Edition 1/2022
Tecan Journal Life Sciences, Diagnostics and Partnering
Generating a cellular infection model for monitoring SARS-CoV-2 replication
Automating a herd of tests
Mitosis as a potential therapeutic target for cancer? A divided topic
Pumping a way for effective gas emission monitoring
Pages 8-9
Pages 10-11
Pages 14-15
Pages 16-17
CEO WELCOME
Empowering customers to scale healthcare innovation globally The speed of development in the biomedical and healthcare sectors over the last two years has been, by necessity, unprecedented. The translation of life sciences research into the clinical environment has accelerated to a previously unimaginable pace to tackle COVID-19, requiring closer collaboration between researchers, technology providers and regulatory authorities than ever before. Although the pandemic is still a major global challenge, the lessons learned are already being applied to other areas. There is a strong belief within the life sciences community that the accomplishments coming out of this pandemic are not lost, and that there needs to be further investment in both research and the development of technologies that help to ensure that the world is better prepared for future healthcare challenges. As a result, the diagnostics sector is now more widely adopting advanced technologies – for example, in oncology-related applications – and the need for clinically-validated genomics and proteomics workflows has never been stronger across multiple disease areas. This transition of innovative technologies from a research environment into the clinically regulated space is only likely to accelerate in the coming years, creating demand for new diagnostic modalities. Tecan is ideally placed to lead the development of this new wave of capable diagnostic technologies, using our expertise as a leading provider of solutions to both the research and IVD markets to actively bridge the gap between the research lab and the clinic. The addition of Paramit Corporation to the Tecan team further strengthens the breadth and depth of our understanding and capabilities, from innovative life sciences solutions and point-of-care devices, to the supply of enabling modules and the design and manufacture of entire clinical workstations. We are very excited about expanding into the medical devices space, empowering our customers to scale healthcare innovation from life sciences to the clinic. In addition to this expansion of the Tecan business through Paramit, we are also continuing to invest strongly in our existing capabilities, developing new platforms, enabling reagents and leading digital solutions for our existing Life Sciences and Partnering customers.
Achim von Leoprechting CEO
2
TECAN JOURNAL 1/2022
CONTENTS
Contents 2
Welcome
4 - 7 Mind the gap: How to navigate the IVDD-IVDR transition
8 - 9 Generating a cellular infection model for monitoring SARS-CoV-2 replication
10 - 11 Automating a herd of tests 8-9
12 - 13 Exploring zoonotic pathogens in
Generating a cellular infection model
Australian livestock
for monitoring SARS-CoV-2 replication
14 - 15 Mitosis as a potential therapeutic target for cancer? A divided topic
16 - 17
Pumping a way for effective gas emission monitoring
18 - 19 Tecan acquires medical device specialist Paramit 19
Leading the debate
12 - 13 Exploring zoonotic pathogens in Australian livestock
Applications and platforms presented in the Tecan Journal may not be available in all markets. Please consult your local Tecan office for information.
TECAN JOURNAL 1/2022
3
REGULATORY AFFAIRS
Mind the gap: How to navigate the IVDD-IVDR transition Is your business IVDR-ready, or are there treacherous gaps in your strategy? We are now approaching the end of the five-year transition to the In Vitro Diagnostic Regulation (IVDR) 2017/746 – a major regulatory overhaul that calls for reclassification and recertification of all in vitro diagnostic (IVD) devices registered in the European Union. With its expanded scope and more stringent requirements, IVDR impacts the entire supply chain, and there’s no time to lose. We can help you take stock of the situation, with a special focus on how to prepare when it comes to managing OEM relationships and new partnerships.
IVDR: Blockbuster or showstopper? The definition of an IVD medical device encompasses a wide range of laboratory
• B etter ability to accommodate new technologies and scientific advances • Facilitation of global trade through
IVDR: Five challenges of the change Before we consider what you can do at this point to ensure as smooth a
developed tests, point-of-care devices,
the promotion of more convergent
transition as possible, here is a brief
instruments, reagents and kits used to
regulations
recap of some of the most notable
analyze human samples and guide clinical decision-making. Until now, most governments have taken a relatively lenient stance on the regulation of IVD devices compared to pharmaceutical drugs and medical devices that come into direct contact with patients. IVDR 2017/746 brings
While the IVDR should ultimately be a
changes and challenges the IVDR
positive step forward for the industry,
brings:
most IVD manufacturers still have a lot
1. Extended IVD definition and scope
of work ahead of them to ensure a smooth transition and avoid IVDR becoming a ‘showstopper’ that freezes them out of EU markets.
Under IVDR, the definition of an IVD device has been clarified and now encompasses more types of devices, including relatively new technologies
European regulations for IVD devices
Timeline to the new IVD regulation
like predictive genetic tests,
into closer alignment with the more
The IVDR came into force in May 2017,
companion diagnostics, and even
rigorous requirements for other
setting the clock ticking on a five-year
medical devices, and seeks to make
transition period for manufacturers
the regulatory process more ‘robust,
selling IVD medical devices into
transparent, predictable and
European markets. As the IVDR is
sustainable’.
phased in, the current IVD Directive
Some of the intended benefits of IVDR
(IVDD 98/79/EC) will be phased out.
include: • H igher standards of quality and safety for IVD devices • M ore clearly defined definitions and regulatory scope • I mproved oversight and traceability
With no grandfathering of devices already on the market, all IVDs must
oversight extends to devices such as home-use genetic tests that are made available to EU citizens through ‘distance sales’ (eg. over the internet) by companies based outside the EU – even if the tests themselves are carried out in non-EU countries.
While five years may seem like ample
2. New device classification system
time to make the transition, there is still much more to be done and considerable uncertainty in the process, particularly since notified
throughout the device lifecycle
bodies (NB) are going through the transition process themselves.
4
makes it clear that regulatory
be transitioned to the new regulation.
across the supply chain, and
The Blog
software. The new regulation also
One of the most dramatic changes introduced by the IVDR is the replacement of the current list-based classification system with a clear set of rules for assigning each device to one of four risk categories, ranging from
TRENDS, NEWS, STORIES AND MUCH MORE! FROM THE EXPERTS TO YOU.
TECAN JOURNAL 1/2022
REGULATORY AFFAIRS
lowest risk (Class A) to the highest (Class D). Under the IVDD classification system, NB oversight was only required for products expressly listed in Annex II of the directive (about 20 percent); the vast majority of IVD devices could ‘self-certify’ without any need for NB involvement. The new regulation turns this ratio on its head, with about 80 percent of devices expected to fall into risk classes B, C or D – all of which require some level of NB oversight. Clearly, this greatly increases the regulatory burden for IVD manufacturers and their NBs. 3. Likely NB bottlenecks With tighter regulations and more IVDs requiring oversight, the workload for NBs will rise sharply. At the same time, the number of available NBs is shrinking. When IVDR-designated NBs do come online, they will likely prioritize working with companies who have already established a relationship with them in advance, and have all their technical documentation in order. 4. Lifecycle approach Compared to IVDD, IVDR takes a more holistic approach that spans the entire
www.tecan.com/blog TECAN JOURNAL 1/2022
5
REGULATORY AFFAIRS
The Blog 6
TRENDS, NEWS, STORIES AND MUCH MORE! FROM THE EXPERTS TO YOU.
TECAN JOURNAL 1/2022
REGULATORY AFFAIRS
product lifecycle, with more
there a dedicated team empowered to
and updated as needed, with
comprehensive measures to
drive the strategy forward?
provisions to facilitate IVDR
encourage continuous evaluation both pre- and post-launch. IVDR retains all existing IVDD requirements and adds new ones, including: • Requirements for manufacturers to establish and demonstrate an effective quality management system (QMS) • M ore stringent requirements for clinical evidence demonstrating conformity • N ew requirements for post-market
Reclassification: Have all IVD products in your pipeline and on the market
What about outsourcing and OEM
been classified according to the new
partnerships?
rules? Has a tracker been set up to
In this shifting regulatory landscape,
indicate the certification strategy (renew IVDD certificate or pursue IVDR certification) and NB submission timeline for each device? Portfolio review: Have cost-benefit and ROI studies been carried out? Does it make sense to rationalize your portfolio, or make adjustments to the
performance monitoring and
product pipeline? Does your strategy
reporting
include exploration of non-EU markets,
• Introduction of unique device
compliance?
and collaborations outside the IVD
OEM partnerships can be a source of great experience and guidance, or they can become your worst nightmare. In light of the extended scope of regulatory oversight that IVDR brings, it is more important than ever to partner with companies you trust, to help you design and develop high quality compliant IVD devices, supply you with the technical expertise and data you need for product
identifiers (UDIs) for improved
medical device industry?
certification, and ensure compliance
traceability throughout the device
NB alignment: Have reclassified
device lifecycle. And of course, those
lifecycle 5. Greater supply chain oversight and device traceability The new regulations have been extended to cover the entire supply chain, adding additional responsibilities for manufacturers as
products been mapped against NB requirements, and suitable NBs identified? Have you reached out to applied for IVDR designation? Can
To learn more about the transition
application and audit process?
to IVDR, watch our webinar at
importers, distributors and authorized
documentation, clinical evidence,
representatives. Each link in the supply
labeling and packaging, QMS, post-
chain has the responsibility to check
market surveillance and reporting.
the previous link, and legal
Have available technical and clinical
manufacturers must appoint a Person
data been reviewed against
Responsible for Regulatory
conformance requirements? Have
Compliance (PRRC) to ensure IVDR
plans been established to acquire
compliance across the chain. IVDR also
outstanding support data?
if needed.
QMS against the new regulations? Has your QMS been updated accordingly? Has a PRRC been appointed and
As we approach the IVDD-IVDR
appropriately trained to ensure
transition, it is important to sanity-
compliance across the supply chain?
check your progress and close any
Transition budget: What is the burn
are a few important items for your checklist: Infrastructure: Is your current business model working for you when it comes to executing your transition plan? Are C-suite leaders – including CFOs and COOs – appropriately engaged, and is
www.tecan.com/ivdr
QMS: Have you reviewed the current
Keep calm, but don’t just ‘carry on’
gaps in your transition strategy. Here
compliant with IVDR requirements.
they send you guidelines for their
Gap analysis: Assess technical
audit suppliers and subcontractors
partners must have a QMS that is
NBs to enquire whether they have
well as other economic operators –
gives NBs discretionary authority to
can be maintained throughout the
rate to date, and does it match with projected spend to the end of the transition period? Quality contracts: Have quality contracts with existing suppliers, contract manufacturers and other economic operators been reviewed
www.tecan.com/blog TECAN JOURNAL 1/2022
7
VIROLOGY
Generating a cellular infection model for monitoring SARS-CoV-2 replication Work to characterize and
Prior to the pandemic, the Institute for
characteristics and, most importantly,
further understand the
Medical Virology – part of Goethe
included a fluorescence cassette as a
University – supported viral diagnostic
good starting point for automatic
efforts at University Hospital Frankfurt.
measurements.”
molecular pathology of SARSCoV-2 became a focus for many virology departments following
However, when the scale of the emerging pandemic became apparent,
Using the Sleeping Beauty transposon
the identification of the novel
the team turned its expertise to
system, the team generated a robust and
virus responsible for COVID-19.
studying SARS-CoV-2. The group
versatile cellular infection system based
Drs Marek Widera, Alexander
realized that existing methods to
on its A549-AT lung cell line, which
monitor and quantify SARS-CoV-2
allowed high throughput SARS-CoV-2
infectivity in cell culture were both time
infection experiments and live cell
Wilhelm and colleagues at University Hospital Frankfurt,
consuming and labor intensive, so
imaging at a low cost.1 Measuring the
began developing a cell line that could
cytopathic effect of the virus – structural
attention to developing an
accurately model the way the virus was
changes in the host cells caused by viral
in vitro cell culture model
infecting humans. Marek explained: “We
infection – was a key criterion for the
that could realistically mimic
actually stopped all work, except on
group, which could be assessed by
SARS-CoV-2, and switched completely
imaging the cells. Marek commented:
to look at methods for quantification,
“Our standard virological assays are
and to assess how infectious the virus
performed by assessing cells manually
is. Automatic approaches to cell-based
under the microscope, which is time and
methods were very limited and so, in
labor intensive, and requires specially
early 2020, we decided to develop a
trained personnel. The user needs a lot
cell line that was very easy to maintain,
of experience to assess whether you
had very convenient proliferation
have a full cytopathic effect or not, and
Germany, turned their
the viral replication cycle, to decipher the mechanism of COVID-19 infection.
Marek Widera (left) and Alexander Wilhelm of University Hospital Frankfurt 8
TECAN JOURNAL 1/2022
VIROLOGY
there is room for user variability, especially when they have been evaluating a large number of samples in a session. We decided to transform neutralization tests, IC 50 tests, antiviral compound testing and also the
he live cell imaging option and the CO2 T control within the measurement chamber were ideal.
determination of the cytopathic effects by combining our newly created A549-AT cell line model with automated measurement and analysis.” “When the Spark® Cyto was launched, we knew this was exactly the instrument we needed,” Marek continued. “The live cell imaging option and the CO2 control within the measurement chamber were ideal. It was also the perfect size, because the restricted space in our biosafety level 3 (BSL-3) laboratory meant that we could not accommodate large devices.” Alexander added: “Working with the Spark Cyto, we found that, in addition to developing our initial idea of working with immunofluorescence, we were also able to evaluate the cytopathic effect with just the system’s bright field imaging capabilities. That was quite surprising for us, as it was a very new idea, which is why we are now developing this further with great technical support from colleagues at Tecan.” “Several hours after infection, we can observe syncytia formation, where the cell membranes of neighboring cells fuse,” Alexander elaborated. “This is something that you can see clearly with the Spark Cyto system. Depending on the virus strain we are using, we see more or less one giant syncytia
formation in the entire well of a
studies, because it is still unclear
96-well plate. This phenomenon is quite
whether immunity or antibody-
homogeneous with our cell line, and
mediated protection continues against
allows for highly standardized readout
new SARS-CoV-2 variants of concern.
assays. Optimizing the instrument’s
This assay system will also be easily
software parameters for A549-AT cells
adaptable to study other viruses with
infected with SARS-CoV-2, we
susceptible cell lines in the future.
developed our own analysis workflow
There are many types of virus-induced
to create standardized protocols for
cytopathic effects, and bright field
investigators to easily and consistently
analysis using the Spark Cyto is a very
quantify the cytopathic effect.”
nice tool to analyze these.”
Alexander continued: “The biggest benefit of this approach is speed. For example, if a company or another lab is testing thousands of compounds with our cell line, it would be up to four times faster with the current systems
1) Widera, M et al. Generation of a Sleeping Beauty transposon-based cellular system for rapid and sensitive screening for compounds and cellular factors limiting SARS-CoV-2 replication. Front. Microbiol. doi: 10.3389/ fmicb.2021.701198
that are available. It’s a combination of the Spark Cyto’s imaging facility and our cell line that enables a low cost and
To find out more about live
really quick readout method. We are
cell imaging with Tecan’s
continuously optimizing our current
Spark Cyto, visit
protocols for future high throughput
lifesciences.tecan.com/sparkcyto
projects, and so we are collaborating with the research and development department at Tecan to build on the success we have already had.” Marek concluded: “We have already had several requests for the cell line, and now have new collaborators who
To learn more about the Medical Virology Team, or to obtain the A549-AT cell model, go to www.kgu.de/einrichtungen/ institute/zentrum-der-hygiene/ medizinische-virologie/team/
are using the cells for different purposes. In our lab, we do large cohort
TECAN JOURNAL 1/2022
9
VETERINARY SCIENCE
Automating a herd of tests The COVID-19 pandemic is an important reminder that pathogens are not only transmitted via air and contact with other humans, but also from animals and through food. This highlights the need for effective diagnostic tools that offer fast testing of animal and environmental samples to help monitor livestock and aquaculture. Qualyse is a French company that does exactly this, using advanced laboratory automation to provide immunoserology and molecular diagnostic testing for up to 12,000 samples a day.
Saint-Denis in Deux-Sèvres, and Tulle in
involved in monitoring these herds,
Corrèze – and use a wide range of
accounting for 50,000 samples a year.
chemistry, microbiology and molecular
We also have a small unit responsible for
biology techniques. Our animal health
monitoring transmissible spongiform
Laboratory testing is an essential part
services in Champdeniers perform both
encephalopathies, such as BSE in cows
of veterinary diagnostics, not just to
ELISAs and molecular diagnostics,
and scrapie in sheep and goats.”
help alleviate or cure diseases in
testing for a wide range of diseases and
domestic animals, but also for
pathogens that can affect animal or
Qualyse’s large workload would not be
biosurveillance to prevent zoonotic
human health.”
possible to manage without laboratory
diseases being transferred from farm
automation. Cédric continued: “We’ve
animals to humans via the food chain.
Mathieu Godillon, Technical
had automated pre-analytical systems
Qualyse is a leading provider of
Immunoserology Manager at Qualyse,
since 2002 but, when we gained the
laboratory services in northern
commented: “In the immunoserology
department of Corrèze – which has a
Aquitaine, France, offering food safety,
unit, we analyze more than 500,000
huge cattle population – as a customer
animal health and environmental
bovine samples a year for
in 2018, we needed to scale up our
testing for everything from cattle and
biosurveillance, which accounts for
testing capacity accordingly. It became
goats to oysters and other shellfish.
almost the entire cattle population
clear that our facilities were undersized
Cédric Trouvé, Production and Quality
across several departments. Deux-
and outdated, so we began looking for
Director at Qualyse, explained: “We
Sèvres also has a significant goat
a supplier to help us implement a high
have three main sites – in La Rochelle in
population for around four months of
throughput workflow. We spoke to
Charente-Maritime, Champdeniers-
the year, and we are the only company
several suppliers during the tender process, and chose to partner with Tecan because the company’s solutions were the best match for our workflow and needs. We were particularly impressed by the Fluent® 1080 Automation Workstation, as its dual liquid handling arms would allow 12 plates – around 1,000 samples – to be processed in a single run.” Almost all of Qualyse’s workload for animal health testing arrives as blood tubes collected from local farms, which are then centrifuged to produce serum samples for analysis. Mathieu added:
Qualyse uses a Fluent 1080 to perform its pre-analytical sample reformatting
10
TECAN JOURNAL 1/2022
VETERINARY SCIENCE
We are very happy with Tecan’s exceptional commitment, from the delivery and installation of the user-friendly instruments to the company’s continued support.
“The Fluent 1080 now performs a
testing. These instruments are
Tecan systems, we have the capacity to
majority of our pre-analytical
extremely reliable, with a proven track
process around 12,000 samples in a
reformatting, transferring spun-down
record in human immunodiagnostics,
day, and generally run between 8,000
serum samples from tubes to two
making them the natural choice for our
and 9,000 per day. This is particularly
identical 96-well daughter plates – a
workflow. Each platform has a capacity
important during seasonal peaks –
‘work plate’ for processing and a
of about 20 microplates a day, and we
when our team works extended shifts
second for archiving – using washable
mainly use these to look for antibodies
of 10 hours – as without the level of
fixed tips. The plates are then moved to
against various infectious or parasitic
automation our Tecan systems offer,
either a Fluent 780 or a Fluent 480
diseases, such as brucellosis,
this would be very difficult to achieve.”
– again using fixed tips – to generate
hypoderma and paratuberculosis.” “We are very happy with Tecan’s
intermediate plates on a disease-bydisease basis. For each serum sample,
Cédric continued: “On the molecular
exceptional commitment, from the
we may be testing for six or seven
diagnostics side, nucleic acid
delivery and installation of the user-
diseases – including brucellosis,
extraction is carried out in a BSL-3 lab,
friendly instruments to the company’s
paratuberculosis and gestational
then we have a Freedom EVO® 100
continued support. Moving forward,
disorders. This can be performed by
which performs PCR set-up,
we intend to move from 96- to
either testing individual samples, or by
dispensing both the extracted DNA or
384-well plates with the help of the
automatically pooling up to 10 samples
RNA and PCR master mixes ready for
Tecan team, adding even more
per well to increase throughput and
the thermal cycler. Since the start of
flexibility to our workflows. We would
reduce costs. We also have a separate
the pandemic, we’ve also been
highly recommend Tecan to those in
Fluent 780 using disposable tips for
working as a subcontractor to perform
the animal health sector who may
when the risk of cross-contamination is
screening of SARS-CoV-2 variants –
benefit from such capabilities,”
more critical, such as performing
running almost 4,000 samples a day at
concluded Cédric.
sample reformatting and pre-analytics
peak times – alongside up to 2,000
for PCR testing, or screening before
samples from our regular workflow on
sales between breeders or export.”
the Freedom EVO.” For Research Use Only. Not for use in diagnostic procedures.
“Once the intermediate plates have
“Prior to the introduction of the Tecan
been generated, they are transferred to
platforms, our main challenge was
a different Tecan platform for testing,”
always the pre-analytical workflow;
Cédric explained. “For the
this is now much faster and very
veterinary diagnostics solutions,
immunoserology workflow, we have
reliable,” Mathieu commented. “The
go to www.tecan.com/veterinary
two Freedom EVOlyzer® platforms,
Tecan workstations allow us to run our
which bring together all the modules
workflow in 96-well plates and, more
To learn more about Qualyse, visit
– pipetting arms, washers and readers,
importantly, let us process a greater
www.qualyse.fr
etc. – required to fully automate ELISA
number of samples. Across all the
To find out more about Tecan’s
TECAN JOURNAL 1/2022
11
VETERINARY SCIENCE
Exploring zoonotic pathogens in Australian livestock Antimicrobial resistance is a growing issue preventing the effective treatment of numerous parasitic diseases in both humans and animals. The lack of effective antimicrobials for the treatment of a growing number of diseases represents a serious threat to global public health, making it imperative that governments and societies around the world take action to tackle this issue. Scientists at the University of Murdoch in Australia are studying antimicrobial resistance in livestock – which can potentially spread to humans – using a statistical approach of surveillance to monitor the situation more closely. Antimicrobial resistance (AMR) is
pathogens that are present in Australian
project is primarily funded by the
causing a growing number of standard
livestock. Sam explained: “Antimicrobial-
Australian government, but we also
antibiotic, antifungal, antiviral and
resistant bacteria that emerge and
have global collaborators. The aim of
antimalarial treatments to become
spread in livestock and other animals
this work is to create a snapshot
ineffective, leading to increased
contribute to the global burden of AMR.
database of populations of enteric
prevalence and spread of many
As a result, there is a significant public
bacteria and, once optimized, use it to
infectious diseases. This issue is not
health concern over the transfer of such
monitor levels of antibiotic resistance
isolated to human medicine, and is a
bacteria to humans via food and the
in livestock all over the world.1 We use
growing concern for veterinary
environment, and the rapid transmission
a range of techniques, including
medicine. It is particularly problematic
of the genes responsible for AMR into
classical antibiotic susceptibility testing
in livestock, due to a combination of
other human pathogens.”
(AST), RT-PCR, NGS, MALDI-TOF and traditional bacteriology methodologies,
relatively concentrated animal
such as gram staining.”
populations and the rise of drug-
“Our lab focuses on determining the
resistant zoonotic pathogens that can
minimum inhibitory concentration
spread between animals and humans.
(MIC) of drugs for bacteria found in
“This type of surveillance project
fecal samples from chickens, pigs,
requires large-scale sampling of
Dr Sam Abraham, a microbiologist at
sheep and cattle – such as E. coli,
indicator organisms to identify AMR,
Murdoch University in Perth, Australia, is
Salmonella, Staphylococcus and
and monitor whether these resistances
investigating AMR at the interface
Streptococcus – and characterizing
are being detected more frequently,”
between human and animal health,
the genomic mechanisms of drug
Sam continued. “Unfortunately, most
primarily by studying zoonotic
resistance in these bacteria. This
countries only use low numbers of animal samples for surveillance, which is unlikely to highlight emerging issues until it is too late. This is because conventional, human-centric surveillance methods are hamstrung by high processing costs and slow turnaround times, making them incompatible with the high volumes of sampling required to accurately depict a population’s AMR status. We therefore need to use high throughput automation and genomics solutions with rapid turnaround times, enabling the analysis of large data sets to help identify emerging problems quickly, and respond to those problems rapidly.” “I was initially introduced to Tecan when I was a postdoc setting up the
Tecan’s automated solutions and library preparation kits are helping Sam Abraham (left) and and his colleagues to study antimicrobial resistance in livestock 12
TECAN JOURNAL 1/2022
first national network on AMR
VETERINARY SCIENCE
surveillance of Australian animals. I saw one of its trade displays for microbiology and chatted to the very knowledgeable team, who helped us to select a solution that would best suit
he number of errors that we generate is also T hugely minimized – the beauty of automation – and this results in excellent quality data.
our AMR screening requirements. In 2016, we were able to purchase our Tecan systems using grants from the
These colonies are then picked and
one researcher working on this at a
Department of Agriculture and
grown – either for a few hours or
time and, as our throughput has
Australian Pork Limited. The Tecan
overnight – in a 96-well plate.”
increased so significantly, others can
this project, partnering with us on the
“From here, there are different routes
is an incredibly efficient time saver.
grant application, and working closely
of analysis depending on the sample
The number of errors that we generate
with us to design an automation set-up
and what we are looking for. Some we
is also hugely minimized – the beauty
that would meet our needs. We
send to MALDI-TOF mass spectrometry
of automation – and this results in
currently have two Freedom EVO® 150
analysis for bacterial identification, or
excellent quality data, which is
workstations, one of which has a
we perform AST in house to determine
fantastic. We are very happy with
number of SciRobotics devices
the AMR profile. We have also recently
the instruments,” Sam concluded.
integrated onto it to create our
integrated next generation sequencing
Robotic Antimicrobial Susceptibility
with our microbiology workflow, using
1) Laird TJ, et al. J Antimicrob Chemother,
Platform (RASP). 2 ”
a Freedom EVO 150 to perform
2021. doi: 10.1093/jac/dkab403. Online
automated library preparation with
ahead of print.
“Our workflow starts with a
Tecan’s Celero™ EZ DNA-Seq library
2) Truswell A, et al. J Antimicrob
homogenized sample, which is
preparation kit. This allows us to rapidly
Chemother, 2021, 76, 1800-1807. doi:
transferred to the Freedom EVO –
perform genotyping or whole genome
10.1093/jac/dkab107.
where it could potentially undergo
sequencing on bacteria that have
various dilutions depending on the
demonstrated AMR. Genotyping gives
sample – and automatically plated out
us the full picture about the resistant
using the PetriPlater™. The plates are
pathogen: is it human-, livestock- or
stacked and stored in a PetriSel™, and
even gull-derived? Is it only a problem
To find out more about Tecan and
all of our tubes and plates are barcoded
for animal health, human health, or both? We can answer all of these
SciRobotics’ colony picking and
so that the samples can be automatically tracked. This makes the
questions with genomics. All of the
whole system very efficient, and
data generated is then sent to and
troubleshooting is much easier if there
stored in our national database.”
spend time on different tasks, which
team here in Australia was pivotal to
are ever any problems. We plate on
For Research Use Only. Not for use in diagnostic procedures.
plating solutions, visit www.tecan.com/colonypicking To learn more about the School of Veterinary and Life Sciences
chromogenic agar, which allows our
“Using automation, we can process
PickoloMI™ robotic colony picker –
5,000 to 10,000 bacterial isolates a
programmed with assistance from
week – around 150 plates a day –
www.murdoch.edu.au/school-of-
Tecan – to easily identify and
compared to a couple of hundred
veterinary-and-life-sciences/
differentiate specific micro-organisms.
manually. This means that we only need
at Murdoch University, go to
TECAN JOURNAL 1/2022
13
DRUG DISCOVERY
Mitosis as a potential therapeutic target for cancer? A divided topic Mitosis plays an essential role in
are disrupted during cancers, leading
growth and cellular replacement,
to uncontrolled proliferation.”
and is often dysregulated in cancers, making the process of therapeutic interest. Researchers
The lab’s aim is to follow this complex signaling cascade at the molecular level, which requires the development
at the University of North
of novel fluorescence microscopy tools
Carolina at Chapel Hill (UNC
for high content screening. Fortunately,
Chapel Hill) are developing
the group was able to draw on
novel cell imaging tools to help them classify key components of mitosis and identify new therapeutic targets.
expertise from within the department, as Klaus Hahn, Thurman Distinguished Professor of Pharmacology, explained:
Nicholas Brown, Assistant Professor in Pharmacology
“My lab focuses on building molecules that are used for a wide range of
groups abutting each other?’ or ‘what
imaging applications in biosensors,
do they sit on?’. This simply isn’t
optogenetics and chemogenetics. We
something you normally do in live cell
Mitosis is the stage of the cell cycle
use them ourselves to study immune
imaging – it is tough to go into that
where replicated chromosomes divide
cells and motility, but my lab is
kind of detail in a live cell. But as a
into two new nuclei, giving rise to
probably best known for the
chemist, these are very interesting
genetically identical cells. In healthy
application of these tools in other labs.
questions to study.”
systems, this process only occurs when
Nick therefore approached me with
we are growing, or need to replace old
what sounded like a really fun and
The joint UNC Chapel Hill team has
or damaged cells. However, cells grow
exciting application of these molecules.
developed a unique fluorescence-
and divide uncontrollably in cancers.
He had this exquisitely detailed cellular
based ‘binder/tag’ approach capable of
Therefore, fully understanding which
system, and wanted to ask molecule
reporting the conformational changes
molecules control mitosis, as well as
level questions, such as ‘which
of individual molecules in live cells
what stage of the process they affect,
conformational changes are
(Figure 1). The advantage of this system
is of interest for the identification of
occurring?’, ‘how are the different
is that only a very short, seven-peptide tag is inserted into the protein of
new therapeutic targets. Nicholas
interest, minimizing the risk of
Brown, Assistant Professor in
disruption to normal protein or cellular
Pharmacology at the UNC Chapel Hill
function. The team is now developing
School of Medicine, explained: “The
and optimizing cell lines with a range of
process of mitosis is controlled by a
tagged proteins for high content
signaling cascade called the spindle assembly checkpoint, at the heart of which is the anaphase-promoting complex (APC). The APC functions as a ubiquitin ligase, adding ubiquitin chains
= binder
screening. Klaus commented:
= tag
biosensor molecules in live cells for
and rounds of cell growth under
proteasome degradation and move the
different conditions. While this is the
cell cycle forward. During normal cell
bread and butter of biosensor
function, the spindle assembly
development, it is normally quite time
checkpoint uses a variety of ‘silencing
consuming. Fortunately, just before
factors’ to inhibit the activity of the cell cycle – but these inhibitory signals 14
TECAN JOURNAL 1/2022
imaging applications is a very tedious process. This means multiple iterations
to macromolecules to target them for
APC – preventing progression of the
“Traditionally, optimizing expression of
Figure 1: Schematic of the binder/tag approach1
starting this project, we were approached by Tecan with the offer to
DRUG DISCOVERY
he Spark Cyto has removed a lot of the T tedium from the workflow, so the people in the lab love it. test the Spark® Cyto plate reader with
“I’ve used Tecan plate readers since I
whole cell cycle, so the Spark Cyto’s
live cell imaging. The company was
was a graduate student, and I’ve always
ability to incubate cells and provide
interested in exploring new ways of
liked the brand, so it was a good
quantitative imaging over a full time
using the system, and we were ready
match,” Nicholas added. “This project is
course is invaluable.”
with some pretty unique applications
still at the test stage, so we’re
here! The Spark Cyto is ideal for this
performing in vitro screening, purifying
1) Liu, B et al. Biosensors based on
type of biosensor development,
all the different tagged assemblies, and
peptide exposure show single molecule
massively speeding up the optimization
making sure that they behave the way
conformations in live cells. Cell, 2021,
process. It offers the sensitivity and
we want them to. Once we’ve
184, 5670-5685.
precision required to detect even low
developed this, we’re planning on
output in vitro fluorescent signals
moving to in vivo testing using our
rapidly in a 384-well microplate format
Tecan system. One of the other things
To find out more about
– something we could not achieve with
that we’re using it for is monitoring the
Tecan’s Spark Cyto, visit
many other high content platforms. The
phases of the cell cycle using a
Spark Cyto has removed a lot of the
separate set of fluorescent reporters.
lifesciences.tecan.com/sparkcyto
tedium from the workflow, so the
This obviously requires much longer
people in the lab love it.”
time periods, as we’re following the
To learn more about the work of the Nicholas G. Brown Lab, go to www.med.unc.edu/pharm/ brownlab To learn about the Hahn lab and some of the imaging tools discussed, visit www.hahnlab.com
The UNC Chapel Hill team (NOTE: Photo taken prior to social distancing)
TECAN JOURNAL 1/2022
15
PARTNERING
Pumping a way for effective gas emission monitoring Continuous emission monitoring systems that detect gases or particulate matter concentrations are important in various industrial settings, where they are used to ensure that potential sources of pollutants comply with environmental regulations. Inspire Analytical Systems (IAS) is a German manufacturer of calibration gas generators for analyzers and sensors that offer highly precise and continuous monitoring of gas emissions. Monitoring the concentrations of gases – particularly toxic pollutants emitted from industrial processes – is a principal health and safety measure. Waste incineration plants, for example, liberate flue gas, and require a gas analyzer to regularly check the emission levels at the end of the incineration process. However, the use of gas analyzers and sensors does not stop at environmental applications. Fabian Kories, CTO at IAS, is responsible for the development of calibration gas generators, and explained: “All analyzers and sensors need to be calibrated, requiring the precise generation of reference gases across a broad range of concentrations. We provide a device – the HovaCAL® – which does exactly that, offering flexible generation of calibration gases, such as volatile organic compounds (VOC) and airborne molecular contaminants (AMC), at concentrations as low as parts per billion. Although a majority of our customers are in industrial emissions monitoring, this is shifting to include other markets, as pollutants are now constantly being monitored in offices, public spaces and manufacturing processes. We are also seeing increasing interest from the healthcare sector, where using breath as a tool for non-invasive diagnosis and monitoring is an exciting area of research. For example, there are ongoing studies to find out if sensors developed with the HovaCAL can be used to monitor the level of anesthesia
16
TECAN JOURNAL 1/2022
PARTNERING
just from a patient’s breath, allowing
as a good opportunity to explore
dynamic adjustments during an
what was available on the market,”
operation.”
Fabian continued. “It was almost perfect timing, because we were
The HovaCAL was originally developed
already in the process of
to allow calibration of standard
redeveloping the HovaCAL. After
emission monitoring gases, including
speaking to several suppliers, we
H 2 O, HCl, NH 3 , HF and HgCl 2 . However,
chose to partner with Tecan, because
during the development process, to the
the growing range of applications for
the company’s pumps offered the best
day-to-day support the company
gas sensors is requiring calibration gas
performance and broadest range of
offers. We were most impressed by
generators to become ever-more
liquid flows suitable for our
how quickly the team was able to
flexible to meet the increasingly
applications. When designing a
supply us with pumps to test for our
diverse needs of the market, creating
system, we always consider the
many applications. Their immediate
new challenges for manufacturers.
highest and lowest flow rates that can
and responsive assistance, along with
Fabian commented: “Much of the focus
be attained without resulting in
suggestions and technical advice,
when developing our devices was the
fluctuations and, with the
allowed us to implement and
robustness of the automated pump.
Cavro® Centris pump, we’re able to
incorporate these pumps into our
The HovaCAL operates by feeding a
achieve higher precision for a broader
devices very quickly. We look forward
liquid, such as an organic solvent or
range of volumes than our old pumps.
to the possibility of future pump
aqueous solution, into an evaporator
It was very straightforward to integrate
iterations that we can adopt to
at a rate of microliters to nanoliters per
the Cavro Centris during the re-
constantly improve our equipment,”
second, which then mixes with a dry
engineering of our product, as the
concluded Fabian.
gas to completely evaporate the liquid
commands are intuitive and similar to
and provide a calibration gas. Unlike
those of other pumps.”
The Cavro Centris pump is central to the HovaCAL device
fluid monitoring applications, we cannot get away with using peristaltic
The redevelopment of the HovaCAL
pumps for this, as they are not
has also opened up opportunities for
resistant to the caustic and organic
use in even more application areas.
solvents we use. We therefore use a
“Our portfolio has now expanded to
syringe pump of the type normally
include industry-specific devices to suit
developed for the medical industry,
a variety of settings. For example, a
which uses PTFE and glass parts that
technician in a waste incineration plant
remain inert and have no ‘memory
is likely to want a portable device for
effects’, making the quality a top
in situ sensor calibration, whereas the
priority.”
size is less relevant to laboratory settings in universities or production
“A couple of years ago, our long-term
plants. Tecan has been an excellent
supplier discontinued the syringe
partner in this, from understanding the
pump we were using, and we took this
specific problems and challenges
For Research Use Only. Not for use in diagnostic procedures.
To find out more about Cavro syringe pumps, go to partnering.tecan.com/cavroliquid-handling-pumps To learn more about IAS, visit www.hovacal.de/en
ecan has been an excellent partner in this, from understanding T the specific problems and challenges during the development process, to the day-to-day support the company offers.
TECAN JOURNAL 1/2022
17
PARTNERING
Tecan acquires medical device specialist Paramit Paramit Corporation is the latest company to join the Tecan Group, bringing with it a wealth of knowledge and experience, as well as a fresh perspective to engineering and manufacturing, that will resonate throughout the whole organization. Paramit was acquired in August 2021, heralding a unique opportunity to combine the expertise of both companies and provide high quality solutions to the life sciences, in vitro diagnostics and medical device markets. Founded in 1990, Paramit is a
to the business. In addition, having
invest time to get a deep and detailed
global contract development and
access to the huge engineering
understanding of Paramit and how the
manufacturing company specializing in
resource pool at Tecan makes it easier
company operates. The entire Tecan
medical devices and life sciences
to address the needs of our mutual
approach has been very collaborative.”
equipment, with an industry-leading
customers, as well as to develop new
OEM approach that complements
connections and showcase our
Madhu Vasudevamurthy, Vice President
Tecan’s Partnering Business. The
capabilities to potential clients.”
of Partnering Systems at Tecan, looks
company combines custom
forward to this next chapter, and the
microfluidics, electronics, optics and
Jeff Johnson, Vice President of Sales
benefits that this acquisition will bring
motion control to help its clients create
and Marketing at Paramit, continued:
for both companies: “I am very happy
a range of products, from handheld or
“Aside from all the technical benefits,
and excited about the new growth
point-of-care devices to benchtop
this partnership has also brought many
opportunities for Tecan and its
instruments and cart-based systems.
practical advantages for Paramit, such
customers as we expand into the
It has expanded from its origins in the
as assistance with FDA approvals.
medical device sector, adding an
US to owning multiple state-of-the-art
Tecan is well-versed in the world of
additional pillar to our portfolio.
development and manufacturing
auditing and regulatory compliance,
Paramit’s long and broad experience in
facilities across the world, including
and dedicates a significant amount of
this sector will accelerate Tecan’s
an award-winning site in Penang,
resources and expertise to this, which
research into new clinical applications
Malaysia.
Paramit can now deploy to help
and open new doors for the company,
navigate regulatory pathways,
helping to expand our quality
Tecan’s acquisition of Paramit opens up
including IVDR. In addition, both
assurance and regulatory affairs skill
a new and exciting development
companies and their customers can
set in this highly regulated area.”
pipeline for the medical device
benefit massively from the expanding
industry, as Faiyaz Syed, Chief
global footprint. For example, if there is
“In addition, acquiring Paramit will
Operating Officer, explained: “Each of
ever an issue with a product that has
extend Tecan’s global footprint, giving
the companies has something unique to
been shipped to Europe, it can now be
us the resources to reach more
bring to the table; at Paramit, we are
serviced regionally by Tecan without
customers in the Americas and Asia,
experts at manufacturing complex
having to ship it back to the US. The
directly benefitting existing customers
electromechanical systems for the
team at Paramit is really pleased with
in these regions. It will also strengthen
medical and life sciences industries,
the progress that this acquisition has
our design, development and
while Tecan has established R&D and
made so far. We have had numerous
manufacturing capabilities, enabling
regulatory teams, bringing vast
discussions over the first few months,
Tecan to serve a broader range of
experience, knowledge and credibility
and I am amazed by the willingness to
customers and applications. Across the
ogether, Tecan and Paramit will bring T reliable and innovative technologies to the medical, in vitro diagnostics and life sciences sectors.
18
TECAN JOURNAL 1/2022
LEADING THE DEBATE
Leading the debate Wael Yared, Chief Technology Officer and Global Head of Research and Development Tecan has shaped the state of lab automation since its earliest days, and will continue to do so. What do
Dr Wael Yared, Executive Vice President, Chief Technology Officer and Head of Research and Development at Tecan
we expect the lab of the coming board, the joint client base will
decade to require?
gain massively from an enhanced breadth of supply chain
The first two inexorable trends in
components and subsystems to
capabilities and manufacturing
lab automation are influenced by
instruments deployed globally – are
expertise. Moreover, this will also
technology developments and user
therefore essential. Large-scale
expand Tecan’s portfolio, offering
expectations in adjacent industries.
instrument metadata also enables
extensive leading-edge OEM
First, self-aware instrumentation drives
the development of predictive
services, as well as up-scaled
robustness and increased availability.
analytical tools.
manufacturing and R&D
We have taken our first few steps with
capabilities. Customers will now
DeckCheck™ – our worktable
Finally, as the importance and benefits
be able to approach Tecan at
recognition solution – and are now
of global connectivity and open digital
any stage of their product
ramping up our component and
ecosystems become more widely
development, from the early
subsystem digitalization efforts
appreciated, we need to recognize the
design phase to production,
towards intelligent automation. The
cybersecurity vulnerabilities these
and receive expert guidance.
second trend is ease of method
initiatives inevitably introduce. At
Together, Tecan and Paramit
scripting and implementation,
Tecan, end-to-end cybersecurity is
will bring reliable and innovative
something users are demanding with
factored in from the outset of system
technologies to the medical, in
increasing urgency. We are actively
development, using a ‘zero trust’
vitro diagnostics and life sciences
exploring new user experience
approach to ensure strict verification
sectors.”
paradigms, alongside cloud-based
protocols are in place. We extend this
method development tools, to reduce
approach all the way through to
To learn more about Paramit, go to
the steep learning curve required of our
deployment and maintenance, with
www.paramit.com
automation end users.
continual risk assessment and monitoring for all live software. With
A distinct but related third trend stems
breaches a potential risk in any industry,
from the emergence of advanced
we focus on ensuring appropriate
simulation. With the advent of our 3DSim* platform, we can now work
controls are in place to protect the
towards the complete digital
customers’ data.
confidentiality and integrity of our
representation of every physical asset, dynamically tracking its entire life cycle.
These five trends, alongside the growth
This enables entirely new modes of user
of key applications in life sciences
engagement, such as enabling assay
research and diagnostics, are at the
development before hardware is even
core of Tecan’s strategy, helping to
available, or remote, interactive
inform the near- to medium-term
troubleshooting for service
development of our platforms’
deployment.
capabilities.
Fourth, we recognize that most labs
To share your thoughts, please email
have more than a single instrument.
empowered@tecan.com
Fleet connectivity, and the aggregation of data at multiple levels – from
*Not available for end customers yet.
TECAN JOURNAL 1/2022
19
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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