Pneumatic alternating pressure membrane cell separation system

Abstract

Described are filtration systems that can be referred to as Pneumatic Alternating Cell Separators (PACS), useful components thereof in the form of assemblies or kits of parts that can be used to build the system, and use of the system for filtering fluids, for instance, in cell culture perfusion systems comprising a filter-containing chamber, an expansion chamber and a gas flow controller.

What is claimed is: 
     
         1 . A fluid filtration system comprising:
 a) at least one fluid storage vessel;   b) at least one filter-containing compartment;   c) at least one fluid transfer line connecting the storage vessel to an entrance end of a filter-containing compartment, which fluid transfer line is capable of directing a fluid from the storage vessel into the entrance end of the filter-containing compartment;   d) at least one expansion chamber with at least two openings, wherein a first opening is connected at an exit end of the filter-containing compartment and wherein a second opening is connected to a gas flow controller, wherein the expansion chamber contains no separation means between the first and second openings, and wherein at least one level sensor is mounted on or in the expansion chamber;   e) at least one gas flow controller for alternately providing the expansion chamber with positive and negative pressure; and   f) at least one fluid harvest port connected to the filter-containing compartment for removing filtered fluid from the filter-containing compartment.   
     
     
         2 . The fluid filtration system of  claim 1 , wherein the expansion chamber is connected to the gas flow controller with a gas line. 
     
     
         3 . The fluid filtration system of  claim 1 , wherein the gas line comprises a filter between the expansion chamber and the gas flow controller. 
     
     
         4 . The fluid filtration system of  claim 1 , wherein the fluid storage vessel is a bioreactor. 
     
     
         5 . The fluid filtration system of  claim 1 , wherein the filter-containing compartment contains a hollow fiber filter. 
     
     
         6 . The fluid filtration system of  claim 1 , wherein at least two level sensors are mounted on or in the expansion chamber. 
     
     
         7 . The fluid filtration system of  claim 6 , wherein the level sensors are capable of measuring a minimal and a maximal fluid level in the expansion chamber, and functionally coupled to the gas flow controller. 
     
     
         8 . The fluid filtration system of  claim 1 , able alternately aspirate the fluid of the system from the storage vessel, through the filter-containing compartment into the expansion chamber, and expelling the fluid from the expansion chamber through the filter-containing compartment back into the storage vessel, wherein fluid aspiration is performed by applying negative pressure into the expansion chamber and fluid expulsion is performed by applying positive pressure into the expansion chamber. 
     
     
         9 . The fluid filtration system of  claim 1 , wherein the negative pressure is obtained by creating a vacuum in the expansion chamber and positive pressure is obtained by injecting gas. 
     
     
         10 . The fluid filtration system of  claim 1 , wherein the filter in the filter-containing compartment comprises a plurality of bundled hollow fibers whose axes extend longitudinally from the entrance end to the exit end of the filter-containing compartment. 
     
     
         11 . The fluid filtration system of  claim 10 , wherein the filter-containing compartment and the expansion chamber are disposable. 
     
     
         12 . An assembly comprising:
 an expansion chamber assembled
 to a filter containing compartment on one side and 
 to an air filter on the other side, 
 able to be coupled to a gas line that can provide positive and negative pressure to the expansion chamber. 
   
     
     
         13 . The assembly of  claim 12 , wherein the assembled components are disposable. 
     
     
         14 . A method for preparing An assembly comprising: an expansion chamber assembled to a filter containing compartment on one side and to an air filter on the other side, able to be coupled to a gas line that can provide positive and negative pressure to the expansion chamber, the method comprising:
 assembling a filter containing compartment onto a first opening of an expansion chamber and assembling an air filter onto a second opening of said expansion chamber.   
     
     
         15 . The assembly of  claim 12 , wherein the space internal to the expansion chamber and filter containing compartment is sterile. 
     
     
         16 . A process for filtering a fluid, the process comprising the steps of:
 a) providing a fluid filtration system comprising:
 at least one fluid storage vessel; 
 at least one filter-containing compartment; 
 a fluid transfer line connecting the storage vessel to an entrance end of the filter-containing compartment, which transfer line is capable of directing a fluid from the storage vessel into the entrance end of the filter-containing compartment; 
 at least one expansion chamber connected on one side to an exit end of the filter-containing compartment allowing for liquid from said compartment to enter the chamber and on the other side to a gas flow controller, which alternately provides negative pressure and positive pressure into the expansion chamber thereby aspirating fluid from the exit end of the filter-containing compartment and expelling fluid back into the exit end of the filter-containing compartment, forming a direct gas-liquid interface without separation means into the expansion chamber; 
 and at least one permeate port connected to the filter-containing compartment for removing filtered fluid from the filter-containing compartment; 
   b) drawing fluid out of the storage vessel through the filter into the expansion chamber by applying negative pressure into the expansion chamber;   c) expelling the fluid from the expansion chamber through the filter back into the storage vessel by applying positive pressure into the expansion chamber;   d) repeating steps b and c generating an alternative tangential flow of fluid through the filter; and   e) removing the filtered fluid from the filtration system.   
     
     
         17 . The process of  claim 16 , wherein the fluid storage vessel is a bioreactor. 
     
     
         18 . The process of  claim 16 , wherein the filter-containing compartment and/or the expansion chamber are disposable. 
     
     
         19 . The process of  claim 18 , wherein the positive pressure and negative pressure are regulated by level sensors which measure the fluid level in the expansion chamber. 
     
     
         20 . The process of  claim 19 , wherein the level sensors are mounted on the expansion chamber. 
     
     
         21 . The process of  claim 16 , wherein the filter-containing compartment contains a hollow fiber filter. 
     
     
         22 . The process of  claim 16 , wherein the negative pressure is obtained by creating a vacuum in the expansion chamber and the positive pressure is obtained by injecting gas into the expansion chamber.