Microfluidic devices for isolating particles

Abstract

In one aspect, a system for isolating particles includes a first array of magnets, a second array of magnets arranged generally in parallel with and spaced apart from the first array of magnets, and a microfluidic device. The microfluidic device includes a substrate, an inlet arranged on the substrate and configured to receive a fluid sample, an outlet arranged on the substrate, a first region of the substrate including a channel connected to the inlet, where the first region of the substrate is arranged to sandwich the channel between the first and second arrays of magnets, and a second region of the substrate in fluid communication with the channel and including a particle capture zone containing a plurality of particle capture sites, where each particle capture site including a receptacle sized to confine a first type of particle and an opening in fluid communication with the receptacle, wherein a size of the receptacle is larger than a size of the opening.

1 .- 36 . (canceled) 
     
     
         37 . A system for isolating particles from a fluid sample, comprising:
 a first array of magnets arranged in a first two-dimensional checkerboard pattern of magnets with directly adjacent magnets in the first array having dipole moments aligned in opposite directions;   a second array of magnets arranged in a second two-dimensional checkerboard pattern of magnets with directly adjacent magnets in the second array having dipole moments aligned in opposite directions; and   a microfluidic device located between the first array of magnets and the second array of magnets, wherein the microfluidic device comprises:
 an inlet configured to receive the fluid sample; 
 an outlet; and 
 one or more channels extending between the inlet and the outlet, wherein at least a portion of at least one of the one or more channels is positioned between the first array of magnets and the second array of magnets. 
   
     
     
         38 . The system of  claim 37 , wherein the second array of magnets is arranged generally in parallel with the first array of magnets. 
     
     
         39 . The system of  claim 37 , wherein the microfluidic device comprises a particle capture zone in fluid communication with the one more channels, wherein the particle capture zone comprises a plurality of particle capture sites. 
     
     
         40 . The system of  claim 39 , wherein at least one of the particle capture sites comprises:
 a receptacle sized to confine a first type of particle; and   an opening in fluid communication with the outlet.   
     
     
         41 . The system of  claim 40 , wherein the size of the receptacle is larger than a diameter of the first type of particle. 
     
     
         42 . The system of  claim 41 , wherein the receptacle allows passage of particles smaller than the opening. 
     
     
         43 . The system of  claim 37 , further comprising:
 a tweezer device configured to displace a particle captured in one of the particle capture sites; and   a receiver device configured to receive the displaced particle.   
     
     
         44 . The system of  claim 43 , wherein the tweezer device comprises an optical source for generating an optical beam, and a lens for focusing the optical beam into one of the particle capture sites. 
     
     
         45 . The system of  claim 37 , wherein at least one particle capture site comprises a first wall and a corresponding second wall, wherein the receptacle is bounded by the first wall and the second wall, and wherein the opening is defined between an end of the first wall and an end of the second wall. 
     
     
         46 . The system of  claim 37 , further comprising a fluid manifold positioned between the particle capture zone and the outlet. 
     
     
         47 . A method for isolating particles, the method comprising:
 providing a first array of magnets and a second array of magnets, wherein the first array of magnets is arranged in a first two-dimensional checkerboard pattern of magnets with directly adjacent magnets in the first array having dipole moments aligned in opposite directions, and wherein the second array of magnets is arranged in a second two-dimensional checkerboard pattern of magnets with directly adjacent magnets in the second array having dipole moments aligned in opposite directions;   providing a microfluidic device between the first array of magnets and the second array of magnets, wherein the microfluidic device comprises one or more channels, wherein at least a portion of at least one of the one or more channels is positioned between the first array of magnets and the second array of magnets; and   flowing a sample fluid comprising a plurality of particles through the one or more channels, wherein at least one first type of particle is bound to a magnetic bead, and wherein a magnetic field extending between the first array of magnets and the second array of magnets within the one or more channels causes the at least one first type of particle to separate from remaining particles in the fluid sample.   
     
     
         48 . The method of  claim 47 , further comprising:
 flowing the fluid sample containing the remaining particles to a particle capture zone of the microfluidic device, wherein the particle capture zone comprises a plurality of particle capture sites.   
     
     
         49 . The method of  claim 48 , wherein at least one of the particle capture sites comprises a receptacle that is larger than a diameter of a second type of particle in the remaining particles, and
 wherein the receptacle allows passage of other remaining particles smaller than the opening.   
     
     
         50 . The method of  claim 49 , further comprising:
 capturing one or more of the second type of particles in at least one of the receptacles of the particle capture sites of the microfluidic device, wherein the one or more second type of particles are not bound to a magnetic bead.   
     
     
         51 . The method of  claim 50 , further comprising:
 displacing the one or more second type of particles from the particle capture sites using an optical tweezer.   
     
     
         52 . The method of  claim 51 , wherein displacing the one or more second type of particles from the particle capture sites comprises displacing a single one of the second type of particles from a single one of the particle capture sites. 
     
     
         53 . The method of  claim 51 , further comprising:
 flowing a first additional fluid through at least the particle capture zone, wherein the first additional fluid comprises a plurality of first fluorescent markers; and   allowing the plurality of the first fluorescent markers to bind to one or more of the second type of particle.   
     
     
         54 . The method of  claim 53 , further comprising:
 optically exciting the first fluorescent markers bound to the one or more second type of particle;   obtaining a first image of the one or more second type of particle; and   determining a characteristic of the second type of particle based on the obtained first image.   
     
     
         55 . The method of  claim 54 , further comprising:
 flowing an elutant through at least the particle capture zone, wherein flowing the elutant causes the fluorescently labeled particles to release from the second type of particle; and   flowing a second additional fluid sample through at least the particle capture zone,   wherein the second additional fluid comprises a plurality of a second type of fluorescent marker, and wherein one of more of the second type of fluorescent markers bind to one or more of the second type of particle.   
     
     
         56 . The method of  claim 55 , further comprising:
 optically exciting one or more of the second fluorescent markers bound to the second type of particle;   obtaining a second image of the second type of particle; and   determining a characteristic of the second type of particle based on the obtained second image.