Acoustic perfusion devices

Abstract

Acoustic perfusion devices for separating biological cells from other material in a fluid mixture are disclosed. The devices include an inlet port, an outlet port, and a collection port that are connected to an acoustic chamber. An ultrasonic transducer creates an acoustic standing wave in the acoustic chamber that permits a continuous flow of fluid to be recovered through the collection port while keeping the biological cells within the acoustic chamber to be returned to the bioreactor from which the fluid mixture is being drawn.

1 . An acoustic cell retention device, comprising:
 a chamber;   at least one ultrasonic transducer coupled to the chamber;   at least one reflector opposite the at least one ultrasonic transducer across the chamber;   the at least one ultrasonic transducer configured to be excited to generate a multi-dimensional acoustic standing wave with the at least one reflector, wherein the multi-dimensional acoustic standing wave is configured to retain cells and pass fluid in which the cells 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 cells 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 cell concentration is increased. 
     
     
         5 . The device of  claim 1 , further comprising a locale in the multi-dimensional acoustic standing wave where the cell 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 cells. 
     
     
         10 . The device of  claim 9 , further comprising an outlet communicating with the chamber for withdrawing the retained cells. 
     
     
         11 . A method for retaining biological material in a fluid mixture, comprising:
 flowing the fluid mixture containing the biological material through an acoustic retention device, the device comprising:
 a chamber; 
 at least one ultrasonic transducer coupled to the chamber; 
 at least one reflector opposite the at least one ultrasonic transducer across the chamber; 
 the at least one ultrasonic transducer configured to be excited to generate a multi-dimensional acoustic standing wave with the at least one reflector; and 
   exciting the at least one ultrasonic transducer to generate the multi-dimensional acoustic standing wave; and   retaining the biological material with the multi-dimensional acoustic standing wave and passing the fluid through the multi-dimensional acoustic standing wave.   
     
     
         12 . The method of  claim 11 , further comprising recirculating the fluid mixture to the chamber. 
     
     
         13 . The method of  claim 11 , further comprising generating a pressure rise and an acoustic radiation force on the biological material at an interface region of the multi-dimensional acoustic standing wave. 
     
     
         14 . The method of  claim 13 , further comprising increasing biological material concentration adjacent to the interface region. 
     
     
         15 . The method of  claim 11 , further comprising increasing biological material 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 biological material is 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:
 retaining the cells using the acoustic cell 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 and reflector;   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.