Automated cell processing with integrated sample preparation and analysis system

Abstract

The present disclosure relates to systems and methods for automated sample preparation and analysis of cell products during cell processing. Generally, a fluid device containing a cell product is transported within a controlled workcell to a sample preparation and analysis system using robotic mechanisms. Samples are prepared for analysis using integrated, automatic modules. Parameters such as cell viability, concentration, and phenotype are assessed to guide workflow adjustments. The system incorporates modules for reagent storage, waste management, and automated fluid device disassembly, enhancing efficiency and sterility. A controller coordinates sample preparation and analysis, maintains records, and ensures compliance with processing criteria. The controller also collects and manages sample analysis results and stores the results in a centralized environment to optimize data analysis and reporting.

Description

ATTY DOCKET No.: CEES-026 / 01WO 337273-2147AUTOMATED CELL PROCESSING WITH INTEGRATED SAMPLE PREPARATION AND ANALYSIS SYSTEMCROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to U.S. Provisional Patent Application Serial No.63 / 740,277 filed December 30, 2024, the contents of which are incorporated herein by reference in their entirety for all purposes.TECHNICAL FIELD

[0002] The present disclosure relates to systems, devices, and methods for automated cell processing and sample preparation and analysis.BACKGROUND

[0003] Cell processing systems are widely used for applications such as cell therapy, drug development, and research. While some current systems may automate or partially automate discrete steps of processing workflows, these systems generally rely on separate, stand-alone analytical devices to assess key parameters such as cell viability, concentration, phenotype, and functionality. Such systems often require manual sample transfer, which increases the risk of contamination, introduces variability, and adds operational complexity. Moreover, the need for manual intervention disrupts workflow continuity, slows down processing times, and impairs real-time decision-making during critical stages of cell processing.

[0004] The separation between processing and analytics also limits the potential for closed-system operations, which are essential for maintaining sterility and compliance with regulatory standards in clinical and industrial environments. Additionally, the lack of direct integration inhibits the ability to monitor and adjust processing conditions dynamically based on analytical feedback, which is crucial for optimizing outcomes and reducing batch failures.

[0005] Therefore, there is a need for a fully integrated and automated cell processing platform that incorporates a physically integrated analysis system. Prior to transferring a sample of cell material into the integrated analysis system, the sample has to be prepared (e.g., mixed and diluted to a desired cell concentration). Accordingly, described herein are systems, devices, and methods for cell processing using a system with sample preparation and analytical capabilities.ATTY DOCKET No.: CEES-026 / 01WO 337273-2147SUMMARY

[0006] The present disclosure relates generally to systems, devices, and methods for automated cell processing. In general, a method for preparing a cell product sample for analysis during automated cell processing may include moving a fluid device from a cell processing instrument bay to a sample preparation module using a robot. Each of the fluid device, the cell processing instrument bay, the sample preparation module, and the robot may be positioned within a workcell. The fluid device may contain a cell product, and a sample of the cell product may be transferred from the fluid device to the sample preparation module. The sample preparation module may be configured to prepare the sample for transfer to an analysis module to determine one or more sample parameters.

[0007] In some variations, transferring the sample to the sample preparation module may include automatically disassembling at least a portion of the fluid device to extract the sample. The fluid device may include a sterile liquid transfer device (SLTD) or a cartridge configured to couple to the processing instrument to process the cell product. The analysis module may be integrated with the sample preparation module, and the sample parameters determined by the analysis module may include one or more of cell viability, cell count, cell concentration, cell recovery, cell diameter, cell size distribution, glucose, lactate, pH, phenotypic markers, chimeric antigen receptor expression, transgenic T cell receptor expression, cell identity markers, cell purity, vector copy number, or combinations thereof.

[0008] In some variations, the analysis module may include one or more of a flow-based bead reader, a polymerase chain reaction (PCR) system, a cell analyzer, a microplate reader, or a cell counter. A first analysis module may be integrated with the sample preparation module, and a second analysis module may also be included. The sample preparation module may be configured to automatically prepare the sample based on a set of preparation parameters, which may include separating the sample, adding a blocking solution, transferring reagents, mixing the sample, incubating the sample, or washing the sample with a buffer. The preparation parameters may include variables such as sample temperature, container temperature, reagent type, mixing technique and duration, centrifugation speed and duration, incubation temperature and duration, blocking solution type, or buffer type.

[0009] The sample preparation and analysis process may be based on a set of transfer parameters, including sample volume, origin sample location, and subsequent sample location. AATTY DOCKET No.: CEES-026 / 01WO 337273-2147label on the fluid device, which may include a barcode or RFID tag, may be scanned to identify the cell product and determine the type of analysis to perform. An electronic record for the cell product may be generated as the sample is prepared and analyzed by the system.

[0010] A system for automated cell processing may include a fluid device containing a cell product, a processing instrument including a receiving bay configured to receive the fluid device, and a sample preparation and analysis system. The sample preparation system may include a sample preparation module, a robot configured to move the fluid device from the processing instrument to the sample preparation system, and an analysis module. Each of the processing instrument receiving bay, the sample preparation system, and the robot may be positioned within a workcell.

[0011] The sample preparation module may include one or more of a sample separator, a sample mixer, and an incubator. In some variations, the sample separator may include a centrifuge, and the sample mixer may include an orbital shaker. The analysis module may include one or more of a flow-based bead reader, a PCR system, a cell analyzer, a microplate reader, or a cell counter. A first analysis module may be integrated with the sample preparation module, and a second analysis module may also be included, where at least one of the first or second analysis modules may include a cell counter.

[0012] In some variations, the system may further include a transfer module including one or both of a fluid device disassembly system having a conveyor and a disassembly tool. The conveyor may be configured to move the fluid device toward the disassembly tool, and the disassembly tool may include a grasper configured to releasably grasp a cap of the fluid device. The disassembly tool may be coupled to a sidewall of the workcell, and the robot may move the fluid device to the conveyor within the workcell.

[0013] In some variations, the sample preparation and analysis system may further include a scanner configured to identify the cell product via a label on the fluid device, wherein the label may include a barcode or RFID tag. The system may also include a reagent storage module configured to store materials for use by the sample preparation module. The reagent storage module may include a scanner to verify the materials and may be refrigerated. The materials may include buffers, cytokines, proteins, enzymes, polynucleotides, transfection reagents, viral vectors, dyes, antibodies, antibiotics, nutrients, cryoprotectants, solvents, cellular materials, small molecules, pharmaceutically acceptable excipients, and combinations thereof.ATTY DOCKET No.: CEES-026 / 01WO 337273-2147

[0014] Additionally, the analysis module may include a waste module configured to store used sample preparation devices and material wastes, which may include fluid devices, vials, well plates, pipette tips, or combinations thereof. A controller may be configured to determine at least a portion of the processing workflow for the cell product based on the analysis of the sample and may generate an electronic record for the cell product. The fluid device may include a sterile liquid transfer device (SLTD) or a cartridge configured to couple to the processing instrument.BRIEF DESCRIPTION OF THE DRAWINGS

[0015] FIG. 1 A is a block diagram of an illustrative variation of a workcell of a cell processing system. FIG. IB is a block diagram of an illustrative variation of a sample preparation and analysis system of the cell processing system. FIG. 1C is a block diagram of an illustrative variation of a controller of the cell processing system.

[0016] FIG. 2 depicts a top view of an illustrative variation of a workcell housing a sample preparation and analysis system.

[0017] FIG. 3 is a block diagram of an illustrative variation of a disassembly instrument of a sample preparation and analysis system.

[0018] FIG. 4A depicts a perspective view of an illustrative variation of a disassembly instrument of a sample preparation and analysis system. FIG. 4B depicts a partial view of the disassembly instrument of FIG. 4A without a fluid device coupled thereto. FIG. 4C depicts another partial view of the disassembly instrument of FIG. 4A with a fluid device coupled thereto. FIG. 4D depicts a side view of an illustrative variation of a portion of a sample preparation and analysis system including the disassembly instrument of FIG. 4A.

[0019] FIG. 5 depicts an exemplary configuration of a sample preparation and analysis system and related workflow.

[0020] FIG. 6 depicts a schematic diagram of an illustrative variation of a cartridge.

[0021] FIG. 7A depicts a perspective view of an illustrative variation of a fluid device in an open configuration. FIG. 7B depicts the fluid device of FIG. 7A in a closed configuration.

[0022] FIG. 8 is a flowchart of an illustrative variation of a method for analyzing a cell product sample during automated cell processing.ATTY DOCKET No.: CEES-026 / 01WO 337273-2147DESCRIPTION

[0023] Disclosed herein are systems, devices, and methods for automated sample preparation and analysis of cell products (e.g., cell-based products) using an integrated and unified sample preparation and analysis system. The analysis of cell products during and after processing is essential to ensure product quality, optimize workflows, and meet regulatory standards.Traditional systems lack integrated analysis capabilities, and therefore rely on manual sampling and off-line analysis, which can introduce delays into the processing workflow, increase the risk of human error during analysis, and increase the risk of contamination of a cell product. In contrast, the systems herein comprise fully integrated and automated analysis capabilities that make overall processing faster and more efficient, minimize human error during analysis, and maintain product sterility. In particular, these systems enable real-time, automatic monitoring of cell product sample parameters within a sterile interior zone of a workcell and without the need for manual intervention. This integration may enhance processing efficiency and data accuracy and support closed-system operations by ensuring sterility and compliance with regulatory requirements. For example, the systems herein may be a controlled, regulated environment to enable consistent and quality sample and analysis data. Indeed, by embedding sample preparation and analytics directly within the processing workflow, the systems herein may enable adaptive processing that ultimately improves the consistency, scalability, and reliability of cell products.

[0024] In general, the systems herein comprise a workcell housing one or more processing instruments, a sample preparation and analysis system, and a robot configured to transfer a fluid device (e.g., reagent container) and / or cartridge carrying a cell product between the one or more processing instruments and the sample preparation and analysis system. The sample preparation and analysis system may be a flexible platform configured to receive the fluid device and / or cartridge, prepare a sample of the cell product therefrom, and determine one or more sample parameters using an analysis module of the analysis system (comprising, e.g., one or more analysis tools). The one or more sample parameters may be used to determine a remainder of a processing workflow for the cell product (e.g., whether adjustments should be made to a predetermined workflow).

[0025] The methods herein may be used with the systems described in detail below. In general, the methods may comprise moving a fluid device or cartridge with a cell product from aATTY DOCKET No.: CEES-026 / 01WO 337273-2147processing instrument to the analysis system within the workcell. Next, the methods may comprise transferring a sample of the cell product to one or more modules within the sample preparation and analysis system (e.g., sample preparation module and / or analysis module), determining one or more sample parameters of the sample, and determining whether a processing workflow for the cell product should be modified based on the sample parameter.

[0026] Exemplary variations of systems, devices, and methods for automated sample preparation and analysis of cell product samples during cell processing are described in further detail below.I. Systems

[0027] Generally, the cell processing systems herein may be automated (fully or partially) and configured for high-throughput processing, sample preparation and analysis of cell products for biomedical applications. The cell product may comprise cells (e.g., allogeneic or autologous cells) in a fluid, such as a media (e.g., cell culture media). The cell product may contain cells from the same or different donors. One or more steps of a cell processing procedure may be performed using the systems and devices described herein. For example, the processing steps may include one or more of enrichment, selection, activation, electroporation, transduction, expansion, formulation, and the like. Additionally, cell product samples may be analyzed to determine one or more parameters performed using the systems and devices described herein. Non-limiting examples of the sample parameters may include one or more of cell viability, cell count, cell concentration, cell recovery, cell diameter, cell size distribution, glucose, lactate, pH, phenotypic markers, chimeric antigen receptor expression, transgenic T cell receptor expression, cell identity markers, cell purity, and vector copy number. Such analyses may be executed within a combined sample preparation and analysis system (or an independent analysis system) of an enclosed workcell, as described in detail herein.

[0028] The systems herein may include a workcell with a housing or enclosure that forms a closed, sterile environment (e.g., an ISO7, ISO8, ISO9, or controlled not classified environment). The workcell may receive a cartridge with a cell product (e.g., cell solution, cell suspension, cells, etc.) In some variations, the workcell may be configured to process and / or analyze a plurality of cell products in parallel. The workcell may be configured to perform one or more cell processing steps on the cell product. In some variations, the cell processing systemATTY DOCKET No.: CEES-026 / 01WO 337273-2147may comprise a workcell having a plurality of processing instruments that may each be configured to independently perform one or more cell processing steps to the cell product. The workcell may include a robot capable of moving the cartridge within the workcell (e.g., between two or more instruments). The system may also include a fluid device (e.g., a plurality thereof) configured to transfer fluid to and / or from the cartridge and the instruments. As is described herein, one or both of the fluid device and the cartridge may be configured to be transferred (e.g., by the robot) to a sample preparation and analysis system within the workcell so that a cell product sample may be extracted from the fluid device and / or cartridge, prepared, and analyzed to determine one or more sample parameters thereof.

[0029] The robot, instruments, and sample preparation and analysis system may be configured to automatically operate such that operator assistance may not be required at any point during a workflow. For example, the robot may receive the cartridge and move the cartridge between locations (e.g., instruments, analysis system, feedthroughs) within the workcell according to a workflow, where each location may be associated with one or more cell processing or analytics steps. After performing one or more steps of the workflow, the robot may be configured to transfer the cartridge out of the workcell (e.g., by the robot via a feedthrough). The systems herein may additionally include one or more controllers (e.g., connected via a network) coupled to the instruments, robot, and / or analysis system and configured to organize execution of and determine adjustments to the workflow.

[0030] An illustrative block diagram of a cell processing system 100 comprising a workcell 110 is shown in FIG. 1 A. The workcell 110 may comprise one or more of a housing 112, instrument 114, a robot 116 (e.g., robotic arm), a reagent vault 118, and a sample preparation and analysis system 120. One or more of the instrument 114, robot 116, reagent vault 118, and sample preparation and analysis system 120 may be enclosed within the housing 112. The housing 112 may comprise a fully, or at least partially, enclosed housing inside which one or more cell processing and product analysis steps may be performed in a fully, or at least partially, automated process. In some variations, the housing 112 may comprise a volume of less than about 800 m3, less than about 700 m3, less than about 600 m3, less than about 500 m3, less than about 300 m3, less than about 250 m3, less than about 200 m3, less than about 150 m3, less than about 100 m3, less than about 50 m3, less than about 25 m3, less than about 10 m3, and less than about 5 m3, including all ranges and sub-values in-between.ATTY DOCKET No.: CEES-026 / 01WO 337273-2147

[0031] The instrument 114 may comprise one or more instruments, such as a plurality thereof. Each instrument 114 may comprise a liquid transfer instrument or a bioprocessing instrument. The fluid transfer instrument may be used for transferring fluid in and out of the cartridge 140 (described herein below), and the bioprocessing instrument may be configured to perform one or more processing steps on the cartridge 140 (e.g., enrichment, selection, activation, electroporation, transduction, expansion, and / or formulation). In some variations, a plurality of one or both of fluid transfer instruments and bioprocessing instruments may be positioned within the housing 112 of the workcell 110. Furthermore, each instrument 114 may comprise a bay for receiving the cartridge 140.

[0032] The workcell 110 may additionally be configured to receive, store, and / or utilize a cartridge 140 and / or fluid device 150 for one or more processing and / or analysis steps. The cartridge 140 and / or fluid device 150 may be provided outside of the housing 112 and received and used therein, as indicated by the dashed lines in FIG. 1 A. In some variations, the cartridge 140 and / or the fluid device 150 may be transferred in and out of the housing 112 via a feedthrough or other access point. In some variations, the robot 116 may be configured to transfer the cartridge 140 and / or the fluid device 150 throughout the workcell 110, such as between instruments 114, the reagent vault 118, and / or the sample preparation and analysis system 120. In some variations, the fluid device 150 may be a sterile liquid transfer device (SLTD). However, it should be appreciated that the fluid device 150 may be configured to transfer any fluid (e.g., cell solutions, liquids), whether sterile or not.

[0033] The cartridge 140 and / or fluid device 150 may be automatically moved using the robot 116 to reduce manual labor in the cell processing steps. For example, the robot 116 may be configured to transfer the cartridge 140 between various components of the system, including but not limited to: between a feedthrough and a processing instrument 112, among two or more processing instruments, and between a processing instrument and the sample preparation and analysis system 120, wherein transfer between any two components may occur in either direction. Similarly, the robot 116 may be configured to transfer the fluid device 150 between various components of the system, including but not limited to: between the reagent vault 118 and a processing instrument 112 (e.g., to a cartridge therein), among the processing instruments, and between a processing instrument and the sample preparation and analysis system 120, wherein transfer between any two components may occur in either direction.ATTY DOCKET No.: CEES-026 / 01WO 337273-2147

[0034] Fluid transfers into and out of the cartridge 140 may also be performed in a fully or partially automated process. For example, one or more fluids may be stored in the fluid device 150 for transferring and / or removing from the cartridge 140. In some variations, the fluid device 150 may be a sample container for collecting samples of a cell product to transfer to the sample preparation and analysis system 120. As explained above, the fluid device 150 may be moved within the system by the robot 116. Accordingly, the workcell 110 may advantageously enable the transfer of fluids in an automated and metered manner for automating and monitoring cell processing. In some variations, the robot 116 may be configured to move more than one cartridge 140 between different instruments 114 to perform a predetermined sequence of cell processing steps. In this way, multiple cartridges 140 may be processed in parallel, as different steps of the cell processing workflow may be performed at the same time on different cartridges. Furthermore, any set of fluid-carrying components of the system may be coupled together for fluid transfer or storge, such as any combination of the cartridge 140, fluid device 150, instrument 114, and reagent vault 118. For example, when the cartridge 140 is coupled to the instrument 114, the robot 116 may be configured to couple the fluid device 150 to the cartridge 140 via the instrument 114 such that a fluid transfer step between the cartridge 140 and fluid device 150 may occur.

[0035] Moreover, the reagent vault 118 may be configured to store reagents, including but not limited to cell culture media, buffer, cytokines, proteins, enzymes, polynucleotides, transfection reagents, non-viral vectors, viral vectors, antibiotics, nutrients, cryoprotectants, solvents, cellular materials, and pharmaceutically acceptable excipients. Additionally, or alternatively, waste may be stored in the reagent vault, or within a fluid device within the reagent vault. In some variations, in-process samples extracted from one or more cartridges may be stored in the reagent vault 118, or in a fluid device 150 within the reagent vault 118. The reagent vault 118 may comprise one or more controlled temperature compartments (e.g., freezers, coolers, water baths, warming chambers, or others, at e.g., about - 80°C, about -20°C, about 4°C, about 25°C, about 30°C, about 37°C, and about 42°C). Temperatures in these compartments may be varied during the cell processing to heat or cool reagents.

[0036] Further, in some variations, the reagents, waste, and / or extracted in-process samples, among others, may be stored within fluid device(s) 150 within the reagent vault 118. To this end, the fluid device(s) 150 may be transferred to a cartridge within the workcell or a cartridge may be moved by the robot 116 (or manually by an operator) to the reagent vault 118. In someATTY DOCKET No.: CEES-026 / 01WO 337273-2147variations, a fluid transfer instrument of the workcell 110 may be a sterile liquid transfer instrument configured to automatically transfer fluid into or out of the cartridge 140 via one or more fluid device(s) 150. The sterile liquid transfer instrument may be stocked with reagents by, for example, a robot 116 that moves fluid device(s) 142 comprising the reagents from a workcell feedthrough or other location to the sterile liquid transfer instrument. In some variations, the robot 116 may move a fluid device 150 from the reagent vault 118 to the sterile liquid transfer instrument. The reagent vault 118 may have automated doors to permit access by the robot 116 to a fluid device(s) 150 stored therein. The fluid device(s) 150 may be configured for pick-and-place movement by the robot 116. In some variations, the reagent vault 118 may comprise one or more sample pickup areas. For example, the robot 116 may be configured to move one or more fluid devices 150 comprising reagents to and from one or more of the sample pickup areas.

[0037] Further, a controller 160 may be communicab ly coupled to the workcell (e.g., to one or more of its components, such as to all of its components). For example, the controller 160 may be coupled to one or more modules of the sample preparation and analysis system 120 (described in detail below) so that the controller 160 may control one or more preparation and / or analysis steps performed by the module(s) and adjust a cell processing workflow in response to analysis performed therein.Sample Preparation and Analysis System

[0038] During cell processing, various analytical tools may be employed to determine cell product parameters. These parameters may be used to inform workflow construction, such as whether a predetermined workflow needs to be modified in view of one or more cell product sample parameters, or which step should follow in a workflow that is not predetermined. As described throughout, the systems herein may comprise a sample preparation and analysis system - within the workcell itself - that can prepare and analyze a sample of a cell product. This integrated, automated system may enable fast cell processing compared to traditional systems, while simultaneously reducing operational complexity and maintaining sterility of the cell sample and system components. In some embodiments, the sample preparation and analysis system may comprise a sample preparation and rapid cell analysis (SPARC) system.

[0039] The sample preparation and analysis system may include one or more modules configured for sample transfer, sample preparation, sample analysis, and reagent and / or wasteATTY DOCKET No.: CEES-026 / 01WO 337273-2147storage. These modules may be integrated through one or more interfaces including, for example: fluidic connections utilizing sterile fittings (in some variations, with integrated leak detection), network connectivity (e.g., with the controller 160) for real-time data acquisition and system control, mechanical alignment features ensuring precise positioning between modules, environmental barrier systems maintaining sterile conditions during inter-module transfers, and / or materials handling systems (e.g., a robot, such as a robotic pipettor). In some embodiments, the modules may be physically integrated or operationally integrated and positioned to optimize sample preparation and analysis workflow. In some variations, the two or more modules of the sample preparation and analysis system may comprise one or more shared components. These shared components may include one or more of: intermediate fluid containers for sample preparation and / or analysis, integrated data management and control interfaces, and a universal power network. In some variations, critical components of the sample preparation and analysis system may be mounted on precision-leveled platforms. Module positioning may incorporate redundant position verification systems including mechanical stops, optical sensors, and electronic position feedback.

[0040] In some variations, the sample preparation and analysis system may include one or more robots. For example, a sample preparation module may include a robot comprising an automatic pipetter configured to prepare samples. The robotic pipetter may incorporate sensors for liquid level detection. In some variations, multi-channel heads may be utilized to enable parallel sample processing.

[0041] Additionally, or alternatively, samples finishing the transfer module may interact with a robotic arm that is configured to transfer samples, reagents, and / or wastes to and from various combinations of modules within the sample preparation and analysis system. This robot may be equipped with one or more end effectors that may feature, for example, integrated barcode readers for continuous sample tracking. The robotic arm may be mounted on a track system to extend its reach. The arm may incorporate multiple degrees of freedom at each joint. The robotic arm may be coupled to a sidewall of the portion of the workcell housing where the sample preparation and analysis system is positioned, such as to a ceiling thereof.

[0042] Moreover, a scanning system comprising one or more scanners may be integrated into the sample preparation and analysis system to facilitate seamless tracking of samples, reagents, and waste materials across modules. The scanner may be communicably coupled to a system controller and used to read encoded data, such as barcodes or RFID tags, on fluid devices and / orATTY DOCKET No.: CEES-026 / 01WO 337273-2147cartridges, sample containers, and reagents. This integration may enable continuous tracking of materials, support automated workflow adjustments, and ensure accurate sample identification throughout preparation and analysis processes. The scanner may be moveably coupled within the sample preparation and analysis system, such as to a sidewall thereof, allowing it to dynamically track materials as they move between modules. Additionally, or alternatively, one or more scanners of the scanning system may be integrated within other components. For example, a scanner may be integrated into a disassembly instrument of the transfer module and / or into an end effector on a robot, as described below.

[0043] Furthermore, the sample preparation and analysis system may include an access point, such as a door or feedthrough to enable operator access to one or more modules of the analysis system. For example, the sample preparation and analysis system may include an analysis module comprising one or more tools for analyzing cell product samples. In some variations, the analysis module may be configured so that one or more of the tools may be removed and / or replaced with other, same or different tools. The access point may thus facilitate configuration and reconfiguration of the analysis module. Additionally, or alternatively, the access point may allow an operator to remove and / or replace reagents and to remove wastes from the analysis system. In some variations, the access point may incorporate safety features such as interlocked door systems preventing access during automated operations and / or status indicators displaying safe-access conditions.

[0044] As explained above, the sample preparation and analysis system may be positioned within the housing of the workcell. The sample preparation and analysis system and workcell may share components like sterilant sources, fluid (e.g., gas) sources and pumping systems, as well as environmental monitoring via a shared controller or network of controllers. Accordingly, the cleanroom environment maintained within the housing may also be maintained within the analysis system. The analysis system may comprise a volume of the workcell housing of less than about 100 m3, less than about 90 m3, less than about 80 m3, less than about 70 m3, less than about 50 m3, less than about 40 m3, less than about 30 m3, less than about 20 m3, less than about 10 m3, or less than about 5 m3, including all ranges and sub-values therebetween.

[0045] In some variations, the modules of the sample preparation and analysis system may be customized to be integrated with each other and with the broader workcell environment, providing a unified cell processing platform. Each module, including the transfer module, sample preparation module, analysis module, reagent storage module, and waste storage module,ATTY DOCKET No.: CEES-026 / 01WO 337273-2147may be specifically designed to operate within the controlled, sterile environment of the workcell. For example, fluidic connections between the modules may utilize proprietary sterile fittings with integrated leak detection and pressure monitoring systems, ensuring compatibility with the system's automated fluid handling infrastructure. Additionally, the physical layout of the modules may be customized to optimize workflow efficiency, with interconnected modules positioned to minimize transfer distances and reduce processing times. Shared mechanical alignment features, such as precision-leveled platforms and universal docking interfaces, may further facilitate accurate positioning and coupling of the modules within the sample preparation and analysis system.

[0046] The integration of the sample preparation and analysis system into the workcell may also involve system-specific customizations. For instance, the sample preparation and analysis system may share sterilization sources, fluid handling pumps, and environmental monitoring systems with the broader workcell, reducing redundancy and improving resource utilization. The housing of the sample preparation and analysis system may include tailored access points for robotic arms or automated pipettors, allowing precise movement of cartridges, fluid devices, and samples between the sample preparation and analysis system and other workcell instruments. Moreover, the scanner(s) integrated into the sample preparation and analysis system may be customized to read encoded data across multiple modules, ensuring continuity in sample tracking and reagent usage. This interconnected design may allow the sample preparation and analysis system to function as an integral part of the workcell, enabling real-time monitoring, adaptive processing, and streamlined cell product analysis.

[0047] FIG. IB is a block diagram of the sample preparation and analysis system 120 of FIG.1 A. The sample preparation and analysis system 120 may comprise one or more of a transfer module 122, a sample preparation module 124, an analysis module 126, a reagent storage module 128, a waste storage module 130, a scanner system 132, access point(s) 134, and robot(s) 136. These modules may be interconnected in various ways, including physically (as described herein), through a unified control network enabling coordinated operation of analyses, as well as automated material handling and monitoring pathways. For example, the scanner system 132 may comprise one or more scanners configured to detect a barcode or other encoded label associated with a sample, reagent, buffer, analysis tool, and any other component of the sample preparation and analysis system. In some variations, a scanner may be integrated into a system component, such as fixedly mounted to a portion of each of one or more modules of theATTY DOCKET No.: CEES-026 / 01WO 337273-2147sample preparation and analysis system. Additionally, or alternatively, a scanner may be configured to move throughout the sample preparation and analysis system to dynamically track a sample throughout transfer, preparation, and analysis. In some variations, a scanner may be provided on a distal end of a robotic arm configured to move about the analysis area via, e.g., a guiderail or track. Thus, the scanner system 132 may integrate the modules via shared automated monitoring pathways. Moreover, in some variations, the scanner system 132 may additionally or alternatively comprise one or more designated scanning stations positioned within the sample preparation and analysis system.

[0048] Additionally, the robot(s) 136, which may comprise at least one robot, such as at least one robotic pipettor, may be configured to transfer the sample from module to module, and in some variations, from component to component within a module. For example, a robotic pipettor may be configured to transfer the sample from the transfer module to the sample preparation module, between each of the stations of the sample preparation module (described in detail below), and, in some variations, from the sample preparation module to the analysis module. The robotic pipettor may additionally or alternatively transfer reagents and buffers from the reagent storage module to the sample preparation module, as well as may transfer waste to the accumulated at any module of the sample preparation and analysis system to the waste storage module. Therefore, like the scanner system 132, the robot(s) 136 may integrate the modules via shared automated material handling pathways.

[0049] Referring to FIG. 2, a top view of a workcell 210 comprising a sample preparation and analysis system 220 is shown. The sample preparation and analysis system 220 may be partially or fully enclosed by a housing 212 of the workcell 210. In some variations, the sample preparation and analysis system 220 may be positioned adjacent to one or more instruments 214 of the workcell 210. This relative positioning may be optimized through coordinated automation features and integrated monitoring systems, such as the scanner system 132 (described in detail below). The sample preparation and analysis system 220 may define an area within the housing 210 comprising one or more integrated modules for sample preparation and analysis. As depicted in FIG. 2, such modules may be integrated such that a sample (e.g., within a fluid device or cartridge) is received by a transfer module 222, then transferred to a sample preparation module 224, then transferred to an analysis module 226. Reagents used during sample preparation and waste accumulated during sample preparation and / or analysis may be transferred to a reagent storage module 130 and a waste storage module 130, respectively (e.g.,ATTY DOCKET No.: CEES-026 / 01WO 337273-2147via robot 136). Components and aspects of the sample preparation and analysis systems herein are described in detail below.Transfer Module

[0050] The transfer module (e.g., transfer module 122) may be configured to receive a fluid device and / or a cartridge containing a cell product to be sampled and analyzed. Accordingly, the transfer module may comprise a receiving bay sized and shaped to receive one or both of a fluid device and a cartridge. In some variations, the transfer module may comprise at least one first receiving bay sized and shaped to receive a fluid device, and at least one second receiving bay sized and shaped to receive a cartridge. The receiving bay may be a support, such as a support comprising at least one wall (e.g., at least a floor). In some variations, the receiving bay may be partially or fully enclosed. In some variations, the receiving bay may comprise an opening or channel within a partition or wall that at least partially surrounds the sample preparation and analysis system. Further, the receiving bay may be positioned within reach of the robot of the workcell (e.g., robot 116 of FIG. 1 A) so that the robot may be capable of transferring a fluid device and / or cartridge from an instrument (e.g., from a receiving bay thereof) to the receiving bay of the transfer module.

[0051] In some variations, the receiving bay may comprise a scanner (e.g., of the scanner system 132) configured to detect data encoded on a label provided on the fluid device or cartridge. In some variations, the receiving bay may be coupled to a downstream component of the transfer module via, for example, a conveyor.

[0052] To extract a cell product sample from a fluid device, for example, the transfer module may comprise a disassembly instrument configured to separate a first portion (e.g., a collar) of the fluid device from a second portion (e.g., a container) thereof. In some variations, the disassembly instrument may receive the fluid device from the receiving bay. In some variations, the receiving bay may comprise a proximal portion of the disassembly instrument. The disassembly instrument will now be described in detail below with reference to FIG. 3 and FIGS. 4A-4C.

[0053] FIG. 3 is an illustrative schematic of a disassembly instrument 303. The disassembly instrument 303 may be configured to receive a fluid device 350 at a transfer stage 370 thereof. The transfer stage 370 may be a movable stage that is configured to be translated along one orATTY DOCKET No.: CEES-026 / 01WO 337273-2147more axes, such as bidirectionally translated along both of a horizontal and a vertical axis. One or more position actuator(s) 376 may be configured to move the transfer stage 370 along a given axis, as is described in detail below. In general, the purpose of repositioning the transfer stage 370 may be to position the fluid device 350 thereon proximal to (e.g., within) a actuator 380 of the fluid device disassembly instrument 303 (e.g., prior to disassembly of the fluid device 350), and / or to at least a portion of the fluid device 350 thereon (e.g., a container thereof) distal to the actuator 380 (e.g., after disassembly of the fluid device 350). The actuator 380 may be configured to apply a force, such as a compressive force or a tension force, to the fluid device 350 (e.g., to a collar thereof), to disassemble the fluid device 350, which may include decoupling a collar from a container of the fluid device 350. In some variations, the actuator 308 may be a pneumatic actuator. In some variations, the actuator 380 may include one or more protrusions, such as one or more hooks, configured to releasably engage one or more complementary recesses on the fluid device 350 (e.g., on the collar thereof). The fluid device 350 is shown in dashed lines to indicate that its components may be local or remote to the fluid device disassembly instrument 303, such as to one or both of the transfer stage 370 and the actuator 380.

[0054] The transfer stage 370 may also be configured to detect and secure the fluid device 350 thereto. For example, the transfer stage 370 may include one or more sensors 372 within a base 378 of the transfer stage 370 to detect a presence of the fluid device 350 relative to the transfer stage 370, such as one or more of a proximity sensor, force sensor, torque sensor, optical sensor, motion sensor, temperature sensor, and the like. In some variations, the sensor(s) 372 may include at least one proximity sensor, such as one or two proximity sensors, within the base 378. Additionally, or alternatively, the sensor(s) 372 may include a data reader (e.g., a scanner) configured to scan a barcode or tag (e.g., radiofrequency identification (RFID)) on a received fluid device or cartridge. In some variations, the sensor(s) 372 may be part of the scanner system of the sample preparation and analysis system (e.g., scanner system 132 of FIG. IB).

[0055] Once the fluid device 350 is detected, transfer stage 370 may secure the fluid device 350 thereto via a lock 374, which may comprise one or more lock pins and fasteners. In some variations, the lock 374 may include a plurality of locking pins, such as two locking pins, configured to extend above a top surface of the transfer stage 370 and couple to an exterior bottom surface of the fluid device 350 (e.g., within a plurality of corresponding recesses therein).ATTY DOCKET No.: CEES-026 / 01WO 337273-2147

[0056] In some variations, the analysis systems herein may include a plurality of disassembly instruments, such as 2, 3, 4, 5, 6, 7, 8, 9, 10, or more than 10 disassembly instruments.Additionally, or alternatively, in some variations, the disassembly instruments may include a plurality of actuators, such as 2, 3, 4, 5, 6, 7, 8, 9, 10, or more than 10 actuators per disassembly instrument. In such variations, disassembly instruments may additionally include a same number of transfer stages or may include fewer transfer stages than actuators. For example, in some variations, a disassembly instrument may include a single transfer stage configured to simultaneously couple to a plurality of fluid devices and simultaneously deliver each of the plurality of fluid devices to a corresponding actuator.

[0057] FIGS. 4A-4C are renderings of a disassembly instrument 430 and aspects thereof. FIG.4A is a perspective view of the fluid device disassembly instrument 430 including a portion 450 of a fluid device (e.g., a container thereof), which may be secured to the transfer stage 402. The transfer stage 402 is disposed along first position actuator 404, which may be a horizontal linear actuator configured to translate the transfer stage 402 horizontally (i.e., along the x-axis indicated in FIG. 4A) toward (proximal to) and away from (distal to) the actuator 410. The transfer stage 402 is also coupled to a second position actuator 406, which may be a vertical linear actuator configured to translate the transfer stage 402 vertically (i.e., along the y-axis indicated in FIG. 4A) toward (proximal to) and away from (distal to) the actuator 410. The actuator 410 may include an opening 412 shaped and sized to receive at least a portion of a fluid device (e.g., a collar thereof, or at least a portion of the collar) therein. During disassembly, actuator 410 may be configured to apply a force to the fluid device therein to decouple a first portion (e.g., collar) of the fluid device from a second portion (e.g., container) of the fluid device. In some variations, the force applied by the actuator 410 may be great enough to retain (e.g., at least temporarily, between about 0.1 seconds (s) and about 10 s, such as about 0.5 s and about 5 s, about 1 s and about 2.5 s, or about 1.5 s and about 2 s) the first portion of the fluid device therein after the second portion is released from the first portion. In some variations, the actuator 410 may be actuated to transition from a tense (“disassembly”) configuration, during which force is applied within the opening 412, to a relaxed (“at rest”) configuration. Further, each of the transfer stage 402, first and second position actuators 404, 406, and actuator 410 are integrated to form the disassembly instrument 430 via frame 408. The frame 408 may be fabricated from a rigid or semi-rigid material such as a metal or a plastic. Further, the frame 408 may include an outlet 414 beneath the actuator 410, where the outlet 414 may have one or moreATTY DOCKET No.: CEES-026 / 01WO 337273-2147dimensions (e.g., a length and / or a width) that are greater than one or more corresponding dimensions of a fluid device (or portion thereof, such as a collar). As such, the portion of the fluid device may be released from the actuator 410 and through the outlet 414 to be discarded. In some variations, a waste container (e.g., a biohazard waste container) configured to receive the removed portion of the fluid device may be positioned underneath the outlet 414.

[0058] FIG. 4B is a perspective view of the transfer stage 402. As shown, the transfer stage 402 may include a sensor 420 and locks 422. The sensor 420 may be a proximity sensor configured to detect a local presence of a fluid device. In some variations, the sensor 420 may additionally be configured to detect when the fluid device has been disassembled by the actuator 410. In some variations, the transfer stage 402 may include a plurality of sensors, such as a plurality of proximity sensors, or a combination of proximity sensor(s), force sensor(s), and / or the like. The locks 422 may be locking pins configured to be actuated to extend above an upper surface 424 of the transfer stage 402 and couple to complementary recesses on a container of the fluid transfer device. Further, the transfer stage 402 may include a base 426 and a raised portion 428 extending upward therefrom. The raised portion 428 may have dimensions that are about equal to or less than corresponding dimensions of an exterior bottom surface (e.g., underside) of the container. In some variations, the locks 422 may be configured to apply a tension force to the container by coupling to and pulling against the container, therefore securing the container (and / or the entire fluid device) over the raised portion 428 and onto the base 426.

[0059] FIG. 4C is a perspective view of a portion of a fluid device 450 (e.g., a container thereof) on the transfer stage 402. In some variations, after the fluid device is disassembled, the transfer stage 402, supporting only the portion of the fluid device 450, may be configured to be repositioned (e.g., via one or both of the first a second position actuators 404,406) distally from the actuator 410. The portion of the fluid device 450 may generally include a fluid container 430 that is exposed after the disassembly. In some variations, the fluid container 430 may be configured to hold a volume of fluid of about 0.5 mL to about 50 mL, such as about 1 mL to about 40 mL, about 3 mL to about 30 mL, about 5 mL to about 20 mL, about 7 mL to about 15 mL, or about 9 mL to about 10 mL (including all ranges and subranges therebetween), such as about 10 mL. A fluid transfer device 440 (e.g., a pipettor) of a fluid transfer system may be configured to transfer some or all of the fluid sample within the fluid container 430 to the remainder of the fluid transfer system for sample preparation prior to analysis. In someATTY DOCKET No.: CEES-026 / 01WO 337273-2147variations, the fluid transfer device 440 may be configured to transfer the fluid sample to at least one sample tube downstream.

[0060] A disassembled fluid device may be transferred from the disassembly instrument to the sample preparation module. In some variations, the transfer module may comprise a robot, such as a robotic arm, configured to couple to the portion of the fluid device and move it to the sample preparation module. Such a robot may additionally or alternatively be configured to move the disassembled fluid device collar and / or container (e.g., after a sample has been extracted therefrom) from the transfer module to a waste module of the sample preparation and analysis system. In some variations, such a robot may be moveably mounted on a sidewall of the portion of the workcell housing enclosing the analysis system, such as to the ceiling thereof. FIG. 4D depicts a partial sideview of analysis system 400 comprising disassembly instrument 430 and robot 440, which may be mounted to an interior surface 444 of a workcell housing 446. In some variations, the robot 440 may be translatable and / or rotatably coupled to the interior surface 444. In some variations, the robot 440 may be configured to grip, via end effector 442, one or more microplates, tubes, fluid devices, cartridges and / or fluid containers therein, reagent storage containers, waste containers, pipette tips, and / or the like and transfer these components within the sample preparation and analysis system to facilitate sample preparation, analysis, and maintenance thereof. For example, the robot 440 may be configured to grip, via the end effector 442, a microplate and deliver it to a tool so that a sample thereof may be analyzed by the tool.

[0061] Also shown in FIG. 4D is a position of a sample preparation module 460 relative to the disassembly instrument 430. The sample preparation module may be positioned directly adjacent to the disassembly instrument 430 to optimize the sample preparation and analysis processes carried out by the analysis system 400. In some variations, a disassembled fluid device may be transferred to the sample preparation module 460 via a conveyor.

[0062] Although the above description may focus on receiving and disassembling a fluid device, the transfer modules herein may additionally or alternatively be configured to receive (e.g., from a robot such as robot 116 of FIG. 1 A) a cartridge containing a cell product. For example, a robot within the sample preparation and analysis system (e.g., robot 136 of FIG. IB, robot 440 of FIG. 4D) may be configured to remove, from a cartridge received by the sample preparation and analysis system, a removable reservoir containing the cell product such that a sample may be extract therefrom. Additionally, or alternatively a robot, such as a roboticATTY DOCKET No.: CEES-026 / 01WO 337273-2147pipettor, may be configured to extract the sample directly from the cartridge (e.g., from a reservoir therein) without removing any components.

[0063] Once the sample is extracted from the fluid device or cartridge, the sample may be moved from the transfer module to the sample preparation module, which may receive a sample of the cell product in a sample container, such as a microplate (e.g., an SBS microplate), tube, vial, or the like. The robot(s) 136, which may include a robotic pipettor, may be used to carry the sample from the transfer module to the sample container. Transferring the sample to the sample preparation module may be based on a set of transfer parameters (e.g., a first set of transfer parameters). In some variations, these parameters may be determined by reading data on a fluid device or cartridge label (e.g., a barcode or RFID tag) via a scanner. The data may comprise cell product identification and / or a type of analysis to run on the cell product. In some variations, the transfer parameters may be conveyed to the sample preparation and analysis system via a controller. A set of transfer parameters may comprise one or more of a sample volume, an origin sample location, and a subsequent sample location. Additional transfer parameter considerations may include temperature requirements during transfer, time constraints for sensitive samples, and / or analysis tool preparation.Sample Preparation Module

[0064] The sample preparation module (e.g., sample preparation module 124) may be configured to prepare a sample for analysis. The module may be designed as a modular platform incorporating a plurality of preparation stations arranged in a reconfigurable layout. In some variations, the stations may comprise regions of a precision-leveled deck with integrated utility connections and standardized docking interfaces (e.g., for power and fluid connections).

[0065] In some variations, the sample preparation module may be configured to prepare a plurality of samples in parallel. Preparing a cell product sample (e.g., an assay thereof) may comprise one or more steps including separating the sample, transferring a blocking solution into the sample, transferring a reagent into the sample, mixing the sample with the reagent, incubating the sample, and / or washing the sample with a buffer. In some variations, one or more preparation steps may be precisely controlled through one or more of automated liquid handling systems with liquid level sensing, real-time pressure and flow monitoring, and integrated sample tracking via RFID or barcode systems (e.g., using the scanner system 132).ATTY DOCKET No.: CEES-026 / 01WO 337273-2147

[0066] Generally, the sample preparation module may be configured to automatically prepare a sample for analysis according to instructions received from a controller. The instructions may comprise a set of preparation parameters, such as one or more of a sample temperature, sample container temperature, a sample container type (e.g., microplate or tube), a type of reagent, a mixing technique, a mixing duration, a centrifugation duration, a centrifugation speed, an incubation temperature, an incubation duration, a type of blocking solution, and a type of buffer. The set of sample parameters may be tailored for each cell product in view of the type of cell product and the type(s) of analysis its sample will undergo.

[0067] The sample preparation module may comprise one or more preparation stations including one or more of a pipetting station, a mixing station, and / or a thermal control station. In some variations, the preparation stations may be arranged in a linear or circular configuration within the analysis system to optimize process flow and minimize transfer distances. In some variations, the preparation stations may be arranged on a bench that is positioned between the transfer module and the analysis module.

[0068] In some variations, one or more robotic pipettors may be positioned adjacent to a corresponding pipetting station of the sample preparation module. A robotic pipettor may feature one or more of adjustable speed control for sensitive samples, a plurality of dispensing modes (e.g., single, multi-dispense, sequential), and automated tip management and disposal (e.g., within the waste storage module). The robotic pipetter may be coupled to a sidewall, such as a ceiling, of the workcell housing surrounding the analysis system. In some variations, the robotic pipettor may be configured to move (e.g., via a track coupled thereto) to and from any combination of the transfer module, the sample preparation module, the reagent storage module, the waste module, and the analysis module.

[0069] In some variations, the sample preparation module may comprise a plurality of at least one type of station. For example, the sample preparation module may comprise two or more pipetting stations, such as one or at least one first pipetting station configured to add reagents to a sample, and at least one second pipetting station configured to subsequently wash the sample with buffer. In some variations, each of a plurality of pipetting stations may comprise a corresponding robotic pipettor. Alternatively, a single robotic pipettor may be configured (e.g., via a track coupled thereto) to move between each of the plurality of pipetting stations.

[0070] A pipetting station may further include a plurality of sample containers and / or racks (e.g., for microplates, tubes, etc.), one or more pipette tip racks, tip disposal access (e.g., aATTY DOCKET No.: CEES-026 / 01WO 337273-2147compartment from the waste storage module positioned proximal to the pipetting station deck). In some variations, the sample containers may be organized on the bench using position verification sensors integrated therein. Further, the pipette tip racks may comprise a plurality of tip types, such as wide bore tips for sensitive cell product samples and / or narrow bore tips for small volumes.

[0071] The mixing station may include one or more sample separators and / or one or more sample mixers. The sample separator(s) and / or mixer(s) may be configured with programmable mixing sequences and / or adjustable speed control. In some variations, a sample separator may comprise a centrifuge, and a sample mixer may comprise an orbital shaker. In some variations, the centrifuge may include a plurality of rotor options for various tube sizes. In some variations, the mixing station may additionally or alternatively include one or more of’ a vertexing station and a magnetic stirrer.

[0072] Moreover, the thermal control station may comprise one or more incubators, coolers (e.g., refrigerators, freezers), and / or thermal plates. The thermal control station may be utilized to adjust or maintain a temperature of the sample and / or of the sample container. For example, a first thermal control station may comprise a cooling thermal plate, a second thermal control station may comprise a warming thermal plate, and a third thermal station may comprise an incubator. In some variations, a single thermal station may comprise a plate configured for both warming and cooling. Any number and type thermal plates may be arranged within the sample preparation module.

[0073] Further, the sample preparation module may comprise a plurality of intermediate fluid containers configured to be used for one or more of mixing, incubation, blocking, and washing a sample being prepared for analysis. The intermediate containers may be transferred to the waste module after use.

[0074] In general, a prepared sample may be transferred from the sample preparation module to the analysis module, which may be positioned along or adjacent to a distal end of the bench of the sample preparation module. In some variations, an interface between these modules may incorporate one or more of: a sealed pass-through chamber, a plurality of routes for parallel processing, and / or a decontamination mechanism (e.g., one or more UV lights).

[0075] Transferring the prepared sample to the analysis module may be based on a set of transfer parameters (e.g., a second set of transfer parameters). The set of transfer parameters may comprise one or more of a sample volume, an origin sample location, and a subsequent sampleATTY DOCKET No.: CEES-026 / 01WO 337273-2147location. The origin location may be, for example, a pipetting station (e.g., configured for sample washing with buffer), and the subsequent location may comprise one or more tools of the analysis module. In some variations, the transfer parameters may be based on real-time scheduling procedures and / or real-time parameter adjustments. Additional transfer parameter considerations may include temperature requirements during transfer, time constraints for sensitive samples, and / or analysis tool preparation.Analysis Module

[0076] The analysis module (e.g., analysis module 126) may comprise one or more analysis tools configured to receive a prepared cell product sample (e.g., in a microplate, tube, as a direct fluid, etc.) and analyze the sample to determine cell product sample parameters. In some variations, a robot (e.g., a robotic arm) may transfer the sample from the sample preparation module to the analysis module. In some variations, the analysis module may comprise a modular, configurable design capable of exchanging at least one first analysis tool for at least one second (same or different) analysis tools. This design may thus support continuous system enhancements and ensure that the analysis system is compatible with evolving and more advanced analytical tools.

[0077] Generally, the analysis module may be configured to automatically analyze a sample according to instructions received from a controller. The controller may be configured to make real-time workflow adjustments in view of the analysis. Such sample parameters determined by the analysis may include one or more of cell viability, cell count, cell concentration, cell recovery, cell diameter, cell size distribution, glucose, lactate, pH, phenotypic markers, chimeric antigen receptor expression, transgenic T cell receptor expression, cell identity markers, cell purity, vector copy number, or a combination thereof.

[0078] The analysis tools of the analysis module may comprise one or more of a flow cytometer, a flow-based bead reader, a polymerase chain reaction (PCR) system, a cell analyzer, a microplate reader, a cell counter, and a cell imager. In some variations, the analysis module may comprise a plurality of areas or stations (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 10 to 15, 15 to 20, or more than 20) each configured to support one or more tools. The plurality of stations may be stacked in one or more rows and / or one or more columns. In some variations, all of the one or more analysis tools may be physically grouped together within the analysis system.ATTY DOCKET No.: CEES-026 / 01WO 337273-2147Alternatively, one or more of a plurality of analysis tools may be positioned at different locations within the analysis system. In some variations, analysis module may comprise at least one bench (e.g., a same or different bench as that of the transfer module) configured to support the one or more analysis tools. In some variations, the analysis module may comprise locks and / or precision-leveled platforms for securing a tool thereon. Each of the one or more tools may be communicably coupled to a system controller and may automatically transmit data comprising the sample parameter(s) of interest to the controller (e.g., controller 160).

[0079] Flow cytometry may enable the measurement of a plurality of cellular characteristics including viability, phenotypic markers, chimeric antigen receptor expression, transgenic T cell receptor expression, cell identity markers, and purity. Cell counting instruments, such as Coulter counters and automated cell analyzers, may be used to determine cell concentration, viability, diameter, and size distribution within the cell product sample. In some variations, a cell counter may be utilized to initially normalize a concentration of a cell product sample prior to the sample being prepared for analysis by the sample preparation station. In general, the analysis module may comprise at least one flow cytometer and at least one cell counter.

[0080] For metabolic parameters, cell analyzers may be used to measure glucose and lactate concentrations along with pH levels in the cell product. When genetic modifications need to be assessed, digital PCR or quantitative PCR techniques may be used to determine vector copy numbers and can validate receptor expression at the genetic level. Determining the vector copy number may enable the system to confirm that important or critical parameters meet the predetermined criteria (e.g., thresholds and / or acceptable ranges), or distributions within the automated cell therapy manufacturing process.

[0081] Moreover, automated plate readers may offer additional capabilities for measuring cell viability through specific assays, as well as pH and various metabolite concentrations. Further, cell imaging systems may provide complementary analysis of cell morphology, size characteristics, and viability (in conjunction with corresponding staining procedures).

[0082] One or more of the sample parameters may be evaluated using one or more (e.g., a plurality of) analysis tools of the analysis module. In some variations, complementary techniques may be employed using two or more tools to ensure accurate characterization of cell product samples. For instance, cell viability analyses may combine data from both an automated cell counters and a flow cytometer. This multi-modal analytical approach may help to ensure thorough analysis of cell products throughout processing.ATTY DOCKET No.: CEES-026 / 01WO 337273-2147

[0083] In some variations, the analysis module may be used prior to or during sample preparation to normalize sample parameters. That is, the sample may be transferred from the sample preparation module (following a first subset of completed sample preparation steps) to the analysis module, and back to the sample preparation module (to complete a second subset of sample preparation steps). For example, the sample may be transferred to a cell counter to normalize cell concentration / cell count with sample dilution. In particular, an automated cell counter (e.g., Countess, Vi-CELL, or the like) may be used to determine both cell count for the sample and to assess what percentage of those cells are viable. This data may then be used to normalize the sample to the correct cell concentration during the remainder of the preparation workflow. In some variations, one or more sample parameters may be normalized one or more times throughout sample preparation and analysis, such as at least two times (e.g., during sample preparation and after a subsequent sample analysis).Reagent Storage Module

[0084] The reagent storage module (e.g., reagent storage module 128) may be configured to store commonly used reagents and buffers for cell product analysis. This module may interact with a robot (e.g., robotic pipetter and / or robotic arm) so that reagents and buffers may be transferred from storage to sample preparation containers at the sample preparation module. In some variations, the reagent storage module may be a discrete module of the sample preparation and analysis system in that it does share components with the reagent vault (e.g., reagent vault 118 of FIG. 1 A). In general, the reagent storage module may comprise a storage volume that is smaller than a storage volume of the reagent vault. Additionally, in some variations, the reagent storage module may store reagents, buffers, and the like in tubes or vials instead of fluid devices, like the reagent vault.

[0085] In some variations, the reagent storage module may comprise at least one storage unit (e.g., cabinet) comprising one or more (e.g., a plurality of) storage compartments. Each storage compartment may be configured to store one or more tubes, vials, containers, or the like comprising a fluid (e.g., reagent or buffer) for use in cell product sample preparation. In some variations, storage unit may comprise door or cover that may automatically expose the storage compartments (e.g., upon detection of a proximal robot and / or scanner), and / or may movable byATTY DOCKET No.: CEES-026 / 01WO 337273-2147a robot so that the storage compartments may be accessed from within the sample preparation and analysis system.

[0086] In some variations, the storage unit may be positioned adjacent to an access point (e.g., access point 134), such as a door or other covered opening that enables operator access to the storage compartments. Accordingly, reagents and buffers stored therein may be replenished. Tracking use of these fluids using one or more scanners (e.g., of the scanner system 132) may inform which fluids need to be replenished. Each reagent or buffer stored within the reagent storage module may comprise a readable label or barcode on an external surface of its tube to enable tracking of the fluids (e.g., via the scanner system 132).

[0087] In some variations, one or more environmental parameters of one or more of the storage compartments may be controlled by a controller (e.g., controller 160). The environmental parameters may include, for example, temperature, humidity, light, and / or the like. Such parameters may be monitored by sensors within the storage compartment. In some embodiments, the temperature may be controlled within a range of between about 4 degrees C and about 8 degrees C, about 3 degrees C and about 5 degrees C, about 2 degrees C and about 6 degrees C, about 0 degrees C and about 10 degrees C, about 0 degrees C and about 12 degrees C, about 0 degrees C and about 14 degrees C, about 0 degrees C and about 16 degrees C, about -2 degrees C and about 10 degrees C, about -2 degrees C and about 8 degrees C, about -4 degrees C and about 10 degrees C, about -4 degrees C and about 8 degrees C, or about -4 degrees C and about 14 degrees C. In some variations, a storage compartment may be configured to maintain a temperature of about 4 degrees C. In some variations, a storage compartment may be configured to maintain a temperature of about 15 degrees C to about 25 degrees C.

[0088] The storage compartments may comprise drawers, cabinets, vaults, carousels, and / or the like. A storage compartment may have a storage capacity of about 5 L to about 250 L, such as about 10 L to about 200 L, about 15 L to about 150 L, about 20 L to about 100 L, about 25 L to about 75 L, or about 30 L to about 50 L, including all ranges and subranges therebetween (e.g., about 20 L, about 50 L, about 100 L, or about 200 L). In some variations, storage compartments of varying capacities may be utilized within the storage unit.ATTY DOCKET No.: CEES-026 / 01WO 337273-2147Waste Storage Module

[0089] The waste storage module (e.g., waste storage module 130) may comprise a waste unit comprising one or more compartments for storing wastes accumulated during sample preparation and analysis. In general, waste comprising one or any combination of used labware like pipette tips and intermediate containers, extra reagent / buffer, disassembled fluid device caps, used tubes and / or microplates, and sample waste may be transferred from one or more of the reagent storage module, the sample preparation module, the transfer module, and the analysis module any suitable number of times during preparation and analysis in order to maintain a clean and orderly environment within the analysis system. Waste may be transferred to the waste storage module via a robot, such as a robotic arm, and / or via channels integrated into the system, such as a tip disposal for a robotic pipettor that is built into the bench of the sample preparation module.

[0090] In some variations, the waste storage module may be configured to separate wastes, such as separate liquid waste from solid waste and / or aqueous waste from organic waste. For example, at least one first compartment of the waste storage module may be configured to store a first type of waste and at least one second fluid compartment configured to store a second, different type of waste. The first and second compartments may be a same or different size. In some variations, a combined total capacity of each of one or more compartments of the waste storage module may be about 1 L to about 500 L, such as about 5 L to about 250 L, about 10 L to about 100 L, about 15 L to about 75 L, or about 25 L to about 50 L, including all ranges and subranges therebetween. A total capacity of the waste storage module may be about 1 L to about 5 L, such as about 1.25 L to about 3 L, about 1.5 L to about 2.75 L, about 1,75 L to about 2.5 L, or about 2 L to about 2.25 L.

[0091] Compartments of the waste storage module may comprise self-sealing lids to prevent spillage and contamination. In some variations, waste compartments may be positioned for easy removal through operator-accessible access points. An access point may comprise a door or other covered opening that enables operator access to the storage compartments. Accordingly, an operator may obtain access to the waste storage module to remove the waste and / or to remove the compartments for cleaning. In some variations, waste compartments may not be contained within a single waste unit, and may instead be spread throughout the analysis system to provide accessible disposal access for one or more of the other modules.ATTY DOCKET No.: CEES-026 / 01WO 337273-2147

[0092] In some variations, the waste storage module may comprise sensors configured to detect a waste level (e.g., a liquid level) within the compartments thereof. The sensors may comprise, for example, one or more bubble sensors and / or one or more cameras. The sensors may be configured to transmit data detected to a system controller (e.g., controller 160), which may be configured to determine whether a current waste level of a given compartment is about equal to or greater than a predetermined threshold waste level. If the current waste level is determined to be about equal to or greater than the threshold level, the controller may generate a notification (e.g., via display 169 of FIG. 1C) instructing an operator to remove the waste, thus preventing waste overflow within the analysis system and workcell. Additionally, or alternatively, in some variations, the waste storage system may be configured to automatically transfer (e.g., pump, via fluidic pathways) accumulated waste to a collection site that is external to the workcell.

[0093] An exemplary configuration of a sample preparation and analysis system 520 is provided in FIG. 5.Cartridge

[0094] In general, the cartridges herein may comprise one or more modules configured to interface with an instrument, and / or with the sample preparation and analysis system. A robot (e.g., robotic arm) may be configured to move a cartridge and / or instrument to perform one or more cell processing steps. For example, a cartridge may comprise a bioreactor module and / or fluid connector (e.g., sterile liquid transfer port) coupled by the robot to a bioreactor instrument of a workcell. Once a predetermined processing step has been completed, the cartridge may be moved by the robot to another instrument of the workcell, or to the sample preparation and analysis system, and another cartridge may be coupled to the bioreactor instrument. The portable cartridge and shareable instruments and systems may increase the efficiency, throughput, and flexibility of a cell manufacturing process. In some variations, the cartridges herein may comprise a barcode or other data encoded label configured to be detected (e.g., scanned by the scanner 132 of the sample preparation and analysis system 120) so that a cell product and its samples may be tracked throughout processing and analysis.

[0095] In some variations, the cartridge may provide a self-contained device capable of performing one or more cell processing steps. The modules may be integrated into a fixedATTY DOCKET No.: CEES-026 / 01WO 337273-2147configuration within the cartridge. Alternatively, the modules may be configurable or moveable within the cartridge, permitting various cartridges to be assembled from shared modules.Similarly stated, the cartridge may be a single, closed unit with fixed components for each module, or the cartridge may contain configurable modules coupled by configurable fluidic, mechanical, optical, and electrical connections. The modules may each be provided in a distinct housing or may be integrated into a singular cartridge housing with other modules. The disclosure may generally show the cartridge modules as distinct groups of components for the sake of simplicity, but may be arranged in any suitable configuration. For example, the components for different modules may be interspersed with each other such that each module is defined by the set of connected components that collectively perform a predetermined function. However, the components of each module may or may not be physically grouped within the cartridge. In some variations, multiple cartridges may be used to process a single cell product through transfer of the cell product from one cartridge to another cartridge of the same or different type and / or by splitting cell product into more cartridges and / or pooling multiple cell products into fewer cartridges.

[0096] Generally, each of the instruments of the workcell may interface with its respective module or modules on the cartridge. As described above, a bioprocessing instrument of the workcell may be configured to perform one or more processing steps of a workflow for a cell product. The cell product may be carried by a cartridge comprising modules configured for the same processing steps (e.g., each configured for one or more of enrichment, selection, activation, electroporation, transduction, expansion, and / or formulation of the cell product). As an example, an electroporation module on the cartridge (if present) may be moved by the system (e.g., by the robot) to an electroporation instrument and may interface with the electroporation instrument to perform an electroporation step on the cell product — and may also interface with common components, such as components of a fluidic bus (e.g., pumps, valves, sensors, etc.). An advantage of such split module / instrument designs is that expensive components (e.g., motors, sensors, heaters, lasers, etc.) may be retained in the instruments of the system while multiple cartridges are processed. The use of disposable cartridges may eliminate the need, in such variations, to sterilize cartridges between use. Furthermore, the utilization of shared instruments may be increased since a plurality of the instruments may be utilized simultaneously in parallel by a plurality of cell manufacturing processes.ATTY DOCKET No.: CEES-026 / 01WO 337273-2147

[0097] In some variations, the cartridges herein may include one or more fluid compartments configured to contain a cell product during transfer from an instrument to the analysis system (e.g., via a robot). Such fluid compartments may be removable to facilitate sample extraction therefrom. In some variations, the fluid compartments may be disposed of (e.g., in the waste storage module of the analysis system) and replaced once a sample has been collected therefrom.

[0098] FIG. 6 is a schematic illustration of a cartridge 600, which may be produced from materials at a cost that make recycling or limited use practical. The cartridge 600 may comprise a fluidic bus 624 fluidically coupled (e.g., via tubing) to a first bioreactor module 614a, a second, larger bioreactor module 614b, a cell selection module 616, a cell sorting module 618, an electroporation module 620, and a counterflow centrifugation elutriation (CCE) module 622. In some variations, the cell selection module 616 may be a magnetic-activated cell selection (MACS) module. The cell sorting module 618 may comprise a fluorescence activated cell sorting (FACS) module.

[0099] The cartridge 600 may comprise a housing 602 that renders the cartridge self-contained, and in some variations may protect the contents (e.g., cell product therein) from contamination. In some variations, the housing 602 may have external dimensions of about 225 mm x about 280 mm * 385 mm, about 225 mm * about 295 mm * 385 mm, and about 450 mm x about 300 mm x about 250 mm, including all values and sub-ranges in-between. In some variations, the cartridge 600 may be about 10%, about 20%, about 30% or more smaller in volume, including all ranges and sub-values in-between. In some variations,the cartridge 600 may be about 10%, about 20%, about 30%, about 50%, about 100%, about 200%, or more in volume, including all ranges and sub-values in-between.

[0100] Sterile liquid transfer ports (SLTPs) 606a - 606k may be fluidically coupled to reservoirs 607a - 607k, and each independently be a flexible bag or a rigid container. In some variations, flexible bags may be configured to hold large volumes and to permit transfer of fluid without replacing transferred fluid with liquid or gas to maintain the pressure in the reservoir, as the bag may collapse when fluid is transferred out and expand when fluid is transferred in. The SLTPs 606a - 606k may be configured to couple to corresponding SLTPs of a fluid device (not shown) so that fluid may be transferred between the cartridge 600 and the fluid device. In general, fluid transfer steps during processing may be facilitated by a fluid transfer instrument, as described above.ATTY DOCKET No.: CEES-026 / 01WO 337273-2147Fluid Device

[0101] The fluid devices herein may be configured to store fluids (e.g., within a reagent vault) and transfer fluid to and from cartridges and the analysis system (e.g., to the sample preparation module). In general, a fluid device may comprise a first portion (e.g., a cap) couplable to a second portion (e.g., a container). In some variations, the fluid devices herein may comprise a barcode or other data encoded label configured to be detected (e.g., scanned by the scanner 132 of the analysis system 120) so that a cell product and its samples may be tracked throughout processing and analysis.

[0102] Illustrative renderings of a fluid device 700 are depicted in FIGS. 7A and 7B. The fluid device 700 may include a container 710 and a collar 720. The container 710 may include an opening 712 and at least one collar coupling feature 703. For example, the coupling feature 703 may facilitate a snap and / or press fit between the collar 720 and the container 710. The collar 720 may include a liquid transfer port 724 (e.g., a sterile liquid transfer port) configured to couple to complementary liquid transfer ports within the cell processing systems herein.Additionally, the collar 720 may include one or more engagement features 728, which may facilitate engagement with other components of the QC systems herein, such as the robot and / or the fluid device disassembly instrument (e.g., fluid device disassembly instrument 303 of FIG.3). Further, the collar 720 may include at least one container coupling feature 702 couplable to a corresponding one of the at least one collar coupling feature 703 of the container 710.

[0103] In some embodiments, as introduced above, the container coupling feature 702 is releasably couplable to the collar coupling feature 703 of the container 710. The container coupling feature 702 and the collar coupling feature 703 may be universally designed such that containers are interchangeably couplable to the collar 720. In this way, a collar 720 may be used with any size and shape container 710. In some variations, a range of containers capable of holding a range of fluid volumes may be used. For example, the container 710 may be capable of holding about 1 mL to about 1 L, or at least about 1 mL, at least about 2 mL, at least about 3 mL, at least about 4 mL, at least about 5 mL, at least about 10 mL, at least about 15 mL, at least about 20 mL, at least about 25 mL, at least about 50 mL, at least about 100 mL, at least about 200 mL, at least about 250 mL, at least about 500 mL, at least about 750 mL, or up to about 2.5 mL, up to about 5 mL, up to about 7.5 mL, up to about 10 mL, up to about 12.5 mL, up to about 15 mL, up to about 17.5 mL, and / or up to about 20 mL (including all ranges and subrangesATTY DOCKET No.: CEES-026 / 01WO 337273-2147therebetween). In one example, the container 710 may be configured to hold a volume of about 10 mL. In some variations, the opening 712 of the container 710 may be couplable to a fluid transport feature (not shown) of the collar 720. To this end, the opening 712 and the fluid transport feature may be couplable by a threaded interface, a compression fit, a press fit, a friction fit, a luer fit, or couplable by another suitable coupling method that permits fluid transfer between the container 710 and the collar 720 without fluid leaks and / or contamination.

[0104] In some embodiments, the one or more engagement features 728 of the collar 720 may be engageable by a robot of a QC system to move and otherwise manipulate the fluid device 700 within the workcell. This may allow for automated pick and place of the fluid device 700 within the QC system. Further, the different storage orientations with a reagent vault of the QC system may be achieved using the one or more engagement features 728. For instance, the one or more engagement features 728 of the collar 720 may be configured to allow for hanging the fluid device 700 in e.g., an inverted orientation with the reagent vault. In some variations, the one or more engagement features 728 may be at least one depression and / or protrusion within or on a surface of the collar 720.

[0105] Similarly, in some variations, the container 710 may include one or more engagement features configured or configurable to permit an orientation on an operational instrument of the QC system, such as on a fluid device disassembly instrument. In one example, an exterior bottom surface 704 (e.g., underside) of the container 710 may include one or more engagement mechanisms configured to releasably engage with a transfer stage of a fluid device disassembly instrument. As will be described in detail herein, the transfer stage may be a mobile stage configured to position fluid device 700, when coupled thereto, adjacent a disassembly actuator during disassembly of the fluid device within the QC systems herein. To couple the fluid device 700 to the transfer stage, the exterior bottom surface 704 thereof may include one or more recesses (e.g., a plurality thereof) configured to receive one or more complementary projections (e.g., locking pins) from the transfer stage.Controller

[0106] The cell processing systems herein may include one or more controllers for monitoring and controlling a cell processing workflow. In some variations, the controllers herein may be integrated with LIMS systems and may be configured for electronic batch record generation. InATTY DOCKET No.: CEES-026 / 01WO 337273-2147general, or more components of a workcell, such as at least a portion of each of the modules of the analysis system, may include or be operably coupled to a controller. As such, the controllers herein may be configured to control analysis and subsequent workflows for one or more cell products being processed. For example, the controllers may be configured to determine whether a workflow for a given cell product should be modified by comparing one or more sample parameters (determined through analysis at the analysis system) to a corresponding criterion (e.g., a threshold or acceptable range of values) and determine that workflow adjustments are needed when at least one of the one or more sample parameters does not meet the criterion (e.g., is above or below the threshold, or out of the acceptable range of values). The controller may then automatically update the workflow for the cell product, and subsequently have another sample of the product analyzed to verify that the criteria for the one or more sample parameters are satisfied.

[0107] Referring to FIG. 1C, a controller 160 (e.g., computing device) of the system 100 may include one or more of a processor 161, memory 163, communication device 165, input device 167, and display 169. The processor 161 may be configured to receive, process, compile, compute, store, access, read, write, and / or transmit data and / or other signals to control one or more components of the system.

[0108] In some variations, the processor 161 may be configured to access or receive data and / or other signals from one or more of workcell 110, server, controller 160, and a storage medium (e.g., memory, flash drive, memory card, database). In some variations, the processor may be any suitable processing device configured to run and / or execute a set of instructions or code and may include one or more data processors, image processors, graphics processing units (GPU), physics processing units, digital signal processors (DSP), analog signal processors, mixed-signal processors, machine learning processors, deep learning processors, finite state machines (FSM), compression processors (e.g., data compression to reduce data rate and / or memory requirements), encryption processors (e.g., for secure wireless data transfer), and / or central processing units (CPU). The processor may be, for example, a general -purpose processor, Field Programmable Gate Array (FPGA), an Application Specific Integrated Circuit (ASIC), a processor board, and / or the like. The processor 161 may be configured to run and / or execute application processes and / or other modules, processes and / or functions associated with the system. The underlying device technologies may be provided in a variety of component types (e.g., metal-oxide semiconductor field-effect transistor (MOSFET) technologies likeATTY DOCKET No.: CEES-026 / 01WO 337273-2147complementary metal-oxide semiconductor (CMOS), bipolar technologies like emitter-coupled logic (ECL), polymer technologies (e.g., silicon-conjugated polymer and metal-conjugated polymer-metal structures), mixed analog and digital, and the like.

[0109] The processor 161 may operate the systems / perform the methods herein using software (executed on hardware), hardware, or a combination thereof. Hardware modules may include, for example, a general-purpose processor (or microprocessor or microcontroller), a field programmable gate array (FPGA), and / or an application specific integrated circuit (ASIC). Software modules (executed on hardware) may be expressed in a variety of software languages (e.g., computer code), including structured text, typescript, C, C++, C#, Java®, Python, Ruby, Visual Basic®, and / or other object-oriented, procedural, or other programming language and development tools. Examples of computer code include, but are not limited to, micro-code or micro-instructions, machine instructions, such as produced by a compiler, code used to produce a web service, and files containing higher-level instructions that are executed by a computer using an interpreter. Additional examples of computer code include, but are not limited to, control signals, encrypted code, and compressed code.

[0110] The memory 163 may be configured to store data and / or information. In some variations, the memory 163 may include one or more of a random-access memory (RAM), static RAM (SRAM), dynamic RAM (DRAM), a memory buffer, an erasable programmable read-only memory (EPROM), an electrically erasable read-only memory (EEPROM), a read-only memory (ROM), flash memory, volatile memory, non-volatile memory, combinations thereof, and the like. In some variations, the memory 163 may store instructions to cause the processor to execute modules, processes, and / or functions associated with the device, such as image processing, image display, sensor data, data and / or signal transmission, data and / or signal reception, and / or communication. Some embodiments described herein may relate to a computer storage product with a non-transitory computer-readable medium (also may be referred to as a non-transitory processor-readable medium) having instructions or computer code thereon for performing various computer-implemented operations. The computer-readable medium (or processor-readable medium) is non-transitory in the sense that it does not include transitory propagating signals per se (e.g., a propagating electromagnetic wave carrying information on a transmission medium such as space or a cable). The computer code (also may be referred to as code or algorithm) may be those designed and constructed for the specific purpose or purposes. In some variations, the memory may be configured to store any received data and / or dataATTY DOCKET No.: CEES-026 / 01WO 337273-2147generated by the controller and / or workcell. In some variations, the memory 163 may be configured to store data temporarily or permanently.[OHl] An input device 167 of the controller may comprise or be coupled to the display 169. The input device 167 may be any suitable device that is capable of receiving input from an operator via, for example, a keyboard, buttons, touch screen, and / or the like. The input device 167 may include at least one switch configured to generate a user input. For example, the input device 167 may include a touch surface for a user to provide input (e.g., finger contact to the touch surface) corresponding to a user input. The input device 167 may include a touch surface configured to detect contact and movement on the touch surface using any of a plurality of touch sensitivity technologies including capacitive, resistive, infrared, optical imaging, dispersive signal, acoustic pulse recognition, and surface acoustic wave technologies. In embodiments of an input device including at least one switch, a switch may have, for example, at least one of a button (e.g., hard key, soft key), touch surface, keyboard, analog stick (e.g., joystick), directional pad, mouse, trackball, jog dial, step switch, rocker switch, pointer device (e.g., stylus), motion sensor, image sensor, and microphone. A motion sensor may receive user movement data from an optical sensor and classify a user gesture as a user input. A microphone may receive audio data and recognize a user voice as a user input.

[0112] Graphical and / or image data may be output on the display 169. In some variations, the display 169 may include at least one of a light emitting diode (LED), liquid crystal display (LCD), electroluminescent display (ELD), plasma display panel (PDP), thin film transistor (TFT), organic light emitting diodes (OLED), electronic paper / e-ink display, laser display, and / or holographic display. In some variations, a GUI may be configured for designing a process and monitoring a product and may be shown on the display 169.

[0113] Further, in some variations, the controller may include the communication device 165, which may be configured to communicate with another controller and one or more databases. The communication device 165 may be configured to connect the controller to another system (e.g., Internet, remote server, database, workcell) by wired or wireless connection. In some variations, the communication device 165 may include a radiofrequency receiver, transmitter, and / or optical (e.g., infrared) receiver and transmitter configured to communicate with one or more devices and / or networks.ATTY DOCKET No.: CEES-026 / 01WO 337273-2147Data Management

[0114] The controllers herein may further include a data management infrastructure configured to centralize, store, and process data generated throughout the cell processing workflow. This infrastructure may enable seamless and integration of analysis (e.g., sample assay) results obtained from the analysis system, as well as reagent lot information, analysis tool (e.g., flow cytometry) configuration specifications, and sample parameter result acceptance criteria. By centralizing this data within a unified environment, the controller may support automated and efficient data analysis, reporting, and decision-making processes. Such centralization may simplify data tracking and reduce operational complexity, as well as provide data integrity and traceability that facilitate regulatory standards.

[0115] In addition to data integration, the data management infrastructure may also provide enhanced batch-to-batch process analysis. For example, the controller may facilitate rapid decision-making using real-time data from automated fluid transfer and analysis tools. Indeed, faster decision-making may reduce variability and the risk of batch failures by providing workflow stability and process consistency.II. Methods

[0116] Described herein are also methods for cell product sample preparation and analysis, such as methods for preparing and analyzing a cell product sample during automated cel processing. The methods may be for use with or executed by the systems and devices described herein, such as with or by the system 100 of FIGS. 1A-1C, and variations thereof. While the methods herein may be described as having particular steps with a particular order, it should be understood that, in some variations: every step of the method may not be performed (e.g., one or more steps may be optional), and / or the steps of the method may be performed in a different order, and / or two or more steps of the method may be performed simultaneously (or overlap), and / or one or more additional steps may be performed.

[0117] FIG. 8 is a flowchart of an illustrative variation of a method 800 for preparing and analyzing a cell product sample during automated cell processing. The method 800 may be an automated process controlled by a system controller. First, step 802 may include moving a fluid device from a processing instrument of a workcell to an analysis system of the workcell. The processing instrument and analysis system may both be fully integrated within the workcell. AATTY DOCKET No.: CEES-026 / 01WO 337273-2147robot may be used to move the fluid device from the processing instrument to the analysis system. The processing instrument may comprise a fluid transfer instrument configured to facilitate coupling of and fluid transfer between a cartridge and the fluid device. In some variations, the robot may additionally or alternatively move the cartridge (e.g., from a processing or fluid transfer instrument, or from a feedthrough of the workcell) to the analysis instrument. In some variations, the step 802 may comprise moving the fluid device from a receiving bay of the instrument to a receiving bay of the sample preparation and analysis system.

[0118] Next, step 804 may include transferring a sample of a cell product carried by the fluid device to a first module of the sample preparation and analysis system. In some variations, prior to step 804, the fluid device may be disassembled by a disassembly instrument of a transfer module of the sample preparation and analysis system. Transferring the sample from the fluid device may comprise extracting an amount of the cell product therein from a portion thereof (e.g., a disassembled container portion) and moving the cell product to a sample container. This extracting and moving may be accomplished using a robot (e.g., a robotic pipettor). Here, the first module of the sample preparation and analysis system may comprise a sample preparation module. In some variations, the sample preparation module may prepare the sample according to a set of preparation parameters comprising one or more of a sample temperature, sample container temperature, a sample container type (e.g., microplate or tube), a type of reagent, a mixing technique, a mixing duration, a centrifugation duration, a centrifugation speed, an incubation temperature, an incubation duration, a type of blocking solution, and a type of buffer.

[0119] Step 806 may include transferring the sample from the first module to a second module of the sample preparation and analysis system. At step 806, the sample may be a prepared sample that has previously undergone one or more preparation steps via the sample preparation module. These steps may include one or more of: separating the sample, transferring a blocking solution into the sample, transferring a reagent into the sample, mixing the sample with the reagent, incubating the sample, and washing the sample with a buffer. Here, the second module may comprise an analysis module. In some variations, transferring the sample from the first to the second module may comprise using a robot (e.g., an end effector thereof that is configured to grip an object) to move the sample to a tool of the analysis module. Additionally, or alternatively, in some variations, transferring the sample from the first to the second module may comprise flowing the sample through tubing fluidically coupling the first and second modules.ATTY DOCKET No.: CEES-026 / 01WO 337273-2147

[0120] One or both of transferring steps 804 and 806 may be controlled according to one or more transfer parameters. The transfer parameters may comprise one or more of a sample volume, an origin sample location, and a subsequent sample location. Additional transfer parameter considerations may include temperature requirements during transfer, time constraints for sensitive samples, and / or analysis tool preparation. The transfer parameters may be determined by reading data on a fluid device, cartridge, or sample container. The data may comprise cell product identification and / or a type of analysis to run on the cell product.

[0121] Next, step 808 may include determining a sample parameter (e.g., a value thereof) of the cell product sample. This step may be executed using an analysis tool of the analysis module to analyze the sample, including using a flow cytometer, a flow-based bead reader, a PCR system, a cell analyzer, a microplate reader, or a cell counter. Accordingly, step 808 may comprise analyzing the sample using the analysis module, or at least a portion thereof (e.g., using at least one tool thereof). The sample parameter may comprise a value of cell viability, cell count, cell concentration, cell recovery, cell diameter, cell size distribution, glucose, lactate, pH, phenotypic markers, chimeric antigen receptor expression, transgenic T cell receptor expression, cell identity markers, cell purity, vector copy number, or a combination thereof. In some variations, step 808 may be repeated to comprise determining a plurality of different sample parameters, and / or determining each of one or more sample parameters a plurality of times. In some variations, a plurality of tools of a same or different type may be used to determine a plurality of different sample parameters. In some variations, a plurality of tools of a same or different type may be used to determine a same sample parameter a plurality of times.

[0122] Finally, step 810 may include determining whether to modify a processing workflow for a cell product based on its sample parameter. The determination may comprise comparing the sample parameter to a criterion for the parameter. The system controller may be configured to execute the comparison analysis. In some variations, the criterion may comprise a threshold value (e.g., floor or ceiling value) or range of acceptable values for the parameter. When the sample parameter does not meet the criterion, the method 800 may further comprise adjusting (e.g., via the controller) the processing workflow. For example, the adjusting may include modifying one or more upcoming processing or analysis steps (e.g., by controlling one or more parameters thereof) or discontinuing processing or analysis of the cell product. Oppositely, when the sample parameter does meet the criterion, the method 800 may further comprise continuing the predetermined workflow for the cell product. In some variations, the method 800 may furtherATTY DOCKET No.: CEES-026 / 01WO 337273-2147include notifying an operator of how the sample parameter compares to the criterion, such as graphically via a display. In some variations, notifying the operator may include automatically generating and / or updating an electronic record (e.g., an electronic batch record) for the product as the sample is prepared and analyzed by the analysis module. This record may include, for example, one or more of: processing and analysis workflow history, analysis results, reagent lot information, analysis tool configuration specifications, and sample parameter result acceptance criteria. In some variations, subsequent data analysis, reporting, and / or deci si on -making related to the cell product (by the controller and / or by an operator) may be based at least in part on the generated electronic record.

[0123] While the method 800 includes two transferring steps 804 and 806 within the sample preparation and analysis system of the workcell, it should be appreciated that any number of transferring steps may occur between any two modules of the sample preparation and analysis system during preparation and analysis of a given sample. For example, as described above with respect to the analysis module of the sample preparation and analysis system, in some variations, a cell product sample may be transferred between the sample preparation module and the analysis module any number of times to normalize one or more parameters of the sample (e.g., cell concentration).

[0124] As another example, fluids (reagents, buffers, etc.) may be transferred between the reagent storage module and the sample preparation module any suitable number of times during sample preparation so that the sample is correctly prepared according to its preparation parameters. Transferring fluids within the sample preparation and analysis system may be accomplished using one or both of a robotic arm (e.g., when transferring samples / fluids within containers) and a robotic pipettor (e.g., when extracting samples / fluid directly from a container).

[0125] As yet another example, waste may be transferred from one or more of the reagent storage module, the sample preparation module (e.g., used labware like pipette tips and intermediate containers, extra reagent / buffer, etc.), the transfer module (e.g., disassembled fluid device caps), and the analysis module (e.g., used tubes and / or microplates, sample waste) used to the waste storage module any suitable number of times during preparation and analysis in order to maintain a clean and orderly environment within the analysis system. Transferring waste to the waste storage module may be achieved using a robot, such as a robotic arm, and / or via channels integrated into the system, such as a tip disposal for a robotic pipettor that is built into the bench of the sample preparation module.ATTY DOCKET No.: CEES-026 / 01WO 337273-2147

[0126] In some variations, a plurality of transferring steps may occur simultaneously, or at least partially overlap, within the analysis system. In some variations, two or more portions of a single sample may undergo two or more corresponding preparation and / or analysis steps and at least partially overlap during these steps.

[0127] In some variations, the method 800 may include detecting (e.g., scanning with a scanner) data encoded on any contained samples, reagents, buffers, and / or the like during sample preparation or analysis within the sample preparation and analysis system. For example, contained samples, reagents, buffers, and / or the like may be scanned before, after, and / or during each transfer step.

[0128] Additionally, or alternatively, in some variations, the method 800 may include monitoring (e.g., via integrated sensors coupled to a controller) a waste level within one or more waste compartments. This monitoring may further comprise clearing a waste compartment (e.g., instructing an operator to do so via a display coupled to the system controller) when the waste level is about equal to or greater than a predetermined threshold level for compartment fullness.

[0129] Moreover, in some variations, the method 800 may include steps for selecting and / or modifying one or more transfer parameters, one or more preparation parameters, and / or one or more sample parameters for the cell product sample. In some variations, the controller may automatically make such selections and adjustments. Additionally, or alternatively, the controller may be configured to receive, via an input device, operator feedback or direct modifications to the transfer, preparation, and / or sample parameter(s).

[0130] Throughout this application, the term “about” is used to indicate that a value includes the inherent variation of error for the device or the method being employed to determine the value, or the variation that exists among the samples being measured. Unless otherwise stated or otherwise evident from the context, the term “about” means within 10% above or below the reported numerical value (except where such number would exceed 100% of a possible value or go below 0%). When used in conjunction with a range or series of values, the term “about” applies to the endpoints of the range or each of the values enumerated in the series, unless otherwise indicated. As used in this application, the terms “about” and “approximately” are used as equivalents.

[0131] Additionally, it should be appreciated that ranges disclosed herein may be exemplary, and include all ranges and subranges therein.ATTY DOCKET No.: CEES-026 / 01WO 337273-2147

[0132] While certain variations are described and illustrated herein, those of ordinary skill in the art will readily envision a variety of other means and / or structures for performing the function and / or obtaining the results and / or one or more of the advantages described herein, and each of such variations and / or modifications is deemed to be within the scope of the inventive variations described herein. More generally, those skilled in the art will readily appreciate that all parameters, dimensions, materials, and configurations described herein are meant to be exemplary and that the actual parameters, dimensions, materials, and / or configurations will depend upon the specific application or applications for which the inventive teachings is / are used. Those skilled in the art will recognize or be able to ascertain using no more than routine experimentation, many equivalents to the specific inventive variations described herein. It is, therefore, to be understood that the foregoing variations are presented by way of example only and that, within the scope of the appended claims and equivalents thereto; inventive variations may be practiced otherwise than as specifically described and claimed. Inventive variations of the present disclosure are directed to each individual feature and / or method described herein. In addition, any combination of two or more such features and / or methods, if such features and / or methods are not mutually inconsistent, is included within the inventive scope of the present disclosure.

Claims

ATTY DOCKET No.: CEES-026 / 01WO 337273-2147CLAIMSWhat is claimed is:

1. A method for preparing a cell product sample for analysis during automated cell processing, comprising:moving a fluid device from a cell processing instrument bay to a sample preparation module using a robot, wherein each of the fluid device, the cell processing instrument bay, the sample preparation module, and the robot are positioned within a workcell, and wherein the fluid device contains a cell product; andtransferring a sample of the cell product from the fluid device to the sample preparation module;wherein the sample preparation module is capable of preparing a sample to be transferred to an analysis module to determine one or more sample parameters.

2. The method of claim 1, wherein transferring the sample to the sample preparation module comprises automatically disassembling at least a portion of the fluid device to extract the sample therefrom.

3. The method of claim 1, wherein the fluid device comprises a sterile liquid transfer device (SLTD) or a cartridge configured to couple to the processing instrument to process the cell product.

4. The method of claim 1, wherein the analysis module is integrated with the sample preparation module.

5. The method of claim 1, wherein the one or more sample parameters comprises a value of cell viability, cell count, cell concentration, cell recovery, cell diameter, cell size distribution, glucose, lactate, pH, phenotypic markers, chimeric antigen receptor expression, transgenic T cell receptor expression, cell identity markers, cell purity, vector copy number, or a combination thereof.

6. The method of claim 1, wherein the one or more sample parameters comprises a first sample parameter, the method further comprising determining one or more second sample parameters of the sample based on the analysis.ATTY DOCKET No.: CEES-026 / 01WO 337273-21477. The method of claim 1, wherein the analysis module comprises a a flow-based bead reader, a polymerase chain reaction (PCR) system, a cell analyzer, a microplate reader, a cell counter, or a combination thereof.

8. The method of claim 1, wherein the sample preparation module is integrated with an analytical module, and wherein the analytical module comprises a first analytical instrument.

9. The method of claim 8, wherein the first analytical instrument comprises a cell counter.

10. The method of claim 1, further comprising determining whether a processing workflow needs to be modified based on the one or more sample parameters.

11. The method of claim 1 further comprising automatically preparing the sample for analysis in the sample preparation module based on a set of preparation parameters.

12. The method of claim 11, wherein automatically preparing the sample for analysis in the sample preparation module comprises one or more of separating the sample, transferring a blocking solution into the sample, transferring a reagent into the sample, mixing the sample with the reagent, incubating the sample, and washing the sample with a buffer.

13. The method of claim 11, wherein the set of preparation parameters comprises one or more of a sample temperature, sample container temperature, a sample container type, a type of reagent, a mixing technique, a mixing duration, a centrifugation duration, a centrifugation speed, an incubation temperature, an incubation duration, a type of blocking solution, and a type of buffer.

14. The method of claim 1, wherein each of transferring the sample to the sample preparation module and transferring the sample to the analysis module is based on a set of transfer parameters.

15. The method of claim 14, wherein the set of transfer parameters comprises one or more of a sample volume, an origin sample location, and a subsequent sample location.

16. The method of claim 1 further comprising scanning a label on the fluid device to identify the cell product therein and determine a type of analysis to perform on the sample.ATTY DOCKET No.: CEES-026 / 01WO 337273-214717. The method of claim 16, wherein the label comprises a barcode or RFID tag.

18. The method of claim 1, further comprising generating an electronic record for the cell product as the sample is analyzed by the analysis module.

19. A system for automated cell processing, comprising:a fluid device containing a cell product;a processing instrument comprising a receiving bay configured to receive the fluid device, wherein the processing instrument is configured to perform a portion of a processing workflow using the fluid device;a sample preparation and analysis system comprising:a sample preparation module comprising a robotic pipetter and configured to prepare a sample of a cell product from the fluid device for analysis; anda robot configured to move the fluid device from the processing instrument to the sample preparation system wherein each of the processing instrument receiving bay, the sample preparation system, and the robot is positioned within a workcell.

20. The system of claim 19, wherein the sample preparation module further comprises one or more of a sample separator, a sample mixer, and an incubator.

21. The system of claim 20, wherein the sample separator comprises a centrifuge.

22. The system of claim 20, wherein the sample mixer comprises an orbital shaker.

23. The system of claim 19, wherein the sample preparation and analysis system further comprises an analytical module comprising one or more of a flow-based bead reader, a polymerase chain reaction (PCR) system, a cell analyzer, a microplate reader, a cell counter, or any combinations thereof.

24. The system of claim 19, wherein the sample preparation and analysis system further comprises a first analysis module integrated with the sample preparation module.

25. The system of claim 24, wherein the sample preparation and analysis system further comprises a second analysis module, where the first analysis module is different from the second analysis module.ATTY DOCKET No.: CEES-026 / 01WO 337273-214726. The system of claim 24, wherein at least one of the first analysis module or the second analysis module comprises a cell counter.

27. The system of claim 19 further comprising a transfer module comprising one or both of a fluid device disassembly system having a conveyor and a disassembly tool.

28. The system of claim 27, wherein the conveyor is configured to move the fluid device toward the disassembly tool.

29. The system of claim 27, wherein the disassembly tool comprises a grasper configured to releasably grasp a cap of the fluid device to remove the cap from a container of the fluid device.

30. The system of claim 27, wherein the disassembly tool is coupled to a sidewall of the workcell.

31. The system of claim 27, wherein the robot is configured to move the fluid device to the conveyor within an interior zone of the workcell.

32. The system of claim 27, wherein the sample preparation and analysis system further comprises a scanner configured to identify the cell product via a label on the fluid device.

33. The system of claim 32, wherein the label comprises a barcode or RFID tag.

34. The system of claim 19, wherein the sample preparation and analysis system further comprises a reagent storage module configured to store materials for use by the sample preparation module.

35. The system of claim 34, wherein the reagent storage module comprises a scanner configured to verify the materials used to prepare the sample by the sample preparation module.

36. The system of claim 34, wherein at least a portion of the reagent storage module is refrigerated.

37. The system of claim 34, wherein the materials comprise buffer, cytokines, proteins, purified proteins, enzymes, polynucleotides, transfection reagents, non-viral vectors, viralATTY DOCKET No.: CEES-026 / 01WO 337273-2147vectors, dyes, antibodies, antibiotics, nutrients, cryoprotectants, solvents, cellular materials, small molecules, pharmaceutically acceptable excipients, and combinations thereof.

38. The system of claim 19, wherein the analysis module further comprises a waste module configured to store used sample preparation devices and material wastes.

39. The system of claim 38, wherein the sample preparation devices comprise fluid devices, vials, well plates, pipette tips, and combinations thereof.

40. The system of claim 19 further comprising a controller configured to determine at least a portion of the processing workflow for the cell product based on the analysis of the sample.

41. The system of claim 40, wherein the control is further configured to generate an electronic record for the cell product.

42. The system of claim 19, wherein the fluid device comprises a sterile liquid transfer device (SLTD) or a cartridge configured to couple to the processing instrument to process the cell product.

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