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 - 75 . (canceled) 
     
     
         76 . An microfluidic device comprising:
 a) at least one microfluidic channel, wherein the channel comprises a first region and a second region in sequence, wherein the cross-sectional area of the second region is greater than that of the first region; and   b) a magnet configured to produce a magnetic field in the second region.   
     
     
         77 . The microfluidic device of  claim 76 , further comprising particles in the second region captured by the magnetic field. 
     
     
         78 . The microfluidic device of  claim 76  comprising a fluidics layer comprising the microfluidic channel, an actuation layer comprising at least one actuation channel and an elastomer layer sandwiched between them. 
     
     
         79 . The microfluidic device of  claim 76 , wherein the second region comprises a diaphragm valve having at least a first position and a second position, wherein the valve has increased cross-sectional area in the second position, and wherein the magnet produces a magnetic field within the valve. 
     
     
         80 . The microfluidic device of  claim 76 , wherein the magnet is movable. 
     
     
         81 . A microfluidic device comprising:
 a) at least one microfluidic channel comprising a first valve, wherein the valve has at least a first position and a second position in which the cross-sectional area of the valve is increased; and   b) a magnet configured to produce a magnetic field within the valve.   
     
     
         82 . The microfluidic device of  claim 81 , wherein the first valve is a diaphragm valve. 
     
     
         83 . The microfluidic device of  claim 82 , wherein the device comprises at least one microfluidic circuit comprising the microfluidic channel and further comprising:
 c) a first port and a second port fluidically connected to the channel;   d) a second channel that converges with the first channel at a nexus wherein the nexus comprises a valve that, when open, allows for fluid communication between said first and second channels and, when closed, interrupts flow fluid communication between the first and second channels but not along the first channel, wherein the second channel is fluidically connected to a third port;   e) a reactor; and   f) at least one diaphragm pump comprising three diaphragm valves configured to pump fluid from the first port and the second port into the first valve, into the reactor and into the third port.   
     
     
         84 . The microfluidic device of  claim 83 , wherein a plurality of circuits share a second port. 
     
     
         85 . The microfluidic device of  claim 83 , wherein the at least one microfluidic channel is a plurality of microfluidic channels and wherein valves in a plurality of different circuits are actuated by a single actuation channel. 
     
     
         86 . The microfluidic device of  claim 83 , wherein the reactor is configured for thermal cycling and the device further comprises a thermal cycler. 
     
     
         87 . The microfluidic device of  claim 81 , further comprising particles in the valve in the second position captured by the magnetic field. 
     
     
         88 . The microfluidic device of  claim 81 , wherein fluid can travel through the valve in both first position and the second position. 
     
     
         89 . The microfluidic device of  claim 81 , wherein the magnet is movable. 
     
     
         90 . The microfluidic device of  claim 81 , further comprising a fluidics layer comprising the microfluidic channel, an actuation layer comprising actuation channels and an elastomer layer sandwiched between them, wherein the first valve is a diaphragm valve formed where the microfluidic channel opens onto the elastomer layer and the actuation channel opens onto the elastomer layer at the valve chamber. 
     
     
         91 . A method comprising:
 a) providing a microfluidic device comprising:
 i) at least one microfluidic channel, wherein the channel comprises a first region and a second region in sequence, wherein the cross-sectional area of the second region is greater than the first region; and 
 ii) a magnet configured to produce a magnetic field in the second region; 
   b) flowing particles through the first region and into the second region; and   c) capturing the particles in the second region with the magnetic field.   
     
     
         92 . The method of  claim 91 , further comprising:
 d) releasing the particles from the magnetic field.   
     
     
         93 . The method of  claim 91 , wherein the particles are bound to at least one analyte. 
     
     
         94 . The method of  claim 91 , wherein the second region comprises a diaphragm valve having a first position and a second position, wherein the valve has increased cross-sectional area in the second position, and wherein the magnet produces a magnetic field within the valve. 
     
     
         95 . A method comprising:
 a) providing a microfluidic device comprising:
 i) at least one microfluidic channel comprising a valve, wherein the valve has a first position and a second position in which the cross-sectional area of the valve is increased; and 
 ii) a magnet configured to produce a magnetic field within the valve; 
   b) positioning the valve in the second position;   c) flowing particles through the channel into the valve; and   d) capturing the particles in the valve with the magnetic field.   
     
     
         96 . The method of  claim 95 , wherein the particles are bound to at least one analyte. 
     
     
         97 . The method of  claim 96 , wherein the analyte comprises a nucleic acid. 
     
     
         98 . The method of  claim 96 , further comprising:
 e) washing the particles with attached analyte(s) in the valve.   
     
     
         99 . The method of  claim 96 , further comprising:
 e) eluting the analyte(s) from the particles and moving the analyte(s) out of the valve.   
     
     
         100 . The method of  claim 95 , further comprising:
 e) releasing the particles from the magnetic field.   
     
     
         101 . The method of  claim 95 , further comprising:
 e) performing a chemical or biochemical reaction on the analyte on the particles in the magnetic field.   
     
     
         102 . The method of  claim 100  wherein releasing the particles comprises moving the valve from the second position to the first position. 
     
     
         103 . A method comprising:
 a) providing a microfluidic device comprising:
 i) at least one microfluidic circuit, wherein the circuit comprises a first microfluidic channel comprising:
 (A) a first port; 
 (B) a second port; 
 (C) a first valve, wherein the valve has a first position and a second position in which the cross-sectional area of the first valve is increased; 
 (D) a second channel that converges with the first channel at a nexus wherein the nexus comprises a valve that, when open, allows for fluid communication between said first and second channels and, when closed, interrupts flow fluid communication between the first and second channels but not along the first channel, wherein the second channel is fluidically connected to a third port; 
 (E) a reactor; and 
 (F) at least one diaphragm pump comprising three diaphragm valves configured to pump fluid from the first port and the second port into the first valve, into the reactor and into the third port. 
 
 ii) a magnet configured to produce a magnetic field within the first valve; 
   b) pumping reagent from the first port and sample from the second port into the channel to form a mixture;   c) pumping the mixture into the reactor and performing a chemical or biochemical reaction on the mixture to create a product; and   d) contacting the analyte in the device with the particles wherein the particles bind analyte;   e) positioning the first valve in the second position;   f) flowing particles through the channel into the first valve; and   g) capturing the particles in the first valve with the magnetic field.   
     
     
         104 . The method of  claim 103 , further comprising:
 h) washing the particles.   
     
     
         105 . The method of  claim 104 , further comprising:
 i) collecting the product.   
     
     
         106 . The method of  claim 103 , wherein the chemical reaction comprises PCR, cycle sequencing, isothermal nucleic acid amplification, ligation, restriction, second strand synthesis, transcription, translation, DNA modification, polymerization, DNA-protein binding, additions, cleavages, cyclization or condensation.