Monitoring and control system for blood processing

• US 20050051466A1
• Filed: 07/01/2004
• Published: 03/10/2005
• Est. Priority Date: 07/02/2003
• Status: Active Grant

• Current Assignee: Terumo BCT, Inc. (Terumo Corporation)
• Original Assignee: Caridianbct Biotechnologies LLC (Baxter International Inc.)
• Inventors: Kolenbrander, Jeremy P., Steward, Jeffrey A., Ladtkow, James R., Carter, Lee F., Scibona, Joseph A., Fletcher, Chris
• Granted Patent: US 7,422,693 B2
• Time in Patent Office: Days
• US Class Current: 210/94
• CPC Class Codes: A61M 1/3693 using separation based on different densities of components, e.g. centrifuging
• CPC Class Codes: B04B 13/00 Control arrangements specially designed for centrifuges; Programme control of centrifuges control arrangements for feed, charge, or discharge B04B11/00
• CPC Class Codes: B04B 2013/006 Interface detection or monitoring of separated components
• CPC Class Codes: G01N 15/042 by centrifuging and investigating centrifugates centrifuges per se B04B
• CPC Class Codes: G01N 15/05 in blood
• CPC Class Codes: G01N 2015/047 by static multidetectors

Abstract

The invention relates generally to methods of monitoring and controlling the processing of blood and blood samples, particularly the separation of blood and blood samples into its components. In one aspect, the invention relates to optical methods, devices and device components for measuring two-dimensional distributions of transmitted light intensities, scattered light intensities or both from a separation chamber of a density centrifuge. In embodiment, two-dimensional distributions of transmitted light intensities, scattered light intensities or both measured by the methods of the present invention comprise images of a separation chamber or component thereof, such as an optical cell of a separation chamber. In another aspect, the present invention relates to multifunctional monitoring and control systems for blood processing, particularly blood processing via density centrifugation. Feedback control systems are provided wherein two-dimensional distributions of transmitted light intensities, scattered light intensities or both are measured, processed in real time and are used as the basis of output signals for controlling blood processing. In another aspect, optical cells and methods of using optical cells for monitoring and control blood processing are provided.

Claims

1. A monitoring system for a density centrifuge blood processing system for separating fluid components and having a separation chamber rotating about a central rotation axis, comprising:

a light source in optical communication with said density centrifuge blood processing system for providing an incident light beam for illuminating an observation region on said density centrifuge blood processing system, thereby generating light transmitted, scattered or both from said observation region;

a light collection element in optical communication with said density centrifuge blood processing system for collecting at least a portion of said light transmitted, scattered or both from said observation region and for directing at least a portion of said light transmitted, scattered or both from said observation region onto a two-dimensional detector; and

the two-dimensional detector positioned to receive and detect said light transmitted, scattered or both from said observation region provided by said light collection element, thereby measuring a two-dimensional distribution of the intensities of said light transmitted, scattered or both from said observation region.

2. The system of claim 1 wherein said two-dimensional distribution of the intensities of said light transmitted, scattered or both from said observation region comprises an image of at least a portion of said density centrifuge blood processing system.

3. The system of claim 1 wherein said two-dimensional distribution of the intensities of said light transmitted, scattered or both from said observation region comprises an image of said at least a portion of said separation chamber.

4. The system of claim 1 wherein said two-dimensional distribution of the intensities of said light transmitted, scattered or both from said observation region comprise an image of said at least a portion of an optical cell of said separation chamber.

5. The system of claim 1 wherein at least a portion of said light transmitted, scattered or both from said observation region is light transmitted through the separation chamber.

6. The system of claim 1 wherein at least a portion of said light transmitted, scattered or both from said observation region is light scattered by the separation chamber or materials therein.

7. The system of claim 1 wherein the two-dimensional detector generates an output signal corresponding to said two-dimensional distribution of the intensities of said light transmitted, scattered or both from said observation region.

8. The system of claim 7 further comprising a centrifugation device controller for receiving the output signal generated by the two-dimensional detector and for adjusting an operating parameter of the density centrifuge blood processing system blood processing system, wherein said centrifugation device controller is communication with the two-dimensional detector.

9. The system of claim 7 further comprising a centrifugation device controller for receiving the output signal generated by the two-dimensional detector and for adjusting a plurality of operating parameters of the density centrifuge blood processing system blood processing system, wherein said centrifugation device controller is in communication with the two-dimensional detector.

10. The system of claim 8 wherein said operating parameter is selected from the group consisting of:

a flow rate of a fluid component out of the separation chamber;

a flow rate of a fluid into the separation chamber; and

the rate of rotation of the separation chamber about the central rotation axis.

11. The system of claim 1 wherein the light collection element and two-dimensional detector are provide in fixed positions relative to the density centrifuge blood processing system.

12. The system of claim 1 wherein the light collection element and two-dimensional detector are provided in fixed orientations relative to said density centrifuge blood processing system.

13. The system of claim 1 wherein at least a portion of said observation region is positioned such that a phase boundary between optically differentiable blood components in said separation chamber is viewable by the two-dimensional detector.

14. The system of claim 1 wherein said two-dimensional distribution of the intensities of said light transmitted, scattered or both from said observation region comprises an image of a phase boundary between optically differentiable blood components.

15. The system of claim 1 wherein the image of a phase boundary between optically differentiable blood components provides a measurement of the position of the phase boundary.

16. The system of claim 1 wherein at least a portion of said observation region is positioned such that a separated blood component in said separation chamber is viewable by two-dimensional detector.

17. The system of claim 1 wherein said two-dimensional distribution of the intensities of said light transmitted, scattered or both from said observation region comprises an image of a separated blood component in the separation chamber.

18. The system of claim 17 wherein the image of the separated blood component in the separation chamber provides a measurement of the composition of the separated blood component.

19. The system of claim 17 wherein said separated blood component is selected from the group consisting of:

a white blood cell containing component;

a platelet containing component;

a plasma containing component; and

a red blood cell containing component.

20. The system of claim 1 wherein at least a portion of the observation region is positioned such that an extraction port of the separation chamber is viewable by the two dimensional detector.

21. The system of claim 1 wherein said two-dimensional distribution of the intensities of said light transmitted, scattered or both from said observation region comprises an image of an extraction port of the separation chamber.

22. The system of claim 21 wherein the image of the extraction port of the separation chamber provides a measurement of the composition of cellular components in extraction port.

23. The system of claim 22 wherein said cellular components are selected from the group consisting of:

red blood cells;

white blood cells; and

platelets.

24. The system of claim 21 wherein the image of the extraction port of the separation chamber provides a measurement of the flux of cellular components through the extraction port.

25. The system of claim 1 wherein said two-dimensional distribution of the intensities of said light transmitted, scattered or both from said observation region comprises an image at least one phase boundary between optically differentiable blood components in the separation chamber and at least one extraction port of the separation chamber.

26. The system of claim 25 wherein the measured image provides simultaneous measurements of a position of at least one phase boundary between optically differentiable blood components along said separation axis of said density centrifuge blood processing system and the composition of a blood components in the extraction port of the separation chamber.

27. The system of claim 1 wherein the observation region is positioned such that leakage of fluid in said separation chamber of the separation chamber is viewable by the two-dimensional detector.

28. The system of claim 1 wherein said two-dimensional distribution of the intensities of said light transmitted, scattered or both from said observation region comprises an image of a sample identification marker or kit identification marker corresponding to a blood sample undergoing processing.

29. The system of claim 28 wherein said sample identification marker or kit identification marker comprises a bar code.

30. The system of claim 1 wherein the observation region is positioned such that improper alignment of said separation chamber is detectable by the two dimensional detector.

31. The system of claim 1 wherein the two-dimensional detector is selected from the group consisting of:

a charge coupled device;

a two-dimensional photodiode array;

a two-dimensional photoconductive array;

a two-dimensional pyroelectric array;

a CCD camera; and

a complementary metal oxide semiconductor detector.

32. The system of claim 1 wherein the two-dimensional detector is a monochrome CCD camera.

33. The system of claim 1 wherein the two-dimensional detector is a color CCD camera.

34. The system of claim 1 wherein the light collection element comprises a lens.

35. The system of claim 1 wherein the light collection element comprises a lens system.

36. The system of claim 1 wherein the light collection element comprises a fixed focus lens system.

37. The system of claim 35 wherein the lens system has a selectively adjustable focal length.

38. The system of claim 1 wherein the light collection element has a fixed field of view.

39. The system of claim 1, wherein the light collection element has a selectively adjustable field of view.

40. The system of claim 1 wherein said two-dimensional detector and light collection element are selectively positionable along a detector axis oriented orthogonal to the central rotation axis.

41. The system of claim 1 wherein the light source is selected from the group comprising:

a xenon lamp;

a light emitting diode; and

an array of light emitting diodes;

42. The system of claim 1 wherein the light source is selected from the group comprising:

a white light emitting diode;

blue light-emitting diode;

a red light-emitting diode; and

a green light-emitting diode.

43. The system of claim 1 wherein the light source comprises a parabolic reflector element.

44. The system of claim 1 further comprising an additional light source, wherein said light source illuminates a first side of said separation chamber and said additional light source illuminates a second side of said separation chamber, and wherein said first and second sides are different sides.

45. The system of claim 44 wherein the additional light source is selected from the group comprising:

a xenon lamp;

a light emitting diode; and

an array of light emitting diodes;

46. The system of claim 1 wherein the light source provides an incident light beam comprising visible light.

47. The system of claim 1 wherein the light source provides an incident light beam comprising infrared light.

48. The system of claim 1 wherein the light source provides an incident light beam comprising ultraviolet light.

49. The system of claim 1 wherein the light source provides continuous illumination of the observation region on the separation chamber.

50. The system of claim 1 wherein the light source is capable of being switched on and off in a manner providing pulsed illumination of the observation region on the separation chamber.

51. The system of claim 1 wherein said separation chamber comprises an optical cell.

52. The system of claim 51 wherein said optical cell comprises:

an extraction chamber having a first external optical surface and a second external optical surface, wherein said first and second external optical surfaces of said extraction chamber are opposing planar surfaces; and

an extraction port having a first external optical surface and a second external optical surface, wherein said first and second external optical surfaces of said extraction chamber are opposing planar surfaces;

wherein said first optical surface of said extraction chamber and said first optical surface of said extraction port are both in the depth of field of the light collection element.

53. The system of claim 52 wherein first optical surface of said extraction chamber and said first optical surface of said extraction port are both substantially in the same plane.

54. The system of claim 1 further comprising a calibration marker, wherein said calibration marker is in said observation region.

55. The system of claim 54 wherein the calibration marker is in the depth of field of the light collection element.

56. The system of claim 54 wherein said two-dimensional distribution of the intensities of said light transmitted, scattered or both from said observation region comprises an image of said calibration marker.

57. The system of claim 1 further comprising an additional light collection element and an additional two-dimensional detector, wherein light transmitted, scattered or both from an additional observation region is collected by the additional light collection element and detected by the additional two-dimensional detector.

58. The system of claim 57 wherein said additional two-dimensional detector measures a two-dimensional distribution of the intensities of said light transmitted, scattered or both from said additional observation region.

59. The system of claim 1 wherein said fluid components are blood components.

60. A monitoring and control system for a density centrifuge blood processing system for separating fluid components and having a separation chamber rotating about a central rotation axis, comprising:

a light source in optical communication with said density centrifuge blood processing system for providing an incident light beam for illuminating an observation region on said density centrifuge blood processing system, thereby generating light transmitted, scattered or both from said observation region;

a light collection element in optical communication with said density centrifuge blood processing system for collecting at least a portion of said light transmitted, scattered or both from said observation region and for directing at least a portion of said light transmitted, scattered or both from said observation region onto a two-dimensional detector;

the two-dimensional detector positioned to receive and detect said light transmitted, scattered or both from said observation region provided by said light collection element, thereby measuring a two-dimensional distribution of the intensities of said light transmitted, scattered or both from said observation region wherein said two dimensional detector generates an output signal corresponding to said two-dimensional distribution of the intensities; and

a centrifugation device controller in communication with said two-dimensional detector for receiving said output signal and for selectively adjusting an operating condition of said density centrifuge blood processing system.

61. The system of claim 60 wherein said two-dimensional distribution of the intensities of said light transmitted, scattered or both from said observation region comprises an image of said at least a portion of said density centrifuge blood processing system.

62. The system of claim 60 wherein said two-dimensional distribution of the intensities of said light transmitted, scattered or both from said observation region comprises an image of said at least a portion of said separation chamber.

63. The system of claim 60 wherein said two-dimensional distribution of the intensities of said light transmitted, scattered or both from said observation region comprises an image an extraction port of said separation chamber.

64. The system of claim 60 wherein the out put signals corresponds to an average intensity of light transmitted through the extraction port.

65. The system of claim 60 wherein said centrifugation device controller comprises a computer or computer processor.

66. The system of claim 60 wherein said centrifugation device controller records the output signal.

67. The system of claim 60 wherein said centrifugation device controller displays the output signal.

68. The system of claim 60 wherein said operating parameter is selected from the group consisting of:

a flow rate of a fluid component out of the separation chamber;

a flow rate of a fluid into the separation chamber; and

the rate of rotation of the separation chamber about the central rotation axis.

69. The system of claim 60 wherein said centrifugation device controller selectively adjusts a plurality of operating parameters of the density centrifuge blood processing system.

70. The system of claim 60 wherein the centrifugation device controller is a means for adjusting the flow rate of one or more separated components out of or into the separation chamber.

71. The system of claim 60 wherein said fluid components are blood components.

72. A method of monitoring a density centrifuge blood processing system for separating fluid components and having a separation chamber rotating about a central rotation axis, comprising the steps of:

illuminating an observation region on a density centrifuge blood processing system with an incident light beam provided by a light source, thereby generating light transmitted, scattered or both from said observation region;

collecting at least a portion of light transmitted, scattered or both from said observation region and directing said light transmitted, scattered or both from said observation region onto a two-dimensional detector; and

measuring a two-dimensional distribution of the intensities of said light transmitted, scattered or both from said observation region.

73. The method of claim 72 wherein said two-dimensional distribution of the intensities of said light transmitted, scattered or both from said observation region comprises an image of said at least a portion of said density centrifuge blood processing system.

74. The method of claim 72 wherein said two-dimensional distribution of the intensities of said light transmitted, scattered or both from said observation region comprises an image of said at least a portion of said separation chamber.

75. The method of claim 72 wherein said two-dimensional distribution of the intensities of said light transmitted, scattered or both from said observation region comprises an image of said at least a portion of an optical cell of said separation chamber.

76. The method of claim 75 wherein a phase boundary between optically differentiable components in the separation chamber is viewable in said image.

77. The method of claim 76 further comprising measuring the position of said phase boundary.

78. The method of claim 75 wherein an extraction port of the separation chamber is viewable in said image.

79. The method of claim 78 further comprises determining the average intensity of light transmitted through a selected a portion of said extraction port.

80. The method of claim 79 further comprising measuring a composition of a component passing through said extraction port.

81. The method of claim 72 further comprising the step of providing a calibration marker in the depth of field of the light collection element.

82. The method of claim 72 wherein said step of illuminating the observation region comprises providing a pulsed incident light beam.

83. The method of claim 72 wherein said step of illuminating the observation region comprises providing a plurality of pulsed incident light beam.

84. The method of claim 82 further comprising the step of selecting the rotational position of the separation chamber corresponding to the two-dimensional distribution of the intensities of said light transmitted, scattered or both from said observation region by selecting the timing and duration of the pulsed incident light beam.

85. The method of claim 84 further comprising the step of selecting different rotational positions of the separation chamber corresponding to the two-dimensional distribution of the intensities of said light transmitted, scattered or both from said observation region for different rotations of said separation chamber.

86. A method of controlling a density centrifuge blood processing system for separating fluid components and having a separation chamber rotating about a central rotation axis, comprising the steps of:

illuminating an observation region on a density centrifuge blood processing system with an incident light beam provided by a light source, thereby generating light transmitted, scattered or both from said observation region;

collecting at least a portion of light transmitted, scattered or both from said observation region and directing said light transmitted, scattered or both from said observation region onto a two-dimensional detector;

measuring a two-dimensional distribution of the intensities of said light transmitted, scattered or both from said observation region,

selectively adjusting an operating condition of said density centrifuge blood processing system based on said two-dimensional distribution of the intensities of said light transmitted, scattered or both from said observation region.

87. The method of claim 86 wherein said two-dimensional distribution of the intensities of said light transmitted, scattered or both from said observation region comprises an image of a phase boundary between optically differentiable components in said separation chamber.

88. The method of claim 87 further comprising the step of measuring the position of the phase boundary between optically differentiable components in said separation chamber.

89. The method of claim 88 wherein the operating condition of said density centrifuge blood processing system is selectively adjusted on the basis on the position of the phase boundary between optically differentiable components in said separation chamber.

90. The method of claim 86 wherein said two-dimensional distribution of the intensities of said light transmitted, scattered or both from said observation region comprises an image of an extraction port of said separation chamber.

91. The method of claim 90 further comprising the step of measuring the composition of fluid components passing through said extraction port of said separation chamber.

92. The method of claim 91 wherein said operating condition of said density centrifuge blood processing system is selectively adjusted on the basis on the composition of fluid components passing through said extraction port of said separation chamber.

93. The method of claim 91 wherein said operating condition of said density centrifuge blood processing system is adjust such that the composition of fluid components passing through said extraction port of said separation chamber is in a predefined range of compositions.

94. The method of claim 86 wherein said two-dimensional distribution of the intensities of said light transmitted, scattered or both from said observation region comprises an image of an extraction port of said separation chamber and a phase boundary between optically differentiable components in said separation chamber.

95. The method of claim 94 further comprising the step of measuring the composition of fluid components passing through said extraction port of said separation chamber and measuring the position of the phase boundary between optically differentiable components in said separation chamber.

96. The method of claim 94 wherein said operating condition of said density centrifuge blood processing system is selectively adjusted on the basis on the composition of fluid components passing through said extraction port of said separation chamber and the position of the phase boundary between optically differentiable components in said separation chamber.

97. The method of claim 86 further comprising the step of providing a calibration marker in the depth of field of the light collection element.

98. The system of claim 86 wherein said operating parameter is selected from the group consisting of:

a flow rate of a fluid component out of the separation chamber;

a flow rate of a fluid into the separation chamber; and

the rate of rotation of the separation chamber about the central rotation axis.

99. The method of claim 86 further comprising the step of selectively adjusting a plurality of operating conditions of said density centrifuge blood processing system.

100. The method of claim 86 wherein said fluid components are blood components.

101. A method for controlling a density centrifuge blood processing system for separating fluid components, said method comprising the steps of:

performing a first measurement of an operating condition of said blood processing device corresponding to a first time;

performing a second measurement of said operating condition of said blood processing device corresponding to a second time;

analyzing said first and second measurements of said operating condition using a predictive data analysis algorithm, wherein operation of said predictive data analysis algorithm generates a predicted operating condition of said blood processing device corresponding to a selected future time;

comparing the predicted operating condition of said blood processing device corresponding to the selected future time to a desired operating condition; and

adjusting at least one setting of said blood processing device based on said comparison of the predicted operating condition of said blood processing device at said future time and the desired operating condition, thereby controlling said blood processing device.

102. The method of claim 101 wherein said first and second measurements comprise measurement of a first and a second position of a phase boundary between optically differentiable fluid components in the density centrifuge blood processing system.

103. The method of claim 101 wherein said first and second measurements comprise measurement of a first and a second composition of fluid components in an extraction port of the density centrifuge blood processing system.

104. An optical cell for a separation chamber of a density centrifuge blood processing system for separating fluid components comprising:

an extraction chamber having a first external optical surface for transmitting at least a portion of an incident optical beam; and

an extraction port having an axial bore for passing fluid components and a first external optical surface for transmitting at least a portion of the incident optical beam;

wherein said first external optical surface of said extraction chamber and said first external optical surface of said extraction port are both positioned within the depth of field of a light collection element.

105. The optical cell of claim 104 wherein first optical surface of said extraction chamber and said first optical surface of said extraction port are both substantially in the same plane.

106. The optical cell of claim 104 wherein the extraction chamber further comprises a second external optical surface for transmitting at least a portion of an incident optical beam;

the second external optical surface positioned opposite said first external optical surface of the extraction chamber.

107. The optical cell of claim 104 wherein the extraction port further comprises a second external optical surface for transmitting at least a portion of an incident optical beam;

the second external optical surface positioned opposite said first external optical surface of the extraction port.

108. The optical cell of claim 104 wherein the external optical surfaces of the extraction chamber and extraction port are optically flat and optically smooth optical surfaces.

109. The optical cell of claim 104 wherein the extraction chamber further comprises a first internal optical surface for transmitting at least a portion of an incident optical beam, the first internal optical surface positioned opposite the first external optical surface of the extraction chamber.

110. The optical cell of claim 104 wherein the extraction port further comprises a first internal optical surface for transmitting at least a portion of an incident optical beam, the first internal optical surface positioned opposite the first external optical surface of the extraction port.

111. The optical cell of claim 104 wherein the extraction chamber further comprises a second internal optical surface for transmitting at least a portion of an incident optical beam, the second internal optical surface positioned between the first external optical surface and first internal optical surface of the extraction chamber.

112. The optical cell of claim 104 wherein the extraction port further comprises a second internal optical surface for transmitting at least a portion of an incident optical beam, the second internal optical surface positioned between the first external optical surface and first internal optical surface of the extraction port.

113. The optical cell of claim 104 wherein the axial bore of the extraction port has an aspect ratio selected of the range of about 0.1 to about 0.4.

114. The optical cell of claim 104 further comprising a calibration marker, wherein said calibration mark occupies the same plane as said first external optical surfaces of said extraction chamber and said extraction port.

115. A method of processing blood comprising the steps of:

providing a two stage blood processing system comprising a density centrifuge blood processing system and an elutriation blood processing system;

flowing blood into said two stage blood processing system, wherein the blood is separated into a plurality of components in the density centrifuge blood processing system including at least one desired component and a plasma containing component;

filling the elutriation blood processing system with said desired component until the elutriation blood processing system is in a filled operating state; and

flushing the elutriation blood processing system when in the filled operating state by flowing the plasma containing component into the elutriation blood processing system, thereby processing said blood.

116. The method of claim 115 further comprising the step of optically measuring the composition of blood components passing through an extraction port of the density centrifuge blood processing system into the elutriation blood processing system.

117. The method of claim 115 further comprising the step of optically measuring the position of the desired component in a separation chamber of the density centrifuge blood processing system and an extraction port of the density centrifuge blood processing system.

118. The method of claim 115 further comprising the step of optically measuring the composition of fluid components in the elutriation blood processing system.

119. The method of claim 115 further comprising the step of optically measuring the position of fluid components in the elutriation blood processing system.

120. The method of claim 115 further comprising the step of determining when the elutriation blood processing system is in the filled operating state by optically measuring the composition of fluid components in the elutriation blood processing system.

121. The method of claim 115 further comprising the step of determining when the elutriation blood processing system is in the filled operating state by optically measuring the position of fluid components in the elutriation blood processing system.

122. The method of claim 115 further comprising the step of determining when the elutriation blood processing system is in the filled operating state by optically measuring the composition, flux or both of blood components passing through an extraction port of the density centrifuge blood processing system into the elutriation blood processing system.

123. The method of claim 115 wherein said desired component is a white blood cell containing component.

124. The method of claim 115 wherein said desired component is a platelet containing component.

125. The method of claim 115 further comprising the step of collecting at least a portion of said desired component in a container.

126. A monitoring system for a fluid processing system having a separation chamber, comprising:

a light source in optical communication with said density centrifuge blood processing system for providing an incident light beam for illuminating an observation region on said density centrifuge blood processing system, thereby generating light transmitted, scattered or both from said observation region;

a light collection element in optical communication with said density centrifuge blood processing system for collecting at least a portion of said light transmitted, scattered or both from said observation region and for directing at least a portion of said light transmitted, scattered or both from said observation region onto a two-dimensional detector; and

the two-dimensional detector positioned to receive and detect said light transmitted, scattered or both from said observation region provided by said light collection element, thereby measuring a two-dimensional distribution of the intensities of said light transmitted, scattered or both from said observation region.