Microfluidic card for RBC analysis

• US 8,034,296 B2
• Filed: 06/30/2006
• Issued: 10/11/2011
• Est. Priority Date: 07/01/2005
• Status: Active Grant

• Current Assignee: Honeywell International Inc.
• Original Assignee: Honeywell International Inc.
• Inventors: Zins, Christopher J., Bardell, Ron L., Padmanabhan, Aravind, Cox, James A.
• Primary Examiner(s): Gakh; Yelena G
• Assistant Examiner(s): XU, XIAOYUN
• Application Number:
  US11/428,289
• Publication Number:
  US 20070031289A1
• Time in Patent Office: 1,929 Days
• Field of Search: None
• US Class Current: 422/73
• CPC Class Codes: B01L 2200/0636 Focussing flows, e.g. to laminate flows
• CPC Class Codes: B01L 2200/0684 Venting, avoiding backpressure, avoid gas bubbles
• CPC Class Codes: B01L 2200/10 Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0887 Laminated structure
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 2400/0415 electrical forces, e.g. electrokinetic
• CPC Class Codes: B01L 2400/0427 Electrowetting
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 2400/086 using baffles or other fixed flow obstructions
• CPC Class Codes: B01L 3/502723 characterised by venting arrangements
• CPC Class Codes: B01L 3/502746 characterised by the means for controlling flow resistance, e.g. flow controllers, baffles B01L3/502738 takes precedence
• CPC Class Codes: B01L 3/502761 specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules investigating characteristics of particles G01N15/00
• CPC Class Codes: B01L 3/502776 specially adapted for focusing or laminating flows
• CPC Class Codes: G01N 15/1404 Handling flow, e.g. hydrodynamic focusing
• CPC Class Codes: G01N 15/1459 the analysis being performed on a sample stream
• CPC Class Codes: G01N 15/1484 microstructural devices
• CPC Class Codes: G01N 15/149 specially adapted for sorting particles, e.g. by their size or optical properties
• CPC Class Codes: G01N 2015/012 Red blood cells
• CPC Class Codes: G01N 2015/1006 for cytology
• CPC Class Codes: G01N 2015/1486 : Counting the particles

Abstract

A microfluidic circuit cartridge for a complete blood count, including analyses of red blood cells. Various parameters of the red blood cells may be attained. The cartridge may have sphering mechanism which has a channel or loop with a configuration for reducing or eliminating cell settling. The channel or loop may incorporate a combination of straight and curve paths in the context of gravity. The channel may alternatively have a hydrophilic or hydrophobic inside surface. Again alternatively, the channel may have an electro-wettable inside surface. Or, the channel may be subject to an electric or magnetic field. There may also be a mechanism for reducing or eliminating clumping of a sample.

Claims

1. A fluidic analyzer system comprising:

a removable cartridge having a microfluidic circuit; and

a housing for holding the removable cartridge; and

wherein;

the microfluidic circuit is for at least partially providing a blood count of a sample; and

the microfluidic circuit comprises;

a first structure for reducing sediment settling of the sample;

a second structure for reducing clumping of the sample;

a sphering mechanism connected to the second structure;

a sheathing mechanism;

a hydrodynamic focusing chamber connected to the sphering mechanism and the sheathing mechanism; and

an optical channel connected to the hydrodynamic focusing chamber for at least partially achieving the blood count.

2. The system of claim 1, wherein the sphering mechanism is for providing a portion of blood to waste so as to maintain a continuous flow through the sphering mechanism to reduce sediment settling of the sample.

3. The system of claim 1, wherein the first structure is at least partially integrated with the sphering mechanism.

4. The system of claim 1, wherein the blood count comprises a red blood count, a platelet count, a mean cell volume determination of RBCs, multi-part differential counts of white blood cells (WBCs), and/or hemoglobin absorbence-based measurements.

5. The system of claim 1, wherein the second structure is for applying a shearing effect on the sample to nearly eliminate clumping of the sample.

6. The system of claim 1, wherein the second structure is a sample injector having a T-junction to a flow channel of the microfluidic circuit.

7. The system of claim 1, wherein channels of the first structure, second structure, sphering mechanism, and/or hydrodynamic focusing chamber, have connecting ends which are about the same size to reduce a presence of bubbles.

8. The system of claim 1, wherein the first structure comprises:

a channel having a continuous path that is approximately straight for a first distance, curved about between 90 and 270 degrees for a second distance and approximately straight for a third distance; and

wherein;

the channel is situated in a field of force having a first direction; and

the first distance and the third distance are approximately parallel to the first direction.

9. The system of claim 8, wherein:

the channel is a sphering channel; and

the field of force is a gravity force.

10. The system of claim 1, wherein the first structure comprises:

a channel; and

wherein;

the channel comprises;

a first segment having an elongated dimension approximately perpendicular to a first direction;

a second segment connected to the first segment, having an elongated dimension that curves about between 90 and 270 degrees; and

a third segment connected to the second segment, having an elongated dimension approximately perpendicular to the first direction;

the channel is situated in a field of force;

the field of force has a force in the first direction; and

the second segment is situated in a plane approximately parallel to the first direction.

11. The system of claim 10, wherein the channel is a sphering channel.

12. The system of claim 1, wherein the first structure comprises:

a channel; and

wherein the channel comprises;

a first segment;

a second segment connected to the first segment;

a third segment connected to the first segment; and

a fourth segment connected to the second and third segments;

the second segment sequentially curves in a first direction and a second direction way;

the third segment sequentially curves the second direction and the first direction;

the channel is situated in a field of force; and

the channel has an elongated dimension approximately perpendicular to a direction of the field of force.

13. The system of claim 12, wherein:

the channel is a sphering channel; and

the field of force is a gravity field.

14. The system of claim 1, wherein the first structure comprises:

a channel; and

wherein the channel comprises;

an inside surface; and

wherein the inside surface is hydrophilic.

15. The system of claim 14, wherein the channel is a sphering channel.

16. The system of claim 1, wherein the first structure comprises:

a channel; and

wherein channel comprises;

an inside surface; and

wherein the inside surface is hydrophobic.

17. The system of claim 16, wherein the channel is a sphering channel.

18. The system of claim 1, wherein the first structure comprises:

a channel; and

wherein the channel comprises;

an inside surface; and

wherein the inside surface is an electro-wetable surface.

19. The system of claim 18, wherein the channel is a sphering channel.

20. The system of claim 18, wherein:

the channel has a first end for an entry of a flow of a fluid;

the channel has a second end for an exit of the flow of a fluid;

the first end has a first terminal;

the second end has a second terminal; and

the first terminal and the second terminal are for an application of an electric potential.

21. The system of claim 20, wherein the inside surface has an energy change with the application of a voltage.

22. The system of claim 1, wherein the first structure comprises

a channel;

and

wherein;

the channel comprises a first end and a second end;

the channel is subject to an electric field; and

the channel has an elongated dimension approximately perpendicular to the electric field.

23. The system of claim 22, wherein the channel is a sphering channel.

24. The system of claim 1, wherein the first structure comprises:

a channel; and

wherein;

the channel comprises a first end and a second end;

the channel is subject to a magnetic field; and

an elongated dimension of the channel is approximately perpendicular to the magnetic field.

25. The system of claim 24, wherein the channel is a sphering channel.

26. A cytometer comprising:

a microfluidic circuit; and

wherein;

the microfluidic circuit comprises;

a shearing mechanism; and

a sphering mechanism; and

the sphering mechanism comprises a channel for sphering red blood cells;

the shearing mechanism comprises an injector attached to the channel to form a junction for providing blood into the channel so as to produce a shear on the blood at a wall in the channel to reduce or eliminate clumping.

27. The cytometer of claim 26, wherein:

the microfluidic circuit is for providing a blood count; and

the blood count comprises red cell indices.

28. A hematology analyzer comprising:

a fluidic circuit for providing a blood count; and

wherein;

the blood count comprises a red blood count, a platelet count, mean cell volume determination of RBCs, multi-part differential counts of white blood cells (WBCs), and/or hemoglobin absorbence-based measurements; and

the fluidic circuit comprises;

a shearing mechanism;

a sphering mechanism connected to the shearing mechanism;

a sheathing mechanism;

a hydrodynamic focusing chamber connected to the sphering mechanism and the sheathing mechanism; and

an optical channel connected to the hydrodynamic focusing chamber for at least partially achieving the blood count.

29. The analyzer of claim 28, wherein

the sphering mechanism comprises a first channel for sphering red blood cells;

the shearing mechanism comprises a second channel attached to a third channel to form a T-like junction for providing blood into the third channel to produce a shear on the blood at a wall in the third channel so as to nearly eliminate clumping of blood cells; and

the first channel is connected to the third channel.