System and Method for Removing a Cryporotectant from a Liquid

Abstract

A system for removing cryoprotectant from a cryoprotectant-containing liquid stored a container comprises a cryoprotectant removal device that receives the cryoprotectant-containing liquid and a cryoprotectant-free dialysate liquid and that is operable to transfer cryoprotectant to the dialysate liquid. A differential conductivity device is arranged to continuously measure the difference in conductivity between dialysate liquid entering the device and dialysate liquid that has received cryoprotectant transferred by the dialyzer discharged from the device. A controller is operable to control the flow of the liquids through the device in response to the measured difference in conductivity, and particularly to stop the flow of the cryoprotectant-containing liquid when the measured differential conductivity indicates that the cryoprotectant has been substantially removed from the liquid.

1 . A system for removing cryoprotectant from a cryoprotectant-containing liquid stored a container comprising:
 a dialyzer having a first inlet to receive the cryoprotectant-containing liquid, a first outlet for discharge of the cryoprotectant-liquid, a second inlet to receive a cryoprotectant-free dialysate liquid and a second outlet for discharge of the cryoprotectant-free liquid, said dialyzer forming a diffusion gradient between said cryoprotectant-containing liquid and the cryoprotectant-free liquid;   a source of cryoprotectant-free dialysate liquid capable of receiving cryoprotectant transferred through said diffusion gradient within said dialyzer;   an outlet fluid line connected to said first inlet and connectable to an outlet of the container;   an inlet fluid line connected to said first outlet and connectable to an inlet of the container, said outlet and inlet fluid lines forming a first fluid circuit between the container of the cryoprotectant-containing liquid and said dialyzer;   a second outlet fluid line connected between said source of dialysate liquid and said second inlet;   a discharge fluid line connected to said second outlet and connectable to a waste container, said second outlet fluid line and said discharge fluid line forming a second fluid circuit between said source of dialysate liquid and said dialyzer;   a first pump disposed in said first fluid circuit for controlling the flow of the cryoprotectant-containing liquid through said first fluid circuit;   a second pump disposed in said second fluid circuit for controlling the flow of the dialysate liquid through said second fluid circuit;   a differential conductivity device disposed between said second outlet fluid line and said discharge fluid line and operable to measure the difference in conductivity between dialysate liquid flowing through said second outlet fluid line and dialysate liquid that has received cryoprotectant transferred by said dialyzer flowing through said discharge fluid line;   and a controller for controlling the operation of said first and/or second pump in response to the measured difference in conductivity.   
     
     
         2 . The system for removing cryoprotectant according to  claim 1 , further comprising:
 a first valve disposed in said first outlet fluid line, said first valve openable to permit and closable to prevent flow of cryoprotectant-containing liquid from the container to said dialyzer; and   a second valve disposed in said second outlet fluid line, said second valve openable to permit and closable to prevent flow of dialysate liquid from said source to said dialyzer,   wherein said controller is configured to open or close said first and/or second valve in response to the measured difference in conductivity.   
     
     
         3 . The system for removing cryoprotectant according to  claim 1 , further comprising:
 a first temperature sensor adjacent said differential conductivity device and arranged to measure the temperature of liquid flowing through said second outlet fluid line; and   a second temperature sensor adjacent said differential conductivity device and arranged to measure the temperature of liquid flowing through said discharge fluid line,   wherein said controller is further configured to adjust the measured difference in conductivity as a function of the temperature sensed by said first and second temperature sensors.   
     
     
         4 . The system for removing cryoprotectant according to  claim 1 , further comprising:
 a source of a priming solution for preparing said dialyzer;   a first priming outlet fluid line connected between said source of priming solution and said first inlet of said dialyzer; and   a second priming outlet fluid line connected between said source of priming solution and said second inlet of said dialyzer.   
     
     
         5 . The system for removing cryoprotectant according to  claim 4 , wherein:
 said first priming outlet fluid line intersects said first fluid circuit so that said first pump is operable to flow said priming solution through said dialyzer; and   said second priming outlet fluid line intersects said second fluid circuit so that said second pump is operable to flow said priming solution through said dialyzer and so that said priming solution flows through said differential conductivity device.   
     
     
         6 . The system for removing cryoprotectant according to  claim 5 , further comprising:
 a third valve disposed in said first priming outlet fluid line, said third valve openable to permit and closable to prevent flow of priming solution from said source of priming solution to said dialyzer; and   a fourth valve disposed in said second priming outlet fluid line, said fourth valve openable to permit and closable to prevent flow of priming solution from said source of priming solution to said dialyzer,   wherein said controller is configured to open or close said third and/or fourth valve in response to the measured difference in conductivity.   
     
     
         7 . The system for removing cryoprotectant according to  claim 1 , further comprising:
 a conductivity cell disposed in said inlet fluid line adjacent said dialyzer, said conductivity cell arranged to measure the conductivity of liquid flowing through said inlet fluid line;   a waste fluid line intersecting said inlet fluid line between said conductivity cell and the inlet to the container of the cryoprotectant-containing liquid, said waste fluid line connectable to a waste container; and   a fifth valve disposed in said waste fluid line between said inlet fluid line and the waste container, said fifth valve openable to permit and closable to prevent flow of liquid from said dialyzer to the waste container,   wherein said controller is configured to open or close said fifth valve in response to the measured conductivity.   
     
     
         8 . The system for removing cryoprotectant according to  claim 7 , further comprising:
 a third temperature sensor adjacent said conductivity cell and arranged to measure the temperature of liquid flowing through said inlet fluid line,   wherein said controller is further configured to adjust the measured conductivity as a function of the temperature sensed by said third temperature sensor.   
     
     
         9 . A method for removing cryoprotectant from a liquid comprising the steps of:
 passing a cryoprotectant-containing liquid and a cryoprotectant-free liquid through a cryoprotectant removal device configured to transfer cryoprotectant from the cryoprotectant-containing liquid to the cryoprotectant-free liquid;   measuring the differential conductivity between cryoprotectant-free liquid entering the device and cryoprotectant-free liquid discharged from the device after receiving cryoprotectant transferred within the device; and   controlling the flow of the cryoprotectant-containing liquid and/or the cryoprotectant-free liquid through the device in response to the measured differential conductivity.   
     
     
         10 . The method for removing cryoprotectant of  claim 9 , wherein the step of controlling the flow comprises continuously comparing the measured differential conductivity value to a predetermined threshold value indicative that the liquid discharged from the device is substantially free cryoprotectant. 
     
     
         12 . The method for removing cryoprotectant of  claim 9 , further comprising the steps of:
 passing a priming solution through the device prior to operating the device to remove cryoprotectant;   upon completion of the priming step, flowing cryoprotectant-containing liquid through the device;   continuously measuring the conductivity of liquid discharged from the device; and   diverting the liquid discharged from the device to a waste container until the measured conductivity reaches a predetermined threshold value indicative that only cryoprotectant-containing liquid is flowing through the device.   
     
     
         13 . The method for removing cryoprotectant of  claim 9 , wherein the measuring step includes measuring the temperature of the cryoprotectant-free liquid entering the device and liquid discharged from the device and adjusting the differential conductivity as a function of the measured temperatures.