Cell sorting device and method of manufacturing the same

Abstract

A system, method and apparatus employing the laminar nature of fluid flows in microfluidic flow devices in separating, sorting or filtering colloidal and/or cellular particles from a suspension in a microfluidic flow device is disclosed. The microfluidic flow device provides for separating a particle within a suspension flow in a microfluidic flow chamber. The chamber includes a microfluidic channel comprising at least one inlet port for receiving a suspension flow under laminar conditions, a first outlet port and a second outlet port. The chamber further includes an interface for translating a particle within the channel. The first outlet port receives a first portion of the suspension exiting the said channel and the second outlet port receives the particle in a second portion of the suspension exiting the channel.

1 .- 71 . (canceled) 
     
     
         72 . A microfluidic device for separating particles according to size comprising a microfluidic channel, and an array comprising a network of gaps within the microfluidic channel, wherein the device employs a field that propels the particles being separated through the microfluidic channel; and wherein a flux of the field from the gaps is divided unequally into a major flux component and a minor flux component into subsequent gaps in the network such that the average direction of the major flux components is not parallel to the average direction of the field, and, when particles are introduced into the array, particles having a size less than a predetermined critical size are transported generally in the average direction of the field, and particles having a size at least that of the critical size are transported generally in the average direction of the major flux component, thereby separating the particles according to size. 
     
     
         73 . The microfluidic device of  claim 72 , wherein the array is an ordered array of obstacles. 
     
     
         74 . The microfluidic device of  claim 73 , wherein the ordered array of obstacles comprises obstacles arranged in rows, wherein each subsequent row of obstacles is shifted laterally with respect to the previous row. 
     
     
         75 . The microfluidic device of  claim 73 , wherein the ordered array of obstacles is tilted at an offset angle θ with respect to the direction of the field. 
     
     
         76 . The microfluidic device of  claim 72 , wherein the field is fluid flow, electrical, electro-osmotic, gravitational, hydrodynamic, pressure gradient, or capillary action. 
     
     
         77 . The microfluidic device of  claim 76 , wherein the field is a fluid flow. 
     
     
         78 . The microfluidic device of  claim 76 , wherein the field is an electrical field. 
     
     
         79 . The microfluidic device of  claim 72 , wherein the particles are single celled organisms, formed bodies as in blood, cells, viruses, nucleic acids, proteins, protein complexes, polymers, emulsions, or colloids. 
     
     
         80 . The microfluidic device of  claim 72 , wherein the particles are DNA molecules. 
     
     
         81 . The microfluidic device of  claim 72 , further comprising a first output, configured to accept particles having at least the predetermined critical size, and a second output, configured to accept particles smaller than the predetermined critical size. 
     
     
         82 . The microfluidic device of  claim 72 , further comprising a boundary, such that, when particles having a size at least as large as the predetermined critical size are introduced into the array, the particles having a size at least as large as the predetermined critical size are transported generally to the boundary, thereby concentrating the particles at the boundary. 
     
     
         83 . A microfluidic device for separating particles according to size comprising: a microfluidic channel, and an ordered array of obstacles within the microfluidic channel, wherein the device employs a field that propels the particles being separated through the microfluidic channel; and the ordered array of obstacles is asymmetric with respect to the average direction of the field, such that, when particles are introduced into the array, particles having a size less than a predetermined critical size are transported in a first direction, and particles having a size at least that of the critical size are transported in a second direction, wherein the first and second directions are different, thereby separating the particles according to size. 
     
     
         84 . The microfluidic device of  claim 83 , wherein the ordered array of obstacles comprises obstacles arranged in rows, wherein each subsequent row of obstacles is shifted laterally with respect to the previous row. 
     
     
         85 . The microfluidic device of  claim 83 , wherein the ordered array of obstacles is tilted at an offset angle θ with respect to the direction of the field. 
     
     
         86 . The microfluidic device of  claim 83 , wherein the field is fluid flow, electrical, electrophoretic, electro-osmotic, gravitational, hydrodynamic, pressure gradient, or capillary action. 
     
     
         87 . The microfluidic device of  claim 86 , wherein the field is a fluid flow. 
     
     
         88 . The microfluidic device of  claim 86 , wherein the field is an electrical field. 
     
     
         89 . The microfluidic device of  claim 83 , wherein the particles are single celled organisms, formed bodies as in blood, cells, viruses, nucleic acids, proteins, protein complexes, polymers, emulsions, or colloids. 
     
     
         90 . The microfluidic device of  claim 89 , wherein the particles are DNA molecules. 
     
     
         91 . The microfluidic device of  claim 83 , further comprising a first output configured to accept particles transported in the first direction and a second output configured to accept particles transported in the second direction. 
     
     
         92 . The microfluidic device of  claim 83 , further comprising a boundary, such that, when particles having a size at least as large as the predetermined critical size are introduced into the array, the particles having a size at least as large as the predetermined critical size are transported generally to the boundary, thereby concentrating the particles at the boundary. 
     
     
         93 . A method for separating particles according to size comprising: introducing the particles to be separated into a microfluidic channel comprising a network of gaps within the microfluidic channel; and applying a field to the particles to propel the particles through the microfluidic channel, wherein a flux of the field from the gaps is divided unequally into a major flux component and a minor flux component into subsequent gaps in the network such that the average direction of the major flux components is not parallel to the average direction of the field, and particles having a size less than a predetermined critical size are transported generally in the average direction of the field, and particles having a size at least that of the critical size are transported generally in the average direction of the major flux component, thereby separating the particles according to size. 
     
     
         94 . The method of  claim 93 , wherein the network of gaps is constructed from an array of obstacles. 
     
     
         95 . The method of  claim 94 , wherein the array of obstacles is an ordered array of obstacles. 
     
     
         96 . The method of  claim 95 , wherein the ordered array of obstacles comprises obstacles arranged in rows, wherein each subsequent row of obstacles is shifted laterally with respect to the previous row. 
     
     
         97 . The method of  claim 95 , wherein the ordered array of obstacles is tilted at an offset angle θ with respect to the direction of the field. 
     
     
         98 . The method of  claim 93 , wherein the field is fluid flow, electrical, electro-osmotic, gravitational, hydrodynamic, pressure gradient, or capillary action. 
     
     
         99 . The method of  claim 98 , wherein the field is a fluid flow. 
     
     
         100 . The method of  claim 98 , wherein the field is an electrical field. 
     
     
         101 . The microfluidic device of  claim 93 , wherein the particles are single celled organisms, formed bodies as in blood, cells, viruses, nucleic acids, proteins, protein complexes, polymers, emulsions, or colloids. 
     
     
         102 . The method of  claim 101 , wherein the particles are DNA molecules. 
     
     
         103 . The method of  claim 93 , further comprising introducing the particles having at least the predetermined critical size into a first output and the particles smaller than the predetermined critical size into a second output. 
     
     
         104 . The method of  claim 93 , further comprising transporting the particles having a size at least as large as the predetermined critical size to a boundary of the microfluidic channel, thereby concentrating the particles at the boundary. 
     
     
         105 . A method for separating particles according to size comprising:
 introducing the particles to be separated into a microfluidic channel comprising an ordered array of obstacles; and   applying a field to the particles to propel the particles through the microfluidic channel, wherein the ordered array of obstacles is asymmetric with respect to the average direction of the field, such that particles having a size less than a predetermined critical size are transported in a first direction, and particles having a size at least that of the critical size are transported in a second direction, wherein the first and second directions are different, thereby separating the particles according to size.   
     
     
         106 . The method of  claim 105 , wherein the ordered array of obstacles comprises obstacles arranged in rows, wherein each subsequent row of obstacles is shifted laterally with respect to the previous row. 
     
     
         107 . The method of  claim 105 , wherein the ordered array of obstacles is tilted at an offset angle θ with respect to the direction of the field. 
     
     
         108 . The method of  claim 105 , wherein the field is fluid flow, electrical, electro-osmotic, gravitational, hydrodynamic, pressure gradient, or capillary action. 
     
     
         109 . The method of  claim 108 , wherein the field is a fluid flow. 
     
     
         110 . The method of  claim 108 , wherein the field is an electrical field. 
     
     
         111 . The microfluidic device of  claim 105 , wherein the particles are single celled organisms, formed bodies as in blood, cells, viruses, nucleic acids, proteins, protein complexes, polymers, emulsions, or colloids. 
     
     
         112 . The microfluidic device of  claim 111 , wherein the particles are DNA molecules. 
     
     
         113 . The method of  claim 105 , further comprising introducing the particles transported in the first direction into a first output and the particles transported in the second direction into a second output. 
     
     
         114 . The method of  claim 105 , further comprising transporting the particles having a size at least as large as the predetermined critical size to a boundary of the microfluidic channel, thereby concentrating the particles at the boundary. 
     
     
         115 . A microfluidic device for concentrating particles, comprising a microfluidic channel, an array comprising a network of gaps within the microfluidic channel, and a boundary, wherein the device employs a field that propels the particles being concentrated through the microfluidic channel; and wherein a flux of the field from the gaps is divided unequally into a major flux component and a minor flux component into subsequent gaps in the network, such that the average direction of the major flux components is not parallel to the average direction of the field, and, when particles having a size at least as large as a predetermined critical size are introduced into the array, the particles are transported generally towards the average direction of the major flux component to the boundary, thereby concentrating the particles at the boundary. 
     
     
         116 . The microfluidic device of  claim 115 , wherein the array is an ordered array of obstacles. 
     
     
         117 . The microfluidic device of  claim 116 , wherein the ordered array of obstacles comprises obstacles arranged in rows, wherein each subsequent row of obstacles is shifted laterally with respect to the previous row; or the ordered array of obstacles is tilted at an offset angle θ with respect to the direction of the field; or a combination thereof. 
     
     
         118 . The microfluidic device of  claim 115 , wherein the field is fluid flow, electrical, electro-osmotic, gravitational, hydrodynamic, pressure gradient, or capillary action. 
     
     
         119 . The microfluidic device of  claim 118 , wherein the field is a fluid flow. 
     
     
         120 . The microfluidic device of  claim 118 , wherein the field is an electrical field. 
     
     
         121 . The microfluidic device of  claim 115 , wherein the particles are single celled organisms, formed bodies as in blood, cells, viruses, nucleic acids, proteins, protein complexes, polymers, emulsions, or colloids. 
     
     
         122 . The microfluidic device of  claim 115 , wherein the particles are DNA molecules. 
     
     
         123 . The microfluidic device of  claim 115 , wherein the microfluidic channel contains more than one array. 
     
     
         124 . The microfluidic device of  claim 115 , further comprising an output, configured to accept particles from the boundary of the array. 
     
     
         125 . A method for separating particles according to size comprising:
 introducing the particles to be separated into a microfluidic channel comprising a plurality of obstacles within the microfluidic channel, wherein the obstacles are an ordered array of obstacles comprising obstacles forming rows, wherein each subsequent row of obstacles is shifted laterally with respect to the previous row; and   applying a field to the particles to propel the particles through the microfluidic channel, such that the average direction of the particles having a size at least that of a predetermined critical size is not parallel to the average direction of the field, and particles having a size less than the predetermined critical size are transported generally in the average direction of the field, thereby separating the particles according to size.   
     
     
         126 . The method of  claim 125 , wherein the ordered array of obstacles is tilted at an offset angle θ with respect to the direction of the field. 
     
     
         127 . The method of  claim 125 , wherein the field is fluid flow, electrical, electro-osmotic, gravitational, hydrodynamic, pressure gradient, or capillary action. 
     
     
         128 . The method of  claim 127 , wherein the field is a fluid flow. 
     
     
         129 . The method of  claim 127 , wherein the field is an electrical field. 
     
     
         130 . The microfluidic device of  claim 125 , wherein the particles are single celled organisms, formed bodies as in blood, cells, viruses, nucleic acids, proteins, protein complexes, polymers, emulsions, or colloids. 
     
     
         131 . The method of  claim 130 , wherein the particles are DNA molecules.