Cartridge for preparing a sample fluid containing cells for analysis

• US 10,335,786 B2
• Filed: 05/30/2014
• Issued: 07/02/2019
• Est. Priority Date: 05/31/2013
• Status: Active Grant

• Current Assignee: PixCell Medical Technologies Ltd. (KLA Corporation)
• Original Assignee: PixCell Medical Technologies Ltd. (KLA Corporation)
• Inventors: Bransky, Avishay, Shiomo, Liron
• Primary Examiner(s): Warden, Jill A
• Assistant Examiner(s): Handy, Dwayne K
• Application Number:
  US14/292,406
• Publication Number:
  US 20140356941A1
• Time in Patent Office: 1,859 Days
• Field of Search: 422502, 422503, 422512, 422551, 422554
• CPC Class Codes: B01L 2200/027 for microfluidic devices
• CPC Class Codes: B01L 2200/0621 Control of the sequence of chambers filled or emptied
• CPC Class Codes: B01L 2200/0689 Sealing
• CPC Class Codes: B01L 2300/044 pierceable, e.g. films, membranes
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0838 Capillaries
• CPC Class Codes: B01L 2300/0867 Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2300/087 Multiple sequential chambers
• CPC Class Codes: B01L 2300/123 Flexible; Elastomeric
• CPC Class Codes: B01L 2400/0481 squeezing of channels or chambers
• CPC Class Codes: B01L 2400/049 vacuum
• CPC Class Codes: B01L 2400/0683 mechanically breaking a wall or membrane within a channel or chamber
• CPC Class Codes: B01L 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B01L 3/502738 characterised by integrated valves microvalves F16K99/0001

Abstract

A cartridge configured for use in a blood analyzer is provided. The cartridge may include a substantially rigid frame, a flow path within the rigid frame, at least one opening in the substantially rigid frame configured to align and stabilize a capillary tube, and a seal within the flow path. The seal may be configured to temporarily obstruct flow through at least a portion of the flow path. The seal may also be configured to open in response to a force exerted via a capillary tube inserted into the at least one opening.

Claims

1. A cartridge configured for use in a blood analyzer, the cartridge comprising:

a substantially rigid frame;

a flow path within the rigid frame;

at least one opening in the substantially rigid frame, the at least one opening defining at least one wall in the substantially rigid frame, the at least one opening being configured to align and stabilize a capillary tube through interaction between the at least one wall and at least one of the capillary tube or a sampler body holding the capillary tube; and

a two-part seal within the flow path, the two-part seal including a first portion configured to establish a seal about the capillary tube after the capillary tube is introduced into the flow path within the rigid frame, the two-part seal also including a second portion separate from the first portion, wherein the second portion is configured to temporarily obstruct flow through at least a portion of the flow path, and wherein the second portion is configured to open in response to a force exerted via the capillary tube after the capillary tube is introduced into the flow path within the rigid frame.

2. The cartridge of claim 1, wherein the force exerted via the capillary tube includes an axial force exerted on at least a portion of the second portion of the two-part seal.

3. The cartridge of claim 1, wherein the capillary tube is configured to receive via capillary action a sample fluid through an outlet of the capillary tube and to introduce the sample fluid to the flow path within the rigid frame through the same outlet of the capillary tube.

4. The cartridge of claim 1, wherein the second portion of the two-part seal is spaced apart from the first portion of the two-part seal.

5. The cartridge of claim 1, wherein the cartridge is configured to retain the capillary tube in the at least one opening during blood analysis in a blood analyzer.

6. The cartridge of claim 1, wherein when the capillary tube is in the flow path within the rigid frame, a blood sample in the capillary tube is sealed from contact with an outside environment.

7. The cartridge of claim 1, wherein the at least one opening includes two openings in the substantially rigid frame.

8. The cartridge of claim 1, wherein the cartridge further includes a flexible reservoir, and wherein the flow path extends between the at least one opening and the flexible reservoir.

9. The cartridge of claim 1, wherein the cartridge is configured to cooperate with a blood analyzer such that after a capillary tube with a blood sample therein is placed into the flow path within the rigid frame, the blood analyzer is configured to automatically inject the blood sample from the capillary tube into the flow path upon placement of the cartridge into the blood analyzer.

10. The cartridge of claim 1, wherein the capillary tube includes a capillary seal opposite to the capillary outlet that determines, at least in part, a volume of sample fluid for introduction into the cartridge, wherein the capillary seal allows at least some air to flow, but blocks fluid flow.

11. The cartridge of claim 10, wherein the capillary seal is movable within the capillary tube through operation of a plunger in order to deliver at least a portion of the volume of sample fluid to the flow path of the cartridge.

12. The cartridge of claim 1, wherein the first portion of the two-part seal is located upstream in the flow path relative to the second portion of the two-part seal.

13. The cartridge of claim 1, wherein the first portion of the two-part seal is located downstream in the flow path relative to the second portion of the two-part seal.

14. The cartridge of claim 1, wherein the first portion of the two-part seal is an O-ring.

15. A cartridge system configured for use in a blood analyzer, the cartridge system comprising:

a cartridge, including;

a substantially rigid portion;

a flexible sheet fixed to the rigid portion, wherein the flexible sheet includes a raised cap disposed over a depression formed in the rigid portion to form a first reservoir;

at least one flow path formed in the rigid portion and configured to establish fluid communication between at least one inlet in the substantially rigid portion and the first reservoir; and

a fluid sampler, including;

at least one capillary tube; and

a membrane disposed within the at least one capillary tube, wherein a location of the membrane within the at least one capillary tube defines a fixed volume of sample fluid to be received by the at least one capillary tube;

wherein the membrane is permeable to air such that when sample fluid enters the at least one capillary tube, air displaced by the sample fluid entering the at least one capillary tube is allowed to flow out of the at least one capillary tube through the membrane; and

wherein the membrane is configured to be pushed by a plunger toward an end of the at least one capillary tube to deliver the fixed volume of sample fluid to the at least one flow path formed in the rigid portion of the cartridge.

16. The cartridge system of claim 15, where the first reservoir contains at least one high molecular weight polymer.

17. The cartridge system of claim 15, further including a seal disposed in the at least one flow path, wherein the seal is configured to temporarily obstruct flow through at least a portion of the at least one flow path, and wherein the seal is configured to open in response to a force exerted via the capillary tube inserted into the at least one opening flow path.

18. The cartridge system of claim 17, wherein the seal includes a flap portion suspended by a first suspension portion of a first thickness and a second suspension portion of a second thickness, wherein the second thickness is greater than the first thickness, and wherein the first suspension portion is configured such that the force exerted via the capillary tube causes the first suspension portion to tear leaving the flap portion suspended primarily by the second suspension portion.

19. The cartridge system of claim 17, wherein the seal includes a flap portion configured to reside within the at least one flow path at substantially a 90 degree angle relative to a longitudinal axis of the at least one flow path.

20. The cartridge system of claim 17, wherein the seal includes a flap portion configured to reside within the at least one flow path at an angle other than 90 degrees relative to a longitudinal axis of the at least one flow path.

21. The cartridge system of claim 17, wherein the seal further includes at least one O-ring positioned such that the O-ring contacts the capillary tube upon insertion of the capillary tube into the at least one flow path.

22. The cartridge system of claim 15 further including at least one filling hole associated with the depression, the at least one filling hole configured to provide fluid to the first reservoir.

23. The cartridge system of claim 15, wherein the flexible sheet includes a second raised cap disposed over a second depression formed in the rigid portion to form a second reservoir, the cartridge further including:

a flow channel connecting the first reservoir to the second reservoir;

a fluid outlet channel associated with the second reservoir; and

a seal disposed within the fluid outlet channel and configured to control a flow of fluid through the fluid outlet channel.

24. The cartridge system of claim 23, wherein the seal includes a peelable bond formed between the rigid portion and the flexible sheet, and wherein the seal is configured to open by breaking the peelable bond formed between the rigid portion and the flexible sheet.

25. The cartridge system of claim 23, further including a buffer compartment formed by a third depression in the rigid portion and a third raised cap in the flexible sheet, wherein the buffer compartment is positioned along a flow path of the cartridge such that a prepared fluid to be analyzed collects in the buffer compartment prior to analysis of the prepared fluid.

26. The cartridge system of claim 15, wherein the membrane is a hydrophobic membrane.

27. A cartridge configured for use in a blood analyzer, the cartridge comprising:

a first blood sample inlet;

a first reservoir containing at least one high molecular weight polymer, a buffer, and a sphering agent;

a first channel connecting the first blood sample inlet and the first reservoir;

a second reservoir;

a second channel connecting the first reservoir to the second reservoir;

a micro-channel flow connected to the second reservoir;

a second blood sample inlet;

a third reservoir containing a first stain;

a third channel connecting the second blood sample inlet to the third reservoir;

a fourth reservoir;

a fourth channel connecting the third reservoir to the fourth reservoir;

a fifth reservoir containing a second stain;

a fifth channel connecting the fourth reservoir to the fifth reservoir, wherein the fifth reservoir is flow connected to the micro-channel;

a viewing area associated with the micro-channel, the viewing area being configured to lie in an optical path of an imager when the cartridge is received by a blood analyzer; and

a hemoglobin inspection area flow connected to the second reservoir, wherein the hemoglobin inspection area is configured to lie in an optical path of a light source when the cartridge is received by the blood analyzer.

28. The cartridge of claim 27, wherein the first stain is an acidic stain and wherein the second stain is an alkaline stain.

29. The cartridge of claim 27, wherein at least one of the first reservoir, second reservoir, third reservoir, fourth reservoir, and fifth reservoir includes a reagent including at least one high molecular weight polymer.

30. The cartridge of claim 27, wherein the first blood sample inlet and the second blood sample inlet are configured to mate with respective first and second capillary tubes.

31. The cartridge of claim 27, further comprising a first seal located in the first channel and a second seal located in the third channel.

32. A cartridge configured for use in a blood analyzer, the cartridge comprising:

a substantially rigid frame;

a flexible sheet fixed to the substantially rigid frame, wherein the flexible sheet includes a raised cap disposed over a depression formed in the substantially rigid frame to form a reservoir, the cartridge further including;

a fluid outlet channel associated with the reservoir; and

a seal configured to control a flow of fluid through the fluid outlet channel, wherein the seal is located in the fluid outlet channel and is formed as a temporary, peelable bond formed between the flexible sheet and the substantially rigid frame;

wherein the seal is configured to block fluid flow through the fluid outlet channel during introduction of a sample fluid into the reservoir and during mixing of the sample fluid with at least one other fluid in the reservoir; and

wherein the seal is configured to open in response to a super-threshold pressure experienced at the seal as a result of pressure applied to the raised cap.

33. The cartridge of claim 32, wherein the sample fluid includes blood and wherein the at least one other fluid includes a high molecular weight polymer.

34. The cartridge of claim 32, further including a high molecular weight polymer disposed within the first reservoir.

35. The cartridge of claim 32, wherein upon opening of the seal, a mixture of the sample fluid and the at least one other fluid is enabled to flow between the flexible sheet and the rigid frame.