SYSTEM AND METHOD FOR METERED DOSAGE ILLUMINATION IN A BIOANALYSIS OR OTHER SYSTEM

• US 20120181937A1
• Filed: 10/26/2011
• Published: 07/19/2012
• 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
• Granted Patent: US 8,466,436 B2
• Time in Patent Office: Days
• US Class Current: 315/151
• 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;

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 a particular color; and

wherein, during operation, the illumination subsystem determines a reference count for each color, for each exposure period, enables the light engine to turn on a particular color, monitors 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, and

when the counter reaches the reference count, disables the particular color currently provided by the light engine, to select a different color.

2. The system of claim 1, wherein the light detector is a photodetector for measuring fluorescence that gates on the illumination, and is gated off when the light-to-frequency count equals the reference count.

3. The system of claim 1, wherein the system triggers on the light detector for quantitative measurements and gates the detector off when the frequency detector count equals a prescribed amount in the reference counter.

4. The system of claim 1, wherein the system further comprises a camera for measuring fluorescence, wherein the system gates on the illumination and is gated off when the light to frequency detector count equals the reference count.

5. The system of claim 1, wherein the system further comprises a camera for imaging and wherein the system gates the camera off when the frequency detector count equals a prescribed amount in the reference counter.

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

7. The system of claim 6, wherein the system is used for detection of fluorescent tags or fluors in a biological sample.

8. The system of claim 7, wherein the system is used for one or more of quantitative analyses, or temporally fast analyses, such as fluorescence imaging, gene expression analysis, various types of sequencing, high resolution fluorescence microscopy, fluorescence life time measurements, various forms of Fö

rster 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 the light engine'"'"'s current monitoring circuit monitors the current through each light source and keeps that constant, 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, wherein the system monitors a portion of the light engine output beam, internal to the light engine, using a light-to-frequency converter or circuitry, and regulates the light output to be the same count for each camera exposure or defined detection period, so that, although the time period that the light source is on may vary slightly, the number of counts does not.

11. The system of claim 1, wherein the light engine is configured to operate in a constant intensity mode, wherein a light intensity monitoring/adjusting circuit monitors the light output 194, and adjusts the intensity levels of one or more sources in real time.

12. 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 that can detect an indication of light flux at the light output;

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 a particular color; and

during operation of the illumination subsystem

determining a reference count for each color,

for each exposure period, enabling the light engine to turn on a particular color,

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, and

when the counter reaches the reference count, disabling the particular color currently provided by the light engine, to select a different color.