Self-compensating radiation sensor with wide dynamic range

• US 6,573,991 B1
• Filed: 04/26/2000
• Issued: 06/03/2003
• Est. Priority Date: 04/26/2000
• Status: Expired due to Fees

• Current Assignee: Athanasios Kasapi, Martin Paul Debreczeny, Oʼneil, Michael Patrick
• Original Assignee: Athanasios Kasapi, Martin Paul Debreczeny, Oʼneil, Michael Patrick
• Inventors: Kasapi, Athanasios, OʼNeil, Michael Patrick, Debreczeny, Martin Paul
• Primary Examiner(s): Font, Frank G.
• Assistant Examiner(s): Punnoose, Roy M.
• Application Number:
  US09/560,265
• Time in Patent Office: 1,133 Days
• Field of Search: 356/336, 356/335, 356/337, 356/338, 356/342, 356/343
• US Class Current: 356/336
• CPC Class Codes: G01N 15/0211 Investigating a scatter or diffraction pattern
• CPC Class Codes: G01N 15/075 by optical means
• CPC Class Codes: G01N 2015/0294 Particle shape

Abstract

A radiation sensing method and device that is used to measure physical properties of materials over a wide dynamic range. The sensor (20) comprises multiple radiation sources and multiple detectors at multiple separation distances. The detected signals from the different sources are separated and then combined mathematically in a manner such that the combination is self-compensated for both component drift and changes in radiation coupling efficiency between the source or detector and the material of interest. In a preferred embodiment, the biomass in a liquid cell culture (54) is measured with high accuracy over a wide dynamic range using optical wavelength radiation. The measurement can be made with the sensor external to the liquid culture container in a manner that is compensated for the thickness of the container window (50).

Claims

1. A method of determining at least one parameter of a medium which comprises the steps of:

a) passing electromagnetic or acoustic radiation originating from each of a plurality of sources through said medium to a plurality of detectors;

b) measuring a plurality of signals corresponding to the portion of radiation detected by each of said detectors that originated from each of said sources;

c) selecting signals from a group consisting of all of said signals, and combining the selected signals in a manner that substantially reduces the sensitivity of the combined result to all of the following factors as compared to said signals considered separately;

intensity of said sources,

sensitivity of said detectors,

coupling efficiency of radiation from said sources into said medium, and

coupling efficiency of said radiation from said medium to said detectors;

wherein said selected signals comprise the signals collected from a plurality of said detectors, each detecting radiation that originated from a plurality of said sources, the separations between said sources and said detectors including at least three unique distances; and

wherein the selection of signals and said combining of the selected signals is carried out at least once whereby at least one said combined result is produced; and

d) relating at least one of said combined results to at least one parameter of the medium.

2. The method of claim 1 wherein said radiation sources are each substantially monochromatic.

3. The method of claim 2 wherein said plurality of sources emit radiation of substantially identical wavelength.

4. The method of claim 1 wherein said sources and said detectors are arranged such that substantially only scattered radiation is detected by said detectors.

5. The method of claim 1 wherein at least one of said combined results is determined from the following equation:

$\log <br><br>\left(\frac{S_{\mathrm{E1D1}}<br><br>S_{\mathrm{E2D2}}}{S_{\mathrm{E1D2}}<br><br>S_{\mathrm{E2D1}}}\right)$

where;

E1 and E2 are a pair of sources from among said plurality of sources, and D1 and D2 are a pair of detectors from among said plurality of detectors;

S_E1D1 is proportional to the intensity of radiation from source E1 that is detected at detector D1;

S_E1D2 is proportional to the intensity of radiation from source E1 that is detected at detector D2;

S_E2D1 is proportional to the intensity of radiation from source E2 that is detected at detector D1; and

S_E2D2 is proportional to the intensity of radiation from source E2 that is detected at detector D2.

6. The method of claim 1 wherein said at least one parameter being determined is related to at least one of:

the concentration of at least one type of particle suspended in said medium, the average size of particles suspended in said medium, the size distribution of particles suspended in said medium, the chemical composition of particles suspended in said medium, the shape of particles suspended in said medium, and the chemical composition of said medium.

7. The method of claim 6 wherein said medium is a liquid culture containing a suspension of cells or microorganisms.

8. The method of claim 7, further including:

a) varying the conditions of said liquid culture, including any combination of the concentration, size, and type of cells or microorganisms, the density, size, and type of gas bubbles, and the rate of stirring;

b) establishing a calibration whereby for the range of said varied conditions, said combined results are related to known values of said at least one parameter of the medium; and

c) utilizing said calibration to arrive at a determination of present said at least one parameter within said liquid culture from said combined results.

9. The method of claim 8 wherein one of said parameters being determined is the biomass suspended in said liquid culture.

10. The method of claim 9 wherein a means is provided to compensate the measurement of biomass for the effect of reflecting objects within the liquid culture other than cells or microorganisms.

11. The method of claim 7 wherein at least one of the parameters is used to control at least one process variable that affects the growth of said cells or microorganisms.

12. The method of claim 1 wherein the accuracy of said parameter determination is improved by at least one of:

a) influencing the intensity of radiation emitted from at least one of said sources to bring at least one of said signals within some optimum range;

b) influencing the amplification of the signal collected from at least one of said detectors to bring at least one of said signals within some optimum range.

13. The method of claim 1 wherein step (a.) is accomplished by immersing a probe within said medium.

14. The method of claim 1 wherein step (a.) is accomplished by mounting a probe externally to a container that holds said medium, said container providing a window into said medium that is substantially transparent to the radiation emitted by said sources.

15. The method of claim 14 wherein the influence of the thickness of said window on the determined value of said parameters is reduced by including at least one of the following:

a) at least one source which emits substantially collimated radiation,

b) substantial collimation of the radiation emitted by at least one of said sources,

c) at least one detector which preferentially detects collimated radiation,

d) substantial collimation of the radiation impinging upon one of said detectors, and

e) mounting said probe a variable distance from the surface of said window.

16. The method of claim 14 wherein specular reflection by said window from said sources to said detectors is reduced by means of at least one of the following:

a) at least one source which emits substantially collimated radiation,

b) substantial collimation of the radiation emitted by at least one of said sources,

c) at least one detector which preferentially detects collimated radiation,

d) substantial collimation of the radiation impinging upon one of said detectors, and

e) mounting said probe a variable distance from the surface of said window.

17. The method of claim 1 wherein the temporal waveform of radiation emitted by each of said sources is distinctly chosen, whereby the contributions to any of said signals due to any of said sources can be separated.

18. The method of claim 1 wherein the influence of background radiation on said detected signals is reduced by at least one of the following:

a) measuring said signals with said sources turned off, and subtracting these from said signals measured with said sources turned on,

b) controlling the temporal waveform of radiation emitted by each of said sources in order to produce signal waveforms that can be distinguished from the signal waveforms caused by said background radiation,

c) placing filters in front of said detectors whose transmittance is substantially less for said background radiation than for radiation originating from said sources.

19. The method of claim 1 wherein said radiation sources include at least one source emitting radiation within the visible to near infrared wavelength regions.

20. The method of claim 19 wherein said radiation sources include at least one additional source emitting radiation within the millimeter to microwave wavelength regions.

21. The method of claim 20 wherein said medium contains at least two particle types differing in relative size or other properties that affect their interaction with radiation, and wherein said parameter being determined is the concentration of at least one of these particle types.

22. The method of claim 1 wherein said sources include sources emitting radiation in at least two different regions of the electromagnetic spectrum.

23. The method of claim 22 wherein the different emission wavelengths of said sources are chosen such that at least one of said emission wavelengths lies substantially within a wavelength region of radiation absorption by a component of the medium, and at least one additional emission wavelength lies substantially outside of wavelength regions of radiation absorption by said component of the medium.

24. The method of claim 23 wherein said component is water and wherein the average path length of radiation traveled in the medium is one of said parameters being determined.

25. The method of claim 24 wherein the average path length of radiation traveled in the medium is used to determine the biomass present in the medium.

26. A method of determining the concentration of at least one type of particle in a medium which comprises the steps of:

a) passing electromagnetic or acoustic radiation originating from each of a plurality of sources through said medium to a plurality of detectors;

b) measuring a plurality of signals corresponding to the portion of radiation detected by each of said detectors that originated from each of said sources;

c) selecting signals from a group consisting of all of said signals, and combining the selected signals in a manner that, compared to said signals considered separately, improves the linearity of the combined result to changes in the logarithm of particle concentration;

wherein the selection of signals and said combining of the selected signals is carried out at least once, whereby at least one said combined result is produced; and

d) relating at least one of said combined results to said concentration of at least one type of particle.

27. The method of claim 26 wherein, compared to said signals considered separately, said combined result has substantially reduced the sensitivity to all of the following factors:

intensity of said radiation sources,

sensitivity of said detectors,

coupling efficiency of radiation from said radiation sources into said medium, and

coupling efficiency of radiation from said medium to said detectors.

28. The method of claim 26 wherein step (a.) is accomplished by mounting a probe externally to a container that holds said medium, said container providing a window into said medium that is substantially transparent to the radiation emitted by said sources.

29. The method of claim 28 wherein the influence of the thickness of said window on the determined value of said parameters is reduced by including at least one of the following:

a) at least one source which emits substantially collimated radiation,

b) substantial collimation of the radiation emitted by at least one of said sources,

c) at least one detector which preferentially detects collimated radiation,

d) substantial collimation of the radiation impinging upon one of said detectors, and

e) a means of mounting said probe a variable distance from the surface of said window.

30. A method of determining the concentration of at least one type of particle in a medium which comprises the steps of:

a) passing electromagnetic or acoustic radiation originating from each of a plurality of sources through said medium to a plurality of detectors;

b) measuring a plurality of signals corresponding to the portion of radiation detected by each of said detectors that originated from each of said sources;

c) selecting signals from a group consisting of all of said signals, and combining the selected signals in a manner that, compared to said signals considered separately, increases the dynamic range over which particle concentration can be measured;

wherein the selection of signals and said combining of the selected signals is carried out at least once, whereby at least one said combined result is produced; and

d) relating at least one of said combined results to said concentration of at least one type of particle.

31. The method of claim 30 wherein, compared to said signals considered separately, said combined result has substantially reduced the sensitivity to all of the following factors:

intensity of said radiation sources,

sensitivity of said detectors,

coupling efficiency of radiation from said radiation sources into said medium, and

coupling efficiency of radiation from said medium to said detectors.

32. The method of claim 30 wherein step (a.) is accomplished by mounting a probe externally to a container that holds said medium, said container providing a window into said medium that is substantially transparent to the radiation emitted by said sources.

33. The method of claim 32 wherein the influence of the thickness of said window on the determined value of said parameters is reduced by including at least one of the following:

a) at least one source which emits substantially collimated radiation,

b) substantial collimation of the radiation emitted by at least one of said sources,

c) at least one detector which preferentially detects collimated radiation,

d) substantial collimation of the radiation impinging upon one of said detectors, and

e) a means of mounting said probe a variable distance from the surface of said window.

34. A device for determining at least one parameter of a medium comprising:

a) a probe comprising a plurality of radiation sources that pass radiation through said medium to a plurality of detectors;

b) a controller for controlling said radiation sources, and measuring a plurality of signals corresponding to the portion of radiation detected by each of said detectors that originated from each of said radiation sources;

c) a processor for selecting signals from a group consisting of all of said signals, and combining the selected signals in a manner that substantially reduces the sensitivity of the combined result to all of the following factors as compared to said signals considered separately;

intensity of said sources,

sensitivity of said detectors,

coupling efficiency of radiation from said sources into said medium, and

coupling efficiency of said radiation from said medium to said detectors;

wherein said selected signals comprise the signals collected from a plurality of said detectors, each detecting radiation that originated from a plurality of said sources, the separations between said sources and said detectors including at least three unique distances;

wherein the selection of signals and said combining of the selected signals is carried out at least once whereby at least one said combined result is produced; and

relating at least one of said combined results to said at least one parameter of the medium.

35. The device of claim 34 wherein all of said sources and all of said detectors are stationary relative to each other.

36. The device of claim 34 wherein said radiation sources are each substantially monochromatic.

37. The device of claim 36 wherein said plurality of sources emit radiation of substantially identical wavelength.

38. The device of claim 34 wherein said sources and said detectors are arranged such that substantially only scattered radiation is detected by said detectors.

39. The device of claim 34 wherein said at least one parameter being determined is related to at least one of the concentration of at least one type of particle suspended in said medium, the average size of particles suspended in said medium, the size distribution of particles suspended in said medium, the chemical composition of particles suspended in said medium, the shape of particles suspended in said medium, and the chemical composition of said medium.

40. The device of claim 39 wherein said medium is a liquid culture containing a suspension of cells or microorganisms.

41. The device of claim 40 wherein at least one of the parameters is used to control at least one process variable that affects the growth of said cells or microorganisms.

42. The device of claim 34 wherein the accuracy of said parameter determination is improved by at least one of:

a) influencing the intensity of radiation emitted from at least one of said sources to bring at least one of said signals within some optimum range;

b) influencing the amplification of the signal collected from at least one of said detectors to bring at least one of said signals within some optimum range.

43. The device of claim 34 wherein said probe is immersed within said medium.

44. The device of claim 34 wherein said probe is mounted externally to a container that holds said medium, said container providing a window into said medium that is substantially transparent to the radiation emitted by said sources.

45. The device of claim 44 wherein the influence of the thickness of said window on the determined value of said parameters is reduced by including at least one of the following:

a) at least one source which emits substantially collimated radiation,

b) substantial collimation of the radiation emitted by at least one of said sources,

c) at least one detector which preferentially detects collimated radiation,

d) substantial collimation of the radiation impinging upon one of said detectors, and

e) a means of mounting said probe a variable distance from the surface of said window.

46. The device of claim 44 wherein specular reflection by said window from said sources to said detectors is reduced by means of at least one of the following:

a) at least one source which emits substantially collimated radiation,

b) substantial collimation of the radiation emitted by at least one of said sources,

c) at least one detector which preferentially detects collimated radiation,

d) substantial collimation of the radiation impinging upon one of said detectors, and

e) mounting said probe a variable distance from the surface of said window.

47. The device of claim 34 wherein the temporal waveform of radiation emitted by each of said sources is distinctly chosen, whereby the contributions to any of said signals due to any of said sources can be separated.

48. The device of claim 34 wherein the influence of background radiation on said detected signals is reduced by at least one of the following:

a) measuring said signals with said sources turned off, and subtracting these from said signals measured with said sources turned on,

b) controlling the temporal waveform of radiation emitted by each of said sources in order to produce signal waveforms that can be distinguished from the signal waveforms caused by said background radiation,

c) placing filters in front of said detectors whose transmittance is substantially less for said background radiation than for radiation originating from said sources.