Microfluidic apparatus and methods for performing blood typing and crossmatching
First Claim
1. A microfluidic cartridge for performing a blood type assay or crossmatch, which comprises:
- a) a body member comprised of a substrate or substrates, said body member enclosing a reaction channel, said reaction channel having a first end and a second end and having a critical dimension configured for establishing laminar flow conditions;
wherein said body member is comprised of an upper body layer and a base body layer, wherein said upper body layer and base body layer are joined by an adhesive core adhesive (ACA) glue layer, said ACA glue layer having a first glue face and a second glue face separated by a supportive core, and further wherein said first glue face and said second glue face of said ACA glue layer are formulated with an additive selected to modify the contact angle of the glue faces, wherein the contact angle of said first glue face is configured for wetting with whole blood and the contact angle of said second glue face is configured for wetting with a reagent solution, and thereby said contact angle of the first glue face and the contact angle of the second glue face are measurably distinct, wherein said contact angle of the first glue face is in the range of 10 to 20 degrees and said contact angle of the second glue face is in the range of 20 to 30 degrees;
b) a first and a second intake channel fluidly joined to said first end of said reaction channel at a staging union;
said first intake channel for conveying a first fluid and said second intake channel for conveying a second fluid;
wherein said staging union is configured with a dual capillary stop for simultaneously releasing said first and second fluids into said reaction channel in response to a start signal, said fluids contactedly flowing in parallel within said reaction channel as lamellae, one on top of the other;
c) a downstream flow control channel fluidly joined to the second end of said reaction channel, wherein the downstream flow control channel is further characterized as comprising an elongate runoff channel segment configured with microfluidic dimensions and reverse tapered walls that broaden from upstream to downstream for sustaining and modulating a passive laminar flow regime in said reaction channel wherein said passive laminar flow regime in said reaction channel is modulated and sustained as a horizontally-stratified laminar fluid diffusion interface characterized by an apparent Reynolds Number between 0.1 and 10, as determined in said reaction channel, for a duration of about thirty seconds to ten minutes, more preferably about thirty seconds to two minutes; and
d) a vent or check valve terminating said downstream flow control channel.
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Abstract
Microfluidic cartridges for agglutination reactions are provided. The cartridges include a microfluidic reaction channel with at least two intake channels, one for an antigen-containing fluid and the other for an antibody-containing fluid, conjoined to a reaction channel modified by incorporation of a downstream flow control channel. At low Reynolds Number, the two input streams layer one on top of the other in the reaction channel and form a flowing, unmixed horizontally-stratified laminar fluid diffusion (HLFD) interface for an extended duration of reaction. Surprisingly, the design, surface properties, and flow regime of microfluidic circuits of the present invention potentiate detection of antibody mediated agglutination at the stratified interface. Antigen:antibody reactions involving agglutination potentiated by these devices are useful in blood typing, in crossmatching for blood transfusion, and in immunodiagnostic agglutination assays, for example.
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Citations
24 Claims
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1. A microfluidic cartridge for performing a blood type assay or crossmatch, which comprises:
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a) a body member comprised of a substrate or substrates, said body member enclosing a reaction channel, said reaction channel having a first end and a second end and having a critical dimension configured for establishing laminar flow conditions;
wherein said body member is comprised of an upper body layer and a base body layer, wherein said upper body layer and base body layer are joined by an adhesive core adhesive (ACA) glue layer, said ACA glue layer having a first glue face and a second glue face separated by a supportive core, and further wherein said first glue face and said second glue face of said ACA glue layer are formulated with an additive selected to modify the contact angle of the glue faces, wherein the contact angle of said first glue face is configured for wetting with whole blood and the contact angle of said second glue face is configured for wetting with a reagent solution, and thereby said contact angle of the first glue face and the contact angle of the second glue face are measurably distinct, wherein said contact angle of the first glue face is in the range of 10 to 20 degrees and said contact angle of the second glue face is in the range of 20 to 30 degrees;b) a first and a second intake channel fluidly joined to said first end of said reaction channel at a staging union;
said first intake channel for conveying a first fluid and said second intake channel for conveying a second fluid;
wherein said staging union is configured with a dual capillary stop for simultaneously releasing said first and second fluids into said reaction channel in response to a start signal, said fluids contactedly flowing in parallel within said reaction channel as lamellae, one on top of the other;c) a downstream flow control channel fluidly joined to the second end of said reaction channel, wherein the downstream flow control channel is further characterized as comprising an elongate runoff channel segment configured with microfluidic dimensions and reverse tapered walls that broaden from upstream to downstream for sustaining and modulating a passive laminar flow regime in said reaction channel wherein said passive laminar flow regime in said reaction channel is modulated and sustained as a horizontally-stratified laminar fluid diffusion interface characterized by an apparent Reynolds Number between 0.1 and 10, as determined in said reaction channel, for a duration of about thirty seconds to ten minutes, more preferably about thirty seconds to two minutes; and d) a vent or check valve terminating said downstream flow control channel. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24)
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Specification