Tecan Journal
Edition 1/2018
Life Sciences, Diagnostics and Partnering
A flexible lab for the future
Stem cell research offers muscular dystrophy hope
Effortless integration
Accessible automation for the novice
Pages 8-9
Pages 16-17
Pages 18-19
Pages 24-25
CEO WELCOME
Welcome Dear Reader, When it was launched in 2014, the Fluent® Automation Workstation represented a step-change in laboratory automation, offering a unique concept built around the application-specific needs of laboratories. From its inception, Fluent was designed to offer more capacity and greater speed while simplifying day-to-day activities. Looking back, we’re pleased to say that it has certainly succeeded, with major industry players such as Roche (pages 8-9) and Ambry Genetics (pages 12-13) embracing the benefits of this powerful platform. As a pioneer of laboratory automation, Tecan continues to push the boundaries with new hardware and software options to suit an ever-expanding range of applications. We will soon be launching the Fluent Gx Automation Workstation to bring the speed and capabilities of the Fluent to regulated laboratories. The platform’s Fluent Gx Assurance Software will provide full sample tracking, electronic records, multi-level user management and a host of other features and utilities to simplify clinical, GCP, GLP, GMP and QC activities. We are excited to be opening up Fluent’s advanced liquid handling capabilities to customers in these regulated environments – complementing our existing offerings for this sector – and hope they enjoy the increased speed and productivity on offer. But the story doesn’t end there. This powerful workstation has also come to the attention of diagnostic instrument manufacturers, and Tecan Partnering recently began its first project using the Fluent platform, collaborating with DiaSorin to develop a complete sample-to-result system for molecular diagnostics. Here at Tecan, we can’t wait to see what comes next. I hope you enjoy the issue, Dr David Martyr CEO
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TECAN JOURNAL 1/2018
CONTENTS
Contents 2
CEO Welcome
4 - 5 The rise of live cell assays 6 - 7 Faster, error-free sample archiving and retrieval for clinical virology
10 - 11 Integrated knowhow
8 - 9
A flexible lab for the future
10 - 11
Integrated knowhow
12 - 13
Taking a Fluent approach to genetic screening
14 - 15 Automation dispenses with time-consuming calculations and preparation
16 - 17 Stem cell research offers muscular dystrophy hope 18 - 19
Effortless integration
20 - 21 More than skin deep 22 - 23
Harnessing the power of ‘friendly’ bacteria
24 - 25 Accessible automation for the novice 16 - 17
26 - 27 Targeting the treatment of solid tumors
Stem cell research offers muscular dystrophy hope
TECAN JOURNAL 1/2018
3
CELL BIOLOGY
The rise of live cell assays Cell-based assays are a core research tool, offering an informative and cost-effective counterpart to
in vitro and animal testing. Where destructive methods involving cell lysis once predominated, live cell assays are now commonplace, with measurements collected in real time, either at a single time point (end-point assays) or repeatedly over the course of minutes, hours or even days (kinetic assays). Compare a movie to a still image, and it is easy to appreciate the added value of kinetic assays, in contrast to the more conventional end-point formats, which capture only a snapshot of the cells’ complex story. Knowing precisely when an event occurred, and how long it lasted, can add a vital dimension to the understanding of dynamic cell behaviors and responses.
Six things your cells would tell you
3) “I need some stability.”
if they could talk:
Random fluctuations in temperature,
kinetic assays, live cell experiments
1) “I can’t breathe.”
gas concentrations and humidity during
can offer more physiologically relevant
Cells depend on accurate and tightly
Environment matters Whether formatted as end-point or
and contextual information than their in vitro cousins, at a fraction of the cost of animal models. However, cell-based experiments that fail to mimic physiological conditions can be meaningless at best and, at worst, misleading. A fundamental factor for success is therefore the ability to maintain an optimal environment throughout the experiment. The importance of adequate environmental control is easy to overlook, because cells can sustain significant stress and damage without any overt changes in assay metrics. If only those cells could talk!
controlled gas and humidity levels to maintain metabolic and respiratory function. Common bicarbonate-buffered culture media require five to 10 percent CO2 to maintain pH between 7.2 and 7.4.
the course of an assay can trigger stress responses, changes in proliferation rates, and other unexpected behaviors – all without you even being aware of it. 4) “The grass is greener next door.”
It can also be advantageous to actively
Reliable and robust results depend on
regulate O2 levels to mimic physiological
consistent environmental conditions
conditions of different cell types or
from well to well, across the entire
tissues. High humidity is also essential
microplate. Variations in humidity can
to prevent evaporation, which can alter
lead to uneven evaporation across the
media salt and nutrient concentrations.
plate, a common source of confounding edge effects. Uneven temperature or
2) “It’s too hot (or too cold).” Strict temperature control is critical for cell health and homeostasis. Even a few degrees of deviation from physiological temperatures can induce heat- or cold-shock responses. Active cooling may be just
gas distribution can be disastrous for cell growth and function, leading to unacceptably large variation across replicates. 5) “Please protect me.”
as important as heating for robust
Contamination is a risk in any live cell
temperature control, particularly when
assay, particularly during experimental
the desired set point is close to ambient.
manipulations. Minimizing human intervention – for example, with automated lid lifting and reagent dispensing – can go a long way to ensuring there are no mishaps.
The Blog 4
TRENDS, NEWS, STORIES AND MUCH MORE! FROM THE EXPERTS TO YOU.
TECAN JOURNAL 1/2018
CELL BIOLOGY
6) “Look at me now!”
As automation and imaging
Monitoring even relatively basic aspects
Your cells are about to do something
technologies continue to break new
of cell health – such as proliferation,
ground, it may be tempting to believe
viability and apoptosis – can provide
the hype that cell-based assays require
significant biological insights. For
expensive high resolution imaging
results that are even more information
equipment. Without a doubt, these
rich, specific biological markers can be
systems have their place in cell biology
simultaneously monitored alongside
research but, in many cases, they
these general cell health indicators. And
are overkill. On the other hand, low
systems with a cell imaging option can
budget solutions like cell counters
extend the application range still further.
simply aren’t sophisticated enough to
Live cell analysis can open up the door
opportunity.
address complex biological questions.
to a wealth of new insights. With the
A multimode microplate reader with
latest advances in multimode kinetic
Finding the sweet spot
kinetic capabilities might just hit the
microplate readers, the possibilities for new discoveries seem almost unlimited.
Fortunately, the technology to maintain
sweet spot in such cases, handling a wide selection of in vitro and live cell
phenomenal, maybe even something that you couldn’t have predicted. To respond at the right time or capture the unexpected, careful experimental design is required to establish appropriate read intervals, timing of stimuli and reagent additions. Automation, remote control and conditional responsiveness can help ensure that you catch the window of
cell health and run long-term kinetic studies continues to improve and keep pace with evolving needs. Better environmental control – combined with kinetic capabilities, sensitive detection and high throughput automation – is
assays without a high price tag. Modular systems can also provide the flexibility to start with more basic applications, and build in additional functionality as needs evolve.
paving the way for new applications. Larger scale studies and phenotypic screens are becoming more accessible than ever before.
www.tecan.com/blog TECAN JOURNAL 1/2018
5
BIOBANKING
Faster, error-free sample archiving and retrieval for clinical virology Virology testing at a molecular
The San Raffaele Hospital is one of the
“A good example of this is HHV-6,”
level is crucial for a fast and
largest hospitals in Italy, with over 1,300
Dr Racca continued. “The frequent
beds, and is internationally recognized
reactivation of HHV-6 following
as a leading center for clinical research.
transplants has recently been associated
Its research hospital (IRCCS, Istituto di
with neurological complications and
Ricovero e Cura a Carattere Scientifico)
even organ rejection but, until this link
request retrospective analysis,
status and close affiliation with the
was made, it was not included in the
sometimes as a means of
neighboring Vita-Salute San Raffaele
viral test panel. San Raffaele Hospital
monitoring drug response or
University and science park have kept
performs a large number of transplants,
the hospital at the vanguard of
predominantly bone marrow, and
molecular medicine for almost two
although it is now tested for routinely,
decades. The hospital’s laboratory of
clinicians have asked us to look at many
microbiology, serology and virology is at
samples retrospectively to assess the
that lead to, for example, organ
the forefront of these efforts, relying on
HHV-6 status of some patients. Our
rejection. The San Raffaele
cutting-edge technologies to enable
extensive knowledge of clinical testing
Hospital in Milan has developed
routine clinical testing and research
workflows, particularly in molecular
activities to run side by side. Dr Sara
diagnostics, means that we are also
Racca, head of the clinical virology
involved in a variety of research and
department, explained: “We are part of a
clinical studies, including the
large group of hospitals – one of 18 sites
development and validation of
sensitive initial diagnosis, but its role doesn’t stop there. Clinicians frequently
identifying drug resistance, and also increasingly to understand the underlying mechanisms
an automated archiving system that allows safe and accurate collection of clinical samples, as well as easy access and retrieval when further testing is required.
The Freedom EVO streamlines post-analytical sample preparation, simplifying the biobanking workflow
Automating our laboratory procedures as much as possible minimizes the infection risk to our staff, as well as saving them time, and has really helped us to avoid errors incurred from repeated manual pipetting. across Lombardy – and we receive over
laboratory instruments and tests. An
250 potentially infectious samples each
efficient biobanking system is essential
day from a large area of Northern Italy,
for this work, enabling us to properly
including the neighboring Emilia-Romagna
manage all our clinical samples and
region. It is very important for us to
patient details.”
store our samples, because clinicians often come back and ask for further
The lab originally archived samples
tests, whether this is in relation to drug
manually, transferring plasma directly
resistance, monitoring therapy, or simply
from primary tubes to cryostorage
asking for a test that wasn’t initially
tubes. In 2014, as part of the laboratory’s
requested.”
collaboration with Abbott Molecular, a Freedom EVO® 100 platform was
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TECAN JOURNAL 1/2018
BIOBANKING
acquired to improve the efficiency of
Following semi-automated real-time
sample collection, processing and
PCR analysis, the original patient
storage – as well as to help the team
samples are transferred onto the
gain better scientific insights from
Freedom EVO workstation, where 900 µl
banked samples. Dr Roee Dvir, a clinical
aliquots of plasma are pipetted into
microbiologist in the department,
small 2D barcoded cryovials. They are
explained: “We chose the Tecan system
then stored in the laboratory’s offline
to automate our post-analytical
-80 oC freezer, which has capacity for
aliquoting and sample archiving
more than 60,000 samples. Dr Dvir
because these tasks were extremely
added: “The Freedom EVOware®
slow and time consuming, occupying
software stores all the data on our
one member of staff full-time, and there
archived samples, allowing us to trace
was a very high potential for pipetting
any sample right back to when we
or labeling errors. We needed a compact
started the biobank in 2014. The
Dr Racca concluded: “The Freedom EVO
and easy-to-use system that was
software automatically matches up the
biobanking workstation has now been in
compatible with the primary sample
barcodes of original samples with the
routine use for three years, and it’s so
tubes taken directly from our clinical
corresponding stored aliquots; we
convenient, allowing us to get on with
analyzers, and that effectively
simply input the patient’s name and
other things while it just runs unattended.
eliminated the need for staff to handle
receive information on where each
The most important thing is that it gives
potentially infectious viruses. We also
sample is stored, and the dates on which
us the option to perform additional
decided to integrate a 2D barcode
they were collected. This enables us to
repetitive liquid handling tasks in the
reader onto the platform to optimize
further investigate key dates in the
future. For example, we are currently
cataloging and retrieval of clinical
patient’s care, such as when medication
planning to automate archiving of CSF
samples, and developed a custom
was changed. We now retrieve cryovials
samples, as there are a number of add-on
software interface that allows the
from storage several times a week for
tests under development in this field, and
Freedom EVO platform to communicate
additional testing.”
the intuitive user interface makes this easy
directly with the LIMS.”
Plasma samples are stored in 2D barcoded cryovials
to achieve. Automating our laboratory procedures as much as possible minimizes the infection risk to our staff, as well as saving them time, and has really helped us to avoid errors incurred from repeated manual pipetting.”
To find out more about Tecan’s biobanking solutions, visit lifesciences.tecan.com/biobanking For more information on the San Raffaele Scientific Institute, go to www.hsr.it/research/about-us
Dr Sara Racca, head of the clinical virology department
TECAN JOURNAL 1/2018
7
DRUG DEVELOPMENT
A flexible lab for the future Automated laboratory workflows are commonplace in the pharmaceutical sector, offering increased throughput and process security throughout the drug discovery process. Most of these systems are dedicated to a specific task or assay, and have been optimized to streamline these repetitive tasks. Roche has taken a different approach for drug metabolism work, creating a centralized automation facility that is agile enough to respond to the changing demands of R&D.
As one of the world’s largest biotech
company is asking for our input on how
“In the drug disposition and safety
companies, Roche develops diagnostic
to redesign labs to encourage flexibility
department, we work closely with
tests and pharmaceutical drugs, from
and support increased collaboration. We
our modeling and clinical colleagues
initial discovery through to clinical trials
are drawing upon our past experience
to design in vivo pharmacokinetics
and commercialization. In 2014, Roche
in former companies and other Roche
studies, predict the potential drug-drug
announced a decade-long venture
labs to help us plan for the future.
interaction liabilities of a compound,
investing three billion Swiss francs in
People are spending less time in the lab
and investigate the enzymes involved
a new Basel research center, with an
than before, as automation frees us to
in the clearance of our compounds.
emphasis on improving sustainability
focus on the areas where we add most
We work across the entire spectrum of
and strengthening communication
value – analyzing data and designing
the process; there is no split between
between research staff. Dr Stephen
experiments to answer specific project
discovery and development as there is
Fowler, who heads up the automation
questions. We continually ask ourselves
in many drug metabolism departments,
team within the drug disposition and
how we can make the most of our
and we are responsible for collating the
safety department, said: “Our current
knowledge and expertise. And how our
information for new drug applications to
way of working has evolved both
familiarity and proximity to the projects
bring to the regulatory authorities.”
naturally and intentionally. Right now,
offer something that we cannot buy
in preparation for the new center, the
externally.”
“Our automated systems are centralized in a core facility with dedicated technicians to organize and program them, providing a service for all 80 researchers in the department. As most of the assays don’t require a high throughput approach, we have decided to use each instrument for multiple assays. We operate nine Tecan instruments – seven Freedom EVO® and two Fluent® instruments – and the two identical Fluent systems can each run 16 or 17 different assay scripts. Different people from the department use the instruments on a weekly or fortnightly basis, and they can book either system using an electronic calendar when a slot is available; one person can run one assay in the morning, and someone else an entirely different assay in the afternoon. Researchers are responsible for running their assays, but we help the process along by hosting the equipment and supporting them to optimize the
Two Fluent workstations are the latest additions to Roche’s core automation facility For research use only. Not for use in clinical diagnostics. 8
TECAN JOURNAL 1/2018
DRUG DEVELOPMENT
utomation frees A us to focus on the areas where we add most value – analyzing data and designing experiments to answer specific project questions. automation and gather good quality data. They don’t need to reconfigure the Tecan instruments; they simply load up the experimental protocol, import their variables, add reagents, and set it running.” Stephen continued: “The Tecan devices are well suited to running multiple different assays. We were fortunate enough to work with the Fluent during its development, and we’ve been involved throughout the planning phases of the system. Tecan has developed the software in line with some functionality we desired, and they’re very open to hearing our ideas. For example, we work with lots of different users and every so often an experiment will be set up with a reagent in the wrong place or with a misaligned plate, which disrupts the assay. We inserted a simple step into the software that brought up a screenshot of a correctly prepared assay for comparison, prior to the user pressing ‘Start’. If one in 20 assays now works where it would have failed, it’s a
Roche’s Stephen Fowler, Pascal Schenk and NaHong Qiu are ‘looking to the future of automation’ to meet the company’s changing R&D needs
worthwhile intervention. It’s great to see Tecan build on this idea, and you can now import JPEGs, videos and different
systems can be used for multiple tasks,
file formats.”
and reconfigured and reprogrammed quite easily. Tecan has provided very
“The future demands flexibility and the
good support whenever we have
ability to quickly adapt to embrace new
questions or encounter programming
opportunities – we can’t simply go out
problems, and has been willing to adapt
and buy a new instrument for every
software and hardware to suit our needs.
new assay that we need to run. If one
We’re really happy with improvements
of our assays is no longer needed, there
that Tecan has made to the software
is always another awaiting automation.
system, so much so, that we have just
We’ve been able to demonstrate that the
bought a third Fluent.”
To find out more about Tecan’s Fluent systems, visit www.tecan.com/fluent To learn more about Roche, visit www.roche.com
TECAN JOURNAL 1/2018
9
CELL BIOLOGY
Integrated knowhow Cell separation has become instrumental in many areas of medical research over the last two decades, and Miltenyi Biotec’s MACS® Technology has become the gold standard technique, having been cited in over 20,000 publications. Combining superparamagnetic microparticles conjugated to specific antibodies with proprietary columns, this technology uses strong magnetic fields to separate specific cell types, allowing retention of both labeled and unlabeled cells for downstream analysis.
Miltenyi Biotec has been helping to
approach: “Cell separation is probably
systems offering high throughput,
advance biomedical research and
the technology that we are best known
more automated cell separation. Our
cellular therapies since 1989, providing
for, but we aim to provide our customers
MultiMACS Cell Separation System is
equipment and instrumentation based
with a one-stop shop for everything to
available as a standalone instrument, but
on its core MACS Technology. Founded
do with cells – from sample preparation
the possibility of integrating it with a
and headquartered in Bergisch Gladbach
through cell separation using our MACS
liquid handling platform was considered
near Cologne, Germany, the company
Technology to analysis, as well as cell
from its inception. Prior to the
now offers solutions to cover the entire
culturing.”
development of the MultiMACS X,
cell processing workflow. Miltenyi Biotec
customers looking for a higher
provides cell biology equipment to both
Miltenyi Biotec has partnered with Tecan
throughput set-up needed to combine
academia and industry, and its
to develop a high throughput cell
our instrument with their own liquid
technology is used for fundamental
separation system, the MultiMACS™ X.
handling system. However, this is a
research, pre-diagnostics and in clinical
Lotta explained the history of the
complex undertaking, and requires a
settings. Lotta Räty, Global Product
partnership: “We started working with
large investment of time and manpower
Manager for Cell Separation Instruments
Tecan a number of years ago, when we
to ensure an optimal workflow and
at Miltenyi Biotec, outlined the company’s
first identified the market for integrated
achieve the desired biological results.”
Lotta Räty demonstrates the MultiMACS X cell separation system
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TECAN JOURNAL 1/2018
CELL BIOLOGY
Ultimately, you’re going to have far more dependable results with automation.
The MultiMACS X combines Miltenyi’s and Tecan’s expertise to offer high throughput cell separation
“Customers expect speed, high
incubation steps, the logistics of moving
entire time whereas, with the MultiMACS X,
throughput and quality results from our
labware around the workdeck, and
it takes five minutes to load, another five
systems, and so they don’t want to have
keeping track of all the samples. One
minutes to unload, and that’s it.”
to invest their time doing this
customer may want to have an additional
optimization and validation. It was
washing step, or separate several
“Another major benefit of automation is
therefore a logical next step for us to
different cell types from one sample, or
the reproducibility that can be achieved.
do this on behalf of our customers and
use a different starting material, and so
This should be a consideration when
create a fully-integrated platform. When
on. There are multiple interdependent
using any set-up, and reducing the
we set about designing the MultiMACS X,
processes, and so the challenge is to
number of hands-on steps minimizes the
we decided that combining our
establish a workflow that produces the
risk of human errors, lowering the overall
instrument with a Tecan Freedom EVO® 100
optimal final result. This is something
variability of your experiment. Ultimately,
liquid handling workstation was the best
specific to each customer, and we don’t
you’re going to have far more dependable
choice, bringing together two systems
leave their lab until they are happy with
results with automation, and partnering
that are well established in the
the system performance, which is
with Tecan has allowed us to meet the
marketplace. But it’s about more than
something that they really appreciate.”
needs of these higher throughput
simply integrating our instrument into a
applications while maintaining the quality
liquid handling system. This blend of our
“The MultiMACS X with the Multi-24
cell biology knowhow and Tecan’s liquid
Column Block allows the separation of
handling and automation expertise
up to 24 samples in parallel. This can be
enables us to offer a complete, validated
numerous different samples or, for very
solution, removing the onus of
large sample volumes, multiple aliquots
equipment assembly and workflow
of the same sample. The system takes
optimization from the customer.”
approximately 45 minutes to process
To find out more about
24 samples, including loading and
partnering with Tecan,
As well as providing a fully validated
unloading the instrument, whereas
hardware solution, Miltenyi Biotec also
processing that many samples manually
visit partnering.tecan.com
tailors the software and workflow to
could take three to five hours. But it isn’t
meet individual customers’ specific
just the total time that should be
needs. Lotta continued: “There are
considered, you also need to factor in
multiple steps to be considered in any
how much hands-on time is involved;
cell-based workflow; dispensing of
processing 24 samples manually requires
samples, reagents and buffers,
the technician to sit at the bench for the
our customers expect,” Lotta concluded.
To learn more about Miltenyi Biotec’s MultiMACS X, go to www.miltenyibiotec.com/ multimacsx
TECAN JOURNAL 1/2018
11
CLINICAL DIAGNOSTICS
Taking a Fluent approach to genetic screening ®
Clinical diagnostics company Ambry Genetics focuses on the identification of germline mutations, detecting large deletions and duplications primarily by next generation sequencing. Automation holds the key to efficient high throughput assays, ensuring optimum productivity.
Ambry Genetics, based in Aliso Viejo,
With the business growing rapidly,
capabilities of the Fluent quickly
California, specializes in genetic clinical
we recently expanded into the adjacent
became clear. As we were already using
diagnostics, offering services such as
building, known as the Ambry Superlab,
the Freedom EVO platform, we were
screening for familial cancers and exome
and this led to the acquisition of 16
also familiar with the liquid classes,
testing to identify previously undetected
Fluent Automation Workstations to
making the transition to the Fluent
mutations. In addition, the company
increase our capacity, speed and
easier. Validation of our workflow scripts
collaborates with universities and other
flexibility.”
was quicker and simpler too, as the
research groups via the AmbryShare™
systems use the same worklist file
program, sharing its large disease
Joy continued: “The Superlab was
database of aggregated anonymous
designed to be as efficient and high
formats.”
data from 11,400+ human genomes. Fast
throughput as possible, with a capacity
“Each of our systems has been tailored
and flexible liquid handling workstations
of thousands of samples per run, and
to our specific requirements, whether it
are essential in this high throughput
the flexibility to swap out different
is a large Fluent 1080 with a carousel
environment, as Director of Assay
assays and chemistries. I looked at a
and stacker, or a medium-sized, dual
Automation Joy Rae-Radecki Crandall
range of liquid handling platforms for
arm Fluent 780 platform. We
explained: “Automation is vital for our
the new facility, evaluating them for their
customized every system for an
work, and we are long-term users of
speed, capacity and flexibility – we
individual assay, with different liquid
Tecan’s liquid handling platforms, with
wanted to be able to customize the
handling arms and integrated third-party
more than 30 Freedom EVO® systems.
systems – and the outstanding
devices where necessary, and took advantage of the Multiple Channel Arm’s capability to switch pipetting heads on-the-fly, changing between 96- and 384-channel formats depending on the assay. Combined with the large deck capacity, this tripled our throughput for these assays. Fluent’s ‘teach-free’ feature also proved very useful with so many workstations to set up, and within six months we had transferred all of our current methods and completed the validation. Critically, the Fluent system’s design gives us the flexibility to easily change the deck layout. Not only does this provide built-in redundancy – switching from a layout customized for NGS to a microarray set-up is quite straightforward – it also allows new chemistries and assays coming onto the
Members of the Ambry Genetics automation team (left to right): Omar Alwatter, Chris Ramirez, Muaeen Obadi, Parker Sankey, Chris Yenzer, Emily Greene, Joy Rae-Radecki Crandall, Nina Do, Andrew Haling, Aarani Arulmoli and Sinead Hawker For research use only. Not for use in clinical diagnostics. 12
TECAN JOURNAL 1/2018
market to be explored without major time and cost implications.”
CLINICAL DIAGNOSTICS
“We are benefitting from time and cost
to include a ‘Confirm’ button on the
savings as well as the increased capacity.
opposite side of the screen to the rest of
We run numerous hit-picking scripts for
the commands. It’s a small thing, but it’s
PCRs, and a 96-well plate that previously
had a big impact. The video feature is
took around eight minutes to complete can
useful too; we can make instructional
be done in about five minutes on the Fluent,
videos showing the user how to set up
trimming at least an hour off our overall
the deck, troubleshoot a run, and
preparation time for that step. The parallel
perform infrequently used protocols,
arm movements are a great advantage,
avoiding the need for hands-on
allowing the Robotic Gripper Arm™ to
refresher training.”
dispose of a used tip box while the Multiple Channel Arm simultaneously picks up new tips, saving about 15 seconds of time, which adds up when you are running numerous plates per day. We have also been able to miniaturize some assays, changing from a 96- to a 384-well format, reducing the amount of sample and reagent used and decreasing the number of tip mounting and disposal movements from four to one. This saves
I looked at a range of liquid handling platforms for the new facility, evaluating them for their speed, capacity and flexibility… the outstanding capabilities of the Fluent quickly became clear.
time and decreases waste, providing considerable additional cost savings.” “FluentControl™, with its TouchTools™
“We write all our scripts in house, and
interface and ‘wizard-like’ guidance,
people really like using the
simplifies user management and the
FluentControl software. They find it
day-to-day operation of the systems.
logical and easy to use, and can usually
Sample security and integrity is our
start writing scripts after about a week’s
number one priority and, with more than
worth of training. There are a lot of
30 users per instrument, we rely on the
variables to set for each script, and the
To learn more about
user management feature to assign
way that they are displayed makes
Ambry Genetics, go to
individual permissions and access to
troubleshooting very easy. It’s a clear,
www.ambrygen.com
scripts. Operators can only see and run
linear thought process, which makes the
those scripts that they have been
software very powerful. Operators also
certified competent for. Automated
enjoy having the option to personalize
barcode reading enables sample tracking
scripts, changing the color of the
and eliminates the potential for human
indicator lights, and even including
error, identifying plate loading errors and
background music to indicate which
notifying the user to take corrective
step of the protocol is being performed!
action. To help avoid accidental click-
They are really engaged with the
through errors, we even have the option
system,” Joy concluded.
To find out more about Tecan’s Fluent Automation Workstation, visit www.tecan.com/fluent
TECAN JOURNAL 1/2018
13
DRUG DISCOVERY
Automation dispenses with time-consuming calculations and preparation Automation brings more than simply speed to the laboratory. Modern software is taking the headache out of serial dilution and normalization calculations, supporting assay development and delivering reliable results for international healthcare company Merck.
Merck KGaA is a global science
“My lab is currently working on a
and technology company working
number of projects in the areas of
in the healthcare, life sciences and
oncology and immuno-oncology, developing
performance materials sectors. The
assays for different targets, such as specific
company – which celebrates its 350th
protein-protein interactions and protein
anniversary in 2018 – operates in over
kinase assays. In March 2017, we
65 countries with approximately 50,000
developed an homogeneous time-
employees. This year, Merck received
resolved fluorescence (HTRF®) assay for
FDA approval for its immune checkpoint
protein-protein interaction studies, and
inhibitor, BAVENCIO® (avelumab),
we wanted to purchase an instrument to
used to treat metastatic Merkel cell
support our assay development and
carcinoma, a rare and aggressive skin
manage the large number of enzyme
cancer. Dr Nina Grossmann, a laboratory
and antibody titrations. We looked at
head within the discovery
the various dispensers on the market
pharmacology department in
before deciding on the Tecan D300e
Darmstadt, Germany, explained: “Our
Digital Dispenser. We really appreciated
department is primarily focused on
the instrument’s ability to work across
small molecule drug discovery, split
a broad volume range – from picoliters
across two sub-departments: cellular
to microliters – as there are not many
and molecular pharmacology. We
dispensers that can do this. We also
handle all kinds of biochemical assays,
use the instrument to support regular
which we miniaturize for high
compound titration testing.”
throughput screening and mode of action studies.”
The main benefits of the D300e have been the increased accuracy and time savings… we probably save ourselves one day per run.
For research use only. Not for use in clinical diagnostics. 14
TECAN JOURNAL 1/2018
DRUG DISCOVERY
Dr Nina Grossmann and lab technician Adrian Schoen with the D300e
“The main benefits of the D300e have
“We use 384-well plates for our assay
been the increased accuracy and time
development and, even though our
savings; assay development is now
technicians are very experienced with
much faster. We really appreciate the
this format, the error rate of the Tecan
reduction in preparation time, which
system is still much lower. The D300e
people often overlook. We simply set up
also helps us prepare for high
the metrics on the instrument – such as
throughput screening using 1,536-well
the titrations we want to carry out – and
plates – which we simply could not
the system does the rest, calculating
pipette by hand – saving us valuable
everything, including the normalization.
reagents.”
To find out more about Tecan’s D300e Digital Dispenser, visit www.tecan.com/D300e To learn more about Merck, go to www.merckgroup.com
If we were to do this by hand, we would have to create different stock solutions
“Whenever we have contacted Tecan
of the buffers, and we simply don’t have
support with questions, we get the
to do this anymore. Preparing a plate
answers we need quickly. For example,
only takes about half an hour on the
we’ve had some queries about using
D300e whereas, previously, doing the
the software and about which
calculations and pipetting by hand took
detergents were most suitable for use
a long time. We also had to use a series
with the digital dispenser. We also had
of titrations to narrow down the
a concern that using automation may
concentration range for further
damage or destroy the protein in some
investigation. The D300e allows us to
way, but we are currently using the
carry out these multiple steps in one
D300e in five different projects and
experiment, and we probably save
have not encountered any problems,”
ourselves one day per run. In addition,
Nina concluded.
the error rate is now much smaller, and the data is more reliable.”
TECAN JOURNAL 1/2018
15
DRUG DEVELOPMENT
Stem cell research offers muscular dystrophy hope Access to human pluripotent embryonic stem cells is enabling Genea Biocells to pioneer novel therapies to treat a number of neuromuscular diseases. Drawing on almost 30 years of research heritage, the company is using its expertise to model spinal muscular atrophy and facioscapulohumeral muscular dystrophy to identify potential therapies.
Cullen Pivaroff and Charles Martin with the Fluent Automation Workstation
Genea Biocells was established in 2017 as
with over 150 cell lines representing more
Genea is primarily focused on two
an independent company born out of the
than 30 diseases.”
conditions; spinal muscular atrophy
R&D arm of Genea Fertility – a world-leading
(SMA) and facioscapulohumeral
IVF clinic in Australia. The team
Monica continued: “We are in our early
muscular dystrophy (FSHD). SMA affects
of 20 scientists based in San Diego,
days as a drug discovery company, and
one in 10,000 people, with a carrier
California, specializes in drug discovery
have three main facets to our
frequency of one in 40 in the general
and therapy development to treat
organization. Firstly, we supply stem cells
population. FSHD is another of the most
neuromuscular diseases. Monica Hayhurst
and media reagents to strategic academic
common muscular dystrophies –
Bennett, director of preclinical research at
partners. We also carry out CRO work in
affecting one in 20,000 – and causes
Genea Biocells, explained: “In the early
collaboration with pharma companies
progressive loss of muscle strength.
days, the IVF clinic made a concerted
that want to focus on muscular
Genea has used its expertise to develop
effort to collect pluripotent embryonic
dystrophies we are not actively pursuing
the world’s first human stem cell model
stem cells that were excluded as part of
ourselves, such as Duchenne. Finally, we
of FSHD, and is using this platform to
preimplantation genetic screening.
have our scalable discovery platform that
search for therapeutic drug candidates.
Patients were asked if they wanted to
differentiates skeletal muscle cells from
“SMA and FSHD are monogenic diseases,
donate these cells for research and, over
human pluripotent stem cells and
which makes them good candidates for
time, we’ve created one of the world’s
supports our in-house assay
screening,” Monica added. “This has
largest and most varied private banks,
development.”
resulted in an abundance of stems cells
For research use only. Not for use in clinical diagnostics. 16
TECAN JOURNAL 1/2018
DRUG DEVELOPMENT
to work with, and has naturally focused
contamination issues. For cell-based
Cullen Pivaroff, a scientist at Genea
our research efforts. We primarily
assays, we manually create the cell
Biocells, added: “I’m fairly new to
concentrate on generating phenotypic
suspension, then the Fluent transfers this
laboratory automation and I have
assays for screening, elucidating
to either 96- or 384-well culture plates. All
discovered that, in addition to eliminating
different metabolic pathways in cells and
downstream manipulations are scheduled
manual work and improving the accuracy,
understanding pretranslational gene
through FluentControl™, from basic media
there are things the system can do that
expression. Once the team has
changes to more complex liquid handling
I simply can’t do manually. I have a
consolidated an assay, it can be passed
procedures involving the dilution of stock
background in cell culture and handling
on to the automation team.”
compounds to biologically relevant
fragile cell types, but the Fluent is so much
concentrations. In addition, we use the
gentler than working by hand; it’s a
Charles Martin, an automation scientist,
system for non-sterile applications,
well-configured and well-built system.”
continued: “Our Fluent® Automation
including immunocytochemistry for high
Workstation is central to everything that
content phenotypic analysis. We process
Charles continued: “There are so many
we do; it’s our workhorse system and is an
around 1,000 compounds – taken from
diverse applications for the Fluent, and
essential part of the screening process,
our small to medium-sized library – per
Tecan really values its working relationships
carrying out all the liquid handling and
screen, and the 384-channel pipetting
with people who are using the system.
supporting our analyzers and imaging
arm is very practical for this work; it’s
I recently went to a users’ round table
platforms. The Fluent system is equipped
obviously faster than an eight-channel
meeting, and it was great to see the
with a Multiple Channel Arm, an
option. I worked with a Freedom EVO®
Tecan engineers and software developers
integrated incubator and a laminar flow
platform in a previous job, so there wasn’t
responding to our suggestions. They
HEPA hood to run our cell-based assays.
a huge learning curve moving to the
seemed really keen to hear our feedback,
The HEPA hood creates a sterile, positive
Fluent, as there are enough similarities
and I’m sure a number of the ideas
pressure environment inside the
between Freedom EVOware® and
discussed will make it into future software
enclosure, and so we have very few
FluentControl.”
updates; they are always looking for ways to keep developing the platform.”
There are things the system can do that I simply can’t do manually.
To find out more about Tecan’s drug discovery solutions, visit www.tecan.com/drugdiscovery To learn more about Genea Biocells, go to www.geneabiocells.com
TECAN JOURNAL 1/2018
17
BIOPROCESSING
Effortless integration Microbioreactors are a convenient research tool, enabling cost-effective screening of a variety of fermentation parameters prior to scale-up and manufacturing of biological products. m2p-labs’ proprietary bioreactor technology offers automated, parallel monitoring of multiple micro-fermentations, and has been proven in applications such as clone screening, media optimization and synthetic biology.
m2p-labs, formed at the end of 2005 as a
extremely important for microbial
“We began the RoboLector project in
spin-off from RWTH Aachen University, is
applications. Most pertinent data for
2009,” commented Sebastian Blum,
a leading international supplier of
fermentations is, in some way, connected
European Sales Director. “We started by
microbioreactor systems for fermentation,
to biomass, and the BioLector offers the
speaking to customers, to get an idea of
screening and bioprocess development.
capacity to do this non-invasively.”
what they wanted from a fully automated
Octavia Deufel, Marketing and
system. We already knew that we wanted
Communications Manager at m2p-labs,
Product Manager Sebastian Hofzumahaus
to go from batch fermentations to
explained: “Our products are mainly used
added: “We have since expanded the range
fed-batch fermentations, as well as
for R&D applications, particularly in the
with a number of additional features and
offering automatic sampling and
chemical, biotechnology and
options, but all of our systems are capable
adjustments, but it became clear that
pharmaceutical sectors. We also have a
of doing 48-well plate fermentation –
users want a very flexible system capable
number of customers in the cosmetics
effectively 48 parallel microbioreactors
of fitting seamlessly into their workflows.
industry and, of course, we supply
– and measuring these key fermentation
We therefore looked for an OEM robotics
equipment to a lot of academic labs. Our
parameters. The difference between the
original benchtop system – the BioLector®
supplier that could provide a modular
models is the level of automation they
I – was designed to allow high throughput
liquid handling option that would be easy
provide. The RoboLector® is therefore
micro-fermentation experiments, with
to integrate with our BioLector systems.
the natural extension of the BioLector
real-time monitoring of important
The Xantus® was the only solution on the
range, enabling full bioprocess control –
parameters, such as biomass, pH value,
making pH adjustments, adding inducers
market with the level of flexibility we
oxygen saturation and fluorescence. The
and feed solutions, etc. – based on the
ability to optically measure biomass is
real-time data or a pre-programmed
unique to our reactors, and this is
schedule, or a combination of both.”
The RoboLector enables full bioprocess control For research use only. Not for use in clinical diagnostics. 18
TECAN JOURNAL 1/2018
wanted to offer to end users – it was a perfect fit.”
BIOPROCESSING
sers want a very U flexible system capable of fitting seamlessly into their workflows. A variety of labware formats can be accommodated
The development of the RoboLector
by ourselves. We have a really good
had recently purchased a RoboLector
proceeded quickly. In just nine months,
relationship with the Tecan team
platform, and we were able to work
m2p-labs moved from initial planning to
as well and, if we encounter a new
together with them to develop this
shipping the first systems to customers.
problem that we don’t really know
option in just a few weeks. It’s a
Sebastian Hofzumahaus described the
how to solve immediately, we can
testament to the flexibility of the Xantus
process: “Most of the Xantus hardware
always get really quick and very solid
robot that we were able to so easily
could be used off-the-shelf, but we
support from Tecan’s personnel and
integrate this new module into our
required a number of small
the expert helpline.”
existing automated platform,” Sebastian
modifications to simplify integration,
Blum concluded.
such as an extended X-axis to enable full
“We are continually honing our software
access to the BioLector system. These
and modules to meet our customers’
adjustments were undertaken quickly
evolving needs. This year, for example,
and efficiently, and we are now able to
we have developed a new pre-culture
To find out more partnering with
offer customers a choice of three
module for the RoboLector. This allows
Tecan, visit partnering.tecan.com
options depending on their throughput.
us to reliably induce all 48 fermentations
The basic model has two pipetting
with the same quantity of cells, further
To learn more about m2p-labs
channels, one with a washable fixed tip,
reducing hands-on time and greatly
and the RoboLector, go to
and the other using disposable tips. We
increasing reproducibility. This module
then offer a four-channel version – again
www.m2p-labs.com
was suggested to us by a customer who
with a single channel using disposable tips – and an eight-channel model, using two channels with disposables tips for maximum throughput.” “The software programming was done almost entirely by us in house, with a little bit of help and support from the Sias software development team,” Sebastian continued. “An important consideration, which influenced our initial decision to choose the Xantus, was the availability of a number of standard software drivers and interfaces. This was a huge benefit, and the support we received during development was great. A number of our service technicians and application specialists have also been on Tecan’s training courses, allowing us to take on most customer service and technical support The RoboLector integrates a number of modules for true walkaway operation
TECAN JOURNAL 1/2018
19
CELL BIOLOGY
More than skin deep LMSM studies the effects of changing environmental parameters on the physiology of bacteria, and has recently began using this expertise to help the cosmetics industry. Many of these investigations involve absorbance-, luminescence- and fluorescence-based assays, requiring strict control of the temperature inside the microplate measurement chamber for reliable results.
The Laboratory of Microbiology Signals
fluorescence in this format but, equally
and Microenvironments (Laboratoire
importantly, we wanted to be able to
de Microbiologie Signaux et
precisely regulate the temperature
Microenvironnement, LMSM) is part
within the measurement chamber.
of the University of Rouen, France.
The Spark reader’s integrated Te-Cool™
First established in 1986, this specialist
module gives us complete control of
microbiology laboratory is home to
the temperature in the measurement
a team of university professors and
chamber, enabling us to perform
assistant professors, engineers, technicians and students engaged in projects investigating how microbiota interact with their environment. LMSM focuses on three particular research areas – sensor systems and transducers, communication in human microbiota, and communication in plant microbiota – and works with a wide range of industrial partners, predominantly in the cosmetics and pharmaceutical industries. Assistant Professor Emeline Bouffartigues explained: “We use a variety of different approaches – including molecular and
microbiological studies within the reader. It also opens the door to new FRET-based applications, and will allow us to broaden our skills in interatomic characterization of protein-protein interactions. Choosing the Spark reader also futureproofs the laboratory to some extent, giving us the capabilities to perform, for example, time-resolved fluorescence and luciferase assays if we have a need to use these assay formats.” Emeline continued: “We have been using the Spark for about six months now, and are pleased with its performance.
biochemical assays and cell cultures –
It offers everything we need in one
to carry out research into the physiology
instrument and has proved efficient
of bacteria in both human and plant
and reliable; our results have been very
hosts, looking at how micro-organisms
reproducible. One of the main uses
adapt to the environment. Many of our
of our Spark reader is for the study of
assays are carried out in a microplate
membrane fluidity in bacteria, which
format to increase throughput and save
employs a fluorescent diphenylhexatriene
reagents, and so we recently invested
(DPH) probe. The Te-Cool module is
in a Spark® multimode reader to assist
invaluable for these experiments, as
with this work.”
membrane fluidity is affected by temperature. Strict control of the
“We needed a reader that could
temperature in the measurement
accurately and reproducibly measure
chamber is therefore essential for
absorbance, luminescence and
reliable and reproducible results,
For research use only. Not for use in clinical diagnostics. 20
TECAN JOURNAL 1/2018
CELL BIOLOGY
Left to right: Ali Tahrioui, Emeline Bouffartigues and Olivier Maillot with LMSM’s Spark readers
and the Spark has made a big difference to our work. It enables us to obtain physiological measurements to help answer important questions about membrane fluidity, complementing the available genetic information.” “We routinely monitor bacterial growth
The Spark reader’s integrated Te-Cool module gives us complete control of the temperature in the measurement chamber.
under different conditions while simultaneously following the expression of reporter genes. Again, the Spark and Te-Cool combination make these studies, which are also affected by
Senior Microbiology Technician
temperature, a lot easier to perform.
Olivier Maillot concluded: “We carefully
The user interface is quite intuitive too,
evaluated the Spark before purchase,
which is a real advantage for us, as a lot
to ensure that it would meet our needs,
of students use the system. They find
and it has exceeded our expectations
To find out more about Tecan’s
the reader easy to use and can work
and helped us to achieve a lot of success
cell biology solutions, visit
independently without the need for
in our investigations. Tecan’s customer
www.tecan.com/cellbiology
in-depth training. Another benefit is for
services are very responsive if we have
fluorescence anisotropy studies, where
any questions, and we have found the
To learn more about LMSM, go to
the Spark allows us to export raw data
Spark so useful that we have just bought
and perform the calculations ourselves.”
a second instrument for the laboratory.”
www.lmsm-lab.fr
TECAN JOURNAL 1/2018
21
FOOD SCIENCES
Harnessing the power of ‘friendly’ bacteria The rising global problem of antimicrobial resistance has led to growing pressure on food producers to eliminate the use of prophylactic antibiotics as an additive in livestock feeds. To help combat the potential risk this poses to animal health, Agro BioSciences is harnessing the power of the microbiota present in the gut of chickens, pigs and cows to try and eliminate the growth of pathogens.
All multicellular organisms – plants and
subsidiary of Arm & Hammer Animal
of livestock microbiota. This ‘Microbial
animals alike – are host to a variety
Nutrition – is harnessing the power of
Terroir™’ affects animals’ health in a
of bacteria, fungi and other microbial
the microbiota to enhance the health
variety of ways, including their growth
organisms. This ‘microbiota’ is essential
and production of livestock. Josh
rates and resistance to pathogens, and
to their survival, and can have a
Rehberger, Molecular Biologist at Agro
so we are adding probiotic bacteria to
significant effect on the health and
BioSciences, explained: “The local
feedstuffs in order to enhance these
taste of plants and animals destined for
environment around livestock can have
beneficial aspects of the microbiota.
the food chain. Agro BioSciences – a
a significant impact on the composition
The current push to eliminate the use of
Left to right: Evan Hutchison, Jesse Thompson, Josh Rehberger and Justin Sawall with Agro BioSciences Fluent platforms For research use only. Not for use in clinical diagnostics. 22
TECAN JOURNAL 1/2018
FOOD SCIENCES
growth-promoting antibiotics in poultry
such a major consideration, we
“A specialist from SciRobotics initially
production in the USA means that one
eventually chose the greater on-deck
helped us to develop the picking
area that we are particularly focusing on
capacity and speed offered by the
profiles during installation, and we
is the ability of the microbiota to help
Fluent® Automation Workstation. The
have since developed these further
reduce pathogen loads in these animals.”
SciRobotics modules hadn’t yet been
ourselves, resulting in huge time savings.
integrated into this system, but it was
The relationship between Tecan and
“One of the key features of our approach
a very smooth process, as I think the
SciRobotics is very beneficial from a
is that the nutritional supplements are
SciRobotics team had already done a
customer’s perspective, ensuring that
specific to each Microbial Terroir, which
lot of the background work.”
we can always get the answers to any queries we have,” Josh concluded.
means that we receive a lot of samples from farms across the country. These
“We now have two Fluent workstations
can be intestinal samples for poultry
in the lab: one equipped with a
but, due to the economic value of the
PetriPlater spiral plater and a high
animals, are more commonly fecal swabs or rumen samples for cattle, and a mix of fecal and intestinal samples for pigs. On average, we receive around 100 samples a day for poultry, and 60 each for cows and pigs. Each sample then needs to be plated on a number of different media –
What really set Tecan apart was the ability to perform automated plating as part of a liquid handling workstation.
usually around three per sample – ready for colony picking and downstream applications. This quickly adds up to
capacity PetriSel™ carousel – as well as two
somewhere in the region of 2,000 colonies
KingFisher™ Presto Purification Systems
To find out more on Tecan’s food
a week that need isolating, so in 2016 we
(Thermo Fisher) – and the other with a
sciences solutions, visit
looked for an automated solution that
Pickolo colony-picker. Both instruments
www.tecan.com/food
would perform the plating, colony picking
are capable of performing fully automated
and some of the downstream sample
plating, freeing up staff, then the plates
To learn more about Agro
preparation steps, allowing laboratory
are moved to an offline incubator to grow
staff to perform other activities.”
overnight. The plates are then loaded onto
BioSciences, go to
the platform equipped with the Pickolo “We looked at the various options on
for automated colony counting and picking.
offer, and what really set Tecan apart was
This system can count and transfer the
the ability to perform automated plating
colonies to 96-well plates far faster than we
as part of a liquid handling workstation;
could achieve by hand, and it’s more accurate
nobody else seemed to be offering that
too, eliminating some of the ‘guesswork’
capability at the time. We were initially
associated with the process. Plates are then
interested in Freedom EVO® platforms, as
split, with one portion archived in our offline
the SciRobotics modules – the PetriPlater™
freezers, and the system with the integrated
and Pickolo™ – were already integrated
KingFisher™ Prestos performs automated
into this system but, as throughput was
DNA isolation on the other.”
www.agro-biosciences.com
TECAN JOURNAL 1/2018
23
CHROMATOGRAPHY
Accessible automation for the novice High throughput bioprocess development is essential for optimizing run parameters prior to scale-up. University College London’s Advanced Centre for Biochemical Engineering is harnessing the possibilities afforded by automation, using custom-built scripts and programs to make its liquid handling platforms accessible to inexperienced users. University College London’s
“A key step in many of our processes
previously run this type of experiment
interdisciplinary Advanced Centre for
is the development of effective
with the RoboColumns, and identified
Biochemical Engineering (ACBE) is a
separations of the biomolecules
early on that users would need intensive
world leader in the development of novel
of interest from other matrix and
training on the instrument to make the
bioprocesses and, in 2013, was awarded
cellular components, and we use*
most of its capabilities. The RoboColumn
a Queen’s Anniversary Prize for Higher
OPUS® RoboColumns® (Repligen) in
experiments are not simple to automate,
and Further Education in recognition of
combination with a Freedom EVO 200
as there is so much movement of labware
its ‘outstanding excellence’. Automation
to support these studies. This approach
and numerous aspirations from different
is at the very heart of its success, and
is highly regarded in both industrial
locations; everything needs to be
the department uses six Freedom EVO®
and academic environments, allowing
coordinated. Working competently with
platforms to accelerate its research. Dr
eight columns to be run in parallel
robotics often requires programming
Spyridon Konstantinidis, a postdoctoral
using the platform’s eight-channel
skills and, as the person with the most
research associate, explained: “We
Liquid Handling Arm™. This enables us
experience in this in the lab, I was having
apply quality by design to bioprocess
to collect more than 70 fractions per
to spend quite a lot of time helping
development, using high throughput
column in 96-well microplates over an
casual users and overseeing their
automation to screen out unfavorable
eight hour run, followed by analysis
programming. We therefore needed to
conditions and determine the ‘sweet
using an Infinite® M200 PRO multimode
find a way to make the automation easily
spot’ for each process through efficient
reader for absorbance and fluorescence
accessible to non-experts. The solution lay
and effective experimentation. This
measurements.”
in developing a custom Freedom EVOware® script to guide end-user inputs, deploy
maximizes the amount of knowledge we have about a process in early
“We purchased the Freedom EVO
compiled applications, generate
development stages, simplifying further
workstation to run these studies in
worklists, and execute common and
downstream activities and scale-up.”
2015,” Spyridon continued. “We had not
advanced commands.” “This ‘scaffolding’ script takes the user though everything step-by-step. The script is divided into five parts, and the first phase asks the user to define the inputs and prepare the system. Custom screens guide the users through the available options, such as the number of columns, fraction size, etc. The software also guides them through preparing the system – putting the columns on the platform, loading solutions, etc. – and this whole process takes approximately 30 minutes. After this initial input phase – which takes only five to 10 minutes – calculations are performed automatically, and worklists are generated. The process does not require any end-user intervention after this point, as the remaining stages –
Spyridon Konstantinidis, postdoctoral research associate at the ACBE *For research use only. Not for use in clinical diagnostics. 24
TECAN JOURNAL 1/2018
CHROMATOGRAPHY
Freedom EVOware allows us to create these custom scripts and access advanced commands to unlock the potential of the system – it’s a very powerful tool.
The platform’s LiHa Arm can process eight RoboColumns in parallel
chromatography, fraction collection,
“Freedom EVOware allows us to
users, and we’ve benefitted from these
measurement and volume determination
create these custom scripts and
sessions; bouncing ideas off them and
of fractions and blanks, and results
access advanced commands to unlock
seeking their advice when it comes to
processing and reporting – are fully
the potential of the system – it’s a
implementing certain commands or
automated.”
very powerful tool. With most other
functions. The driving force behind our
platforms, you never even get to see
custom script was making automation
“There are a total of 165 inputs to manage,
this software architecture, and so the
more readily available, and we now
due to the high levels of flexibility that
options are limited. But Tecan’s software
have seven students who have used the
we need. However, the beauty of this
gives developers these tools and allows
platform unsupervised to complete their
method is that we can carry out many
them to innovate. As a result, we’ve been
investigations – it’s been a real success.”
different separations using one deck
able to generate a lot of commands
configuration, and so a majority of these
with our own custom programs; it’s a
inputs are classed as ‘defaults’, avoiding
massive step forward for our work and
any alterations to the script. One of the
enables the platforms to carry out very
benefits of developing our own script is
sophisticated actions.”
that we can also program the platform to perform separations in parallel with
“The support from Tecan has also
different durations, and this additional
been helpful. Every January, Tecan
functionality is a real bonus.”
runs a training course for first-time
To find out more about Tecan’s liquid handling solutions, visit www.tecan.com/ parallelchromatography To learn more about ACBE’s work, go to www.ucl.ac.uk/ biochemeng/research
TECAN JOURNAL 1/2018
25
BIOTECHNOLOGY
Targeting the treatment of solid tumors Tessa Therapeutics has developed a virus-specific T cell therapy for the treatment of solid tumors, which has shown promising results in early trials. Stringent quality control, including time-resolved fluorescence cytotoxicity assays performed on a multimode reader, is essential for this work.
S park offers the best of both worlds, combining the sensitivity of filters with the flexibility of monochromators in one reader.
Singapore-based Tessa Therapeutics
advanced nasopharyngeal carcinoma
is a clinical stage biopharmaceutical
therapy, which is currently undergoing
company aiming to revolutionize cancer
an international multi-center Phase III
treatment by redirecting the body’s
trial. In addition, we are conducting
anti-viral immune response to recognize
a Phase I trial of therapies for HPV-
and kill malignant cells. The company
associated malignancies – cervical and
is working with a growing network of
oropharyngeal cancers – and hope to
commercial and academic partners –
start Phase II trials soon.”
including the Baylor College of Medicine, the Parker Institute for Cancer
Working with partners across the globe
Immunotherapy, and the National
means that Tessa has had to build robust
Cancer Centre Singapore – to jointly
operational, quality control and supply
advance cancer immunotherapy
chain capabilities to allow it to
research and develop a portfolio of
successfully deliver VST therapies to
virus-specific T cell (VST) combination
a large patient pool internationally.
therapies to address a wide range of tumors.
Ruijuan continued: “Before any of our products enter a clinical trial they must
Unlike many other cell therapies, Tessa’s
undergo stringent QC testing. As part of
proprietary VSTs have the ability to
this process, we perform time-resolved
infiltrate and survive within solid tumors.
fluorescence cytotoxicity assays to
This allows them to migrate to the tumor
determine the cell-killing efficiency of
site and kill malignant cells with minimal
the VSTs prior to batch release of the
side effects. These VSTs can also
product for clinical trials. About two
self-renew, re-activate and expand when
years ago, we decided to upgrade our
encountering a virus-associated cancer
old fluorescence microplate reader to a
antigen, leading to a sustained and
multimode instrument, and looked at the
durable anti-tumor response in patients.
various systems available on the market.
This approach has already shown
We chose the Spark® for a number of
exciting results in the treatment of
reasons, including previous positive
advanced nasopharyngeal carcinoma,
experience of Tecan readers,
leading to the world’s largest Phase III
competitive pricing and the company’s
trial of a T cell immunotherapy for any
reputation in the field. Sensitivity was
cancer indication. Ruijuan Du, head of
another important consideration; Spark
quality control at Tessa Therapeutics,
offers the best of both worlds,
explained: “The company is involved
combining the sensitivity of filters with
in all stages of immunotherapy
the flexibility of monochromators in one
development, from fundamental
reader. We use the filter-based optics for
research to the coordination of late
our cytotoxicity assay because it offers
stage, multi-center clinical trials.
extra sensitivity, but we also have the
We are already dedicating resources to
option to use monochromators if we
planning scale-up and commercialization
need to.”
strategies, most notably for our
For research use only. Not for use in clinical diagnostics. 26
TECAN JOURNAL 1/2018
BIOTECHNOLOGY
Tessa Therapeutics is researching the use of its proprietary VSTs for a wide range of solid tumor indications
“We are really pleased with our Spark
“We work closely with specialists from
reader, and use it several times a week
our local distributor, SciMed, who provide
for QC batch testing. It allows us to
after-sales services, training and support
rapidly and accurately acquire specific
for our Spark reader. This includes
fluorescence read-outs, and is easy
preventive maintenance and periodic QC
to use, accurate and reliable. The
checks using Tecan’s MultiCheck™ plate
SparkControl™ dashboard is very user
and software – which has a useful
friendly, with straightforward, icon-driven
Pass/Fail feature – to quickly and easily
operation; we can store our methods on
check that the reader is operating on the
the instrument and then start a run with
basis of the determined parameters with
the click of a button. Operators need
defined limits. The company’s engineers
hardly any training, which is ideal, and
also help with troubleshooting if
the assay reproducibility from week to
necessary, and work flexibly to meet our
week is excellent.”
needs. It’s good to have local support to
To find out more about the Spark reader’s capabilities, visit www.tecan.com/spark-fluorescence To learn more about Tessa Therapeutics, go to www.tessatherapeutics.com
rely on,” Ruijuan concluded.
TECAN JOURNAL 1/2018
27
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