Detecting microorganisms in blood utilizing physical and chemical changes in blood

• US 7,952,693 B2
• Filed: 11/03/2008
• Issued: 05/31/2011
• Est. Priority Date: 11/06/2007
• Status: Expired due to Fees

• Current Assignee: Claro Scientific, LLC
• Original Assignee: Claro Scientific, LLC
• Inventors: Smith, Jennifer M., Huffman, Debra, Garcia-Rubio, Luis H., LeParc, German F., Serebrennikova, Yulia M.
• Primary Examiner(s): STAFIRA, MICHAEL PATRICK
• Application Number:
  US12/263,807
• Publication Number:
  US 20090115996A1
• Time in Patent Office: 939 Days
• Field of Search: 356 39- 42
• US Class Current: 356/39
• CPC Class Codes: C12Q 1/04 Determining presence or kind of microorganism; Use of selective media for testing antibiotics or bacteriocides; Compositions containing a chemical indicator therefor C12Q1/6897 takes precedence
• CPC Class Codes: G01N 2021/3144 for oxymetry
• CPC Class Codes: G01N 2021/3155 Measuring in two spectral ranges, e.g. UV and visible
• CPC Class Codes: G01N 2021/4747 Concentric bundles
• CPC Class Codes: G01N 21/31 Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry G01N21/72 takes precedence
• CPC Class Codes: G01N 21/474 Details of optical heads therefor, e.g. using optical fibres
• CPC Class Codes: G01N 21/8507 Probe photometers, i.e. with optical measuring part dipped into fluid sample

Abstract

An approach to detecting microorganisms in blood uses the changes of hemoglobin and the physical and chemical properties of blood to detect the presence of microorganisms in blood. Spectrophotometric measurements are taken several wavelengths across the UV-Vis-NIR portion of the electromagnetic spectrum, and a deconvolution is performed quantitatively to interpret distinct spectral characteristics of blood enabling the detection of microorganisms.

Claims

1. A method for assessing the presence of microorganisms in blood, comprising:

(a) emitting electromagnetic radiation into at least one blood sample;

(b) measuring wavelength-dependent spectra of reemitted electromagnetic radiation from said blood sample, wherein said measuring is of one or both of transmittance signals and reflectance signals; and

then

(c) deconvoluting said spectra to determine hemoglobin composition and a partial pressure value associated with at least one of oxygen and carbon dioxide, respectively, thereby to assess the presence or absence of microorganisms in said blood sample.

2. A method according to claim 1, wherein said spectra are quantitatively interpreted in terms of the physical and chemical properties of blood.

3. A method according to claim 1, wherein said deconvoluting determines the presence or absence of multiple types of microorganisms in blood.

4. A method according to claim 1, wherein said spectra can be measured as a function of time or at any discrete time point.

5. A method according to claim 1, wherein said measuring is of signals selected from a group consisting of:

diffuse transmittance signals;

diffuse reflectance signals;

angular transmittance signals; and

angular reflectance signals.

6. A method according to claim 1, wherein said re-emitted electromagnetic radiation comprises wavelengths in the ultraviolet range, the visible range, and/or the near-infrared range.

7. A method according to claim 1, wherein said deconvoluting step quantifies the physical properties of blood components.

8. A method according to claim 1, wherein said deconvoluting step (i) comprises at least one of linear or non-linear models and (ii) resolves said spectra into a particle-related physical characterization.

9. A method according to claim 1, wherein said deconvoluting step identifies and quantifies at least one form of hemoglobin.

10. A method according to claim 1, wherein said assessing comprises detecting the presence or absence of microorganisms.

11. A method according to claim 1, further comprising extracting identifying characteristics of the microorganisms from the spectra, wherein said identifying characteristics are selected from a group consisting of kinetic growth parameters and physical characteristics.

12. A method according to claim 11, wherein the growth parameters include doubling times and respiration rates and the physical characteristics include size and shape.

18. The method of claim 1, wherein the presence or absence of microorganisms is assessed in accordance with changes in properties of blood induced by one or more microbial metabolites.

19. A method according to claim 18, further comprising identifying at least one microorganism.

13. An apparatus configured to assess the presence of microorganisms, comprising:

(a) a spectrometer configured to measure spectra of a plurality of wavelengths emitting from a sample of blood at a plurality of points in time;

(b) a transmission cell and/or a reflectance probe operably connected to said spectrometer; and

(c) a computer that (i) is connected operationally to said spectrometer and (ii) is configured to perform deconvolution on said spectra, thereby to assess the presence or absence of microorganisms in said sample by conducting an operation selected from a group of operations consisting of;

determining hemoglobin composition and a partial pressure value associated with at least one of oxygen and carbon dioxide, respectively; and

monitoring changes in hemoglobin composition in said sample.

14. An apparatus according to claim 13, wherein said deconvolution (i) comprises at least one of linear or non-linear regression techniques and (ii) can resolve said spectra into at least one form of hemoglobin.

15. An apparatus according to claim 13, wherein at least one of a reflectance probe and a transmission cell are operably connected to said spectrometer.

16. An apparatus according to claim 13, wherein said spectrometer includes a diode array.

17. An apparatus according to claim 15, wherein a reflectance probe is operably connected to said spectrometer and is configured to operate without making contact with a container in which said sample is located.

20. A method of assessing the presence of at least one microorganism in blood, comprising:

(a) emitting electromagnetic radiation into at least one blood sample in a thermodynamically closed container;

(b) measuring wavelength-dependent spectra of re-emitted electromagnetic radiation from said blood sample to obtain measured spectral values, wherein said measuring is of one or both of transmittance signals and reflectance signals;

(c) measuring partial pressure values associated with at least one of oxygen and carbon dioxide in a headspace above said blood sample to obtain measured partial pressure values;

(d) deconvoluting said spectra to determine hemoglobin composition in accordance with said measured spectral values and said measured partial pressure values; and

(e) assessing the presence or absence of microorganisms in accordance with said deconvoluting.

21. A method according to claim 20, wherein said spectra are quantitatively interpreted in terms of the physical and chemical properties of blood.

22. A method according to claim 20, wherein said deconvoluting determines the presence or absence of multiple types of microorganisms in blood.

23. A method according to claim 20, wherein said measuring is of signals selected from a group consisting of:

diffuse transmittance signals;

diffuse reflectance signals;

angular transmittance signals; and

angular reflectance signals.

24. A method according to claim 20, wherein said re-emitted electromagnetic radiation comprises wavelengths in the ultraviolet range, the visible range, and/or the near-infrared range.

25. A method according to claim 20, wherein said deconvoluting step quantifies the physical properties of blood components.

26. A method according to claim 20, wherein said deconvoluting step (i) comprises at least one of linear or non-linear models and (ii) resolves said spectra into a particle-related physical characterization.

27. A method according to claim 20, wherein said deconvoluting step identifies and quantifies at least one form of hemoglobin.

28. A method according to claim 20, wherein said assessing comprises detecting the presence or absence of microorganisms.

29. A method according to claim 20, further comprising extracting identifying characteristics of the microorganisms from the spectra, wherein said identifying characteristics are selected from a group consisting of kinetic growth parameters and physical characteristics.

30. A method according to claim 29, wherein

the growth parameters include doubling times and respiration rates;

and

the physical characteristics include size and shape.

31. The method of claim 20, wherein the presence or absence of microorganisms is assessed in accordance with changes in properties of blood induced by one or more microbial metabolites.

32. A method according to claim 31, further comprising identifying at least one microorganism.

33. A method for assessing the presence of microorganisms in blood, comprising:

(a) emitting electromagnetic radiation into at least one blood sample;

(b) measuring wavelength-dependent spectra of reemitted electromagnetic radiation from said blood sample at multiple points in time, wherein said measuring is of one or both of transmittance signals and reflectance signals; and

then

(c) deconvoluting said spectra to monitor changes in hemoglobin composition within said blood sample, thereby to assess the presence or absence of microorganisms in said blood sample.

34. A method according to claim 33, wherein said spectra are quantitatively interpreted in terms of the physical and chemical properties of blood.

35. A method according to claim 33, wherein said deconvoluting determines the presence or absence of multiple types of microorganisms in blood.

36. A method according to claim 33, wherein said measuring is of signals selected from a group consisting of:

diffuse transmittance signals;

diffuse reflectance signals;

angular transmittance signals; and

angular reflectance signals.

37. A method according to claim 33, wherein said re-emitted electromagnetic radiation comprises wavelengths in the ultraviolet range, the visible range, and/or the near-infrared range.

38. A method according to claim 33, wherein said deconvoluting step quantifies the physical properties of blood components.

39. A method according to claim 33, wherein said deconvoluting step (i) comprises at least one of linear or non-linear models and (ii) resolves said spectra into a particle-related physical characterization.

40. A method according to claim 33, wherein said deconvoluting step identifies and quantifies at least one form of hemoglobin.

41. A method according to claim 33, wherein said assessing comprises detecting the presence or absence of microorganisms.

42. A method according to claim 33, further comprising extracting identifying characteristics of the microorganisms from the spectra, wherein said identifying characteristics are selected from a group consisting of kinetic growth parameters and physical characteristics.

43. A method according to claim 42, wherein (A) the growth parameters include doubling times and respiration rates and (B) the physical characteristics include size and shape.

44. A method according to claim 33, wherein partial pressure values associated with at least one of oxygen and carbon dioxide are determined from the deconvoluted spectra.

45. The method of claim 33, wherein the presence or absence of microorganisms is assessed in accordance with changes in properties of blood induced by one or more microbial metabolites.

46. A method according to claim 33, further comprising identifying at least one microorganism.