Tecan Journal Edition 02/2021

Edition 2/2021

Tecan Journal Life Sciences, Diagnostics and Partnering

Increasing the amplitude of global COVID-19 testing

A sure BET for workflow automation

Computational biomedicine at the forefront of epigenomics

Robotic biology for the lab of the future

Pages 8-9

Pages 18-19

Pages 26-27

Pages 30-31

CEO WELCOME

Changing perspectives in a global market The COVID-19 pandemic has highlighted some of the weaknesses in current biosurveillance and diagnostics, as well as drug and vaccine development strategies, but has also demonstrated the incredibly rapid progress that can be made when the life sciences community pulls together for a single cause. This type of coordinated effort only really seems to be feasible in times of global crisis, but serves as an inspiring demonstration of what can be achieved through focused collaboration, and we’re proud to have played our part here at Tecan.

Fortunately, many of the lessons learned during the pandemic can be applied to dealing with future outbreaks, or even to completely different areas of life sciences and medicine. One of the clear messages from this crisis has been the need for research, diagnostics and production laboratories to become more adaptable to sudden changes in their workflows and throughput. Providing labs and hospitals with this flexibility is one of our core strengths, and this is further boosted by the design and manufacturing capabilities of the latest addition to the Tecan family – Paramit Corporation.

Over 30 years, Paramit has built a strong reputation as a leading CDMO in the medical devices and life sciences sectors, with an impressive track record in handheld and point-of-care devices, as well as benchtop instruments and cart-based robotic surgery and patient monitoring systems. This acquisition will further extend Tecan’s capabilities in life sciences and in vitro diagnostics, as well as opening up the market for medical mechatronics. Driving scalable innovation from research to the clinic is a common strength and focus for Paramit and Tecan, and our joint future will be further boosted by Paramit’s R&D facilities in Boston and Silicon Valley, and advanced production centers in both North America and Malaysia.

We’ll be sharing more about how this new member of the Tecan family will help us to expand our capabilities in the near future but, for now, I hope you enjoy this issue of the Tecan Journal, Achim von Leoprechting CEO

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TECAN JOURNAL 2/2021

CONTENTS

Contents 2

Welcome

4 - 7 Genomics research beyond COVID-19:

embracing the new normal

8 - 9

I ncreasing the amplitude of global

COVID-19 testing

10 - 11

B olstering the assay arsenal to investigate COVID-19

14 - 15 Drug repurposing for the battle

12 - 13

Innovation in COVID-19 testing by Dutch

against COVID-19

public-private partnership

14 - 15 Drug repurposing for the battle against COVID-19

16 - 17

Easing the burden of flow cytometry

sample preparation

18 - 19 A sure BET for workflow automation 20 - 21

Taking the guesswork out of diagnostics

22 - 23 Don’t miss a beat with live cell imaging 18 - 19 A sure BET for workflow automation

24 - 25 Fluorescence imaging shines a light on

systems biology

26 - 27 Computational biomedicine at the forefront of epigenomics

28 - 29 Fighting neglected and

non-communicable diseases

30 - 31 Robotic biology for the lab of the future

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 2/2021

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COVID-19 COVID-19

Genomics research beyond COVID-19: embracing the new normal In the ‘new normal’ post-COVID-19 world, how can genomics labs be better prepared to respond quickly to the unexpected? How can they deliver reliable and insightful genetic sequencing results faster and more efficiently? What is the best way to scale up operations without being limited by benchtop tasks? In this article, Tecan talks to Dr Davide Scaglione, CTO of innovative NGS service provider IGATech, to get his perspective on how to embrace the new normal and put the latest genomics technologies to work to improve the health of humans, animals and the planet.

Genetic sequence information is key to

application focuses are genotyping

service than they could get with a

cracking many of the world’s most

systems, de novo assembly techniques,

typical NGS service provider.

pressing problems. As Italy’s leading

and integration of customized

NGS service provider, IGATech has a

protocols with analytical pipelines.

growing reputation as an innovator in

Our company’s vision is to support our customers beyond simply providing

strategies for genotyping and advanced

What was the driving force behind the

sequencing capabilities. We take the

genomic research. The company has

creation of IGATech?

time to explore and understand their

sequenced the DNA of more than 250

Our company has its roots in the

final goals, select the best

types of organisms, and applied its expertise across diverse areas such as tracing food origin and safety, increasing the efficiency of plant and animal breeding, improving diagnostics and routine clinical care, and supporting sustainable development.

Who better then to comment on the challenges of thriving in today’s demanding research environment?

Davide Scaglione is Chief Technology Innovation Officer at IGATech. He is in charge of the development of new sequencing-based applications, bioinformatics operations and coordinating business activities. After a PhD in plant genetics at the University of Turin in collaboration with the University of Georgia, he spent a one-year postdoc at the Genome Center in Davis (California). He also worked as Head of Innovative Analytical Development at Merck KGaA, and has authored several scientific publications, mainly in plant genomics and bioinformatics. His major

The Blog 4

Institute of Applied Genomics (IGA) in Udine, which initially became renowned for its work in plant genetics, and has grown into a leading center of excellence for structural and functional genomics in living organisms. In 2009, the IGA established IGATech as an NGS service company, equipping it with the latest Illumina and third-generation sequencing platforms. Today, we are the number one provider of genomic research services in Italy. Our mission is to support academic and industrial research to help apply the power of genomics to address important

methodologies and bioinformatics strategies for their project, and help them implement solutions that will deliver robust answers to their questions. The added value is that the customer comes to us, explains what they want to achieve, and then they can trust us to provide the best solution for them. We are not trying to give them a one-size-fits-all paradigm. This really differentiates us from NGS service providers who take a more commoditized approach.

Tell us more about the types of

biological questions, using whatever

solutions and services you provide.

organisms are most appropriate.

These can essentially be grouped into three main areas. The first is our core

How are you helping your customers

genomics research service, where we

solve today’s big challenges in

apply state-of-the-art sequencing and

genomics research?

bioinformatics methods to explore

Questions in genomics are, by nature,

genomic structure and function in

very complex, and it often takes a tailored approach to ensure robust and meaningful results. That means many of our customers need a more dedicated

many different contexts, from soil metagenomics to the transcriptomics or epigenetics of space-flight specimens. The second key focus is agri-genomics, where we apply

TRENDS, NEWS, STORIES AND MUCH MORE! FROM THE EXPERTS TO YOU.

TECAN JOURNAL 2/2021

COVID-19

custom-tailored genotyping-bysequencing techniques – often coupled with de novo assembly of genomes – to help researchers and food producers understand the molecular basis of traits that are important for commercialization

lexibility is key, because each new project F can be very different from the last in terms of the strategies and protocols involved.

or preservation of species. The third, and most recent, area is the characterization of genetically-engineered cell lines for the production of biologics or for application in regenerative medicines.

As an NGS service provider, what are some of the challenges you and your customers face in today’s evolving research environment?

Shifting our focus from a commoditized to customized approach means that we have a greater heterogeneity of applications than many of our competitors. This means we are always developing new protocols to offer the best service to our customers. It’s not just a case of continuous improvement, but also of continuously reshaping our procedures, which is time consuming.

Flexibility is key, because each new project can be very different from the last in terms of the strategies and protocols involved.

As the pandemic has shown us, in our crowded and highly mobile world, new and serious threats can arise unexpectedly, which means we and our customers need to be prepared to adapt and respond at short notice.

Customized NGS services are going to be in increasing demand as these global pressures continue to escalate and the questions we ask get more complex. As our customers potentially feel the bite of tighter budgets,

www.tecan.com/blog TECAN JOURNAL 2/2021

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COVID-19

workforce limitations and time pressures,

and increase reproducibility, minimizing

What do you see next on the horizon

they will also need this type of dedicated

batch effects in large studies. This

when it comes to automation?

support to deliver on their commitments.

brings added value to our customers,

Fortunately, full integration and

and that is absolutely key for us.

What steps are IGATech taking to meet these challenges?

You mentioned having DNA

To satisfy the growing demand and stay

quantification and normalization

competitive, we know that we will need

integrated into automated workflows

automation of the entire NGS workflow is now available for the first time with the DreamPrep™ NGS workstation. The number of applications and compatibility with commercial kit

to standardize procedures wherever

for NGS – why is that so crucial?

possible, and automation can really help

Good question. We are currently

growing. Looking to the future, it will be

here. For example, much of the NGS

running a lot of applications based on

important to anticipate where the high

sample preparation process can be

Tecan’s Allegro® Targeted Genotyping

volume analysis will be, so we can

completely automated – not only library

system and standard genotyping-by-

extend this completely hands-off

preparation, but also DNA extraction,

sequencing methods. Both methods

approach to those areas. For example,

quantification and normalization.

involve pooling materials, which means

long read sequencing is becoming more

that accurate quantification and

mainstream, so there will likely be a lot

Ideally, with the right automation

normalization are critical to the quality

of research that needs to be repeated

platform in place, we would be able to

of the results.

from scratch. At some point, the

take in any type of raw material – such

protocols is already extensive and

increase in volumes may justify having a

as plant leaves, blood or tissue – and

The problem is that these procedures

complete automation solution for that

implement protocols to allow nucleic

are labor intensive and time consuming,

workflow. Similarly, single cell

acid extraction and preparation of high

so we can spend up to half the time just

sequencing is another trend that could

quality libraries without disrupting

for quality control and normalizing large

lead to a lot of research that was done

operations in the lab. This would not

batches of samples. That means we’re

with RNA-Seq being repeated at the

only increase productivity, but also fit

spending half the time on relatively

single cell level. We are also

with our customer-oriented strategy,

trivial tasks, which are nevertheless key

collaborating with industry for

because it would enable us to offer our

to avoiding experimental failure. Having

production-oriented implementation of

customers a more complete solution.

this part of the process hands-off and

NGS. Our perception is that, while NGS

They just provide the raw material, and

completely automated is therefore the

has continued to rapidly evolve and

we return the insights.

right way to go for us. Not only could

release fascinating methods and insights

automation cut the total time almost in

year after year, effective application of

Our plan is to implement our most

half, but it would also take a lot of error

NGS in more niche contexts still

common preparation applications – such

out of the process.

demands a higher degree of

as those for RNA-Seq, DNA-Seq, and

reproducibility. Automation is one of

maybe also one day Meta-Seq – on a

the first steps to make NGS a more

fully automated, walkaway platform that

appealing asset to industry, and close

is designed specifically for the types of

collaboration between genomics

challenges we are facing. This will allow

technology innovators and Tecan is sure

us to scale up the volume of our most

to lead to exciting new developments.

common applications, without overwhelming benchtop operations. This will also free up expert staff to focus on

For Research Use Only. Not for use in diagnostic procedures.

the communication with clients, experimental design and data review

To find out more about how

that are our main value propositions.

Tecan solutions are supporting

Perhaps most importantly, having a fully fledged automation system should improve the integrity of the whole process, because it would make the process more resilient to human errors

The Blog 6

TRENDS, NEWS, STORIES AND MUCH MORE! FROM THE EXPERTS TO YOU.

TECAN JOURNAL 2/2021

innovators like IGATech to push the boundaries of genomic research, visit www.tecan.com/ngs

COVID-19

www.tecan.com/blog TECAN JOURNAL 2/2021

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COVID-19

Increasing the amplitude of global COVID-19 testing The scale of the challenge for clinical diagnostics labs around the world quickly became apparent when the SARS-CoV-2 pandemic hit in 2020. Assays to identify the virus were rapidly developed to isolate patients and monitor the spread of the virus but, with shortages of reagents and labware, and the sheer number of samples expected, scaled-up testing was desperately needed. Thermo Fisher Scientific supplies labs with the qPCR equipment that was central to testing, but wanted to do more to support the global efforts, and so set about developing a solution for high throughput screening.

The Genetic Sciences Division of

have tremendous knowledge and

instrument processes each sample and

Thermo Fisher Scientific provides an

experience within the company, and I

dispenses it into four, barcoded 96-well

industry-leading portfolio of research

first turned to colleagues from the

deep well plates in a state where there is

products for genetic testing and, prior

Sample Preparation and Analytical

no longer any live virus. These plates are

to the COVID-19 pandemic, focused on

Instrumentation groups – who already

then transferred to the second Fluent

supporting scientists working in

had experience of automated

780, which can be housed in a standard

academic, pharmaceutical and

instruments and cooperative robots –

lab, and combines samples into a single

agricultural research. qPCR was a

to see what we could build internally. It

384-well plate for RNA extraction, qPCR

central pillar of the team’s capabilities

soon became apparent that we would

and analysis. A single LIMS system

and, with the technique becoming

need outside partners for certain

connects both stages, and stores all the

recognized as the gold standard for

elements of the project.”

sample tracking information from the

SARS-CoV-2 identification, the division

barcoded plates. The system gives labs

was called upon to support clinical

Elliot added: “We looked at a few

a full workflow capacity of 8,000

testing efforts. The first development

different liquid handling options and

samples a day.”

was the TaqPath™ COVID-19 Combo Kit

Tecan consistently came out top on our

– for labs to screen for the virus on their

list of requirements. Despite the

Developing intuitive software was a key

existing qPCR machines – and this

restrictions of the pandemic, the

part of the challenge, to ensure that

quickly gained Emergency Use

company could meet our needs for

users could easily manage the workflow.

Authorization (EUA) from the FDA.

supply and continuity for a large number

Robert explained: “Our colleagues from

However, customers were asking for

of instruments and, in particular, tips and

the Analytical Instrumentation group

more scale and the option to move from

plastics, which was a big issue at the

had previously programmed APIs to

testing hundreds of samples a day, to

time. However, most importantly, Tecan

interact with Tecan liquid handling

thousands. Elliot Shelton, General

was the only company to approach us

platforms and so our proprietary

Manager, and Robert Balog, Director of

with a true spirit of partnership that

Momentum™ software was already

R&D, of the division were enlisted to

would help us meet the challenges we

compatible with Fluent scripts. We then

produce a high throughput testing

were facing. It quickly rose up the ranks

worked with the Tecan team to develop

platform to meet this demand, and the

as our clear partner of choice.”

custom scripts and, where possible,

Amplitude™ Solution was born.

integrated Introspect™ software into the Robert continued: “Many of our

systems, depending on the customers’

Robert explained: “It was mid-April

customers had told us that they didn’t

IT set-ups and firewalls. The software

2020, and I was walking the dogs with

have large enough biosafety level 2

has been able to give us valuable

my family when I was contacted by the

(BSL-2) areas to house the complete

insights into how the systems are

president of the division about a

workflow, and so we designed the

working, and the data coming back to

completely new project for the

Amplitude Solution so that it could be

us from the field has been really helpful

company, a high throughput automated

adopted by labs of different sizes and

to find high priority issues and start to

solution that could carry out 10,000

layouts. For that reason, it is based on

quickly address any errors.”

COVID-19 tests a day. We had the EUA

two Fluent® Automation Workstations

for the TaqPath in manual mode as a

– both with Tecan Cavro liquid handling

The first installations of the Amplitude

starting point, and wanted to change as

pumps – set up as two distinct

Solution started in September 2020 and

little as possible when automating it so

platforms. A Fluent 1080 workstation

the customer response to the system

that we could get fast approval. We

handles live virus in a BSL-2 lab; the

has been overwhelming.

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TECAN JOURNAL 2/2021

COVID-19

ost importantly, Tecan was the only M company to approach us with a true spirit of partnership that would help us meet the challenges we were facing.

Elliot continued: “We went into this not really knowing what the market adoption was going to be, we just saw an unmet need. It was great to see how quickly this system was adopted, and especially how fast we were able to fulfill orders and schedule installations.

This was another area where it was fantastic to have Tecan as our partner because, with such unprecedented demand, it was important to be able to coordinate enough field support to successfully install and train users on these machines. Tecan’s global presence enabled us to quickly complete installations in all corners of the world.”

Elliot concluded: “A year and a half ago, this group was less than 100 people, now we are more than 1,000.

Rapid scaling and the collaboration with Tecan has allowed us to support our customers and try to make a difference in combating the pandemic.

Moving forward, the intention is to

To find out more about Tecan’s

continue to build our presence in this

Fluent Automation Workstations,

space, and leverage the competencies and infrastructure that we’ve built as a result of COVID-19. We plan to continue developing and deploying new assays to tackle new disease areas, and really fulfill the promise to our customers that the system isn’t

visit lifesciences.tecan.com/fluent To learn more about Thermo Fisher Scientific’s Amplitude Solution, go to www.thermofisher.com/amplitude

just a one-application purchase.”

TECAN JOURNAL 2/2021

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COVID-19

Bolstering the assay arsenal to investigate COVID-19 The COVID-19 pandemic has

PTP Science Park is a business

on multiple fronts. Stefano di Giovine,

highlighted the importance of

consortium that operates in a wide

COO of PTP Science Park, explained:

range of sectors, including agri-food,

“At the beginning of the COVID-19

life sciences and bioeconomics. The

pandemic in March 2020, PTP Science

company’s position at the forefront of

Park already had the facilities and the

scientific research allowed it to ramp

ability to analyze the virus. We started

the pandemic, the laboratories

up its diagnostic and research

with a small number of samples but,

at PTP Science Park in Lodi,

capabilities in response to the

thanks to Tecan’s state-of-the-art

Italy, quickly enhanced their

COVID-19 pandemic. The science hub

automation solutions – such as the

is still engaged in various projects, but

Freedom EVO® workstation – we

its extensive research facilities, staff

already had the capacity to evaluate

and resources have been focused

up to 2,000 samples per day. More

towards the battle against COVID-19

recently, in March this year, we started

biosurveillance to understand, control and limit the spread of human diseases. In response to

set-up, introducing various assays to gain a deeper understanding of the virus. Researchers now not only diagnose COVID-19, but also measure anti-SARS-CoV-2 antibody levels after infection and vaccination to learn about the pathogenesis of the disease and how our immune systems respond to infection.

Laboratory automation has been essential to scale up testing at PTP Science Park 10

TECAN JOURNAL 2/2021

COVID-19

ecan’s instruments and assay kits have T allowed us to act swiftly in response to the pandemic and really make an impact.

a drive-in facility to enable us to take in even more samples. To date, we have processed about 160,000 samples, and are the primary laboratory in the Lodi area – supporting care homes and hospitals.”

Located within PTP Science Park is the SMeL laboratory, which was added to the regional crisis unit in response to the pandemic. It is authorized to operate as a specialized medical laboratory, and carries out various tests using a biosurveillance toolkit that includes qPCR for diagnostic testing of oropharyngeal swabs, and quantitative serological assays for SARS-CoV-2 IgG, IgM and IgA antibodies, to evaluate the immune response post-infection or post-vaccination.

The Thunderbolt® analyzer provides fully automated, benchtop ELISA testing

immunizing antibodies. We expect a Stefano continued: “Our activity with

real boom in testing requests in the

SARS-CoV-2 is not limited to

coming months with all of the clinical

diagnostics. We are one of the few

studies underway.”

laboratories in the region authorized to sequence and report new variants,

“The scope of our research continues

partly thanks to Tecan’s assays and the

to expand as the pandemic progresses.

DreamPrep™ NAP workstation. We

Recently we started a small, local

also have a program funded by the

research project to evaluate the levels

Lombardy Region and the Cariplo

of IgG antibodies against the virus

Foundation called ‘COVID in pets’, to

before and after vaccination. Again,

investigate whether animals can catch

using Tecan’s SARS-CoV-2 S1/RBD

and transmit the virus.”

IgG Ab ELISA we can accurately gather this data and find variations

“The demand for serological testing to

in peak antibody levels following

check for antibodies in response to the

vaccination.”

vaccine has increased dramatically.

Using Tecan’s SARS-CoV-2 S1/RBD IgG

“Tecan’s instruments and assay kits

To find out more about Tecan’s

Ab ELISA, we can detect antibodies

have allowed us to act swiftly in

SARS-CoV-2 S1/RBD IgG Ab ELISA

against the virus spike protein’s

response to the pandemic and really

kits, visit

receptor binding domain, which allows

make an impact, especially in the

us to examine variations in the immune

region. Ongoing viral surveillance with

www.tecan.com/interrogate-

response to the virus. For example, we

PCR testing and ELISA kits will help us

have found that some people gain

discover new variants and continue

immunity after contracting COVID-19,

building our knowledge on how our

while others have been infected up to

immune systems respond to infection,”

three times as they fail to generate

concluded Stefano.

covid-19-with-tecan-sars-cov-2igg-elisa To learn more about PTP Science Park, go to www.ptp.it

TECAN JOURNAL 2/2021

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COVID-19

Innovation in COVID-19 testing by Dutch publicprivate partnership When the SARS-CoV-2 pandemic hit in 2020, researchers from the Hubrecht Institute in Utrecht, Netherlands, felt compelled to support the national COVID-19 testing strategy, which was suffering with limited capacity. Recognizing that the gold standard PCR test worked well to identify SARS-CoV-2 positive patients, the institute’s challenges lay in the logistics and a need to automate the process. A fortuitous introduction to an automation expert from Genmab was the start of a successful collaboration, which grew to involve a number of additional partners, and has significantly increased the capacity of SARS-CoV-2 testing in the Netherlands through the development of the STRIP-1 robot.

Day-to-day, scientists at the Hubrecht

intensive manual process, together with

Institute are focused on pioneering

the requirement for large volumes of

research in developmental and stem

liquid reagents – which were suffering

cell biology. However, during the first

global shortages at the time – were

COVID-19 lockdown in the Netherlands

limiting the number of tests that could

in March 2020, two group leaders from

be processed. We initially investigated

the Institute – Wouter de Laat and

potential alternatives to standard qPCR

Marvin Tanenbaum – set about using

testing, but quickly realized the assay

their molecular biology expertise to

itself was very sensitive, and the biggest

support the national SARS-CoV-2

challenge was the logistics of carrying

testing strategy. Wouter explained: “An

out the tests.”

Identifying the need to automate the workflow, a chance meeting in a local park led the Hubrecht scientists to be introduced to Martijn Bosch, an automation expert from Genmab – a biotechnology company coincidentally situated opposite the Hubrecht Institute on the Utrecht Science Park. Wouter continued: “The Hubrecht and Genmab are very different organizations and, although we are across the street, we don’t normally interact. However, in this unusual circumstance, it quickly became clear that we had the exact same attitude – we wanted to do something useful, and we had the complementary skills to try and make a difference.”

Martijn added: “As an antibody company we do a lot of very high throughput screening, and so I knew that there

The Hubrecht Institute’s location on the Utrecht Science Park proved essential to collaborative efforts

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TECAN JOURNAL 2/2021

should be potential to apply a similar set-up to COVID-19 screening, with the

COVID-19

possibility of being able to process tens of thousands of samples a day.”

Martijn set about designing the STRIP-1 – initially nicknamed ‘The Beast’ – and chose a Fluent® Automation Workstation.

He explained: “I had worked with Tecan automated systems for about 15 years, and immediately knew they would be

he Fluent system allows the whole RNA T extraction process to be carried out in 384-well format, increasing the speed and reducing the quantity of reagents required.

able to produce the platform we needed, so I worked closely with a team at Tecan Labwerx™ to realize the

“The Fluent system allows the whole

It’s delivering results for COVID-19

system. We built it around a Fluent 1080

RNA extraction process to be carried

testing now, but can be repurposed for

with two LiCONiC incubators at either

out in 384-well format, increasing the

other large-scale testing. In addition,

side, but what made our system different

speed and reducing the quantity of

we will be prepared should we face a

to other Fluent workstations was that we

reagents required. Plates are then

future pandemic.”

used two Robotic Gripper Arms™. This

manually moved for qPCR analysis, and

allowed us to set up two different

the barcodes allow automatic digital

processes on one workdeck, increasing

return of the results to the right person.

the overall speed of the workflow. To

We worked with IT company Bodegro

make sure that the magnetic beads

to manage the sample tracking and

used for the RNA isolation step were

integrate the data management

kept in suspension, a V&P Scientific

throughout the process.”

SpinVessel® was introduced. We

To find out more about Tecan’s lab automation solutions for SARS-

ensured full traceability throughout the

Following this successful installation

process by using barcoded sample

and validation of the STRIP-1 platform

tubes and plates, which were scanned

at the PAMM medical diagnostics

using a Ziath DataPaq™ Mirage scanner

laboratory in Veldhoven in December

integrated into the system.”

2020, the team that collaborated to

For more information on Tecan

CoV-2 testing, visit www.tecan.com/covid19

bring it about were finally able to meet

Labwerx customized automation

“One of the big challenges we faced

in person when Hugo de Jonge, the

solutions, visit

was getting the samples from the

Dutch Minister of Health, Welfare and

www.tecan.com/labwerx

patients into the system. We worked

Sport, visited STRIP-1 at the PAMM

with Micronic – which supplied sample

laboratory in January 2021. The Dutch

tubes prefilled with a lysis buffer and

government has since ordered five

controls – so that any virus present was

more systems, with each platform

deactivated as soon as the patient swab

capable of processing more than

was collected, making the sample

10,000 samples in 24 hours. Martijn

handling safer for staff. We also built

finished: “Through this extraordinary

an IntelliXcap™ decapper into the

collaboration and the use of Tecan

system with a special adapter for the

laboratory automation platforms,

Micronic caps.”

we’ve produced a very flexible system.

To learn more about the Hubrecht Institute’s STRIP-1 platform, go to www.hubrecht.eu/strip-1-testrobot-for-covid-19-testing To find out more about Genmab, visit www.genmab.com

TECAN JOURNAL 2/2021

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COVID-19

Drug repurposing for the battle against COVID-19 The race has been on since the start of the pandemic to develop vaccines and drugs to fight against the SARS-CoV-2 virus. Vaccine development has proven successful, with vaccine roll-out underway in many countries, but the need remains to identify drugs that can treat the disease for those who have not been vaccinated, or for those where the vaccine is not effective enough to prevent disease. Researchers at the Fraunhofer Institute for Translational Medicine and Pharmacology (ITMP) in Hamburg, Germany, have been using high throughput drug approaches to screen compound libraries for candidate antiviral drugs.

The SARS-CoV-2 virus was identified,

have time to wait for these disease

rapidly analyzed in in vivo efficacy

isolated and sequenced within a short

mechanisms to be fully elucidated

studies, and ultimately clinical trials.

time of this novel pathogen emerging

before beginning screening for drugs

Philip explained: “In January 2020, our

into the community. However, at that

that could directly treat or alleviate the

collaborator – Professor Sandra Ciesek

time, the precise details of how the

symptoms in COVID-19 patients.

from the Institute for Medical Virology

viral infection affects tissues and

at University Hospital Frankfurt – had

organs, or how this contributes to the

Dr Philip Gribbon, Head of Innovation

access to some of the first clinical

development of disease, were not clear.

Area Drug Screening & Compound

isolates of the coronavirus in Europe,

This knowledge of infection and

Repurposing, and his colleagues at

and established an assay to screen

disease-related mechanisms is normally

Fraunhofer ITMP are experienced in

against the virus on a very short

critical to developing medicines,

carrying out screening assays to

timescale. Working closely with

allowing researchers to target key virus

identify compounds that can be

Professor Ciesek, we then began

replication, or virus-host interactome

repurposed. They understood that

screening Fraunhofer ITMP’s collection

associated pathways with small

screening known drugs and drug

of over 5,500 bioactive compounds,

molecule compounds or biologicals.

analogs against SARS-CoV-2 would

including 3,000 clinical stage drugs,

Unfortunately, the growing global

allow them to identify candidate

for their antiviral activity.”

crisis meant that researchers did not

compounds with the potential to be

The Fluent Automation Workstation in use in the laboratory at Fraunhofer ITMP 14

TECAN JOURNAL 2/2021

COVID-19

The workflow for the original assay was

characterize the effect of different

programs, especially since vaccines

a collaborative effort, as Philip

spike mutations on viral entry efficiency

are typically not 100 percent effective

described: “Our laboratory uses a

and profile compounds or biological-

at preventing the disease, and there is

Fluent® Automation Workstation to run

based inhibitors. Some of these assays

still the risk of new variants emerging

high throughput screening assays, as

are highly automated, so the Fluent has

that may evade vaccine protection.

this system offers the precision and

certainly proved adaptable to many

Drug repurposing efforts allow

flexibility that we need to run complex

different workflows.”

candidates to be quickly identified and

assays in a 96-well, or even 384-well,

taken into Phase II and III clinical

format. We wanted to capitalize on

efficacy trials, while potentially

these capabilities in the fight against the virus, and so we used the Fluent to plate out the compound libraries for the initial SARS-CoV-2 screen. At that point, we sent the plates to a biosafety level 3 (BSL-3) lab in Frankfurt for testing, as whole virus was used in the screening assay. This meant relatively complex plate logistics, due to the

This system offers the precision and flexibility that we need to run complex assays in a 96-well, or even 384-well, format.

limited degree of laboratory

reducing the need for the extensive Phase I safety testing normally necessary with novel compounds.

Philip concluded: “The high throughput, flexible automation offered by the Fluent platform has supported this effort, and will continue to be invaluable in drug screening, not just for COVID-19, but for a host of diseases. The urgent need created by

automation in the BSL-3 environment

this pandemic has really identified new

but, within three months, we had

All of the data on COVID-19 generated

areas in which lab automation could

published the first results online,1 and

by this research has been made public

prove invaluable in the future.”

eventually uploaded the primary data

to support the global community in

to ChEMBL and the Image Data

combating the virus. Philip continued:

1. Ellinger, B. et al. A SARS-CoV-2

Repository databases to assist global

“We work closely with the teams in the

cytopathicity dataset generated by

research efforts.”

European Bioinformatics Institute and

high-content screening of a large drug

the ELIXIR Research Infrastructure, Since reporting these initial results,

who set up the EU’s COVID-19 data

Philip and his team have continued to

portal. We’ve tried to be as open as

develop new assays and partner with

possible about the data that we’ve

labs around the world to further our

been able to generate. For the cell-

understanding of the virus. Philip

based assays, we’ve reported the

added: “Our Fluent platform has been

activities in ChEMBL but, rather than

repurposing collection. Sci Data, 2021, 8,70.

working hard on COVID-19 screening

just giving a percentage effect or IC 50 ,

over the last year. We’re still using it to

we’ve uploaded the primary image

support compound plate logistics – for

data for the entire screen into a data

example, we recently shipped 10,000

repository. This means scientists on a

compounds to a collaborator to screen

global basis can reanalyze the data,

To find out more about Tecan’s

against the SARS-CoV-2 spike protein

and generate additional hypotheses or

– as well as using the system to run

insights. We’re also working with the

drug discovery solutions, visit

selectivity assays and target-based

European Open Science Cloud and the

screens against some of the main viral

European Commission to use the

entry and replication-associated

methodologies we’ve established for

targets. We are adapting the Fluent to

our datasets to help other groups to

perform screens using lentiviral

mobilize their data towards public

infection systems developed by our

resources.”

itmp.fraunhofer.de

Hamburg, which express the SARS-

Antivirals to treat COVID-19 will be an

To access the COVID-19 Data

CoV-2 spike protein on the surface of

important part of beating the disease.

Portal, visit covid19dataportal.org

lentiviral particles. This will allow us to

They serve to support vaccination

lifesciences.tecan.com/ drugdiscovery To learn more about Fraunhofer ITMP, go to

collaborators at the University Clinic in

TECAN JOURNAL 2/2021

15

FLOW CYTOMETRY

Easing the burden of flow cytometry sample preparation Flow cytometry (FCM) is a powerful analytical tool with applications spanning a variety of disciplines.

Sample preparation prior to cytometry, however, is traditionally slow and prone to human error, which can drain precious time and resources from laboratories already under constant pressures. Sysmex has developed a unique automation solution to rapidly accelerate sample preparation for FCM applications – heightening efficiency and flexibility to ease the strain on laboratory professionals.

Sysmex’s mission is to shape the

world. Over recent years, the company

for quality control testing of water and

advancement of healthcare by

has expanded its FCM capabilities in

beverages, and for research.

providing instruments, reagents and

response to customer demand,

software for in vitro testing of blood,

ensuring it continues to provide for the

As the clinical testing market

urine and other bodily fluids. The

needs of the hematology market. Its

expanded, Sysmex recognized that

company’s integrated R&D,

FCM portfolio now covers various

sample preparation was an obvious

manufacturing, sales and support

applications, including clinical testing for

bottleneck in the clinical FCM testing

network supplies products to more

leukemia, malignant lymphoma and HIV/

workflow, slowing the entire analytical

than 190 countries throughout the

AIDS, as well as providing instruments

process. Shogo Takatani, Vice President of FCM Business Development at Sysmex, explained: “Many of our clinical FCM customers were struggling with the burdensome process of sample preparation.

Leukemia and lymphoma testing are especially arduous, as you need to add up to 100 types of monoclonal antibody reagents to multiple tubes.

This is really time consuming and, because of the tedious nature of the work, there is a high chance of error, which can greatly impact the accuracy of results. Seeing the burden this was on our customers, we realized there was a need for greater automation in these steps, not only to increase throughput, but also to minimize manual labor and limit the chance of human error. This would then allow the highly skilled laboratory professionals to focus more on clinical data analysis and interpretation.”

“Our FCM application specialists understood our customers’ pain points, but we needed a partner with the knowledge and experience to develop an appropriate automated solution.

We approached Tecan and, using its Cavro® Omni Flex platform as a starting

PS-10 team members from Sysmex and Tecan pictured outside Tecan’s facility in San Jose, CA (NOTE: Photo taken prior to social distancing) 16

TECAN JOURNAL 2/2021

point, we developed an innovative sample preparation system, the PS-10,

FLOW CYTOMETRY

specifically for FCM. Some existing technologies were integrated directly into the new instrument, including the Cavro Omni Robot for general purpose pipetting, and the Cavro Centris Pump to provide the precise flow rate control needed in FCM preparation. These form the main operating components of the PS-10, with other modules from both Tecan and Sysmex completing the design.”

“The new sample preparation system

(Left to right) Hiroyuki Koga, Masaki Shiba and Yoichi Nakamura from Sysmex in front of a prototype PS-10 instrument (NOTE: Photo taken prior to social distancing)

has proven the perfect solution to the labor-intensive FCM testing workflow.

The PS-10 automates antibody cocktailing and sample preparation, which vastly increases throughput and cuts down the chance of human error, giving our customers more confidence in the results of their work. Using Tecan’s Freedom EVOware® software, the system simply produces a file to export, ready for FCM analysis, and

e contacted Tecan first because of its W proven experience in innovating liquid handling automation. The company’s long history and established reputation as an OEM partner further cemented the decision to collaborate.

stores all the information regarding reagents and procedures to ensure full traceability. The instrument can also

product development cycle between

be tailored to match specific

our head office in Kobe, Japan, Tecan’s

To find out more about the Cavro

laboratory needs, and is compatible

hardware team in California, USA, and

with antibody reagents from various

Omni Flex, visit

its software development team in

manufacturers.”

Mainz, Germany. This combined

partnering.tecan.com/omniflex

experience proved crucial to the

To find out more about Tecan

“We contacted Tecan first because of

success of the project. We set out to

its proven experience in innovating

help our customers to increase their

liquid handling automation. The

efficiency and get more consistent

company’s long history and

results by eliminating user variability.

established reputation as an OEM

That’s exactly what we’ve done with

partner further cemented the decision

the PS-10 and, since its launch in 2019,

To learn more about the Sysmex

to collaborate. Getting this instrument

many laboratories have chosen the

PS-10, go to https://us.sysmex-

from idea to market was a true global

instrument, which now plays an

flowcytometry.com/ps-10-

effort between our teams, involving

integral role in their FCM testing

sample-preparation-system

communication over the entire

workflows.”

Synergence™ OEM systems engineering, visit www.tecan.com/synergence

TECAN JOURNAL 2/2021

17

OEM SYSTEM DEVELOPMENT

A sure BET for workflow automation Bacterial endotoxin testing (BET) is an important quality control check for the pharmaceutical and biomedical industries, ensuring that injectable or intravenous drugs and implantable medical devices are safe to use. Lonza offers a wide range of reliable BET solutions for QC labs, including high throughput, automated systems for microplate-based endotoxin detection.

Endotoxins are large molecules found

Automation is the obvious solution to

in the outer membrane of Gram-

this challenge, and Lonza wanted to

negative bacteria, helping the bacteria

build on the success of its early PyroTec®

to survive in harsh environments. This

Platform – a Freedom EVO®-based

role in nature makes the presence of

system mainly used in the dialysis

endotoxins difficult to control in a

market – by creating a fully automated,

laboratory environment, as they are

integrated BET system specifically for

resistant to extreme conditions,

QC activities in the pharmaceutical and

including high heat and chemical

biomedical sectors. Ruth continued:

treatments. Unfortunately, when

“The PyroTec® PRO Automated Solution

present in ng/kg concentrations in

offers users the ability to move away

vivo, endotoxins can cause symptoms

from manual benchtop endotoxin

such as fever and pyrogenic shock,

detection protocols to a fully automated

making it essential that parenteral

workflow. It has been developed from

medicines – drugs using non-oral

the outset for mid-sized pharma and

means of administration – vaccines and

biotech companies around the world

implantable medical devices are

performing QC testing in GMP

routinely tested for the presence of

environments, where reliable

endotoxins during production. Ruth

technology and strong support are

Noé, a Senior Product Manager at

critical. Many of these customers are

Lonza, has been working in this area

already using manual, plate-based

for 20 years, and explained the

testing solutions, and might have

process: “Our partners test production

automated other processes in areas like

waters, raw materials, in-process

chemistry, so it’s a natural progression.”

samples and manufactured products to both meet the regulators’ requirements and to mitigate contamination risk in their processes. For pharmaceutical companies, around 60-70 percent of all BET is on production waters and, if any contamination is detected, it can impact the final product integrity, so testing needs to be both fast and highly reliable for corrective and preventative action to be taken in a timely manner.”

18

TECAN JOURNAL 2/2021

OEM SYSTEM DEVELOPMENT

e are very happy W with our ongoing relationship with Tecan.

Moving forward, we have a clear product development roadmap for our BET portfolio.

The PyroTec® PRO System offers a fully automated endotoxin detection workflow (NOTE: Photo taken prior to social distancing)

Lonza’s goal for the PyroTec® PRO

worked with Tecan to develop a

WinKQCL® Software allows users to

System was to provide a user-friendly,

special firmware that takes the

save and manage the data on a central

fully integrated automated system to

temperature readings at a slightly

database, accessible to any authorized

help increase the productivity of BET

different time point than usual, to

individuals within the company – at any

for its customers. Ruth commented:

confirm testing is performed within

site – streamlining data management

“From our previous experience working

the specified temperature range. The

and giving our customers greater

with the Tecan Synergence™ team on

system also features an additional

flexibility.”

the original PyroTec® System, it was an

insulation plate to help minimize

obvious choice to use this partnership

temperature fluctuations.”

“We are very happy with our ongoing relationship with Tecan and are

when discussing the development of the PyroTec® PRO System, as it was

A lot of focus when developing the

constantly working with the Tecan

evolution rather than revolution. Tecan

PyroTec® PRO System was on the

team to keep our customers happy,

has extensive experience with liquid

software. Ruth explained: “Scripting

from the initial installation to making

handling and automation, and we have

the workstation’s movements in

sure that processes and documentation

the expertise in endotoxin testing, so

Freedom EVOware® was really just the

are updated and adhered to. Moving

putting the two together is great. We

first step, as our vision for this system

forward, we have a clear product

also take pride in the fact that both

was that customers could simply set up

development roadmap for our BET

companies have experience in the

their samples using a template within

portfolio with Tecan, including the

GMP-QC environment, where many

our WinKQCL® Endotoxin Detection &

possibility of future system iterations

other suppliers may not.”

Analysis Software, populate the deck,

based on new decks, platforms and

click go, walk away and come back to

readers,” concluded Ruth.

“The PyroTec® PRO System is based on

results later. However, about 30-40

a proven and reliable technology

percent of all tests are on sample

– Tecan’s Freedom EVO 150 workstation

matrices that require dilution or

– with both a Liquid Handling Arm™

additional diluents or additives – such

and a Robotic Manipulator Arm™ to

as magnesium chloride – to overcome

completely automate the liquid

assay interference before running.

handling processes. Crucially, the

Scripting for each individual sample in

system also features an integrated

Freedom EVOware simply wasn’t

Sunrise™ absorbance microplate reader

feasible so, with Tecan’s support, our

to allow walkaway measurement and

software developers created a Lonza

data acquisition. Endotoxin detection

patented dynamic scripting interface

To learn more about product

assays must be performed within a

that seamlessly integrated our

disclaimers and Lonza’s

specific temperature range to comply

market-leading WinKQCL® Endotoxin

automated endotoxin testing, visit

with pharmacopeial regulations, so

Detection & Analysis Software with the

www.lonza.com/endotoxin-

temperature management is critical for

system. Whether the data is from a

automation

the acceptance of the results. We

manual or automated process, the

To find out more about Tecan Synergence, go to www.tecan.com/synergence

TECAN JOURNAL 2/2021

19

METAGENOMICS

Taking the guesswork out of diagnostics Metagenomics is rapidly emerging as a promising method for disease diagnosis, but the need for manual processing is delaying turnaround times and limiting clinical uptake. Dr John Rossen, Head of Global Research & Development and Product Strategy for Europe at IDbyDNA Inc, discusses how the company has developed a test that can give detailed diagnostic reports on pathogens associated with respiratory infections and urinary tract infections, and how automation will speed the transition of this assay from research to routine testing in clinics.

Patients who present with an unknown

investigate all pathogens and host

detailed analysis of several key aspects

respiratory complaint are typically

responses at once. It enables

– such as antimicrobial resistance

given a single, conventional molecular

comprehensive analysis of all microbial

markers – and is more expensive than

test or bacterial culture test for a

and host genetic material – including

more targeted approaches.

suspected target organism, which is

bacteria, viruses and fungi – to help

decided by the physician. This leads to

identify pathogens that were

San Francisco Bay area-based

concerningly low diagnostic success

previously missed. Investigating the

company IDbyDNA has developed an

rates, with no causative pathogen

genomes of the entire microbiome also

innovative Precision Metagenomics

detected in 60 percent of pneumonia

provides insights into complex

approach to overcome the limitations

cases. Clinical shotgun metagenomics

coinfections, and helps to predict

of shotgun sequencing. This

offers an alternative strategy to

resistance or virulence phenotypes

sequencing strategy, combined with

diagnosing disease, by providing a

that can worsen disease outcomes.

advanced AI, is already being used for

broad, unbiased and culture-

However, shotgun sequencing also has

diagnosing respiratory and

independent technique that can

some drawbacks, as it does not allow

genitourinary infections, as well as to

Dr John Rossen (center) with members of the IDbyDNA team 20

TECAN JOURNAL 2/2021

METAGENOMICS

identify antimicrobial resistance

Dr Rossen continued: “We currently

an individual level, as undetected

markers, and the company is now

perform the wet lab work manually,

coinfections often worsen the disease

looking at automating its workflow to

which, as you can imagine, is not

progression. Precision Metagenomics

improve the throughput for clinical

particularly feasible for labs routinely

is the best unbiased and culture-free

samples. Dr John Rossen, Head of

performing high volume diagnostics,

method for the identification of a

Global Research and Development and

with hundreds of cases that they need

pathogen, and automation can make

Product Strategy for Europe at

to investigate. Although still much

assays commercially viable in clinics

IDbyDNA, discussed the role of

faster than conventional culture

for the future of disease diagnosis.

automation in turning newly developed

testing, performing sequencing

This is what IDbyDNA is aiming to

research use only assays into

processes manually can take a long

provide: precise insights for better

commercially viable diagnostic tests:

time, and it is very labor intensive,

health,” Dr Rossen concluded.

“Our company is bringing Precision

delaying the turnaround time for test

Metagenomics into the clinical space,

results and increasing the incidence of

initially focusing on respiratory and

errors. The next obvious step our

genitourinary infections. Some viral

customers are asking for is to

respiratory infections are already

automate the library preparation and

detected by molecular diagnostics –

enrichment process, to make Precision

mainly using real-time PCR – but we

Metagenomics a realistic alternative to

wanted to take this one step further,

real-time PCR for precise disease

using Precision Metagenomics to

diagnostics in clinics.”

detect all the known pathogens causing respiratory disease, instead of a single

“Automation of any molecular

target. You get a clearer overall picture

diagnostics workflow needs to begin

of the interaction between various

with a liquid handling workstation that

organisms, as well as identifying

can perform sample extraction, library

coinfections or predicting antibiotic

preparation and any other pipetting

resistance, both of which can influence

task in the pathway. This will remove

the outcome of treatment and disease.”

much of the labor that goes into preparing hundreds of samples a day,

“We initially began with respiratory

and will increase our throughput

indications, creating an assay that

dramatically. The sequencing data can

provides a thorough genomic

then be run through our automated,

investigation of over 270 pathogens

AI-driven data analysis solution with

and around 1,200 different

syndrome-specific reporting – such as

antimicrobial resistance alleles. This

selective reporting of pathogens

means that a patient presenting with

commonly linked to genitourinary

COPD symptoms can be given the

infections – to provide clinicians with a

same assay as a patient with

clear interpretation of results in a

suspected TB, for example, so it is not

diagnostic report.”

With automated sample preparation, the sky is the limit for metagenomic sequencing, and we can really begin to appreciate its potential for diagnostic testing and tracing outbreaks of disease.

disease specific. We then adapted this approach to develop one workflow

“With automated sample preparation,

that could be used for almost every

the sky is the limit for metagenomic

disease area, including respiratory

sequencing, and we can really begin to

infections, genitourinary infections,

appreciate its potential for diagnostic

sepsis and many more.”

testing and tracing outbreaks of

To find out more about Tecan’s solutions for automated clinical diagnostics, visit diagnostics.tecan.com

disease. One thing that the COVID-19 IDbyDNA has already completely

pandemic has shown us all is that it is

To learn more about IDbyDNA,

automated its data analysis and

not only important to detect a virus,

go to www.idbydna.com

reporting, and is now looking to

but also to do surveillance and

automate its laboratory workflows.

understand the disease landscape on

TECAN JOURNAL 2/2021

21

DETECTION

Don’t miss a beat with live cell imaging US-based company zPREDICTA™ has created a novel 3D technology that reconstructs physiologically-relevant and organ-specific human microenvironments for drug discovery and development. High throughput cell imaging and real-time cytometry of these 3D cultures can give a day-by-day account of cellular behavior and modulations of various immune cell populations to evaluate the efficacy of anticancer drugs.

Too often, drugs that are tested in

human microenvironments, so that they

preclinical trials later fail in human

behave in the same way as they do in

clinical trials due to their lack of

patients. We began by developing

efficacy. This is largely because drug

tumor-specific models to simulate the

discovery tends to rely on either

complex human organ environment for

non-physiological 2D cell culture or

testing various anticancer drug types

physiologically-irrelevant mouse

– including small molecules, antibodies,

models that can only go so far in

antibody drug conjugates and CAR-T

representing human diseases or the

cells – and have since branched out into

complex landscape of the human tissue

other organ-specific models.”

immune response. Tissue specialist

22

TECAN JOURNAL 2/2021

zPREDICTA, based in California, USA,

Julia continued: “Our work really

has developed a novel 3D culture

focuses on immune oncology

technology for the recapitulation of

applications, looking at the interaction

physiologically-relevant and organ-

between different cell populations to

specific human microenvironments.

determine how various types of drugs

This platform mimics the native

can trigger immune cell responses. We

architecture and behavior of human

routinely perform large-scale drug

cells of the tissue of interest, and is

testing studies and acquire data from

available for various organ-specific

different doses and at various time

research focal areas, including

points, which can be tedious and

reconstructed bone marrow (r-Bone™),

extremely difficult to do manually

breast (r-Breast™), lung (r-Lung™) and

without making mistakes or transfer

stomach (r-Stomach™). This

errors. We wanted to increase our

comprehensive 3D culture approach

throughput and accuracy with

conserves many cellular and

automation and, in 2016, invested in a

extracellular elements, and is the

D300e Digital Dispenser from Tecan,

closest drug developers can get to

which made a tremendous difference to

human tissues in preclinical trials.

our workflows.”

Dr Julia Kirshner, founder and CEO of

“Our success with the D300e has

zPREDICTA, explained: “Our company

helped us build a trusting working

was established with the goal of

relationship with Tecan, and we have

creating more accurate and predictive

since collaborated on more projects,”

model systems for drug developers to

Julia added. “Recently, we’ve been

test new compounds, so that they are

optimizing the Spark® Cyto plate reader

actually effective in clinic. In oncology

for high throughput cell imaging and

– or any disease field for that matter –

real-time cytometry in our 3D cultures.

drugs need to be tested against models

The conventionally static method of

that match the conditions found in

examining cells under a microscope is

DETECTION

e needed something more sophisticated W that could give us good quality images – especially from 3D cultures – and the Spark Cyto does just that. labor intensive and time consuming, often taking days and requiring constant refocusing and plate movement to capture the right shot.

“The versatile Spark Cyto multimode

Instead, we wanted to invest in a high

reader is also a valuable tool for

throughput imager, but the lower-end

multiplexing analyses.

systems were not of a high enough

Physiologically-relevant 3D cultures

quality, and we couldn’t risk trading off

are far superior to other modeling

image resolution for throughput. We

methods for predicting clinical

needed something more sophisticated

outcomes, however, they are often

that could give us good quality images

more expensive and time consuming

– especially from 3D cultures – and the

to build than 2D cultures. By

Spark Cyto does just that.”

multiplexing assays, we can gather more readouts and information from

“The system saves us a huge amount

each experiment, saving time and

of time by capturing good quality, fast

resources. For example, with the

and dynamic images of our 3D

Spark Cyto, we have been able to

cultures, and automatically indexing

develop a multiplexed, sequential

the image to the same spot each time.

protocol of LIVE/DEAD cell staining

It also overlays each fluorescent

followed by CellTiter-Glo® analysis, all

channel for easy comparison and to

with just one compact instrument.”

avoid lengthy post-processing. The For Research Use Only. Not for use in

images can be captured in real time,

“Both the D300e and the Spark Cyto

thanks to the flexible temperature and

have been really beneficial for our

carbon dioxide controls, giving us a

regular workflows, and are routinely

clear picture of the step-by-step cell

applied to all internal and most

response to drug treatment. The

customer projects. The systems are

fluorescence capability of the

easy to maintain, and the software has

To find out more about Tecan’s

Spark Cyto allows us to follow the

been updated remotely by Tecan, so that we could continue operating

Spark Cyto, visit

behavior of different labeled cell types within the extracellular matrix, which

throughout the COVID-19 pandemic.

would be very difficult to achieve

We have established a great

otherwise. This is a real added bonus

relationship with Tecan that I feel we

for our customers too, as they often

can both benefit from, and I look

want to know whether immune cells

forward to this continuing in the

are capable of reaching a target area

future,” Julia concluded.

unaided, and this allows us to give them a concrete answer and day-by-

diagnostic procedures.

Tecan D300e Digital Dispenser is a product of HP Inc. CA, USA.

www.tecan.com/sparkcyto To find out more about Tecan’s D300e Digital Dispenser, visit www.tecan.com/d300e To learn more about zPREDICTA, go to www.zpredicta.com

day account.”

TECAN JOURNAL 2/2021

23

DETECTION

Fluorescence imaging shines a light on systems biology Chromosomal tagging using advanced fluorescent labeling techniques can help us to understand cells at a systemic level.

Researchers in Germany have developed a universal approach for CRISPR-Cas12a-assisted PCR tagging of mammalian genes, using scalable live cell imaging to optimize their methods.

The Knop Lab at the University of

a Knop Lab PhD student working in

enables the rapid creation of

Heidelberg’s Center for Molecular

collaboration with the German Cancer

mammalian cell lines with targeted

Biology is researching the processes

Research Center, explained: “Our group

large chromosomal insertions, such as

that regulate cell signaling, cell

focuses on answering questions about

green fluorescent protein (GFP). These

differentiation, protein quality control

how cells work, and obtaining a

proteins can then be visualized with a

and homeostasis in yeast and in

systemic understanding of them. The

microscope or cell imaging system. The

clinically-relevant mammalian systems.

aim is to develop tools and methods for

aim is to establish a universal, scalable

The group combines live cell imaging

use by the wider research community,

and high-fidelity method to tag

with a range of fluorescence-based

to answer biological questions and

proteins in mammalian cells, enabling

techniques to observe protein function

develop a better understanding about

researchers to tag and target as many

and investigate biomolecular

cells’ behavior.”

proteins as possible.”

environment. These functional

“My focus is on method development,”

The group’s PCR tagging method

high-content imaging methods are

Krisztina continued. “Currently, I am

involves the transfection of a gene-

combined with genetic and genomic

working on optimizing a PCR tagging

specific PCR cassette into the target

approaches to explore the cellular

method, a one-step procedure for

cells, together with a helper plasmid

processes of interest. Krisztina Gubicz,

chromosomal gene tagging that

containing a Cas12a endonuclease,

interactions in their natural

The Knop Lab team (NOTE: Photo taken with respect to social distancing measures and COVID regulations within Germany.)

24

TECAN JOURNAL 2/2021

DETECTION

fusing a tag – such as GFP – onto the gene of interest. The process uses two gene-specific tags – termed M1 and M2 – with homology arms ranging from 50 to 90 nucleotides for targeted integration by homology-directed repair-based (HDR-based) genome editing. The M2 tagging oligo also provides a protospacer sequence for the Cas12a endonuclease. The generic template cassette contains a Cas12aspecific crRNA gene consisting of a promoter and crRNA direct repeat, as

The Knop Lab is taking advantage of the Spark Cyto’s fluorescence imaging and cytometry capabilities capabilities for PCR tagging experiments

well as providing the fluorescent tag and additional features, such as a selection marker. Expression of the crRNA gene inside the cell directs Cas12a expressed from the helper plasmid to a target locus close to the insertion site, causing a double strand break. The linear tagging cassette is then incorporated into the genome at this site by HDR. The homology arm of the M1 tagging oligo directs in-frame fusion of the tag with the target open reading frame, leading to the expression of a tagged protein.

Krisztina continued: “When developing this universal method for CRISPR-Cas12a-assisted PCR tagging of mammalian genes, we initially relied on fluorescence microscopy methods for live cell imaging, and still use this technique extensively. However, we wanted a more scalable approach, and so acquired a Spark® Cyto, a multimode plate reader with fluorescence imaging and cytometry capabilities. This system

I t’s a much faster way to analyze cells than microscopy, because it not only enables live cell imaging, but also allows us to take advantage of the Image Analyzer software package to immediately quantify the success and efficiency of tagging experiments. only enables live cell imaging, but also

controlling the reader temperature at

allows us to take advantage of the

37 °C, we also plan to take advantage of

Image Analyzer™ software package to

the integrated gas control function to

immediately quantify the success and

maintain levels of CO 2 in the future. It’s

efficiency of tagging experiments. Most

been an interesting journey getting to

of the time, we’re working with a single

know the Spark Cyto and discovering

fluorophore at this stage, but we can

what we can use it for, and we’ve

also use the Spark Cyto’s multicolor

enjoyed excellent support from Tecan,”

application to automatically analyze

concluded Krisztina.

multiple channels, to perform

is a great addition to the lab, giving us

colocalization studies or introduce

another way to gather information

additional labels.”

For Research Use Only. Not for use in

about the cells, and the success of the fluorescent tagging process. It allows us

“Although we mainly use the Spark Cyto

to rapidly image mammalian cells in a

for end-point measurements, we also

high quality and reliable way, and is

have the option to incubate cells inside

ideal for optimization studies, as it can

the reader if necessary. Most

simultaneously image the entire

experiments only take a couple of

microplate. This is a real advantage if

minutes per plate, but it’s good to know

we have several set-ups to evaluate, as

that we can incubate the cells in the

we can image every well used in the

measurement chamber if we need to, to

To learn more about the Knop Lab,

study. It’s a much faster way to analyze

make sure that they remain viable

go to www.knoplab.de

cells than microscopy, because it not

throughout the experiment. As well as

diagnostic procedures.

To find out more about Tecan’s Spark Cyto, visit www.tecan.com/sparkcyto

TECAN JOURNAL 2/2021

25

COVID-19

Computational biomedicine at the forefront of epigenomics The advent of new genetics technologies has exploded in the last decade. Since the unravelling of the human genome project in 2003, and with recent discoveries in the field of epigenetics, we are starting to understand not only how and when genes are expressed, but which post-translational modifications are important in disease, and how we can manipulate them therapeutically. Professor Christopher E Mason has developed new technologies to catalog genetic and epigenetic changes caused by everything from cancers to novel viruses, and these tools have proven invaluable during the COVID-19 pandemic.

Since the first discoveries in the field of

large consortium tracking microbial

patients’ samples and swabs from

epigenetics in the 1950s, it has been

changes in urban environments. Initially,

hospital surfaces, etc.”

understood that all the inheritable

we were doing everything by hand, but

changes occurring within a cell cannot

our rapidly growing workload meant

The lab still had to adapt its workflow

be explained simply by the DNA

that we urgently needed a robust

to accommodate the unexpected

sequence itself. We now know that both

platform that could reliably and

increase in throughput due to testing of

environmental and lifestyle changes

continuously process the large numbers

COVID-19 patient samples. Dr Mason

can influence whether genes are

of samples we had coming in. Crucially,

expanded: “Since the beginning of the

expressed or silenced, and these factors

it needed to be something we could

pandemic, we have been involved in

can have potentially damaging effects

easily fit into our lab and allow us to hit

numerous projects, both for getting

on our health, such as making us more

the ground running. I heard about the

new testing methods onto the market

prone to developing certain diseases.

DreamPrep™ NAP workstation through

and for tracking the emergence of new

Professor Christopher E Mason is an

a number of our collaborators, and

strains as a result of viral evolution, to

expert in computational and systems

Tecan has a good reputation in the field,

help understand the implications for

genomics, having worked in the field for

so I contacted the company to see what

disease development, treatment and

over 15 years. He is one of the founding

we could do.”

vaccination. This means that our

directors of the MetaSUB International

workflow has been pretty much 5am to

Consortium. Through his research, he

“We were quickly able to set up and run

10pm every day. We really felt that this

has developed a wide knowledge of the

a high throughput platform using the

was a time where we could be most

epigenome and epitranscriptome –

DreamPrep NAP workstation to extract

useful to the wider society, and so we

DNA- and RNA-level modifications,

and process genetic material collected

worked as much as we could!”

respectively – to gather vast amounts

from either clinical samples, or from the

of data that will allow a better

environment – sewage, public benches,

“The DreamPrep NAP has fitted

understanding of how some of these

city subways, etc. I am very much an

seamlessly into our workflow, saving us

seemingly unrelated pathways interact

omnivore of genetics, so when I’m

time, energy and costs. Without it, I

in disease progression. Dr Mason

looking at viruses, I like to find them all,

don’t think we would have been able to

explained: “I oversee a combination of

which is why we use a shotgun

process anywhere near as many

molecular and computational biology

sequencing approach. This is the real

COVID-19 samples as we did, especially

research programs using ‘wet work’ at

fun part of science – pure discovery –

with the need to reduce the number of

the lab bench and the design of new

and in the environmental samples we’ve

staff we had in the lab at any one time. It

algorithms and machine learning to

been collecting, we’ve seen anywhere

has been a true workhorse, and very

process and make sense of the data

from 30 to 60 percent new species,

reliable, with the preprogrammed

that is generated and discover its

annotating them and tracking their

protocols working well. The support

biomedical meaning.”

evolution as we went. This very broad,

from Tecan has also been very

flexible approach meant that, when the

responsive. Any time we’ve had an issue

“Prior to the COVID-19 pandemic, we

pandemic hit, we were already very well

or questions, we’ve had someone on the

mostly processed cancer and

set up to provide a rapid platform to

phone really quickly, or coming to check

microbiome samples, the latter as part

track SARS-CoV-2 genetic material from

it out, which is essential in this kind of

of a project called MetaSUB, which is a

various sample types, including both

situation,” Dr Mason concluded.

26

TECAN JOURNAL 2/2021

COVID-19

For Research Use Only. Not for use in diagnostic procedures.

To find out more about Tecan’s DreamPrep NAP workstation, go to www.tecan.com/ dreamprep-nap-workstation For general information on nucleic acid purification visit www.tecan.com/nap

It has been a true workhorse, and very reliable, with the preprogrammed protocols working well.

To learn more about the MetaSUB consortium, visit www.metasub.org

TECAN JOURNAL 2/2021

27

DRUG DISCOVERY

Fighting neglected and non-communicable diseases Carbonic anhydrases (CAs) catalyze the reaction between water and carbon dioxide to regulate pH and fluid balance in vivo. Deviations in CA activity have been shown to correlate with bone, lung and liver diseases, as well as obesity, type II diabetes and even epilepsy. Professor Areej Abuhammad and her team at the University of Jordan are interested in developing novel therapies to counteract imbalances in CA activity, using protein crystallography to investigate a wide range of potential inhibitors.

Carbonic anhydrases are a large group

X-ray crystallography to investigate the

great. And being very simple to set up,

of zinc metallo-enzymes that can

structure of proteins, and how the

and offering versatile applications, it is

reversibly catalyze water and carbon

ligands and inhibitors bind to them.

perfect. Setting up a new lab is always

dioxide – forming hydrogen and

This knowledge is very important for

difficult, especially when working with a

bicarbonate – to alter pH and carbon

structure-based drug discovery,

tight budget, but the Tecan team and

dioxide concentrations. Areej

making it easier to make an informed

local distributor were very supportive,”

Abuhammad, an Associate Professor in

decision on what needs to be altered,

Areej concluded.

Medicinal Chemistry at the University

as well as finding out which functional

of Jordan, is combining her background

groups are responsible for the activity.”

in computer-aided drug design, structural biology and medicinal

“A microplate reader is obviously a key

chemistry to investigate selective

instrument in our research, as we

inhibitors for CA. Areej explained: “The

perform a lot of enzyme activity assays,

function of carbonic anhydrases is to

screening a variety of different

control the pH in the body and, through

inhibitors and enzyme isoforms. I

it, a variety of biological processes.

therefore needed an instrument that

They are therefore linked to the

offers high sensitivity and can handle

etiology of many different pathogenic

small sample sizes, which is essential to

diseases.”

reduce the cost of screening. I also wanted a monochromators-based

“I have always been interested in

system, as we need the flexibility to

neglected diseases; I did my Master’s

perform a wide range of experiments,

degree on avian influenza and, during

screening as many different conditions

my PhD, I worked on drug discovery for

as we want without the limitation of

tuberculosis in the Departments of

filter sets.”

Pharmacology and Biochemistry at the University of Oxford. I moved back to

“After working with a Tecan instrument

Jordan after finishing my PhD, and

during my PhD, I decided to buy an

used the knowledge that I acquired to

Infinite® M Plex reader for our lab in

set up a protein crystallography lab to

Jordan, as this was the best for our lab.

perform research on CAs, combining

It offers the sensitivity and the

drug repurposing with fragment-based

accuracy level we need, while being

drug discovery.”

easy to set up and use. This intuitive operation, together with the system’s

“I am working with isozymes of CAs,

robustness, is something that I really

screening for the new inhibitors and

like about it. We have a lot of Master’s

testing their enzymatic activity. I am

students – as well as offering some

interested in knowing exactly how the

training to undergraduates – and they

inhibitors impact the enzyme; if they

are naïve to the sensitivity of these

inhibit or activate it, and how the

instruments when they first enter the

kinetics work. I also crystallize the

lab. Having a system that can withstand

proteins with the inhibitors and use

this without it compromising results is

28

TECAN JOURNAL 2/2021

DRUG DISCOVERY

I t offers the sensitivity and the accuracy level we need, while being easy to set up and use.

To find out more about Tecan’s Infinite M Plex, visit www.tecan.com/infinite200pro To learn more about Areej Abuhammad’s research, go to www.researchgate.net/profile/ Areej-Abuhammad

TECAN JOURNAL 2/2021

29

DRUG DISCOVERY

Robotic biology for the lab of the future Laboratory automation is increasingly common in life sciences research, helping to tackle some of the challenges that come with manual workflows, including inefficient operation, limited throughput and challenges of reproducibility. However, most automated platforms still require human operators to set up reagents, transfer plates between machines, and clean down afterwards. Dr Koichi Takahashi and his colleagues at the RIKEN Center for Biosystems Dynamics Research in Japan are developing a new type of laboratory automation workflow system that combines humanoid and other types of robots, creating a prototype for the lab of the future.

Dr Takahashi, principal investigator in

robot that can do experiments on its

Tokyo and Keio – we have been

the Laboratory for Biologically

own. We have a multidisciplinary team

developing a prototype robotic

Inspired Computing at RIKEN, and his

with experience in programming,

biology laboratory, where various

team are working on the application of

mathematics and lab-based skills, but

types of robots will interact together

artificial intelligence (AI) and machine

our common language is systems

to conduct different protocols. To do

learning techniques to mitigate the

biology, and our goal is to combine the

this, we are using a humanoid robot

overwhelming complexity in modeling

expertise of human beings, robots and

called LabDroid and linking systems

cellular systems. Dr Takahashi

AI.”

together with a common description

explained: “We are trying to

programming language called

understand very complicated life

Dr Takahashi continued: “Through a

systems with the help of computers

JST MIRAI funded collaborative

and AI. As part of that activity, we are

research project – involving RIKEN,

Most laboratory automation systems

focusing on developing a new type of

AIST and the universities of Tsukuba,

do not offer a complete workflow,

Imagining a robot room in the lab of the future 30

TECAN JOURNAL 2/2021

LabCode.”

DRUG DISCOVERY

requiring human operators to prepare

e have a multidisciplinary team with W experience in programming, mathematics and lab-based skills, but our common language is systems biology, and our goal is to combine the expertise of human beings, robots and AI.

reagents and act as the link between different machines, but robots can

able to carry out the entire process

offer an alternative. Dr Takahashi

without human intervention.”

described: “LabDroid is a high performance, dexterous humanoid

Dr Takahashi concluded: “I believe that

robot. It is about the same size as a

the fifth paradigm of science will be

human, and can mimic human

automation, after experimentation,

movements with delicate precision,

theory, simulation and data. It will be a

making use of standard lab equipment

paradigm change because automation

without modification. Because robots

is a strong – and even crucial – weapon

are very accurate and precise, they do

to combine data- and model-driven

not make mistakes, improving

approaches to accelerate research

reproducibility compared to manual

processes, especially when we want to

operation.”

understand the overwhelming complexity of cellular systems which are beyond our cognitive capacity. We

For full integration between different robots and machines, they need to be able to communicate through the same

Dr Koichi Takahashi of the RIKEN Center for Biosystems Dynamics Research

are going to continue working on cell culture with different types of cells, and we are trying to implement the system

programming language. However, most automation systems operate using their

The research team carried out a proof

for ‘omics’ experiments. We want to

own unique language, a challenge that

of concept study using a genome

showcase the power of our software to

the team looked to address. Dr

editing protocol from the University of

combine different types of robots and

Takahashi elaborated: “LabCode

Tokyo. Dr Takahashi explained: “The

many different types of experimental

interprets a command, and

protocol involves cell seeding and

protocols, maximizing the potential of

automatically generates programs that

culture, followed by DNA extraction

the entire system to develop the lab of

can be understood by different

and barcoding. LabDroid is good at

the future.”

hardware from various vendors, using

the cell culture, and we used the

separate transcription languages. This

Freedom EVO for the DNA extraction,

allows machines to be connected to

as it is very efficient for liquid handling

one network and interpret the same

tasks. To describe the workflow using

command codes. For example, we use

LabCode, we gave the compiler the

To find out more about Tecan’s

the Freedom EVO® platform for liquid

environmental definitions of the machine hardware and the

Freedom EVO platform, visit

handling, which has a nice open API interface, so we could construct our

dependencies between the protocol

software using this easily interpreted

components, and it generated the

information with some help from Tecan

workflow through dynamic

engineers. We can also use LabCode to

programming, providing the

capture tacit knowledge from human

instructions for the human operators,

operators, and feed this into the control

LabDroid and the Freedom EVO with

of the robots.”

the optimum settings. The system was

For Research Use Only. Not for use in diagnostic procedures.

lifesciences.tecan.com/ freedomevo To learn more about RIKEN Center for Biosystems Dynamics Research, go to www.bdr.riken.jp

TECAN JOURNAL 2/2021

31

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