Microfluidic devices and methods for performing serum separation and blood cross-matching

• US 10,386,377 B2
• Filed: 05/07/2014
• Issued: 08/20/2019
• Est. Priority Date: 05/07/2013
• Status: Active Grant

• Current Assignee: Revvity Health Sciences Incorporated (Revvity, Inc.)
• Original Assignee: Micronics Inc. (Sony Group Corp.)
• Inventors: Kolb, Andrew W., Elmufdi, Carolina L., Battrell, C. Frederick
• Primary Examiner(s): Martinez, Rebecca L
• Application Number:
  US14/889,366
• Publication Number:
  US 20160109467A1
• Time in Patent Office: 1,931 Days
• Field of Search: None
• CPC Class Codes: B01L 2200/027 for microfluidic devices
• 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 2300/0681 Filter
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0867 Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2300/0883 Serpentine channels
• CPC Class Codes: B01L 2300/163 Biocompatibility
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 2400/0481 squeezing of channels or chambers
• 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
• CPC Class Codes: B01L 3/502753 characterised by bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation separation in general B01D; microapparatus for analysis using electrophoresis G01N27/44791; sample preparation G01N1/28
• 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: G01N 33/491 by separating the blood components G01N15/05 takes precedence
• CPC Class Codes: G01N 33/80 involving blood groups or blood types or red blood cells white blood cells G01N33/56972
• CPC Class Codes: G01N 33/86 involving blood coagulating time or factors, or their receptors

Abstract

Microfluidic cartridges or devices for serum separation and blood cross-match analysis are provided. The devices may include a serum separation subcircuit alone or in combination with a solute mixing subcircuit. The serum separation subcircuit promotes on-cartridge clotting of a blood sample and manipulates the flow of the separated serum sample for subsequent cross-match analysis with a second blood sample, for example. The solute mixing subcircuit includes at least two intake channels, one for a whole blood sample from, for example, a blood donor and the other for the separated serum sample from, for example, a transfusion recipient. The solute mixing subcircuit further includes a serpentine mixing channel conjoined to a downstream channel. Under vacuum generated by a conjoined finger pump, the two input streams fill the serpentine mixing and downstream channels due to capillary action, enabling visualization of an agglutination reaction.

Claims

1. A microfluidic device comprising:

a) a fluid separation subcircuit comprising;

i) a microfluidic channel having a first end and a second end;

ii) a sample inlet fluidly connected to the first end of the microfluidic channel configured for receiving a blood sample;

iii) a composite membrane interposed between the sample inlet and the first end of the microfluidic channel, wherein the composite membrane is capable of activating blood coagulation and removing selected particles from the blood, wherein the composite membrane comprises a glass fiber filter; and

iv) an on-device pump fluidly connected to the second end of the microfluidic channel; and

b) a solute mixing subcircuit comprising;

i) a serpentine mixing channel, said mixing channel having a first end and a second end and having a critical length for enabling solute mixture by diffusion;

ii) first, second, and third intake channels fluidly joined to said first end of said mixing channel at a staging union;

said first intake channel for conveying a first fluid, said second intake channel for conveying a second fluid, and said third intake channel for conveying a third fluid;

wherein said staging union is configured with micro-passive valves for simultaneously releasing said first, second, and third fluids into said staging union and into said mixing channel, and for simultaneously mixing said first second, and third fluids in said staging union and in said mixing channel;

iii) a downstream channel fluidly joined to the second end of said mixing channel, wherein the downstream channel has a width greater than the width of the mixing channel;

iv) a pump for controlledly initiating fluid flow across said micro-passive valves, wherein said pump is fluidly connected to said downstream channel, and initiates flow by a suction stroke; and

v) a vent terminating said downstream channel,

wherein the fluid separation subcircuit and solute mixing subcircuits are fluidly connected.

2. The microfluidic device of claim 1, wherein the composite membrane comprises at least two membranes.

3. The microfluidic device of claim 1, wherein the composite membrane further comprises a porous membrane.

4. The microfluidic device of claim 1, wherein the composite filter further comprises an activator of blood coagulation.

5. A method for performing a cross match of a donor blood sample and a recipient blood sample, the method comprising:

a) introducing the donor blood sample into the sample inlet of the microfluidic device of claim 1 and contacting the donor blood sample with the composite membrane to separate donor serum from the donor blood sample;

b) contacting the donor serum with the recipient blood sample in the mixing channel; and

c) observing the presence or absence of an agglutination reaction.

6. The microfluidic device of claim 1 wherein the first fluid comprises a particulate suspension of red blood cells, the second fluid comprises separated serum, and the third fluid comprises a diluent.

7. The microfluidic device of claim 1 wherein the composite membrane includes platelet activating factor.

8. The microfluidic device of claim 1 wherein the composite membrane includes collagen.

9. The microfluidic device of claim 1 wherein the composite membrane includes hollow beads.