Method and apparatus for concentrating molecules

Abstract

A method and apparatus for continuously separating or concentrating molecules that includes flowing two fluids in laminar flow through an electrical field and capturing at one of three outputs a fluid stream having a different concentration of molecules.

1 . A device for separating molecules contained in a first fluid comprising:
 a) a channel having an upstream end and a downstream end, the channel comprising a first inlet at the upstream end to introduce a first fluid containing molecules into the channel at a first concentration;   b) a second inlet to the channel at the upstream end to introduce a second fluid into the channel in laminar flow with the first fluid;   c) a first electrode interface associated with the first fluid along a first linear portion of the channel;   d) a second electrode interface associated with the second fluid along a second linear portion of the channel;   e) a first outlet at the downstream end for receiving said first fluid;   f) a second outlet at the downstream end for receiving said second fluid; and   g) a third outlet at the downstream end positioned at about the interface between the first fluid and the second fluid for receiving an output stream with a concentration of molecules greater than the first concentration.   
     
     
         2 . The device of  claim 1  where the first electrode interface is an opening in the channel in fluid communication with the first fluid flow. 
     
     
         3 . The device of  claim 1  where the second electrode interface is an opening in the channel in fluid communication with the second fluid flow. 
     
     
         4 . The device of  claim 2  where the first opening is separated from a first electrode reservoir by a first ion-permeable barrier. 
     
     
         5 . The device of  claim 3  where the second opening is separated from a second electrode reservoir by a second ion-permeable barrier. 
     
     
         6 . The device of  claim 4  where the first electrode reservoir interfaces with a first external electrode. 
     
     
         7 . The device of  claim 5  wherein the second electrode reservoir interfaces with a second external electrode. 
     
     
         8 . The device of  claim 7  comprising a power source for applying a voltage to the electrodes. 
     
     
         9 . The device of  claim 7  comprising a control for changing the polarity of the electric field. 
     
     
         10 . The device of  claim 7  comprising a control for changing the strength of the electric field. 
     
     
         11 . The device of  claim 7  wherein the electrodes generate an electric field across the channel transverse to a length of the channel. 
     
     
         12 . The device of  claim 11  wherein the electric field is sufficient to cause at least a portion of the molecules in the first fluid to move towards the second fluid. 
     
     
         13 . The device of  claim 12  where the movement of the molecules in the first fluid towards the second fluid results in an accumulation of the molecules at the interface. 
     
     
         14 . The device of  claim 1  wherein the channel is molded in a substrate. 
     
     
         15 . The device of  claim 1  wherein the channel is etched into a substrate. 
     
     
         16 . The device of  claim 1  where the width of the channel is approximately 0.5 mm to 5 mm. 
     
     
         17 . The device of  claim 1  where the depth of the channel is from about 10 μm to about 100 μm. 
     
     
         18 . The device of  claim 1  where the length of the channel is from about 2.3 cm to about 5 cm. 
     
     
         19 . The device of  claim 1  where the width of the third outlet is determined by the following formula: (width of channel)/(2*desired concentration factor) 
     
     
         20 . The device of  claim 1  comprising a third input port placed at the upstream end to introduce a buffer solution into the first fluid stream. 
     
     
         21 . The device of  claim 1  where the device contains flowing streams of first and second fluids. 
     
     
         22 . The device of  claim 1  where the electrophoretic mobility of a target molecule in the first fluid is substantially different from its electrophoretic mobility in the second fluid. 
     
     
         23 . The device of  claim 1  where the conductivity of the first fluid is substantially different from the conductivity of the second fluid. 
     
     
         24 . The device of  claim 1  where the solubility of a target molecule in the first fluid is substantially different from its solubility in the second fluid. 
     
     
         25 . A device for separating molecules contained in a first fluid comprising:
 a) a channel having an upstream end and a downstream end, the channel comprising a first inlet at the upstream end to introduce the first fluid containing molecules into the channel;   b) a second inlet to the channel at the upstream end to introduce a second fluid into the channel in laminar flow with the first fluid;   c) a pair of electrodes positioned proximate to the channel for applying a voltage to produce an electric field across the channel transverse to a length of the channel;   d) a first outlet at the downstream end for receiving said first fluid;   e) a second outlet at the downstream end for receiving said second fluid; and   f) a third outlet at the downstream end positioned at about the interface between the first fluid and the second fluid for receiving an output stream with a concentration of molecules greater than the first concentration.   
     
     
         26 . The device of  claim 25  where a first ion-permeable barrier separates a first electrode from the channel and a second ion-permeable barrier separates a second electrode from the channel. 
     
     
         27 . The device of  claim 26  where the ion-permeable barriers form opposite walls of the channel. 
     
     
         28 . The device of  claim 26  where the first and second ion-permeable barriers are comprised of first and second arrays of channels. 
     
     
         29 . The device of  claim 25  comprising a power source for applying a voltage to the electrodes. 
     
     
         30 . The device of  claim 25  comprising a control for changing the polarity of the electric field. 
     
     
         31 . The device of  claim 25  comprising a control for changing the strength of the electric field. 
     
     
         32 . The device of  claim 25  wherein the electrodes generate an electric field across the channel transverse to a length of the channel. 
     
     
         33 . The device of  claim 25  wherein the electric field is sufficient to cause at least a portion of the molecules in the first fluid to move towards the second fluid. 
     
     
         34 . The device of  claim 25  where the movement of the molecules in the first fluid towards the second fluid results in an accumulation of the molecules at the interface. 
     
     
         35 . The device of  claim 25  wherein the channel is molded in a substrate. 
     
     
         36 . The device of  claim 25  where the channel is etched in a substrate. 
     
     
         37 . The device of  claim 25  where the width of the channel is approximately 0.5-5 mm. 
     
     
         38 . The device of  claim 25  where the depth of the channel is from about 10 μm to about 100 μm. 
     
     
         39 . The device of  claim 25  where the length of the channel is from about 2.3 cm to about 5 cm. 
     
     
         40 . The device of  claim 25  where the width of the third outlet is determined by the following formula: (width of channel)/(2*desired concentration factor) 
     
     
         41 . The device of  claim 25  also comprising a third inlet placed at the upstream end to introduce a buffer solution into the first fluid stream. 
     
     
         42 . The device of  claim 25  where the device contains flowing streams of first and second fluids. 
     
     
         43 . The device of  claim 25  where the electrophoretic mobility of a target molecule in the first fluid is substantially different from its electrophoretic mobility in the second fluid. 
     
     
         44 . The device of  claim 25  where the conductivity of the first fluid is substantially different from the conductivity of the second fluid. 
     
     
         45 . The device of  claim 25  where the solubility of a target molecule in the first fluid is substantially different from its solubility in the second fluid. 
     
     
         46 . A method for separating molecules from a fluid comprising:
 flowing a first fluid into a channel, the first fluid having a first conductivity;   simultaneously flowing a second fluid into the channel in laminar flow with the first fluid, the second fluid having a second conductivity substantially different from the first conductivity;   applying an electric field transverse to a length of the channel, whereby at least a portion of molecules in the first fluid are caused to migrate towards the second fluid;   flowing a portion of the first fluid from the channel through a first outlet placed to receive the first fluid;   flowing a portion of the second fluid from the channel through a second outlet placed to receive the second fluid; and   flowing a portion of both fluids containing a greater concentration of molecules than the first fluid through a third outlet placed at about the interface between the first fluid and the second fluid.   
     
     
         47 . The method of  claim 46  where the pH of the first fluid is selected to be either higher or lower than the isoelectric point of the target molecule. 
     
     
         48 . The method of  claim 46  where the voltage applied is from about 200 to about 1000 V/cm 
     
     
         49 . The method of  claim 46  where the first conductivity is below about 20 mS/cm. 
     
     
         50 . The method of  claim 46  where the second conductivity is from about 10 to about 1000 times that of the first conductivity. 
     
     
         51 . The method of  claim 46  comprising accumulating molecules at about the interface between the first fluid and the second fluid. 
     
     
         52 . The method of  claim 46  where the flow rate of the first fluid and the second fluid through the channel is from about 0.001 to 1 mL/min.