Tecan Journal
Edition 1/2017
Life Sciences, Diagnostics and Partnering
Synthetic biology in the real world
A smarter approach to LC-MS sample prep
Finding the perfect match
Designed for exibility, built for speed
Pages 4-5
Pages 8-9
Pages 16-17
Pages 30-31
CEO WELCOME
Welcome Dear Reader, I would like to begin by welcoming SPEware Corporation to the Tecan family. SPEware is a leading US provider of mass spectrometry sample preparation products, and offers a range of smart consumables and instrumentation designed to simplify customer workflows in this rapidly expanding field. SPEware’s portfolio is a perfect match for the Tecan range of automation workstations, and this innovative technology enables our global customer base to benefit from walkaway SPE-based sample preparation for a variety of MS applications. As the laboratory automation sector becomes increasingly focused on applicationdriven solutions, it is more important than ever to work with knowledgeable providers with an in-depth understanding of laboratories’ needs, both today and in the future. This acquisition reflects our ongoing commitment to providing customers with complete, end-to-end solutions to simplify laboratory workflows, and complements our existing MS sample prep consumables, including the AC Extraction Plate™. Full integration of the SPEware technology and product range with Tecan workstations will provide unrivalled throughput and flexibility for laboratories looking to automate MS workflows, as well as helping to improve the consistency and reliability of results. More on this topic, along with our customary mix of customer stories and novel applications, can be found in this issue of the Tecan Journal. Dr David Martyr CEO
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TECAN JOURNAL 1/2017
CONTENTS
Contents 2
CEO Welcome
4 - 5 Synthetic biology in the real world – automating the creation of new lifeforms
10 - 11 Putting the pieces together
6 - 7
How to reliably get more data from less volume
8 - 9
A smarter approach to LC-MS sample prep
10 - 11
Putting the pieces together
12 - 13
Vectoring in on success
14 - 15 Putting milk to the test 16 - 17 Finding the perfect match 18 - 19
A (cyto)genetic revelation
20 - 21 Effective sample preparation minimizes mass spectrometry maintenance
22 - 23
Lighter work for many hands
24 - 25 A natural affinity 26 - 27 Faster processing for biosimilars 28 - 29 Time saved in diagnostic vitamin B testing 30 - 31 Designed for flexibility, built for speed 14 - 15 Putting milk to the test
TECAN JOURNAL 1/2017
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SYNTHETIC BIOLOGY
Synthetic biology in the real world – automating the creation of new lifeforms Synthetic biology is, quite literally, the creation of new genetic constructs and novel micro-organisms with innovative functions. Together with systems biology, it provides a platform for translating advances in genomics, proteomics and molecular biology into real-world applications. Automating DNA synthesis Recent advances in robotics and liquid handling technologies are enabling synthetic and systems biologists to fully automate the design and production of the basic components of life. This ability to define and control the various steps involved in synthesizing genes,
more quickly and efficiently, with
commented Almer van der Sloot, a Senior
uncompromised accuracy. The various
Research Associate in the Institute’s
applications and collaborative ventures
Systems Biology and Synthetic Biology
described below give a taste of the
Research Unit. “We can now routinely
scope and commercial implications
perform 48 or even 96 DNA assembly
of the field at present, as well as the
reactions from start to finish in the time it
directions in which it could develop.
used to take us to do about 12 manually. Importantly, automation has also
promoters and other genomic control
An assembly line for life
regions with increasingly high precision
One need look no further than the
is making it possible for scientists to
Massachusetts Institute of Technology’s
reprogram the activities and capabilities
Synthetic Biology Center to get a sense
of bacterial, yeast and mammalian cells. Automated instruments and computer-controlled robotic systems have propelled synthetic biology from the research and development laboratory to commercial-scale, real-world industrial applications. This approach allows many of the time-consuming and labor-intensive tasks intrinsic to synthetic biology workflows – such as colony picking and liquid dispensing – to be performed
improved accuracy and reproducibility.” Producing drugs, chemicals, biofuels and more
of the breadth of applications being
Synthetic biology approaches are
investigated. Researchers at MIT are
also being widely explored for
developing genetic circuits capable of
biomanufacturing processes. For
regulating numerous cellular functions,1
example, Elanco Animal Health, a
with potential uses in areas as diverse as
division of Eli Lilly, is using Enbiotix’s
biofuel development and drug discovery.
engineered phage technology to develop
By automating specific protocols and
bacteriophage-based antimicrobial
processes within their workflow, the
therapies targeting specific infectious
MIT team has been able to fabricate
veterinary diseases. This type of ‘phage
plasmid constructs encoding these novel
therapy’ represents a complementary
biological circuits on a much larger scale.
antibacterial strategy to help reduce the
“Scaling up this process on a robotic
use of antibiotics.
system gives us higher throughput and repeatability, without the variability
Another example of synthetic
inherent in manual procedures,” said
biology-based production is Amyris’
researcher Dr Jonathan Babb.
use of microbial engineering to develop plant-derived ingredients for cosmetics
The Blog 4
Similarly, scientists at the University
and lubricants. The company uses its
of Montreal’s Institute for Research in
µPharm™ discovery and production
Immunology and Cancer have used
platform to create stable libraries of
automation to streamline the cloning
analogs of natural compounds. This
and DNA assembly workflow they use
technology offers rapid design and
to design artificial cell signaling circuits
scale-up of fermentation processes for
and sensors.2 “Automation has given
the production of target molecules in
us a dramatically higher throughput,”
engineered yeast strains.
TRENDS, NEWS, STORIES AND MUCH MORE! FROM THE EXPERTS TO YOU.
TECAN JOURNAL 1/2017
SYNTHETIC BIOLOGY
Global energy company Repsol is also applying synthetic biology technology to bioproduction, in this case for the development of micro-organisms capable of generating advanced biofuels via novel metabolic routes.3 Jose Miguel Seoane, a researcher in the biotechnology department at Repsol’s Madrid Technology Center, explained: “The investigation of new biological applications involves screening large numbers of mutants of different micro-organisms, enabling the best performing candidates to be selected for further studies. As we test thousands of different mutations, automated high throughput screening is the key to our success.” Building in flexibility Computer-controlled robotic systems can be used to automate virtually all aspects of the synthetic biology workflow, including next generation sequencing, DNA extraction, PCR set-up and clean-up, cell transformation and transfection, colony picking, biochemical and cell-based assays, and protein purification and expression screening. The flexibility and open architecture of
1) Reprogramming nature. Tecan Journal 3 2012, 22-23. 2) Designer proteins. Tecan Journal 3 2015, 20-21. 3) Developing the fuels of the future. Tecan Journal 2 2015, 20-21.
the Freedom EVO® workstation make it ideal for these applications, offering a complete solution for accelerating
For more information on Tecan’s
workflows and improving productivity
synthetic biology solutions, visit
for virtually any laboratory.
lifesciences.tecan.com/ syntheticbiology
www.tecan.com/blog TECAN JOURNAL 1/2017
5
LOW VOLUME PIPETTING
How to reliably get more data from less volume
The industrialization of biology
The industry-wide drive to generate
has become possible thanks to
more data has also created a demand
the automation of repetitive tasks – such as liquid handling – making 24/7 operation feasible.
for reliable assay miniaturization. Moving manual steps, such as pipetting, onto automated liquid handling solutions enables the reliable
This cost-saving automation
dispensing of lower volumes, which can
addresses several major
result in both reagent and sample cost
concerns for biology workflows. Firstly, automation brings consistency that reduces the risk of expensive errors that
savings. This is especially true when increasingly sensitive assays are used to screen libraries of potential drug candidates that are available in very limited amounts.
can, for example, delay the publication of your paper in a respected peer-reviewed journal, or hold up the development of a drug. The ability to implement
Dispensing at the lower specified limits of liquid handling platforms – in the microliter or sub-microliter range – can pose particular challenges for the manufacture of low volume disposable
low-error automation may
tips. This is especially true for highly
even be critical for regulatory
sensitive techniques, such as next
acceptance in clinical applications. Secondly, automation enables personnel to concentrate on key competencies and be more productive.
generation sequencing (NGS), where it is advisable to use high quality disposable tips from the manufacturer of the liquid handling instrument, as these issues are addressed during development.
Achieving economy of scale Massive technological advances have reduced the cost of sequencing the human genome from $10M to under $1,000 in less than 10 years, with NGS being the major driver. As a result, the bottlenecks have shifted from sequencing to library preparation. This process can be tedious and error prone when performed manually, as each library must be carefully prepared using time-consuming and resource-intensive processes (see further reading). Automation of library preparation minimizes errors, reduces hands-on time and increases throughput. It can, for example, ramp up the efficiency of NGS for monitoring clinical trials, helping to accelerate clinical development projects. Success in many NGS protocols relies on accurate and reproducible dispensing of carefully quantified library samples to ensure optimal cluster generation, and also carefully controlled dispensing of small volumes of expensive reagents. Failure can result in time-consuming and expensive resequencing. To meet these needs, automated library preparation is now available to the majority of labs interested in streamlining NGS processes.
The Blog 6
TRENDS, NEWS, STORIES AND MUCH MORE! FROM THE EXPERTS TO YOU.
TECAN JOURNAL 1/2017
LOW VOLUME PIPETTING
More with less – low volume pipette
trays, ANSI/SLAS format trays and
tips for high precision sub-microliter
nested trays, which improves throughput
dispensing
and lengthens walkaway times. Tecan’s 10 µl disposable tip can be used with
Consistently generating more data
the Liquid Handling Arm™ or Flexible
from lower reaction volumes relies on
Channel Arm™ of Freedom EVO® and
dispensing small volumes accurately
Fluent® liquid handling platforms
and reproducibly. This is why Tecan
respectively. The 10 µl disposable tips
has developed a portfolio of new 10 µl
are available in non-filtered and filtered
disposable pipette tips that increase
formats, and at two purity levels:
Further reading Baym M et al. Inexpensive multiplexed library preparation for megabase-sized genomes. PLoS One, 22 May 2015, 10(5). Lamble S et al. Improved workflows for high throughput
the precision of sub-microliter liquid handling. The result is improved success
• Tecan Pure has been developed
library preparation using the
rates in a number of applications,
for genomics research, forensics and
transposome-based Nextera®
including genomics research, cell-based
molecular diagnostics. These tips are
assays, forensics, molecular diagnostics
guaranteed to be free from human DNA,
system. BMC Biotechnol.
and microbiology.
PCR inhibitors, RNase and DNase.
The new 10 µl tips enable you to pipette
• Tecan Sterile is intended for cell-based
as little as 0.5 µl with confidence. This
assays and screens, and microbiology
gives an important advantage in
applications. These tips are guaranteed
applications that require low volume
to be sterile and free from human DNA,
pipetting due to high assay sensitivity,
RNase, DNase, pyrogens and endotoxins.
20 Nov 2013, 13, 104.
the expense of the reagent or the scarcity of the sample.
These tips, combined with the precision of automated liquid handling, will provide
An added benefit is that the new 10 µl
you with a reliable platform on which
tips are longer, enabling you to use a
to develop robust assay protocols
wider range of labware with deeper
that help you consistently generate
wells, such as PCR and 384-well plates.
more data from lower dispensed
The carrier choice is flexible, with a
volume.
range of formats including standard
www.tecan.com/blog TECAN JOURNAL 1/2017
7
MASS SPEC SAMPLE PREP
A smarter approach to LC-MS sample prep SPEware is the latest member
Routine analysis by mass spectrometry
and support of SPE consumables from
of the Tecan Group, providing
(MS) is now commonplace in a variety
a range of suppliers. Today it has grown
of sectors, including toxicology, drug
into a complete SPE solution provider,
discovery, forensics and hospital
as founder and CEO Phil Dimson
medicine. Despite this, sample clean-up
explained: “We started out very
and pre-analytical processing is still the
simply, working as a distributor and
analysis. The company
major challenge for these laboratories,
demonstrating the benefits of SPE
combines its proprietary smart
as traditional liquid-liquid extractions are
sample prep to our customers. We sold
chemistry consumables and
time consuming, difficult to automate
consumables from a variety of sources,
and don’t provide sufficient selectivity
and used our knowledge and
for more complex samples, creating a
understanding to show customers how
significant bottleneck. To overcome
SPE-based sample clean-up could
these issues, many laboratories have
increase the quality and reproducibility
help them achieve efficient
turned to solid phase extraction (SPE)
of their data, as well as reduce
laboratory workflows.
techniques, which not only represent a
maintenance requirements for
more time- and cost-effective approach
expensive MS instrumentation. As the
to sample clean-up, they are also more
popularity of this technology grew,
automation friendly, helping to increase
we found that more and more of our
throughput and improve reproducibility.
customers were not only looking to
However, a majority of companies
improve their data, they also wanted
advanced sample preparation solutions for laboratories performing mass spectrometry
positive pressure processors with an in-depth understanding of customers’ needs to
This application-focused approach is completely unique in the market, providing customers with a one-stop shop to support everything from sample reception to mass spec analysis. Jim Leontis and Phil Dimson, SPEware
offering SPE sample preparation
help streamlining their workflows.
solutions simply provide the chemistry
More laboratories were using MS to test
and consumables required to perform
more analytes, and so they needed
the extraction, with little consideration
systems capable of processing hundreds
of how this can be practically
of samples a day, which naturally led to
implemented in the laboratory workflow
automation. We launched our first
or the impact of varying sample
automated processor in 2000, and this
processing parameters on downstream
proved to be the big breakthrough
analytical results.
for us, as nobody else was offering a combination of chemistry, automation
SPEware Corporation, founded in 1997,
and workflow expertise.”
was originally created to serve the
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TECAN JOURNAL 1/2017
emerging MS sample preparation
Jim Leontis, Director of Sales, took up
market, offering independent supply
the story: “Our understanding of this
MASS SPEC SAMPLE PREP
synergy between efficient workflows
last five percent that helps them to
and clean analytical results has been
achieve reliable, high quality sample
the foundation of our growth, and
preparation and reproducible results.”
today we offer a wide range of solutions that combine proprietary
Phil continued: “Until now, we have only
SPE consumables – using our high
been able to offer the benefits of this
performance CEREX® microparticulate
comprehensive service to the North
chemistry – with dedicated automated
American market, and so becoming part
processors and application support.
of the Tecan Group was a logical next
This application-focused approach is
step for the business. By combining our
completely unique in the market,
smart consumables and existing
providing customers with a one-stop
automated processors with Tecan’s
shop to support everything from
liquid handling and workflow automation
David Martyr, CEO of Tecan,
sample reception to mass spec analysis.”
expertise and worldwide support
commented: “We are excited to
network, we now have the opportunity
welcome SPEware to the Tecan Group.
“Our technical expertise is what really
to offer complete SPE sample
The company’s range of market-leading
sets SPEware apart. We have a
preparation solutions to the global
smart consumables and automated
dedicated laboratory with a team of
market. Integration of our consumables
processors is a natural fit for our
application scientists – a mix of
and processing options onto the
advanced liquid handling platforms,
automation specialists, chemists and
company’s liquid handling workstations
offering customers a real advantage
mass spectrometry experts – who work
will not only enable us to provide truly
for MS sample prep. This will allow us
directly with customers to assist them
turnkey solutions – including all the
to provide fully integrated solutions
in tailoring our solutions to their exact
hardware, software, consumables and
that offer exceptional time- and
workflow needs. While it may be
technical support required for successful
cost-savings for laboratories large and
possible for a customer to perform a lot
automation of MS sample preparation
small, anywhere in the world.”
of this work themselves, our in-depth
– it will also allow us to further increase
understanding of their processes can
throughput and better serve highly
make a big difference – providing that
regulated environments.”
To find out more about the SPEware range of sample preparation products, visit www.spewarecorporation.com
SPEware can provide assistance and advice on every step of the MS workflow TECAN JOURNAL 1/2017
9
DRUG DISCOVERY
Putting the pieces together Biomolecular interaction analysis plays an important role in the pharmaceutical industry. SensiQ Technologies has optimized surface plasmon resonance technology for drug discovery applications, developing an automated system that can provide rapid affinity data for prompt identification of candidate fragment activities.
Early stage drug discovery is a numbers
explore, as well as identifying technology
game, often requiring hundreds or
partners we can collaborate with to
thousands of compounds to be
move this field forward.”
screened to identify potential drug
Tom Jobe, Chief Operating Officer, SensiQ Technologies, Inc.
candidates that interact with the
Over the past decade, SensiQ has
therapeutic target of interest.
established a broad range of SPR-based
Biomolecular interaction analysis (BIA)
instruments to streamline BIA, including
using label-free surface plasmon
the SensiQ Pioneer family of fully
resonance (SPR) is regarded as the gold
automated benchtop systems. Tom
standard approach for the binding
continued: “We first introduced the
affinity and kinetic studies performed as
Pioneer platform around six years ago
part of this process. SensiQ
and, over time, this system has been
Technologies, Inc. in Oklahoma City,
updated and enhanced, and new
USA, has developed a portfolio of
versions introduced for specific
label-free SPR devices for the life
applications. We currently offer a choice
sciences market, enabling the
of three systems, including the latest
generation of real-time data on the
addition to the range, the Pioneer FE for
interactions between molecules. Tom
fragment screening. This is a cutting-edge
Jobe, the company’s Chief Operating
area of pharma research, where large
Officer, explained: “SensiQ was founded
libraries of protein fragments are used to
12 years ago, with a focus on developing
create molecules so small that the body’s
new SPR-based tools for life scientists.
immune system does not attack them.
It is this combination of pinpoint positioning accuracy and very high resolution liquid handling that has enabled us to create the extremely sensitive Pioneer FE system. Our main market is pharma research,
The Pioneer FE has been developed in
principally early stage drug discovery
collaboration with a leading biotech
applications, where scientists are
company to optimize this process; it’s
looking for molecules that fit together
very much a case of fine-tuning our
very well and could eventually be
automated platform to offer superior
developed into novel therapeutics. We
throughput and sensitivity for binding
keep a very close eye on ongoing
affinity studies. The system uses our
developments in this sector, using
patented OneStep® gradient injection
feedback from both our customers and
technology, which helps to accelerate
key opinion leaders to enhance our
library screening by uniquely offering
products and develop new solutions
the ability to determine full kinetics and
that will streamline BIA studies. This
affinity from a single SPR injection.”
helps us to decide which areas to
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TECAN JOURNAL 1/2017
DRUG DISCOVERY
“When you design a new system, you
accuracy and very high resolution liquid
have a choice between developing all
handling that has enabled us to create the
the components in house, or using
extremely sensitive Pioneer FE system.”
established OEM solutions. We considered the in-house option but, as
“With any OEM product, it is also vital that
OEM components that suited our needs
system support will be available for a long
were already available, it made more
period, and Tecan’s history and reputation
sense to go down this route. We looked
were definitely an advantage. The local
at the various options available on the
Tecan team has been very supportive, and
market, and the resolution and accuracy
we have been able to work with Tecan on
offered by the Tecan Cavro® range was
a number of innovations for SPR
very compelling. We looked to the Tecan
automation. This partnership has also
team to recommend the most
given us greater insight into the direction
appropriate automation solutions for our
markets and technology are taking, which
purposes, and they suggested the Cavro
helps to guide our next generation of
Robotic Sample Processor (RSP) and
instruments. Working with Tecan to plan
Cavro Centris pumps. It is this set-up’s
where we are going next is very helpful,”
combination of pinpoint positioning
Tom concluded.
To find out more about Tecan Cavro components, visit partnering.tecan.com To learn more about SensiQ Technologies, go to www.sensiqtech.com
The Pioneer FE has been developed to simplify fragment analysis experiments TECAN JOURNAL 1/2017
11
CELL BIOLOGY
Vectoring in on success Genetic modification of mammalian cells is now a routine daily activity in academic and industrial R&D laboratories around the world, with viral vectors – such as lentivirus – commonly used to create new cellular models for a wide range of applications. SIRION Biotech specializes in the development of innovative gene delivery systems, helping to improve transduction and performance for both basic research and preclinical studies.
Viral vectors allow the efficient delivery
at SIRION, explained: “Our work centers
adeno-associated virus – offering
of genetic material into mammalian cells.
on providing individually engineered
methods suitable for both in vitro and in
This technology is now commonly used
genetic tools to modify mammalian cell
vivo applications. For many clients, we
in basic and medical research, enabling
lines. A majority of our business is in the
produce small to medium-sized batches
cell and molecular biologists to develop
preclinical sector, and ranges from
of vectors for use in their own
cellular models of healthy and diseased
designing and supplying viruses for use
laboratories, but we can also build full
tissues. SIRION Biotech, on the outskirts
in external laboratories, to partnerships
cellular models to over express, knock
of Munich, Germany, specializes in the
and collaborations aiming to develop
down or otherwise regulate one or more
creation of custom viral vectors for a
new vector technologies which will later
genes of interest.”
range of industrial and academic
be used in clinical applications, such as
research fields, including oncology,
gene therapies or the creation of
Silke Schrödel, Laboratory Head for Cell
neuroscience, regenerative medicine,
alternative vaccines.”
Culture, took up the story: “To build a
gene therapy, CAR-T cell therapy and
cellular model, we generally start by
vaccine development. Dr Carl Christel,
“We work with all the major viral vector
generating the viral vectors encoding
Senior Manager of Sales and Marketing
systems – adenovirus, lentivirus and
the gene of interest. We use lentiviral
The SIRION Biotech laboratory team
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TECAN JOURNAL 1/2017
CELL BIOLOGY
vectors 95 percent of the time, because
consistent results, even for cell lines with
this allows stable integration of genetic
low contrast. Just like the cell counting
material into the genome of most
algorithm, confluence measurements
dividing and non-dividing cells. We then
can be performed without the need for
transduce the target cell line using these
any complex adjustments.”
viral carriers, followed by extensive characterization – including various QC
“The system provides a standardized
checks and functional assays, depending
environment for our cells; we have full
on the project – and this is the stage
control over the temperature, humidity
where the Tecan reader comes into play.”
and gas partial pressures within the
To find out more about Tecan’s Spark reader, visit www.tecan.com/spark To learn more about SIRION Biotech go to www.sirion-biotech.com
reader chamber. This allows longer “We have used an Infinite® 200 PRO to
in-reader incubations without affecting
perform functional assays for a number
the consistency of results. The ability to
of years now, and have recently begun
incubate our cells in the reader also
evaluating the Spark® 10M for several
allows longer-term studies to be
applications. The Spark represents an
performed, without the operator needing
‘all-in-one’ system that is very well suited
to shuttle the plate back-and-forth
to our needs, and we have already
between the reader and a standard
tested the cell counting, luminescence
microplate incubator.”
and confluence modes for the assessment of our cellular models. It is
“We pride ourselves on the exceptional
very intuitive, and doesn’t require any
quality standards we adhere to for all our
complex adjustments between cell lines,
viral vectors and cellular models; we feel
helping us to accelerate and standardize
that this is what sets us apart from our
our processes, as well as ensuring that
competition internationally. We are trying
we meet the highest quality standards.”
to stay ahead of the game in terms of quality, and the Spark reader fits well
“The automated cell counting feature is
with this high standard. It provides us
a particularly interesting option, as
with a lot of flexibility for different
nearly every new project requires us to
experimental set-ups, helping us to
handle a new cell line. So far we have
deliver reliable and reproducible genetic
worked with over 200 different cell
tools to our clients,” Carl concluded.
types, and the instrument’s cell counting algorithm makes analyzing such a broad spectrum of cell types very straightforward; it is much easier and more reliable than manual cell counting methods. We are also using the cell confluence tool to monitor how specific genetic modifications influence cell
This allows longer in-reader incubations without affecting the consistency of results.
growth. This module offers very
TECAN JOURNAL 1/2017
13
FOOD SCIENCE
Putting milk to the test Milk testing plays an essential role in the dairy industry, ensuring the quality and safety of the end product. RAUDSZUS Electronic in Bavaria provides customized front-end sample preparation solutions to help laboratories cope with the high throughput demands of this work, enabling complete automation of the testing process, and has also recently introduced automated ELISA testing of milk for disease and pregnancy.
To accommodate wide-ranging throughput demands, RAUDSZUS systems incorporate Sias® Xantus® pipetting solutions from Tecan which can be tailored to individual needs. Michaela continued: “Each of our customers has specific demands and requires a different degree of automation. A small laboratory may only need to integrate a single sample preparation solution and analyzer, while a larger organization might connect several analyzers via a track system. It is important that our systems can be customized to provide exactly what the customer needs, and partnering with Tecan allows us to do this.” Several of RAUDSZUS’ automated systems are based on the Sias Xantus instrument
Dairy products depend on high quality
laboratories with front-end sample
raw materials. Milk testing is therefore
preparation solutions for integration with
essential, and so samples are collected
laboratory analyzers, and works with
from dairy farms and transported to
Tecan to provide tailored systems for
specialist laboratories to ensure the
its customers. Michaela Raudszus-
quality of the product. Typically, this
Weidenschlager, Head of Sales and
involves high throughput analysis of
Project Management, explained: “Some
various milk constituents, including
routine sample preparation is required
inhibitor testing, spore analysis and
before any testing can take place,
disease screening. More recently, there
including warming and mixing samples,
has been growing demand for ELISA
uncapping and recapping vials, and
testing for various analytes in milk, further
sub-sampling for further analysis. When
increasing throughput needs. Automation
this is done manually, it is time consuming
is essential for efficient, cost-effective
and there is always the potential for
sample processing, offering labor savings
human errors and inconsistencies. Over
and ensuring reproducibility, and a
the last few years, we have seen more
growing number of companies are turning
and more laboratories – even small ones
to laboratory automation solutions that
– wanting to automate their analyses, not
include liquid handling stations, track
only to reduce costs, but also to ensure
systems and RFID traceability.
that every sample is treated identically.
“Our automation solutions handle all the sample preparation steps required for fully automated milk analysis. This
Our role is to provide automated RAUDSZUS Electronic, based near
solutions that can be integrated with
Munich in Germany’s Bavarian forest, is
existing laboratory analyzers to eliminate
focused on supplying milk testing
manual processing.”
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TECAN JOURNAL 1/2017
Michaela Raudszus-Weidenschlager, Head of Sales and Project Management
FOOD SCIENCE
It is important that our systems can be customized to provide exactly what the customer needs, and partnering with Tecan allows us to do this.
standardizes procedures, enhancing
– with no user-to-user variation – the
reproducibility and eliminating manual
process is full traceable as every action
handling errors. One big advantage of
is logged, and staff are freed up for
the Sias Xantus systems is the ability
other activities.”
to cherry-pick samples. Each customer uses vials with different dimensions,
“We have worked successfully with the
and the distance between them varies.
Sias Xantus for over a decade now. Our
The pipetting arm can be set up to
own in-house knowledge and experience
accommodate these differences, allowing
is perfect for installations using existing
multiple samples to be transferred
applications or equipment, and is
directly into a microplate in one step
complemented by support from Tecan
using a multi-channel pipetting arm. This
when designing a bespoke system for a
is much quicker than sample-by-sample
specialist process. In just a few hours we
transfer, and is a big improvement.
can visit the company and discuss every
Equally important is the option to choose
detail of the project, using our combined
disposable or washable fixed tips;
expertise to devise a solution that
although the majority of customers
simplifies the customer’s workflow,”
choose fixed tips, there are occasions
Michaela concluded.
To find out more about the Sias Xantus, visit partnering.tecan.com/products/sias To learn more about RAUDSZUS Electronic, go to www.raudszus.de
when disposable tips are a necessity.” “Recently, there has been a surge in ELISA testing, particularly for pregnancy markers, as this is much cheaper for farmers than a veterinary call-out. When milk samples are sent to the laboratory, they simply request this additional test on an ad hoc basis, and the result is delivered via an online database. This is a huge benefit for farmers and has led to a large increase in ELISA sample numbers, with some laboratories now running as many as 50 microplates a day. Larger platforms are needed to cope with this demand, and we are currently installing a fully automated solution with two pipettors and an integrated plate reader at a customer site, enabling end-to-end processing from receipt of the initial sample to result readout. This offers several advantages; each step is perfectly timed and performed in the correct order
Several analyzers can be connected via a track system
TECAN JOURNAL 1/2017
15
MOLECULAR GENETICS
Finding the perfect match The success of hematopoietic stem cell donation is highly dependent on a close match between the donor and recipient human leukocyte antigen (HLA) alleles. DKMS Life Science Lab performs HLA typing of over a million potential donors a year, relying on automation to provide a cost-effective, high quality solution that delivers reliable high sample throughput.
Johanna Andreas, Automation Specialist
rejection. Some patients are fortunate
of samples are screened each week, which
enough to find a donor within their own
would be difficult – if not impossible – to
family, but the majority will depend on a
do manually. Automation is the obvious
donation from a completely unrelated
solution, allowing procedures to be
person. However, the likelihood of
standardized and more samples
finding a suitable donor outside the
processed, more rapidly and with greater
family is very low. To maximize the
reliability, helping to reduce the number of
chances of finding a match in as short a
repeat analyses required. This saves both
time as possible, donor registries have
staff time and reagent costs, ensuring that
been established around the world.
analytical workflows are as efficient and cost effective as possible. Johanna
With over six million registered donors,
Andreas, Automation Specialist in the
DKMS is the world’s largest bone marrow
Laboratory Technology Department,
Hematopoietic stem cell transplantation
donor center, and its Life Science Lab in
explained: “Our laboratory types around
is a treatment option for patients
Dresden, Germany, is one of the most
1.3 million samples a year – 25,000 a
suffering from certain cancers of the
advanced genotyping service providers
week! To cope with this workload, we use
blood, such as multiple myeloma or
globally. Rapid, reliable HLA typing of
liquid handling workstations to automate
leukemia. For the transplant to be
potential donors is essential, requiring the
our protocols, helping to streamline the
successful, it is essential that the donor’s
extraction of DNA from blood or buccal
various workflows.”
HLA type closely matches the recipient’s
swab samples to determine the exact
HLA type, minimizing the potential for
genetic profile of the donor. Vast numbers
Johanna continued: “When blood samples arrive at the laboratory, they are automatically aliquoted from blood collection tubes into 96-well plates, ready for DNA isolation. Until recently, this was performed on an older Tecan liquid handling platform which, after nearly 10 years of service, has been replaced by a Freedom EVO® 150. With just a single Liquid Handling Arm™ (LiHa), this is the most basic Tecan platform in our lab, but it offers straightforward, robust performance for this simple, highly repetitive task.” “Once the DNA has been isolated, it is quantified by fluorescence measurements using an Infinite® 200 PRO reader. This was originally a standalone instrument, which in 2016 was integrated into an additional new Freedom EVO 150; the fifth of its kind in our lab. Prior to this, DNA
Automation on a Freedom EVO platform enables cost-effective, high throughput HLA typing 16
TECAN JOURNAL 1/2017
MOLECULAR GENETICS
quantification was a tedious job for the
ready for HLA amplicon sequencing and
lab personnel, as each plate had to be
analysis using Illumina next generation
measured independently. This new
sequencing technology.”
platform also features a plate storage carousel – based on a LiCONiC LPX220 –
In addition to offering higher throughput
as well as a refillable trough for SYBR®
capabilities, automation helps to enhance
Green dye reagent. This set-up enables the
the quality and reliability of analytical
quantification of 70 plates in a single
protocols. This is reflected by the low
run, a real time and workload saver.”
number of repeat analyses performed by the laboratory. “Despite an ever-increasing
“The samples are then reformatted on
workload – we are now typing tens of
a Freedom EVO 200 workstation,
thousands of samples each week – the
sorting them into 384-well plates
number of repeat measurements we
containing either low or high
perform is steadily decreasing. Our PCR
concentrations of DNA in preparation
assays look at 12 different loci and, even if
for the next stage of the typing process,
an analysis is inconclusive and needs to be
PCR. This workstation uses two LiHas
repeated, we still save time by performing
to reformat two separate panels in
automated cherry-picking overnight – also
To find out more about Tecan’s
parallel, helping us to manage our high
on Tecan platforms.”
molecular diagnostics solutions,
throughput requirements.”
The Freedom EVO offers straightforward, robust pipetting of samples
visit www.tecan.com/genomics “We have been using our Tecan liquid
“We have successfully automated both
handling workstations for almost 10 years
To learn more about DKMS, visit
microplate- and microfluidics-based PCR
now, and are very happy with them. The
protocols on two additional liquid handling
large workdecks have space for a selection
www.dkms-lab.de
platforms – a Freedom EVO 150 and a
of different carriers, making the systems
Freedom EVO 200. The PCR method of
very versatile and giving us the flexibility
choice is dependent on the DNA
to use them for a range of assays. Most
concentration of the sample. For high
importantly, they are reliable systems and,
concentration samples, we use the
in the case of any issues, we receive good
microfluidics-based assay. The samples,
support. This is absolutely essential when
molecular identifiers and master mixes are
you have such a high sample throughput,
transferred to the sample inlets of a 192.24
as any unplanned downtime can cause a
Dynamic Array™ IFC (Fluidigm), and
huge backlog to build up very quickly,”
target-specific primers are added. The
concluded Johanna.
entire reaction takes place within the chip, and so the reagent volumes used are really small – the total assay volume is less than 10 nanoliters – which helps reduce the cost of the assay. For low concentration DNA samples, PCR is performed in 384-well plates. Finally the PCR products are harvested, pooled, purified and quantified,
Most importantly, they are very reliable, [which] is absolutely essential when you have such a high sample throughput. TECAN JOURNAL 1/2017
17
MEDICAL GENETICS
A (cyto)genetic revelation Specialist laboratories engaged in molecular genetics and cytogenetics are turning to automation to cope with ever-increasing sample numbers, implementing tailored solutions designed to handle a range of materials and meet specific testing needs.
Dr Sarah Volpert, Head of Cytogenetics & Cancer Cytogenetics Laboratories, amedes-group
y implementing B automated protocols, we have standardized quality and improved reproducibility. 18
TECAN JOURNAL 1/2017
The amedes group is a network of 60
wagnerstibbe of Laboratory Medicine,
laboratories and medical practices
Hemostasis, Human Genetics and
located across Germany and Belgium
Microbiology in Hannover – focus chiefly
that provides interdisciplinary medical
on genetic analyses, employing state-of-
diagnostic services for patients, doctors
the-art technologies for molecular
and hospitals, as well as delivering
genetics and cytogenetic investigations.
specialist laboratory management
To cope with ever-increasing sample
services to more than 40 hospital
numbers and standardize procedures,
laboratories. The laboratories offer a
the laboratories have implemented
wide range of tests, including standard
identical automation solutions tailored
and specialist laboratory medicine,
to their workflows, helping to ensure the
microbiology, gynecology, oncology,
quality and reliability of these complex
pathology, endocrinology, cytology,
processes within each lab and between
hemostasis, dysplasia, prenatal medicine
the two sites. Dr Sarah Volpert, Head of
and genetics, processing more than
Cytogenetics & Cancer Cytogenetics
150,000 samples per day.
Laboratories, amedes-group, explained: “Our main focus is on human genetics,
Two of the group’s German laboratories
particularly prenatal screening and
– the MVZ Department of Laboratory
diagnosis, and oncology. We use a
Medicine and Clinical Genetics Rhein/
variety of molecular genetic techniques
Ruhr in Essen and the amedes MVZ
– Sanger and next generation
The Tecan Integration Group customized the Freedom EVO to fit amedes’ exact needs
MEDICAL GENETICS
The amedes team
sequencing, and array technologies – as
the company as the instruments are high
results of genetic analyses to decide on
well as cytogenetics by routine analysis
quality and we are familiar with their
the most appropriate course of
of G-banded chromosomes and
operation. We also set great store by
treatment. Not only is the system time
fluorescence in situ hybridization (FISH).
good service and know from past
and cost efficient, but there are benefits
In the past, this work has been done
experience that the company responds
for staff too; as much less hands-on
manually. However, with sample numbers
quickly if we need help, which is essential
time is required, highly qualified,
continually rising and a need to reduce
to avoid any delays in sample analysis.”
experienced members of staff now have
the time to results without compromising
extra time to focus on more interesting,
on quality, optimizing our processes to
“With the help of the Tecan Integration
make the workflow as efficient as
Group (TIG), we transferred our manual
possible was essential. Automation was
processes onto a Freedom EVO®*
“We have a very good relationship with
the logical way forward.”
platform adapted to our needs, and are
Tecan. It is a well-known brand that we
reaping the benefits. However good
have faith in, and the company gives us
Sarah continued: “As one of the largest
scientists are, there will always be
very good support. We have local
cytogenetic laboratories in Germany, we
individual differences in manual
representatives who we know, and the
handle a wide range of materials,
techniques; by implementing automated
central hotlines always guarantee quick
including chorion and amniotic cells,
protocols, we have standardized quality
communication, which is important for
fetal and peripheral blood, and bone
and improved reproducibility.
us. We really appreciate the company’s
marrow aspirates and tumor tissues from
Turnaround times are also increasingly
personal approach,” Sarah concluded.
cancer patients. It is really important to
important. Automating our processes as
have the flexibility to adapt our sample
much as possible enables us to operate
preparation processes to the individual
for 12 hours, six days a week, starting
requirements of each specimen type,
earlier and taking advantage of the
To find out more about
and also to be able to expand to
system’s huge capacity to run larger,
Tecan’s clinical diagnostics
accommodate more samples in the
48-sample batches when we need to.
future, if necessary. We needed a
This is particularly beneficial at peak
solutions, visit www.tecan.com/
bespoke automated platform tailored to
periods, helping to reduce the
meet the specific demands of our
underlying run times and allowing
workflows. We have used Tecan
results to be reported more rapidly,
platforms in our clinical laboratories for a
which is especially important in prenatal
long time and so, although we looked at
diagnostics and oncology, where
other systems, it made sense to stay with
clinicians increasingly depend on the
less routine tasks.”
clinicaldiagnostics To learn more about amedes, go to www.amedes-group.com
*Not for clinical use in the USA
TECAN JOURNAL 1/2017
19
CLINICAL DIAGNOSTICS
Effective sample preparation minimizes mass spectrometry maintenance Testosterone levels are typically determined using automated immunoassay analyzers, but this has limitations. Liquid chromatography-tandem mass spectrometry (LC-MSMS) offers a selective and accurate alternative, and the Center for Advanced Laboratory Medicine at the University of California San Diego is using a novel extraction technology to automate sample preparation for this technique.
Senior CLS Specialist Judy Stone
Judy continued: “Reliable, accurate
“When I moved to UCSD-CALM,
results must also be cost effective to
I approached Tecan about doing some
be useful for patient care. In terms of
collaborative studies using a
materials, analytes such as testosterone
Freedom EVO® workstation and the
can often be measured at a lower cost
AC Extraction Plate, starting with
using LC-MSMS compared to an
testosterone analysis. Most clinical
automated immunoassay analyzer.
laboratories do these tests on an
However, the trade-off is that LC-MSMS
automated immunoassay instrument,
is labor intensive; sample preparation
which works well for samples from men
involves a great deal of pipetting, and
with normal testosterone levels, but is
there is always concern about the risk of
not always the best technique for
mixing up samples. In addition, there are
samples from women, children or men
ergonomic considerations associated
with low serum testosterone. LC-MSMS
with manual processes. Automating
offers better accuracy and selectivity,
sample preparation on a liquid handling
but robust and reliable preparation of
workstation can help with these issues.”
large sample numbers is difficult using
The University of California San Diego Center for Advanced Laboratory Medicine (UCSD-CALM) uses state-ofthe-art technologies to provide diagnostic medicine and pathology services, as well as developing new
ith cleaner extracted samples, instruments W need maintenance less often, minimizing unplanned downtime and sample backlogs.
diagnostic assays for therapeutic applications. Mass spectrometry (MS)
“I was working at another laboratory
manual liquid-liquid extraction. This
is an important analytical tool in the
when Tecan launched the
process can be tedious and hard to
laboratory, but the challenge is
AC Extraction Plate™ for MS sample
automate, and requires some expertise
developing and validating reliable,
preparation. I tried it, and found it so
to use routinely with acceptable
reproducible sample preparation
simple to use; I just manually pipetted
performance. In contrast, the
methods suited to a clinical setting.
the samples into the plate and used the
AC Extraction Plate is extremely simple,
Judy Stone, Senior CLS Specialist in the
existing instrument parameters, and it
requiring just a plate shaker and
Toxicology Laboratory, explained: “I’ve
worked the first time, which was very
accurate pipetting, which can be
been working with MS for about 25
impressive. However, we had just
reproducibly performed by the
years, initially with gas chromatography-
invested a huge amount of time and
Freedom EVO. We can prepare a batch
mass spectrometry. More recently, the
resources in validating a different
of samples on the liquid handling
focus has been on LC-MSMS. This has
sample preparation method and,
platform with as little as 15 minutes of
become the technique of choice for
as this process was almost complete,
hands-on time, or from start to finish in
many applications, with laboratories
it simply wasn’t realistic to change
about 90 minutes, which is a significant
developing and validating new methods
direction at that point.”
labor savings. Manual preparation can
for testing patient samples.” 20
TECAN JOURNAL 1/2017
CLINICAL DIAGNOSTICS
take from 30 minutes of hands-on time
“Ultimately, our goal is to increase
unplanned downtime and sample
for a small batch to two and a half hours
both our test menu and the number
backlogs. When it comes to MS
for larger numbers of samples. The
of samples performed per test on a
sample preparation, I firmly believe
results after using the AC Extraction Plate
daily basis. We already perform
that clean-up is worth the time,”
for sample preparation were so
25-hydroxyvitamin D testing by mass
Judy concluded.
reproducible during validation that we
spectrometry, and plan to automate
are considering whether we actually
the manual pipetting steps of this
need to run a full set of 11 calibration
process on the Freedom EVO in the
standards with each batch of samples.
future. We are also developing an
AC Extraction Plate visit
If comparable results can be obtained
AC Extraction Plate method for
www.tecan.com/acplate
with just two standards per batch –
1,25-dihydroxyvitamin D, which will be
the highest and lowest concentration
challenging as it is present at much
To learn more about UCSD-
calibrators – or using a standard curve
lower levels than 25-hydroxyvitamin D.
CALM, go to pathology.ucsd.
from another day updated with a couple
In the long term, investment in sample
of key calibrators, this is a clear benefit
preparation techniques such as the
edu/ucsd_center_for_advanced_
to the laboratory. We are retrospectively
AC Extraction Plate makes sense as, with
studying our data to see if this is viable,
cleaner extracted samples, instruments
and it looks very promising so far.”
need maintenance less often, minimizing
To find out more about Tecan’s
laboratory_medicine.htm
Automation helps eliminate tedious manual pipetting TECAN JOURNAL 1/2017
21
DRUG DISCOVERY
Lighter work for many hands Drug development pipelines are under ever-increasing pressure to deliver more comprehensive data in a shorter timeframe, while reducing costs and making in vitro assay results more relevant to in vivo drug behavior. Assay automation and miniaturization has become essential for the oncology research team in Bayer’s Pharmaceuticals Division.
Knowledge of the relationship between
Recent trends towards assay
technologies – such as Tecan’s D300e
the dose, bioavailability and clinical
miniaturization have significantly
Digital Dispenser – capable of
effects of a drug candidate are
reduced the cost and effort for drug
reproducible dispensing in the nano- to
fundamental to the development of new
titration studies, with a shift towards
picoliter range. The ability to dispense
therapeutics. Without in-depth
performing these experiments earlier on
drug candidates directly into assay plates
characterization of the effects of a
in the drug development workflow.
has transformed the workflows of the
compound at a biochemical and cellular
Collecting more comprehensive data on
oncology research laboratories at Bayer,
level, it would be impossible to safely
early compounds supports the process
as Carmen Wegner, biology lab assistant,
progress drug candidates to the clinical
of compound optimization and
explained: “We have three teams in
phases of development. Drug titration
identification of the most promising
oncology research, more than 60 people
studies are, therefore, at the heart of the
candidates for the next steps of
overall, and we perform a wide range of
drug development process, with many
investigation. The reduction in assay
different activities on a daily basis. Our
hundreds of dose-response curves
volumes has been driven by the
group is primarily responsible for
generated each day across the globe.
development of novel liquid handling
performing functional assays, testing
The D300 has changed the way Bayer’s Pharmaceuticals Division approaches many assays
22
TECAN JOURNAL 1/2017
DRUG DISCOVERY
compounds from our chemical department against human or animal cellular models of various cancers.” “The timescales for our development projects have become much shorter,
The way our laboratory approaches many assays has really changed.
so anything that helps to accelerate research is much appreciated. We acquired the first D300 Digital Dispenser in 2013 and, since then, the way our laboratory approaches many assays has really changed. The Tecan D300s are very easy to use, and only require a brief introduction. After loading the assay plate and the Dispensehead cartridge containing the compound, the instrument takes care of everything else. This saves a great amount of staff time in planning and setting up experiments. There is no need for manual pipetting anymore, and the D300 performs calculations automatically – based on your target final concentrations.” “Direct digital dispensing allows nanoliters – or even picoliters – of compound to be reliably added to a microplate well, which we couldn’t achieve manually. This eliminates the need for serial dilutions – as well as media changes for many cell-based assays – which also saves a lot of staff time, and reduces the amount of compound, reagent and consumables waste.”
To find out more about Tecan’s
“We now have five D300 instruments
D300e Digital Dispenser, visit
in the department – with more than
www.tecan.com/d300e
60 users. We find the software intuitive, and the systems are usually maintenance
To learn more about the
free. We only need Tecan’s technical
Pharmaceuticals Division of
support to help us program special
Bayer go to
applications. Overall, we are very excited about the instruments.”
www.pharma.bayer.com
TECAN JOURNAL 1/2017
23
DRUG DISCOVERY
A natural affinity Receptor binding assays form an integral part of the preclinical screening service provided by Eurofins Pharma Discovery Services division. The first stage of the protocol is the transfer of tissue samples to a 96-well plate, a process that must be carefully performed to avoid any cross-contamination.
Pharma Discovery Services Receptor binding assays are a key tool in
liquid handling platform. This has a
third workstation – a Freedom EVO 100
the pharma industry, enabling scientists
number of benefits: it is highly flexible –
– customized for our tissue dispensing
to study a compound’s affinity for a
allowing a variety of sample transfer
protocols.”
chosen receptor. Compounds are
requirements to be accommodated –
dispensed into a microplate, then
assay plate preparation is consistent,
The tissue dispensing process begins with
membrane receptors and the
and cross-contamination is virtually
uploading the assay plate preparation
radiolabeled ligands are added. This is
eliminated compared to manual
requirements to the LIMS. Barcoded low
followed by an incubation step, after
processes. In addition, the automated
residual volume troughs containing the
which the radioligand-receptor complex
tissue dispensing platform provides
tissue preparations – five tissue types per
is harvested, and the amount of
full sample traceability, which is
batch – are loaded onto the workstation
radioactivity is determined to
increasingly being demanded by
and scanned by a PosID™ Positive
calculate the degree of binding
customers in this sector. Scientists gain
Identification System. Information
that has occurred.
too, as they have extra time to devote
corresponding to the barcode
to other tasks. Andy Chou, an associate Eurofins Pharma Discovery Services division, based in Taipei, Taiwan, is a contract
scientist in the Molecular Operation Department, explained: “Our department mainly performs
identification is extracted from the LIMS and a Freedom EVOware® worklist is created for the preparation of 96-well assay plates. Up to six 96-well assay
research organization with a
receptor binding assays, which
plates per batch are placed on the carrier,
worldwide customer base of
involve several liquid handling
and the preparations are transferred into
pharmaceutical companies
steps. These include dispensing
the plates via a MultiChannel Arm™ 96
engaged in drug discovery.
of test compounds and tissue
(MCA96) using disposable tips. Once the
The company has several
preparations, as well as the
transfer is complete, a report is generated
decades of experience in
addition of radioligands. More
for each assay plate and exported to the
preclinical screening and
than 10 years ago, we automated
LIMS, ensuring sample traceability.
offers a comprehensive
our compound dilutions on a
Downstream processing – incubation,
service portfolio. To help
Freedom EVO® platform,
harvesting and radioactivity
with its radioligand receptor
followed a few years later by the
measurements – then takes place.
binding assays, Eurofins
installation of a second system
has automated its tissue
for addition of the radioligands.
Phyllis Tsai, also an associate scientist in
dispensing process on a
More recently, we have added a
the Molecular Operation Department,
The risk of cross-contamination was always a big concern, but automated pipetting using disposable tips eliminates this problem.
24
TECAN JOURNAL 1/2017
DRUG DISCOVERY
The Eurofins team
continued: “With a diverse range of
consistency of the assay plates prepared
requests from our customers, we need
is good too, with the inter-plate variation
To find out more about
to be extremely flexible in terms of the
around 2 % CV. Implementing automated
Tecan’s molecular diagnostics
assays we perform, and the Freedom EVO
procedures that employ barcode reading
solutions, visit
helps us to achieve this. Of all the systems
– importing and exporting data directly
www.tecan.com/cellbiology
we assessed, it was the platform best
from and to the LIMS – is another key
suited to our needs, enabling us to pipette
benefit, linking each tissue preparation to
by row or column – 8- and 12-channel
a specific position in the microplate. This
dispensing – using the MCA96. It also
ensures we maintain the sample
allows us to pipette into two rows of a
traceability that is vital to our customers,”
microplate simultaneously, a functionality
Andy concluded.
To learn more about Eurofins Pharma Discovery Services, go to www.eurofinspanlabs.com
that is not available on other liquid handling workstations. Another important feature of the system is its ability to incorporate our customized 24-well troughs, which have a low residual volume
The Freedom EVO offers flexibility and sample traceability for receptor binding assays
Dispensing compounds Adding membrane receptor
of less than 0.8 ml, on a Te-Shake™ shaker. Tissue preparations are very precious, and
Adding radiolabeled ligand
it is important to minimize any waste as far as possible; the customized troughs significantly reduce the tissue volume
Incubation
required for our assays.” Harvesting
“Previously, the risk of cross-conta mination was always a big concern, but
Counting on the reader
automated pipetting using disposable tips eliminates this problem, increasing the robustness of our assay results. The
Radioligand binding assay workflow
TECAN JOURNAL 1/2017
25
BIOPROCESSING
Faster processing for biosimilars The biosimilars market is expanding rapidly as the patents expire for an increasing number of high profile biopharmaceutical agents. The complex nature of biologics requires extensive characterization of the production techniques and in vivo effects of new biosimilars before they can be released onto the market. Coherus Biosciences is using advanced laboratory automation to help screen chromatography conditions as part of its downstream purification processes for new biosimilars.
The importance of biologically-derived therapeutics is of ever growing importance to the pharmaceutical sector, offering more specific and targeted therapies for the treatment of a wide range of conditions and diseases. Unlike generic versions of small molecule drugs, which have chemically identical active ingredients to marketed products, most biologics are heterogeneous preparations composed of multiple protein or antibody subspecies, as well as a variety of other closely associated biomolecules. They are therefore complex to both manufacture and purify, and this presents a major challenge for follow-on manufacturing of generic versions of these medicines – known as biosimilars – once their patents expire. Coherus Biosciences – based in Redwood City, California – develops, manufactures and markets high quality biosimilar therapeutics with the aim of reducing healthcare costs for treating chronic or life threatening diseases. Founded in 2010 by a group of like-minded industry veterans with extensive experience in the biopharmaceutical industry, the company focuses on inflammatory diseases and
Brian Williamson with Coherus’ Fluent Laboratory Automation Solution
cancers, aiming to expand access to biologically-derived medicines.
biologic. Chromatography is commonly
downstream laboratory, explained: “In
used to separate target molecules from
our development program, we screen
Downstream processing is an essential
the rest of the production cell culture,
many different chromatography
element of the biosimilar workflow,
requiring rigorous screening of
conditions and media to identify
ensuring reliable and reproducible
chromatography conditions to enable
protocols capable of separating out
manufacture of a product showing the
efficient extraction and recovery. Brian
various proteins of interest from all the
same in vivo effect as the original
Williamson, a senior scientist in Coherus’
other cell culture components, such as
26
TECAN JOURNAL 1/2017
BIOPROCESSING
Our Tecan systems are enabling us to run new types of experiments that were not previously possible, generating much more data and making it much easier to answer questions and find solutions for our manufacturing environment. degraded proteins and product-related
the lab, as this frees up the Freedom EVO
contaminants. We built up our
platform for large-scale screening of
laboratory from scratch on a limited
chromatography conditions,” Brian
budget, but I requested automated
continued. “The Fluent has an eight-
equipment to help accelerate the whole
channel Flexible Channel Arm™ with
downstream development cycle. It’s
disposable tips, which not only allows us
obviously a commitment on my part, as
to quickly perform repetitive liquid
there’s a significant learning curve with
handling tasks – such as preparing
any advanced laboratory equipment, but
cultures and batching plates – it also
being able to automate chromatography
gives us the flexibility to run PhyTip®
experiments is very helpful; it allows us
columns (PhyNexus) for small-scale
to very quickly screen conditions to find
and lower-fidelity separations. This
a protocol that is suitable for use in a
technology is ideally suited to sample
manufacturing environment.”
preparation applications, offering rapid clean-up of eight samples in parallel for
“I was already familiar with the various
our analytical laboratory.”
options on the market, and chose Tecan liquid handling platforms because I had
“Our Tecan systems are enabling us to
some limited experience of using the
run new types of experiments that were
company’s instruments in a previous role,
not previously possible, generating
and I could see how well they would fit
much more data and making it much
into our whole development workflow.
easier to answer questions and find
A lot of work has been done in this field
solutions that are appropriate to
with Atoll MediaScout® RoboColumns® –
implement in a manufacturing
it’s clearly a front runner in the sector –
environment. Both systems, each with
and combining this technology with the
a different focus, are great time savers
Freedom EVO® platform is ideal, allowing
and really benefit our workflow; the
us to run eight chromatography
Freedom EVO/RoboColumns
separation experiments in parallel. There
combination is clearly the way to go for
are other systems on the market that
large-scale chromatography condition
offer a similar approach, but they just
screening, and the Fluent offers more
don’t have the degree of fidelity that this
advanced automation, with higher
combination does.”
precision and reproducibility. The
The Freedom EVO allows complete automation of the Atoll MediaScout RoboColumns workflow
support we receive from Tecan is also “We are now running about 16 columns
fantastic; we always get a quick reply to
every day, with each cycle of eight
any questions we have, which is a really
experiments taking six to 10 hours. This
good way to resolve issues that come
gives us an eight-fold increase in
up,” Brian concluded. Up to eight chromatography experiments can be run in parallel
throughput compared to manual methods, as a researcher could only run two or three columns a day. The samples collected from the MediaScout
To learn more about Tecan’s
columns are then either analyzed in our
bioprocessing solutions, visit
laboratory to find chromatography
www.tecan.com/bioprocessing
conditions that can be scaled up for manufacturing purposes, or by our
For more information on
analytical laboratory to support other
Coherus Biosciences, go to
studies or regulatory filings.”
www.coherus.com
“We have also purchased a Fluent® 480 Laboratory Automation Solution to perform general liquid handling tasks in
TECAN JOURNAL 1/2017
27
CLINICAL DIAGNOSTICS
Time saved in diagnostic vitamin B testing Mass spectrometry is rapidly becoming the method of choice for quantitative analysis of micronutrients such as vitamins B1, B6, B12 and D, as well as for steroids, hormones and many other drugs. For clinical laboratories, the bottleneck of MS-based techniques is not the analysis, but the pre-processing of the samples to remove proteins and other biological molecules that could interfere with the results.
The role of micronutrients in maintaining
Holland. It is a very busy laboratory,
platform following a demonstration in
good health and well-being in an aging
reporting over 10,000 patient results
Amsterdam. Our aim was to completely
population has become increasingly well
every day, so we need rapid and
automate the LC-MS sample preparation
understood over the past 30 years, but it
efficient analytical processes to ensure
and so, based on Tecan’s advice,
is only in the last decade or so that reliable
we can manage this workload.”
we purchased a Freedom EVO 150
assays to effectively detect dietary or
workstation.”
metabolic deficiencies of many of these
“We originally began quantifying
nutrients have become common. This
vitamins B1 and B6 over 20 years
The laboratory’s Freedom EVO was
combination of better understanding and
ago on a HPLC system, however, the
commissioned in the summer of 2016,
more effective testing has seen a huge
assay involves a derivatization step
and has been optimized to work in
increase in the number of requests clinical
followed by a lengthy analysis time. It
a 96-well microplate format. Plates
laboratories receive from both primary
also requires a lot of manual pipetting
containing patients’ hemolyzed whole
and secondary care, requiring a change
– technicians needed to spend several
blood samples, calibrators and quality
in working practices to accommodate
hours at a time performing very
control samples are placed on the deck
their growing workloads.
repetitive tasks – and so we recently
of the instrument, and trichloroacetic
looked into automating the sample
acid (TCA) is added to each well to
Requests for vitamins B1 (thiamine)
preparation to increase throughput,
precipitate out the plasma proteins.
and B6 (pyridoxine) – which play roles
reduce variability and eliminate pipetting
The plate is then sealed and spun down
in energy uptake from carbohydrates
errors. Instead of simply automating
in a centrifuge, and the supernatant
and fats respectively, as well as being
our existing protocol, we chose to
from each well is transferred to a fresh
involved in many other metabolic
switch to an ultra high performance
96-well plate using the Tecan system.
pathways – are among those that have
liquid chromatography with tandem
This analysis-ready plate is then
seen a large increase. The Clinical
MS (UHPLC-MSMS) technique, using
re-sealed and transferred to a
Chemistry Department at Noordwest
an automation-friendly protein
standalone UHPLC-MSMS system.
Ziekenhuisgroep (Northwest Clinics)
precipitation step for pre-analytical
Edwin continued: “Although we did not
Alkmaar in the
have any previous
Netherlands now
experience with
processes over 19,000 assays a year for each of these metabolites alone. Edwin ten Boekel, a Clinical Chemist in the
Most importantly, automation of sample preparation on the Freedom EVO has halved the time required for processing the same number of samples.
department,
Tecan platforms, once you familiarize yourself with the Freedom EVO, the system is very easy to use. The customer support from Tecan has also
explained: “Our
been good; they
department is one of two laboratories
sample processing. We investigated
are friendly and we never have to wait
that are part of the Northwest Clinics,
several systems to automate this
long for replies to our queries. We have
serving a population of around 600,000
sample preparation, and I was very
now implemented several protocols on
people across the province of North
impressed with the Freedom EVO®
the instrument, and the reproducibility
28
TECAN JOURNAL 1/2017
CLINICAL DIAGNOSTICS
and repeatability of the automated
to increase traceability, which is obviously
procedure is improved compared to our
very important in a diagnostics lab.
prior pipetting procedures. We carried
Most importantly, automation of sample
out a control experiment by repeatedly
preparation on the Freedom EVO has
processing different batches of the same
halved the time required for processing
samples, and obtained a CV of less than
the same number of samples. This not
five percent, which is well within our
only eliminates the need for staff to
acceptable limits. By using a handheld
repetitively pipette samples, it also
barcode scanner and barcoded
releases them for other tasks,”
microplates, we have also been able
Edwin concluded.
To find out more on Tecan’s clinical solutions, visit diagnostics.tecan.com For more information on Noordwest Ziekenhuisgroep, go to www.nwz.nl/English/About-us
NWZ’s Freedom EVO offers fully automated pre-analytical processing
TECAN JOURNAL 1/2017
29
BIOMEDICAL ENGINEERING
Designed for flexibility, built for speed Multidisciplinary research calls for multifunctional laboratory equipment capable of rapidly switching between applications. Staff in the Department of Biomedical Engineering at the TU Eindhoven understand that having the right instruments for your workflow can allow more users to benefit and help to accelerate research. – despite the age of our Safire2 reader – but the growing number of bioluminescence studies we are now performing, as well as an increase in students in the lab, means that we had effectively run out of instrument capacity. We looked at the various systems on the market, and the Spark® was an excellent match for our needs. The ability to switch between filter- and monochromator-based measurements is ideal for a multidisciplinary group, and the Spark’s bioluminescence module has a 40 filter set that enables you to perform complete luminescence scans, which is a huge advantage for assay development. Having all three readers from the same manufacturer also simplifies staff training and equipment maintenance.” Members of the Chemical Biology Group
“One of the biggest advantages for our lab is the system’s Te-Cool™ option,
Biomedical engineering is a broad
antibody-based sensors to DNA-based
which was launched just before we
field, with scientists from numerous
reaction networks, nuclear receptors
purchased our Spark reader. Because
disciplines coming together to develop
and supramolecular architectures.
we’re such a big lab, our readers are
innovative solutions to challenges in
It’s a very busy environment.”
in high demand and constant use.
the pharmaceutical, diagnostic and
Being able to accurately set the assay
healthcare sectors. The Chemical
This multidisciplinary team requires
temperature and actively cool the
Biology Group in Eindhoven University
laboratory equipment that is equally
measurement chamber is therefore
of Technology’s Department of
versatile, enabling a wide range of
a real boost to our productivity. For
Biomedical Engineering is even more
activities to be performed quickly and
example, one user’s assay may require
diverse than most, as it was formed by
easily. “All our instruments need to
the measurement temperature to be
merging together three existing research
be both robust and flexible,” Anniek
fixed at 37 °C, while the next user
groups. The laboratory is now home to
continued. “We have had two Tecan
may want to perform an experiment
over 120 researchers, with a wide range
multimode readers – a Safire2™ and
at 20 °C. Previously, this could lead to
of research interests. Anniek den Hamer,
an Infinite® F500 – in the laboratory
long delays while waiting for the reader
a PhD student in the group, explained:
since the group was created, and
to cool and equilibrate to the correct
“We’re a big lab with a lot people – not
perform a variety of measurements,
temperature, with this time effectively
just PhD students and postdocs, but also
including absorbance, fluorescence
‘lost’. To speed up this process for our
undergraduate and masters students
intensity, fluorescence polarization
Infinite and Safire readers, we have
– working on different biotechnologies
and bioluminescence. We have always
resorted to opening the measurement
and applications; everything from
been very happy with the reliability
chamber and using a fan to accelerate
protein-protein interactions and
and performance of these instruments
cooling, but this is far from ideal, and is
30
TECAN JOURNAL 1/2017
BIOMEDICAL ENGINEERING
not particularly effective on a warm day. This issue is completely eliminated by the Spark’s Te-Cool module. You simply set it to the temperature you want, and it quickly and efficiently heats or cools the measurement chamber to the target value. This saves a huge amount of time, and allows us to perform more experiments on any given day.” “The SparkControl™ software is also very intuitive to use. Anyone who has experience with the Infinite’s iControl™ software can use the new system with virtually no training, and it’s very easy to explain to new users, which is particularly useful for teaching undergraduate or masters students with limited lab experience. Each user can also save and share their individual protocols – which saves a lot of time when switching between measurement modes or assay types – and if we have any queries, the Tecan helpdesk is always very quick to respond. Overall, we’re very pleased with the Spark system and the Te-Cool module, it’s proving to be a very versatile instrument.”
One of the biggest advantages for our lab is the system’s Te-Cool option.
To find out more about Tecan’s Spark multimode reader, visit www.tecan.com/spark To learn more about TU Eindhoven’s Department of Biomedical Engineering, go to www.tue.nl/en/university/ departments/biomedicalengineering/
The Spark reader was purchased to help cope with the lab’s increasing number of students
The lab’s Safire2 reader has performed reliably for many years
TECAN JOURNAL 1/2017
31
The Blog TRENDS, NEWS, STORIES AND MUCH MORE! FROM THE EXPERTS TO YOU. www.tecan.com/blog
Every lab. Every day. Empowered. Australia +61 3 9647 4100 Austria +43 62 46 89 330 Belgium +32 15 42 13 19 China +86 21 220 63 206 France +33 4 72 76 04 80 Germany +49 79 51 94 170 Italy +39 02 92 44 790 Japan +81 44 556 73 11 Netherlands +31 183 44 81 74 Singapore +65 644 41 886 Spain +34 935 95 2531 Sweden +46 8 750 39 40 Switzerland +41 44 922 81 11 UK +44 118 9300 300 USA +1 919 361 5200 Other countries +43 62 46 89 33 Tecan Journal, Customer Magazine of Tecan Trading AG., ISSN 1660-5276 Design: OTM/London www.otmcreate.com Photography: Günter Bolzern/Zürich www.bolzern.tv Editor in Chief: Tecan Trading AG, Antonietta Allocca Editor: kdm/UK www.kdm-communications.com Editor: UP THERE, EVERYWHERE/Sweden upthereeverywhere.com Print: DAZ Druckerei Albisrieden AG/Zurich www.daz.ch Address: Tecan Trading AG, Marketing Communications, Seestrasse 103, CH-8708 Männedorf, Switzerland, hello@tecan.com, www.tecan.com To register for the Tecan Journal please go to www.tecan.com/journal © 2017 Tecan Trading AG, Switzerland, all rights reserved.
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Tecan Group Ltd. makes every effort to include accurate and up-to-date information within this publication, however, it is possible that omissions or errors might have occurred. Tecan Group Ltd. cannot, therefore, make any representations or warranties, expressed or implied, as to the accuracy or completeness of the information provided in this publication. Changes in this publication can be made at any time without notice. All mentioned trademarks are protected by law. In general, the trademarks and designs referenced herein are trademarks, or registered trademarks, of Tecan Group Ltd., Mannedorf, Switzerland. A complete list may be found at www.tecan.com/trademarks. Product names and company names that are not contained in the list but are noted herein may be the trademarks of their respective owners. For technical details and detailed procedures of the specifications provided in this document please contact your Tecan representative. This journal may contain reference to applications and products which are not available in all markets. Please check with your local sales representative: www.tecan.com/contact