Re-Circulation Loop in CFF/TFF Single Use Path Flow
The disclosed subject matter relates to an automated CFF/TFF system that provides the operations of system treatment with a system treatment solution(such as buffer) and filtration of a solution (e.g., a biofluid) can be accomplished in succession without having to re-configure the system (such as re-routing the fluid conduits) that could compromise the integrity of the system. As a result, there will be reduced contamination risk, reduced volume of buffer required and will save time for the filtration process.
1 . An automated CFF/TFF system configured to utilize flexible tubing, comprising
a cabinet having sides that define a cabinet interior and a cabinet exterior, the cabinet including:
a plurality of pinch valves such that the portion of the valve through which the flexible tubing passes is positioned on the cabinet exterior,
a plurality of pumps such that the portion of the pump through which the flexible tubing passes or is connected is positioned on the cabinet exterior, and
a plurality of sensor connectors such that when a sensor is connected thereto the portion of the sensor to which the flexible tubing is connected is positioned on the cabinet exterior; and
an electronic data processing network at least partially positioned in the cabinet interior, the electronic data processing network connected to and capable of at least one of receiving, transmitting, processing and recording data associated with at least one of the plurality of pumps, the plurality of pinch valves and the plurality of sensor connectors,
wherein the plurality of pumps, the plurality of pinch valves and the plurality of sensor connectors are proximate to a path for the flexible tubing configured to form a fluid circuitry including a reservoir and a CFF/TFF filtration module through which a fluid stream of a solution may be conducted through the automated CFF/TFF system, the fluid circuitry comprising:
a feed conduit to provide fluid communication between an outlet of the reservoir and a feed inlet of the CFF/TFF filtration module,
a retentate conduit to provide fluid communication between a retentate outlet of the CFF/TFF filtration module and an inlet of the reservoir,
a permeate conduit to provide fluid communication with a permeate outlet of the CFF/TFF filtration module, and
a re-circulation loop conduit to provide fluid communication between the permeate conduit and the retentate conduit.
2 . The automated CFF/TFF system of claim 1 , wherein the plurality of pumps and the plurality of valves are capable of driving and regulating the fluid stream through the automated CFF/TFF system.
3 . The automated CFF/TFF system of claim 1 , wherein the plurality of sensor connectors when connected to a sensor are capable of acquiring data about the fluid stream as it flows through the automated CFF/TFF system.
4 . The automated CFF/TFF system of claim 1 , wherein the electronic data processing network is capable of connecting to and determining the performance of the CFF/TFF filtration module.
5 . The automated CFF/TFF system of claim 1 , wherein the fluid circuitry further includes a second reservoir suitable for containing the solution and having a second reservoir outlet that is in fluid communication with the reservoir.
6 . The automated CFF/TFF system of claim 1 , wherein the plurality of pumps includes a peristaltic pump or a piston pump.
7 . The automated CFF/TFF system of claim 6 , wherein the piston pump is single use.
8 . The automated CFF/TFF system of claim 1 , wherein the flexible tubing, the sensors, the reservoir and the CFF/TFF filtration module are single use.
9 . A method of using an automated CFF/TFF system, the method comprising:
providing an automated CFF/TFF system configured to utilize flexible tubing comprising:
a cabinet having sides that define a cabinet interior and a cabinet exterior, the cabinet including:
a plurality of pinch valves such that the portion of the valve through which the flexible tubing passes is positioned on the cabinet exterior,
a plurality of pumps such that the portion of the pump through which the flexible tubing passes or is connected is positioned on the cabinet exterior,
a plurality of sensor connectors such that when a sensor is connected thereto the portion of the sensor through which the flexible tubing is connected is positioned on the cabinet exterior; and
an electronic data processing network at least partially positioned in the cabinet interior, the electronic data processing network connected to and capable of at least one of receiving, transmitting, processing and recording data associated with at least one of the plurality of pumps, the plurality of pinch valves and the plurality of sensors,
wherein the plurality of pumps, the plurality of pinch valves and the plurality of sensors are proximate to a path for flexible tubing configured to form a fluid circuitry including a first reservoir, a second reservoir, a third reservoir and a CFF/TFF filtration module through which a fluid stream of a solution may be conducted through the automated CFF/TFF system, the fluid circuitry comprising:
a feed conduit to provide fluid communication between an outlet of the first reservoir and a feed inlet of the CFF/TFF filtration module,
a retentate conduit to provide fluid communication between a retentate outlet of the CFF/TFF filtration module and an inlet of the first reservoir,
a permeate conduit to provide fluid communication with a permeate outlet of the CFF/TFF filtration module,
a re-circulation loop conduit to provide fluid communication between the permeate conduit and the retentate conduit,
a second reservoir feed conduit to provide fluid communication between the first reservoir and the second reservoir,
a third reservoir feed conduit to provide fluid communication between the first reservoir and the third reservoir, and
a drain;
connecting a sensor to at least one of the plurality of sensor connectors;
forming the fluid circuitry using flexible tubing to connect the first reservoir, the second reservoir, the third reservoir, the CFF/TFF filtration module, the plurality of pinch valves, the plurality of pumps and the plurality of sensors;
configuring the plurality of pumps and plurality of valves to provide a system treatment solution to the first reservoir from the second reservoir;
providing a system treatment solution to the first reservoir from the second reservoir;
configuring the plurality of pumps and plurality of valves to circulate the system treatment solution from the first reservoir through the feed conduit, the CFF/TFF filtration module, the retentate conduit, the permeate conduit and the recirculation loop conduit to return to the first reservoir;
circulating the system treatment solution from the first reservoir through the feed conduit, the CFF/TFF filtration module, the retentate conduit, the permeate conduit and the recirculation loop conduit to return to the first reservoir;
configuring the plurality of pumps and plurality of valves to drain the system treatment solution from the automated CFF/TFF system using the drain;
draining the system treatment solution from the automated CFF/TFF system using the drain;
configuring the plurality of pumps and plurality of valves to provide a solution for filtration to the first reservoir from the third reservoir;
providing a solution for filtration to the first reservoir from the third reservoir;
configuring the plurality of pumps and plurality of valves to filter the solution for filtration from the first reservoir through the CFF/TFF filtration module; and
filtering the solution for filtration from the first reservoir through the CFF/TFF filtration module.
10 . The method of claim 9 , further including driving and regulating the fluid stream through the automated CFF/TFF system using the plurality of pumps and the plurality of valves.
11 . The method of claim 9 , further including acquiring data about the fluid stream through the automated CFF/TFF system using the plurality of sensors.
12 . The method of claim 9 , wherein the CFF/TFF filtration module includes sensors capable of determining the performance thereof, connecting the electronic data processing network to the CFF/TFF filtration module so as to at least one of receiving, transmitting, processing and recording data associated with CFF/TFF filtration module and determining the performance of the CFF/TFF filtration module using the electronic data processing network.
13 . The method of claim 9 , wherein
the drain is in fluid communication with the permeate conduit and the recirculation loop conduit; and
draining the system treatment solution includes circulating the system treatment solution from the first reservoir through the feed conduit, the automated CFF/TFF filtration module, the retentate conduit, the permeate conduit, the recirculation loop conduit to the drain such that the flow in the retentate conduit proceeds to the recirculation loop conduit and the flow from the recirculation loop conduit and the flow from the permeate conduit exit the automated CFF/TFF system through the drain.
14 . The method of claim 9 , wherein the system treatment solution includes buffer.
15 . The method of claim 9 , wherein the solution for filtration includes a biofluid.
16 . The method of claim 9 , wherein the electronic data processing network controls the steps of:
configuring the plurality of pumps and plurality of valves to provide a system treatment solution to the first reservoir from the second reservoir;
providing a system treatment solution to the first reservoir from the second reservoir;
configuring the plurality of pumps and plurality of valves to circulate the system treatment solution from the first reservoir through the feed conduit, the CFF/TFF filtration module, the retentate conduit, the permeate conduit and the recirculation loop conduit to return to the first reservoir;
circulating the system treatment solution from the first reservoir through the feed conduit, the CFF/TFF filtration module, the retentate conduit, the permeate conduit and the recirculation loop conduit to return to the first reservoir;
configuring the plurality of pumps and plurality of valves to drain the system treatment solution from the automated CFF/TFF system using the drain;
draining the system treatment solution from the automated CFF/TFF system using the drain;
configuring the plurality of pumps and plurality of valves to provide a solution for filtration to the first reservoir from the third reservoir;
providing a solution for filtration to the first reservoir from the third reservoir;
configuring the plurality of pumps and plurality of valves to filter the solution for filtration from the first reservoir through the CFF/TFF filtration module; and
filtering the solution for filtration from the first reservoir through the CFF/TFF filtration module,
wherein the fluid circuitry remains unchanged during the above steps.
17 . The method of claim 9 , wherein at least one of the plurality of pumps is a piston pump and the piston pump, the flexible tubing, the plurality of sensors, the first reservoir, the second reservoir, the third reservoir and CFF/TFF filtration module are single use.
18 . An automated CFF/TFF system, comprising
a cabinet having sides that define a cabinet interior and a cabinet exterior, the cabinet including:
a plurality of pinch valves such that the portion of the valve through which the flexible tubing passes is positioned on the cabinet exterior,
a plurality of pumps such that the portion of the pump through which the flexible tubing passes or is connected is positioned on the cabinet exterior, and
a plurality of sensor connectors including a sensor connected to at least one of the plurality of sensor connectors, the portion of the sensor to which the flexible tubing is connected is positioned on the cabinet exterior;
an electronic data processing network at least partially positioned in the cabinet interior, the electronic data processing network connected to and capable of at least one of receiving, transmitting, processing and recording data associated with at least one of the plurality of pumps, the plurality of pinch valves and the plurality of sensors; and
flexible tubing forming a fluid circuitry including a reservoir and a CFF/TFF filtration module through which a fluid stream of a solution may be conducted through the automated CFF/TFF system, the fluid circuitry comprising:
a feed conduit to provide fluid communication between an outlet of the reservoir and a feed inlet of the CFF/TFF filtration module,
a retentate conduit to provide fluid communication between a retentate outlet of the CFF/TFF filtration module and an inlet of the reservoir,
a permeate conduit to provide fluid communication with a permeate outlet of the CFF/TFF filtration module, and
a re-circulation loop conduit to provide fluid communication between the permeate conduit and the retentate conduit.
19 . The automated CFF/TFF system of claim 18 , wherein at least one of the plurality of pumps is a piston pump and the piston pump, the flexible tubing, the plurality of sensors, the reservoir and CFF/TFF filtration module are single use.
20 . The automated CFF/TFF system of claim 18 , wherein the electronic data processing network is connected to and capable of determining the performance of the CFF/TFF filtration module.