PORTABLE SAMPLE ANALYZER CARTRIDGE

• US 20050255600A1
• Filed: 05/12/2005
• Published: 11/17/2005
• Est. Priority Date: 05/14/2004
• Status: Active Grant

• Current Assignee: Honeywell International Inc.
• Original Assignee: Honeywell International Inc.
• Inventors: Padmanabhan, Aravind, Cabuz, Cleopatra, Cox, James A.
• Granted Patent: US 8,071,051 B2
• Time in Patent Office: Days
• US Class Current: 436/63
• CPC Class Codes: B01L 2200/027 for microfluidic devices
• CPC Class Codes: B01L 2200/04 Exchange or ejection of cartridges, containers or reservoirs
• CPC Class Codes: B01L 2200/0636 Focussing flows, e.g. to laminate flows
• CPC Class Codes: B01L 2200/146 Employing pressure sensors
• CPC Class Codes: B01L 2300/0672 Integrated piercing tool
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0877 Flow chambers
• CPC Class Codes: B01L 2300/14 Means for pressure control
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B01L 9/527 for microfluidic devices, e.g. used for lab-on-a-chip
• CPC Class Codes: G01N 15/1484 microstructural devices
• CPC Class Codes: G01N 2015/012 Red blood cells
• CPC Class Codes: G01N 2015/018 Platelets
• CPC Class Codes: G01N 2015/019 Biological contaminants; Fouling
• CPC Class Codes: G01N 2015/1413 Hydrodynamic focussing
• CPC Class Codes: G01N 2015/1486 Counting the particles
• CPC Class Codes: G01N 2035/00891 Displaying information to the operator
• CPC Class Codes: G01N 35/00722 Communications; Identification

Abstract

A sample analyzer cartridge for use at a point of care of a patient such as in a doctor'"'"'s office, in the home, or elsewhere in the field. By providing a removable and/or disposable cartridge with all of the needed reagents and/or fluids, the sample analyzer can be reliably used outside of the laboratory environment, with little or no specialized training.

Claims

1. A disposable analysis cartridge capable of performing at least part of a blood sample measurement, comprising:

two or more flow cytometry analysis channels, each adapted for hydrodynamically focusing a sample and to support optical light scattering measurements; and

fluid directing means for directing flow of a sample fluid to at least one of the two or more flow cytometry analysis channels.

2. The disposable analysis cartridge of claim 1 further comprising:

one or more light absorption based measurement channels.

3. The disposable analysis cartridge of claim 1 further comprising:

one or more channels fluidly connected to the fluid directing means;

one or more flow sensors for measuring flow rates within at least selected ones of the one or more channels.

4. The disposable analysis cartridge of claim 3 further comprising:

one or more pressure sensors for measuring a pressure within at least selected ones of the one or more channels.

5. The disposable analysis cartridge of claim 4 further comprising:

a controller for determining if the fluid in the at least selected ones of the one or more channels has a viscosity that is outside of a predetermined threshold.

6. The disposable analysis cartridge of claim 1 further comprising:

one or more storage reservoirs, each for storing a reagent.

7. The disposable analysis cartridge of claim 6 wherein the reagent is selected from the group of:

isotonic solutions (dilution), hypotonic solutions (lysing), sphering agents, buffering agents, lysing agents, antibodies, cytochemical stains, fluorescent stains.

8. The disposable analysis cartridge of claim 7 wherein the reagent is in a liquid form.

9. The disposable analysis cartridge of claim 7 wherein the reagent is in a lyophilized form.

10. The disposable analysis cartridge of claim 1 further comprising an on-board whole blood acquisition device.

11. The disposable analysis cartridge of claim 10 wherein the whole blood acquisition device is a lancet.

12. The disposable analysis cartridge of claim 1 further comprising an on-board whole blood storage loop.

13. The disposable analysis cartridge of claim 12 wherein at least part of the on-board whole blood storage loop is coated with an anticoagulant.

14. The disposable analysis cartridge of claim 13 wherein the anticoagulant is an ethylenediaminetetraacetic acid (EDTA).

15. The disposable analysis cartridge of claim 1 wherein a first one of the two or more flow cytometry analysis channels is adapted to support the measurement of one or more white blood cell parameters, and a second one of the two or more flow cytometry analysis channels is adapted to support the measurement of one or more red blood cell parameters.

16. The disposable analysis cartridge of claim 15 wherein at least one of the one or more white blood cell parameters relate to a total white blood cell count.

17. The disposable analysis cartridge of claim 15 wherein at least one of the one or more white blood cell parameters relates to white blood cell differentiation.

18. The disposable analysis cartridge of claim 15 wherein at least one of the one or more white blood cell parameters relates to cell volume.

19. The disposable analysis cartridge of claim 15 wherein at least one of the one or more red blood cell parameters relate to a red blood cell count.

20. The disposable analysis cartridge of claim 15 wherein at least one of the one or more red blood cell parameters relates to a platelet count.

21. The disposable analysis cartridge of claim 15 wherein at least one of the one or more red blood cell parameters relates to a cell diameter.

22. The disposable analysis cartridge of claim 15 wherein at least one of the one or more red blood cell parameters relates to a hemoglobin concentration.

23. The disposable analysis cartridge of claim 15 further comprising one or more storage reservoirs each for storing a reagent, wherein at least one of the reagents is mixed with the sample fluid that is directed to the first one of the two or more flow cytometry analysis channels.

24. The disposable analysis cartridge of claim 23 wherein at least one of the reagents that is mixed with the sample fluid that is directed to the first one of the two or more flow cytometry analysis channels is a red blood cell lysing agent.

25. The disposable analysis cartridge of claim 24, wherein at least one of the reagents is mixed with the sample fluid that is directed to the second one of the two or more flow cytometry analysis channels.

26. The disposable analysis cartridge of claim 25 wherein at least one of the reagents that is mixed with the sample fluid that is directed to the second one of the two or more flow cytometry analysis channels is a red blood cell sphering agent.

27. The disposable analysis cartridge of claim 1 further comprising an absorption channel that is adapted to support optical absorption measurements.

28. The disposable analysis cartridge of claim 1 further comprising an extinction channel that is adapted to support optical extinction measurements.

29. A method for analyzing a blood sample comprising:

providing a portion of the blood sample to a first measurement channel in a disposable analysis cartridge;

providing a portion of the blood sample to a second measurement channel in the disposable analysis cartridge;

lysing the red blood cells from the blood sample after the sample is provided to the first measurement channel in the disposable analysis cartridge;

providing the lysed red blood cell sample to a first flow cytometry analysis channel, wherein the first flow cytometry analysis channel is adapted to hydrodynamically focus the lysed red blood cell sample; and

directing a light beam on the lysed red blood cell sample in the first flow cytometry analysis channel, and detecting the light scatter energy at two or more detector angles.

30. The method of claim 29 further comprising the step of determining one or more white blood cell parameters from the detected light scatter energy from the first flow cytometry analysis channel.

31. The method of claim 29 further comprising the step of staining one or more white blood cells in the blood sample after the sample is provided to the first measurement channel in the disposable analysis cartridge.

32. The method of claim 29 further comprising the step of differentially lysing one or more white blood cell types in the blood sample after the sample is provided to the first measurement channel in the disposable analysis cartridge.

33. The method of claim 29 further comprising the steps of:

sphering the red blood cells in the blood sample after the sample is provided to the second measurement channel in the disposable analysis cartridge;

providing the sphered red blood cell sample to a second flow cytometry analysis channel, wherein the second flow cytometry analysis channel is adapted to hydrodynamically focus the sphered red blood cell sample; and

directing a light beam on the sphered red blood cell sample in the second flow cytometry analysis channel, and detecting the light scatter energy at two or more detector angles.

34. The method of claim 29 further comprising the step of detecting a light extinction condition using one or more detectors.

35. The method of claim 33 wherein the sphering of red blood cells is done on-the-fly on a disposable cartridge.

36. The method of claim 35 wherein the sphering is performed by mixing a sphering agent with the red blood cells.

37. The method of claim 36 wherein the exposure time of the red blood cells to the sphering agent is controlled to within a predefined time range.

38. The method of claim 33 further comprising the step of determining one or more red blood cell parameters from the detected light scatter energy from the second flow cytometry analysis channel.

39. The method of claim 33 further comprising the step of providing two or more wavelengths of light on the sample in the second flow cytometry analysis channel.

40. The method of claim 33 further comprising the step of polarizing the light beam prior to providing the light beam on the sample in the second flow cytometry analysis channel.

41. The method of claim 40 further comprising the step of detecting a polarized extinction condition using one or more detectors.

42. The method of claim 33 further comprising the step of determining two or more red blood cell parameters from the detected light scatter energy from the second flow cytometry analysis channel.

43. The method of claim 33 further comprising the step of:

providing a light beam on the sample in the second flow cytometry analysis channel, and detecting an absorption value that corresponds to the light absorbed by the sample in the second flow cytometry analysis channel.

44. The method of claim 33 wherein the one or more detector angles includes an on-axis detector angle.

45. The method of claim 33 further comprising the step of determining a measure of the refractive index of at least one red blood cell.

46. The method of claim 33 further comprising the step of determining a measure of the diameter of at least one red blood cell.

47. The method of claim 33 further comprising the step of determining a sample volume of the sample that passes through the second flow cytometry analysis channel.

48. A method for analyzing a blood sample comprising:

providing a portion of the blood sample to a first measurement channel in a disposable analysis cartridge;

providing a portion of the blood sample to a second measurement channel in the disposable analysis cartridge;

sphering the red blood cells in the blood sample after the sample is provided to the second measurement channel in the disposable analysis cartridge;

providing the sphered red blood cell sample to a first flow cytometry analysis channel, wherein the first flow cytometry analysis channel is adapted to hydrodynamically focus the sphered red blood cell sample; and

directing a light beam on the sphered red blood cell sample in the first flow cytometry analysis channel, and detecting the light scatter energy at one or more detector angles.

49. A disposable analysis cartridge capable of performing at least part of a blood sample measurement, comprising:

two or more flow cytometry analysis channels, at least a first one of the flow cytometry analysis channels is adapted to hydrodynamically focus a sample and to support an electrical measurement of the sample as it passes through the first flow cytometry analysis channel; and

fluid directing means for directing fluid to at least the first one of the flow cytometry analysis channels.

50. A disposable analysis cartridge capable of performing at least part of a blood sample measurement, comprising:

two or more flow cytometry analysis channels, at least a first one of the flow cytometry analysis channels is adapted to hydrodynamically focus a sample and to support a fluorescent tag measurement of the sample it passes through the first flow cytometry analysis channel; and

fluid directing means for directing fluid to at least the first one of the flow cytometry analysis channels.

51. A disposable analysis cartridge capable of performing at least part of a blood sample measurement, comprising:

two or more flow cytometry analysis channels, at least a first one of the flow cytometry analysis channels is adapted to hydrodynamically focus a sample and to support a light absorption and/or light extinction measurement of the sample as it passes through the first flow cytometry analysis channel; and

fluid directing means for directing fluid to at least the first one of the flow cytometry analysis channels.

52. The disposable analysis cartridge of claim 51 further comprising an absorption channel that is adapted to support optical absorption measurements, and wherein the fluid directing means is adapted to direct fluid to the absorption channel.

53. The disposable analysis cartridge of claim 51 further comprising an extinction channel that is adapted to support optical extinction measurements, and wherein the fluid directing means is adapted to direct fluid to the extinction channel.

54. A disposable analysis cartridge capable of performing at least part of a blood sample measurement, comprising:

two or more reagent storage reservoirs, a first one for storing a lysing reagent and a second one for storing a sphering reagent;

a first flow sensor in fluid communication with the first one of the reagent storage reservoirs;

a second flow sensor in fluid communication with the second one of the reagent storage reservoirs;

a lysing on the fly channel in fluid communication with the first one of the reagent storage reservoirs;

a sphering on the fly channel in fluid communication with the second one of the reagent storage reservoirs; and

a first flow cytometry analysis channel for hydrodynamically focusing a sample and for supporting optical light scattering measurements, the first flow cytometry analysis channel in fluid communication with the lysing on the fly channel; and

a second flow cytometry analysis channel for hydrodynamically focusing a sample and for supporting optical light scattering measurements, the second flow cytometry analysis channel in fluid communication with the sphering on the fly channel.