Solutions for manufacturing cell therapy products must be designed with safety and flexibility in mind. Instruments designed for closed manufacturing reduce the error associated with manual cell processing to create a safer product. Similarly, targeted gene delivery methods like transfection improve safety and performance of cell therapy products. Flexible solutions that facilitate scale-up can make it easier to transition from research to manufacturing by facilitating scalable and flexible nonviral delivery for cGMP cell therapy processing.
This resource guide contains information about:
- Optimizing multiple electroporation conditions simultaneously
- Solutions designed for electroporation process development through scale-up from research and solutions designed for process development at scale
- A comparison of post-electroporation viability and transfection efficiency between two systems
- How Gibco™ CTS™ products enable GMP compliance
- How closed, modular systems can deliver efficiency and cost savings
Download this resource guide to learn more about the benefits of a closed, modular, large-scale electroporation system.
CTS Xenon Electroporation System
Large-scale nonviral delivery for cell therapy
CTS Xenon Electroporation System
The Gibco™ Cell Therapy Systems™ (CTS™) Xenon™ Electroporation System is a closed, modular, large-scale platform that offers full control over electroporation parameters for optimal performance.
The CTS Xenon Electroporation System delivers superior transfection performance and viability. The system enables electroporation of up to 2.5 x 10? cells in a 25 mL run to support both process development and manufacturing work in clinical cell therapy.
The Gibco™ CTS™ Xenon™ SingleShot Electroporation Chamber is designed for rapid electroporation of 1 mL of cells at a recommended concentration range of 20 x 106 to 100 x 106 cells/mL for process development applications, while the Gibco™ Xenon™ MultiShot Electroporation Cartridge, designed for clinical research process development, enables consistent electroporation of volumes up to 25 mL in under 25 minutes in a closed, GMP-compliant system.
Flexible, programmable protocols for a range of cell types and payloads make the CTS Xenon Electroporation System ideal for process development and manufacturing work in clinical cell therapy.
Key benefits
High speed and large volume—transfect up to 2.5 x 109 T cells/25 mL in less than 25 minutes
Scalable, proven performance and viability—up to 90% gene knockout and 80% cell viability
Process flexibility—user-programmable system enables you to create and optimize electroporation protocols for various cell types and payloads, from process development through commercial manufacturing
Efficient nonviral transfection—can be used to deliver DNA, RNA, and protein payloads
Closed-system processing—Xenon MultiShot Electroporation Cartridge helps enable sterile welding to PVC or C-Flex™ tubing
Full control of electroporation parameters for optimum performance with each cell type and payload
The CTS Xenon system gives you full control over electroporation parameters—the embedded graphical user interface (eGUI) allows you to easily optimize protocols for a variety of cell types and payloads.
Controllable parameters include voltage, pulse width, pulse number, and pulse interval delay.
Graphical depiction of a user-generated electroporation pulse profile.
The effects of voltage, pulse width, and pulse number on transfection efficiency and post-electroporation viability as determined by design of experiment (DOE).
The CTS Xenon Electroporation System offers the unique benefit of allowing users to optimize multiple electroporation conditions simultaneously. The figures on this page illustrate the impact of the various parameters on transfection efficiency and viability. Furthermore, the range and combination of each of these parameters is determined by in-depth analysis of the system’s electronics, temperature, and pressure during electroporation.
Allowable electroporation parameters based on power and temperature limits of the instrument and chamber.
System specifications
The CTS Xenon Electroporation System
Helps enable 21 CFR Part 11 compliance with an available security, audit, and e-signature (SAE) software upgrade
Is compatible with Open Platform Communications-Unified Architecture (OPC-UA)
Assists Thermo Fisher™ Connect Platform for cloud-based data storage
Instrument specifications
Recommended process volume cell concentration
20 × 106 to 100 × 106
Electroporation volumes
1 mL (CTS Xenon SingleShot chamber); 5–25 mL (Xenon MultiShot cartridge)
Electroporation chamber volume
1 mL
Run time for 5–25 mL electroporation volume
7–22 min
Electroporation pulse voltage range
500–2,500 V
Electroporation pulse width range
1–30 ms
Electroporation pulse interval range
500–1,000 ms
Number of electroporation pulses
1–10
Cell mixer rotation speed
60 rpm
Precooling technology
Peltier
Precooling temperature setting range
10–30°C
CTS Xenon SingleShot chamber
The CTS Xenon SingleShot chamber was developed specifically to help process developers refine their electroporation conditions as they scale up from research-scale electroporation.
Range: 20 × 106 to 100 × 106 cells in a 1 mL sample volume
Enables electroporation to be performed in a shared, Class C cleanroom, leading to cost-effective transfer and scale-up
Chamber material: Tritan™ MX711 copolyester
Gamma-sterilized
Xenon MultiShot cartridge
The Xenon MultiShot cartridge provides flexibility for process development at scale, and can be used to support closed-system processing.
Range: 1 × 108 to 2.5 × 109 cells in a 5–25 mL sample volume
Enables electroporation to be performed in a shared, Class C cleanroom leading to cost-effective transfer and scale-out
Compatible with Luer connectors and sterile welding
Tube material: DEHP-free PVC and C-Flex
Chamber material: Tritan MX711 copolyester
Gamma-sterilized
CTS Xenon system software interface
User-friendly eGUI is capable of fine-tuning protocol parameters for each combination of cell type and payload
The OPC-UA interface allows connectivity to a 21 CFR Part 11–compliant system or MES/LIS software
The software can be locked for operator manufacturing mode (requires upgrade to SAE module)
CTS Xenon system software and firmware updates can be installed by the customer through the eGUI
The system has the capability to connect to the cloud via the Connect Platform
Genome editing using the CTS Xenon system and electroporation buffers
Gibco™ CTS™ Xenon™ Electroporation Buffer supports the transfection of a variety of mammalian cells, including human primary cells, and payloads (e.g., plasmid DNA, mRNA, miRNA, or siRNA) for gene upregulation or downregulation applications.
Gibco™ CTS™ Xenon™ Genome Editing Buffer is designed to improve performance with gene editing–specific payloads (e.g., TALEN and CRISPR-Cas9) for applications based on knock-in or knockout in a variety of human primary cells.
Both CTS Xenon Electroporation and Genome Editing Buffers were designed specifically for use with the CTS Xenon system. They are available in 100 mL bottle and bag formats for convenient process development and closed-system manufacturing scale-up.
For additional specifications, go to thermofisher.com/xenon
Neon Transfection System CTS Xenon Electroporation System
Scale up and optimize your transfection efficiency in the closed, modular CTS Xenon Electroporation System
Seamless translation
The CTS Xenon Electroporation System can help you transition from research to commercial manufacturing by facilitating scalable and flexible nonviral delivery for cGMP cell therapy processing. Benchmarked against the Invitrogen™ Neon™ Transfection System, the CTS Xenon system enables transfection in volumes of up to 25 mL without a drop in performance,
as shown by post-electroporation viability and transfection efficiency, depicted in the following figures.
Briefly, primary T cells isolated from apheresis products from three healthy donors were transfected using Cas9/gRNA to knock out the endogenous T cell receptor (TRAC) and knock in a double-stranded, linear DNA expressing a second-generation CAR construct. Cells were transfected on the Neon Transfection System (100 µL), or the CTS Xenon instrument with either a CTS
Xenon SingleShot chamber (1 mL) or a Xenon MultiShot cartridge (9 mL), or were left untransfected (0). Cells were assessed through flow cytometry using the Invitrogen™ Attune™ NxT Flow Cytometer three days after transfection for gene expression
of anti-CD19 on the CAR T cells. Cells were also assessed for viability utilizing Gibco™ Trypan Blue Solution.
Transfection efficiency
Knockout and knock-in performance in CAR T cells. Cells were characterized after 72 hours as untransfected (TCRαβ+, gray), knocked out but not knocked in (TCRαβ–CAR–, light blue), or as successfully knocked out and knocked in (TCRαβ–CAR+, dark blue). Across all donors, successful knock-in percentages on the CTS Xenon system ranged from 21.9% to 45.6%, exceeding the values on the Neon system.
Viability in CAR T cells. Cells were assessed for viability after 72 hours using Trypan Blue Solution. For the three donors, cell viability on the CTS Xenon system ranged from 64.6% to 83.6%.
Cell surface markers
Preservation of CD4 vs. CD8 T cell ratio. CD4 and CD8 T cells were identified by flow cytometry. Non-electroporated cells (condition 0) were gated on live, single, and untransfected (TCRαβ+ cells), while electroporated cells were gated on live, single, and knocked out (TCRαβ– cells). Proportions of CD4 (dark blue) and CD8 (light blue) T cells remained largely consistent between non-electroporated cells and cells electroporated with the Neon system (100 µL) and with the CTS Xenon system (1 and 9 mL).
For more performance data, go to thermofisher.com/xenon
Enabling GMP compliance Cost effectiveness of closed, modular systems Gibco™ CTS™ products are specifically designed to enable clinical and commercial cell and gene therapy manufacturing and are backed by testing and regulatory support.
Regulatory support files (RSF) for the CTS Xenon SingleShot Chamber, CTS Xenon Genome Editing Buffer, and CTS Xenon Electroporation Buffer are available by request at thermofisher.com/regulatory.
The RSF includes detailed information about the instrument and the single-use consumables, including materials of construction, biocompatibility, extractable testing summaries, integrity of consumable sterility, stability testing, and instrument safety compliance standards.
The CTS Xenon Electroporation System, CTS Xenon SingleShot Chamber, CTS Xenon Genome Editing Buffer, and CTS Xenon Electroporation Buffer are manufactured under ISO 13485 regulations, adhering to all compliance guidelines.
CTS Xenon software can be locked for operator manufacturing mode.
The OPC-UA interface, the industry-standard machine communication language, enables connection to an MES/LIM or 21 CFR Part 11–compliant system.
The CTS Xenon system includes a modular, closed cell therapy instrument that can enable a path from research to commercial manufacturing, helping to deliver efficiency and cost savings.
Closed systems reduce the cost of cleanroom spaces—A closed system that operates in a Class C manufacturing facility can reduce the size of a Class B lab space required for open processing systems by up to 90%.*
Modular designs enable increased instrument efficiency and utility—Manufacturing processes can be optimized using technologies that are ideally suited to each step.
Time-consuming processes such as cell expansion can be decoupled from rapid processes such as buffer-exchanging and concentrating, reducing the investment in facilities and capital equipment by up to 70%.*
Avoid process development delays—Utilizing the same system or platform from research through process development and commercial manufacturing can help you avoid process delays associated with changing systems.
* Claims based on CAR T therapy, 7-day incubation, 2,000 patients per year, from: James D (2017) How short-term gain can lead to long-term pain. Cell Gene Therapy Insights 3(4): 271-284.
Getting started with the CTS Xenon Electroporation System
Customer experience and support
SmartStart orientation training enables your success. Every CTS Xenon Electroporation System comes with SmartStart orientation training to help your lab quickly become efficient at using the CTS Xenon system. Led by professional trainers, the orientation provides interactive education that includes theoretical and hands-on training.
SmartStart orientation includes:
General instrument setup and operation
Training on the Xenon system software covers eGUI and protocol optimization using CTS Xenon SingleShot chambers
Discussion of custom protocols to suit your cells and payload
Step-by-step explanation of available tools on the instrument and software using starting protocols as examples
Protocol creation training to enable you to customize starting protocols or create new customized protocols
Installation qualification and operational qualification (IQ/ OQ) package; it is available with additional AB Qualification Service that includes an on-site visit from a field service engineer within 2 years of installation
Field application scientists will work together with you to support ongoing protocol development
Annual preventative maintenance and instrument service will be available through the Instrument Services team
Protocol optimization
Your optimization of the CTS Xenon Electroporation System can begin with the use of the 6 CTS Xenon SingleShot optimization protocols:
Top 5 performing protocols from 24-well optimization from the Neon system
T cell design of experiment (DOE) condition identified and validated during CTS Xenon system development
Products that meet your need at every step of the workflow, from research through commercial manufacturing
Thermo Fisher Scientific has built a fit-for-purpose portfolio of modular instrumentation platforms, consumables, reagents, and media designed to support closed, large-scale cell therapy manufacturing. Our goal is to enable automation of the end-to-end manufacturing workflow, from cell isolation and activation to gene modification and expansion.
Clinical trial kit production • Clinical packaging,
Additional resources
See the CTS Xenon system in action. Check out how-to videos and a virtual tour at thermofisher.com/xenon
To view protocols and learn more about how to use the CTS Xenon system with different cell types and payloads, go to thermofisher.com/xenon
For more information, or to request a demo or quote, go to thermofisher.com/xenon
Field application scientists can train in your lab or remotely and cover a variety of topics around the instrument, software, and applications.
View recent webinars, application notes, handbooks, posters, and more in our Cell and Gene Therapy Learning Center at thermofisher.com/cgtlearningcenter
For technical support or help, contact us at thermofisher.com/us/en/home/technicalresources
To request regulatory support files, contact us at thermofisher.com/regulatory
See our product and service selection tool for a complete list of cell and gene therapy products and services at thermofisher.com/cellgenetherapytool
High-quality materials, services, and support offered every step of the journey, from discovery to clinical research to commercial cell and gene therapy manufacturing. Learn more at thermofisher.com/ctssupport
Learn about our solutions to help you achieve your cell therapy goals from research to commercialization at thermofisher.com/cellandgenetherapy
For more information about our latest technology offerings, go to thermofisher.com/cgtask
Ordering information | ||
Description | Quantity | Cat. No. |
CTS Xenon Electroporation Instrument* | 1 | A52727 |
Xenon SingleShot Electroporation Chamber** | 1 mL, 6 pk | A53444 |
CTS Xenon SingleShot Electroporation Chamber* | 1 mL, 6 pk | A50305 |
Xenon MultiShot Electroporation Cartridge (coming soon)** | 5–25 mL, 1 pk | A53445 |
CTS Xenon MultiShot Electroporation Cartridge (coming soon)* | 5–25 mL, 1 pk | A50306 |
CTS Xenon Electroporation Buffer* | 100 mL bottle | A4997901 |
CTS Xenon Electroporation Buffer* | 100 mL bag | A4997902 |
CTS Xenon Genome Editing Buffer* | 100 mL bottle | A4998001 |
CTS Xenon Genome Editing Buffer* | 100 mL bag | A4998002 |
* For Research Use or Manufacturing of Cell, Gene, or Tissue-Based Products.
** For Research Use Only.
Service plan bundle Cat. No.
CTS Xenon Electroporation System
+ AB Assurance service extended warranty (for 2 years total coverage)
+ IQ/OQ services
CTS Xenon Electroporation System
+ AB Assurance service extended warranty (for 2 years total coverage)
A53520
A53340
Additional products Quantity Cat. No.
CTS Rotea Counterflow Centrifugation System* + 2-year warranty (including OQ after PM) + IQ/OQ services
1 A50757†
A47695‡
Attune NxT Flow Cytometer** 1 A28993
5.0 mg | A45221 | |
CTS Dynabeads CD3/28* | 10 mL | 40203D |
CTS OpTmizer Pro SFM, bottle format* | 1 L | A4966101 |
CTS OpTmizer Pro SFM, bag format* | 1 L | A4966103 |
CTS Immune Cell Serum Replacement* | 50 mL | A2596101 |
CTS TrueCut Cas9 Protein (coming soon)* 2.5 mg A45220
* For Research Use or Manufacturing of Cell, Gene, or Tissue-Based Products. CAUTION: Not intended for direct administration into humans or animals.
** For Research Use Only. Not for use in diagnostic procedures.
† North America and Europe.
‡ Rest of world.
thermofisher.com/xenon
Intended use of the products mentioned in this document varies. For specific intended use statements, please refer to the Instructions for Use (IFU). © 2022 Thermo Fisher Scientific Inc. All rights reserved. All trademarks are the property of Thermo Fisher Scientific and its subsidiaries unless otherwise specified. C-Flex is a trademark of
Saint-Gobain Performance Plastics Corporation. Tritan is a trademark of Eastman Chemical Company. COL34724 0322