Liquid handling for filtration and preparative chromatogrphy

Abstract

A method and system are provided for high-precision separation of pharmaceutical or biotechnology liquids. The separation can be in accordance with direct flow filtration, tangential flow filtration or preparative chromatography. Movement of the pharmaceutical or biotechnology liquid within a flow path is controlled according to a selected pattern. Selected patterns include automatically and progressively increasing the flow rate within the unit, automatically and progressively increasing the pressure within the unit or initially proceeding according to a relatively high constant flow rate and switching to a relatively high constant pressure at a time when a given parameter is attained.

1 - 26 . (canceled) 
     
     
         27 . A system for high-precision separation of pharmaceutical or biotechnology liquids, comprising:
 a reservoir adapted to contain a pharmaceutical or biotechnology liquid having target bio-molecules dissolved or suspended within a carrier liquid;   a separation unit having an inlet and an outlet and separation elements which are adapted to separate target bio-molecules and carrier liquid;   a processor-controlled pump unit adapted to move the pharmaceutical or biotechnology liquid within a flow path between the reservoir and separate at least some of the target bio-molecules from the liquid;   a pressure monitor adapted to monitor pressure at a location along the flow path;   said processor-controlled pump unit includes control logic which control movement of the liquid containing target bio-molecules through to the separation unit, said control logic achieving the following:
 initially moving the liquid containing target bio-molecules to the separation unit at a constant flow rate range during a constant flow rate stage, 
 selecting a switching scheme by which the constant flow rate stage for the liquid containing target bio-molecules ceases and a constant pressure stage within the flow path is initiated at a switching point that is reached at substantially the same time at which the constant flow rate stage ceases, 
 defining the switching point according to achievement of a predetermined high pressure value within the flow path, and 
 ceasing, at the switching point, the constant flow rate stage and allowing the flow rate to reduce toward a low flow rate that is slower than the constant flow rate range, and increasing the pressure within the flow path from a low pressure toward the constant pressure range within the flow path, thereby initiating said constant pressure stage at approximately the switching point, said constant pressure range being greater than said low pressure, and said ceasing and initiating being according to said switching scheme; and 
   collecting target bio-molecules as a purified pharmaceutical or biotechnology product.   
     
     
         28 . The system in accordance with  claim 27 , wherein said system is adapted to carry out direct flow filtration upon the pharmaceutical or biotechnology liquid, and wherein said separation unit purifies target bio-molecules by separating same from the carrier liquid and undesirable contaminants. 
     
     
         29 . The system in accordance with  claim 27 , wherein said system is adapted to carry out tangential flow filtration upon the pharmaceutical or biotechnology liquid, and wherein said separation unit purifies target bio-molecules by separating same from the carrier liquid and undesirable contaminants. 
     
     
         30 . The system in accordance with  claim 27 , wherein said separation unit is preparative chromatography column, and wherein said system is adapted to carry out loading the pharmaceutical or biotechnology liquid onto a preparative chromatography column which contains an insoluble matrix that preferentially retains the target bio-molecules or undesirable contaminants within the liquid, thereby achieving separation and purification. 
     
     
         31 . The system in accordance with  claim 27 , wherein said separation unit includes a plurality of separation components having filtration porosities which differ in pore size, said separation components of different pore sizes being connected in an in-line fashion. 
     
     
         32 . A system for high-precision separation of pharmaceutical or biotechnology liquids, comprising:
 a reservoir adapted to contain a pharmaceutical or biotechnology liquid having target bio-molecules dissolved or suspended within a carrier liquid;   a separation unit having an inlet and an outlet and separation elements which are adapted to separate target bio-molecules and carrier liquid;   a processor-controlled pump unit adapted to move the pharmaceutical or biotechnology liquid within a flow path between the reservoir and the separation unit and to separate at least some of the target bio-molecules from the liquid;   said processor-controlled pump unit includes control logic which controls movement of the liquid containing target bio-molecules to the separation unit, said control logic achieving the following:
 initially moving the liquid containing target bio-molecules to the separation unit at a low flow rate, 
 selecting a flow rate increase scheme by which the flow rate of the liquid containing target bio-molecules is increased from the low flow rate to a high flow rate, 
 defining the high flow rate according to achievement of a predetermined value of a parameter within the flow path, and 
 increasing the flow rate to the separation unit from the low flow rate to the high flow rate according to the flow rate increase scheme, said increasing terminating upon achievement of the predetermined parameter value; and 
   a collector adapted to collect target bio-molecules as a purified pharmaceutical or biotechnology product.   
     
     
         33 . The system in accordance with  claim 32 , further including a monitor associated with the flow path, said monitor being a flow rate sensor, a pressure sensor, a volume monitor or a timer which senses the predetermined parameter value which is selected from the group consisting of a maximum flow rate, a maximum pressure along the flow path, a predetermined volume and a time limit. 
     
     
         34 . The system in accordance with  claim 32 , wherein said system is adapted to carry out direct flow filtration upon the pharmaceutical or biotechnology liquid, and wherein said separation unit purifies target bio-molecules by separating same from the carrier liquid and undesirable contaminants. 
     
     
         35 . The system in accordance with  claim 32 , further including a feedback loop adapted to transmit parameter information in association with said controlling movement of the liquid for facilitating said increasing of the flow rate to the separation unit. 
     
     
         36 . The system in accordance with  claim 35 , wherein said separation unit includes a plurality of separation components having filtration porosities which differ in pore size, said separation components of different pore sizes being connected in an in-line fashion. 
     
     
         37 . A system for high-precision separation of pharmaceutical or biotechnology liquids, comprising:
 a reservoir adapted to contain a pharmaceutical or biotechnology liquid having target bio-molecules dissolved or suspended within a carrier liquid;   a separation unit having an inlet and an outlet and separation elements which are adapted to separate target bio-molecules and carrier liquid;   a processor-controlled pump unit adapted to move the pharmaceutical or biotechnology liquid within a flow path between the reservoir and the separation unit and to separate at least some of the target bio-molecules from the liquid;   a pressure monitor at a location along the flow path;   said processor-controlled pump unit includes control logic which controls movement of the liquid containing target bio-molecules to the separation unit, said control logic achieving the following:
 initially moving the liquid containing target bio-molecules to the separation unit at a low pressure, 
 selecting a pressure increase scheme by which the pressure of the liquid containing target bio-molecules is increased from the low pressure to a high pressure, 
 defining the high pressure according to achievement of a predetermined high pressure value along the flow path, 
 monitoring said pressure with said pressure monitor along the flow path and 
 increases the pressure from the low pressure to the high pressure according to the pressure increase scheme, said increasing terminating upon achievement of the predetermined high pressure value along the flow path; and 
   collecting target bio-molecules as a purified pharmaceutical or biotechnology product.   
     
     
         38 . The system in accordance with  claim 37 , wherein said system is adapted to carry out direct flow filtration upon the pharmaceutical or biotechnology liquid, and wherein said separation unit purifies target bio-molecules by separating same from the carrier liquid and undesirable contaminants. 
     
     
         39 . A method for high-precision separation of pharmaceutical or biotechnology liquids, comprising:
 providing within a reservoir a pharmaceutical or biotechnology liquid having target bio-molecules dissolved or suspended within a carrier liquid;   controlling movement of the pharmaceutical or biotechnology liquid within a flow path which includes moving the liquid from the reservoir to a separation unit having an inlet, a retentate outlet and at least one permeate outlet;   monitoring pressure at a pressure monitoring location along the flow path;   passing the liquid containing target bio-molecules through the inlet of the separation unit and separating at least some of the target bio-molecules therefrom;   controlling movement of the liquid containing target bio-molecules to the separation unit, said controlling movement including:
 initially moving the liquid containing target bio-molecules to the separation unit while the pressure monitoring location registers a high pressure of said liquid, 
 selecting a pressure decrease switching scheme by which the pressure of the liquid containing target bio-molecules is decreased from the high pressure to a low pressure of said liquid, 
 defining the low pressure according to achievement of a predetermined low pressure value at the pressure monitoring location, and 
 automatically decreasing the pressure from the high pressure to the low pressure according to the pressure decrease switching scheme, said decreasing pressure being effected by modulated operation of at least one pressure control valve along at least one location of the flow path from the retentate outlet, the permeate outlet or both in response to monitored pressure readings at said at least one flow path location, said decreasing pressure automatically terminating upon achievement of the predetermined low pressure value along the flow path; and 
   collecting target bio-molecules as a purified pharmaceutical or biotechnology product.   
     
     
         40 . The method in accordance with  claim 39 , wherein said method carries out tangential flow filtration upon the pharmaceutical or biotechnology liquid and purifies target bio-molecules by separating same from the carrier liquid and undesirable contaminants. 
     
     
         41 . The method in accordance with  claim 39 , wherein said pressure decrease scheme automatically and progressively decreases the flow rate in a step-wise fashion or in a continuously decreasing fashion. 
     
     
         42 . A method for high-precision separation of pharmaceutical or biotechnology liquids, comprising:
 providing within a reservoir a pharmaceutical or biotechnology liquid having target bio-molecules dissolved or suspended within a carrier liquid;   controlling movement of the pharmaceutical or biotechnology liquid within a flow path which includes moving the liquid from the reservoir to a separation unit having an inlet and an outlet;   passing the liquid containing target bio-molecules through the inlet of the separation unit and separating at least some of the target bio-molecules therefrom;   controlling movement of the liquid containing target bio-molecules to the separation unit, said controlling movement including:
 initially moving the liquid containing target bio-molecules to the separation unit by pumping same at a high rate of flow of said liquid, 
 selecting a flow rate decrease switching scheme by which the flow rate of the liquid containing target bio-molecules is decreased from the high rate of flow to a low rate of flow of said liquid, said decrease in flow rate being effected by modulating said pumping in response to output readings of an electronic flow meter along at least one location of the flow path from a retentate outlet, a permeate outlet or both, 
 defining the low flow rate according to achievement of a predetermined value of a parameter within the flow path, said predetermined parameter value being s elected from the group consisting of a maximum flow rate, a maximum pressure along the flow path, a predetermined volume, and a time limit, and 
 automatically decreasing the rate of flow of said liquid to the separation unit from the high flow rate to the low flow rate according to the flow rate decrease switching scheme, said decreasing automatically terminating upon achievement of the predetermined parameter value; and 
   collecting target bio-molecules as a purified pharmaceutical or biotechnology product.   
     
     
         43 . The method in accordance with  claim 42 , wherein said flow rate decrease scheme automatically and progressively decreases the flow rate in a step-wise fashion or in a continuously decreasing fashion. 
     
     
         44 . The method in accordance with  claim 42 , wherein said method carries out tangential flow filtration upon the pharmaceutical or biotechnology liquid and purifies target bio-molecules by separating same from the carrier liquid and undesirable contaminants. 
     
     
         45 . A method for high-precision separation of pharmaceutical or biotechnology liquids, comprising:
 providing within a reservoir a pharmaceutical or biotechnology liquid having target bio-molecules dissolved or suspended within a carrier liquid;   controlling movement of the pharmaceutical or biotechnology liquid within a flow path which includes moving the liquid from the reservoir to a separation unit having an inlet and an outlet;   passing the liquid containing target bio-molecules through the inlet of the separation unit and separating at least some of the target bio-molecules therefrom;   controlling movement of the liquid containing target bio-molecules to the separation unit, said controlling movement including:
 initially moving the liquid containing target bio-molecules to the separation unit at a high rate of flow of said liquid and while a pressure monitoring location of the flow path registers a high pressure of said liquid, 
 selecting a flow rate decrease switching scheme by which the flow rate of the liquid containing target bio-molecules is decreased from the high rate of flow to a low rate of flow of said liquid, 
 selecting a pressure decrease switching scheme by which the pressure of the liquid containing target bio-molecules is decreased from the high pressure to a low pressure of said liquid, 
 defining the low flow rate according to achievement of a predetermined value of a parameter within the flow path, said predetermined parameter value being selected from the group consisting of a maximum flow rate, a maximum pressure along the flow path, a predetermined volume, and a time limit, 
 defining the low pressure according to achievement of a predetermined low pressure value at the pressure monitoring location and 
 automatically decreasing the rate of flow of said liquid and automatically decreasing the pressure to the separation unit from the high flow rate to the low flow rate according to the flow rate decrease switching scheme and according to the pressure decrease switching scheme, said decreasing automatically terminating upon achievement of the predetermined parameter value; and 
   collecting target bio-molecules as a purified pharmaceutical or biotechnology product.   
     
     
         46 . The method in accordance with  claim 45 , wherein said decrease schemes automatically and progressively decrease the flow rate and the pressure in a step-wise fashion or automatically and progressively decrease the flow rate and the pressure in a continuously decreasing fashion. 
     
     
         47 . The method in accordance with  claim 45 , wherein said method carries out tangential flow filtration upon the pharmaceutical or biotechnology liquid and purifies target bio-molecules by separating same from the carrier liquid and undesirable contaminants.