Systems and methods for in situ spectroscopic measurements

• US 20050264817A1
• Filed: 05/27/2005
• Published: 12/01/2005
• Est. Priority Date: 05/27/2004
• Status: Active Grant

• Current Assignee: Digimarc Corporation, Finesse Solutions, Inc. (Thermo Fisher Scientific Incorporated)
• Original Assignee: Envision Instruments, LLC
• Inventors: Havard, John M., Williams, Paul C.
• Granted Patent: US 7,319,522 B2
• Time in Patent Office: Days
• US Class Current: 356/442
• CPC Class Codes: G01N 21/0303 Optical path conditioning in cuvettes, e.g. windows; adapted optical elements or systems; path modifying or adjustment G01N21/031 - G01N21/15 take precedence
• CPC Class Codes: G01N 21/532 with measurement of scattering and transmission
• CPC Class Codes: G01N 21/645 Specially adapted constructive features of fluorimeters
• CPC Class Codes: G01N 21/6486 Measuring fluorescence of biological material, e.g. DNA, RNA, cells G01N21/6428 takes precedence
• CPC Class Codes: G01N 21/8507 Probe photometers, i.e. with optical measuring part dipped into fluid sample

Abstract

A circularizated semiconductor laser diode (CSLD), such as for example a vertical cavity surface emitting laser (VCSEL) may be used for optical measurements. The CSLD may be used in a cell density probe to perform cell density determination and/or turbidity determination, such as in a biotech, fermentation, or other optical absorbance application. The cell density probe may comprise a probe tip section made from a polytetrafluoroethylene material, which provides sealability, ease of manufacture, durability, cleanability, optical semi-transparency at visible and near infrared wavelengths, and other advantages. The probe tip advantageously provides an optical gap that allows for in situ measurements of optical measurements including but not limited to absorbance, scattering, and fluorescence.

Claims

1. A method for making photometric measurements, comprising the steps of:

emitting a beam of incident light from a circularized semiconductor laser diode (CSLD) in a photometric device such that the emitted light is incident on a sample; and

collecting and analyzing light transmitted through the sample.

2. The method of claim 1, wherein the CSLD is selected from a VCSEL, a laser diode having a circularizing lens mounted on one of its facets, and a laser diode having a circularizing lens inside its package.

3. The method of claim 1, wherein the step of emitting light from the CSLD comprises emitting the light through a polytetrafluoroethylene material or a moldable glass material of the photometric device.

4. The method of claim 1, wherein the light transmitted through the sample is collected on a detector positioned opposite the CLSD and analyzed to make an optical absorbance measurement.

5. The method of claim 4, wherein the optical absorbance measurement is used to determine cell density in the sample.

6. A method for making photometric measurements, comprising the steps of:

emitting a beam of incident light from a circularized semiconductor laser diode (CSLD) in a photometric device such that the emitted light is incident on a sample; and

collecting and analyzing fluorescent emissions occurring in the sample as a result of the incident light.

7. The method of claim 6, wherein the fluorescent emissions are collected at a detector positioned off the axis of the incident light beam.

8. A method for making photometric measurements, comprising the steps of:

emitting a beam of incident light from a circularized semiconductor laser diode (CSLD) in a photometric device such that the emitted light is incident on a sample; and

collecting and analyzing light scattered by the sample as a result of the incident light.

9. The method of claim 8, wherein the scattered light is collected at a detector positioned off the axis of the incident light beam.

10. An optical measurement system, comprising:

means for emitting a beam of incident light from a circularized semiconductor laser diode (CSLD) in a photometric device such that the emitted light is incident on a sample volume; and

means for collecting and analyzing light that is transmitted through, scattered by, or emitted within the sample volume.

11. The optical measurement system of claim 10, wherein the means for collecting and analyzing light comprise a detector positioned opposite the CLSD.

12. The optical measurement system of claim 10, wherein the means for collecting and analyzing light comprise a detector positioned off the axis of the beam of incident light.

13. The optical absorbance measurement system of claim 10, wherein the CSLD is selected from a VCSEL, a laser diode having a circularizing lens mounted on one of its facets, or a laser diode having a circularizing lens inside its package.

14. The optical measurement system of claim 10, further comprising:

means for detecting and processing the emitted light after at least some of the light has been absorbed;

means for controlling the CSLD;

means for initializing the photometric device;

means for controlling the photometric device

means for determining fluorescent em from at least the detected and processed light; and

means for communicating with the photometric device.

15. The optical measurement system of claim 10, further comprising:

means for detecting and analyzing fluorescent emissions occurring in the sample;

means for controlling the CSLD;

means for initializing the photometric device;

means for controlling the photometric device

means for communicating with the photometric device.

16. The optical measurement system of claim 10, further comprising:

means for detecting and analyzing scattered light emitted in the sample;

means for controlling the CSLD;

means for initializing the photometric device;

means for controlling the photometric device

means for communicating with the photometric device.

17. An article of manufacture, comprising:

a machine-readable medium for a photometric device, and having instructions stored thereon and executable by a processor to;

emit light from a CSLD of the photometric device; and

use the light emitted from the CSLD in connection with optical measurements.

18. An apparatus for measuring optical absorbance, comprising:

a tip section comprising a first light source and a first detector, wherein the first light source emits a first light beam at a first wavelength across a first optical gap towards the first detector, such that the first detector receives the first light beam after the first light beam passes through the first optical gap and generates a first signal representative of the light received at the first detector; and

a processor coupled to the first detector to determine an absorbance based on the first signal.

19. The apparatus of claim 18, wherein the tip section is made from a polytetrafluoroethylene material.

20. The apparatus of claim 18, wherein the first light source comprises a VCSEL.

21. The apparatus of claim 18, wherein the first light source emits at a wavelength in the range of approximately 200 nm to 2000 nm.

22. The apparatus of claim 18 wherein the first light source emits at a near-infrared wavelength.

23. The apparatus of claim 18, further comprising a second detector to detect a characteristic of the first light beam prior to the first light beam being passed through the first optical gap.

24. The apparatus of claim 18, wherein the first and/or the second detectors comprise photodiodes.

25. The apparatus of claim 18, further comprising an aperture positioned between the first light source and the first optical gap to substantially prevent light from the first light source from reaching the first detector via a path within the polytetrafluoroethylene material that is external to the first optical gap.

26. The apparatus of claim 18, wherein the tip section further comprises:

a second light source and a second detector, wherein the second light source emits a second light beam at a second wavelength across a second optical gap towards the second detector, such that the second detector receives the second light beam after the second light beam passes through the second optical gap and generates a second signal representative of the light received at the second detector, such that the second signal is also coupled to the processor.

27. The apparatus of claim 18, further comprising a machine-readable medium coupled to the processor and having software stored thereon that can cooperate with the processor to determine the absorbance.

28. The apparatus of claim 18, further comprising electronic circuitry means for supporting operation of the apparatus.

29. The apparatus of claim 18, wherein the determined absorbance is related to cell density.

30. The apparatus of claim 18, further comprising either one or both a wired interface and a wireless interface coupled to the processor to allow communications with the apparatus.

31. The apparatus of claim 18, further comprising means for verifying proper operation of at least some elements of the apparatus.

32. The apparatus of claim 18, further comprising a second light source transmitting a second light beam parallel to the first beam and through the first optical gap onto a second photodetector, the second light source emitting at a different wavelength than the first light source.

33. The apparatus of claim 32, wherein the first light source emits at a near-infrared wavelength and the second light source emits at an ultraviolet wavelength.

34. The apparatus of claim 32, wherein the first light source emits at a near-infrared wavelength and the second light source emits at a visible wavelength.

35. The apparatus of claim 32, wherein the first light source emits at a near-UV wavelength and the second light source emits at a visible wavelength.