Systems and methods for exchange of buffer solutions

Abstract

Systems and methods for exchanging buffer solutions are disclosed. In accordance with some embodiments, the methods and systems for buffer exchange may be automated and/or the methods and systems may include mixing during filtering operations.

1 - 54 . (canceled) 
     
     
         55 . An automated method for removal of a low molecular weight carrier from an admixture comprising a high molecular weight component or a microorganism and the low molecular weight carrier, the method comprising:
 placing a plurality of individual reservoirs containing the admixture into a receiver plate of a pressure chamber, each of the individual reservoirs containing a semi-permeable membrane;   pressurizing the pressure chamber with air or an inert gas to pressurize the individual reservoirs and thereby force the low molecular weight carrier through the semi-permeable membrane to produce a carrier-depleted residue;   detecting an amount of the low molecular weight carrier that was removed from the individual reservoirs; and   
       replacing an amount of the low molecular weight carrier to the individual reservoirs, the amount of the low molecular weight carrier replaced to the individual reservoirs being based on the detected amount of the low molecular weight carrier that was removed from the individual reservoirs. 
     
     
         56 . The automated method of  claim 55 , further comprising mixing the admixture while pressurizing the individual reservoirs to reduce fouling of the semi-permeable membrane. 
     
     
         57 . The automated method of  claim 56 , wherein mixing occurs in a direction normal to a flow direction of the first buffer solution passing through the semi-permeable membrane to reduce fouling. 
     
     
         58 . The automated method of  claim 55 , wherein the high molecular weight component comprises a protein, a peptide, an antigen, an antibody, an enzyme, DNA, or RNA. 
     
     
         59 . The automated method of  claim 55 , wherein the semi-permeable membrane is characterized by a molecular weight cut off of 100 kDa or less. 
     
     
         60 . The automated method of  claim 59 , wherein the semi-permeable membrane is characterized by a molecular weight cut off of 10 kDa or less. 
     
     
         61 . The automated method of  claim 55 , wherein each individual reservoir has a working volume of 75 ml or less, 25 ml or less, 16 ml or less, 8 ml or less, 4 ml or less, 1 ml or less, 750 μl or less, 500 μl or less, or 250 μl or less. 
     
     
         62 . The automated method of  claim 55 , wherein at least 3, at least 5, at least 10, at least 12, at least 16, at least 48, or at least 96 individual reservoirs are simultaneously replaced with the low molecular weight carrier. 
     
     
         63 . The automated method of  claim 55 , wherein the amount of the low molecular weight carrier that was removed from the individual reservoirs is detected by sensing an amount of the admixture in the reservoirs. 
     
     
         64 . The automated method of  claim 55 , wherein the amount of the low molecular weight carrier that was removed from the individual reservoirs is detected by acoustic sensing, capacitance, light reflectance, pressurization time, or weight measurement. 
     
     
         65 . The automated method of  claim 55 , wherein the detected amount of the low molecular weight carrier that was removed from the individual reservoirs is a detected volume. 
     
     
         66 . An automated system for removing a low molecular weight carrier from an admixture comprising a high molecular weight component or a microorganism and the low molecular weight carrier, the system comprising:
 a pressure chamber;   
       a plate within the pressure chamber configured to receive a plurality of individual reservoirs having a semi-permeable membrane, wherein the pressure chamber is configured to create a pressure difference using air or an inert gas across the semi-permeable membrane to force the low molecular weight carrier through the semi-permeable membrane and produce a carrier-depleted residue in the reservoir;
 a sensor for detecting the level of the low molecular weight carrier removed from the reservoirs; and 
 
       a dispensing system for replacing an amount of the low molecular weight carrier to the reservoirs, the amount replaced being based on the sensed level of the low molecular weight carrier removed from the reservoirs. 
     
     
         67 . The automated system of  claim 67 , further comprising a mixer for mixing the admixture while removing the low molecular weight carrier from the admixture. 
     
     
         68 . The automated system of  claim 67 , further comprising a waste container for collecting the low molecular weight carrier forced through the semi-permeable membrane. 
     
     
         69 . The automated system of  claim 67 , wherein the semi-permeable membrane is characterized by a molecular weight cut off of 100 kDa or less. 
     
     
         70 . The automated system of  claim 69 , wherein the semi-permeable membrane is characterized by a molecular weight cut off of 10 kDa or less. 
     
     
         71 . The automated system of  claim 67 , wherein each reservoir of the plurality of individual reservoirs has a volume of 75 ml or less, 25 ml or less, 16 ml or less, 8 ml or less, 4 ml or less, 1 ml or less, 750 μl or less, 500 μl or less, or 250 μl or less. 
     
     
         72 . The automated system of  claim 67 , wherein the plurality of reservoirs comprises at least 2, at least 3, at least 5, at least 10, at least 12, at least 16, at least 48, or at least 96 reservoirs. 
     
     
         73 . The automated system of  claim 67 , wherein the receiver plate comprises at least 2, at least 3, at least 5, at least 10, at least 12, at least 16, at least 48, or at least 96 openings to receive the plurality of reservoirs.