Microfluidic and nanofluidic devices, systems, and applications

Abstract

The present invention discloses the integration of programmable microfluidic circuits to achieve practical applications to process biochemical and chemical reactions and to integrate these reactions. In some embodiments workflows for biochemical reactions or chemical workflows are combined. Microvalves such as programmable microfluidic circuit with Y valves and flow through valves are disclosed. In some embodiments microvalves of the present invention are used for mixing fluids, which may be part of an integrated process. These processes include mixing samples and moving reactions to an edge or reservoir for modular microfluidics, use of capture regions, and injection into analytical devices on separate devices. In some embodiments star and nested star designs, or bead capture by change of cross sectional area of a channel in a microvalve are used. Movement of samples between temperature zones are further disclosed using fixed temperature and movement of the samples by micropumps.

1 .- 30 . (canceled) 
     
     
         31 . A system comprising: a first microfluidic device comprising: a first microfluidic circuit comprising an inlet, an outlet, a pump and at least one first functional component selected from a reactor, a capture region, a temperature cycling zone, a hot zone, a cool zone, separation channel, analysis circuit, mixer, bead processing unit, and a magnet, wherein the pump is configured to pump fluid through the circuit; and a second microfluidic device comprising: a plurality of second microfluidic circuits, each comprising an inlet, and outlet and at least one functional component which is different than a first functional component; wherein the first and second components are configured to engage in a plurality of positions, wherein in each position the outlet of the first circuit is mated with the inlet of one of the second circuits to allow fluid to flow from the first circuit into the mated second circuit. 
     
     
         32 .- 38 . (canceled) 
     
     
         39 . A method comprising:
 I) providing a system comprising: a first microfluidic device comprising:
 a first microfluidic circuit comprising an inlet, an outlet, a pump and at least one first functional component selected from a reactor, a capture region, a temperature cycling zone, a hot zone, a cool zone, separation channel, analysis circuit, mixer, bead processing unit, and a magnet, wherein the pump is configured to pump fluid through the circuit; and 
 a second microfluidic device comprising: a plurality of second microfluidic circuits, each comprising an inlet, and outlet and at least one functional component which is different than a first functional component; wherein the first and second components are configured to engage in a plurality of positions, wherein in each position the outlet of the first circuit is mated with the inlet of one of the second circuits to allow fluid to flow from the first circuit into the mated second circuit; and 
   II) performing a method comprising:
 a) performing a first operation on a first sample in a first microfluidic circuit of a first microfluidic device comprising: a microfluidic layer, an actuation layer and elastomer layer sandwiched between them, wherein: the microfluidic layer comprises a microfluidic channel; the actuation layer comprises at least one actuation channel opening into a valve chamber, which valve chamber is disposed along the microfluidic channel; and wherein fluid flows along the channel whether or not the elastomeric membrane is displaced, but displacement of said elastomeric membrane modulates fluid flow along said channel, thereby forming a diaphragm valve; 
 b) engaging the first and second microfluidic devices of the system so that the output of the first circuit is mated with the inlet of a first of the second microfluidic circuits; 
 c) moving first sample after the operation from the first circuit into the first of the second circuits; 
 d) performing a second operation on the received first sample in the first of the second circuits; 
 e) performing the first operation on a second sample in the first microfluidic circuit; 
 f) engaging the first and second microfluidic devices so that the output of the first circuit is mated with the inlet of a next, different one of the second microfluidic circuits; 
 g) moving second sample after the operation from the first circuit into the next of the second circuits; and 
 h) performing the second operation on the first reacted sample in the first of the second circuits. 
   
     
     
         40 .- 42 . (canceled) 
     
     
         43 . A method of making a microfluidic device comprising: joining a plurality of layers to form a plurality of microchannels and diaphragm valves; wherein said plurality of layers are sandwiched together; wherein said at least two layers of said plurality of layers are selected from the group consisting of an elastomeric membrane, an actuation layer, a microfluidic layer; a valve layer, heat spreaders, a vias layer, an interface layer, and a cover layer. 
     
     
         44 .- 49 . (canceled) 
     
     
         50 . A microfluidic device comprising: a) a microfluidic channel; b) a first temperature zone disposed along the channel having a temperature above ambient temperature; c) a second temperature zone disposed along the channel having a temperature below ambient temperature; and d) a positive displacement pump disposed along the channel and configured to pump liquid into the first and second temperature zones. 
     
     
         51 .- 62 . (canceled) 
     
     
         63 . A microfluidic device comprising: a microfluidic layer comprising a microfluidic channel, wherein the channel comprises at least one tight bend comprising two channel segments connected with each other and oriented in an acute angle; and means for producing a magnetic field that produces a magnetic field in the area of the tight bend, wherein paramagnetic particles flowing through the tight bend are retarded by the magnetic field. 
     
     
         64 .- 75 . (canceled)