Tecan Journal Edition 02/2020

Page 1

Tecan Journal

Edition 2/2020

Life Sciences, Diagnostics and Partnering

Racing against a pandemic

Improving quality of HIV diagnosis in Kenya

Using saliva to study hormones

Print your own DNA

Pages 12-13

Pages 14-15

Pages 18-19

Pages 26-27


CEO WELCOME

Welcome to this unique issue of the Tecan Journal In this unprecedented time, we consider it a privilege to be part of the international effort to turn the tide on COVID-19, working alongside the scientific and clinical communities to accelerate research and the discovery of treatment options, and scale up population testing. From viral RNA extraction, PCR set-up and NGS automation to serology testing, we are using our product portfolio – as well as our service and applications knowhow – as part of a highly collaborative approach to help contain the SARS-CoV-2 outbreak. The dedication and expertise of our staff, working hand-in-hand with laboratories and partners on the front line, has been truly exceptional in this difficult time. They have worked – literally around the clock at times – to plan workflows and install systems within the shortest deadlines, while still delivering the highest standards of performance and compliance. I would like to thank the entire Tecan team for their ongoing commitment and passionate support in these challenging circumstances. 2020 may not have been the 40th anniversary celebration we had hoped for, but I look forward to seeing customers and colleagues at events around the world once the acute threat of COVID-19 has been curbed. In the meantime, this issue of the Tecan Journal contains details of some of the novel coronavirus-related projects we have been involved in, as well as an exciting showcase of customer stories from around the globe. I hope you all stay safe and enjoy this issue, Achim von Leoprechting CEO

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CONTENTS

Contents 2

Welcome

4 - 7 Pandemic preparedness: scaling up for the healthcare industry

8 - 9 A beacon of light in the coronavirus pandemic 10 - 11 Customized solution supports automated compound management in core facility

14 - 15

12 - 13

Racing against a pandemic

Improving quality of HIV diagnosis in Kenya

14 - 15 Improving quality of HIV diagnosis in Kenya 16 - 17

Transferrable skills

18 - 19 Using saliva to study hormones 20 - 21

A sensitive subject

22 - 23 A smooth path for novel biologics 24 - 25 Generating success in regenerative biology 26 - 27 Print your own DNA 28 - 29 A jump start for nucleic acid processing

28 - 29 A jump start for nucleic acid processing 30 - 31 Empowering CORE oncology research

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 2/2020

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COVID-19

Pandemic preparedness: scaling up for the healthcare industry How do you prepare for the

The response of these laboratories has

The UK Government has recently

unexpected? The COVID-19 pandemic

been remarkable and heroic in most

identified five pillars critical for scaling

has brought to light how challenging it

cases, with great demonstrations of

up its testing programs, 2 based on the

is for labs and production facilities to

ingenuity and tireless devotion. An

available scientific research. Harvard

scale up quickly in times of need. The

inspiring example is the UK Biocentre,

University also published a document

sudden surge in demand for laboratory

which developed an automated sample

on ‘Pandemic Resilience’, 3 which

solutions at the very time that we are

handling and testing process from

reported the need for fast scale-up of

experiencing unprecedented

scratch in a matter of months.

multiple levels of testing in order to

constraints on the workforce and global

Manufacturers have also stepped up in

control the pandemic. Rapid scale-up is

supply chains is a wake-up call. This has

addressing this unprecedented

no small feat, but modularity in design

put pressure on infrastructures in every

challenge, with molecular diagnostics

of laboratory solutions and test

sphere connected to the healthcare

company Cepheid producing a test that

equipment may be key to achieving

industry – from R&D and manufacturing

can deliver results in under 45 minutes.1

some of the goals outlined in these

to clinical diagnostics. Even relatively

While this is the first global pandemic

documents. By working with modules, it

small labs and organizations have been

of this scale, it is unlikely to be the last,

means that no new solution has to be

required to rapidly shift focus and

and that forces us to reflect and

designed completely from scratch,

massively expand their outputs at an

consider what we can learn for the next

which can drastically reduce the time to

unprecedented rate. There is, however,

time, and how we can be better

implementation. A good example

a silver lining: the current pandemic

prepared.

during COVID-19 has been the rapid

compels healthcare industry leaders to

deployment of next generation

question the agility and scalability of

Rapid scale-up and custom

sequencing (NGS) and PCR-based

their laboratory solutions – both now

solutions are essential

techniques to analyze patient samples.

and in the future.

To meet such extreme challenges, the

Modular workflows for efficient nucleic

ability to adapt quickly to novel threats

acid extraction and purification are

and scale up operations accordingly is

allowing researchers to analyze

The current COVID-19 pandemic

essential. With COVID-19, we have seen

thousands of isolates using a variety of

represents one of the greatest global

the potential cost of delay, as well as

downstream methods. As discussed by

challenges of our time: a novel and

the speed at which global situations

Dr Christopher Mason, Associate

highly contagious airborne virus with

can change. Clinical infrastructures and

Professor at Weill Cornell Medical

initially no diagnostic test and currently

testing labs need sufficient agility to

College, a modular automation

no vaccines. The pandemic strikes at a

develop novel analysis methodologies

approach makes it easier for multiple

time when the world has never been

and/or modify existing protocols.

types of experiments and functionalities

more interconnected, meaning

Scale-up capacity is critical to enable

to be carried out and integrated on the

geographic barriers that previously may

rapid test validation and processing of

same platform.4 This allowed the Mason

have provided a natural means to curb

growing numbers of samples. At the

lab to add techniques such as RT-qPCR,

the spread are non-existent. The scale

same time, equipment manufacturers

isothermal assays and immunological

of the pandemic has put immense strain

need to be ready to quickly interpret

profiling to their DNA purification, to

on laboratories conducting serological

current research needs and medical

better understand heterogeneity in the

and PCR testing, as well as on those

knowledge in order to deliver tailored

viral populations.

labs screening drug candidates for

and cost-efficient solutions as soon as

treatments and working to develop an

possible.

An unprecedented challenge

effective vaccine as quickly as possible.

The Blog 4

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COVID-19

Agility is key to scaling up… and scaling back down again When scaling up or implementing a new analytical test or production process, it makes sense to establish and test new equipment and workflows when the pressure is off. That means installing and optimizing the set-up of

ith novel biological threats, the transition W from research to in vitro diagnostics also has to be fast and seamless, and companies that can provide both have a significant edge.

laboratory solutions before the demand for their use is at a peak. This poses somewhat of a conundrum: if the lab is at low capacity now, how quickly will it be able to adapt and validate its operating procedures to enable effective, cost-efficient use of high capacity automation equipment? Likewise, when demand later tapers off, will the lab be able to return to costefficient, low capacity production using the same equipment, or will that new high throughput system become a ‘white elephant’ with a high depreciation cost? An optimal solution is a lab automation set-up and integrated accessories that function well at low capacity but can be seamlessly scaled up when capacity increases. Modular solutions – especially those that are purpose-built to be compatible with commonly used off-the-shelf kits – are especially well-suited for pandemic responses, when solutions need to be rolled out fast. For example, as the COVID-19 pandemic expands, laboratories have had to scale up testing using high throughput approaches to isolate the viral RNA for downstream analysis. These workflows typically involve time-consuming steps such as scripting, protocol reconfiguration and

workflow optimization to ensure robust

The power of partnering

results. To avoid bottlenecks at this

For organizations that are considering

sample preparation stage, the entire process needs to be integrated into the overall workflow and scaled up quickly. Moreover, the automation solution needs to be compatible with preferred commercial kits, as well as being easily adaptable to accommodate new kits and protocols that may be introduced at a later time. Recently, Zymo Research and Tecan announced their partnership to launch a ready-to-go processing solution to streamline viral DNA/RNA extraction from nasopharyngeal swabs, oropharyngeal swabs, saliva, sputum, plasma and serum. “Nucleic acid extractions can be one of the most challenging, frustrating and time-consuming portions of a workflow to automate,” said Ryan Kemp, Director of Nucleic Acid Solutions at Zymo Research. “With push-to-start sample purification, the DreamPrep™ NAP workstation* is uniquely positioned to help labs around the world quickly and effectively scale their testing to accommodate a much larger number of tests and, ultimately, mitigate the spread of the virus.”

developing or scaling up production of a test kit, automated solution or other equipment for a rapid pandemic response, it is essential to have a thorough understanding of the full process workflow, as well as an appreciation of the viewpoints of all relevant stakeholders involved in its use, purchase, validation and maintenance. Getting this information quickly can be challenging in times of crisis when resources and staff may be limited. One way to accelerate the process is to engage with an experienced partner who understands the industry, including the customer base and the regulatory landscape. There are many providers for various manufacturing and workflow optimization needs, so it makes sense to research them and find out what they can really provide. When considering potential partners, their manufacturing capabilities are an important piece of the puzzle, but not the only piece. Beyond conducting a thorough audit, including a site evaluation, it is essential to find

www.tecan.com/blog TECAN JOURNAL 2/2020

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COVID-19

indicators that a manufacturing

Traversing the changing

travel and maintain physical distance.

partner can be trusted to deliver.

regulatory landscape

The workforce at large has done

Service contracts, lifecycle

In times of global crisis, regulatory

surprisingly well at adapting to this new

management and a vertically

guidelines and approval processes

remote working structure. However,

integrated business are all important

can often change quickly and

laboratory personnel often don’t have

factors to consider. A compatible

unexpectedly. During the current

the option to work from a distance due

culture and good communication

pandemic, for example, the FDA

to a lack of automation and remote

mechanisms are also key to ensuring

posted multiple updates on its

operation capabilities. Remote

that a partner can correctly interpret

website 5 on any given day. Many of

operation and monitoring features have

the project requirements, even in the

these posts included regulatory

quickly shifted from being a

heat of a crisis. Of course, any

implications for testing and

productivity gimmick to an essential

manufacturing partner should also be

manufacturing. It is therefore essential

feature to keep laboratory workers

able to provide tangible proof that

that partners are not just familiar with

safe during a global pandemic.

they really can deliver. Ideally, this

current regulations, but are flexible

When incorporating remote working

should include years of industry

and experienced enough to interpret

features into an automation project,

experience, a demonstrated track

new guidelines and legislation, and

look for providers who have a track

record and workable prototypes that

incorporate them seamlessly into an

record with these advanced features,

can be validated and tested.

ongoing project on the fly. This offers

and can demonstrate their reliability.

a huge advantage if you need to

Working remotely has made software,

respond quickly to get laboratory

connectivity and security paramount,

solutions to market.

and untested systems are not going to

Since trust takes time to develop, it is best to start conversations with potential partners as early as possible

cut it. It is important to find a solution

– ideally before any crisis occurs –

Remote monitoring and digital

that can work quickly, and integrates

when there is still time to build strong

communication are no longer

with current workflows, before

relationships. This advanced

optional

capacity is high and the pressure is on.

groundwork gives a project with a manufacturing partner the best chance possible to hit the ground running when the time comes.

The Blog 6

The COVID-19 pandemic has increased the remote workforce. Working from

Expecting the unexpected

home has been mandated in many

The COVID-19 pandemic has highlighted

countries to help reduce commuter

the value of quality lab automation while

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

TECAN JOURNAL 2/2020


COVID-19

illuminating some potential pitfalls. To

References

cope with a rapidly spreading pathogen

1) Nicole Wetsman. Newly approved novel coronavirus test gives results in 45Â minutes. The Verge. March 2020. https://www.theverge. com/2020/3/23/21191055/rapidcoronavirus-test-hospital-fda

or other emerging global health threat, adaptable solutions need to be developed and rolled out more quickly than ever before. Key to being better prepared for the next crisis may be the availability of more modular end-to-end solutions, such as those developed for nucleic acid purification and NGS sample prep, with the capacity to scale up and down quickly to meet changing demands in the lab. With novel biological threats, the transition from research to in vitro diagnostics also has to be fast and seamless, and companies that can provide both have a significant edge.

2) Department of Health and Social Care. COVID-19 – Scaling up our testing programmes. April 2020. https://assets.publishing.service.gov.uk/ government/uploads/system/uploads/ attachment_data/file/878121/coronaviruscovid-19-testing-strategy.pdf

4) Christopher E. Mason. COVID-19: A New Guest in the City-Biome. March 2020. https://tecan2.sharefile.com/share/ view/s5d7a29266fd4544b 5) U.S. Food and Drug Administration. Coronavirus Disease 2019 (COVID-19). May 2020. https://www.fda.gov/emergencypreparedness-and-response/ counterterrorism-and-emerging-threats/ coronavirus-disease-2019-c *For research use only. Not for use in clinical diagnostics.

3) Edmond J. Safra Center for Ethics at Harvard University. Roadmap to Pandemic Resilience. April 2020. https://ethics.harvard.edu/files/centerfor-ethics/files/ roadmaptopandemicresilience_ updated_4.20.20.pdf

emote operation and monitoring R features have quickly shifted from being a productivity gimmick to an essential feature to keep laboratory workers safe during a global pandemic.

www.tecan.com/blog TECAN JOURNAL 2/2020

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COVID-19

A beacon of light in the coronavirus pandemic UK Biocentre has been central to the UK Government’s response to the COVID-19 pandemic, repurposing its entire facility to become a national center for SARS-CoV-2 molecular testing. To help meet an ambitious target of 100,000 tests per day across the country, the organization has established a new mega-lab, partnering with Tecan to design and commission a suite of liquid handling automation platforms in just a few weeks.

UK Biocentre is a government-funded,

The situation changed dramatically in

about repurposing our entire

not-for-profit company based in Milton

March 2020, when UK Biocentre was

laboratory, turning it into a national

Keynes. It was originally established to

approached by the government to

coronavirus testing center with a

receive, process and store vast numbers

become a national coronavirus testing

capacity of delivering tens of thousands

of biological samples on behalf of large

center, part of the UK’s network of

of tests per day.”

academic research projects across the

newly constructed Lighthouse Labs, a

country. Prior to the COVID-19

nationwide group of mega-labs set up

Tony continued: “We discussed the

pandemic, this world-leading sample

to dramatically increase the capacity

size and importance of the challenge

management and high capacity

for SARS-CoV-2 testing. UK Biocentre

as a team, and started planning

bioprocessing facility received hundreds,

CEO Dr Tony Cox explained: “We had

exactly what we would need to deliver

or even thousands, of predominantly

been watching the pandemic sweep

that scale of testing in a short time

blood samples each day for processing,

across Asia and into Europe, and knew

period. As we were being asked to

DNA extraction, and storage in its large

what was coming. On the 19 th of March,

increase our throughput by several

automated biobank. These samples were

the UK government, recognizing our

orders of magnitude, it was clear that

then made available on request to

experience in processing large

we needed to reach out for help, and

participating research groups.

numbers of samples, approached us

that a highly automated process was essential to deliver the scale required at a national level.” “Within nine weeks, we had completely refitted a 35 by 15 meter empty space as a new mega-lab and grown from a staff of 47 to 300, predominantly made up of volunteer lab scientists. We now have a suite of 24 Freedom EVO® liquid handling platforms that provide rapid, coordinated sample processing, with the capacity to process tens of thousands of samples each day and turnaround times of just a few hours. At the moment, the testing kits we receive contain live virus, which must be deactivated in a Class IIA biosafety cabinet before the sample can be processed. That’s quite

Automation has been key to the UK Biocentre’s ability to rapidly scale up molecular testing

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COVID-19

ur processes are continually being O optimized and developed, and Tecan’s field application specialists are working side-by-side with us to achieve this.

a bottleneck in the workflow. However, the formulation of the swab testing kits will soon be changed to include an inactivating buffer, eliminating the need for this step. We will then be able to safely unpack the samples and place the tubes straight into racks and onto our automated platforms without using biosafety cabinets, which will significantly increase our processing capacity. The entire automated workflow is connected to Tecan’s Introspect™ software, which provides valuable real-time information on sample throughput and consumables usage, effectively monitoring productivity to help the lab process samples as efficiently as possible and avoid unnecessary delays.”

With so many Tecan systems in one lab, each instrument has been given its own name

“We are continuously scaling up testing to meet demand and are

instruments running. Our processes

and I’m not sure that I could ask an

preparing to deliver testing levels at

are continually being optimized and

awful lot more. It’s been fantastic,”

least one, and possibly two, orders of

developed, and Tecan’s field

Tony concluded.

magnitude higher than our current

application specialists are working

capacity. It’s a huge challenge, but it’s

side-by-side with us to achieve this.”

achievable thanks to the support of our volunteers and by working with

“There’s nothing like being set an

our partners to further streamline the

extraordinary challenge to pull teams

automated workflow. It’s not just

together and bring out the best in

about installing and commissioning

people to achieve success. The sheer

the Tecan systems; it takes an

investment of time and energy, in a

immense logistical and procurement

shared effort to make it all work, has

To learn more about UK Biocentre,

effort to maintain a constant supply of

been quite astounding. I’ve been really

go to www.ukbiocentre.com

reagents and consumables to keep the

pleased with the response from Tecan,

To find out more about Tecan’s solutions for COVID-19 testing, visit www.tecan.com/covid19

www.tecan.com/covid-19 TECAN JOURNAL 2/2020

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CUSTOM AUTOMATION

Customized solution supports automated compound management in core facility G-protein coupled receptors

Researchers at the iHuman Institute of

structure of these proteins, and we work

(GPCRs) have an integral role

ShanghaiTech University, China, are

closely with a very skilled imaging group

working to resolve various protein tissue

that can determine the finer detail of

structures. This data will help scientists

protein and cell structures, offering a

to understand more about the body as a

wealth of information.”

in the development of various diseases, and are therefore a key focus for many researchers

whole, as well as on a molecular and

investigating novel drug targets

cellular basis, in order to develop

“As a core facility, we help other

or attempting to understand

treatments for a range of diseases and

scientists at the university prepare

more about human health.

improve human health. Dr Yueming Xu,

samples for high throughput assays, so

Director of the Assay Development Core

if they are studying a particular GPCR

at the university, explained the workflow

and want to screen for ligands which

of the lab: “Our group works on high

can bind to it, that’s where we step in.

throughput screening processes, mainly

We manage a large biobank – a

laboratory solutions for

focusing on the structure and function

compound library that covers all 826

compound management in their

of GPCRs. This requires screening for

GPCRs in the human body – where we

busy core facility, and are using

ligands that bind to G-proteins and

have at least three sets of different

activate signaling pathways in the

constructs for each of the receptors,

human body. We have worked on many

so over 2,000 plasmids in total. These

different GPCRs, and have publications

samples are stored in an automated

looking into cannabinoid, serotonin and

freezer, and we use a customized Tecan

dopamine receptors, to name a few. Our

liquid handling workstation – based on

expertise is in resolving the molecular

a Freedom EVO® 200 platform – to

Scientists at ShanghaiTech University have implemented Tecan Labwerx™ customized

these automated systems to process high throughput assays, ultimately resolving important GPCR structures.

Yueming Xu and the team at the iHuman Institute of ShanghaiTech 10

TECAN JOURNAL 2/2020


CUSTOM AUTOMATION

centrifuge, stacker, sealer/peeler and

I mplementing the Tecan Labwerx solution has really helped us to manage our workload, which is important for a large lab in a core facility that is shared between various institutions and departments across the university.

capper/decapper. This level of automation has now taken over a huge portion of our workflow. We originally set up our experiments with a semi-automated desktop liquid handler; each plate took around 20 to 30 minutes for two people to prepare, and we needed to manually label them ourselves. On the Tecan system, we only need one member of staff to monitor it from time-to-time, and we can prepare 12 to 16 plates a day. Last

prepare the plasmids and manage the

and that we would have a fully

year, this allowed us to process 40,000

compound library, as well as occasionally

operational system up and running as

compounds into three different formats

helping us to prepare the screening assays.”

quickly as possible.”

– 2D barcoded tubes, 384-well plates for

The Assay Development Core first

The Assay Development Core now has a

decided to explore automated systems

tailored solution that fits all of its

for its DNA preparation workflow in

requirements. “We take the compound

“Implementing the Tecan Labwerx

2015, looking at the various off-the-shelf

plates out of the freezer and load them

solution has really helped us to manage

options available before choosing a

into the automated Cytomat™ 10 Hotel.

our workload, which is important for a

Tecan Labwerx customized solution.

The system spins them down in the

large lab in a core facility that is shared

Yueming continued: “I joined the

integrated centrifuge and replicates

between various institutions and

iHuman Institute in 2014, and a year

them, performing serial dilutions as

departments across the university. I have

later we started to consider automation

required to generate the assay plates.

shared my positive experiences with

options. We needed a solution that

These plates are then automatically

Tecan with other researchers at the

could be used to prepare and back up

sealed and returned to the hotel, ready

university and now, within our core

our biobank library, and we also wanted

for us to take out and run our

facility, there are three other groups using

to see if we could automate the plasmid

experiments. Running the workflow is

Tecan instruments for various projects –

extraction process. We had an outline of

easy and reliable; as the instrument is

such as phage display, PCR set-ups and

the kind of system that we were

automated, we know that there is no

cell-based assays,” Yueming concluded.

planning to build, and talked to a few

chance of human error in the process.

different companies to discuss our

We actually have two workflows that

requirements, as we were not quite sure

run perfectly using the same platform,

what kind of integration we could have.

as we use the system to both prepare

Each company gave us an integration

the compound libraries and process the

proposal and, after discussing our

plasmids. We initially thought that if we

experimental plan with various experts,

wanted to switch the process, then we’d

it was Tecan that stood out from the

need to rearrange the layout on the

crowd, offering us a very detailed plan

workstation, but the two different

of exactly how everything would work

set-ups can actually be run on different

– it was a full solution. This made me

days without making any changes.”

acoustic dispensers, and regular 96-well

confident that Tecan understood the lab’s needs, that the set-up would be

“It’s fantastic to have one compact

customized exactly to our application,

system that has an integrated

plates – for different applications.”

To find out more about Tecan’s Labwerx solutions, visit www.tecan.com/labwerx To learn more about the iHuman Institute, go to ihuman.shanghaitech.edu.cn

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COVID-19

Racing against a pandemic The emergence and outbreak of the novel coronavirus SARS-CoV-2 at the end of 2019 has created an urgent need for testing to help limit the spread of COVID-19. AusDiagnostics has used its patented, multiplexedtandem PCR technology to develop a test to detect SARS-CoV-2 and distinguish between the different causes of coronavirus-like infections.

Infectious diseases are one of the

microbiology. Since then, we have grown

at a time and, while their symptoms

greatest threats to public health

our product range to cover everything

indicate one pathogen, they actually

worldwide, with recent major outbreaks

from respiratory diseases and food

have a much higher level of something

including Ebola, Zika and, most recently,

pathogens to cyanobacteria and cattle

else entirely! It’s therefore much better

SARS-CoV-2 (COVID-19). Molecular

parasites. We pride ourselves on working

to test for a complete panel of diseases,

testing is essential for the detection of

closely with our customers to ensure

because if you test for just one – and

these RNA viruses, and Sydney-based

they have a reagent kit that exactly

you find a positive – the patient may

AusDiagnostics supplies a range of

matches their needs – including altering

only be treated for that indication,

highly multiplexed molecular tests used

existing panels to meet national or

rather than the pathogen that is most

by the medical, veterinary, food, water

regional legislation.”

important to treat.”

Keith Stanley, Managing Director,

“Our patented multiplexed-tandem PCR

Following the outbreak of COVID-19,

explained the company’s origins: “We

technology allows the detection of

AusDiagnostics developed several kits

launched AusDiagnostics in 2006 to

multiple targets in one sample, without

that can be used to detect the presence

commercialize a novel technique for

compromising analytical sensitivity and

of the SARS-CoV-2 virus. The fast spread

multiplexing PCR. At the time, it was the

specificity. Multiplexing offers a

of this novel coronavirus means that

start of the H5N1 (avian) influenza

complete picture of what is wrong with

testing is vital to reduce transmission

outbreak, so we were initially focused on

a patient. For example, 10 to 15 percent

and distinguish between patients

designing tests and panels for

of people have more than one infection

infected with COVID-19 and other

and environmental sectors. Professor

infections with similar symptoms. Keith continued: “For each test we develop, we look for the best place to position our primers in the whole genome of the virus, and our validation studies show that our products are close to 100 percent sensitive and specific. Our main screening kit has two targets for SARS-CoV-2 plus influenza A, influenza B and RSV, while our other kits have 16 or 24 respiratory targets. Using two targets for SARS-CoV-2 on the one panel makes it very unlikely that a sample that is positive for both targets could be a false positive. Two different sets of primers – each consisting of four primers – have to bind, which requires eight separate hybridizations to get a positive result. A further advantage is that having two targets helps to protect against mutations. In a single target test, there is a danger of false negatives if AusDiagnostics’ Ultra-Plex systems offer walkaway, multiplex processing for molecular detection 12

TECAN JOURNAL 2/2020

your amplicon falls in the region where a


COVID-19

mutation has occurred. By using two targets, we can look for drift in the ratio between targets in our customers’ data, to see if we can pick up changes that may be occurring. Our workflow also has two PCR steps, which has the advantage of making our test very sensitive, and so we pick up positives that even a reference lab may miss.” The company’s technology allowed it to respond very quickly to the COVID-19 crisis, positively testing its first clinical sample by the 31st of January – less than three weeks after the first sequence was published – and achieving CE marking by the beginning of March. Keith added: “We’re now producing a quarter of a million of these tests a month here in Australia, and another 150,000 a month in the UK. These tests are designed for throat or nasal swabs, and run on our bespoke molecular diagnostics systems.”

The AusDiagnostics Ultra-Plex 96 uses four Cavro ADPs to conduct a two-step PCR workflow in as little as 3.5 hours

that are likely to occur if done manually; running a test is as simple as putting your name in, uploading the sample IDs, selecting the panel you’re going to run and pressing go.” “We wanted to get this platform to market quickly, and decided to

The Cavro Air Displacement Pipettor (ADP) was a great solution, as it was ready made, reducing engineering research and speeding up the development of our full platform. Each of AusDiagnostics’ molecular diagnostic platforms consists of two main elements – a sample processor and a real-time PCR analyzer. When developing its latest platform – the Ultra-Plex 96 system, which launched in early 2020 – the company turned to Tecan to help reduce time to market. Keith continued: “The Ultra-Plex 96 can conduct a two-step PCR workflow in parallel, and it has a built-in 96-well thermal cycler on the workdeck. The system can run an assay panel with 768 individual PCR results in as little as 3.5 hours, with the ability to reload samples every two hours, making it perfect for the volume of samples that need to be screened during a pandemic. The automation reduces the risk of errors

use an off-the-shelf pipetting mechanism. We turned to Tecan to meet this need because we were already using 10 Freedom EVO® 150 liquid handling workstations in the production of our kits, and so we trust the company’s technology inherently. The Cavro® Air Displacement Pipettor (ADP) was a great solution, as it was ready made, reducing engineering research and speeding up the development of our full platform. We had already developed some of our own pipetting heads, and so we could admire the cleverness of Tecan’s technology, as well as see that the component met our precision and reproducibility needs. We were able to easily integrate the ADP into our own

robotic platform, and it communicates seamlessly via a USB port.” “There is huge demand for our platform at the moment, from both hospital and private laboratories; we are shipping to customers as quickly as we can. We appreciate the cooperation and collaboration that we have had from Tecan throughout this project, and the team has been very proactive in helping us to find the right solution at each phase. We were even alerted when Tecan started to offer clear disposable tips that would help us reduce the cost to our customers. The Tecan team has also helped with scheduling parts deliveries, checking our stock levels and delaying shipment if we weren’t ready or, more likely in the current situation, speeding up an order if we were running low. Our platform and kits are really making a difference in this pandemic, and Tecan has helped us to achieve this.”

To find out more about Tecan’s Cavro ADP, visit www.tecan.com/cavro-adp To learn more about AusDiagnostics, go to www.ausdiagnostics.com

TECAN JOURNAL 2/2020

13


PUBLIC HEALTH

Improving quality of HIV diagnosis in Kenya Gaining an accurate diagnosis of HIV is essential to ensure that patients get the right treatment, and that the disease is contained as much as possible. In Kenya, where HIV is prevalent, the quality of testing across the country is being monitored through a program established in 2007 that sends out manually produced proficiency testing panels. The demand for this service has grown immensely with the development of point-ofcare testing and, to address this, the National Public Health Laboratory has turned to automation to produce more samples in a shorter timeframe and with improved accuracy.

An estimated 1.5 million people in Kenya

misdiagnosis of HIV status has

false negative results could potentially

are living with HIV, making efficient and

increased, as Sophie Mwanyumba,

lead to a public health disaster.”

accurate diagnosis essential in order to

Production Manager for the Ministry of

effectively treat patients and keep the

Health, discussed: “Accurate HIV

“In 2007, we implemented a national

disease under control. The recent

detection is incredibly important;

proficiency program that significantly

introduction of rapid HIV testing (RHT)

wrongly diagnosing someone as HIV

improved quality assurance for HIV

at the point of patient care has meant

positive when they are actually negative

diagnostics. To begin with, just 24

that screening is far more widely

can potentially lead to distressing

facilities took part, however, since then,

available across the country. However,

domestic issues on an individual basis,

testing has spread out to the point of

because diagnostic methods are far

and there have been cases in the past

patient care as well as the traditional

simpler than before, much of the

where legal action has been taken

central laboratories; the quality control

analysis is now performed by healthcare

because of a false positive result.

service must now cover individual

workers with varying degrees of training

Equally importantly – and although

healthcare providers as well as larger

and skill. As a result, the risk of

research is limited – it is evident that

facilities, and has grown to include over

The Freedom EVO platform has transformed the production of proficiency testing panels at Kenya’s National Public Health Laboratory

14

TECAN JOURNAL 2/2020


PUBLIC HEALTH

20,000 participants, which is a huge

2,000 samples in the same time frame.

increase! Twice a year, we prepare and

Overall, it takes around two weeks to

send out six unknown positive and

complete the whole process. Even

negative proficiency testing panels to

though the workflow is not yet fully

each provider for routine testing using

automated, having the platform has

their usual methods. They then send us

already reduced the entire sample

back their results and, from that, we can

preparation turnaround time from three

evaluate their accuracy, and provide

months to only one, and we still have

corrective action guidance to those with

the capacity to do more.”

incorrect results.”

To find out more about the Freedom EVO 200, visit https://lifesciences.tecan.com/ freedom-evo-platform To learn more about the National Public Health Laboratory in Kenya, go to nphl.go.ke

“The proficiency testing program, aided Sophie continued: “For many years, we

by automation, has been revolutionary

prepared the proficiency testing panels

in enabling us to assure the quality of

manually, carrying out the entire

RHT across Kenya, and this has led to

pipetting procedure by hand. There

huge improvements. There has been a

were, however, several drawbacks to this

progressive downward trend in the

method: it took a long time to prepare

percentage of incorrect results reported

the samples; manual errors were much

by service providers; it is now less than

more likely; and it was a very laborious

five percent. Looking forward, we are

process for skilled staff. In 2015, we

planning to expand our proficiency

acquired a Freedom EVO® 200 system

testing program and use the system for

with the aim of speeding up and

quality assurance of hepatitis B and

improving the sample production

syphilis screening. Thanks to the

workflow. Some members of the team

Freedom EVO, we have the opportunity

were apprehensive at first as they were

to enhance quality assurance for many

so used to performing everything

biomarkers in the future,” Sophie

manually, but the Tecan team was very

concluded.

helpful and supportive, working with us directly to train our staff and on-site engineers so that we could all use the system fully and effectively. Now, it is fantastic; the platform has really given us the upper hand in production quality, helping us to prepare accurate volumes and ensure the samples are dispensed correctly. We can dispense 14,400 samples in a period of only two hours,

he platform has really given us T the upper hand in production quality, helping us to prepare accurate volumes and ensure the samples are dispensed correctly.

compared to manually pipetting just

TECAN JOURNAL 2/2020

15


COVID-19

Transferrable skills The COVID-19 pandemic has required an unprecedented level of collaboration within the scientific community, as labs around the world aim to characterize and understand the SARS-CoV-2 virus in order to develop and implement new diagnostic tests, therapeutics and vaccines. This cooperative approach has led to some unexpected partnerships, as techniques and knowhow from across numerous disciplines are brought together to accelerate research and testing activities. Professor Nir Friedman’s team at the Hebrew University of Jerusalem has been at the center of one such situation, using its knowledge of workflow automation from investigating yeast genomics to develop a novel large-scale sequencing-based assay for the detection of SARS-CoV-2. The research conducted by Professor

“The lab is a mix of molecular and

labeled knock out yeasts, but have

Nir Friedman’s team at the Hebrew

computational biologists, so we tend

more recently started to use DNA-Seq,

University of Jerusalem is normally

to run large-scale analyses, screening

RNA-Seq and ChIP-Seq techniques to

focused on investigating the

thousands of strains of yeast for many

gain an even deeper understanding.

transcription machinery of eukaryotes,

studies. Automation is obviously well

The Freedom EVO platform allows us

however, the group has recently found

suited to this work, and we have been

to perform these studies on a large

itself at the forefront of efforts to

using a Freedom EVO® workstation for

scale – keeping the lab’s

develop a straightforward molecular

over 10 years. Our unique instrument

computational biologists happy – by

diagnostics workflow for COVID-19

configuration also includes a

providing fast and efficient nucleic

testing in Israel. Researcher Dr Ayelet

microplate reader, a FACS analyzer

acid extraction.”

Rahat explained: “Our normal activities

and an automated fluorescence

have nothing to do with diagnostics or

microscope, all fully integrated with

“When the COVID-19 pandemic spread

coronaviruses; we primarily use yeast

the Tecan platform to provide

across the globe, it was this experience

as a model organism to look at the

completely automated data

of high throughput nucleic acid

various molecules associated with

acquisition. We were originally using

processing that became crucial.

chromatin and transcription, such as

this set-up in combination with an

We were in the process of shutting

histones and promoters.”

extensive library of fluorescently-

down the lab to comply with Israeli

Professor Friedman’s group at the University of Jerusalem (NOTE: Photo taken prior to social distancing) 16

TECAN JOURNAL 2/2020


COVID-19

This highlighted how important local support is for laboratory automation. government advice, when we received a call from the Hadassah Medical Center, which operates two large university hospitals in West Jerusalem. They were having trouble sourcing commercial RNA extraction kits to

immediate solution to the diagnostics

“One of the most important aspects of

perform RT-qPCR-based diagnostic

laboratory in the hospital.”

this workflow – which has already been published* – is that it does not require

testing, and wanted our help in developing a generic diagnostic

“We originally chose the Tecan

bespoke reagents. Once you have

protocol suitable for high throughput.

instrument due to a combination of its

purchased the paramagnetic beads,

Although this seemed a long way from

flexibility – allowing us to integrate

you simply run the protocols using

our yeast work, we obviously agreed

various analytical devices onto the

buffers that are easy to make in any lab.

to help.”

platform – and the excellent support

This is crucial in a pandemic situation,

provided by Tecan’s local distributor

where there is unprecedented demand

“We initially attempted to create an

Neotec Bio, and both of these factors

on supply chains, and commercial

RNA extraction protocol using filter

have been very important for this

extraction kits may not be readily

plates and a vacuum system, but this

project. Dr Moshe Cohen from Neotec

available. We are very pleased to have

proved unsuitable for the kind of

has been instrumental in helping us to

been able to contribute, however

throughput we were trying to achieve.

develop the new workflow, offering

unexpectedly, to the efforts to fight the

One of the PhD students in the lab,

technical support and advice. For

pandemic, and have also gained

Alon Chappelboim, suggested adapting

example, we were used to working in

experience and capabilities from this

ideas from the barcoded beads

small sample volumes, and so initially

project that will benefit our routine

technology we were already using for

developed the protocol to work with 30

research activities going forward,”

single cell RNA-Seq. This approach

to 35 microliters of samples. However,

Ayelet concluded.

allows us to capture viral RNA in

this led to a relatively high limit of

individual patient samples, then release

detection, meaning that patients with

the barcoded RNA from the beads,

very low viral titers were at risk of

pool the samples together for RT-PCR,

receiving false negative results. Moshe

sequence the pooled samples, and use

suggested we switch to deep-well

the barcodes to link the results back to

plates, allowing us to move to larger

individual patients. This protocol –

sample volumes. We had no experience

To find out more about Tecan’s

developed in association with Dr Naomi

with these plates, but he helped us to

nucleic acid purification solutions,

Habib’s lab from the Edmond and Lily

adapt the protocol and instrument

visit www.tecan.com/nap

Safra Center for Brain Sciences at the

settings very quickly to accommodate

university – is still under development.

the new format, and this highlighted

To have a closer look at the robotic

However, the first step of viral RNA

how important local support is for laboratory automation. We also had

set-up at Professor Friedman’s lab,

capture on magnetic beads could replace commercial RNA extraction

help from a number of other local

protocols and this, followed by the

scientists to optimize and refine the

conventional RT-qPCR test, will give an

workflow – it was a real team effort.”

*Sars-CoV2 RNA purification with homemade SPRI beads for RT-qPCR test www.protocols.io/view/sars-cov2-rnapurification-with-homemade-spri-beadbeswjefe

go to http://systemsbio.cs.huji. ac.il/Friedmans_Lab/Robotic_ Facility.html

TECAN JOURNAL 2/2020

17


IMMUNOASSAYS

Using saliva to study hormones Hormones are specialist chemical messengers that provide a communication system between different parts of the body. They affect everything from growth and metabolism to appetite and mood, while also playing a vital role in puberty and fertility. When hormone imbalances occur, they can lead to a number of health issues, including infertility and menopausal problems in women. Medicare PLUS is using saliva testing to identify these hormone level imbalances for individuals across Slovenia and further afield.

Hormones play a vital role in regulating

Slovenia – specializes in hormone testing

“Much of our work is helping middle-

the function of many organs – including

to diagnose and monitor a range of

aged women who are suffering from a

the reproductive tract, bones, kidneys,

conditions. Aleš Koščak, CEO of

sudden change in health or mood, but

liver and muscles – and only need to be

Medicare PLUS, explained: “We test for

we also help younger patients who are

present in the body in tiny amounts to

two main groups of hormones. The first

having problems with irregular – or a

have dramatic effects. As a result, even a

is the hormones that affect our daily

lack of – periods due to hormonal

slight imbalance in the complex cascade

well-being and can lead to stress,

imbalance. For instance, about 10

of reactions that occur between glands

burnout and depression, including

percent of women with high levels of

that secrete these hormones and the

cortisol, dehydroepiandrosterone

testosterone have polycystic ovary

delivery of a chemical message to a

(DHEA) and melatonin. These can be

syndrome, with symptoms including

target tissue or organ can lead to health

used to assess the health of the adrenal

irregular or absent menstruation and

issues. For example, the levels of various

gland and its impact on the thyroid. The

infertility. In contrast, low levels of sex

reproductive hormones in women need

other group – which makes up the

hormones can lead to fatigue, malaise

to modulate precisely and frequently to

majority of our work – is the sex

and osteoporosis. To help an individual

control the menstrual cycle, the ability to

hormones and, for women, our studies

understand and manage their health

become pregnant, and the menopause.

mainly focus around progesterone,

problems, it’s often best to examine the

Medicare PLUS – based in Ljubljana,

estradiol and testosterone.”

hormone balance as a whole, including the daily cortisol profile and levels of all the sex hormones in combination with blood test results, such as cholesterol and hemoglobin levels.” The company uses saliva testing to analyze the free levels of hormones in a patient. Aleš continued: “We use saliva samples as we are able to measure free levels of hormones, which are biologically available and unbound. You can’t get these sorts of results from blood tests because around 95 to 99 percent of steroid hormones circulating in the blood are bound to carrier proteins and inactive. Results from saliva diagnostics therefore provide a more accurate representation of the true concentrations of these hormones in the body, offering a better indication of how they may be responsible for any

Some of the Medicare PLUS team: Petra Okoren, lab engineer (left), Bianca Bevc, head nurse (middle) and Aleš Koščak, CEO (right)

18

TECAN JOURNAL 2/2020

patient symptoms.”


IMMUNOASSAYS

ll of the kits have been A developed to work on the same assay principles, which makes [them] very simple and intuitive for us to use.

“The benefits of saliva testing extend to the patient too. For some people, having blood taken is a painful and stressful process – and this stress can even affect results when looking at cortisol levels – whereas the non-invasive nature of saliva testing is stress free, eliminating the problem entirely. It’s also much easier to study the fluctuations in hormones over time, which is especially useful when looking at the menstrual cycle of women suffering from fertility

percent. Tecan also runs an independent

problems, or to look at ‘before and after’

quality control scheme as an additional

effects of treatments, such as hormone

service that allows us to compare the

replacement therapy for post-

performance of our testing results

menopausal women. Patients can take

against other labs, which is vital to meet

samples in the comfort of their own

our external quality control regulations

home, and take them multiple times per

set by the Ministry of Health.”

day, because samples don’t need further processing or special storage conditions.

“The Tecan team has been very

This sort of frequent sampling outside of

supportive to our team over the years

a lab/clinic would be nearly impossible

– they have a lot of knowledge and

using blood collection.”

expertise in the area, and always have answers to our technical questions.

“I had used Tecan’s saliva immunoassay

When Medicare PLUS was founded,

kits in a previous role, and knew I

saliva testing was a relatively new

wanted to continue to use them when

concept in Slovenia. It’s since grown in

we established saliva testing here at

popularity, and now we test samples

Medicare PLUS. All of the Tecan ELISA

from all over Slovenia, and also from

kits we use – estradiol, progesterone,

neighboring countries, such as Croatia,

cortisol, testosterone, DHEA and

Italy, Serbia and Bosnia. Patients are

melatonin – have been developed to

able to come to us directly for a sample

To find out more about Tecan’s

work on the same assay principles,

collection kit, or via a referral from their

range of saliva diagnostics kits,

which makes it very simple and intuitive

doctor. On top of this, we have also

visit www.tecan.com/ibl

for us to use the different kits for all of

partnered with several affiliated clinics

our testing workflows. The kits are very

to help meet the demand for this

To learn more about Medicare

reliable too, consistently performing to

service, and we believe that the need

PLUS, go to

the high standards we require and

for this service will continue to grow,”

generating very low CVs of under eight

concluded Aleš.

www.medicareplus.si/en/

TECAN JOURNAL 2/2020

19


CELL BIOLOGY

A sensitive subject Determining if a new cosmetic product, pharmaceutical ingredient or chemical substance is harmful to humans is a key prerequisite for product safety and consumer protection. Traditionally, skin sensitization testing relied on animal models, but these approaches are expensive, time consuming and raise ethical questions, while only offering limited human relevance and accuracy. SenzaGen has developed a unique, in vitro approach to sensitization testing, combining cell biology and flow cytometry with genomics-based screening and machine learning-assisted classifications.

The use of animal models for safety

and created a need for alternative

pharmaceutical and medical device

testing of pharmaceuticals is coming

strategies for skin sensitization testing.

industries – as researchers and

under increasing scrutiny due to a

This led to the spin out of Swedish

regulators are becoming increasingly

combination of financial and ethical

start-up SenzaGen from Lund

aware of the scientific shortcomings of

pressures, and a growing scientific

University’s Department of

animal testing, and companies working

awareness that the results of these

Immunotechnology, as company CEO

in these areas try to reduce the cost of

studies can be inaccurate or

Axel Sjöblad explained: “SenzaGen was

safety testing. Our flexible technology

misleading. Although animal testing is

created to provide an advanced in vitro

platform has allowed us to develop a

still mandatory for the regulatory

approach to sensitization testing that

range of scalable assays to meet the

approval of pharmaceutical products,

combines cell biology, genomics and

needs of these different markets and,

many other sectors are moving away

machine learning to classify substances

today, we offer four distinct tests –

from the use of animal studies in

as either sensitizing or non-sensitizing.

GARDskin, GARDpotency, GARDair and

determining product safety. Probably

The ban on animal testing in the

GARDskin Medical Device.”

the most prominent of these is the

cosmetics industry was the driving

cosmetics industry, where animal

force behind the company’s founding

Ulrika Mattson, Senior Application

testing has already been banned in

– and this remains a key market for us

Scientist at SenzaGen, took up the

many jurisdictions worldwide for a

– but we have since expanded into a

story: “Our GARD assays can essentially

number of years.

number of other areas.”

be divided into six steps; the first two

The EU ban on the use of animals to

“There is growing demand for this type

involve genomics and machine learning.

test the safety of cosmetics or their

of service across many other sectors –

The process begins with our own

ingredients came into force in 2013,

including the chemicals,

human myeloid leukemia cell line,

are cell based, and the remaining steps

SenzaCells, which we expose to varying concentrations of the test compounds that we receive from our customers. Following overnight incubation, we then perform a cell cytotoxicity analysis using flow cytometry, and isolate RNA from the cells for transcriptomic analysis by hybridization, based on a custom gene panel unique to each assay. Finally, we use our in-house machine learning algorithms to analyze all the data and determine which compounds are sensitizing.” Ulrika continued: “The accuracy of the first steps – creating serial dilutions of each of the test substances, dosing the SenzaCells, and cell harvest for both cell cytotoxicity analysis and RNA isolation – is crucial to the outcome The Fluent workstation provides Ulrika Mattson (pictured) and the SenzaGen team with consistency and reliability for the GARD assays

20

TECAN JOURNAL 2/2020

of the process. We were initially performing these steps manually, but


CELL BIOLOGY

Crucially, we immediately had a good connection with the local Tecan representative, who worked hard to understand our exact requirements and what we wanted to achieve through automation.

Axel Sjöblad, CEO of SenzaGen

quickly realized that automation of this

a good connection with the local

portion of the workflow, which is time

Tecan representative, who

consuming and requires very precise

worked hard to understand our

and accurate pipetting, would be really

exact requirements and what we

beneficial. This was primarily because

wanted to achieve through automation

of the release of resources and

before we even purchased the system.”

consistency automation offers, rather than to increase throughput, although

“Although we had not previously

Axel added: “The Fluent platform fits

automation obviously gives us the

worked with Tecan, I have over 20

very well into our workflow, consistently

capacity to cope with significant

years of experience in laboratory

and reliably performing the routine

expansion in the future. We looked at

automation and, for me, it is very

operations that are crucial for our

the various solutions on the market that

important to factor in the support you

process. This has helped us to create a

could meet our requirements, and

will receive when choosing a solution

technology platform that outperforms

eventually chose the Fluent®

for your lab. For example, when we first

all the in vivo and in vitro tests currently

Automation Workstation, because it

established our automated protocols,

on the market, and provides a real and

offers very precise, fast and accurate

we were experiencing poor cell viability

practical alternative to replace the one

pipetting, and could be configured to

compared to manual processing, but

million mice a year currently used for

be very flexible to accommodate our

the support we received from Tecan’s

skin sensitization testing.”

development needs, which is an

field application specialists helped us

important consideration for a company

to resolve this issue by using gentle

in the commercialization and growth

pipetting parameters in combination

phase. The system also has a number of

with the company’s wide bore tips. This

integrated options – such as a tilting

kind of advice is vital to getting the

carrier to reduce dead volumes, and a

most out of any automated solution, as

HEPA filter hood to prevent

even seemingly straightforward

contamination – that were

pipetting operations pose technical

To learn more about SenzaGen,

important for our workflow.

challenges when you require absolute

go to https://senzagen.com

Crucially, we immediately had

consistency and reproducibility.”

To find out more about Tecan’s cell-based screening solutions, visit www.tecan.com/cellbiology

TECAN JOURNAL 2/2020

21


BIOPROCESSING

A smooth path for novel biologics Cell culture is at the heart of the production process for many biopharmaceuticals, but finding the optimal conditions to maximize yield can be a complex and time-consuming process. Traditional process development relies on costly and labor-intensive set-ups, significantly limiting throughput and the range of experimental conditions that can be assessed. Scientists in Roche Pharma Research and Early Development (pRED) have adopted an alternative approach, combining single-use microbioreactors with advanced automation and analytical platforms to streamline the workflow. The production of large biological

establishing a highly productive final

were asked by the management to look

molecules for therapeutic use is

process. Fermentation development

for a way to do even more process

complex, requiring expression of the

has historically relied on performing

development for more complex

target peptide, protein or antibody in

parallel experiments using a number of

biotherapeutic candidates, as well as

suitable host systems, followed by

shake flasks or two-liter bioreactors,

double the number of projects we

extraction and purification to yield the

with continuous sampling to enable

performed per year. This clearly wasn’t

final drug. Efficient expression requires

process monitoring and analytics.

going to be possible with our existing

not just the right host organism and

Unfortunately, this approach is both

workflow – a very hands-on process

clone, but also the right physical

time consuming and labor intensive,

– without significantly increasing

conditions and chemical environment

with one researcher able to handle just

headcount, which wasn’t an option.”

to promote production. Exploring these

a few bioreactors simultaneously.

numerous parameters to optimize

“We looked at the various solutions on

biotherapeutic production is a very

When the Bioprocess Research

the market and chose the Ambr® high

time-consuming process, requiring cell

Department at the Roche site in

throughput, single-use microbioreactor

expansion followed by numerous

Penzberg, Germany, was challenged

system from Sartorius. We now have

fermentations in parallel to identify the

with significantly increasing the number

two different types of Ambr system:

best candidate and conditions for its

of proteins it produced, the team

four Ambr 15s, which can run up to 48

expression. As such, the more data

realized they needed to look for an

parallel fermentations of up to 15 ml,

points that can be obtained for each

alternative solution. Pawel Linke, a lab

and five Ambr 250s that allow us to run

variable, the greater the probability of

automation specialist, explained: “We

12 larger scale, 250 ml fermentations simultaneously. This shift represented a huge increase in capacity, allowing us to run four or five times as many experiments with the same number of staff. However, it also created new challenges, as we significantly increased the number of samples to be analyzed. We therefore needed a way of efficiently processing up to 250 samples every day, before analyzing them on a Cedex Bio HT Analyzer from our sister division Roche Diagnostics.” “We have a huge number of laboratory automation systems here in Penzberg and, based on this experience, we decided that a Tecan liquid handling platform would be the best fit for our needs. A key requirement for our

The Cedex Bio HT Analyzer’s microplate-based sampling system allows easy transfer of samples between devices

22

TECAN JOURNAL 2/2020

workflow was the ability to integrate a large centrifuge to spin down the samples before analysis, and the


BIOPROCESSING

e now have two different sized Fluent systems W with slightly different configurations, giving us more than enough capacity to process samples for every Ambr bioreactor every day.

The Fluent workstation is fully integrated into the lab’s workflow and the SDC middleware solution

Fluent® Automation Workstation’s

some onboard analytics. Although both

provides the relevant information to the

ability to mount a Hettich

have cooling modules, we have now

Cedex Bio HT Analyzer. This means that,

ROTANTA 460 robotic centrifuge

developed a workflow based on sealed,

although each platform is effectively a

below the worktable was a real

pre-pierced plates that can be accessed

standalone instrument, the software

benefit. We simply place the samples

by the LiHa. This avoids evaporation

environment is as automated as the

from the bioreactors on the workdeck,

without the need for cooling, further

physical process. It’s a very smooth

and the system is able to automatically

simplifying the workflow.”

workflow, and provides a feedback loop back to the bioreactor. We developed

load them into the centrifuge using its Robotic Gripper Arm™ (RGA). Once

“When we first implemented this set-up,

this approach because we have many

spun down, the Fluent platform splits

the Cedex Bio HT Analyzer required 15

different researchers in the lab, working

the supernatant into several aliquots in

samples to be loaded into a metal rack

on a number of different projects. The

different labware formats, depending

for processing, but we have since

touchscreen user interface on the Fluent

on the downstream application.”

worked with our Roche Diagnostics

workstations makes it very easy for

Custom Biotech colleagues to develop a

people to walk up and use the systems

“We now have two different sized

96-well microplate-based sampling

with only minimal training – we have

Fluent systems with slightly different

system, allowing us to more efficiently

around 30 regular users – with a couple

configurations, giving us more than

transfer large numbers of samples

of ‘key users’ to handle protocol

enough capacity to process samples

between devices. We have also

development and maintenance tasks. All

for every Ambr bioreactor every day,

implemented Sm@rtline Data Cockpit

together, it’s a great fit for our needs.”

although we do not have this many

(SDC) middleware (AGU GmbH) to

experiments running in parallel at

streamline the flow of data between the

present. The smaller system is

Ambr, Fluent and Cedex instruments.

equipped with an RGA for labware

This solution is able to take the sample

movements and an eight-channel

IDs from Ambr systems and provide

To find out more about Tecan’s

Liquid Handling Arm™ (LiHa) for

that information to Tecan’s

Fluent Automation Workstation,

pipetting, while the larger system has a

FluentControl™ software. The Fluent

visit www.tecan.com/fluent

third arm equipped with a Multiple

platform uses an integrated barcode

Channel Arm™, allowing entire 96-well

scanner to confirm the identity of each

microplates to be duplicated or

sample, associates that ID with all the

transferred simultaneously. Each

aliquots it generates for downstream

platform also has an integrated Tecan

analysis, and exports the information

microplate reader on the workdeck for

back to SDC. The middleware then

For more information about Roche’s Cedex Analyzers, go to custombiotech.roche.com/cedex

TECAN JOURNAL 2/2020

23


CELL BIOLOGY

Generating success in regenerative biology Stem cells offer the potential to revolutionize the treatment of many currently incurable conditions, as well as providing invaluable research tools to further our understanding of biological processes. Since stem cell pioneer Dr James Thomson derived the first human embryonic stem cell line in 1998, this has grown into a whole new field of biology. Dr Thomson and his team at the Morgridge Institute for Research are still at the forefront of this research, using their vast knowledge and experience to develop novel therapeutic approaches and tackle many of the unanswered questions in developmental biology.

The Morgridge Institute for Research in

explained: “The Thomson Lab’s work

species – such as a mouse and a human.1

Wisconsin is home to a wide array of

encompasses a broad spectrum of stem

It’s almost a complete mystery what

scientific disciplines, from regenerative

cell-based research. On one hand,

determines the intrinsic rate of

biology to medical engineering and

they’re using stem cells to try and

differentiation of cells, and the slow

high throughput computing. Major

understand the biological underpinnings

pace of human cell development is

discoveries in the Thomson Lab over

of cell development while, on the other,

currently one of the limitations of stem

the last two decades have propelled the

they’re investigating how this

cell-based therapies; it takes a long time

Morgridge Institute to a world-leading

knowledge could be translated into

to produce specialized mature cells. If

position in the field of stem cell and

therapeutic approaches that are

we can understand the mechanism

regenerative biology. This remains the

ultimately intended for the clinic. For

governing this developmental clock, we

focus of the lab today, as Chris Barry, a

example, the lab has investigated the

could potentially speed it up to produce

former researcher in the Thomson Lab

timing mechanisms underpinning

these therapies in a more clinically-

who now works for the International

different mammalian gestation periods,

relevant timeframe.”

Society for Stem Cell Research,

looking at the differences between “The knowledge gained from this work feeds into the lab’s other research as well, where one of the major areas of interest is vascular biology, as cardiovascular disease is the world’s leading cause of mortality. For instance, vascular grafts have a lot of therapeutic potential but, unfortunately, many patients experience rapid progression of disease into these grafts following surgery. The lab is therefore investigating how to differentiate stem cells into specialized blood vessel cells that can resist this deterioration and avoid rejection by the immune system. Alongside this work, the lab is also exploring stem cellbased therapies for a variety of other conditions, such as stroke, liver disease and diabetes.” Like many stem cell laboratories around the world, the Thomson Lab uses laboratory automation as part of its

The Thomson Lab brings together expertise from across the field of stem cell and regenerative biology

24

TECAN JOURNAL 2/2020

workflow. Mitchell Probasco, Project Manager of Automation, explained how


CELL BIOLOGY

its Tecan systems are instrumental to

– sampling every four minutes for 10

Chris continued: “This latest study only

the research. “We have a Freedom

hours. This has enabled us to achieve a

really investigated the early stages of

EVO® workstation with an integrated

significantly higher resolution and

differentiation, looking at what

Infinite® M1000 microplate reader in the

accuracy – something that would have

happens in the first 10 hours from the

lab. These were originally acquired to

been impractical or impossible to

triggering stimulus. As the team looks

perform high throughput screening to

otherwise attain.”

beyond this time frame, we should be

determine the optimal culture

able to gain a wider understanding of

conditions for stem cells, testing

Rhonda Bacher from the Department of

the underlying developmental process.

different media components and

Biostatistics at the University of Florida

The lab also plans to further improve

parameters. We soon realized the

has been collaborating with the

the automated workflow to achieve

automation systems were capable of

Thomson Lab on this project,

even higher resolution than the current

doing far more, and had the idea of

developing the statistical tools required

four-minute sampling frequency, and

using the Tecan system to do time-

to effectively analyze the data. She

for a longer duration. This will enable

course experiments investigating

added: “As this is a new approach to

them to look even closer at a part of

differentiation rates.”

differentiation research, there weren’t

biology that is rarely studied, as well as

many existing methods that were

expanding ongoing projects to include other cell types and lineages.”

utomation has been key to this, A eliminating the need for manual sampling and allowing us to follow cell differentiation at a temporal resolution that has rarely been achieved before.

1) Barry, C et al. Automated minute scale RNA-seq of pluripotent stem cell differentiation reveals early divergence of human and mouse gene expression kinetics. PLoS Comput Biol, 2019, 15(12), e1007543 2) Bacher, R et al. Trendy: segmented regression analysis of expression dynamics in highthroughput ordered profiling experiments. BMC Bioinformatics, 2018, 19, 380.

“Traditionally these experiments would

capable of analyzing the high frequency

have involved sampling the cells

longitudinal data we were generating.

perhaps once a day at most. However,

We therefore developed a novel

cellular differentiation is an ongoing

method called ‘Trendy’, which is also

process that happens on the scale of

now available for other labs to use. 2

minutes, not days, so we wanted to

Using this approach, it is clear that one

sample the cells more frequently and

of the major advantages of automation

consistently in order to capture those

is that it reduces background noise in

events. Automation has been key to

the data. This makes the analysis much

To learn more about the work of

this, eliminating the need for manual

cleaner and allows more accurate

the Thomson Lab, go to

sampling and allowing us to follow cell

interpretation, especially for long

www.morgridge.org/research/

differentiation at a temporal resolution

time-course experiments like these.”

regenerative-biology/thomson-lab

To find out more about Tecan’s cell biology solutions, visit www.tecan.com/cellbiology

that has rarely been achieved before

TECAN JOURNAL 2/2020

25


COVID-19

Print your own DNA The COVID-19 pandemic sweeping the globe has highlighted the need for the rapid development of new diagnostic tests, therapeutics and vaccines in response to emerging infectious diseases. Advanced gene assembly techniques represent a powerful tool to aid these efforts, and are currently allowing the construction of synthetic SARS-CoV-2 genomes for research and development activities. Codex DNA is at the forefront of this approach, using its knowhow and BioXp™ 3200 system to supply labs across the globe with the gene constructs required to accelerate the design and optimization of vaccines and treatments.

underscored the need for ready access

was asked to create large libraries of

to genome constructs to develop

constructs with the speed and

effective vaccines.

precision required to address the potential H1N1 influenza pandemic, he

Gibson Assembly® is now one of the most commonly used molecular

Dr Dan Gibson, inventor of the Gibson

immediately opted for an automated

cloning methods around the world,

Assembly method and Chief

system. That platform was effectively

allowing multiple DNA fragments to be

Technology Officer at Codex DNA, was

an early prototype of the BioXp 3200

joined in a single, isothermal reaction.

approached by the pharmaceutical

system. We then set about developing

It led to the development of the first

industry to develop a system that

this device into a robust and reliable

synthetic gene and the first synthetic

would allow the rapid production of

automated instrument for widespread

cell, but it was during the emergence

synthetic H1N1 genome constructs.

deployment in labs across the globe.”

of H1N1 influenza (swine flu) that a

That request eventually became the

more translational application for this

BioXp 3200 system. Brian Donnelly,

Laurence Warden, Codex DNA’s Vice

technology came to light. The risk of

Chief Commercial Officer at Codex

President of Engineering and

an H1N1 influenza pandemic

DNA, filled in the details: “When Dan

Instrumentation, took up the story: “I

The Codex DNA team (NOTE: Photo taken prior to social distancing) 26

TECAN JOURNAL 2/2020


COVID-19

his rapid turnaround time has been vital T in accelerating vaccine development research in the current COVID-19 crisis.

came on board specifically to develop

correct Z-height for each pipetting step.

the BioXp system, as the company had a

This pressure sensing function has also

lot of molecular biology expertise, but

proved very useful as an analytical tool. If

didn’t have the necessary instrument

there is an issue during nucleic acid

development experience. We decided to

processing, we can go back and look at

undertake the entire system development

the data logs for every pipetting step to

project in house, creating a platform from

see if there is a pressure spike due to, for

the ground up, including the housing,

example, a piece of foil or debris

thermal cyclers, chillers, etc. The one

occluding a tip during aspiration. This

exception to this was the liquid handling

ability to pull pressure logs and error

components. Our protocols require

codes is extremely beneficial for

several liquid transfers, ranging from just

troubleshooting, and we haven’t fully

three or four microliters up to 180, and

explored all the options the ADP offers

we knew from experience that it would

yet. We certainly wouldn’t have been able

be challenging to develop an accurate

to replicate such an intelligently designed

and reliable pipettor for this application.”

and sophisticated system in the accelerated timeframe we needed. Using

“We looked at the OEM liquid handling

the ADP, it took just 18 months from the

technologies available, and the Cavro® Air

start of the project to the production of

Displacement Pipettor (ADP) from Tecan

the first instrument.”

ticked all the boxes. It is very compact, provides built-in tip ejection capabilities

The BioXp 3200 system was launched in

and, crucially, offers pressure-based

2015, allowing labs to build up to 32

liquid level detection (pLLD). Although

complex constructs in a single overnight

the ADP was very new at the time, we

run. With an ever-growing global install

had previous experience with Tecan

base of hundreds of systems, Codex DNA

liquid handling platforms and OEM pump

and the BioXp system have been

technologies, so we were confident that

perfectly positioned to help labs

it would be well built and reliable.

investigating the SARS-CoV-2 virus and

Although there were a few challenges

developing novel vaccines. Brian

early in the integration process, Tecan’s

continued: “A unique feature of our

engineers worked with us to develop an

system is that every single reagent

improved power filtering strategy, and we

cartridge is completely custom. Our

haven’t suffered from these problems

customer chooses the gene sequences

again – our test rigs have completed over

they want, and places an order via our

three times the number of runs outlined

online portal. We then design and build

in our design specification.”

the cartridge to make their target genes,

The BioXp 3200 system

desired constructs – doing in a few hours or days what would take scientists weeks or months to do manually. Thanks to our in-house bioinformatics capabilities and DNA design expertise, the entire process – from placing an order to shipping – usually takes less than 24 hours. This rapid turnaround time has been vital in accelerating vaccine development research in the current COVID-19 crisis, and we received several orders for construct libraries within a few days of the first whole SARS-CoV-2 genome sequence being published.”

To find out more about Tecan’s ADP, visit www.tecan.com/components

and ship it to their lab. When the “The ADP’s pLLD capabilities have

customer inserts the cartridge into the

To learn more about Codex DNA,

allowed us to create an automated

system, the platform automatically runs

go to www.codexdna.com

calibration algorithm to determine the

the correct protocol and generates the

TECAN JOURNAL 2/2020

27


COVID-19

A jump start for nucleic acid processing The ever-increasing throughput and ever-decreasing cost of next generation sequencing have made this technology a practical and affordable solution for everything from molecular diagnostics and antimicrobial susceptibility testing to crop research and environmental monitoring. For many of these applications, the bottleneck in the workflow – which can account for considerable hidden costs – lies in sample extraction. Tecan has partnered with Zymo Research to offer labs an automated and optimized solution for nucleic acid processing.

optimization of workflows to achieve

for improved sample collection and

efficient, unbiased extraction. Founded

extraction, so we began developing kits

in 1994, Zymo Research has been

for everything from blood and urine to

offering solutions to aid nucleic acid

feces and soil samples.”

processing (NAP) since the early days of NGS. Ryan Kemp, Director of Nucleic

“This eventually led us into the

Acid Solutions at Zymo Research,

microbiome space, where we

NGS has made the transition from a

explained: “The company was originally

discovered that inherent bias in

research tool to a routine testing

created to exploit a number of

extraction techniques and a lack of

technique over the last decade or so,

proprietary yeast technologies, but we

standardization between methods

but pre-analytical sample handling

quickly moved into nucleic acid

could result in more than ten-fold

remains a challenge for many labs. The

purification, and became well known

differences in measurements. We

way samples are processed can

for our epigenetics offerings. Working

therefore created a suite of products

dramatically affect sequencing results,

side-by-side with many labs performing

aimed at improving accuracy and

requiring careful standardization and

NGS meant that we could see a need

consistency for this fast-growing area, including the development of the first commercially available mock microbial community standards, designed to assess the bias and sensitivity of workflows in microbiomics and metagenomics studies. This was an important development for the field, allowing labs to compare the results from their workflows and protocols to a qualified microbiome profile.” “Consistency is essential for any pre-sequencing sample preparation workflow, helping to ensure reproducible and reliable results. Optimized, precise sample processing is even more important for applications such as microbiome analysis or environmental testing, where sample volumes are often very small, and microbial titers are even smaller. In these circumstances, even slight contamination or small variations in sample processing can lead to significant unintentional bias, making NAP an ideal candidate for automation.”

The Fluent Automation Workstation is now an integral part of Zymo Research’s service lab workflow 28

TECAN JOURNAL 2/2020


COVID-19

The results are more reproducible than when the extraction is performed manually by an experienced technician. The recently launched DreamPrep™ NAP workstation has been created specifically to simplify nucleic acid extraction workflows, and Zymo Research has worked with Tecan to create optimized, automated protocols for a number of Zymo Research extraction kits, including the ZymoBIOMICS™ 96 MagBead DNA Kit for microbiome studies. Ryan continued: “Our goal was to provide a solution that simply and reliably purified NGS-ready nucleic acid. Tecan’s specialists worked side-by-side with us to streamline and parallelize the workflow as much as possible,

Ryan Kemp, Director of Nucleic Acid Solutions at Zymo Research

Dr Keith Booher, Services Projects Manager at Zymo Research

combining our knowledge of the chemistries and downstream workflow

workflow, and we could see from our

the COVID-19 pandemic spread across

with their liquid handling and

experience collaborating on the

the globe. Although we are a Research

programming expertise to create an

DreamPrep NAP protocol development

Use Only company, this kit is well suited

extremely fast, robust protocol. We

that the Fluent offered the versatility

for extraction of both the

chose a modular approach to developing

we required.”

nasopharyngeal and oropharyngeal swab samples used for molecular

the scripts, which ensured reliable operation and allowed easy transfer or

“Starting with the modular scripts

diagnostics. Being able to automate the

adaption. We used a Fluent® 1080 for

co-developed with Tecan, we have now

extraction is obviously essential for the

development, then transferred the

implemented a wide range of our DNA

type of high throughput testing

scripts to the DreamPrep NAP, which is

and RNA extraction kits on the

required in a pandemic, and the

based on the smaller Fluent 480

platform, which provides very good

modular approach we took when

workstation. This was very

purity and yields,” Keith continued.

scripting the DreamPrep NAP

straightforward and proved to be a good

“The guided workflow means that one

workflows has made it much easier to

test to demonstrate both the robustness

person can easily process many

rapidly implement testing on other

and flexibility of the modular approach.”

samples in a day, without the need for

Tecan platforms. We have even been

specialist training. It is also very

able to transfer the workflow to a

The throughput and consistency

reliable, which is important when your

number of Freedom EVO® workstations

offered by the automated, modular

customers have trusted you with their

fairly easily, despite the differences in

workflow are now benefitting

precious samples. I was even pleasantly

the two platforms’ software, because of

customers of Zymo Research’s NGS

surprised that the results are more

the way the scripts were developed.”

services business, as well as those

reproducible than when the extraction

using its extraction kits. Dr Keith

is performed manually by an

Booher, Services Projects Manager,

experienced technician.”

To find out more about Tecan’s

explained: “We were already using some automation in our service lab, but

The benefits provided by automation

DreamPrep NAP workstation

the diversity of sample types we

have also contributed to the global fight against SARS-CoV-2, offering a

featuring Zymo Research, visit

receive – blood and tissue samples, cell culture pellets, plant specimens, etc.

straightforward sample preparation

– meant that we were performing most

workflow for high throughput testing.

of the extraction by hand, due to the

Ryan added: “Alongside the

variety of different extraction protocols

ZymoBIOMICS kit, one of the first kits

required. As this side of the business

we chose to develop scripts for was the

has grown, it was logical to look at

Quick-DNA/RNA™ Viral MagBead Kit,

automating this portion of the

which really came to the forefront when

www.tecan.com/dreamprep-napworkstation To learn more about Zymo Research, go to www.zymoresearch.com

TECAN JOURNAL 2/2020

29


CELL-BASED ASSAYS

Empowering CORE oncology research Christophe Deben and the team at the University of Antwerp’s Center for Oncological Research (CORE) were the lucky recipients of a fully loaded Tecan Spark® Cyto plate reader with live cell imaging and realtime cytometry, after winning a Tecan competition in October 2019. The center is now using the instrument to support its revolutionary research in immuno-oncology. The Spark Cyto competition, which ran

lab is primarily focused on translational

no longer be relevant to a patient’s

from April to September 2019, required

research and combination therapies for

tumor. Instead, we work closely with

labs to submit a written proposal

non-small-cell lung cancers and

Antwerp University Hospital, using

explaining how they would use this

pancreatic cancers. At present, my own

material from tumor biopsies to

unique plate reader’s live cell imaging

work is on the use of patient-derived

generate both 2D and 3D spheroid

and real-time cytometry capabilities to

organoids in in vitro studies to

models, allowing us to study how

further their research and advance

characterize oncogenic signatures and

individual cancers respond to therapy.”

scientific understanding. A panel of

explore novel therapies.”

expert judges selected a shortlist from

“The culture conditions for each tumor

over 100 entries, and each finalist was

“When you use commercially-available

type need to be optimized to grow in

invited to give a short webinar

cancer cell lines for experiments, you

the lab as an organoid, so any

presentation providing further details

can see if a certain therapy has an

technology that makes these studies

of their research plan. The winner was

effect or not, but the downside is that

more streamlined and efficient is a

Dr Christophe Deben, a postdoctoral

these cell lines have been in culture for

huge advantage. Previously, we relied

researcher at the University of

a very long time. This means that the

on standard flow cytometry or basic

Antwerp, who explained his work: “Our

cells acquire characteristics that may

microplate-based assays for these

Christophe Deben and the team at the University of Antwerp’s Center for Oncological Research

30

TECAN JOURNAL 2/2020


CELL-BASED ASSAYS

experiments, but the drawback of those techniques is that you need a lot of cells to form a large enough number of organoids to study. This is very expensive, and can be difficult to achieve with limited patient material. My goal was to miniaturize all the assays, but still get enough data; I wanted to do everything in 384-well plates, reducing the number of cells required, as well as the amount of media and reagents. This was why I entered the competition to win the

sing the Spark Cyto for this work is U fantastic, giving us much deeper insight compared to standard singleplex methods. I let my imagination run wild in creating the experimental set-up for the competition, and it amazes me that nearly everything I thought of is possible with the Spark Cyto!

Spark Cyto, and it’s opened up a world of possibilities!” The Spark Cyto is proving the perfect

“We have also recently purchased a

application specialists – have been

partner for CORE’s research, combining

D300e Digital Dispenser from Tecan,

very good. We’ve learnt a lot from

the features of multiple analytical

which allows us to ‘print’ drugs of

each other, making adjustments to the

instruments into one system.

interest in very small volumes directly

protocol and software to work

Christophe continued: “We already had

into a microplate. This instrument can

optimally with our 3D spheroids. For

an older live cell imaging instrument,

be used with the Spark Cyto to give us

now, our work is purely research, but

but it’s not really made for spheroid

even more experimental data, by

our long-term goal is to move into a

work. Plus, with the Spark Cyto, you

allowing us to test different drug

clinical setting. Using the Spark Cyto

can multiplex live cell imaging with just

combination strategies and therapies

for this work is fantastic, giving us

about anything. I can now combine it

in much less time. For example, I

much deeper insight compared to

with different fluorescent markers, as

studied two or three drug

standard singleplex methods. I let my

well as assays based on luminescence.

combinations during my PhD, but it

imagination run wild in creating the

Using the Spark Cyto, I can get so much

was a lot of work and was incredibly

experimental set-up for the

more information about how the cells

time consuming, taking a full year to

competition, and it amazes me that

are responding to certain therapies,

perform all the assays. Now, I could do

nearly everything I thought of is

offering more clinical understanding

the same experiments in a month – this

possible with the Spark Cyto! The

and allowing better translation of in

set-up is an amazing time saver, and

versatility of the instrument means that

vitro results into the likely responses

has really increased both the speed

we can use it for nearly every line of

that can be expected in patients. I

and reproducibility of our research. In a

research running at CORE, and we look

really can do everything that I want to

clinical setting, doctors want to test

forward to where it will take us,”

do with just one experiment now –

patient samples with up to 18 different

Christophe concluded.

instead of having to visit several labs to

clinically-approved compounds at a

use various instruments – and I can

time, which would now not be a

monitor everything in real time, it’s

problem with the Spark Cyto and

fantastic. Most of our experiments are

D300e. We are not limited to certain

now automated, so I can spend more of

combinations or drugs, and can quickly

my time analyzing data or further

see which combinations work best in

optimizing our assays, rather than

vitro – it opens the doors for

physically running the experiment. With

personalized medicine.”

To find out more about Tecan’s Spark Cyto, visit www.tecan.com/sparkcyto To learn more about the Center for Oncological Research, go to

a couple of hours’ work in the lab, I can prepare the samples and load them into

“We are extremely grateful to Tecan

www.uantwerpen.be/en/research-

the Spark Cyto, then simply let it run

for picking our lab as the winner of this

groups/core/

– generating a week’s worth of data for

competition, and our interactions with

analysis.”

the company – particular the

TECAN JOURNAL 2/2020

31


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Tecan Group Ltd. makes every effort to include accurate and up-to-date information within this publication, however, it is possible that omissions or errors might have occurred. Tecan Group Ltd. cannot, therefore, make any representations or warranties, expressed or implied, as to the accuracy or completeness of the information provided in this publication. Changes in this publication can be made at any time without notice. All mentioned trademarks are protected by law. In general, the trademarks and designs referenced herein are trademarks, or registered trademarks, of Tecan Group Ltd., Mannedorf, Switzerland. A complete list may be found at www.tecan.com/trademarks. Product names and company names that are not contained in the list but are noted herein may be the trademarks of their respective owners. For technical details and detailed procedures of the specifications provided in this document please contact your Tecan representative. This journal may contain reference to applications and products which are not available in all markets. Please check with your local sales representative: www.tecan.com/contact


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