Tecan Journal
Edition 2/2016
Life Sciences, Diagnostics and Partnering
Detecting tumor ‘castaways’ could revolutionize cancer diagnosis
Seeing more clearly
A more powerful approach to biomarker discovery
HMGB1 – a silent partner in cancer?
Pages 4-5
Pages 8-9
Pages 18-19
Pages 30-31
CEO WELCOME
Welcome Dear Reader, The launch of this issue coincides with the 2016 AACC Clinical Lab Expo. This annual event gives us the chance to showcase the breadth and depth of our solutions – from standalone devices for end users to the development and support of OEM solutions through Tecan Partnering. It also provides an opportunity to demonstrate one of our key strengths at Tecan – the capacity to support customers as they move from research to clinical applications. Our unrivalled ability to bridge the gap between these markets stems from our close ties with the life sciences research communities. Tecan solutions are empowering our customers’ research every day, and this ensures that we gain valuable experience at the forefront of emerging technologies – from NGS and mass spectrometry to liquid biopsies and single molecule detection. Combining this with our extensive workflow automation know-how, gained through many years of working in partnership with hundreds of customers worldwide, has given us an in-depth understanding of different workflows. This experience helps us to turn our customers’ cutting-edge laboratory developed tests into bespoke automated workflows. Through Tecan Partnering, we can guide customers – from emerging companies to leading diagnostics providers – through the instrument development process, using our broad portfolio of high quality, IVD-ready components, platforms and systems to ensure a fast time to market. Our dedicated team can guide you through system development – from early concepts and prototyping to serial production – creating fully compliant industrial and diagnostic solutions ready for global roll out. And it doesn’t stop there; we can also provide ongoing technical support, servicing, lifecycle management and staff training. This unique combination of automation expertise, commercial understanding and worldwide support is why we are the partner of choice. Dr David Martyr CEO
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TECAN JOURNAL 2/2016
CONTENTS
Contents 2
CEO Welcome
4-5
Detecting tumor ‘castaways’ could revolutionize cancer diagnosis
12 - 13 In safe hands
6-7
Epigenetics – adding a new layer to health
8-9
Seeing more clearly
10 - 11
Igniting research on the open seas
12 - 13
In safe hands
14 - 15
Futureproofing biobanking procedures
16 - 17
Building functionality into the antibody supply chain
18 - 19
A more powerful approach to biomarker discovery
20 - 21
Consistency for a changing market
22 - 23
A modern elixir of life
24 - 25
Miniaturizing separation science
26 - 27
Automation – an extension of the analyst
28 - 29
A 3D revolution
30 - 31
HMGB1 – a silent partner in cancer?
16 - 17 Building functionality into the antibody supply chain
Introducing The Blog www.tecan.com/blog
TECAN JOURNAL 2/2016
3
CANCER DIAGNOSIS
Detecting tumor ‘castaways’ could revolutionize cancer diagnosis We may well be on the threshold of a new hope for oncology. An exciting form of analysis is poised to have a profound effect on how we manage cancer patients – in diagnostics, prognostics and drug monitoring. Automation will be key to its success.
When circulating tumor DNA (ctDNA)
miss, leading to over- or under-treatment.
is sloughed off from tumors, it can
For example, in early stage breast cancer,
be detected in liquid biopsies of just
many patients receive chemotherapy,
a few milliliters of blood. This could
even though large-scale clinical trials have
revolutionize oncology by diagnosing
shown that only 10-15 % of patients really
cancers earlier and more efficiently.
benefit from it. ctDNA tests can help to
Dr Theresa Zhang is Vice President of
identify those patients that would benefit
Research Services at Personal Genome
from chemotherapy. They can be used to
Dr Theresa Zhang, Vice
Diagnostics, and is enthusiastic about
determine whether the patient has residual
President of Research
the potential of this new form of testing.
tumor cells that are shedding ctDNA
Services, Personal
“Measuring ctDNA will help us with earlier
into the blood, which will point to a high
Genome Diagnostics
detection in the future,” she said. “It will
chance of recurrence.
be invaluable, not just in studying minimal residual disease, but also in reducing the
2. An early warning system in drug
levels of over-treatment.”
monitoring
In the lab, automation will play an essential role in these new tests. It will help to achieve cost-effective throughput, and also provide the control over contamination that is critical to find the needle in the haystack; a few mutant DNA copies shed from a tumor into the blood, surrounded by thousands, or even tens of thousands, of normal copies. ctDNA tests could change oncology in many ways: 1. Deciding suitability for chemotherapy
the body, often detects how a patient is responding to treatment earlier than conventional approaches, such as imaging. Increased levels of ctDNA can be detected months before imaging can detect that the tumor has returned. “It’s exciting for us to detect a molecular relapse so early,” commented Dr Zhang. “This means that we know when the therapy has stopped working long before the imaging assay indicates there is a problem.” 3. Non-invasive testing for real-time information
of risk assessment can be a bit hit and
TECAN JOURNAL 2/2016
of ctDNA, released from any lesion in
surgery, then the tumor tissue is analyzed and the need for chemotherapy. That kind
4
treatment is another hot area. The analysis
For many cancers, diagnosis is followed by to help decide on the risk of recurrence
Introducing The Blog
Using ctDNA to monitor response to drug
The tumor evolves during treatment or as the disease progresses. This means that the archival tissue is not informative
TRENDS, NEWS, STORIES AND MUCH MORE! FROM THE EXPERTS TO YOU.
CANCER DIAGNOSIS
enough to guide treatment decisions
in plasma, then it means you have cancer.
later on. Being able to do a test
We now know that some white blood
non-invasively, and get real-time
cells may mutate clonally and shed
information, is therefore valuable.
mutated DNA into blood as we age,
ctDNA analysis offers an excellent
but these can be easily identified.”
alternative to serial biopsies, especially for late-stage cancer patients, as their tumors tend to shed more ctDNA into
So how is it done?
Automation is key Dr Zhang believes that laboratory automation is essential when it comes to analyzing ctDNA: “Automation is key whenever a high complexity assay – such as next generation sequencing – is involved, because the techniques are too
Early last year, Personal Genome
complicated to be scaled up in a reliable
Diagnostics launched PlasmaSelect-R™.
and controlled manner. What’s more,
This automated diagnostics procedure
automation is critical for highly sensitive
analyzes ctDNA and interrogates
ctDNA tests. We need to detect one
sequence mutations, copy number
mutant molecule out of a background
Analyzing ctDNA also gives an insight
changes and translocations in a panel of
of 1,000 or, in the future, 10,000 wild
into possible mechanisms of drug
63 clinically actionable genes.
type molecules. This means that
the blood, making it easier to detect. 4. Discovering mechanisms of drug resistance
contamination has the potential to be a
resistance by the tumor. By comparing baseline, pretreatment ctDNA results
Detection is based on next generation
real problem. While automation certainly
with blood samples taken throughout
sequencing, and the company is aiming
provides cost effectiveness, it’s also the
the treatment, it is possible to determine
at CLIA approval in the near future. Many
key to controlling contamination.”
if tumors have acquired new mutations
pharmaceutical companies have already
– and if these new mutations have contributed to resistance. Issues to be aware of
used PlasmaSelect-R for retrospective analysis of their clinical trial samples. It helps them to understand the genetic landscape of the patients enrolled in their clinical trials, which is often
Very few procedures are perfect, and
uncharacterized, since patients have
there may be some disadvantages
gone through many lines of treatment.
As a non-invasive way to detect and monitor tumors, ctDNA testing is showing great promise. But it could also have benefits beyond these applications, providing patients with greater peace of mind and less need for chemotherapy.
with ctDNA analysis. However, they are outweighed by the advantages. Dr Zhang commented: “With the current detection approach, not all the tumors shed detectable levels of ctDNA. And if the detection method is not sensitive enough, you may miss patients. But the biological background is very low for ctDNA – it only comes from cancers. The dogma is that if you find ctDNA
Previously, the pharmaceutical companies had to rely on archival tumor blocks taken years before the trial, which meant that they missed the real-time status of the tumor. Wherever possible, they are now using liquid biopsies to assess the molecular landscape of the cancer they are treating.
www.tecan.com/blog TECAN JOURNAL 2/2016
5
EPIGENETICS
Epigenetics – adding a new layer to health Do you feel overwhelmed with advice on what to eat and drink, or how to exercise to improve and protect your health? Pregnant women in particular are advised not to expose their developing child to alcohol, pollutants and stress. This is sound advice, since exposure at the fetal stage can have implications for generations to come. The science behind this is called epigenetics.
Epigenetic studies are delivering a
Sweden. Harvests were unpredictable
jumped to an amazing 32 years! The
better understanding of how to tackle
for many years after, with periods of
grandfathers’ single season of gluttony
some key diseases. This has not only
crop failure and famine often followed
somehow affected their grandsons.
changed how we view the impact of
by massive harvests, and the good
our lifestyle on our own bodies but,
people of Överkalix gorged themselves
Later work showed that the paternal
remarkably, even on generations to
during these periods of plenty.
granddaughters of women who experienced gluttony or famine when
come. Epigenetics changes how genes switch on or off, without changing
Fast forward to 1984, and Lars Olov
they were in the womb or before
the DNA sequence. Nevertheless,
Bygren at Sweden’s renowned
puberty also had dramatically differing
epigenetic changes are heritable. They
Karolinska Institute was studying the
life expectancies. This was another
not only regulate gene expression in our
health of the Överkalix population.
example of what Bygren called ‘early
own cells, and predispose us to certain
Looking at births in 1905, Bygren
influences that give late replies’. His
diseases, but amazingly, these
discovered that grandsons of Överkalix
discovery clearly showed that these
modifications have now been linked
boys who had experienced good
experiences led to heritable traits, but
to disorders affecting subsequent
harvests – going from normal eating to
remained unpublished, and it was only
generations. Let’s take a look at
gorging themselves during a single
when the concept of ‘transgenerational
how this mechanism of heritability
season just before puberty, as sperm
responses’ was widely accepted almost
was discovered.
were maturing – had an average six year
two decades later that his results
reduction in life expectancy compared
received the recognition they deserved.
Feast and famine In 1800, there was a total crop failure in Överkalix, northern
with grandsons of Överkalix boys who had experienced famine during the same stage of their development. This reduced life expectancy was often attributed to diabetes and, once the data was adjusted for socioeconomic variations, the difference in longevity
What is epigenetics? Epigenetics is the study of changes in gene expression that occur without changes in the DNA sequence. Examples include DNA methylation and histone modification, and different cells in the body have specific epigenetic profiles that modify gene expression for the cell’s function. These epigenetic changes can persist throughout a cell’s life, and even be passed on. Gametogenesis – the creation of sperm and eggs – is of particular interest in epigenetics research. During development, the fertilized egg forms a blastocyst containing pluripotent stem cells. These cells have the potential to form any cell type – their genetic slate has
Introducing The Blog 6
TECAN JOURNAL 2/2016
TRENDS, NEWS, STORIES AND MUCH MORE! FROM THE EXPERTS TO YOU.
EPIGENETICS
been wiped clean – but epigenetic
that immune cells called regulatory
Some even
changes from either parent could
T-cells displayed asthma-inducing
contend that
potentially be passed on. Later, female
changes in expression of the Foxp3
epigenetics finally
fetuses form ovaries and egg cells while
gene, due to epigenetic tags on Foxp3
reveals the bankruptcy
still in the womb. Astoundingly, this
which could last a lifetime, and even be
of the overly-simplified
means that at one point in pregnancy,
passed on.
concept of ‘nature versus nurture’. Continued research
three generations – the pregnant ‘grandmother’, her unborn daughter
New insights, novel therapeutic
will expand our understanding,
whose ovaries are under development,
strategies
and reveal more about the role of
These examples emphasize the impact our lifestyles have, not only on ourselves, but also on our descendants. Even though epigenetic changes may eventually wear off, smoking, poor
epigenetics in normal cell function and disease. As our knowledge of epigenetics deepens, the doors will open to a whole new dimension of the mechanisms underpinning human health.
eating and toxin exposure can be carried forward in gametes.
Further reading
Understanding epigenetic gene
and the forming eggs which will then be ready to conceive children later in life – are in essence simultaneously exposed to the same environmental stresses, such as famine or gluttony. In contrast, sperm first form during puberty in boys, and so the environment cannot start imprinting epigenetic markers until this time.
regulation opens up new possibilities
Air Pollution Causes Epigenetic
for the development of novel drugs.
Changes That May Trigger
The first FDA-approved epigenetic drug
Asthma, Discover magazine
– azacitidine – was released in 2004 for
http://discovermagazine.com/
the treatment of patients with a group of rare and deadly blood malignancies called myelodysplastic syndromes. Azacitidine is thought to inhibit the methylation enzymes that put epigenetic tags on genes in blood precursor cells. Since 2004, the FDA
2015/sept/15-something-in-air Why Your DNA Isn’t Your Destiny, Time magazine http://content. time.com/time/magazine/ article/0,9171,1952313,00.html
has approved three other epigenetic Another example of disease-related
drugs that might work by stimulating
Dawson, MA; Kouzarides, T. Cancer
epigenetic modification was outlined
tumor suppressor genes that are
Epigenetics: From Mechanism to
by Dr Kari Nadeau, now at Stanford
epigenetically silenced when the tumor
University. She discovered that children
develops. The recent emphasis on
Therapy. Cell, 2012, 150(1), 12-27.
exposed to excessive air pollution were
epigenetics also extends beyond the
more likely to develop asthma due to
pharmaceutical industry. Nestlé has
epigenetic changes affecting genes
committed to a six year research
which prevent the immune system from
program to study how epigenetics is
overreacting to allergens, such as
involved in maternal and early life
airborne pollutants. Dr Nadeau showed
nutrition and health.
www.tecan.com/blog TECAN JOURNAL 2/2016
7
DRUG DISCOVERY
Seeing more clearly Degenerative eye diseases affect millions of people around the world, causing progressive loss of vision and, in some cases, complete blindness. Researchers in Australia are using stem cell technologies to investigate ways of halting, or even reversing, the effects of common eye diseases. The Centre for Eye Research Australia (CERA) was established in 1996 to investigate both the causes of and possible treatments for eye diseases, combining population health and clinical epidemiology with advanced laboratory studies. Based at the Royal Victorian Eye and Ear Hospital in Melbourne, CERA’s Neuroregeneration Research and Clinical Genetics Units are investigating potential treatments for blinding diseases – such as glaucoma, age-related macular degeneration (AMD) and inherited retinal dystrophies – using induced pluripotent stem cells (iPSCs) to generate cellular models of disease. Associate Professor Alice Pébay, Head of the Neuroregeneration Research Unit, explained: “Obtaining ocular tissue samples from living patients has historically been a barrier to developing new treatments for blinding diseases. The advent of techniques allowing the generation of iPSCs from adult tissue has been a major breakthrough, providing powerful new tools for disease modeling. Using these methods, we can now derive iPSCs directly from patient biopsies, then differentiate them into specific retinal cell types to create in vitro models of the ocular condition of interest. This enables us to study the complex genetics and molecular mechanisms of diseases such as glaucoma and AMD and, equally importantly, undertake large-scale drug screening programs to find potential cures.” The group uses the protocols developed by Yamanaka and colleagues to reprogram somatic cells taken from skin biopsies of individual patients, generating iPSC lines which form the basis of their research. “Once we had successfully created patient-derived
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TECAN JOURNAL 2/2016
DRUG DISCOVERY
The large-scale disease modeling team at CERA
stem cell lines, we needed to establish
requirements, and so we approached
our research; retinal pigment epithelium
robust protocols for the maintenance
the Tecan Integration Group (TIG)
cells – which are dysfunctional in AMD
of our cell cultures,” Alice added.
through our local Tecan offices to create
and inherited retinal dystrophies –
“This is a fairly labor-intensive and
a bespoke Freedom EVO® system
and retinal ganglion cells, which are
time-consuming process and, because
offering sterile working conditions
affected in glaucoma and other optic
our intention was to undertake
and an integrated 84-plate LiCONiC
neuropathies. This work is also being
large-scale studies – looking for
incubator. As with any new venture, it
performed on the Freedom EVO, with
potentially very small drug effects that
took us some time to develop a culture
the aim of generating and maintaining
might halt the progression of these
maintenance protocol robust enough for
the large quantities of fully differentiated cells we require for our disease modeling
We’ve made more iPSC lines in the last few months than we had over the preceding couple of years.
and drug screening programs.” “Our ultimate goal is to find solutions for major blinding eye diseases that affect Australians, and to pioneer vision regeneration programs to give hope to people who have lost their sight. Very
pathologies – it was not practical to
use with our iPSC lines, but it is now
few labs globally are equipped to
continue performing this manually.
working well, allowing us to generate
perform this type of work, and we hope
Automation was clearly the way forward,
large quantities of cells for our research.
that this approach will lead to new
and would also help to minimize the
In fact, we’ve made more iPSC lines in
targets and novel therapies for the
variability between cell samples, giving
the last few months than we have over
prevention and treatment of common
us greater confidence that our protocols
the preceding couple of years.”
and devastating diseases. It’s very
would be reliable enough to detect even small changes in cellular behavior.”
exciting,” Alice concluded. The automated platform and the associated offline equipment were
To find out more about Tecan’s
Associate Professor Alex Hewitt, Head
acquired thanks to generous donations
of Clinical Genetics, continued the story:
from the Joan and Peter Clemenger
“Our main aim for automation was to
Foundation and the Phillip Neal Bequest.
free up staff time and standardize the
Alice continued: “Our next task is to
cultures we produced as much as
create protocols to efficiently passage
To learn more about CERA, go to
possible. There was no off-the-shelf
and differentiate the iPSCs into the
www.cera.org.au
solution on the market that met all our
patient-specific cell types of interest to
cell biology solutions, visit www.tecan.com/cellbiology
TECAN JOURNAL 2/2016
9
MARINE BIOLOGY
Igniting research on the open seas Fluorescence measurements are helping a microbial ecologist to investigate the undersea environment, studying microbial enzyme hydrolysis in subseafloor rocks, and how microbes respond to oil spills.
world gather samples for their individual projects, performing some initial analyses on-board ship, followed by further studies back on dry land. Assistant Professor Jason Sylvan from the Department of Oceanography at Texas A&M University took part in a recent IODP drilling expedition, the first of a series of cruises to gather samples from the boundary between the ocean crust and the mantle below. Samples from these subseafloor rocks were then analyzed on board, using fluorescence-based assays to study the Subseafloor rocks play host to a range of novel microbial communities
rates of phosphatase activities in the microbial communities
The International Ocean Discovery
encountered. Jason
Program (IODP) operates scientific
explained: “People
cruises that give researchers the
have been trying
opportunity to explore subseafloor
to investigate the
sediments and rocks, and the subseafloor
boundary between
environment. Scientists from around the
the ocean crust
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TECAN JOURNAL 2/2016
MARINE BIOLOGY
and the mantle for a long time. This
phosphate, sealed, and then maintained
reader. I particularly like the temperature
expedition visited an area of the Indian
at an in situ temperature of about 10 °C.
control feature, which enables continuous
Ocean south east of Madagascar, where
The fluorescent tag remains inactive
incubation studies, taking multiple
this boundary is shallower than in most
until the phosphate is cleaved, and so
measurements over several hours. Its
other places – around 5 kilometers
the change in fluorescence is analogous
small footprint was another attraction,
below the seafloor – making it easier
with the rate of enzyme-mediated
simplifying transport between the lab
to obtain samples.”
hydrolysis. By sub-sampling and taking
and the ship, and occupying minimal
fluorescence measurements over a
space on board. The low volumes
Jason continued: “Samples are obtained
period of several weeks, I obtain an
required are also an advantage, allowing
by drilling into the rock beneath the
indication of the microbial activity. It is
measurements to be taken on even small
ocean, collecting sequential 10 meter
a very straightforward way to determine
quantities of sample. On previous cruises,
sections of rock which are then divided
the general metabolic rate for a
I used a fluorometer with a single cuvette,
into 1.5 meter sections for analysis.
microbial community that you know little
and measurements took so much longer
As a microbiologist, I have to ensure
about and, as this type of measurement
to complete. I run anything from one
that my samples are not exposed to
is quite common in microbial ecology,
plate every few days to large numbers
contamination from the air or manual
the results are comparable with those
of plates in a single day and, using a
handling, and so immediately place
of other studies.”
microplate reader – rather than taking measurements one at a time in a cuvette
one sample per core in a bag to keep it clean, rinsing it well with distilled water
“The same fluorescence method is used
– can be the difference between being
before analysis to wash off anything that
in my lab to examine how the microbial
able to do an experiment or not. With the
might be on the outside. Working in a
community responds to an oil spill,
Spark, I can set up the experiment and
filter-equipped enclosure that removes
looking at exposure to oil, and to oil plus
walk away, running a suite of samples
particulates in the air, we break open the
dispersant chemicals. In any clean-up
over the course of an hour compared to
rock and take samples from its center,
operation, the aim is to use detergents to
an entire day. And because I’m saving
ensuring that we are only examining
break the oil down into smaller droplets,
time, I can take replicate measurements,
in situ communities.”
increasing the surface area to allow
which helps to generate even better
faster microbial degradation. While the
results,” Jason concluded.
“I establish the biomass by cell counting
theory is good, it may be that some of
under a microscope, and also store
the species that you want to degrade the
samples at -80 °C for identification of
oil don’t like the detergent. Equally, other
the microbes by DNA analysis back
species may be very happy because they
in the lab. A big part of the study is
are actually eating the detergent and not
the investigation of microbial enzyme
the oil. This kind of research helps us to
hydrolysis. This involves fluorescence
understand how best to respond to any
measurements in a Spark® 10M multimode
future oil spillages.”
To find out more about Tecan’s Spark 10M reader, visit www.tecan.com/spark10m To learn more about the Department of Oceanography at Texas A&M University, visit
reader. The live sample is added to sterile synthetic sea water media along with a
“I chose Spark for these projects based
fluorescent substrate, methylumbelliferyl
on my past success with an older Tecan
ocean.tamu.edu
…because I’m saving time, I can take replicate measurements, which helps to generate even better results.
IODP drillship JOIDES Resolution (Credit: William Crawford and IODP) TECAN JOURNAL 2/2016
11
PARTNERING
In safe hands Ongoing technical support and training can be a major concern for laboratory instrument providers looking to outsource development of new platforms. Can the OEM supplier provide sufficient training for engineers and applications specialists? Will ongoing support be available for the lifetime of the instrument? And what happens if in-house engineers can’t ďŹ x a problem?
Training in this kind of low pressure environment is invaluable as a service engineer.
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TECAN JOURNAL 2/2016
PARTNERING
Effective routine maintenance and
the technical training necessary to
together and aligned correctly, and
responsive technical support are vital
install, service and repair it.”
that the differing maintenance and
for clinical laboratories, ensuring correct
calibration requirements for each system
and efficient operation of equipment
Mohammed Mattar, Customer Service
are adhered to. It really has been very
and allowing the laboratory to provide
Supervisor at Siemens Egypt, added:
comprehensive; our trainer – Roger
timely turnaround of results. As a
“Most of our training is provided by
– has been very open, answering all
result, all major healthcare equipment
other engineering staff from within the
our questions in a logical way, and has
providers have dedicated service
global Siemens service organization, but
provided the level of insight we need to
organizations that are responsible
Tecan runs a dedicated training program
effectively support this system.”
for both the upkeep of equipment at
for the Quadriga BeFree at its global
customer sites and the provision of
headquarters in Männedorf, Switzerland.
Mohammed Mattar continued: “Training
expert technical and application support
This ensures we have the appropriate
in this kind of low pressure environment is
when required. Although most of these
knowledge and technical understanding
invaluable as a service engineer, giving you
organizations will provide in-house
of the platform, and gives us a chance
the opportunity to get hands-on and really
training for their application specialists
to draw on the company’s many years
explore an instrument with the assistance
and service engineers, this may not
of experience for troubleshooting any
of a knowledgeable trainer. This helps
always be possible when instruments
issues we may encounter.”
you to develop a picture in your head
are designed and manufactured by a third-party OEM provider.
of how the machine works – and what Shawqi Mohammed Ibrahim, Field Service
issues there could be – before you get to
Engineer & Healthcare Informatics
a customer site, where the customer is
Siemens Healthineers has a long-standing
Specialist from Siemens Saudi Arabia,
obviously keen to get the instrument back
relationship with Tecan’s Partnering
took up the story: “The training is divided
online as quickly as possible.”
Business, working with the company to
into a theoretical element and hands-on
provide advanced liquid handling and
work with the instrument. The theoretical
logistics solutions to complement its
section gives an overview of the system
To find out more about Tecan’s
advanced diagnostic testing product
– looking at the important parts, what
OEM solutions, visit
portfolio. The Quadriga BeFree®
they do and how they work – then the
System is an example of how this
practical section covers how to install
partnering.tecan.com
approach benefits customers, offering
and set up the machine, as well as how to
seamless integration of a sample
troubleshoot, strip and rebuild the various
processing module with up to three
modules. As this platform is connected
BEP® III Systems to provide an effective
with our BEP III Systems, it is also very
high throughput solution for blood
important that everything is connected
To learn more about Siemens Healthineers, go to www.healthcare.siemens.com
donor screening. Frontline support for this platform is provided through Siemens’ global service network, with expert technical back-up from Tecan’s engineering and application Expertline team if an immediate solution cannot be found. Based on Tecan’s advanced liquid handling know-how, the Quadriga BeFree includes a number of technologies not found on other instruments in the Siemens portfolio, requiring the company’s engineers to undertake specific training to ensure effective product support. Mohammed Fatouh, IB & Service Process Manager at Siemens Egypt, explained: “Although the Quadriga BeFree has been on the market for a number of years, this platform has not been available in Egypt until now. Our sales team was keen to offer this instrument to new and existing customers – ensuring we maintain our leading position in the market by providing complete automated solutions
Left to right: Mohammed Mattar, Shawqi Mohammed Ibrahim and Mohammed Fatouh at Tecan’s
– and so it was vital that we undertook
Männedorf training center
TECAN JOURNAL 2/2016
13
BIOBANKING
Futureproofing biobanking procedures The Heidelberg CardioBiobank –
range of studies aimed at improving the
then kept in cryostorage until required
part of Heidelberg University
diagnosis and treatment of numerous
for clinical or molecular studies, either
conditions. As our understanding
in house or by external partners.
in many fields – such as cardiology
We are also a core biobank for many
and oncology – has increased, many
large-scale projects and international
Hospital – collects thousands of patient samples every year for cryostorage and use in national and European medical research projects. Since moving from the
institutions have also established disease-specific biorepositories to complement the general population
main hospital campus into a new,
biobanks. One such facility is the
purpose-built facility, the biobank
Heidelberg CardioBiobank at Heidelberg
has established a state-of-the-art
University Hospital, Germany. Part of
automated workflow to improve the throughput, quality and consistency of its sample processing, helping to drive forward large-scale cardiology studies across Europe.
one of the largest internal medicine
consortia, including the European FP7 ‘BestAgeing’ consortium, the European Horizon 2020 ‘NISCI’ collaboration, and the German Centre for Cardiovascular Research’s TORCH (translational registry for cardiomyopathies) registry. In addition, we collaborate with biobanks worldwide on issues
departments in Europe, it is perfectly
such as collection techniques, sample
positioned to recruit participants for
and quality management, and the
a wide range of clinical studies, such
development of SOPs and analytical
as the investigation of novel disease
processes.”
biomarkers. Dr Tanja Weis, Head of the Heidelberg CardioBiobank, explained:
The increasing focus of genomics and
“Our main focus is the collection and
personalized medicine in many medical
Biobanks have played an increasingly
preparation of high quality biological
specialties means that the Heidelberg
prominent role in medical research over
samples – predominantly from patients
the last two decades, supporting a wide
with heart muscle diseases – which are
CardioBiobank is now responsible for the preparation and storage of over 100,000 patient sample aliquots annually. This increasing workload has meant that many of the routine sample processing activities – which were previously performed manually – have now been automated, significantly increasing the speed of its protocols, as well as enhancing the yield and quality of DNA extracted. Tanja continued: “The biobank was established about eight years ago with just a few -80 °C freezers and liquid nitrogen tanks, which rapidly grew to around 70 freezer units! However, these occupied a great deal of space and took a lot of effort to maintain. Automation became essential and so, when the biobank moved into a purpose-built laboratory on the university’s life sciences campus two years ago, we installed a fully automated LiCONiC STC cryostore with the capacity for 1.2 million samples. At the same time, we invested in a Freedom EVO®-HSM workstation for
The Heidelberg CardioBiobank team
14
TECAN JOURNAL 2/2016
BIOBANKING
ReliaPrep™ DNA purification*,
Freedom EVO-HSM’s straightforward
also use the excellent 3D simulation tool
taking advantage of the partnership
touchscreen operation guides the
a lot, enabling any potential problems
between Tecan and Promega to
technician through setting up and
such as a mechanical collision to be
implement automated large volume
starting the run, leaving them free
DNA extraction.”
to carry out other tasks while the
identified and resolved before starting
automated extraction is performed. The step-by-step instructions also mean
The yield and quality of the DNA extracted has significantly improved, which is an unexpected but very welcome benefit.
that less experienced technicians can be taught to use the platform within just a few hours, if necessary, without affecting the results.” “We currently extract samples from 32 patients per run in about four hours, giving us a throughput of up to 64 samples a day for a normal eight hours operation, with a maximum of 192 extractions per day for 24-hour use. This has increased the speed of extraction by a factor of at least 10,
“Implementation of the system went
perhaps more; the system will pay for
very smoothly. After Tecan had
itself within a short time. In addition, the
completed the installation, a Promega
yield and quality of the DNA extracted
specialist visited the biobank and, in
has significantly improved, which is an
two days, had commissioned the system
unexpected but very welcome benefit.”
and trained four of our staff to use the platform, which is supplied with
“The next bottleneck in our workflow
pre-installed, validated protocols. Unlike
was sample aliquoting. When performed
other suppliers, Promega demonstrates
manually, this is a slow, repetitive
the performance of the DNA extraction during site acceptance testing with a unique biological acceptance test (BAT), using specific, well characterized blood samples to provide a precise, clearly defined reference point. We also validated the system using samples from the biobank and, within a week, were
process with the potential for human errors, and so we have also invested in a Freedom EVO 150 workstation to automate these laborious activities.
the run.” “There were many reasons for choosing the Tecan workstations, including quality, performance, reliability, durability and robustness in daily operation, and especially the partnership with Promega. The systems give us the flexibility to adapt our processes as our needs change, futureproofing our procedures, and are also compatible with the new LIMS system due to be implemented, which is crucial. In addition, I have confidence that the systems will be supported for many years, and know that I can communicate directly with local technical experts if I need to, which is invaluable,” Tanja concluded.
To find out more about Tecan’s Freedom EVO-HSM workstation, visit www.tecan.com/reliaprep To learn more about the Heidelberg CardioBiobank, go to www.heidelberg-cardiobiobank. com
We currently run about 20 separate protocols on the platform, giving us the versatility to aliquot different sample
routinely using the workstation. It has
types – including blood, serum, plasma,
been in use every day since then.”
urine and cerebrospinal fluid – for a wide
* For research use only. Not for use in clinical diagnostics.
range of studies, and virtually eliminating “Previously, DNA was manually
human errors. All our technicians find
extracted using standard kits from
it very easy to operate the system, and
a range of providers. Although this
to write specific scripts for individual
worked, it was time consuming and not
studies. The Tube Inspection Unit (TIU)
as effective as the automated process
is a big advantage, helping to enhance
in terms of quality and quantity. The
the performance of the system, and we
TECAN JOURNAL 2/2016
15
IMMUNOLOGY
Building functionality into the antibody supply chain The Monash Antibody Technologies Facility (MATF) in Victoria, Australia, has added a new dimension to its high throughput service, offering screening for antibody functionality. This time-consuming phase is crucial for many projects, and can now be outsourced to MATF, where comprehensive and flexible automation completes testing in a fraction of the time.
Section of a mouse testis stained with RBM5 antibody (red), binding partner (green) and nuclear stain (blue) (Courtesy of Moira O’Bryan)
16
TECAN JOURNAL 2/2016
IMMUNOLOGY
MATF is a core facility based at Monash University with a global reputation for producing high quality, high affinity monoclonal antibodies for biomedical research projects around the world. Approximately half of the MATF’s projects stem from the medical and biochemistry faculties at the university, with the remainder from academic institutes, large pharmaceutical and small biotech companies further afield. Dr Caroline Laverty, Head of Robotics and Manager at MATF, explained: “Our core business is monoclonal antibodies. We are quite unique with regard to our high throughput capabilities, but our important differentiating factor is delivery of a high quality product. We are an ISO 9001 certified facility,
Members of the MATF RoboCore team
Without our automation we would need upwards of 20 people to achieve the same output – that’s five times our current head count.
and have a great deal of combined knowledge in the antibody field,
Until recently, MATF has supplied
smooth and very easy to teach. The way
including pharmaceutical industrial
its customers with antibodies that
the deck is configured is ideal for us; we
experience from myself and the facility’s
have been tested by microarray and
can add or take away modules, carriers
director Professor Mark Sleeman. Our
ELISA to confirm that they bind to
or other pieces of equipment very easily.
projects are highly varied, because
the corresponding antigen, at which
And there are other simple, yet really
they all depend on customer-focused,
point the customer has screened
useful things. For example, if an assay
versatile screening strategies that
them in house for functionality. This is
stops halfway through a protocol for any
deliver exactly what the customer
particularly true for the growing field of
reason, it can find itself in space rather
wants. We have tried-and-tested core
therapeutic antibodies. However, this is a
than having to go back to home each
methodologies which we add specific
very time-consuming part of the process
time. The 10 Freedom EVOs® we have
details to, according to what is required
which often takes months. For this
are brilliant – they’re very reliable and
– How many antibodies? What sort of
reason, and at the request of customers,
robust – but the Fluent is something
antigen? How many screening samples?
MATF has invested in a new Fluent®
quite different.”
What is the intended end use? – which is
Laboratory Automation Solution that
where we build in the flexibility.”
can complement this phase of screening.
Caroline concluded: “Our relationship
Caroline explained that the new system
with the Tecan team in Australia is really
“Our robotic systems are very much
will enable them to scale up functional
the icing on the cake, and we actively
integrated into how we find antibodies,
cell-based assays developed internally or
promote this well-built partnership.
and how we screen them. We also
by customers to screen hybridomas. “We
We rely on the service Tecan provides,
operate a smaller liquid handling facility –
will be able to tell them at an early stage
because we have an obligation to our
RoboCore™ – and automation makes the
that the antibodies not only bind, but
customers. We quote timelines and quality
job easier for us and gives us the power
that they are also functional, potentially
and, to achieve that, we need all of our
to be diverse. For every project, we are
saving the customer months, if not
instrumentation to be working all of the
able to generate far higher numbers of
years, of work.”
time. The back-up and application support
hybridomas – and hence a bigger pool
are fundamental for our processes, and
of antibodies for potential screening –
Caroline’s background is in the
I don’t believe that any automation
than would be possible manually. Most
application of automation to varied
company other than Tecan can provide
of the time we’re effectively looking for
laboratory procedures, and she said of
us with that level of assurance.”
a needle in a haystack. The robotics we
the Fluent: “This system is fundamentally
have mean that we can start with a really
different, in ways which are essential
big haystack, and still effectively screen
when you’re trying to deal with so many
it to find the needle. Automation also
To find out more about Tecan’s
projects on the go at the same time. The
gives our staff ‘headspace’ to think
Fluent Laboratory Automation
demographic of our customers’ projects
about the science; it reduces the
is quite wide – these antibodies may be
Solution, visit
amount of staff needed in the lab. We
for anything from veterinary medicine
looked into this a couple of years ago,
to medical research and diagnostics
and without our automation we would
– and we expect to be running up to
need upwards of 20 people to achieve
10 screening campaigns at any one time.
the same output – that’s five times our
The Fluent has been configured to
current head count.”
give us maximum flexibility; it is slick,
www.tecan.com/fluent To learn more about the Monash Antibody Technologies Facility, go to platforms.monash.edu/matf
TECAN JOURNAL 2/2016
17
PROTEOMICS
A more powerful approach to biomarker discovery SomaLogic is using its unique proteomics technology – the SOMAscan® assay – to help identify new biomarkers for a wide range of disease states. Capable of simultaneously measuring thousands of proteins in low volume biological samples, this technique is ideal for the detection of low abundance proteins, perfectly complementing existing technologies for basic science, biomarker discovery and pharmaceutical research.
Biomarker discovery is now at the
allowing precise quantification using
achieve the necessary throughput. It
forefront of medical, diagnostic and drug
standard DNA measurement techniques.
was clear that automation was the way
discovery research, helping to provide
Using our specialized SOMAmer®
forward, making it easier and more
greater insight into many diseases
reagents, this approach enables us to
reliable to perform the assay with fewer
and identify new therapeutic targets.
translate a difficult protein quantification
people. We initially automated the
The size and complexity of the human
problem into a far easier, more
workflow using a liquid handling system
proteome makes the identification of
reproducible and widely accessible
with two 96-channel pipetting arms, but
disease-specific protein biomarkers both
quantitative DNA analysis. Our current
this platform was incompatible with the
difficult and time consuming, requiring
version of the SOMAscan assay is able
SELEX (systematic evolution of ligands
quantitative analysis of thousands of
to measure over 1,300 separate protein
by exponential enrichment) process
individual proteins in complex biological
analytes, over eight logs of dynamic
used to design our SOMAmer reagents,
matrices such as serum, plasma and
range, in just 65 μl of sample, and can
which required independent control
cell lysates. A wide range of proteomic
be performed using various biological
of each pipetting channel. We wanted
methods have been developed to
matrices – including serum, plasma,
to be able to run both workflows on a
offer multiplexed measurement of a
cell supernatants and cell, tissue or
single platform, and chose the Freedom
broad spectrum of protein analytes,
organ lysates.”
EVO® system based on its very high
with mass spectrometry emerging as a front runner. However, many of these techniques offer poor sensitivity for low abundance proteins – requiring extensive depletion steps to access any proteins in the lower end of the dynamic range – have highly limited sample throughput, and reproducibility that disallows detection of smaller signals.
utomation has more than tripled the A throughput of the SOMAscan assay, and the team here is now working with Tecan and our field application specialists to make it even quicker and easier to run.
Colorado-based life sciences company
Throughput is a key consideration for
flexibility and the ease with which we
SomaLogic has developed a unique
any biomarker discovery workflow,
could configure the instrument for
technology allowing the measurement of
particularly for the pharmaceutical
different processes.”
a broad range of protein concentrations
sector, requiring effective and
in small sample volumes, complementing
reproducible liquid handling to
“We selected the Freedom EVO 200
existing techniques and providing
ensure accurate results. Dr Stephan
because of the large number of reagents,
improved measurement of low
Kraemer, Director of Assay Execution,
assay plates and devices – including
abundance proteins. Dr Tim Bauer,
commented: “When we first developed
two Te-VacS™ modules and four shakers
Associate Director at SomaLogic,
the SOMAscan assay in a microplate
(Q.Instruments) – which needed to be
explained: “Our technology – the
format, we were running it manually.
fitted onto the workdeck,” Stephan
SOMAscan assay – converts a protein
Three technicians needed to stand
continued. “The system also has both
concentration into a DNA concentration,
side-by-side, pipetting in parallel to
an eight-channel Liquid Handling Arm,
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TECAN JOURNAL 2/2016
PROTEOMICS
To find out more about Tecan’s protein science solutions, visit www.tecan.com/proteinscience To learn more about SomaLogic, go to www.somalogic.com
Dr Stephan Kraemer with one of SomaLogic’s Freedom EVO platforms
allowing independent control of
the logistical challenges of shipping
individual pipetting channels, and
their samples to us for analysis. The
a MultiChannel Arm™ (MCA) for
use of standardized protocols should
simultaneous pipetting into all 96 wells
also allow direct comparisons of results
of an assay plate. This gives us the
between sites.”
flexibility to perform either the SOMAscan assay or the SELEX target
“We have only recently placed the
identification workflow on the same
first instruments with customers,
instrument, or to run both together.”
but the feedback we have received so far has been very positive. Automation
Tim added: “Since introducing our
has more than tripled the throughput
first Freedom EVO platform, we
of the SOMAscan assay, and the team
have purchased three additional,
here is now working with Tecan and
almost identical systems, and we are
our field application specialists to
very happy with both the precision
make it even quicker and easier to run,”
and robustness of the instruments.
Stephan concluded.
Now that we have established our automated workflows in house, we are working with Tecan to optimize and place instruments using the same configuration at customer sites around the world, initially focusing on human serum and plasma samples. This will allow customers to run more samples much more quickly, without
TECAN JOURNAL 2/2016
19
CLINICAL DIAGNOSTICS
Consistency for a changing market PerkinElmer Healthcare Diagnostics (Shanghai) Co develops and manufactures instruments for the processing and analysis of clinical samples in hospital laboratories across China. A pioneer of time-resolved fluorescence techniques in this market, the company prides itself on creating cutting-edge automated solutions to address unmet needs in infectious disease diagnostics.
The in vitro diagnostics (IVD) market
who understand the demands of the
facility develops and manufactures a
has very specific needs when it comes
diagnostics sector, ensuring ongoing
range of Sym-Bio brand IVD instruments
to laboratory automation, requiring
support and allowing the development
for use in hospitals across China,
highly integrated solutions that are
of new solutions to address an ever-
focusing primarily on the detection
both robust and easy to use. Unlike the
changing market.
of infectious diseases. Combining
life sciences research sector – where
our proprietary TRF immunoassay
flexibility and adaptability are often
PerkinElmer Healthcare Diagnostics
technologies with advanced laboratory
essential to guarantee productivity
(Shanghai) Co – formerly Shanghai
automation, our aim is to provide
as project needs change – automated
Sym-Bio Life Science Co – is a leading
convenient and cost-effective testing
systems for clinical laboratories should
provider of diagnostics instruments and
for a range of diseases, many of which
offer highly reproducible results
related reagents for Chinese hospitals.
are not served by other solutions on
over several years, while requiring
Originally founded to develop and
the market.”
only minimal maintenance and user
commercialize novel time-resolved
expertise. The use of high quality OEM
fluorescence (TRF) techniques, the
When developing its EasyCuta 1260
components is therefore key to the
company is now a major innovator in
automatic time-resolved fluorescence
long-term success of IVD instruments,
the local IVD market, with a dedicated
analyzer, the company chose to partner
providing consistent performance over
R&D center in Taicang, Jiangsu Province.
with Tecan, taking advantage of the
time. However, it is just as important to
Torres Cai, Instrument Sourcing
company’s liquid handling expertise
work with knowledgeable OEM partners
Supervisor, commented: “Our Taicang
and strong local presence to ensure the success of the project. Cai explained: “Precise transfer of samples and reagents is crucial for the accuracy and reproducibility of immunoassay results, making syringe pumps the most important component in the EasyCuta 1260. When selecting an OEM supplier, our product developers looked not only for the best technical solution, but also for a very high level of technical and application support. Staff from Tecan’s local organization, based in nearby Shanghai, were very responsive and knowledgeable, giving us confidence in both the solutions and support on offer.” “After discussing the needs of our instrument with the Tecan team, we chose the Cavro® XLP syringe pump for the EasyCuta 1260 project.
Tecan Cavro components are essential to the consistent and reliable operation of the
Each instrument contains six individual
EasyCuta instruments
XLP pumps which are required to
20
TECAN JOURNAL 2/2016
CLINICAL DIAGNOSTICS
perform advanced liquid handling reliably for long periods, so it was crucial that our engineers understood how to maximize long-term performance. We received very good support from Tecan during instrument development and validation; the company provided periodic training for our engineers to
Precise transfer of samples and reagents is crucial for the accuracy and reproducibility of immunoassay results.
ensure we could optimize instrument performance and provide appropriate maintenance schedules, and its application experts were always available to answer any questions we had. Since its launch in 2013, we have installed EasyCuta 1260 platforms in over 400 hospitals, and we have been very happy with the performance of both the instrument and the Cavro pumps.” In 2014, PerkinElmer began developing a second system – the EasyCuta MiNi – to provide a lower throughput solution for smaller hospitals. “Based on feedback from existing EasyCuta 1260 customers,
To find out more about Tecan
we took this opportunity to enhance
Cavro components, visit
the instrument workflow and shorten
www.tecan.com/components
turnaround times,” Cai continued. “In addition to modifying the assay method slightly, we chose to use the Cavro ADP (Air Displacement Pipettor) to allow faster liquid transfers, helping to reduce the overall processing time. Working with Tecan made it very straightforward
To learn more about PerkinElmer Healthcare Diagnostics (Shanghai), go to www.perkinelmer.com.cn/ products/default.xhtml
to transfer our method from syringe pumps to pipettor technology, and this is one of the benefits of working with a leading OEM supplier with a diverse product portfolio.”
TECAN JOURNAL 2/2016
21
CELL BIOLOGY
A modern elixir of life Scientists at Tokyo University of Technology are searching for foodstuffs that can slow the aging process. Focusing on mitochondrial regulation, researchers from the university’s School of Bioscience and Biotechnology are using cell-based assays to help identify food components with anti-aging properties.
Since time immemorial, people have
production, reducing the amount of
time-course assays. “The ability to
dreamt of discovering ways of holding
food required and limiting the stress on
perform measurements that are
back the aging process. A group of
the body. As many foods contain these
both quantitative and time-based
researchers in Japan are seeking to
organic acids, it is possible to consume
is a great advantage. Previously,
turn this long-held dream into reality,
them as part of a normal diet.”
it was not possible to satisfy both needs simultaneously; it had to
looking at the anti-aging properties of specific foodstuffs. This research
Professor Satoh and his team are
be one or the other. Quantitative
focuses on the effect of various food
screening for compounds that are able
fluorescence measurements made
components on mitochondria, which
to promote mitochondrial activity using
using a conventional microplate reader
are believed to play an important role in determining the survival or death of the cells and are more strongly influenced by reactive oxygen species (ROS) than other organelles. Professor Takumi Satoh, Head of the Anti-aging Food
aving this quality and breadth of data H makes a real difference when preparing manuscripts for publication.
Laboratory, Advanced Food Course at Tokyo University of Technology’s
microplate-based cellular assays, aided
give satisfactory one-off readings,
School of Bioscience and Biotechnology,
by a Spark® 10M multimode microplate
but there is no capability to make
explained: “I believe that the ability
reader. He continued: “We culture
repeat measurements over time
of food components to activate
adherent cells in microplates and, using
for cell-based assays. Conversely,
mitochondria is important for anti-aging.
a fluorescent dye, we can visualize
fluorescence microscopy is well suited
Consequently, we are searching for
changes in mitochondrial membrane
to measurements over extended time
compounds in food that can enter and
potential and monitor intracellular
periods, but this method can only
stimulate mitochondria directly. We are
ROS levels caused by test compounds.
collect data from a single cell. The
currently investigating various organic
We have initially been working on the
Spark 10M was therefore an important
acids, such as 3-hydroxybutyric acid,
establishment of this method using the
breakthrough for our work. We now
which is from a group of compounds
Spark reader, and have already started
have a microplate reader that makes
known as ketone bodies that have been
to see some exciting results.”
it possible to simultaneously assay a population of cells – measuring
reported to prolong the lifespan of C. elegans. These are relatively small
The Spark reader’s integrated Gas
ROS concentrations or mitochondrial
compounds and, unlike compounds
Control Module (GCM™) is capable
membrane potentials – both
such as glucose, some can enter the
of precise regulation of temperature
quantitatively and temporally, allowing
mitochondria directly without the need
and carbon dioxide concentration,
us to determine everything in one go.
for prior catalysis in the cytoplasm.
which maintains cell health and
We can also run multiple experiments
This results in very efficient energy
allows researchers to perform longer
at once, usually in 24-well microplates.”
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TECAN JOURNAL 2/2016
CELL BIOLOGY
“It is a great benefit for our work to be able to ensure that the cells are alive and healthy for the duration of the assay. Both the temperature and the carbon dioxide concentration can be tightly controlled, allowing complete assays to be carried out under the same conditions as within a cell culture incubator. Until now, this combination of features was not available, so the length of time during which measurements could be taken was very limited.” “Another really good thing is that we can run assays continuously for many hours. A common problem with fluorescence microscopy is the non-specific
Professor Satoh and student Zhang Jian with the Spark reader
background effect, which increases with prolonged exposure time. However, with the Spark 10M, the measurements are made very quickly, minimizing background interference and allowing us to collect data over much longer periods. Having this quality and breadth of data makes a real difference when preparing
To find out more about Tecan’s Spark 10M reader, visit www.tecan.com/spark10m To learn more about the
manuscripts for publication. Moreover,
Tokyo University of Technology’s
its operation is simple, making it very
School of Bioscience and
easy to use, especially when compared
Biotechnology, visit
to some other instruments I have seen.
www.teu.ac.jp/english/
It is very good for our experiments,”
departments/010614.html
Dr Satoh concluded.
TECAN JOURNAL 2/2016
23
PROTEIN SCIENCE
Miniaturizing separation science The development and characterization of new chromatography media is both complex and time consuming. At Merck KGaA in Darmstadt, Germany, the implementation of automated miniature column chromatography protocols has helped to improve throughput and reduce the amount of material required, allowing more measurements to be performed in less time. Protein purification is a crucial step in
must be performed to characterize the
development, and within six months
the production of biopharmaceuticals,
different candidates, including the
had successfully developed and
and is frequently performed using
determination of selectivity, and static
validated our automated miniature
chromatographic processes. To help
and dynamic binding capacities. The
column chromatography method. We
biotech companies accelerate their
dynamic binding capacity is determined
can screen eight columns in parallel,
product development, manufacturers
under flow conditions, and was
completing dynamic binding capacity
are continually striving to develop new
previously carried out using standard 1,
determinations and resin selectivity
chromatography media, screening
5 or 10 ml lab-scale columns. However,
measurements in three to six hours,
prototype resins with novel functionalities
a large amount of feed material was
depending on the operating
and improved performance to extend
required for each column, and
parameters, compared to over 24 hours
their product portfolio.
evaluation of all the different
for sequential testing on a conventional
candidates was very time consuming.
system. We use 5- to 10-fold less feed
The Chromatography R&D and
We needed to reduce the feed amount
material, and the labor intensity is
Manufacturing Science and Technology
and perform more measurements in
reduced, freeing up more time for us
(MSAT) groups of Merck’s life science
less time, and this led us towards
to perform other valuable tasks.”
business are both engaged in the
miniature column chromatography.”
development of specialist
Senior Applications Engineer Andreas
chromatographic media – such as
André Kiesewetter, an MSAT
Stein added: “We received valuable
Fractogel®, Eshmuno® and ProSep® – for
Applications Engineer, takes up the
support from Tecan during the
the effective and efficient purification
story: “We decided to upgrade our
implementation period, and also
of biomolecules, as well as the creation
in-house robotic capabilities to include
benefitted from the availability of an
of supporting resin performance
state-of-the-art automated miniature
application note describing the optimum
application data. The groups actively
column chromatography using Atoll
performance settings for automated
support the company’s worldwide
RoboColumns®, a proven, user-friendly
miniature column chromatography.
customer base through a network of
technology that can be easily
Programming the workstation is easy
scientists and engineers, as well as
implemented on a liquid handling
to learn, and the integration between
10 M Lab™ collaboration centers
platform. We compared various
Freedom EVOware® and other programs,
located across the globe. The M Lab
workstations, eventually deciding that
such as visual basic scripts, is a huge
collaboration centers in Europe, Asia,
the close collaboration between Atoll
advantage; a system with an open
and the US are equipped with similar
and Tecan – and the popularity of the
program is much more flexible.”
liquid handling platforms configured
technology – made the combination of
for miniature column chromatography,
RoboColumns and the Freedom EVO®
“Automated high throughput
ensuring that customers receive the
workstation the ideal solution for both
experiments generate many samples for
same level of support regardless of
resin and application development
analysis, which could potentially create
location, as well as simplifying method
assays. We can also take advantage of
a bottleneck. Now that the miniature
transfer between sites for flexible
the system’s liquid handling capabilities
column chromatography application is
allocation of resources. Peter Menstell,
to perform dilutions and other sample
running really well, our aim is to go a
Applications Engineer from the
preparation steps in our workflows.”
step further and automate the analytics, establishing a fully integrated workflow
Chromatography R&D group, explained: “When a new resin is under
André continued: “We ran the first trials
to alleviate any possible hold-ups,”
development, a variety of experiments
after just a few weeks of protocol
concluded Andreas.
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TECAN JOURNAL 2/2016
PROTEIN SCIENCE
We use 5- to 10-fold less feed material, and the labor intensity is reduced, freeing up more time for us to perform other valuable tasks.
To find out more about Tecan’s protein science solutions, visit www.tecan.com/proteinscience To learn more about Merck’s life science business, go to www.merckmillipore.com
From left to right, Peter Menstell, André Kiesewetter and Andreas Stein
TECAN JOURNAL 2/2016
25
CLINICAL DIAGNOSTICS
Automation – an extension of the analyst Reputation and accreditation are essential for clinical reference laboratories, helping to win new business and ensure a steady flow of work from existing customer labs. With diagnostic testing demands increasing year-on-year, Carpermor continually invests in cutting-edge assays and state-of-the-art laboratory automation to maintain the quality and efficiency of its services.
all diagnostic disciplines, and quality is
in question. They allow us to process
the most important aspect of our work;
the necessary volume of samples in a
we are accredited by both the College
reproducible and reliable manner, and
of American Pathologists (CAP) and
we do not have any problems with the
our national accreditation authority,
accuracy or repeatability of our ELISAs,
Entidad Mexicana de Acreditación.”
which has helped with our overall workflow by minimizing the need for
Mario continued: “With such a large
repeat testing. As with any technology,
workload and just 185 staff, laboratory
there was a learning period where we
automation is now crucial to ensure
needed to ‘tame’ the equipment to our
that we maintain the level of service
needs, but the Tecan platforms have
our customers expect, in terms of
been excellent since we completed this
both quality and turnaround times.
process. We effectively think of the
Carpermor is an international
Previously, we worked entirely
instruments as working prostheses – an
reference laboratory in Mexico City,
manually – with various individual
extension of the analyst. The flexibility
offering a full range of routine and
washers, readers, etc. – but the rapidly
of the equipment is another advantage,
specialist clinical diagnostic services
increasing number and diversity of
allowing us to perform a wide range
to healthcare providers across Mexico,
tests we needed to perform made this
of protocols on a single platform, and
Carpermor’s Elena Alcántara and Mario Garcia
this has helped us to move away from
Laboratory automation is now crucial to ensure that we maintain the level of service our customers expect.
isotopic analyses for many analytes.”
as well as participating in contract
unsustainable. Our main requirement
we have been trying to replace all our
and academic research projects
for any automated equipment within
assays that rely on isotope analysis
globally. The laboratory prides itself
the lab is that it is extremely reliable,
with either chemiluminescence- or
on its exceptional levels of customer
as our throughput means that even a
ELISA-based methods. Our relationship
satisfaction, using state-of-the-art
short period of downtime can lead to
with IBL International has been crucial
technology to ensure a fast and
a significant backlog. We also need
to achieving this, and we have been
efficient service for its 1,500 customer
equipment that is very versatile, helping
able to work closely with both the
labs. Mario Garcia, General Manager for
us to cope with a constantly changing
company and its distributor here in
Carpermor’s Laboratory and Analytical
portfolio of assays. For these reasons,
Mexico to achieve our goals. Although
Centers, explained their approach: “We
we chose Tecan’s Freedom EVOlyzer®
we are not generally well served by
strive towards service excellence and
and Freedom EVO® platforms to
major diagnostics providers in Latin
exceptional accuracy, providing a high
perform the bulk of our ELISA testing.”
America – they are quite inflexible
Elena Alcántara, a member of the laboratory team at Carpermor, explained: “Isotopic techniques are both complex and expensive, and so
quality, efficient and competitively
to our local needs and you have to
priced service for both routine and
“We have worked with Tecan for a
do a lot of the work yourselves – we
highly specialized testing. We perform
number of years, and the quality of
have found that this was not the case
over 32 million analyses a year across
these workstations has never been
with IBL International. The company’s
26
TECAN JOURNAL 2/2016
CLINICAL DIAGNOSTICS
Each platform offers the flexibility to run
Carperpor’s workflow relies on Freedom EVOlyzer and Freedom EVO platforms to automate
multiple protocols, working as an extension of
ELISA testing
the analyst
attitude is very refreshing; we have
kits and the performance of our Tecan
always found them to be very flexible
platforms. Our ELISA portfolio is still
to our requirements, and we get an
growing, and we will soon need another
answer to any queries we have within
Freedom EVOlyzer, so we hope to
24 hours. They are certainly in tune
continue with Tecan and IBL assays for
with our needs.”
many years to come,” Elena concluded.
“The IBL assay kits themselves are also very good. They are all fully validated,
To find out more about the IBL
which is obviously important in an
range of diagnostic assays, visit
accredited lab, and the convenience
www.tecan.com/immunoassays
of the infectious disease assays has helped us to resolve a bottleneck in our workflow. The expiry characteristics of the assay reagents are another important consideration, particularly for low volume tests that we do not perform regularly. The IBL kits are very stable,
To find out more about Tecan’s diagnostic automation portfolio, visit diagnostics.tecan.com To learn more about
with long expiry dates, which simplifies
Carpermor’s services, go to
logistics and ensures we can meet our
www.carpermor.com.mx
turnaround time targets, even for tests that we rarely perform. Overall, we are very happy with both the IBL ELISA
TECAN JOURNAL 2/2016
27
3D CELL CULTURE
A 3D revolution A novel 3D cell culture platform is enabling scientists to generate microtissues that closely mimic the behavior of human tissues from virtually any cell type. This proprietary technology is easily automated, offering speed and versatility, combined with consistency and reproducibility, for high throughput applications. Classical 2D cell culture is a well-proven
or days required by other methods –
Chris continued: “Scaffold-free methods
technique widely used in biological
and is easily automated on a liquid
are also extremely dependent on cell
assays, drug screening and many other
handling workstation. Chris Millan,
type and donor, and may not always be
research areas. However, cells grown in
Chief Technical Officer at CellSpring,
able to form 3D structures, whereas 3D
a monolayer behave very differently to
explained: “3D Bloom offers several
Bloom can incorporate virtually any cell
cells in a real tissue, and so the response
advantages compared to other
type into the system. A further restriction
of 2D cultured cells to drugs under
methods of creating 3D microtissues.
of the spheroid technique is that it is not
development is not an ideal indicator
Scaffold-free approaches – spheroids
generally possible to have more than
of the likely in vivo response. The 3D
and hanging-drops – for example, take
10,000 cells per microtissue. This limits
Bloom® Biopolymer Platform from
three to five days to generate a 3D
the downstream readout, as it is difficult
CellSpring, an ETH Zurich spin-out,
structure. With 3D Bloom, two
to generate enough DNA or protein to
is showing promise for improving
naturally-derived biopolymers are
establish what is happening with those
the predictive capabilities of in vitro
sequentially pipetted into a standard
cells. In contrast, 3D Bloom is viable
preclinical testing for drug safety and
multiwell plate, where a spontaneous,
over a very wide range – from 5,000 to
efficacy. This proprietary technology
cell-friendly cross-linking reaction
2 million cells per microtissue – removing
can generate 3D microtissues in just
assembles the cells into a 3D structure
this limitation. Variability is another
30 minutes – far less than the hours
in as little as 30 minutes.”
potential issue; scaffold-based processes use materials isolated from animals and consequently may vary between batches by as much as 50 %. Our technology, being very chemically defined, offers almost 100 % reproducibility.” “At the moment, our focus is on high throughput testing of new cancer drugs, looking specifically at the expression of targets of interest to pharmaceutical companies, which are generally over expressed by cells cultured in our system. As a result, the sensitivity of the system to candidate drugs is higher than with conventional methods, which is an advantage when you’re trying to compare numerous different formulations to determine the best candidates,” said Chris. “Performing this work manually is both time consuming and operator dependent, and so automation is clearly the way forward. Through the ETH Innovation and Entrepreneurship Lab (ieLab), we made contact with Tecan, and have worked closely with the company since then to automate our technology on a Freedom EVO® platform.”
3D Bloom allows rapid, automated generation of 3D cell cultures
28
TECAN JOURNAL 2/2016
3D CELL CULTURE
“Initially, Tecan’s specialists worked side by side with us, showing us how to program the system and automate our 3D cell culture method. The Freedom EVO proved extremely straightforward to operate, and we can easily adjust the scripts ourselves if necessary. It’s been incredible; speed and reproducibility have improved tremendously. We can now reliably process 10 plates in the time it takes to run a single 96-well plate manually, and staff are free to carry out other tasks. In the next phase of the collaboration, we plan to investigate co-culture models, incorporating different cell types into a single microtissue. This cannot be performed manually – you do not have enough control when positioning small droplets by eye – but the liquid handling platform should be able to accomplish it quite easily. It’s very apparent to us that we will be selling our products
CellSpring’s Kramer Schmit (CEO, left) and Chris Millan (CTO, right) are hoping the partnership with Tecan will expand the potential of the 3D Bloom platform for screening applications
exclusively for automated platforms, and particularly the Freedom EVO, which will also form the basis of our in-house service offering. There is no doubt that automation has helped us get to market much faster than would otherwise have
It’s been incredible; the speed and reproducibility have improved tremendously.
been possible, and the collaboration has gone so well that we are now entering into a co-marketing agreement with Tecan,” Chris concluded.
To find out more about Tecan’s 3D cell culture solutions, visit www.tecan.com/3dcellculture To learn more about CellSpring, go to www.cellspring.co
TECAN JOURNAL 2/2016
29
IMMUNOLOGY
HMGB1 – a silent partner in cancer? Many people in the life science and medical communities will never have heard of HMGB1 or, to give it its full title, high mobility group box 1 protein. Despite this, it is the most common nuclear protein after the histones – with around a million copies per cell – and plays a key role in the body’s response to everything from trauma and infection to a stroke and heart attack. Dr Michael T Lotze, Professor of Surgery, Immunology and Bioengineering at the University of Pittsburgh School of Medicine, discusses the clinical interest in this remarkable protein for the diagnosis and treatment of patients with cancer. Dr Michael T Lotze, University of Pittsburgh School of Medicine
Cell death in animals normally occurs via a highly regulated, carefully controlled process known as apoptosis. Designed to avoid the cell contents spilling out into the surrounding tissue and causing damage to neighboring cells, it results in the formation of carefully packaged apoptotic bodies which can be quickly and easily engulfed by phagocytic immune cells. In contrast to this, cancer cells do not undergo a programmed cell death, instead experiencing the unscheduled necrotic cell death normally associated with cellular trauma. Necrosis results in the loss of membrane integrity, leading to the release of the cellular carcass material into the extracellular space. A clinical interest One of the proteins released into tissues and the blood by the death of cancerous cells is HMGB1, a chromatin protein normally associated with the packaging of DNA in the cellular nucleus. In most animals, the presence of HMGB1 in the extracellular space is a critical ‘alarm signal’ – known as a damage-associated molecular pattern (DAMP) – triggering an inflammatory immune response to repair the damage. It also affects the surrounding cells directly by inducing autophagy, a ‘self-preservation’ mechanism which helps the intact cells to survive and repair themselves. Under normal circumstances, this would be 30
TECAN JOURNAL 2/2016
IMMUNOLOGY
beneficial, but when the cell death is a result of chemotherapy, and the target cell that is being instructed to survive is a tumor cell, then you obviously have a problem. This not only promotes survival of the tumor cells, but it can also reduce their susceptibility to chemotherapy drugs. In addition, the localized presence of HMGB1 can suppress immunity, hindering natural antitumor responses such as T cell activation. As a result, there is now significant interest in inhibiting HMGB1 in cancer patients – either directly, or up- or downstream – to suppress autophagy and the ‘self-preservation’ response in tumor cells. Early studies combining traditional chemotherapy with HMGB1-targeting immunotherapy have been remarkably successful in patients with pancreatic and kidney cancers, and additional trials are now being launched. HMGB1 isn’t only a problem at the tumor site either. Effective chemotherapy can lead to a significant and sustained rise in circulating HMGB1 – as well as other intracellular molecules, such as uric acid, potassium and nucleic acids – as the tumor responds to treatment. When released into the bloodstream,
HMGB1 is a key mediator for the immune system, signaling cellular stress, and can play a vital role as a biomarker for arthritis, stroke, cancer and sepsis.
these molecules are filtered out by the kidneys, leading to a serious, and potentially fatal, form of kidney damage
other approaches – nothing else comes
known as tumor lysis syndrome.
close – and the company also offers
Scan the
a range of complimentary products,
QR code to
We know that HMGB1 is a critically important molecule, not just in cancer, but also in… many other biological processes. Furthering research One of the major challenges of HMGB1 is the availability of appropriate tools for
such as the Anti-HMGB1 Chicken IgY Neutralizing Polyclonal Antibody, making it faster and easier to conduct our
download the poster
investigations. We know that HMGB1 is a critically important molecule, not just in cancer, but also in autoimmunity, trauma, infection, myocardial infarction, stroke and many other biological processes that are not yet fully understood. It’s becoming increasingly clear that it is
To find out more about IBL’s HMGB1 ELISA kits, visit www.tecan.com/immunoassays
important throughout medicine, and having the right tools available will help
To learn more about
us to further our understanding and
Dr Lotze’s research, go to
improve clinical approaches in the future.
www.immunology.pitt.edu/ person/michael-lotze-md
research. Although many immunology and biochemistry groups around the world have attempted to develop ELISAs for the accurate quantification of HMGB1, it wasn’t until the launch of IBL International’s HMGB1 ELISA* that a reliable method was available. This assay system is intrinsically more effective than
The IBL HMGB1 ELISA Kit is CE marked for IVD use in Europe, but is for research use only in the USA. *Developed by Shino-Test Corporation, Japan, in co-operation with Prof Dr Ikuro Maruyama of Kagoshima University, this product is exclusively distributed worldwide by IBL International, except in Japan, China (incl. Hong Kong) and Taiwan. TECAN JOURNAL 2/2016
31
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