Apparatus for performing optical measurements on blood culture bottles

• US 7,643,134 B2
• Filed: 08/16/2005
• Issued: 01/05/2010
• Est. Priority Date: 08/19/2004
• Status: Active Grant

• Current Assignee: Becton, Dickinson & Co
• Original Assignee: Becton, Dickinson & Co
• Inventors: Berndt, Klaus W.
• Primary Examiner(s): Punnoose; Roy
• Application Number:
  US11/573,673
• Publication Number:
  US 20080259313A1
• Time in Patent Office: 1,603 Days
• Field of Search: 356/39, 356/239.4, 356/239.5, 356/239.6, 382/133, 382/134
• US Class Current: 356/39
• CPC Class Codes: G01N 21/51 inside a container, e.g. in an ampoule G01N21/53 takes precedence

Abstract

An apparatus and method for rapidly distinguishing positive blood cultures from negative bloodcultures in sealable containers, and for determining the combination of blood volume and hematocrit in a sealable container. The apparatus comprises an optical source for illuminating the culture with a light beam under an oblique angle to generate an asymmetric spatial distribution of backscattered light, which is imaged onto an imaging detector connected to a data analyzer.

Claims

1. A system for performing optical measurements on a container comprising a liquid, the system comprising:

an optical source adapted to direct a light beam onto a wall of the container at a first location, wherein the light beam deviates from a normal to the container wall at the first location by a first angle, generating an asymmetric spatial distribution of backscattered light from the liquid near the first location;

an imaging device adapted to image the asymmetric spatial distribution of backscattered light wherein the imaging device is located to substantially avoid imaging the portions of the light beam reflected by outer and inner bottle wall surfaces;

an imaging detector adapted to record at least parts of the imaged asymmetric spatial distribution of backscattered light; and

a data analyzing system connected to the imaging detector adapted to extract analytical features of the asymmetric spatial distribution of backscattered light.

2. A system according to claim 1, further comprising a cylindrical container comprising a liquid.

3. A system according to claim 2, wherein the container is a blood culture bottle comprising blood and growth media.

4. A system according to claim 3, wherein the data analyzing system is further adapted to provide data to determine at least one parameter selected from the group consisting of the presence or absence of a developed microorganism population, the volume of the liquid sample, and the hematocrit value of the liquid sample.

5. A system according to claim 4, wherein the data analyzing system comprises synchronous detection devices.

6. A system according to claim 2, wherein the optical source is adapted to produce the light beam to propagate within a plane substantially perpendicular or substantially parallel to the container'"'"'s axis of symmetry.

7. A system according to claim 2, wherein the first location is on a cylindrical part of the container.

8. A system according to claim 2, wherein the first location is on a non-cylindrical part of the container.

9. A system according to claim 8, wherein the first location is on the bottom of the container.

10. A system according to claim 1, wherein the optical source is selected from the group consisting of a laser and a light emitting diode.

11. A system according to claim 1, wherein the optical source is adapted to emit light with a wavelength of about 500 to about 1500 nm.

12. A system according to claim 11, wherein the optical source is adapted to emit light with a wavelength of about 640 to about 720 nm.

13. A system according to claim 1, wherein the optical source is adapted to modulate the intensity of the light beam.

14. A system according to claim 1, wherein the first angle is between about zero and about 90 degrees.

15. A system according to claim 14, wherein the first angle is between about 25 and about 45 degrees.

16. A system according to claim 15, wherein the first angle is about 35 degrees.

17. A system according to claim 1, wherein the imaging device is selected from the group consisting of a lens and an array of optical fibers.

18. A system according to claim 1, wherein the imaging device is adapted to move along an axis to record at least parts of the imaged asymmetrical spatial distribution of backscattered light.

19. A system according to claim 1, wherein the imaging detector is a photodetector.

20. A system according to claim 19, wherein the photodetector is selected from the group consisting of an opto-electronic camera, a digital 2D camera, a 2D CCD array and a linear CCD array.

21. A system according to claim 19, wherein the photodetector is adapted to move along an axis to record at least parts of the imaged asymmetrical spatial distribution of backscattered light.

22. A method for performing optical measurements on a container comprising:

providing a container comprising a liquid sample;

directing a light beam onto an optically transparent wall of the container at a first location, such that the light beam deviates from a normal to the container wall at the first location by a first angle, generating an asymmetric spatial distribution of backscattered light from the liquid sample in the container near the first location;

detecting at least a portion of the asymmetric spatial distribution of backscattered light while substantially avoiding detecting portions of the light beam reflected by outer and inner container wall surfaces; and

extracting analytical features from the asymmetric spatial distribution of backscattered light.

23. A method according to claim 22, wherein the light beam is directed from an optical source selected from the group consisting of a laser and a light emitting diode.

24. A method according to claim 23, wherein the optical source is adapted to provide an intensity-modulated light beam.

25. A method according to claim 22, further comprising:

directing the light from the source through a lens, to focus the beam onto the wall of the container.

26. A method according to claim 22, wherein the step of directing the light beam comprises:

emitting a light beam at a wavelength of about 500 nm to about 1500 nm.

27. A method according to claim 26, wherein the wavelength is about 640 nm to about 720 nm.

28. A method according to claim 22, wherein the container is a cylindrical bottle, and wherein the light beam propagates within a plane substantially perpendicular or substantially parallel to the bottle'"'"'s axis of symmetry.

29. A method according to claim 22, further comprising the step of:

imaging the asymmetric spatial distribution through an imaging device.

30. A method according to claim 29, wherein the imaging device is selected from a lens and an array of optical fibers.

31. A method according to claim 29, wherein the detecting step comprises detecting at least parts of the imaged spatial distribution of backscattered light with a photodetector.

32. A method according to claim 31, wherein the photodetector is selected from the group consisting of an opto-electronic camera, a digital 2D camera, a 2D CCD array and a linear CCD array.

33. A method according to claim 22, wherein the liquid sample comprises blood and growth media, and wherein the step of extracting analytical features from the asymmetric spatial distribution of backscattered light comprises:

analyzing data to determine at least one parameter selected from the group consisting of the presence or absence of a developed microorganism population, the volume of the liquid sample, and the hematocrit value of the liquid sample.

34. A method according to claim 33, wherein the analyzing of data is performed by a data analyzing system connected to an imaging detector, wherein the data analyzing system is adapted to record at least parts of the imaged spatial distribution of backscattered light.

35. A method according to claim 34, wherein the data analyzing system comprises synchronous detection devices.

36. A method according to claim 22, wherein the first angle is between about zero and about 90 degrees.

37. A method according to claim 36, wherein the first angle is between about 25 and about 45 degrees.

38. A method according to claim 37, wherein the first angle is about 35 degrees.

39. A method according to claim 22, wherein the container is cylindrical, and wherein the first location is on a cylindrical part of the container.

40. A method according to claim 22, wherein the container is cylindrical, and wherein the first location is on a non-cylindrical part of the container.

41. A method according to claim 40, wherein the first location is on the bottom of the container.

42. A method according to claim 22, further comprising the step of:

moving the imaging detector along an axis to record parts of the asymmetrical spatial distribution of backscattered light.

43. A method comprising the steps of:

providing a container comprising a sample that comprises growth media and blood;

directing a light beam onto an optically transparent wall area of the container at a first location, such that the light beam deviates from a normal to the container wall at the location by a first angle, generating an asymmetric spatial distribution of backscattered light from the mixture of growth media and blood in the container near the first location;

detecting at least a portion of the asymmetric spatial distribution of backscattered light from the mixture of growth media and blood in the container near the first location with a detecting device while substantially avoiding detecting portions of the light beam reflected by outer and inner container wall surfaces;

extracting analytical features from the asymmetric spatial distribution of backscattered light; and

determining the volume and the hematocrit value of the sample in the sealable container by comparing the extracted analytical features or data generated therefrom with calibration information.

44. A method according to claim 43 further comprising the step of imaging the asymmetric spatial distribution through an imaging device.

45. A method according to claim 44, wherein the imaging is performed into a plane.

46. A method according to claim 43, wherein the step of extracting comprises:

using a data analyzing system connected to the detecting device, wherein the detecting device comprises a photodetector, and wherein the data analyzer system is adapted to record at least parts of the asymmetric spatial distribution of backscattered light and is further adapted to extract the analytical features from the recorded asymmetric spatial distribution of backscattered light.

47. A method according to claim 43 wherein the step of extracting comprises:

extracting one or more features selected from the group consisting of a maximum recorded backscattering intensity (IMAX) analytical feature, a backscattering intensity at the light impact point (IALIP) analytical feature, a full-width-at-half-IMAX (FWHM) analytical feature, and a slope of the slowly decaying flank of the asymmetric spatial distribution of backscattered light (SL) analytical feature.

48. A method according to claim 47 wherein the extracted analytical features are extracted from the asymmetric spatial distribution of backscattered light as measured along the X-axis, wherein the X-axis is oriented along the container wall within a plane comprising the light beam, and wherein the extracted analytical features comprise a full-width-at-half-IMAX in the X-axis (FWHMX) and a slope in the X-axis (SLX).

49. A method according to claim 48, wherein the slope SLX is an inverse of the distance along the X-axis of a recorded light distribution over which the intensity decreases by a first factor.

50. A method according to claim 48, further comprising the step of extracting the full-width-at-half-IALIP (FWHMX*) as measured along the X-axis.

51. A method according to claim 47, wherein the extracted analytical features are extracted from the asymmetric spatial distribution of backscattered light as measured along the Y-axis, wherein the Y-axis is oriented along the container wall within a plane perpendicular to the container wall;

wherein the asymmetrical spatial distribution comprises the area of IMAX, but extending perpendicular to the X-axis; and

wherein the extracted analytical features comprise a full-width-at-half-IMAX in the Y-axis (FWHMY) and a slope in the Y-axis (SLY).

52. A method according to claim 51, wherein the slope SLY is an inverse of a distance along the Y-axis of a recorded light distribution over which the intensity decreases by a second factor.

53. A method according to claim 51, further comprising the step of extracting a slope measured along a Y-direction parallel to the Y-axis in a plane comprising the area of IALIP.

54. A method according to claim 51, further comprising the step of extracting the width FWHMY*;

and wherein FWHMY* is a full-width-at-half-IALIP and is measured along a Y-direction parallel to the Y-axis in a plane comprising the area of IALIP.

55. A method according to claim 51, wherein a slope SLY* is an inverse of the distance along the Y-axis of a recorded light distribution over which the intensity decreases by a third factor.

56. A method according to claim 43, wherein the step of extracting comprises:

accumulating the number of pixels in a two-dimensional image of the asymmetrical spatial distribution of backscattered light having a pixel intensity that exceeds a first threshold.

57. A method according to claim 43, wherein the step of extracting comprises:

summing substantially all pixel intensities in a two-dimensional image of the asymmetrical spatial distribution of backscattered light.

58. A method according to claim 43, wherein the step of determining comprises:

generating a first processed analytical feature by combining two or more of the extracted analytical features; and

determining the combination of the volume and the hematocrit value of the blood culture based on the first processed analytical feature.

59. A method according to claim 43, wherein the step of determining comprises calculating the mathematical product of the volume and the hematocrit value.

60. A method comprising the steps of:

providing a container comprising a sample that comprises growth media and blood;

directing a light beam onto an optically transparent wall area of the container at a first location, such that the light beam deviates from a normal to the container wall at the first location by a first angle, generating an asymmetric spatial distribution of backscattered light from the mixture of growth media and blood in the container near the first location;

detecting at least a portion of the asymmetric spatial distribution of backscattered light from the mixture of growth media and blood in the sealable container near the first location with a detecting device while substantially avoiding detecting portions of the light beams reflected by outer and inner container wall surfaces;

extracting analytical features from the asymmetric spatial distribution of backscattered light; and

determining a presence or absence of a developed micro-organism population within the container by comparing the extracted analytical features or data generated therefrom with calibration information.

61. A method according to claim 60, further comprising the step of imaging the asymmetric spatial distribution through an imaging device.

62. A method according to claim 61, wherein the imaging is performed into a plane.

63. A method according to claim 61, wherein the step of determining comprises:

generating a first processed analytical feature by combining two or more of the extracted analytical features;

comparing the first processed analytical feature with a first constant, and determining that the blood culture bottle is absent of developed micro-organisms if the first processed analytical feature is greater than the first constant; and

determining that the presence of developed micro-organisms is likely in the blood culture bottle if the first processed analytical feature is less than the first constant.

64. A method according to claim 63, further comprising:

comparing the first processed analytical feature with a second constant if it has been determined that the first processed analytical feature is less than the first constant.

65. A method according to claim 63, wherein the first processed analytical feature is generated according to the following equation:

66. A method according to claim 63, wherein the first constant is about 2.5 and the second constant is about 1.3.

67. A method according to claim 60, wherein the step of extracting comprises:

using a data analyzing system connected to the detecting device;

wherein the detecting device comprises a photodetector; and

wherein the data analyzing system is adapted to record at least parts of the asymmetric spatial distribution of backscattered light and is further adapted to extract analytical features from the recorded asymmetric spatial distribution of backscattered light.

68. A method according to claim 60, wherein the step of extracting comprises:

extracting one or more features selected from the group consisting of a maximum recorded backscattering intensity (IMAX) analytical feature, a backscattering intensity at the light impact point (IALIP) analytical feature, a full-width-at-half-IMAX (FWHM) analytical feature, and a slope of the slowly decaying flank of the asymmetric spatial distribution of backscattered light (SL) analytical feature.

69. A method according to claim 68, wherein the extracted analytical features are extracted from the asymmetric spatial distribution of backscattered light as measured along the X-axis, wherein the X-axis is oriented along the container wall within a plane comprising the light beam;

and wherein the extracted analytical features comprise a full-width-at-half-IMAX in the X-axis (FWHMX) and a slope in the X-axis (SLX).

70. A method according to claim 69, wherein the slope SLX is an inverse of a distance along the X-axis of a recorded light distribution over which the intensity decreases by a first factor.

71. A method according to claim 69, further comprising the step of extracting a full-width-at-half-IALIP (FWHMX*) as measured along the X-axis.

72. A method according to claim 68, wherein the extracted analytical features are extracted from the asymmetric spatial distribution of backscattered light as measured along the Y-axis, wherein the Y-axis is oriented along the bottle wall within a plane perpendicular to the bottle wall;

wherein the asymmetric spatial distribution comprises the area of IMAX, but extending perpendicular to the X-axis; and

wherein the extracted analytical features comprise a full-width-at-half-IMAX in the Y-axis (FWHMY) and a slope in the Y-axis (SLY).

73. A method according to claim 72, wherein the slope SLY is an inverse of a distance along the Y-axis of a recorded light distribution over which the intensity decreases by a second factor.

74. A method according to claim 72, further comprising the step of extracting a slope measured along a Y-direction parallel to the Y-axis in a plane comprising the area of IALIP.

75. A method according to claim 72, further comprising the step of extracting is a width FWHMY*;

and wherein FWHMY* is a full-width-at-half-IALIP and is measured along a Y-direction parallel to the Y-axis in a plane comprising the area of IALIP.

76. A method according to claim 72, wherein a slope SLY* is an inverse of a distance along the Y-axis of a recorded light distribution over which the intensity decreases by a third factor.

77. A method according to claim 60, wherein the step of extracting comprises:

accumulating a number of pixels in a two-dimensional image of the asymmetrical spatial distribution of backscattered light having a pixel intensity that exceeds a first threshold.

78. A method according to claim 60, wherein the step of extracting comprises:

summing substantially all pixel intensities in a two-dimensional image of the asymmetrical spatial distribution of backscattered light.

79. A method according to claim 60, wherein the step of determining comprises:

plotting, or performing a calculation indicative of such plotting, two or more of the extracted analytical features of the container on a two-dimensional graph along with the identical extracted analytical features from a calibration set; and

verifying the presence or absence of the developed micro-organisms based on the proximity of the plotted extracted analytical features of the container with that of the plotted extracted analytical features of the control blood culture bottle.

80. A method comprising the steps of:

providing a container comprising a sample that comprises growth media and blood;

directing a light beam onto an optically transparent wall area of the container at a first location, such that the light beam deviates from a normal to the container wall at the first location by a first angle, generating an asymmetric spatial distribution of backscattered light from the mixture of growth media and blood in the container near the first location;

detecting at least portions of the asymmetric spatial distribution of backscattered light from the mixture of growth media and blood in the container near the first location with a detecting device while substantially avoiding detecting portions of the light beams reflected by outer and inner container wall surfaces;

extracting analytical features from the asymmetric spatial distribution of backscattered light; and

determining the presence of a developed micro-organism population within the blood culture bottle by comparing the generated data with calibration information by repeating the steps of directing, detecting, extracting and determining one or more times.

81. A method according to claim 80, wherein the repeating is performed at intervals of about ten minutes.

82. A method according to claim 81, wherein the repeating is performed at the intervals of about ten minutes, for a period of about five days.