Tecan Journal Edition 01/2022

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

The Blog TRENDS, NEWS, STORIES AND MUCH MORE! FROM THE EXPERTS TO YOU. www.tecan.com/blog

Every lab.

Every day.

Empowered.

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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.

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