Microfabricated Cell Sorter

Abstract

The invention provides a microfabricated device for sorting cells based on a desired characteristic, for example, reporter-labeled cells can be sorted by the presence or level of reporter on the cells. The device includes a chip having a substrate into which is microfabricated at least one analysis unit. Each analysis unit includes a main channel, having a sample inlet channel, typically at one end, and a detection region along a portion of its length. Adjacent and downstream from the detection region, the main channel has a discrimination region or branch point leading to at least two branch channels. The analysis unit may further include additional inlet channels, detection points, branch points, and branch channels as desired. A stream containing cells is passed through the detection region, such that on average one cell occupies the detection region at a given time. The cells can be sorted into an appropriate branch channel based on the presence or amount of a detectable signal such as an optical signal, with or without stimulation, such as exposure to light in order to promote fluorescence.

1 . A device for sorting biological material comprising:
 a microfabricated substrate having at least one main channel and at least two branch channels which meet at a junction,   a detection region upstream and proximate to the junction comprising a detection apparatus for evaluating the biological material according to at least one characteristic as the material passes through the detection region,   a discrimination region downstream from the detection region,   a flow control system responsive to the detection apparatus and adapted to direct biological material through the discrimination region into a branch channel.   
     
     
         2 . A device of  claim 1 , wherein at least one of the main and outlet channels communicates with a reservoir. 
     
     
         3 . A device of  claim 1 , wherein the substrate is comprised of silicon. 
     
     
         4 . A device of  claim 1 , wherein the substrate comprises a silicone elastomer. 
     
     
         5 .- 6 . (canceled) 
     
     
         7 . A device of  claim 1  wherein the flow control system is electro-osmotic. 
     
     
         8 . A device of  claim 1  wherein the flow control system is electrophoretic. 
     
     
         9 . A device of  claim 1  wherein the flow control system is dielectrophoretic. 
     
     
         10 . A device of  claim 1  wherein the flow control system is pressure driven. 
     
     
         11 . A device of  claim 1  wherein the flow control system is microvalve. 
     
     
         12 . A device of  claim 1  wherein the flow control system is optical trapping. 
     
     
         13 . A device of  claim 1  wherein the flow control system is flow stoppage-based control. 
     
     
         14 . A device according to  claim 1  wherein the flow control is provided by a voltage gradient between the branch channels and the junction. 
     
     
         15 . A device according to  claim 14  wherein the voltage gradient is generated by electrodes in the branch channels. 
     
     
         16 . A device of  claim 1  wherein the flow control is by a pressure gradient between one or more channels and the junction. 
     
     
         17 . A device of  claim 16  wherein pressure driven flow control is provided by capillary action at one or more channels of the substrate. 
     
     
         18 . A device of  claim 1  wherein the flow control comprises one or more valves. 
     
     
         19 . A device of  claim 17  wherein the flow control comprises one or more valves. 
     
     
         20 . A device of  claim 1  wherein the flow control is reversible. 
     
     
         21 .- 37 . (canceled) 
     
     
         38 . A method for sorting a fluid mixture of cells comprising:
 providing the mixture of cells to a main channel of a microfabricated substrate, wherein the main channel is in fluid communication with at least two downstream branch channels which meet at a junction;   producing a flow of fluid in the channels;   interrogating each cell for a predetermined characteristic as it passes a detection region associated with the main channel;   generating a signal indicating the results of the interrogation;   directing the flow of each cell into a selected branch channel according to the signal.   
     
     
         39 - 42 . (canceled) 
     
     
         43 . A method of  claim 38  wherein the flow is controlled by electro-osmosis, electrophoresis, dielectrophoresis, pressure gradient, microvalve, optical trapping and flow stoppage. 
     
     
         44 - 50 . (canceled)