Acoustophoresis device with modular components

Abstract

An acoustophoresis device made up of modular components is disclosed. Several modules are disclosed herein, including ultrasonic transducer modules, input/output modules, collection well modules, and various connector modules. These permit different systems to be constructed that have appropriate fluid dynamics for separation of particles, such as biological cells, from a fluid.

1 . A modular acoustophoresis device, comprising:
 (A) An ultrasonic transducer module comprising:
 (i) a housing defining a primary flow channel between a first end and a second end of the housing; 
 (ii) at least one ultrasonic transducer at one side of the primary flow channel; 
 (iii) at least one reflector at another side of the primary flow channel opposite the at least one ultrasonic transducer; 
 (iv) a first attachment member at the first end of the housing; and 
 (v) a second attachment member at the second end of the housing; 
   wherein the first and second attachment members of the ultrasonic transducer module are adapted to cooperatively engage with or fit with other associated modules of the acoustophoresis device.   
     
     
         2 . The modular acoustophoresis device of  claim 1 , wherein the first attachment member and the second attachment member of the ultrasonic transducer module are reversibly connectable. 
     
     
         3 . The modular acoustophoresis device of  claim 1 , further including a port on a side of the housing between the at least one transducer and the at least one reflector. 
     
     
         4 . The modular acoustophoresis device of  claim 1 , further including:
 (B) a collection well module comprising:
 (i) a housing including a well that tapers downwards in cross-sectional area from a single inlet to a vertex, and a drain line connecting the vertex to a port on a side of the housing; and 
 (ii) an attachment member at the inlet, the attachment member adapted to connect the collection well module to the ultrasonic transducer module. 
   
     
     
         5 . The modular acoustophoresis device of  claim 4 , wherein the attachment member of the collection well module is complementary to the second attachment member of the ultrasonic transducer module. 
     
     
         6 . The modular acoustophoresis device of  claim 1 , further including:
 (C) an angled collection well module comprising:
 (i) a housing including a first opening and a second opening that lead into a common well that taper downwards in cross-sectional area to a vertex, and a drain line connecting the vertex to a port on a side of the housing; 
 (ii) a first attachment member at the first opening adapted to connect the collection well module to the ultrasonic transducer module; and 
 (iii) a second attachment member at the second opening adapted to connect the collection well module to the ultrasonic transducer module; 
 (iv) wherein the first opening is located at an acute angle relative to a base of the housing. 
   
     
     
         7 . The modular acoustophoresis device of  claim 1 , further including:
 (D) a U-turn inlet/outlet module comprising:
 (i) a housing with an upper end and a lower end; 
 (ii) a flow channel including a first end and a second end; 
 (iii) an inlet port and an outlet port at the first end of the flow channel; 
 (iv) an opening defining the second end of the flow channel and located at the lower end of the housing; and 
 (v) an attachment member at the lower end of the housing, the attachment member adapted to connect the inlet/outlet module to the ultrasonic transducer module; 
 (vi) wherein the flow channel is shaped such that fluid flows from the inlet port through the opening and then to the outlet port. 
   
     
     
         8 . The modular acoustophoresis device of  claim 7 , further comprising a wall in the flow channel between the inlet port and the outlet port. 
     
     
         9 . The modular acoustophoresis device of  claim 8 , wherein the wall is placed so that a cross-sectional area of the flow channel for the inlet port is smaller than a cross-sectional area of the flow channel for the outlet port. 
     
     
         10 . The modular acoustophoresis device of  claim 8 , wherein the wall extends out of the opening at the lower end of the housing. 
     
     
         11 . The modular acoustophoresis device of  claim 8 , wherein the wall is spaced apart from the upper end of the housing so as to form a pressure relief passage between the inlet port and the outlet port. 
     
     
         12 . The modular acoustophoresis device of  claim 1 , further including:
 (E) a port module comprising:
 (i) a housing defining a single flow channel between an upper end and a lower end of the housing; and 
 (ii) an attachment member at the lower end of the housing, the attachment member adapted to connect the port module to the ultrasonic transducer module. 
   
     
     
         13 . The modular acoustophoresis device of  claim 1 , further including:
 (F) a connector module comprising:
 (i) a housing with an upper end, a lower end, and a side; 
 (ii) a first opening on the upper end of the housing; 
 (iii) a second opening on the side of the housing, a flow channel being defined between the first opening and the second opening; 
 (iv) a first attachment member at the upper end of the housing; and 
 (v) a second attachment member at the side of the housing which is complementary to the first attachment member. 
   
     
     
         14 . The modular acoustophoresis device of  claim 13 , wherein the connector module further comprises:
 (vi) a third opening on the lower end of the housing, the flow channel also joining the first opening and the second opening to the third opening; and   (vii) a third attachment member at the lower end of the housing which is complementary to the first attachment member.   
     
     
         15 . The modular acoustophoresis device of  claim 1 , further comprising:
 (G) a connector module comprising:
 (i) a housing with an upper end, a lower end, and a side; 
 (ii) a first opening on the upper end of the housing; 
 (iii) a second opening on the lower end of the housing, a straight flow channel being defined between the first opening and the second opening; 
 (iv) a first attachment member at the upper end of the housing; and 
 (v) a second attachment member at the lower end of the housing, wherein the first attachment member is the same as the second attachment member. 
   
     
     
         16 . The modular acoustophoresis device of  claim 15 , wherein the first attachment member and the second attachment member of the connector module (G) are both female members. 
     
     
         17 . The modular acoustophoresis device of  claim 15 , wherein the first attachment member and the second attachment member of the connector module (G) are both male members. 
     
     
         18 . The modular acoustophoresis device of  claim 1 , further including:
 (H) a variable-volume collection well module comprising:
 (i) a housing including a well with a constant cross-section, an inlet at an upper end, and a bottom end; and 
 (ii) a plunger that provides a floor to the well, the plunger adapted to move through the well from the bottom end towards the upper end. 
   
     
     
         19 . The modular acoustophoresis device of  claim 1 , further including a plurality of tenons at the first end of the housing and a plurality of mortises at the second end of the housing, the tenons and mortises adapted to be press-fitted together. 
     
     
         20 . The modular acoustophoresis device of  claim 1 , wherein the first and second attachment members of the transducer module include internal or external threads, such that the transducer module and the other associated modules can be removably screwed together. 
     
     
         21 . An acoustophoresis device, comprising:
 a first module comprising:
 a primary flow channel; 
 at least one ultrasonic transducer at one side of the primary flow channel; 
 at least one reflector at another side of the primary flow channel opposite the at least one ultrasonic transducer; and 
 a first attachment member at a first end of the first module; and 
   a second module comprising:
 a second attachment member at a first end of the second module; 
   wherein the first attachment member and the second attachment member are adapted to cooperatively engage with or fit with each other.   
     
     
         22 . A method of manufacturing an acoustophoresis device, comprising:
 forming a first module that includes a primary flow channel;   providing at least one ultrasonic transducer at one side of the primary flow channel;   providing at least one reflector at another side of the primary flow channel opposite the at least one ultrasonic transducer; and   forming a first attachment member at a first end of the first module; and   forming a second module that includes a second attachment member at a first end of the second module;   wherein the first attachment member and the second attachment member are formed to cooperatively engage with or fit with each other.   
     
     
         23 . The modular acoustophoresis device of  claim 1 , wherein the acoustophoresis device is connected upstream to a bioreactor and downstream to a secondary filtration or chromatographic separation device. 
     
     
         24 . The device of  claim 23 , wherein the secondary filtration device comprises a DFF filter operated at an increased volumetric throughput resulting from the acoustophoresis device being free of a pressure drop. 
     
     
         25 . The modular acoustophoresis device of  claim 1 , wherein the device has at least two ultrasonic transducer modules (A) connected in series. 
     
     
         26 . An acoustophoresis device that achieves at least a 90% reduction in each of total cell density, Nephelometric Turbidity Units (NTU), and total protein recovery of the media from a bioreactor containing cells with at least 6×10̂6 cells/mL, 60% viability and 800 NTU. 
     
     
         27 . An acoustophoresis device that has at least 30 cm̂3 acoustic chamber volume per 15×10̂6 cells/mL at a flow of 2.5 liters per hour. 
     
     
         28 . An acoustophoretic system, comprising at least two acoustophoretic devices of  claim 1 , connected in series.