Systems for isolating and transplanting pancreatic islets

Abstract

A microfluidic device can include an upstream passage, a sample passage, a bifurcating passage, and a combining passage. The upstream passage can be configured to provide a focusing stream. The sample passage can be configured to provide a sample stream. The bifurcating passage can include a specified bifurcating flow resistance. The combining passage can be configured to create a combined stream from the focusing stream and the sample stream, where the focusing stream can direct the sample stream away from the upstream passage and toward the bifurcating passage. A first portion of the combined stream can be discharged through the bifurcating passage. The main discharge can be configured to discharge a second portion of the combined stream. The main discharge can include a main discharge resistance that is selectable to vary the main discharge resistance relative to the bifurcating flow resistance.

1 . A microfluidic device comprising:
 an upstream passage configured to provide a focusing stream;   a sample passage configured to provide a sample stream;   a bifurcating passage including a specified bifurcating flow resistance;   a combining passage configured to create a combined stream from the focusing stream and the sample stream, the focusing stream directing the sample stream away from the upstream passage and toward the bifurcating passage;   wherein a first portion of the combined stream is discharged through the bifurcating passage; and   a main discharge configured to discharge a second portion of the combined stream, the main discharge including a main discharge resistance that is selectable to vary the main discharge resistance relative to the bifurcating flow resistance.   
     
     
         2 . The microfluidic device of  claim 1 , the main discharge further comprising:
 a main discharge multiplexer configured to selectively vary the main discharge resistance.   
     
     
         3 . The microfluidic device of  claim 2 , the bifurcating passage further comprising:
 a bifurcating passage multiplexer configured to selectively vary the bifurcating passage resistance.   
     
     
         4 . The microfluidic device of  claim 1 , wherein:
 the upstream passage is configured to deliver the focusing stream to selectably determine a particle size accepted by the bifurcating passage.   
     
     
         5 . The microfluidic device of  claim 1 , wherein:
 the upstream passage and the sample passage are configured to create a pinch width in the combining chamber to direct the sample stream towards the bifurcating passage.   
     
     
         6 . The microfluidic device of  claim 5 , wherein the upstream passage is configured to deliver the focusing stream at a laminar flow rate and the sample passage is configured to deliver the stream flow at a laminar flow rate. 
     
     
         7 . A microfluidic system comprising:
 a sample passage configured to deliver a sample stream;   a plurality of upstream passages each configured to provide one of a plurality of focusing streams;   a plurality of bifurcating passages, each of the plurality of bifurcating passages disposed downstream of one of the plurality of upstream passages and configured to discharge a portion of the sample stream;   a plurality of combining passages, each of the plurality of combining passages configured to create a combined stream from one of the plurality of focusing streams and the sample stream, each of the plurality of focusing streams directing the sample stream away from the plurality of upstream passages and toward one of the bifurcating passages disposed downstream of the one of the upstream passages; and   a main discharge configured to discharge a second portion of the combined stream.   
     
     
         8 . The microfluidic system of  claim 7 , the main discharge further comprising:
 a main discharge multiplexer configured to selectively vary a main discharge resistance.   
     
     
         9 . The microfluidic system of  claim 8 , further comprising:
 a bifurcating passage multiplexer coupled to each of the bifurcating passages, the bifurcating passage multiplexer configured to selectively vary a bifurcating passage resistance of each of the bifurcating passages.   
     
     
         10 . The microfluidic system of  claim 9 , further comprising:
 a main discharge sensor coupled to the main discharge and configured to produce a main discharge signal as a function of a sensed condition of the main discharge;   a bifurcating passage manifold coupled to a discharge of each of the bifurcating passages; and   a bifurcating passage sensor coupled to the bifurcating passage manifold and configured to produce a bifurcating passage signal as a function of a sensed condition of the bifurcating passage manifold.   
     
     
         11 . The microfluidic system of  claim 10 , further comprising:
 a controller configured to operate the main discharge multiplexer and the bifurcating passage multiplexer as a function of one or more of the main discharge signal and the bifurcating passage signal.   
     
     
         12 . The system of  claim 8 , wherein:
 each of the plurality of upstream passages is configured to provide the focusing flow to create a selection width upstream of each of the plurality of bifurcating passages.   
     
     
         13 . A microfluidic sorting system comprising:
 a microfluidic device comprising:
 an upstream passage; 
 a sample passage; 
 a bifurcating passage comprising a specified bifurcating flow resistance; and 
 a main discharge including a main discharge resistance that is selectable to vary the main discharge resistance relative to the bifurcating flow resistance; 
   a main discharge multiplexer configured to selectively vary the main discharge resistance; and   a controller configured to select the main discharge resistance as a function of a condition of the microfluidic sorting system.   
     
     
         14 . The microfluidic sorting system of  claim 13 , further comprising:
 a bifurcating passage multiplexer configured to selectively vary the bifurcating passage resistance.   
     
     
         15 . The microfluidic sorting system of  claim 14 , further comprising:
 a main discharge sensor coupled to the main discharge and configured to produce a main discharge signal as a function of a sensed condition of the main discharge.   
     
     
         16 . The microfluidic sorting system of  claim 15 , further comprising:
 a bifurcating passage manifold coupled to a discharge of each of the bifurcating passages; and   a bifurcating passage sensor coupled to the bifurcating passage manifold and configured to produce a bifurcating passage signal as a function of a sensed condition of the bifurcating passage manifold.   
     
     
         17 . The microfluidic sorting system of  claim 16 , wherein:
 the controller is configured to select the main discharge resistance and the bifurcating passage resistance as a function of at least one of the main discharge signal and the bifurcating passage signal.   
     
     
         18 . The microfluidic sorting system of  claim 13 , wherein the controller is configured to select main discharge resistance and the bifurcating passage resistance to:
 separate acinar from islets;   separate large islets from small islets; and   separate viable islets from non-viable islets.   
     
     
         19 . The microfluidic sorting system of  claim 13 , wherein the microfluidic device further comprises:
 a plurality of upstream passages each configured to provide one of a plurality of focusing streams; and   a plurality of bifurcating passages, each of the plurality of bifurcating passages disposed downstream of one of the plurality of upstream passages and configured to discharge a portion of the sample stream.   
     
     
         20 . The microfluidic sorting system of  claim 13 , wherein the bifurcating passage comprises a restriction sized to be about 80 percent of a diameter of an acinar diameter.