Automated cell processing systems and methods

Abstract

A system for automated processing of a plurality of batches, each batch being derived from one biological sample, the system comprising an enclosure which can be closed and sterilized, each batch of the plurality of batches comprising one or more cell processing container; a plurality of reagent containers for holding reagents within the enclosure; at least one reagent dispenser within the enclosure for dispensing reagents during said automated processing; a quality control system within the enclosure for analyzing at least one characteristic of a batch during said automated processing; a harvester within the enclosure for harvesting batches; a robotic system within the enclosure, configured for transporting cell processing containers, decapping or otherwise opening cell processing containers, pipetting reagents or liquids from cell processing containers, and aspirating liquids from cell processing containers, during said automated processing; a tracker for electronically tracking the plurality of batches after its introduction to the enclosure; and a control unit (CU) communicatively coupled to the at least one reagent dispenser, the quality control system, the harvester, the robotic system and the tracker for controlling said automatic processing of said batches.

What is claimed is: 
     
         1 . A system for automated processing of a plurality of batches, each batch being derived from one biological sample, the system comprising:
 an enclosure which can be closed and sterilized for the automated processing of the plurality of batches, each batch of the plurality of batches comprising one or more cell processing container;   a plurality of reagent containers for holding reagents within the enclosure;   at least one reagent dispenser within the enclosure for dispensing reagents during said automated processing;   a quality control system within the enclosure for analyzing at least one characteristic of a batch during said automated processing;   a harvester within the enclosure for harvesting batches;   a robotic system within the enclosure, configured for at least one of transporting cell processing containers, decapping or otherwise opening cell processing containers, pipetting reagents or liquids from cell processing containers, and aspirating liquids from cell processing containers, during said automated processing;   a tracker for electronically tracking the plurality of batches after its introduction to the enclosure; and   a control unit (CU) communicatively coupled to the at least one reagent dispenser, the quality control system, the harvester, the robotic system and the tracker for controlling said automatic processing of said batches,   wherein the plurality of batches comprises a first batch and a second batch, the system being configured to receive the second batch into the enclosure before the first batch is transported out of the enclosure,   the CU being configured to automatically process the first batch and the second batch within the enclosure at the same time, without cross contamination from the other of the first batch and the second batch,   wherein:   the CU is configured to ensure that cell processing containers are not left uncovered during said automated processing except during addition or removal of materials, wherein only cell processing containers from one batch at a time are opened to the environment, such that only one batch is exposed to the environment inside the enclosure at any one time,   such that cross-contamination between the first batch and the second batch is prevented.   
     
     
         2 . The system of  claim 1 , further comprising one or more of:
 a particle counter communicatively coupled to the CU for measuring a particle count inside the enclosure, wherein the CU is configured to allow receiving of the second batch into the enclosure responsive to the particle count satisfying a predetermined criterion; and   an air flow system for controlling an air pressure inside the enclosure to be greater than an air pressure outside the enclosure, wherein the air flow system is configured to push particles and contaminants out and away from uncovered cell processing containers.   
     
     
         3 . The system of  claim 1 , wherein the enclosure is at least a class 100 environment or at least a class 10 environment. 
     
     
         4 . The system of  claim 1 , wherein:
 the enclosure is defined at least in part by a top wall, a first side wall and a second side wall extending opposite the first side wall, and a bottom wall;   the enclosure has an air inlet port defined in one or more of the top wall, the first side wall, the second side wall and the bottom wall;   the enclosure has an air outlet port disposed in one or more of the top wall, the first side wall, the second side wall and the bottom wall,   the air flow system being configured to direct air flow into the enclosure via the air inlet port and air flow out of the enclosure via the air outlet port,   an air flow within the enclosure being laminar.   
     
     
         5 . The system of  claim 1 , further comprising a tracker communicatively coupled to the CU for electronically tracking the batch after its introduction to the enclosure. 
     
     
         6 . The system of  claim 1 , wherein the CU is configured to control automatic processing of batches based on a signal received from the quality control system. 
     
     
         7 . The system of  claim 1 , wherein each of the at least one reagent dispenser, the quality control system, the harvester, and the robotic system is configured to operate on any one of a first batch and a second batch such that, when the first batch is being operated on by one of the at least one reagent dispenser, the quality control system, the harvester, and the robotic system, the second batch is being operated on by another of the at least one reagent dispenser, the quality control system, the harvester, and the robotic system. 
     
     
         8 . The system of  claim 1 , further comprising an automatic sterilizer communicatively coupled to the CU for automatically sterilizing the enclosure before introducing the second batch into the enclosure. 
     
     
         9 . The system of  claim 1 , further comprising a waste receptacle selectively fluidly connected to the enclosure at a location remote from a center of the closed enclosure and/or in a configuration that prevents particles in the waste receptacle from entering the enclosure, wherein an air pressure in the waste receptacle is controlled to be lower than an air pressure inside the enclosure. 
     
     
         10 . The system of  claim 9 , wherein the enclosure is connected to the waste receptacle by a conduit configured to prevent backsplashing of waste material deposited into the conduit for disposal into the waste receptacle. 
     
     
         11 . The system of  claim 1 , wherein one of the plurality of reagent containers is placed outside of the enclosure and connected to one of the at least one reagent dispensers by a fill line. 
     
     
         12 . The system of  claim 1 , wherein the quality control system is one or more of:
 a flow cytometer;   a plate reader;   a microscope; and   a PCR machine.   
     
     
         13 . The system of  claim 1 , wherein the harvester comprises at least one of:
 a container for holding a solution;   a freezer or a cryofreezer; and   a packaging system configured to place the batch in a transport container.   
     
     
         14 . The system of  claim 1 , further comprising an isolator, the enclosure being selectively fluidly connected to the isolator, and objects from outside the system being received into the enclosure via the isolator, and/or objects from inside the enclosure being passed out of the system via the isolator. 
     
     
         15 . The system of  claim 14 , wherein an air pressure inside the enclosure is greater than an air pressure in the isolator and an air pressure inside the isolator is greater than an air pressure adjacent to the isolator in a direction other than the enclosure, or an ambient air pressure outside the system. 
     
     
         16 . The system of  claim 14 , further comprising a biological safety cabinet (BSC), wherein the isolator is selectively fluidly connected to the BSC, and objects from outside the system are received into the isolator via the BSC, and objects from inside the enclosure are passed out of the system by passing from the enclosure to the isolator and from the isolator to the BSC via the isolator. 
     
     
         17 . The system of  claim 1 , wherein:
 the enclosure is a first enclosure;   the plurality of reagent containers is a plurality of first reagent containers;   at least one reagent dispenser is an at least one first reagent dispenser;   the quality control system is a first quality control system for analyzing at least one characteristic of a first batch;   the harvester is a first harvester; and   the robotic system is a first robotic system;   
       the system further comprising:
 an incubator disposed outside the first enclosure, the first enclosure being selectively fluidly connected to the incubator; 
 a second closed and sterile enclosure selectively fluidly connected to the first enclosure or to the incubator; 
 a plurality of second reagent containers; 
 at least one second reagent dispenser; 
 a second quality control system for analyzing at least one characteristic of a second batch; 
 a second harvester; and 
 a second robotic system, 
 the CU being communicatively coupled to the at least one first and second reagent dispenser, the first and second quality control system, the first and second harvester and the first and second robotic system for controlling automatic processing of the first and second batches without handling by a human operator. 
 
     
     
         18 . The system of  claim 1 , comprising one or more of:
 a centrifuge, a cell sorter, or a magnet for automatically purifying cell mixtures or obtaining a cell pellet;   an incubator for incubating cells;   automated system for determining cell number or cell confluency in a sample;   automated system for conducting quality control and/or quality assurance analysis;   a sterilizer for sterilizing the enclosure; and   a robotic system for cryopreservation of batches and/or a manipulator for manipulating samples or reagents at subzero temperatures.   
     
     
         19 . The system of  claim 1 , comprising one or more of the following automated components:
 (1) a robotic aspirator housed within the enclosure and configured for use with disposable tips;   (2) a decapper housed within the enclosure and configured to decap a screwcap lid of a container;   (3) a liquid fill system housed inside the enclosure and configured for direct filling of liquid from a supply container disposed inside or outside the enclosure into a cell processing container disposed inside the enclosure; and   (4) a tilt system configured for tilting a cell processing container disposed thereon, for removal or collection of cells or media therefrom.   
     
     
         20 . The system of  claim 18 , wherein the sterilizer is configured to allow sterilization of the enclosure without removing the batches from the system.