Acoustic perfusion devices

Abstract

Methods are disclosed for separating beads and cells from a host fluid. The method includes flowing a mixture containing the host fluid, the beads, and the cells through an acoustophoretic device having an ultrasonic transducer including a piezoelectric material driven by a drive signal to create a multi-dimensional acoustic standing wave. A drive signal is sent to drive the at least one ultrasonic transducer to create the multi-dimensional acoustic standing wave. A recirculating fluid stream having a tangential flow path is located substantially tangential to the standing wave and separated therefrom by an interface region. A portion of the cells pass through the standing wave, and the beads are held back from the standing wave in the recirculating fluid stream at the interface region. Also disclosed is an acoustophoretic device having a coolant inlet adapted to permit the ingress of a cooling fluid into the device for cooling the transducer.

1 . An acoustic bead retention device, comprising:
 a chamber;   at least one ultrasonic transducer coupled to the chamber;   the at least one ultrasonic transducer configured to be excited to generate a multi-dimensional acoustic standing wave that is configured to retain beads and pass fluid in which the beads are entrained.   
     
     
         2 . The device of  claim 1 , further comprising a recirculation path communicating with the acoustic chamber. 
     
     
         3 . The device of  claim 1 , wherein the multi-dimensional acoustic standing wave is further configured to generate a pressure rise and an acoustic radiation force on the beads at an interface region of the multi-dimensional acoustic standing wave. 
     
     
         4 . The device of  claim 3 , further comprising a locale adjacent to the interface region where the bead concentration is increased. 
     
     
         5 . The device of  claim 1 , further comprising a locale in the multi-dimensional acoustic standing wave where the bead concentration is increased. 
     
     
         6 . The device of  claim 1 , wherein the multi-dimensional acoustic standing wave is further configured to generate an acoustic radiation force with an axial force component and a lateral force component that are of the same order of magnitude. 
     
     
         7 . The device of  claim 1 , further comprising a control system coupled to the at least one ultrasonic transducer to obtain feedback for control of the at least one ultrasonic transducer. 
     
     
         8 . The device of  claim 7 , further comprising a flow rate monitor coupled to the control system to obtain feedback for control of the flow rate. 
     
     
         9 . The device of  claim 1 , further comprising an inlet communicating with the acoustic chamber for providing media to the chamber to permit media exchange for or washing of the retained beads. 
     
     
         10 . The device of  claim 9 , further comprising an outlet communicating with the chamber for withdrawing the retained beads. 
     
     
         11 . A method for separating biological material in a fluid, comprising:
 providing beads that are functionalized with a material with an affinity for the biological material to the fluid;   flowing the fluid containing the biological material through an acoustic retention device, the device comprising:
 a chamber; 
 at least one ultrasonic transducer coupled to the chamber; 
 the at least one ultrasonic transducer configured to be excited to generate a multi-dimensional acoustic standing wave; and 
   exciting the at least one ultrasonic transducer to generate the multi-dimensional acoustic standing wave; and   retaining the beads with the multi-dimensional acoustic standing wave; and   capturing the biological material with the beads.   
     
     
         12 . The method of  claim 11 , further comprising recirculating the fluid containing the biological material to the chamber. 
     
     
         13 . The method of  claim 11 , further comprising generating a pressure rise and an acoustic radiation force on the beads at an interface region of the multi-dimensional acoustic standing wave. 
     
     
         14 . The method of  claim 13 , further comprising increasing bead concentration adjacent to the interface region. 
     
     
         15 . The method of  claim 11 , further comprising increasing bead concentration in the multi-dimensional acoustic standing wave. 
     
     
         16 . The method of  claim 11 , further comprising exciting the at least one ultrasonic transducer to generate the multi-dimensional acoustic standing wave with an axial force component and a lateral force component that are of the same order of magnitude. 
     
     
         17 . The method of  claim 11 , further comprising:
 obtaining feedback from the at least one ultrasonic transducer; and   controlling the at least one ultrasonic transducer in accordance with the feedback.   
     
     
         18 . The method of  claim 11 , further comprising flowing media through the chamber while the beads with the captured biological material are retained to perform a media exchange for or washing of the biological material. 
     
     
         19 . A method for providing a media exchange for cells or for washing cells, comprising:
 capturing the cells with beads that are functionalized with an affinity for the cells;   retaining the beads with the captured cells using the acoustic bead retention device of  claim 1 ; and   flowing a fluid into the chamber and through the multi-dimensional acoustic standing wave.   
     
     
         20 . A method for retaining material in a fluid, comprising:
 generating a multi-dimensional acoustic standing wave with an acoustic transducer;   trapping and clustering the material in the multi-dimensional acoustic standing wave to permit the material to grow in size and exit the multi-dimensional acoustic standing wave; and   generating an acoustic edge effect with the multi-dimensional acoustic standing wave to form a barrier to entry to the multi-dimensional acoustic standing wave for the material.