationship with said first discrete element collector lens separated by from about 0.1 to 5 cm from said first discrete element collector and distal from said sample having a greater focal length and a larger f number in the range of about 1-10 for focusing said collimated light collected by said first discrete element collector lens, wherein said beam does not interact with said discrete element collector system;

means for filtering emitted light to isolate sample emission from excitation wavelength;

photodetecting means for detecting light transmitted by said discrete element collector system; and

means connected to said photodetecting means for relating a signal from said photodetecting means to the presence of analyte in said sample.

14. A device according to claim 13, wherein said area controlling means comprises a single or multi-lens system and said second lens is a Fresnel lens.

15. A device according to claim 13, wherein said sample is irradiated at an angle normal to said sample and the irradiating light passes through a hole in said discrete element collector system.

16. A device according to claim 13, wherein said sample is irradiated at an angle at other than normal to said sample and the irradiating light.

17. A device according to claim 13, wherein said sample support is at least partially transparent;

and further comprising;

a reflector below said sample for transmitting light to said discrete element collector system.

18. A method for detecting low levels of emitted light from a sample, said method comprising:

activating a sample suspected of being capable of emitting light upon activation;

collecting light from said sample with a discrete element collector system, said collector system having a first discrete element collector catadioptric lens proximal to said sample having a small focal length and a low f number in the range of about 0.05-2 for collecting and collimating emitted light; and

a second lens in light receiving relationship to said first discrete element collector lens separated by from about 0 to 50 cm from said first discrete element collector and distal from said sample having a greater focal length and a larger f number in the range of about 1-10 for focusing said collimated emitted light collected by said first discrete element collector;

detecting light transmitted by said discrete element collector system, wherein the level of light detected is related to the level of light emitters in said sample.

19. A method according to claim 18, wherein said irradiating is at different portions of said sample and said detecting is as to each of said portions of said sample.

20. A method according to claim 18, wherein said first discrete element collector lens is a catadioptric lens, said lens having a f-number in the range of about 0.075-1.

21. A method according to claim 18, wherein said activation is irradiation and said activating comprises irradiating said sample with light at an excitation wavelength range.