System and method for metered dosage illumination in a bioanalysis or other system

• US 8,466,436 B2
• Filed: 10/26/2011
• Issued: 06/18/2013
• Est. Priority Date: 01/14/2011
• Status: Active Grant

• Current Assignee: Lumencor, Inc.
• Original Assignee: Lumencor, Inc.
• Inventors: Jaffe, Claudia B., Jaffe, Steven M., Larsen, David
• Primary Examiner(s): Owens, Douglas W
• Assistant Examiner(s): HAMMOND, DEDEI KHALIEAH
• Application Number:
  US13/282,108
• Publication Number:
  US 20120181937A1
• Time in Patent Office: 601 Days
• Field of Search: None
• US Class Current: 250/458.1
• CPC Class Codes: F21V 23/0457 the sensor sensing the operating status of the lighting device, e.g. to detect failure of a light source or to provide feedback to the device
• CPC Class Codes: G01J 1/4257 applied to monitoring the characteristics of a beam, e.g. laser beam, headlamp beam monitoring arrangements for lasers in general H01S3/0014
• CPC Class Codes: G01N 2021/6419 Excitation at two or more wavelengths
• CPC Class Codes: G01N 2021/6439 with indicators, stains, dyes, tags, labels, marks
• CPC Class Codes: G01N 21/64 Fluorescence; Phosphorescence
• CPC Class Codes: G01N 21/6408 with measurement of decay time, time resolved fluorescence
• CPC Class Codes: G01N 21/6428 Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" in vivo A61B5/00; immunoassay G01N33/53
• CPC Class Codes: G01N 21/645 Specially adapted constructive features of fluorimeters
• CPC Class Codes: G01N 21/6458 Fluorescence microscopy fluorescence microscopes per se G02B21/0076 and G02B21/16
• CPC Class Codes: G01N 2201/061 Sources
• CPC Class Codes: H05B 45/22 using optical feedback

Abstract

A system and method for metered dosage illumination in a bioanalysis or other system includes an illumination system or subsystem that can provide optimized amounts of excitation light within the short exposure times necessary to measure fast biological activity. The amount of light can be precisely measured to provide quantitative results. The light flux can be precisely controlled to generate a prescribed minimum amount of light, in order to reduce adverse lighting effects on both fluors and samples. The system and method is particularly useful in any quality-control, analysis, or assessment-based environment. Typical research and development applications can include quality control, instrument calibration, and light output standardization; while clinical and diagnostics applications can include clinical monitoring, bioassay calibration and control for diagnostics, treatment and or therapeutic evaluation.

Claims

1. A system for providing metered dosage illumination for use in a bioanalysis or other system, comprising:

a light engine that can provide a plurality of different colors of light as a light output;

a light detector that can detect an indication of light flux at the light output wherein the light detector monitors a portion of the light output, internal to the light engine;

a light-to-frequency converter that can convert the indication of light flux as detected by the light detector to a pulse train, the frequency of which pulse train is proportional to the light flux;

a counter that can compare an ongoing count as indicated by the pulse train, to a preset reference count for each of the plurality of different colors of light; and

wherein, during operation, the system

determines a reference count for each color of the plurality of different colors of light,

for an exposure period, enables the light engine to turn on a particular color of the plurality of different colors of light,

monitors the indication of light flux in the light output, as detected by the light detector and converted to the pulse train counted by the counter for the particular color of the one or more of the plurality of different colors of light, and

when the ongoing count reaches the reference count for the particular color of the one or more of the plurality of different colors of light, causes the light engine to turn off said particular color.

2. The system of claim 1, further comprising a fluorescent light detector for measuring fluorescence from a sample in response to the light output from the light engine;

wherein the fluorescent light detector gates on when the light engine turns on said one or more of the plurality of different colors of light; and

wherein the fluorescent light detector is gated off when the ongoing count reaches the reference count for all of the one or more of the plurality of different colors of light.

3. The system of claim 1, wherein the system triggers on a camera for quantitative measurements and gates the camera off when the ongoing count reaches the reference count for each of the one or more of the plurality of different colors of light.

4. The system of claim 1, wherein the system further comprises a camera for measuring fluorescence, wherein the system triggers the camera to begin an exposure period when the light engine turns on one of the plurality of different colors of light;

and

wherein the system triggers the camera to end the exposure period when the ongoing count reaches the reference count for each of the plurality of different colors of light.

5. The system of claim 1, wherein the system further comprises a camera for imaging and wherein the system triggers the camera to begin an exposure period when the light engine turns on one of the plurality of different colors of light;

and

wherein the system triggers the camera to end the exposure period when the ongoing count reaches the reference count for each of the plurality of different colors of light.

6. The system of claim 1, wherein the system is used as part of a bioanalysis system.

7. The system of claim 1 wherein the system is used as part of a bioanalysis system which, is used for detection of fluorescent tags or fluors in a biological sample.

8. The system of claim 1, wherein the system is used as part of a bioanalysis system which is used for one or more of:

quantitative analyses, temporally fast analyses, fluorescence imaging, gene expression analysis, sequencing, high resolution fluorescence microscopy, fluorescence life time measurements, Forster Resonance Energy Transfer (FRET) Microscopy, and high content screening.

9. The system of claim 1, wherein the light engine is configured to operate in a constant current mode, wherein a current monitoring circuit monitors the current through one or more light source and keeps the current constant, through said one of more light source, to provide a constant current light output of generally constant dosage.

10. The system of claim 1, wherein the light engine is configured to operate in a metered dosage mode, so that, although the time period that the light engine is on may vary slightly, the number of counts does not.

11. A method for providing metered dosage illumination for use in a bioanalysis or other system, comprising the steps of:

providing a light engine that can provide a plurality of different colors of light as a light output;

providing a light detector internal to the light engine that can detect an indication of light flux in the light output for each of said plurality of colors;

providing a light-to-frequency converter that can convert the indication of light flux as detected by the light detector to a pulse train, the frequency of which pulse train is proportional to the light flux;

providing a counter that can compare an ongoing count as indicated by the pulse train, to a preset reference count for each of said plurality of colors; and

during operation of the illumination system

determining a reference count for each of said plurality of colors,

for an exposure period, enabling the light engine to turn on a particular color of said plurality of colors,

monitoring the indication of light flux at the light output, as detected by the light detector and converted to the pulse train counted by the counter for the particular color of said plurality of colors, and

when the ongoing count reaches the reference count for the particular color of said plurality of colors, turning off the particular color.