Fluidic units and cartridges for multi-analyte analysis

• US 10,022,720 B2
• Filed: 06/08/2016
• Issued: 07/17/2018
• Est. Priority Date: 06/12/2015
• Status: Active Grant

• Current Assignee: Cytochip Inc.
• Original Assignee: Cytochip Inc.
• Inventors: Shi, Wendian, Ding, Yuzhe
• Primary Examiner(s): Sines, Brian J.
• Application Number:
  US15/176,729
• Publication Number:
  US 20160361715A1
• Time in Patent Office: 769 Days
• Field of Search: 422 681, 422502, 422503, 422554, 422560, 422561, 436 43, 436180
• CPC Class Codes: A61B 10/0096 Casings for storing test samples A61B10/0038 and A61B10/0045 take precedence; preservation of living parts of the human or animal body A01N1/02; containers for retaining a material to be analysed B01L3/50; containers for enzymology or microbiology C12M1/16; swab-sampler being part of enzymology or microbiology container C12M1/30
• CPC Class Codes: A61B 5/150022 for capillary blood or interstitial fluid
• CPC Class Codes: B01L 2200/141 Preventing contamination, tampering
• CPC Class Codes: B01L 2200/143 Quality control, feedback systems
• CPC Class Codes: B01L 2300/0627 Sensor or part of a sensor is integrated
• CPC Class Codes: B01L 2300/0645 Electrodes
• CPC Class Codes: B01L 2300/0681 Filter
• CPC Class Codes: B01L 2300/0861 Configuration of multiple channels and/or chambers in a single devices
• CPC Class Codes: B01L 2300/0864 comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
• 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 2300/0887 Laminated structure
• CPC Class Codes: B01L 2300/14 Means for pressure control
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 2400/0409 centrifugal forces
• CPC Class Codes: B01L 2400/0457 passive flow or gravitation
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 2400/0688 surface tension valves, capillary stop, capillary break
• CPC Class Codes: B01L 2400/088 by specific surface properties
• CPC Class Codes: B01L 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B01L 3/502723 : characterised by venting arrangements
• CPC Class Codes: B01L 3/50273 : characterised by the means or forces applied to move the fluids micropumps F04B19/006, of the membrane type F04B43/043
• CPC Class Codes: B01L 3/502738 : characterised by integrated valves microvalves F16K99/0001

Abstract

A fluidic device for a cartridge for testing biological samples is disclosed herein. In an embodiment, the fluidic device includes a fluidic chamber, at least one microfluidic channel in fluid communication with the fluidic chamber, a venting port configured to apply a pneumatic force to the fluidic chamber, at least one passive valve located within the at least one microfluidic channel and configured to allow or stop fluid flow through the at least one microfluidic channel based on a pressure difference, and a controller configured to control the pneumatic force applied to the fluidic chamber via the venting port.

Claims

1. A fluidic device for analyzing a fluid sample, the fluidic device comprising:

a cartridge device configured to receive the fluid sample, the cartridge device including;

a fluidic chamber;

at least one microfluidic channel in fluid communication with the fluidic chamber;

a venting port configured to apply a pneumatic force to the fluidic chamber; and

at least one passive valve located within the at least one microfluidic channel and configured to allow or stop fluid flow through the at least one microfluidic channel based on a pressure difference; and

a controller configured to control the pneumatic force applied to the fluidic chamber via the venting port,

wherein the cartridge device is configured to be received by the fluidic device in a vertical or tilted position such that at least a portion of fluid inside the fluidic chamber is pulled by gravity in a direction away from the venting port or towards a bottom of the fluidic chamber.

2. The fluidic device of claim 1, wherein the cartridge device is configured to be held in the vertical position by a housing of the fluidic device.

3. The fluidic device of claim 2, wherein the venting port is located at a top portion of the fluidic chamber when the fluidic chamber is held in the vertical position.

4. The fluidic device of claim 2, wherein the at least one microfluidic channel is located a height below the venting port when the fluidic chamber is held in the vertical position.

5. The fluidic device of claim 2, wherein the at least one microfluidic channel includes a first microfluidic channel and a second microfluidic channel, the first microfluidic channel located a height above the second microfluidic channel with the fluidic chamber held in the vertical position.

6. The fluidic device of claim 1, wherein the at least one passive valve includes at least one of:

(i) a hydrophobic patch;

(ii) a hydrophilic patch;

(iii) a sudden diameter enlargement of a hydrophobic channel; and

(iv) a sudden diameter shrink of a hydrophobic channel.

7. The fluidic device of claim 1, wherein the controller is configured to control the pneumatic force applied to the fluidic chamber via the venting port based on (i) a pressure (P₀) associated with the venting port, and (ii) a pressure (P₁) associated with the at least one microfluidic channel.

8. The fluidic device of claim 7, wherein the controller is configured to store fluid in the fluidic chamber by controlling the pneumatic force applied to the fluidic chamber via the venting port according to the following equations:

−

Δ

P_in−

ρ

gh≤

P₀−

P₁≤

Δ

P_out−

ρ

gh, if h≥

0; and

P₁−

P₀≤

Δ

P_in, if h<

0,

wherein (i) Δ

P_in is a first threshold pressure associated with a first direction of fluid entering the fluidic chamber, (ii) Δ

P_out is a second threshold pressure associated with a second direction of fluid leaving the fluidic chamber, and (iii) ρ

gh is the hydraulic pressure of the fluid.

9. The fluidic device of claim 7, wherein the controller is configured to transfer fluid into the fluidic chamber by controlling the pneumatic force applied to the fluidic chamber via the venting port according to the following equations:

P₁−

P₀>

Δ

P_in+ρ

gh, if h≥

0; and

P₁−

P₀>

Δ

P_in, if h<

0,

wherein (i) Δ

P_in is a threshold pressure associated with a direction of fluid entering the fluidic chamber, and (ii) ρ

gh is the hydraulic pressure of the fluid.

10. The fluidic device of claim 7, wherein the controller is configured to transfer fluid out of the fluidic chamber by controlling the pneumatic force applied to the fluidic chamber via the venting port according to the following equation:

P₀−

P₁>

Δ

P_out−

ρ

gh,

wherein (i) Δ

P_out is a threshold pressure associated with a direction of fluid leaving the fluidic chamber, and (ii) ρ

gh is the hydraulic pressure of the fluid.

11. The fluidic device of claim 1, wherein the fluidic chamber includes at least one filter membrane with a pore size smaller than known particles in the fluid.

12. The fluidic device of claim 1, wherein the cartridge device includes a plurality of fluidic chambers, and wherein the controller controls the pneumatic pressure applied to respective venting ports of the plurality of fluidic chambers independently of each other.

13. The fluidic device of claim 12, wherein the plurality of fluidic chambers includes a first fluidic chamber and a second fluidic chamber, the first fluidic chamber and the second fluidic chamber in fluid communication via only one microchannel.

14. The fluidic device of claim 1, wherein the fluidic chamber has a size of about 0.1 mm to 50 mm in width, 0.1 mm to 50 mm in depth and 0.1 mm to 100 mm in height, and wherein the microfluidic channel has a cross section size about 0.1 μ

m to 5 mm in width and 0.1 μ

m to 5 mm in depth.

15. The device of claim 1, wherein the cartridge device includes at least two microfluidic channels in fluid communication with the fluidic chamber, and wherein the controller is configured to transfer fluid out of the chamber via at least one of the microfluidic channels.

16. The fluidic device of claim 1, wherein the pneumatic force applied at the venting port is ambient pressure or atmospheric pressure.

17. The fluidic device of claim 1, wherein the fluidic chamber has a volume larger than a volume of the fluid sample received therein, and wherein an air gap exists between the venting port and the fluid sample received therein.

18. The fluidic device of claim 1, wherein the cartridge device is configured to receive a fluid sample with air bubbles in the fluidic chamber, and wherein at least a portion of the air bubbles is separated from the sample in the fluidic chamber by gravity.

19. The fluidic device of claim 18, wherein the controller is configured to generate at least a portion of the air bubbles in the fluid sample by applying a pneumatic force to the cartridge device.

20. The fluidic device of claim 18, wherein the cartridge device is configured to allow at least a portion of the air bubbles to exit the venting port.

21. The fluidic device of claim 1, wherein the controller is configured to transfer the fluid sample out of the fluidic chamber by transferring at least a portion of the fluid sample through one microfluidic channel and at least another portion of the fluid sample through another microfluidic channel.

22. The fluidic device of claim 1, wherein the controller is configured to transfer two or more fluid samples separately into the fluidic chamber to form a sample mixture.

23. The fluidic device of claim 1, wherein the controller is configured to transfer two or more fluid samples separately into the fluidic chamber, and to transfer the two or more fluid samples separately out of the fluidic chamber by flowing the two or more fluid samples through a microfluidic channel.

24. The fluidic device of claim 11, wherein the fluidic chamber is configured to receive a fluid sample with cells, a fluid sample with blood cells, or a fluid sample with particles carrying nucleic acids, and wherein the filter membrane has pore sizes smaller than at least a portion of the cells, the blood cells or the particles carrying nucleic acids.

25. The fluidic device of claim 11, wherein the cartridge device is configured to be in fluid communication with a microfluidic channel on one side of the filter membrane, and to be in fluid communication with another microfluidic channel on another side of the filter membrane.

26. The fluidic device of claim 1, wherein the cartridge device further comprises at least one fluidic structure for sample measurements, and wherein at least one sensing signal is measured from a fluid sample in the fluidic structure.

27. The fluidic device of claim 26, wherein the fluidic structure comprises a sheathless channel for a cytometer analysis of cells or particles in the fluid sample, and wherein at least one of the following signals is measured:

(i) an optical sensing signal; and

(ii) an impedance sensing signal.

28. The fluidic device of claim 26, wherein the fluidic structure comprises a chamber, and wherein at least one optical sensing signal is measured from a fluid sample in the chamber.

29. The fluidic device of claim 26, wherein the fluidic structure comprises one or more sensing zones, and wherein at least one of the sensing zones is coated with antigens to capture antibodies in a fluid sample in the sensing zones.

30. The fluidic device of claim 26, wherein the fluidic structure comprises one or more electrodes, and wherein at least one electrical signal is measured from a fluid sample in contact with the one or more of electrodes.