Xuri Brochure - GE Healthcare Life Sciences

Xuri . Believe in
better futures.
™
Finding solutions. Advancing breakthrough cell therapies.
www.gelifesciences.com/xuri
Our commitment
Engineering innovation
GE Global Research Center is the hub of technology development for all of GE’s businesses
with employees representing many disciplines of science and technology. Our scientists
and engineers redefine what’s possible by finding answers to some of the world’s toughest
problems and driving growth for our businesses. We innovate twenty-four hours a day, with
sites in Niskayuna, New York; San Ramon, California; Bangalore, India; Shanghai, China; Munich,
Germany; and Rio de Janeiro, Brazil.
For more information visit www.ge.com/research
Building the infrastructure
Our Enterprise Solutions team brings together expertise in process development, product
offerings, and facility planning through co-ordinated project management, to provide an
integrated solution for cell manufacturing
GE Healthymagination
GE is committed to creating better health for more people. Healthymagination is a $6B strategy
to revolutionize the world’s health by improving the quality, access and affordability of care.
We believe it’s time for a better, simpler system – one in which innovation helps lower the cost
of care and improve the quality of outcomes for more people.
For more information visit www.healthymagination.com
Collaborations
We are proud to be working in collaboration with prestigious institutes to enable progress of
the cell therapy field through mutual learning and sharing of resources.
Karolinska University Hospital, Stockholm, Sweden
A collaboration which is exploring and advancing future technologies and workflow needs to
make cell therapy a reality in a clinical setting.
University of California, San Francisco
A collaboration aimed at overcoming the lack of blood forming stem cells available as therapies
to patients suffering from life-threatening diseases such as lymphoma, myeloma, leukemia,
and sickle cell anemia.
2
Believe in better futures
Cell based therapy has the potential to transform treatment for millions of patients suffering
from life-threatening diseases. Through our scale and innovation we are committed to
accelerating access to safe and ground-breaking treatments addressing some of healthcare’s
toughest challenges.
From research to manufacturing
Xuri cell therapy technologies support every stage of your project from clinical research
through process development to manufacturing. Xuri reagents are dedicated cell therapy
ancilliary products following USP<1043> standards*. Our products deliver integrated
solutions that support the transition from research to clinic and help make cellular therapies
a clinical reality.
Faster to clinic
Our products and processes are designed to deliver your therapies to patients as quickly
as possible. We ease your regulatory path by engineering our Xuri instruments to approved
standards for cell therapy applications and we can work with you to optimize processes that
provide scalable solutions to meet your biomanufacturing needs. You will also receive specialist
technical support that will maximize production efficiency while controlling costs and ensuring
your therapies are produced quickly and on time.
* Meet USP <1043> ‘ancillary materials for cell, gene, and tissue-engineered products’, within the responsibilities applicable to a supplier.
Other aspects of USP <1043> will be the responsibility of the end-user to assess. GE Healthcare cannot fulfill USP <1043> in regards to
application and therapy specific aspects (e.g., use in finished therapeutic, assessment of removal from a finished therapeutic, and possibly
biocompatibility, cytotoxicity, or adventitious agent testing).
3
Seamlessly go from research
to manufacturing
To bring a cell therapy product from research to the clinic and into commercial-scale
manufacturing quickly, on budget, and with minimal process optimization both the
regulatory and technical requirements of increasing scale should be taken into account
from the initial process setup.
We understand the requirements for each phase of cell therapy production and our
products and services ease the progression to commercialization because they can be
readily incorporated in to cell manufacturing SOPs.
Clinical research
• Facilitated regulatory approval
process due to extensive
validation, references, and
adherence to USP<1043> for
cell expansion products
• Simplified set up of your
protocols with dedicated
technical support and
application-specific proof data
• Minimal process revision
required by GMP facilities for
clinical cell manufacturing
Process develoment
• Minimal process revision to
achieve robust cell production
in a regulated environment
due to a direct correlation
with products used in the
research phase
• Easier transition for future
scale-up or scale- out manufacturing process setup
Manufacturing
• Minimal process adaptation
from development phase
for timely lock-down
• Financially viable process
setup
• Reduced risk of error with
automated process and
standard reagents
• Follows USP<1043>, GAMP5,
and CFR part 11 standards
• Reliable and consistent QC
release standards attained and
minimized operator variability
from automated solutions
Products
Cell isolation
Percoll™ Plus*
Ficoll-Paque™ PREMIUM*
Percoll™ Plus*
Ficoll-Paque™ PREMIUM*
Percoll™ Plus*
Ficoll-Paque™ PREMIUM*
Xuri W25 System
Xuri IL2
Xuri MSC medium
Xuri W25 System
Xuri IL2
Xuri MSC medium
Cell expansion
Xuri W5 System
Xuri IL2
Xuri MSC medium
* For in vitro use only
4
Immunotherapy: Cell isolation
Making immunotherapy a reality
GE Healthcare products maximize your chances of success in cell therapy
manufacturing by helping to preserve as many precious cells as possible during
both the initial cell separation and the expansion of immune cells. They can be
readily included in cell manufacturing SOPs facilitating regulatory approval and
easing the progression from research to manufacturing.
Cell separation
Cell selection
Cell activation
and expansion
Cell harvest and
concentration
Cell infusion
into patient
Typical immunotherapy workflow.
Cell isolation
With a proven track record of over 30 years and citations in thousands of peerreviewed articles, Ficoll-Paque and Percoll density gradient media have a solid
reputation for consistent performance and reproducible results in manual cell
separation of immune cells.
• Reduce the risk of losing precious cells right from the first step of manipulation
• Maximize your chances of getting a sufficient number of functional cells for and
from expansion
• Rely on what has been tested, published, and approved by 1000s of researchers,
experts, and colleagues
Our density gradient centrifugation media provide a targeted, approach to isolating
a multitude of immune cell types (Table 1). Different in their density and format,
Ficoll-Paque PREMIUM and Percoll PLUS provide you with full flexibility for your
specific requirements.
Table 1. Types of material that can be isolated using Ficoll-Paque PREMIUM and Percoll PLUS products
Cells
Ficoll-Paque™ PREMIUM
(ready-to-use solution)
Percoll™ PLUS
(adjustable density for full control)
T-cells
√
√
NK- cells
√
√
CD34+
√
√
DC’s
√
√
Organelles
√
Viruses
√
Note. Although both reagents can be used successfully to isolate multiple immune cell types, Ficoll-Paque PREMIUM is
provided as a ready-to-use solution whereas the density of Percoll PLUS solution can be adjusted as required.
5
Immunotherapy: Cell isolation
Ficoll-Paque PREMIUM
Percoll PLUS
Ficoll-Paque PREMIUM products are sterile, ready-to-use
density centrifugation media solutions manufactured
under a Quality Management System certified to
ISO 13485:2003 and follow USP <1043> standards for
facilitated adoption into cell therapy manufacturing
protocols*. Ficoll-Paque PREMIUM solutions are
optimized to obtain different types of mononuclear cells
from peripheral blood, bone marrow, and umbilical cord
blood by density gradient centrifugation.
For flexibility and in order to maximize recovery of
precious patient cells, the density of Percoll PLUS can be
adjusted up to 1.3 g/ml depending on the cell type to be
isolated. Percoll PLUS is useful as a first step to enrich
for cell populations before attempting finer resolution
and can be used for isolation of cells, viruses, and
subcellular particles.
There are three densities of ready-to-use Ficoll-Paque
PREMIUM solutions available.
6
Particularly appropriate to minimize risk of cytotoxicity,
this low endotoxin reagent (<2 EU/ml) is non-toxic,
almost chemically inert, and does not adhere to
membranes.
Ficoll-Paque PREMIUM
For the isolation of mononuclear cells from human peripheral blood,
bone marrow, and umbilical cord blood
Ficoll-Paque PREMIUM 1.073
For the isolation of lower-density human mononuclear cells
(e.g., mesenchymal stem cells or monocytes)
Ficoll-Paque PREMIUM 1.084
For the isolation of a broad range of human mononuclear cells including
those of a higher density and for separating blood cells from mice or rats
Immunotherapy: Cell expansion
Cell expansion
GE Healthcare cell expansion systems, bioreactors, and reagents are designed to address the
technical and manufacturing needs of laboratories and units producing cells for cell therapy
and progressing towards scale-out or scale-up. The systems are suitable for use in regulated
environments and can be used in clinical research, process development, and manufacturing.
Xuri Cell Expansion Systems help you progress the manufacture of cells from research
to the clinic in a seamless way thanks to their scalability and the functionally closed
Cellbag™ bioreactors.
• Advanced control of your culture
- Specific technical features for optimal control and monitoring of the expansion systems
- Full product traceability and specifications
• Designed to safeguard your cells
- Functionally closed systems
- Follow USP <1043> ‘ancillary materials for cell, gene, and tissue-engineered products’,
within the responsibilities applicable to a supplier*
- Include alarm system and remote control
Cellbag bioreactors
Cellbag bioreactors are single-use functionally closed cell
culture bags that can be used in conjunction with Xuri Cell
Expansion Systems. They are available in a range of sizes to
accommodate culture volumes from 0.3 to 25 L (Fig 1).
Validation data and Cellbag Drug Master File data are
available to demonstrate biocompatibility; the user
is however advised to validate suitability for specific
applications.
Cellbag bioreactors are manufactured from multilayer,
laminated, clear USP Class VI plastics. They are sterilized by
gamma radiation at 25 to 40 kGy and individual radiation
indicators are affixed to each bag. Each lot is also tested
for bacterial endotoxin levels and lot release requires an
endotoxin level below 0.125 EU/mL.
• No sterilization or cleaning steps required.
• Single-use functionally closed bags minimize the risk
of cross-contamination.
• Easily connected to Xuri Cell Expansion Systems
• Can be customized to meet your changing needs
Cellbag bioreactor1
Working volume
Cellbag 2 l
300 ml2 to 1 l
Cellbag 10 l
500 ml to 5 l
5
Cellbag 20 l
1 to 10 l
6
Cellbag 50 l
5 to 25 l
3
1
4
2
1. Spare luer port/optional pH probe
2. Outlet air filter
3. Oxywell2 port
4. Y dip tube for Perfusion harvest
5. Needleless sampling port
6. Inoculation/Feed line
Fig 1. Typical Cellbag bioreactor configuration.
1
All Cellbag bioreactor sizes are available with internal perfusion filter for perfusion
cultures and/or can be equipped with single-use optical pH (pHOPT) and DO
(DOOPT II) sensors.
2
Cellbag bioreactors with optical sensors require 300 ml minimal working volume.
Depending on application and configuration, it might be possible to cultivate
below the recommended minimum volume. However, it is highly recommended
to stay above this volume for applications that require high agitation and pH and
DO control. The temperature, pH, and DO sensors need to be submerged in liquid
throughout the complete rocking cycle to function correctly
* Other aspects of USP <1043> will be the responsibility of the end-user to assess. GE Healthcare cannot fulfil USP <1043> in regards to application
and therapy specific aspects (e.g., use in finished therapeutic, assessment of removal from a finished therapeutic, and possibly biocompatibility,
cytotoxicity, or adventitious agent testing).
7
Immunotherapy: Cell expansion
Xuri Cell Expansion System W5
Xuri Cell Expansion System W5 (formerly known as
WAVE Bioreactor™ 2/10 System) is ideally suited
to research-scale cell culture or for the early stage
of scale-up and scale-out prior to the commercial
manufacture of cell-therapy products.
This easy-to-use system allows production of large
numbers of cells in a single-use Cellbag bioreactor
more efficiently and cost-effectively than manual tissue
culture flask-based systems. The system is suitable
for culture volumes from as low as 300 mL up to a
total of 5 L. Its use has been optimized for expansion
of lymphocytes including T cells (1, 2, 4, 5) and NK cells
(3, 6) (Table 2).
The use of the gas mixer and pump delivers continuous
perfusion of fresh medium into the culture while
maintaining a closed environment and ensuring
maximal cell growth with minimal risk of contamination.
Xuri Cell Expansion System W5 offers the following
benefits.
• Minimized risk of culture contamination and crosscontamination of samples
• Production of high cell densities
• Initial protocol optimization for a seamless transition
to commercial-scale manufacturing equipment
• Minimal cost of disposables
Table 2. Cell densities achieved using Xuri Cell Expansion
System W5
Cell type
Yield (cells/mL)
T
1.5 x 107 (5)
TIL
1.5 x 107 (2)
NK
9.8 x 106 (3)
Inflated plastic bag
forms a disposable
cultivation chamber
wave
Cell
culture
media
Inflated plastic bag
forms a disposable
cultivation chamber
Cell
culture
media
wave
Rocking
Motion
Wave action sweeps up
cells and prevents setting
wave
Fig 2. Xuri Cell Expansion System W5 is suitable for use in
clinical research.
8
Wave action
cells and pr
wave
Rocking
Motion
Fig 3. Gentle rocking of the Cellbag bioreactor ensures efficient
mixing of culture media.
Immunotherapy: Cell expansion
Xuri Cell Expansion System W25
Xuri Cell Expansion System W25 has been specifically
designed for cell therapy manufacturing applications.
To allow for easy progress from the research
environment without the need to re-validate, Xuri Cell
Expansion System W25 utilizes the same single-use
Cellbag bioreactors as the Xuri Cell Expansion System
W5. The Xuri Cell Expansion System W25 is suitable for
processing volumes from 300 mL up to 25 L using the
appropriate base tray and Cellbag bioreactor.
This functionally closed system is based on proven
wave rocking technology which provides mixing and
aeration to the culture resulting in high cell densities
whilst minimizing the risk of contamination. The Xuri
Cell Expansion System W25 is enhanced by sensors
to monitor your cell expansion and is operated via
UNICORN™ control software.
Lid
Graphical user
interface
Xuri Cell Expansion W25 Pump
Peristaltic pump
Xuri Cell Expansion System W25 Base Unit
Rocker, temperature sensors,
scale, embedded controller,
and dual hard drives
Tray
Client computer
Installed with
UNICORN software
Xuri Cell Expansion W25
Cellbag Control Unit (CBCU)
Gas flow/mix controller,
pH, and DO sensors
System setup and integration of subunits
Xuri W25 Base Unit
Xuri W25 Pump
• Acid/base flow
• Feed/harvest flow
• Media addition
• Rocking
• Weight
measurement
• Temperature
measurement
UNICORN software
•
•
•
•
Administration
System control
Method editor
Evaluation
Xuri W25 CBCU
• Gas flow/mix
• pH measurement
• DO measurement
Controller with dual hard drives
LAN
OPC
SCADA
(not included)
UNICORN
database
Firewall
UNICORN software
At home or within
enterprise network
E-mail
notifications
Fig 4. Xuri Cell Expansion System W25 overview. The System Control module on the client computer is used to start and monitor the
cultivation process. One UNICORN client can control up to three Xuri Cell Expansion System W25 instruments simultaneously. SCADA
= supervisory control and data acquisition, OPC = open platform communications, LAN = local area network.
9
Immunotherapy: Cell expansion
Xuri Cell Expansion System W25 offers the following
advantages in addition to those provided by the
Xuri Cell Expansion System W5.
• Advanced control of cell expansion through
process monitoring and remote operation with
UNICORN software.
• Suitability for use in a regulated environment with
full operational traceability and adherence of the
software to CFR part 11 and GAMP5.
• Backup storage of data in the base unit.
• Minimized hands-on time with control of up to three
systems simultaneously from a single UNICORN client.
Connection of up to 32 systems to one database (Fig 4).
• Easy to scale-out through the connectivity of multiple
systems and scale-up through the use of trays of
increasing size.
1.2 1.2
× 10×101010
Xuri Cell Expansion System W25 is intended for a
variety of cell culture applications, and in particular,
expansion of primary T-lymphocytes (Fig 5). This system
delivers reliable and accurate performance across
research, process development, and manufacturing
environments allowing the set up from a single unit to
be easily scaled-out by connecting multiple units or
scaled-up by utilizing a larger volume tray.
The environment within the Cellbag bioreactor is
controlled by the Cellbag Control Unit (CBCU) and Xuri
W25 Pump. The CBCU regulates the amount of oxygen
and nitrogen gas that flows into the culture. The Xuri W25
Pump enables perfusion of fresh medium and removal
of used medium without the need to open the system.
XuriXuri
CellCell
Expansion
Expansion
System
System
W5W5
XuriXuri
CellCell
Expansion
Expansion
System
System
W25
W25
Total cell no.
Total cell no.
1.0 1.0
× 10×101010
0.8 0.8
× 10×101010
0.6 0.6
× 10×101010
0.4 0.4
× 10×101010
0.2 0.2
× 10× 10
10
10
0 0
0 0
2 2
4 4 6 6 8 8
Days
Days
of culture
of culture
10 10 12 12
Fig 5. Total cell number of T cells obtained by culturing on
either Xuri Cell Expansion System W5 (circles) or Xuri Cell
Expansion System W25 (squares). T cells were cultured in
Cellbag bioreactor 2 L with a perfusion rate of 500 mL/24 h
(day7), 750 mL/24h (day8), 750 mL/24 h (day9).
Xuri IL-2
Xuri IL-2 is an essential growth factor for expansion
of T-lymphocytes in cell therapy manufacture. Batchspecific biological activity information helps to improve
reproducibility and removes the need for revalidation
and optimization upon setup of a new culture. A
detailed protocol to support expansion of T cells in Xuri
Cell Expansion Systems is provided. As with other Xuri
reagents, Xuri IL-2 facilitates incorporation in regulatory
submissions because it follows USP<1043> for cell therapy
ancillary material manufacturing requirements*.
Xuri IL-2 offers the following benefits:
• Reproducibility without revalidation.
• Minimized process development time.
• Improved scale-out capacity.
• Assisted inclusion in T cell expansion protocols using
Xuri Cell Expansion Systems.
• Facilitated submission to regulatory authorities through
its designation as dedicated cell therapy ancillary
material following USP <1043>* for ex vivo cultivation.
* USP <1043> ‘ancillary materials for cell, gene, and tissue-engineered products’, within the responsibilities applicable to a supplier. Other aspects
of USP <1043> will be the responsibility of the end-user to assess. GE Healthcare cannot fulfill USP <1043> in regards to application and therapyspecific aspects (e.g., use in finished therapeutic, assessment of removal from a finished therapeutic, and possibly biocompatibility, cytotoxicity, or
adventitious agent testing). 10
Stem cell therapy: Cell isolation
Making stem cell therapy a reality
Mesenchymal stromal cell isolation
The relatively easy harvesting and expansion procedures of mesenchymal stromal
cells (MSCs) together with their ability to differentiate into osteoblasts, adipocytes, and
chondroblasts under standard in vitro conditions, may make them suitable for several
autologous and allogeneic transplantation settings. Factors challenging the adoption of
MSCs for cell therapy at a commercial level are the variability in cell culture conditions,
safety, and the long term supply issue, all of which result from the inclusion of serum.
Xuri MSC products eliminate the need for serum-based components, follow USP<1043>*,
and are available with a comprehensive product documentation support file to facilitate
risk assessment and validation in cell therapy production.
Ficoll Paque PREMIUM 1.073
Ficoll-Paque PREMIUM products are sterile, ready-to-use
density centrifugation media solutions manufactured
under Quality Management System certified to ISO
13485:2003 and follow USP <1043> for adoption into cell
therapy manufacturing protocols*.
Ficoll-Paque PREMIUM 1.073 can specifically isolate
MSCs for ex vivo expansion in manufacturing of cellbased therapies.
Isolation of MSCs from bone marrow with
Ficoll-Paque PREMIUM 1.073 has yielded:
• Higher numbers of MSC clonogenic precursors than
upon isolation with Ficoll-Paque PREMIUM 1.077.
• High-performing MSC, which exhibit high expression
of the key MSC markers.
• MSC which can differentiate into multiple
mesenchymal lineages.
Days to reach P4
• Reduced ex vivo expansion time for optimized
cell-based clinical applications compared to
Ficoll-Paque PREMIUM 1.077.
Fig 6. Flow cytometry analysis of MSC obtained at P4.
Representative FACS plot phenotype of MSC from the 1.073
group, analyzed with a multicolor antibody panel
40
39
38
37
36
35
34
32
31
30
29
1.077
1.073
P=0.03
Fig 7. Comparison of MSC growth kinetics after isolation with
Ficoll-Paque PREMIUM (1.077 g/ml) and Ficoll-Paque PREMIUM
1.073. Time required for MSC to reach P4 when isolated with
Ficoll-Paque PREMIUM 1.073 or 1.077.
* USP <1043> ‘ancillary materials for cell, gene, and tissue-engineered products’, within the responsibilities applicable to a supplier. Other aspects
of USP <1043> will be the responsibility of the end-user to assess. GE Healthcare cannot fulfill USP <1043> in regards to application and therapyspecific aspects (e.g., use in finished therapeutic, assessment of removal from a finished therapeutic, and possibly biocompatibility, cytotoxicity, or
adventitious agent testing).
11
Stem cell therapy: Cell expansion
Mesenchymal stromal cell expansion
Xuri MSC Medium Serum-free/Xeno-free
Xuri MSC Medium Serum-free/Xeno-free has been
developed to ensure sustainability of MSC cultures when
reaching higher volumes and broader applicability in
cell therapy. It enables safe and efficient expansion
of MSCs after isolation from different tissue origins
(including bone marrow, adipose tissue, and umbilical
cord) without the use of animal-derived components or
undefined serum (Fig 8).
Xuri MSC Medium Serum-free/Xeno-free is intended for
use with Xuri MSC Attachment Solution for the expansion
of cells to the high numbers required for therapeutic doses,
without the high variability of conventional medium systems.
Xuri MSC Medium: 5 days
Xuri MSC Medium Serum-free/Xeno-free offers the
following benefits.
• Reliable, fast, and efficient cell expansion.
• Reproducibile cell culture conditions with consistent
performance across batches.
• Expansion of hMSC from different tissue sources.
• Facilitated submission to regulatory authorities with
comprehensive product documentation support file
and adherence to supplier related responsibilities of
USP<1043>*
• Easy set up with clear instructions for use and helpful
advice on scaling up
αMEM + 10% FBS: 7 days
Xuri MSC Attachment Solution
Xuri MSC Attachment Solution facilitates the adherence
of hMSCs cultivated under serum-free conditions, and
improves culture reproducibility. It is designed and
validated for use with Xuri MSC Medium Serum-free/Xenofree and provides support in regards of USP <1043> for
cell therapy ancilliary products*. Cultivation of MSC with
other attachment reagents is possible but may lead to
high variability and is not recommended.
Fig 8. Comparison of cell yields. Representative images of cells
at the end of P3 showing how culture in Xuri MSC Medium provides
healthy looking cells aligning to each other and at higher
density. Cells were from the same donor but cultured in (a) Xuri
MSC medium, or (b) serum-supplemented basal medium (αMEM).
Table 3. Characterization of bone marrow-derived hMSCs cultured in Xuri MSC medium.
P(3)
Positive marker
CD90-APC
P(6)
Mean (standard deviation)
>95%
99.85% (0.05%)
99.68% (0.08%)
CD73-PE
>95%
99.93% (0.09%)
99.97% (0.05%)
CD105-PerCP
>95%
99.01% (0.33%)
97.71% (0.95%)
<2%
0.26% (0.09%)
0.29% (0.05%)
Negative marker
CD45-FITC
CD34-FITC
<2%
0.04% (0.02%)
0.09% (0.05%)
CD14-FITC
<2%
1.47% (0.27%)
0.88% (0.25%)
CD19-FITC
<2%
0.02% (0.01%)
0.02%(0.01%)
HLA-FITC
<2%
0.02% (0.01%)
0.03% (0.02%)
Note: Data show the mean from cultures using three different batches of Xuri MSC Medium and two different batches of
Xuri MSC Attachment Solution.
* USP <1043> ‘ancillary materials for cell, gene, and tissue-engineered products’, within the responsibilities applicable to a
supplier. Other aspects of USP <1043> will be the responsibility of the end-user to assess. GE Healthcare cannot fulfill USP
<1043> in regards to application and therapy-specific aspects (e.g., use in finished therapeutic, assessment of removal
from a finished therapeutic, and possibly biocompatibility, cytotoxicity, or adventitious agent testing). 12
Cell therapy: Scale-up
Large scale-up biomanufacturing
Our Xcellerex™ portfolio provides innovative
biomanufacturing products and solutions
that transform the speed and economics
of producing quality therapeutic proteins
including biosimilars and vaccines. These
platforms can be applied to large-scale cell
therapy manufacturing.
Our Xcellerex range includes XDR stirred-tank
bioreactors, XDM Quad and XDUO Quad SingleUse Mixing systems, and related single-use
assemblies. Xcellerex products are tried and
tested, and to date, more than 20 therapeutic
proteins and vaccines have been manufactured
for clinical trials using Xcellerex products.
Fig 9. Xcellerex XDR-10 Bioreactor System, single vessel sized
for the bench top and handling volumes from 4.5 to 10 L.
XDR bioreactors are designed to provide a
simple and economic option for improved
scale-up efficiency. XDR bioreactor systems
are available in six different volumes from
10 L to 2000 L and employ robust automation
for advanced process control, reproducible
performance, and comprehensive data
management. Configurations and accessories
are available to customize the system to serve
your specific needs.
Fig 10. Xcellerex XDR 50–2000 bioreactors with automation:
single-use stirred tank bioreactors for handling volumes up
to 2000 L.
13
Cell therapy: Imaging
Cell analysis
GE’s advanced technologies for imaging cells at the molecular level are opening up new
frontiers in the study of diseases like AIDS, Alzheimer’s, and breast cancer. Our super-resolution
microscopy systems and high- throughput and high-content imaging technologies are
being used to increase the understanding of disease at the molecular level to help drive the
development of more effective medicines and vaccines.
Cytell™ Cell Imaging System
IN Cell Analyzer systems
DeltaVision™ systems
Cytell is an affordable, intuitive benchtop
image cytometer that streamlines and
simplifies cell analysis to save you time
and allow you to progress your research
more rapidly. Routine cell assays, such
as cell viability and cell cycle can now be
run on Cytell, freeing up time on more
sophisticated instruments for more
complex, in-depth assays. Key to the
simplification are the on board Bioapps,
that allow you to do data analysis,
visualisation and report generation at
the touch of a button.
IN Cell Analyzer systems are designed to
deliver the throughput and performance
you need for both high-content analysis
(HCA) and high-content screening (HCS)
of fixed and live cells. IN Cell Analyzer
system hardware and software combine
to form a total solution for high-content
cellular analysis.
Combining advanced optical
engineering with the latest
technological developments in both
high-resolution and super-resolution
techniques, the DeltaVision Elite and
DeltaVision OMX™ systems offer
highly flexible microscopy platforms
supporting a wide range of cell imaging
needs including live cell imaging.
Fig 11. The Cytell Cell Imaging System is a
bench top multifunctional cell imager that
delivers routine cellular data automatically.
Fig 12. The IN Cell Analyser 2200 Imaging
System is a super-fast, sensitive, and flexible
wide-field cell imaging system for a broad
range of high-content assays.
14
Fig 13. The DeltaVision Elite is a fully
integrated and flexible high-resolution
imaging system for most imaging
applications. Systems specifications
Xuri Cell Expansion
Systems specifications
Xuri Cell Expansion System W25 specifications
Control system
UNICORN 6.3 or later version
Dimensions, W × H × D
Base Unit
Tray 10
Tray 20
Tray 50
Lid 10
Lid 20
Lid 50
Cellbag Control Unit
Pump
404 × 560 × 205 mm
475 × 430 × 60 mm
740 × 480 × 70 mm
800 × 610 × 70 mm
475 × 430 × 230 mm
740 × 480 × 245 mm
800 × 610 × 260 mm
276 × 360 × 117 mm
275 × 280 × 115 mm
Weight
Base Unit
Tray 10
Tray 20
Tray 50
Lid 10
Lid 20
Lid 50
Cellbag Control Unit
Pump
24 kg
4.5 kg
7.3 kg
9.5 kg
1.7 kg
3.3 kg
3.9 kg
4.8 kg
3.8 kg
Power supply
100 to 240 V, ~ 50 to 60 Hz
Power consumption
1500 VA
Enclosure protective class
IP 21
Gas supply
External air supply, 1.0 to 1.5 bar
External CO2 supply, 1.0 to 1.5 bar
External O2 supply, 1.0 to 1.5 bar
Normal
capacity
1.3 l/min
0.2 l/min
0.7 l/min
Operating ambient temperature range
15°C to 32°C
Operating humidity range
20% to 80% (non condensing)
Fast-fill capacity
3.5 l/min
0.5 l/min
1.7 l/min
Xuri Cell Expansion System W25 Base Unit
Rocking speed control range*
2 to 40 rpm
Rocking angle control range
2° to 12°
*
Rocking motion control range
15% to 100%
Media weight control range
0.5 to 25 kg
Scale, absolute accuracy
± 0.050 kg + 1% of load kg
Temperature sensor
Pt100 Class A
Temperature measurement range
2°C to 50°C
Temperature control range
20°C (or ambient temperature + 5°C) to 40°C
Temperature control accuracy
(incl. measurement error)
± 0.5°C
15
Systems specifications
Xuri Cell Expansion System W25 Cellbag Control Unit
Gas flow control range
0 to 1000 ml/min
Gas flow total accuracy
(process value to reference flow)
± 10 ml/min + 3% of read value
Fast-fill flow
~ 3 l/min
CO2 control range
0% to 15%
CO2 measurement accuracy
± 0.3% + 3% of read value when mixed only with air/N2
Total CO2 accuracy (process value
to reference CO2 content)
± 0.7% + 3% of read value
O2 control range
0% to 50% when mixed with N2,
21% to 50% when mixed with air
O2 measurement accuracy
± 0.6% + 1% of read value within 0% to 50% when mixed only with air/N2
Total O2 accuracy
± 1.2% + 1% of read value
pH measurement range
4.5 to 8.5
pH measurement accuracy
± 0.05 for pH 6.75 to 7.25
± 0.1 for pH 6.5 to 7.5
pH control range
6.0 to 8.0
Total pH accuracy
(process value to reference pH)
± 0.1 for pH 6.75 to 7.25
± 0.15 for pH 6.5 to 7.5
DO measurement range
0% to 250% air saturation
DO measurement accuracy
± 5% air saturation (excl. atmospheric pressure variations)
DO control range
0% to 100% air saturation
Total DO accuracy (process value
to reference DO)
± 10% air saturation (excl. atmospheric pressure variations)
Xuri Cell Expansion System W25 Pump
Pump flow-rate range
100 ml to 144 l/d
(0.07 to 100 ml/min)
Pump flow accuracy
± 0.1 ml/min + 5% of read value after calibration
Accumulated pumped-volume accuracy
± 10% of measured volume
Supported tubing dimensions
i.d. 0.5 to 4.8 mm (1/50” to 3/16“)
wall thickness: 1.6 mm (1/16”)
When cultivating in a 50 l Cellbag bioreactor at maximum working volume of 25 l, rocking speed and angle multiplied should not exceed 240 rpm
degrees. For example, if the rocking angle is set to 12 degrees, the rocking speed should not be set higher than 20 rpm.
*
16
Systems specifications
Xuri Cell Expansion System W5 general specifications
Application
Used for the expansion of human cells in suspension
Construction
Stainless steel and aluminum
Dimensions
230 × 330 × 160 mm
Dimensions with kit
489 × 330 × 200 mm
Weight
4.2 kg
Rocking rate
3 rocks/min to 40 rocks/min
Rocking angle
2° to 9°
Power
145/210 VA
Operating conditions
5ºC to 30°C with lid, 15ºC to 30°C without lid. < 95% rh non-condensing
Voltage
100–240 VAC
Includes
Cellbag holder
Xuri Cell Expansion System W5 Air Controller
Application
Used to inflate and ventilate Cellbag bioreactors with air containing a
variable CO2 concentration
Construction
Stainless steel and aluminum
Frequency range
50–60 Hz
Weight
2.7 kg (6 lb)
Width
320 mm (12.59 in)
Height
200 mm (7.9 in)
Depth
170 mm (6.69 in)
Voltage
100–120/220–240 VAC
Xuri Cell Expansion System W5 Pump
Application
Used to pump feed or remove liquid harvest from Cellbag disposable
bioreactors
Standalone or with BASE20/50EHT-L series, pH20, and WAVEPOD
Construction
Stainless steel and aluminum
Frequency range
50–60 Hz
Weight
1 kg (2.2 lb)
Width
103 mm (4 in)
Height
108 mm (4.24 in)
Depth
193 mm (7.6 in)
Voltage
100–120/220–240 VAC
17
Ordering information
Ordering information
Product
Pack size
Ficoll-Paque PREMIUM
6 × 100 mL
17-5442-02
6 × 500 mL
17-5442-03
Ficoll-Paque PREMIUM 1.084
6 × 100 mLl
17-5446-02
Ficoll-Paque PREMIUM 1.073
6 × 100 mL
17-5446-52
Percoll PLUS
1L
17-5445-01
250 mL
17-5445-02
10 µg
29-0627-89
1 mg
29-0627-90
Xuri MSC Medium Serum-free/Xeno-free
500 mL
29-0643-32
Xuri MSC Attachment Solution
1 mL
29-0624-57
Xuri Cell Expansion System W25 Base Unit
Base unit
29-0645-68
Xuri Cell Expansion System W25 Cellbag Control Unit pH
Gas flow/mix and pH
29-0646-00
Xuri IL-2
Code number
Xuri Cell Expansion System W25 Cellbag Control Unit Full Gas flow/mix, pH, and DO
29-0646-02
Xuri Cell Expansion System W25 Pump
29-0645-71
Tray 10
For up to 5 L culture
29-0652-31
Tray 20
For up to 10 L culture
29-0652-32
Tray 50
For up to 25 L culture
29-0444-74
Lid 10
To fit Tray 10
29-0652-31
Lid 20
To fit Tray 20
29-0652-35
Lid 50
To fit Tray 50
29-0652-37
Filter Heater
1 unit
29-0652-52
Bag sensor adapter, 2.5 m assembly
Fiber cable for pH and DO control
28-9841-89
UNICORN 6.3.2 Workstation Package,
software and license
29-0469-18
UNICORN 6.3 Remote license
29-0203-51
UNICORN 6.3 Dry license
29-0203-55
Cellbag 2L
1 unit
28-9378-00
Cellbag 10L
1 unit
28-9378-01
Cellbag 10L (perfusion and dissolved oxygen)
1 unit
28-9376-62
Cellbag 2L (perfusion and dissolved oxygen)
1 unit
28-9376-52
Xuri Cell Expansion System W5
1 unit
29-0368-37
Xuri Perfusion Controller
1 unit
28-9884-64
CO2MIX20
1 unit
28-9377-95
Xuri W5 Lid
1 unit
28-9376-33
Xuri W5 Filter Heater
1 unit
28-9376-32
18
References
References
1. Rapoport, A. P. et al. Rapid immune recovery and graft-versus-host disease-like engraftment
syndrome following adoptive transfer of co-stimulated autologous T cells. Clin. Cancer Res.
15(13), 4499–507 (2009).
2. Sadeghi, A. et al. Large-scale bioreactor expansion of tumor-infiltrating lymphocytes. J. of
Immunol. Methods 364 (1-2), 94–100 (2011).
3. Sutlu, T. et al. Clinical-grade, large-scale, feeder-free expansion of highly active human natural
killer cells for adoptive immunotherapy using an automated bioreactor. Cytotherapy 12(8),
1044–55 (2010).
4. Levine, B. L. Personalized cell-based medicine: activated and expanded T cells for adoptive
immunotherapy. Bioprocessing J. 6(2), 14–19 (2007).
5. Tran, C. A. et al. Manufacturing of large numbers of patient-specific T cells for adoptive
immunotherapy: an approach to improving product safety, composition, and production
capacity. J. Immunother. 30(6), 644–54 (2007).
6. Spanholtz, J. et al. Clinical-grade generation of active NK cells from cord blood hematopoietic
progenitor cells for immunotherapy using a closed-system culture process. PLoS One 6(6),
e20740 (2011).
19
www.gelifesciences.com/xuri
GE and GE monogram are trademarks of General Electric Company. Cellbag, Cytell, DeltaVision, DeltaVision OMX, Ficoll Paque, Percoll, UNICORN, Xuri, WAVE,
WAVE bioreactor, and Xcellerex are trademark of General Electric Company or one of its subsidiaries.
© 2014 General Electric Company—All rights reserved. First published Apr. 2014.
Xuri Cell Expansion System W25, Xuri Cell Expansion System W5, Ficoll-Paque, Percoll, MSC medium and IL2 products are for research use or further
manufacturing use only—not for use in therapeutic or diagnostic procedures*. They are not CE marked for in vitro diagnostic use nor are they medical devices.
Drug manufacturers and clinicians are responsible for obtaining the appropriate IND/BLA/NDA approvals for clinical applications.
Cellbag bioreactors with integrated optical sensors are sold under a sublicense from Sartorius Stedim Biotech under US patent numbers 6,673,532, 7,041,493,
and/or its foreign equivalents.
GE Healthcare UK Limited, Amersham Place, Little Chalfont, Buckinghamshire, HP7 9NA, UK
29-1078-09 AA 04/2014