Apparatus and method for analyzing a liquid in a capillary tube of a hematology instrument

• US 7,207,939 B2
• Filed: 10/03/2002
• Issued: 04/24/2007
• Est. Priority Date: 10/03/2002
• Status: Expired due to Fees

• Current Assignee: Coutler International Corp.
• Original Assignee: Coulter International Corp.
• Inventors: Husher, Frederick K.
• Primary Examiner(s): Jaworski; Francis J.
• Application Number:
  US10/264,077
• Publication Number:
  US 20040065143A1
• Time in Patent Office: 1,664 Days
• Field of Search: 600370-372, 600437-438, 436/70, 436 73- 74, 422/44, 422/73, 422 99-102
• US Class Current: 600/370
• CPC Class Codes: G01N 11/04 through a restricted passage, e.g. tube, aperture
• CPC Class Codes: G01N 15/05 in blood
• CPC Class Codes: G01N 2291/02466 Biological material, e.g. blood
• CPC Class Codes: G01N 2291/02818 Density, viscosity
• CPC Class Codes: G01N 2291/02836 Flow rate, liquid level
• CPC Class Codes: G01N 29/024 by measuring propagation velocity or propagation time of acoustic waves
• CPC Class Codes: G01N 33/491 by separating the blood components G01N15/05 takes precedence

Abstract

An apparatus and method for determining the density and fluid-type of a fluid flowing in a capillary tube, the velocity and viscosity of a blood sample flowing in a capillary tube, the erythrocyte sedimentation rate (ESR) of a blood sample after flow has been brought to an abrupt stop in a capillary tube, and/or the zeta sedimentation rate (ZSR) of a blood sample after flow has been brought to an abrupt stop in a capillary tube. These measurements are accomplished by directing a waveform pulse, such as an ultrasound pulse, at a pre-determined frequency transversely across the capillary tube and sample fluid, and by determining the flight of time of the pulse through the capillary tube and sample fluid and/or the Doppler shift of the echo signals reflecting off cells moving forwardly or transversely within a flowing, or stationary, blood sample.

Claims

1. A device for analyzing a blood sample, comprising:

a capillary tube defining a path of travel for flow of a blood sample in vitro; and

a sensor assembly located about said capillary tube and having a launch sensor for emitting an ultrasound pulse into said capillary tube in a direction perpendicular to said path of travel, and

a second sensor located forward along said path of travel relative to said launch sensor and canted at an angle relative to said path of travel so that said second sensor is aligned to receive echo signals of said ultrasound pulse that reflect off cells moving forward within said path of travel, wherein said device is adapted for measuring erythrocyte sedimentation rate (ESR) or zeta sedimentation rate (ZSR) of a blood sample.

2. A device according to claim 1, wherein said launch sensor is a piezo crystal transducer.

3. A device according to claim 1, wherein said capillary tube defines a straight path of travel adjacent said sensor assembly.

4. The device according to claim 1, wherein said launch sensor emits said ultrasound pulse in a direction perpendicular to said path of travel and along a diameter of said capillary tube.

5. The device according to claim 4, wherein a single launch sensor is utilized to emit said ultrasound pulse and receive an echo signal of said ultrasound pulse that propagates into said capillary tube in a direction away from said launch sensor and perpendicular to said path of travel and that is reflected back toward said launch sensor.

6. The device according to claim 1, further comprising:

said sensor assembly having at least one sensor for emitting a waveform pulse at a predetermined frequency into said capillary tube perpendicularly across said path of travel and for receiving at least one of said pulse and an echo of said pulse after said pulse propagates at least partially through said capillary tube and said path of travel; and

a signal processing circuit in communication with said sensor assembly.

7. The device according to claim 6, wherein, when air alone is located in said capillary tube, said signal processing circuit is adapted to determine wall thickness and inner diameter of said capillary tube based on echo signals received by said sensor assembly.

8. The device according to claim 1, further comprising a signal processing circuit interconnected to said second sensor and adapted to measure Doppler shift of echo signals received by said second sensor whereby cell velocity of the cells moving forward along said path of travel can be determined.

9. The device according to claim 8, wherein said signal processing circuit is adapted to capture Doppler shift measurements from echo signals received by said second sensor reflecting from cells located at two or more different spatial locations within said capillary tube so that a curve of velocity of cells across a cross section of said capillary tube can be generated.

10. The device according to claim 9, wherein said two or more spatial locations include locations along a central longitudinal axis of said capillary tube and about midway between said central longitudinal axis and an inner diameter wall of said capillary tube.

11. The device according to claim 1, further comprising means for abruptly halting the flow of the blood sample through said capillary tube.

12. The device according to claim 11, further comprising a signal processing circuit which interconnects to said second sensor and which is adapted to take Doppler shift measurements of echo signals received by said second sensor after flow of the blood sample in said capillary tube is caused to be abruptly halted by said means, said Doppler shift measurements are from echo signals received by said second sensor from a reflection of said ultrasound pulse off cells moving forward along said path of travel.

13. The device according to claim 12, wherein said signal processing circuit is adapted to capture Doppler shift measurements from echo signals corresponding to those received by said second sensor reflecting from cells located along a central longitudinal axis of said capillary tube.

14. The device according to claim 12, wherein said signal processing circuit interconnects to said launch sensor and is adapted to take Doppler shift measurements of echo signals received by said launch sensor after flow of the blood sample in said capillary tube is caused to be abruptly halted by said means, said Doppler shift measurements are from echo signals received by said launch sensor from a reflection of said ultrasound pulse off cells moving transversely relative to said path of travel.

15. The device according to claim 11, further comprising a signal processing circuit which interconnects to said launch sensor and which is adapted to take Doppler shift measurements of echo signals received by said launch sensor after flow of the blood sample in said capillary tube is caused to be abruptly halted by said means, said Doppler shift measurements are from echo signals received by said launch sensor from a reflection of said ultrasound pulse off cells moving transversely relative to said path of travel.

16. The device according to claim 15, wherein said signal processing circuit is adapted to capture Doppler shift measurements from echo signals corresponding to those received by said launch sensor reflecting from cells located about midway between said central longitudinal axis and an inner diameter wall of said capillary tube.

17. The device according to claim 1, wherein said sensor assembly comprises a separate receiving sensor engaging said capillary tube opposite said launch sensor utilized to receive said ultrasound pulse that propagates completely through said capillary tube and path of travel.

18. The device according to claim 1, further comprising:

a separate receiving sensor engaging said capillary tube opposite said launch sensor for receiving at least one of said pulse and an echo of said pulse after said pulse propagates completely through said capillary tube and said path of travel.

19. The device according to claim 1, wherein said capillary tube is made of a material selected from the group consisting of polyurethane and a material having a relatively low density similar to polyurethane.

20. The device according to claim 1, wherein said capillary tube further comprises a housing that encloses said sensor assembly about said capillary tube, said housing being made of a material which is of a higher density than that of said capillary tube so that said ultrasound pulse reflects off said housing.

21. The device according to claim 1, wherein said device forms a part of a multifunctional hematology instrument having a blood aspiration drawing mechanism interconnected to said capillary tube at an upstream location relative to said sensor assembly.

22. The device according to claim 1, wherein said device forms a part of an automated blood smear slide maker having a wedge component for producing a monolayer smear of cells, and wherein at least one of hold time, smear velocity and acceleration of said wedge component is determined as a function of flight time and Doppler shift measurements taken by said sensor assembly.

23. The device according to claim 1, further comprising a signal processor in communication with said at least one sensor for measuring at least one of flight time of the received pulse/echo and Doppler shift of said echo.

24. A method for analyzing a fluid sample, comprising:

flowing a blood sample in vitro in a path of travel within a capillary tube of the device of claim 1;

emitting a waveform pulse of a predetermined frequency into said capillary tube and perpendicularly into said path of travel;

receiving said pulse by a sensor after said pulse propagates at least partially though said capillary tube and said path of travel; and

measuring at least one of flight time and Doppler shift of said pulse received during said receiving step and determining at least one of ESR and ZSR therefrom.

25. The method according to claim 24, wherein the pulse is an ultrasound pulse.

26. The method according to claim 25, wherein the ultrasound pulse emitted during said emitting step is directed substantially perpendicular to the path of travel of the blood sample and along a diameter of the capillary tube.

27. The method according to claim 26, wherein, during said receiving step, an ultrasound pulse is received after it has propagated at least once completely through the capillary tube and path of travel, and during the measuring step, the flight time of the ultrasound pulse that propagated at least once through the capillary tube and path of travel is determined and utilized to determine the density of the fluid sample.

28. The method according to claim 27, further comprising the step of monitoring the presence or lack thereof of noise reflections of the ultrasound pulse off particles in the fluid sample to distinguish between isotonic fluids and blood.

29. The method according to claim 28, further comprising the step of reporting the presence of air, isotonic fluids or blood within the capillary tube based on information obtained during said measuring and monitoring steps.

30. The method according to claim 26, wherein, during said receiving step, echo signals from the ultrasound pulse reflecting off cells moving forward within the capillary tube are received, and during the measuring step, the Doppler shift of the echo signals is measured to determine the velocity of the blood sample, whereby the velocity measurement of the blood sample combined with information concerning the density of the blood sample is utilized to determine the viscosity of the blood sample.

31. The method according to claim 30, wherein during said measuring step, Doppler shift measurements are taken from echo signals which reflect from cells located at least at two different spatial locations within a cross-section of the capillary tube, and wherein a profile curve of blood velocity across the cross section of the capillary tube is generated.

32. The method according to claim 31, wherein the spatial locations include locations along a central longitudinal axis of the capillary tube and about midway between the central longitudinal axis and an inner diameter wall of the capillary tube.

33. A method for analyzing a fluid sample comprising:

flowing a blood sample in vitro in a path of travel within a capillary tube;

emitting a waveform ultrasound pulse of a predetermined frequency in direction directed transversely across the path of travel of the blood sample;

receiving said pulse by a sensor after said pulse propagates at least partially through said capillary tube and said path of travel;

stopping the flow of the blood sample in an abrupt manner within the capillary tube;

wherein said emitting step is accomplished after the flow of the blood sample is abruptly stopped;

wherein, during said receiving step, echo signals are simultaneously received from the ultrasound pulse reflecting off cells moving forward relative to the path of travel within the capillary tube and off cells moving transversely relative to a central longitudinal axis of the capillary tube after the flow of the blood sample is abruptly stopped; and

wherein, during said measuring step, the Doppler shift of the echo signals are measured to determine the rate of decay of velocity of forward moving cells and the rate of decay of velocity of cells moving in a transverse direction;

whereby the measured rate of decay of the velocity of forward moving cells is utilized to determine an ESR value for the blood sample and the rate of decay of velocity of the cells moving transversely is utilized to determine a ZSR value for the blood sample.

34. The method according to 33, wherein during said measuring step, Doppler shift measurements for determining the rate of decay of velocity of forward moving cells are obtained from echo signals which reflect from cells located along the central longitudinal axis of the capillary tube.

35. The method according to claim 34, wherein during said measuring step, Doppler shift measurements for determining the rate of decay of velocity of cells moving in a transverse direction is taken from echo signals which reflect from cells located about midway between the central longitudinal axis and an inner diameter wall of the capillary tube.