Tecan Journal Edition 02/2019

Tecan Journal

Edition 2/2019

Life Sciences, Diagnostics and Partnering

rom tennis elbow to F heart failure – regenerative medicine for life

A step closer to simpler liquid biopsy screening

Developing novel influenza inhibitors

Interfering with heart disease

Pages 8 - 9

Pages 26 - 27

Pages 28 - 29

Pages 30 - 31

CEO WELCOME

Welcome to my first Tecan Journal as CEO Having come from the OEM side of Tecan, where I was Head of the Partnering Business division, I understand that IVD companies choose Tecan because of our automation expertise.

This knowhow is our heritage, but customers – from start-ups to industry leaders – choose Tecan for more than just engineering experience. We’re in the fortunate position of providing automation solutions across a whole spectrum of life sciences research, from academia to drug discovery, meaning that we are familiar with emerging technologies as they make the transition from the lab bench to the clinic. This allows us to better serve our IVD customers, helping them to deploy novel technologies quickly and robustly, and in compliance with the relevant regulations.

Our close relationship with both our research and IVD customers also means that we understand their diverse workflows and applications. This allows us to offer more complete solutions to help eliminate bottlenecks and improve productivity, through both our Life Sciences instrument portfolio and Tecan Labwerx™ custom automation services. Increasingly, laboratories are looking for turnkey solutions that include not only automation hardware, but also workflow-oriented software, enhanced data analysis, and reagents and consumables. This is the goal of our new Tecan Synergence™ brand, which has been created to provide a unique, structured and flexible approach to the development of automated OEM solutions for both the diagnostics and life sciences markets. Together with our Tecan Cavro® brand OEM liquid handling components, this ensures the strength in depth that distinguishes us from other companies in the automation arena, helping to drive forward research that will enhance healthcare and wellbeing globally.

I hope you enjoy reading this issue, Achim von Leoprechting CEO

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TECAN JOURNAL 2/2019

CONTENTS

Contents 2

Welcome

4 - 5 Major discovery or fake news? Don’t let cytometry assays fool you

6 - 7

Pumping up genomics: how to engineer better NGS sample prep systems

8 - 9 From tennis elbow to heart failure – regenerative medicine for life

12 - 13 Keeping an eye on stem cells

10 - 11 Taking the stress out of cortisol measurements 12 - 13

Keeping an eye on stem cells

14 - 15

A strong automation foundation

16 - 17 Powerful customization automates NMR workflow 18 - 19

Transforming peptide synthesis for the 21st century to fill a GAP in the market

20 - 21 Cartoon characters bring automated genetic profiling to life

18 - 19 Transforming peptide synthesis for the 21st century to fill a GAP in the market

22 - 23

Algae in the next generation of materials

24 - 25 Real-time insights for better productivity 26 - 27 A step closer to simpler liquid biopsy screening 28 - 29 Developing novel influenza inhibitors 30 - 31

Interfering with heart disease

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 2/2019

3

CELL BIOLOGY

Major discovery or fake news?

Don’t let cytometry assays fool you With ‘fake news’ topping the headlines these days, we’re painfully aware that hearing just part of the whole story can lead to seriously wrong ideas that can have embarrassing or even disastrous consequences. The same is true when analyzing cell populations. Every individual cell has its own story to tell, so population averages and random samples are often misleading.

When running assays on a cell imaging system, microplate reader or flow cytometer, can you be sure you are getting the whole truth? If not, it may be time to consider whole-well imaging.

Every cell counts in cytometry

Do you know what you’re missing?

culture surface, the ability to assess the

To get a complete understanding of

To get the most from assays performed

entire cell population at once may be

what’s happing in a cell culture, it makes

on adherent cell cultures, you’ll want to

essential to ensure reproducible and

sense to collect information from all the

know what is happening to each and

reliable results.

cells in the sample, without disrupting

every cell, and where it’s happening – in

their behavior and complex interactions.

every well of the plate, and in context

• Cell confluence – Accurate assessment

An average intensity measurement

with all the other cells in the culture.

of cell confluence is often critical for

made with a microplate reader will not

Otherwise, you are not getting the most

pinpointing the optimal time window

tell you the whole story. Microscope

out of the sample statistically. Even

for actions such as initiation of imaging,

images that capture only a portion of

more importantly, you are likely to miss

addition of test compounds/reagents/

the well will not tell you the whole story.

valuable information about:

fluorescent probes, or collection of end-point measurements. Uneven cell

Flow cytometry of individual cells that have been stripped from the culture dish

• Cell position and distribution –

distribution or viability across the well

and separated from their neighbors will

Cells are dynamic entities; they move

can easily skew confluence assessments

not tell you the whole story.

around, get vital cues from their

that are based on population sampling.

neighbors, hang together in colonies, Not only can incomplete information be

and orient themselves towards or

• Sub-population responses –

perilously misleading, you may also fail

away from various stimuli. They rely on

Cultured cell populations are typically

to notice serendipitous occurrences –

spatial information to know when to

heterogeneous with respect to many

like a rare interaction between cells that

stop dividing, and to function correctly

factors, including cell cycle phase,

defies current theory, or an emerging

in tissue maintenance, development

gene expression, viability, uptake of

clonal population that is expressing

and regeneration. Image-based

fluorescent probes and sensitivity to

unusually high levels of a critical

information about the location and

drugs or stimuli. As a result, population-

byproduct. Goodbye serendipity, hello

orientation of individual cells can

averaged measurements or sampling of

‘fake news’.

therefore give you valuable clues about

only a sub-set of the total population

what is happening within the culture

may give misleading or ambiguous

as a whole, and can be enabling for

results. For example, does a low well-

many adherent cell assays, such as cell

intensity reading collected with a plate

migration and wound healing. Because

reader reflect a high response from a

cell position and distribution can vary

small percentage of cells in the well, or a

significantly with time and across the

low-level response from the majority of

The Blog 4

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

TECAN JOURNAL 2/2019

CELL BIOLOGY

cells? Are the cells imaged at the center

The bottom line is that every cell

of probes and detection modalities. Of

of the well behaving the same as those

matters, because every cell is telling

course, not all cell imaging platforms

on the periphery? Without whole-well

an important part of the story. If you

perform the task as well or as efficiently

information, such questions are difficult,

capture just a few images from an entire

as you need them to, particularly if your

if not impossible, to answer

well, or rely on a population-averaged

work involves kinetic analysis of living

with confidence.

measurement, you are settling for a

cells. It therefore pays to research what

smaller effective sample size (less robust

is available on the market, and know

• Rare events and phenotypes –

statistics) and literally throwing away

which factors are critical to enabling

Capturing rare events and cell

valuable data!

high quality whole-well imaging for both fixed and live-cell assays.

phenotypes is often essential for applications as diverse as clonal

Get the whole story with whole-well

selection, elucidation of molecular

imaging

mechanisms in disease and pathogen detection. It is easy to miss rare, transient or localized events if your detection system averages the responses or does not interrogate enough cells in a single pass. For the most statistically robust results, it makes sense to analyze every cell in the sample. This includes taking a look at cell morphology, which can tell you a lot about cell health, viability, function and developmental state.

• Assay quality – A colleague in the pharmaceutical industry once wasted six months thinking he had discovered a powerful inhibitor, when the truth was that the decrease in assay activity was an artifact due to overly forceful addition of compound into the well. Why didn’t he notice this sooner? Because he

The answer? One of the best and least destructive tools for capturing all of the individual cell data from hundreds or even thousands of cells at a time is whole-well imaging. Reliable whole-well imaging, where the entire

If you suspect your cell-based assays are telling you only half the story, check out our new Spark® Cyto, the first live cell imaging microplate reader to offer real-time cytometry.

Visit www.tecan.com/sparkcyto

well area is captured in a single shot, has only entered the mainstream relatively recently. Even more recent is the emergence of whole-well imaging capabilities for multimode plate readers. Progress has been slow, largely because of the technical challenges inherent in achieving sufficient resolution and definition at the well edges without compromising too much on acquisition speed.

Whole-well imaging increases the power of multimode microplate readers

was imaging at the center of the well,

Fortunately, the technical obstacles

when the damage was being initiated

are being overcome, and there are

at the edge, where the liquid dispense

now more types of systems on the

head was positioned. This is just one

market that offer whole-well imaging.

of many examples where looking at

Multimode microplate readers with

the entire well can provide important

whole-well imaging capabilities are

clues about assay quality, such as edge

particularly powerful, because they give

effects, mixing problems and more.

you the freedom to use a broad range

www.tecan.com/blog TECAN JOURNAL 2/2019

5

OEM COMPONENTS

Pumping up genomics: how to engineer better NGS sample prep systems With high throughput genomics impacting every corner of biology, the demand for more efficient next generation sequencing (NGS) workflows is growing rapidly. Automating the process of NGS sample preparation is crucial to avoid inaccuracies due to human error, bottlenecks that delay sequencing results, and the additional expense of re-running sequences.

What are the most important factors for an engineer to consider when selecting a pump to meet the stringent performance required for an automated NGS library preparation system?

First, a very short background in NGS

Different steps in NGS sample prep

sample preparation. The first step in

workflows require pipetting a wide

reliably and comparably, test after

preparing samples for NGS is to extract

range of volumes. In an automated NGS

test and across labs, is essential to

and purify DNA or RNA from a biological

sample prep instrument, it is critical

measuring and monitoring results and

sample. The next step is called library

for the liquid handling pump to deliver

trends.

preparation, which involves cutting the

the exact volumes required of each

DNA or RNA of interest into fragments,

reagent at each step. The precision

then selecting specific fragments to be

and accuracy of the pump are leading

speed to match liquid viscosity, reagent

sequenced. The resulting collection of

factors in ensuring high quality sample

addition and workflow times takes the

ready-to-sequence fragments is called

and library prep.

guesswork out of testing/prep.

• Consistency – Testing each sample

• Speed variability – Adjusting pump

a library. Here, we use the term ‘sample prep’ to encompass the entire process

A pump for automated NGS sample

of preparing sequencing-ready samples

prep must deliver reliable, reproducible

at a premium, it is essential to maintain

for NGS.

and accurate results

their purity. A pump with disposable

• Cross-contamination – With samples

Long-term research studies, crop

tips minimizes the possibility of cross-

Pump precision and accuracy are

and livestock strain improvement,

contamination and inaccurate results.

essential for high quality NGS

and environmental studies require

library prep

samples taken from different sources at

NGS itself is a very high throughput

different times. In clinical applications,

accurately dispensing or aspirating

process, so automating the upstream

diagnostic results must be consistent

key reagents or target fragments is

sample prep workflow is essential

over time, among patients, and even

essential, because incorrect volumes can

to enable fast and efficient parallel

across different medical centers. For all

significantly compromise the results.

processing with minimal manual

of these applications, consistent liquid

intervention. Compared to other

handling pump performance is critical

Pump flexibility enables the use of

high throughput genomic analysis

to help ensure that the NGS results are

different NGS workflows and kits

technologies, NGS is very costly, and

reliable and consistent every time, in

Automated NGS sample prep instruments

data analysis can take weeks or even

every lab. Consider these factors when

process a multitude of samples and kits,

months to complete. A poor quality

choosing a liquid handling pump for

each with different reagents and protocols

library may yield poor sequence data,

your NGS application:

for specific sequencing applications.

or none at all. At a minimum, you risk

• Accuracy – Ensuring that you are

Each NGS workflow requires pipetting

wasting expensive or limited samples, and the cost of lost time on the sequencer can be even greater.

The Blog 6

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

TECAN JOURNAL 2/2019

OEM COMPONENTS

discrete samples and reagents at varying volumes, viscosities and speeds. So many variables and requirements make selecting a pump for NGS liquid handling especially challenging. Consider pump options that accommodate workflow flexibility, such as varying flow rates, tip types, volume ranges and step sizes, as well as ports or valves that enable multiple fluid distribution channels.

NGS liquid handling pump performance and flexibility give a competitive edge The NGS market is exploding, demand is increasing and, as a result, new NGS applications are being introduced frequently. Even with this flood onto the market, NGS sample processing is still costly and time consuming. Automating the NGS sample prep process is crucial – using the right liquid handling pump for this automation is imperative. Sloppy sample prep is unacceptable and avoidable. Liquid handling pumps must live up to extremely high standards for precision, accuracy, consistency and flexibility. Automated NGS sample prep systems that accommodate various workflows and kits have a competitive edge in the market.

www.tecan.com/blog TECAN JOURNAL 2/2019

7

DRUG DEVELOPMENT

From tennis elbow to heart failure – regenerative medicine for life Regenerative medicine aims to stimulate the body’s own repair mechanisms to heal damage to tissues or organs. A wide range of biological materials – from extracellular matrix components and platelet lysates to stem cells – can be used to induce targeted tissue regeneration, but require careful formulation, extraction and purification for clinical use. Researchers at Celixir are exploring the potential of this approach to treat ‘tennis elbow’, a common repetitive strain injury affecting around two percent of the global population.

Recent advances in our understanding

This biotherapeutic, which is currently

As with any biological product – and

of cellular and molecular biology have

in Phase II trials, contains platelet lysate

especially biopharmaceuticals derived

resulted in a number of novel

materials that aid the regeneration of

directly from primary donor materials

bioengineering techniques being

injured tendons near the surface of the

– stringent product testing and quality

translated from a research environment

skin. Celixir’s Sheyla Galvez-Peisl

control is vital to ensure the safety and

to clinical applications. UK-based

explained: “Human platelet lysate (hPL)

efficacy of the final product, requiring

biopharmaceutical company Celixir is

is an excellent source of anti-

robust analytical methods and workflows.

focused on the development of off-the-

inflammatory components, growth

Sheyla continued: “Each batch of our

shelf cell and gene therapies to treat

factors and other biomolecules that

product is rigorously characterized, using

incurable or poorly treated diseases,

can stimulate tendon repair. Using a

a number of ELISA-based techniques to

including cancer and heart failure. The

proprietary platelet lysis technology,

quantify the various active components.

company’s pipeline currently features a

we are able to extract these

We use commercially available ELISA kits

number of products in clinical or

components from platelet-rich plasma

for most of our product analyses, but

preclinical trials, including a topical gel

with minimal residual matrix materials.

have adapted the assay protocols to

– Tendoncel – for the treatment of

This hPL is then formulated into a gel to

work with gel-based, instead of liquid,

lateral epicondylitis (tennis elbow).

create Tendoncel.”

samples. The ELISA workflow obviously requires a reliable multimode reader for routine assay processing, but it is equally important that we have a flexible system for assay development and validation.

The instrument software is also an important consideration in a regulated environment, to ensure process security and compliance with FDA regulation 21 CFR part 11 for electronic records and signatures. We looked at the various options available on the market, and the combination of the Spark® reader and Magellan™ Tracker software was perfect for our needs.”

“We now have two Spark systems, one at our headquarters here in Stratford-uponAvon and the other at our manufacturing facility in Greece. It is crucial that any assays developed and validated here can be precisely and reliably reproduced at the manufacturing site, and the Magellan Tracker software is ideal for this. It

Members of Celixir’s UK-based Science Group (left to right): Beatriz Canals, Cristina Sum, Daniel Sancho, Dr Lee Chapman, Dr Huw Davies and Sheyla Galvez 8

TECAN JOURNAL 2/2019

DRUG DEVELOPMENT

It is crucial that any assays developed and validated here can be precisely and reliably reproduced at the manufacturing site.

enables you to set individual access

QC assays for our Heartcel product.

“Tecan helped us a lot when we first

rights and permissions for each user,

Based on immunomodulatory progenitor

acquired the system as, like any new

allowing the administrator – in this case

cells, this therapy is designed to treat

technology, you need to become

me – to lock the assay parameters. This

patients with ischemic heart disease

familiar with its capabilities to make

ensures compliance and guarantees

undergoing coronary artery bypass

the most of it. Tecan’s application

that the assay is performed in exactly

grafts, so we need a system capable of

support team was very responsive

the same way every time.”

measuring cell-based assays. In addition,

when we had questions or needed

we have the NanoQuant Plate™ for low

guidance on setting up new

“We don’t just use the Spark reader for

volume sample measurements. This is

protocols, and we always get a quick

ELISA validation though,” Sheyla added.

ideal for DNA or RNA quantification, as

reply if we have any technical

“We also use it for the detection of

it only requires two microliters of

questions,” Sheyla concluded.

mycoplasma and other contaminants,

sample, and does not need calibration

and are in the process of validating new

– it’s used almost every day.”

To find out more about Tecan’s Spark mulitmode reader, visit www.tecan.com/spark To learn more about Celixir, go to www.celixir.com

The Spark reader provides all the functionality necessary for a regulated environment

TECAN JOURNAL 2/2019

9

CLINICAL RESEARCH

Taking the stress out of cortisol measurements The Health Psychology Lab at Brandeis University in the USA is using gold standard luminescence assays to monitor cortisol and other salivary biomarkers of stress. In addition to its own research projects, the Health Psychology Lab offers assay services and technical advice for non-profit and government institutions, from sample collection through to data analysis.

For years, clinical biomarker research

share our equipment and expertise in

biomarker – and the number of

relied on the analysis of blood, urine or

measuring salivary biomarkers of stress

publications on the subject – has grown

cerebrospinal fluid and, while this works

with the scientific community in the USA

exponentially. Previously, acute stress

well for most studies, the invasive

and, with the university’s support, we set

testing was typically performed in a

sampling processes involved could

up a non-profit business that we run in

laboratory setting, taking blood samples

potentially skew results in investigations

parallel with our own teaching and

via a catheter to monitor cortisol levels.

into biomarkers of acute or chronic

research programs.”

Not only is this invasive, but it is not

stress conditions, such as cortisol. Not

possible to monitor chronic stress by

surprisingly, this led to the development

Nicolas took up the story: “Over the

collecting samples for cortisol analysis

of non-invasive saliva-based tests,

couple of decades since saliva assays

over several days in people’s homes. The

including immunoassays.

were introduced, the use of cortisol as a

development of saliva assays was a big

In the late 1990s, Dr Jutta Wolf and Dr Nicolas Rohleder, now joint principal investigators of the Health Psychology Lab at Brandeis University, were working in Germany in the laboratory of Professor Clemens Kirschbaum, who played a major role in developing salivary cortisol assays. The experience they gained there in performing cortisol assays to support academic researchers worldwide served them well when, after postdocs in Canada, they moved to Brandeis in 2008 and set up the Health Psychology Lab. Jutta explained: “When we came to Brandeis, the university helped us to set up a lab to analyze blood and saliva samples for our own biological psychology research.

However, we were not using the equipment all the time, and we felt that we could do more with it.”

Jutta continued: “Saliva testing had captured the interest of researchers keen to avoid drawing blood samples for biomarker studies, as it is an easily collectable medium. However, academic researchers are not always in a position to run these assays and often rely on the services of other laboratories, even sending samples abroad for analysis. We thought that it would be a good idea to

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TECAN JOURNAL 2/2019

Dr Nicolas Rohleder and Dr Jutta Wolf, who set up the Health Psychology Lab at Brandeis University

CLINICAL RESEARCH

step forward. Samples can be collected

for many years, long before we came to

The combination of these kits and the

at home, stored at room temperature or

Brandeis,” said Jutta. “A lot of companies

Infinite reader provides a complete

in the fridge and then mailed to the lab,

offer assay kits for cortisol or other

laboratory solution that delivers high

where they are frozen for as long as

stress hormones in blood or saliva. The

quality results, which the lab backs up

necessary prior to analysis; cortisol is a

assays we use have the advantage of

with support for everything from

very stable marker and the

being very stable, reliable and

sample collection and analysis to advice

measurements will still be valid. That’s

economical. We find the luminescence

on sample-specific aspects for

a huge advantage compared to blood

assay superior to traditional ELISAs; it

institutional review boards and research

samples, which very often require

has fewer steps – reducing the possibility

grant proposals. Nicolas explained:

immediate processing and therefore

of human errors – and offers better

“Most of our customers are

on-site access to laboratory equipment,

resolution and sensitivity. Bulk kits are

psychologists and psychiatrists working

such as centrifuges and ultra-low

available too, which is very convenient.”

in biobehavioral research, and we analyze a lot of adolescent or infant and

temperature freezers.”

Nicolas continued: “We installed an

child samples for developmental

“Saliva testing has allowed researchers

Infinite 200 PRO multimode reader in

psychology studies. Often, customers

to learn a lot about the circadian

the lab to allow us to measure

ask us for advice and, as researchers

rhythms of cortisol and other steroids,

luminescence, complementing our

ourselves, we are in a good position to

as well as stress markers such as

existing ELISA reader, a Tecan Sunrise™.

help with anything, from the best way

salivary α-amylase,” he continued.

As we were already familiar with the

“It enables monitoring of changes in

company’s software, it was very easy to set up and run the cortisol luminescence

ne of the biggest advantages of the new O multimode reader is its speed. Previously, it took two or three minutes to measure a plate… With the Infinite, we can read a plate in under a minute. circadian rhythms and gives an indication of chronic stress exposure and its effects, for example, in clinical conditions like depression or posttraumatic stress disorder. That’s a

to collect samples to how to analyze and interpret the data that is generated, which is the difference between our lab and others offering similar services.”

Jutta concluded: “Tecan is very accommodating and responsive; the support we receive from the company helps us to achieve the fast turnaround times that our customers need and that is really appreciated.”

assay, and straightforward to transfer our existing methods for DHEA, DHEAS, testosterone, estrogen and progesterone

To find out more about Tecan’s

onto the Infinite. We also run α-amylase

range of saliva diagnostic kits,

assays, which we measure using the

visit www.tecan.com/saliva-

huge transformation that has come

Sunrise absorbance reader.” Jutta added:

about because of the development

diagnostics-feature

“One of the biggest advantages of the

of saliva-based cortisol assays.”

new multimode reader is its speed.

Previously, it took two or three minutes

The Brandeis lab performs cortisol

to measure a plate, which was a rate

measurements using Tecan’s Cortisol

limiting factor with the potential to cause

Saliva Luminescence Immunoassay and

sample backlogs and restrict

an Infinite 200 PRO multimode reader.

throughput. With the Infinite, we can

“We’ve used these saliva cortisol assays

read a plate in under a minute.”

®

To learn more about the Health Psychology Lab at Brandeis University and its assay service, go to www.bio.brandeis.edu/ healthpsych

TECAN JOURNAL 2/2019

11

CELL BIOLOGY

Keeping an eye on stem cells Stem cell research has seen explosive growth in recent years, with the technology holding promise for the treatment and cure of a wide range of conditions, from cancer, diabetes and heart disease to neurological conditions, inherited disorders and conditions of aging, including age-related macular degeneration (AMD). The Stem Cell Institute (SCI) at the University of Minnesota, founded in 1999, was the first integrated stem cell institute to be established in an academic environment, and focuses on basic and translational research with these versatile cells.

The ability of stem cells to differentiate

(iPSCs), primarily because they can be

group researches an array of diseases

into a variety of other cell types offers

generated from any individual, and can

that currently have no cure or effective

the potential to treat and cure a range

be used to model diseases, discover

treatment. One major focus is dry AMD,

of diseases and benefit patients

patient-specific drug responses and

a disease affecting older individuals

worldwide. The University of Minnesota

potentially generate autologous cells

that causes patients to lose their

SCI is a collaborative center for

for transplant therapies.

central vision. This condition is highly prevalent in the Northern European

researchers from 25 university departments, focused on gaining a

Dr James Dutton, Associate Professor

population that settled in Minnesota,

greater understanding of stem cell

at the SCI and the Department of

and I work closely with Professor

biology and the potential uses of this

Genetics, Cell Biology and

Deborah Ferrington from the

technology. It has an emphasis on the

Development, and Director of the SCI

Department of Ophthalmology and

study of induced pluripotent stem cells

Innovation Facilities, explained: “My

Visual Neurosciences to investigate this

Associate Professor James Dutton and Professor Deborah Ferrington in the dedicated stem cell laboratory

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TECAN JOURNAL 2/2019

CELL BIOLOGY

The platforms are very intuitive to use and can replicate everything that we used to do by hand – we can even control the speed, pressure and pattern of pipetting.

area. Our studies center on

of the iPSCs into RPE and set up for the

mitochondrial dysfunction in the retinal

drug screening process on them. We

pigment epithelium (RPE) – a single cell

designed the systems to suit our needs,

layer at the back of the eye – that is

including an integrated HEPA filter

damaged in the eyes of AMD patients.

hood to create a sterile environment, a

Much of the initial work was conducted

LiCONiC automated incubator to hold

using eyes donated to the Lions Gift of

the plates, a Cytation™ 1 Cell Imaging

Sight eye bank, however, to move this

Multi-Mode Reader to monitor cell

research to our AMD patient

confluence and morphology, and an

population, we needed to find a way to

integrated centrifuge for spinning

look at RPE cells from living individuals.

down cells during passage.

We have done this by taking a 2 mm

Additionally, there are two EchoTherm™

biopsy of the conjunctival layer

IC20 dry baths on the deck for sample

covering the white part of the eye,

and media temperature control, and a

reprogramming these cells to produce

barcode reader to track samples

iPSCs that then undergo a

throughout the process. The platform

differentiation protocol that causes

has three arms: an eight-channel Liquid

derived RPE, as well as generating

them to become RPE cells. Using these

Handling Arm™, a MultiChannel Arm™

results from the preliminary drug

iPSC-RPE cells, we are able to screen a

384 and a Robotic Gripper Arm™, which

screens. The aim is to add to our data

range of potential candidate drugs,

together, are able to perform all tasks

over the next few years so that we can

aiming to find effective ways of

associated with cell handling. The

start to see what drugs can help AMD

maintaining or improving mitochondrial

Tecan Labwerx™ Group has been

patients. At the same time, we are

function.”

especially good at ensuring full

planning to automate a number of

connectivity between all the equipment

other differentiation protocols on the

from third-party manufacturers.”

platforms to make other cell types from

“Scaling up this process of making

iPSCs, such as glial cells and neurons.

iPSC-derived RPE and testing the cells in a targeted drug screen would be

“The platforms are very intuitive to use

From there, we would like to expand

extremely difficult without automation;

and can replicate everything that we

into more technically difficult

we would need a large team of people,

used to do by hand – we can even

procedures such as organoid and 3D

and it would be very slow and prone to

control the speed, pressure and pattern

cultures – it’s an exciting time,”

error. However, until recently,

of pipetting. We can measure colony

concluded James.

automation of iPSC derivation, culture

size and cell density to track growth

and differentiation has been

using the integrated imager, and the

The University of Minnesota SCI is

complicated and technically

systems automatically perform daily

supported by the UMN Academic

challenging. We needed to find a

media changes at the differentiation

Health Center.

user-friendly, cost-effective

stage when the iPSCs are converted

automation platform that would

into RPE cells, saving us hours of

perform these methods efficiently,

‘people power’. The Tecan team is now

demonstrate scalability and

refining its scheduling software to

commercial viability, and would fit in

further complement our system, so that

the space we had available.”

we can connect our entire protocol and

All systems or products are tailor-made one-offs that were exclusively developed on customer demand.

For research use only. Not for use in clinical diagnostics.

minimize the need for human input.

“With support from a generous

This will increase efficiency and, using

To find out more about Tecan’s

philanthropic donor, we looked at a

multiple platforms, the workflow could

number of options and chose two

easily be scaled up to a commercial

cell biology solutions, visit

Fluent® 780 platforms, and the

level if necessary.”

department refurbished laboratory

www.tecan.com/cellbiology To learn more about the Minnesota

space specifically to house these units.

“We now have data from both donor

The systems are excellent; we can

eyes and living patients, and we are

Stem Cell Institute, go to

perform the whole end-to-end process

building up a patient cell bank of

www.stemcell.umn.edu

of derivation, culture and differentiation

conjunctival cells, iPSCs and iPSC-

TECAN JOURNAL 2/2019

13

OEM SYSTEM DEVELOPMENT

A strong automation foundation Rapid advances in genomic and molecular diagnostic techniques have seen these technologies make a rapid transition from the research bench to the clinic. As with any test used for diagnostic applications, ease of use and reproducible, reliable results are crucial to the successful uptake of molecular methods, meaning that many IVD suppliers are turning to laboratory automation. Sansure Biotech has successfully developed a market for qPCR-based diagnostic technologies in China, and has partnered with Tecan to offer complete automation of its nucleic acid extraction and screening workflows.

Molecular diagnostics is now widely

these applications, reproducible and

widespread adoption of new

used in a clinical setting, providing

effective pre-analytical sample

molecular diagnostic technologies.

valuable insights into areas as diverse

processing is crucial for reliable

as prenatal screening, risk

results. This can be difficult to achieve

Chinese IVD manufacturer Sansure

management, infectious disease

manually in a busy, multidisciplinary

Biotech captures the importance of

diagnostics and oncology drug

hospital or clinical laboratory, making

effective laboratory automation, and

susceptibility testing. For a majority of

automation essential for the

its ethos – combining accurate and

Members of the forward-thinking Sansure R&D team

14

TECAN JOURNAL 2/2019

OEM SYSTEM DEVELOPMENT

e are gradually establishing a W reputation – both domestically and around the world – for our accessible qPCR technologies.

reproducible testing with ease of use

split, with large international suppliers

were able to solve any issues quickly

and accessibility – has seen the

– such as Abbott or Roche – adopting

and efficiently. We have very stringent

company grow rapidly since it was

full automation, while the domestic

requirements for our suppliers in order

founded in 2008. From the launch of its

providers generally offer semi-

to ensure the quality and consistency

first products in 2010, it took just six

automated solutions. We chose to go

of our solutions, and the Tecan liquid

years for the company to become the

down the full automation route to make

handling systems are very reliable. If

second largest corporation in the

our systems as straightforward as

we do have an issue – such as

molecular diagnostics market in China,

possible for the end user, and looked for

instruments being damaged during

supplying over 2,000 hospitals and

an experienced liquid handling company

transport – the company is very quick

laboratories across the country. Mr Xu

to partner with. As an internationally

to respond. This type of support is

Fan, Vice President of Sansure,

recognized supplier of reliable

crucial from an OEM supplier and has

explained its approach: “Our aim is to

automated liquid handling systems,

formed the strong foundations of our

popularize qPCR technologies as an

Tecan was our first choice, and we have

long-term partnership.”

affordable and accessible solution for

established a strong cooperative

diagnostics and healthcare

partnership with the company.”

“Tecan also has very strong after-sales support and is continuously optimizing

management. Since the beginning, we have been dedicated to creating a

“The Freedom EVO® 100 workstation is

both its technologies and service

complete product portfolio for

the automation core of our platform,

offerings, which in turn helps us to do

molecular laboratories, from upstream

which we then develop by integrating

the same, creating a positive cycle that

nucleic acid extraction kits and full

our own technologies to create a

complements each other’s advantages.

automation to downstream PCR. Our

complete solution, from nucleic acid

Our aim now is to further develop our

R&D center in Changsha is focused on

extraction to downstream PCR. The

automated solutions with the

developing products that not only

biggest advantages of this set-up are

introduction of additional features and

provide high quality, reliable results, but

the reliability and productivity it offers.

modules, organically combining our

are also easy to use in a variety of

We already have market-leading

reagents and technologies with Tecan’s

different laboratory environments. This

extraction reagents, allowing high

platforms to grow the market for our

approach has been very successful, and

sensitivity, and automation ensures

products,” Mr Fan concluded.

we are gradually establishing a

reproducible processing while greatly

reputation – both domestically and

increasing throughput compared to

around the world – for our accessible

manual processing, further increasing

qPCR technologies.”

our competitiveness in the sector.”

Automation of its workflows has been

“You will inevitably encounter

crucial to Sansure’s success. “IVD

challenges with any major product

companies generally have two options

development, and this is particularly

when it comes to automation; semi-

true for advanced automation systems

automated or fully automated systems,”

combining components and

Biotech, go to

Mr Fan continued. “The molecular

technologies from multiple providers.

eng.sansure.com.cn

diagnostics market in China is currently

With strong support from Tecan, we

To find out more about Tecan Partnering and Tecan Synergence, visit www.tecan.com/partnering To learn more about Sansure

TECAN JOURNAL 2/2019

15

OEM SYSTEM DEVELOPMENT

Powerful customization automates NMR workflow Nuclear magnetic resonance (NMR) spectroscopy is becoming increasingly popular for high throughput applications, including compound library QC testing, protein-ligand screening and, more recently, screening of biological fluids for clinical research. Serving this diverse market poses a challenge to NMR instrument manufacturers such as Bruker BioSpin, requiring the development of modular and flexible automated sample preparation platforms to ensure optimal results.

NMR/LC-MS systems, with a choice of

but they can be as small as 100 mm long

five systems to suit different liquid and

with an internal diameter of just 0.8 mm

solid sample types.”

for certain applications,” Ulrich continued. “To avoid a detrimental effect

“One of the main requirements for

on NMR resolution, all liquid transfers –

sample preparation is the transfer and

especially adding and mixing internal

Bruker BioSpin – part of the Bruker

mixing of samples directly in the long,

standards or solvents – need to be

Corporation – is the leading global

thin glass tubes commonly used in NMR

performed without creating air bubbles,

supplier of NMR technologies for

workflows. The standard tube size is

foam or concentration gradients.

research applications. Sixty years since

around 18 cm long and 5 mm in diameter,

Automation of these liquid handling

the development of its first NMR spectrometer, the company’s systems are now relied on by researchers across the biomedicine, pharmaceutical development, clinical research, process chemistry and food safety sectors.

Reproducible pre-analytical sample preparation is essential for many of these applications, making automation of these processes highly desirable to allow larger studies and ensuring more consistent and reliable results. Dr Ulrich Braumann, Group Leader and Product Manager for NMR Hyphenation at Bruker BioSpin, explained: “Around 10 to 15 years ago, we started looking for an automated sample preparation solution to complete our NMR package, as this element of the workflow is quite demanding. Our NMR systems are used for a wide variety of applications, so we needed a robotic platform that was modular and flexible, and could be extended to incorporate further applications in the future. We identified the Xantus® platform from Sias (now Tecan) as the best solution, and our long-term collaboration has led to the development of the SamplePro family of instruments. These systems are now our standard sample preparation offerings for NMR spectroscopy and combined

16

TECAN JOURNAL 2/2019

Automation of pre-analytical sample handling helps to ensure accurate and reliable NMR results

OEM SYSTEM DEVELOPMENT

control strategy, so the system always knows the identity and geometry of all the containers on the workdeck. For example, if you set up the system for 96 samples, you can open the door halfway through and change the position of the sample plate or tube rack, as the system is set up to pipette from a barcodelabeled microplate well into a barcodelabeled NMR tube, not from position X to position Y. The robot knows where to restart, and continues from the correct position, avoiding sample mix-ups.”

Ulrich continued: “Using Tecan’s development kit, we have been able to create a comprehensive software solution that can control the Xantus and communicate with our NMR systems, allowing the creation of the SamplePro LAB2NMR – a fully The SamplePro’s barcode-oriented workflow allows a variety of NMR labware formats to be accommodated

integrated, walkaway system that prepares samples and sends them directly to the NMR spectrometer. This

ost of our installations are for quite M specialized applications so modularity and customization support – as well as quality – were key in choosing an automation partner.

system has a second robotic arm with a gripper tool to transfer the samples, and features extra shielding to protect the sample preparation platform from the NMR’s magnetic field. Our relationship with Sias, and now Tecan, has been very important in allowing us to provide this level of integration and flexibility to our customers. Most of our

steps with the SamplePro Tube platform

“A big advantage of the Xantus

installations are for quite specialized

enables precise and accurate results,

instrument for us is that everything is

applications so modularity and

while minimizing the need for user

modular and flexible. It is available in

customization support – as well as

intervention. This is particularly

different deck sizes to suit various

quality – were key in choosing an

important for customers in the

applications and throughputs, and can

automation partner,” Ulrich concluded.

pharmaceutical and clinical research

incorporate a wide range of standard

markets, where viscous plasma samples

modules for shaking, heating and

are common, and pose additional

vacuum extraction, as well as gripper

biosecurity risks. This is also a good

arms for manipulating the different

To find out more about Tecan

example of how our partnership with

sample tray types. Many of our systems

Partnering and Tecan Synergence,

Tecan benefits customers. The

also have a Peltier cooling device, which

visit www.tecan.com/OEM-products

SamplePro Tube uses a custom-

was developed specifically for us. All the

developed, patented ‘downholder’ and

labware and devices that are placed on

centering system which both secures the

the workdeck are barcoded, and the

glass NMR tubes in place and guides the

robot uses an arm-mounted barcode

piercing needles – which may be only 0.5

reader to identify exactly what’s on the

mm wide – into the tube caps to avoiding

platform. This flexibility has allowed us

needle damage and liquid spillage.”

to develop a barcode-oriented software

To learn more about Bruker BioSpin’s automated NMR solutions, go to www.bruker.com/ products/mr/nmr/automation

TECAN JOURNAL 2/2019

17

LC-MS

Transforming peptide st synthesis for the 21 century to fill a GAP in the market GAP Peptides has developed a novel approach to synthesizing high crude purity peptides that minimizes solvent and raw material consumption, while simultaneously reducing waste. Laboratory automation is helping this start-up company to accelerate its research and development, a process crucial to achieving commercial success. The company founders have collaborated with Tecan to establish a unique liquid handling platform, designed and built specifically to meet its workflow needs.

Scientific interest in peptides has

the consumption of raw materials and

reactor and increasing the amount of

expanded exponentially over the past

minimize solvent waste, producing

solvent waste generated. With GAP-PS,

decade, and today these biomolecules

peptides faster and with higher purity

we attach a specifically designed small

are ubiquitous across a range of sectors.

compared to other methods.”

molecule protecting group to the

The marketing potential is huge. In the

C-terminus of the first amino acid,

therapeutic sector alone, a compound

Cole took up the story: “Traditional

which ensures solubility in the reaction

annual growth rate in excess of 10 % – in

solid phase peptide synthesis is

solvent; with everything in solution, we

the region of 25 to 40 billion dollars – is

performed on a polymer support.

can use a smaller reactor and reduce

projected over the next few years. The

However, the peptide never actually

solvent waste. The synthesized

complexity of synthesizing these

dissolves in the reaction solvent, and

peptide is isolated by selective

peptides presents a challenge for

that means that the synthesis is often

precipitation after an aqueous

manufacturers, who must achieve high

not very efficient, resulting in lower

extraction step, offering a simple

purity in a cost-effective manner and, at

purity. The process also uses a large

purification process to match that of

the same time, adopt more

volume of solvent to swell and

solid phase techniques. This allows us

environmentally friendly processes.

suspend the resin, requiring a larger

to keep the benefits of solid phase

GAP Peptides, based in Lubbock, Texas, has developed an innovative process that addresses these issues, helping manufacturers to bring new synthetic peptides to market at an affordable price point. When performed manually, simultaneous synthesis of the multiple peptides needed for research can be very time consuming, so the company has automated the process on a Fluent® 1080 Automation Workstation.

CEO and Managing Director Caroline Brooks explained: “Our work is based on a novel synthesis strategy, Group Assisted Purification-Peptide Synthesis (GAP-PS), developed by our CSO Dr Cole Seifert and his research adviser, Dr Guigen Li, during his PhD studies at Texas Tech University. This unique synthesis approach will help manufacturers to improve yields, reduce

18

TECAN JOURNAL 2/2019

Cole Seifert (left) and Carder Brooks co-founded GAP Peptides in 2017

LC-MS

single person working manually could A synthesize one, maybe two, 10-amino acid peptides in about a week. In contrast, the Fluent can generate 24 peptides, completing the process in about three days.

Fixed steel tips provide reliable septa piercing

workstation. Partnering with Tecan was

liquid handling platform,” said Caroline.

an obvious choice for Caroline: “Tecan

“It gives us a tremendous capacity that

is well known in the life sciences arena

we just wouldn’t have if we did our

for its experience and in-depth

research manually, enabling the

knowledge of chemistry and automation,

synthesis of as many as 24 peptides at

and we very quickly discovered the

any time. This allows us to go to market

company’s expertise in designing and

with all the proof necessary to gain

planning a customized instrument to

credibility, giving potential customers

meet our needs. This expert insight

confidence that our technology works.

made it stand out and gave us the

Without an automated liquid handling

confidence to choose Tecan.”

system, this would be a very slow and painful process.”

Carder Brooks, General Counsel at synthesis while increasing the reaction

GAP, added: “Tecan’s experience in

efficiency – which enhances the

developing customized platforms and

peptide purity – and the scalability of

integrating third-party devices into the

the process.”

hardware and software played a major part in our choice of system. We

Cole expanded on the time savings offered by automation: “A single person working manually could synthesize one, maybe two, 10-amino acid peptides in about a week. In contrast, the Fluent

To enable commercial adoption of its

explained that we needed a custom-

GAP-PS technology, the company

designed workstation to automate a

needs to provide substantial data

novel peptide synthesis. While others

demonstrating the purity, yield, length

said it could not be achieved, Tecan’s

and complexity of the peptides

response was that, although it had

produced. Implementation of a fully

never done anything like this before, it

automated liquid handling system is the

had all the components necessary and

key to achieving this, and GAP chose a

was confident that it could assemble

is the integration of all the third-party

Fluent 1080 to increase throughput,

and program a platform to meet our

modules into the Tecan operating

enabling reliable, consistent data to be

needs, supporting us all the way from

software, but the company has

generated more rapidly. Tecan tailored

design to implementation.”

managed to create a user-friendly

can generate 24 peptides, completing the process in about three days, which makes a huge difference to our throughput.”

“Peptide chemistry is very complex, as

interface that simplifies the workflow,

the system to the company’s workflow, integrating a SciRobotics TubeEyeX™, a

“The beauty of the Fluent is that it

allowing us to make changes to meet

ppSPE device, an IKA shaker and a

enables us to show the capabilities of

our specific needs relatively quickly

Porvair sample concentrator – the first

our technology in a way that would be

and easily. It’s been a good

time this has been done on a Fluent

impractical without an automated

collaboration,” concluded Caroline.

To find out more about Tecan’s Fluent Automation Workstation, visit www.tecan.com/fluent To learn more about GAP Peptides, go to www.gappeptides.com

The Fluent Automation Workstation has been customized for GAP-PS peptide synthesis

Blue food coloring is used to allow the TubeEyeX to distinguish between the layers during the aqueous extraction step TECAN JOURNAL 2/2019

19

GENOMICS

Cartoon characters bring automated genetic profiling to life Genetic testing is at the forefront of modern medicine, and powerful tools are now available to identify inherited DNA characteristics that are potentially detrimental to health or conversely show susceptibility to targeted therapies. One such service, the Sanford Chip, has been developed by Sanford Health as a screening tool to identify pathogenic and likely pathogenic genetic variations that can be used to estimate the risk of some cancers and cardiac conditions.

Sanford Health is one of the largest

‘mirrored’ systems to increase

“We chose Tecan systems largely on

healthcare providers in the US, based in

throughput and capacity, and ensure

the recommendation of other

Sioux Falls, South Dakota, with 44

that each stage of the process is

industry leaders, but also because

hospitals and 1,400 physicians delivering

covered when either one of a pair of

they fitted our needs better than

services to patients in many US states

instruments is out of action for

alternative solutions we looked at;

and nine other countries. One of the

maintenance. “Once we receive blood

they are user friendly and offer the

organization’s most recent initiatives is

samples from our patients, it’s a

automation that we need. This

the development of a new laboratory

complex process to get to the

brings a lot of accuracy to the

service based on personalized medicine

laboratory results,” Michael

process, ensuring high throughput

and genetic testing. Michael Mboob,

continued. “The DNA is extracted on

and excellent quality while

Director of Operations at Sanford

one system, quantified on another,

minimizing errors, particularly in

Medical Genetics and Genomics

normalized on the next – all samples

pipetting. It also speeds up

Laboratories, explained: “The Sanford

are diluted to 60 ng/μl – plated onto

mundane tasks, taking hours or days

Chip is a laboratory developed test

the microarray chip on the fourth

to do things that would take days or

combining pharmacogenetic testing – to

instrument, and then the chip is

weeks to do manually; our team of

improve the efficacy of medication and

processed on the fifth.”

33 lab technicians can process

side effects – and a screening array for variants in 57 genes linked to potentially life-threatening health conditions, including breast and ovarian cancer.

Launched in May 2018, this service was made possible through a generous gift by philanthropist Denny Sanford to set up the Sanford Imagenetics initiative. So far, this service has only been available to existing adult Sanford Health patients, but it has already been successful in identifying genetic changes that could affect the way a patient responds to commonly prescribed medicines, enabling physicians to offer the right drug at the right dose – the basic principle of personalized medicine.”

The Sanford Chip service is reliant on 11 Freedom EVO® and two Fluent® systems, based in the central lab facility in Sioux Falls; there are effectively six pairs of

20

TECAN JOURNAL 2/2019

Gregory Jefferson working with the Tecan platforms in one of Sanford Health’s regulated laboratories

GENOMICS

“ [Tecan systems] bring a lot of accuracy to the process, ensuring high throughput and excellent quality while minimizing errors.

over a thousand samples each week for the three-day protocol.”

“Although the Freedom EVO and Fluent systems have separate workflows, we have deliberately designed our lab around lean principles to reduce the distance needed to move the chips and plates between the instruments. Our laboratory information management system collects all the data and ties everything together, and we use Tecan’s Introspect™ dashboard to check instrument performance and error logs – its remote log-in is particularly useful when we have so many systems to keep track of. Then, once the appropriate quality assurance and control procedures have been verified, the data is sent to our laboratory directors and

Katherine Moodie (left) and Danny Lee (right) preparing samples for Sanford Chip testing

pharmacists for in-depth review and interpretation before being forwarded

comply with clinical standards, and meet

Timon and Pumbaa from the Lion King,

on to genetics counselors, physicians

CLIA, CAP and other regulatory lab

and Woody from Toy Story, plus other

and patients.”

directives. This type of service had not

cartoon friends, are helping to provide

been set up in a primary care setting

genetic insights into personalized

“Tecan has supported us on site at each

before, so extensive validation was key

medicine and ultimately improving

new installation to make sure that we are

to ensure the accuracy of results. On top

patient care,” Michael concluded.

getting the best out of each instrument’s

of that, the data interpretation itself is

performance, and has also been very

very complex, and we needed to build

helpful in quickly resolving any issues

and validate bioinformatics pipelines to

we’ve had since everything has been up

ensure that genetic testing reports were

and running. It has taken about 18

clear and comprehensible, both for our

months to set up the service and,

team and for the physicians who would

although every one of our Tecan

be using them to guide patient care.”

To find out more about genomics solutions from Tecan, visit www.tecan.com/genomics To learn more about the Sanford

systems is customized, this was not a time-limiting factor; it took a

“Finally, to keep things light for our

Chip, go to imagenetics.

considerable amount of time to get

hard-working technicians, we have the

sanfordhealth.org/sanford-chip

everything aligned to work efficiently,

option to name our lab instruments, so

TECAN JOURNAL 2/2019

21

CELL BIOLOGY

Algae in the next generation of materials Improving sustainability

Petroleum-derived materials have a

Checkerspot, explained: “We screen

in the materials industry is

negative impact on the environment,

thousands of strains of heterotrophic

with many global initiatives being

microalgae in our molecular foundry to

implemented to encourage more

identify strains that express the highest

sustainable practices and protect the

levels of novel triglycerides. We then

by today’s world, including

future health of the planet. Naturally-

take those fatty acid building blocks and

climate change and the use of

derived molecular building blocks offer

apply our knowledge of chemistry and

toxic chemicals. Checkerspot,

a number of useful attributes for

materials science to produce high

a start-up materials company,

materials science, with a significantly

performance materials that we can

smaller carbon footprint, yet these

either fabricate into products ourselves,

remain largely unexplored or

or work with our partner companies to

underutilized, because novel plant-

deliver novel compounds.”

vital to help address some of the biggest issues faced

is using biotechnology to harness the power of nature, fermenting algae to produce

derived materials are challenging to

novel bio-based oils for use

manufacture on a large scale.

Genét continued: “We’re also working

in materials in the outdoor

Checkerspot, based in Berkeley,

on ways to improve lipid profiles and

recreational sector and an

California, is taking a new approach,

increase how much oil is made per unit

focusing on the development of greener

of time, as well as the types of fatty

high performance materials by starting

acids and lipid titers. Our strain

at the molecular level. The company has

improvement team uses a variety of

established a process to make oils via

mutagens and selection strategies to

the fermentation of algae, as Genét

improve strain performance, while our

Garamendi, Head of Strategic

genetic engineering group uses a more

Relationships and Communications at

rational approach to introduce genes

expanding number of other applications.

Kevin Ward operating Checkerspot’s Freedom EVO platform

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TECAN JOURNAL 2/2019

CELL BIOLOGY

The Freedom EVO has revolutionized our workflow; it only takes about half an hour to set up, and it picks and inoculates 350 colonies per hour, freeing up time for our staff to focus on other activities.

A brightfield image showing the formation of large oil droplets within individual microalgae cells

that we suspect will improve or modify

and inoculate 1,400 colonies. To scale up

which enables us to consistently find

fatty acid synthesis.”

this process, we needed a platform that

strains that are significantly improved

seamlessly integrated on-deck colony

over their parents, and eliminate lineages

“Our initial focus is on producing

picking with liquid handling to inoculate

with no commercial value. This allows us

performance materials for the outdoor

cellular growth assays. We looked at a

to more effectively use limited resources.

recreational sector, where properties

range of solutions to increase our

We have also established that our

such as hydrophobicity or wicking are

throughput and reduce the associated

discoveries at the screening scale are

vital. Additionally, sustainability is a core

manual labor, but they were either very

linearly predictable up to several hundred

value for consumers in the outdoor

expensive, required multiple instruments,

liters, in terms of oil profiles and titers.

sector, who tend to have an emotional

or took up too much space. Tecan was

The Freedom EVO is enabling things

connection to the environment. Using

able to combine colony picking and liquid

which we simply couldn’t do before; I’ve

algae to produce oils has a far lower

handling on one Freedom EVO® 200 with

already written additional scripts for

environmental impact than the

an integrated SciRobotics Pickolo™,

other applications, as our intention is to

petroleum-derived products that they

making the solution more compact and

automate as much as possible. This is an

replace, helping to tackle climate change

cost effective. With a single tip, this

exciting time for our company and we

and reduce the use of toxic chemicals.”

platform can pick a colony and split the

are eager to use this technology in the

sample between experiment inoculation

creation of more sustainable and higher

Checkerspot’s workflow relies on

and incubation in media, so that we can

performance materials,” concluded Kevin.

screening thousands of algal strains – a

go back to colonies of interest. It has

time-consuming and labor-intensive task

also completely automated our

when performed manually. Kevin Ward,

surrogate assays to track how well the

a scientist in the molecular biology and

algae cells are growing.”

strain development group, added: “We

To find out more about Tecan’s colony picking solutions, visit

were picking algal colonies manually

“The Freedom EVO has revolutionized

using a toothpick, transferring them to

our workflow; it only takes about half an

a 96-well plate to grow, then inoculating

hour to set up, and it picks and inoculates

experiments to select algae that grow

350 colonies per hour, freeing up time for

faster and produce more oil to lower the

our staff to focus on other activities. The

cost of production. On average, it was

platform has also reduced our CVs from

taking two people eight hours to pick

around 20 percent to under five percent,

www.tecan.com/pickolo To learn more about Checkerspot, go to www.checkerspot.com

TECAN JOURNAL 2/2019

23

SOFTWARE

Real-time insights for better productivity Understanding how and when laboratory automation assets are being used is crucial to maximize productivity and enable effective resource planning in high throughput facilities. California’s Ambry Genetics has a portfolio of almost 60 Fluent® and Freedom EVO® liquid handling platforms, and has worked closely with Tecan on the development of Introspect™, a cloud-based service that provides a comprehensive overview of precisely when and how laboratory automation systems are being used.

Ambry Genetics, a Konica Minolta

Managing the lab’s huge testing

“This information is available as part of

company, is a leading provider of

workload of up to 3,000 samples a day,

the log files for each instrument, but

genetic clinical diagnostic services,

and ensuring that resources are used as

we had no way to centralize and

including familial cancer screening and

effectively and efficiently as possible, is

visualize that data without a lot of

exome testing. In 2016, the company

a major challenge, as Director of Assay

manual processing. We initially looked

Automation Joy Rae-Radecki Crandall

at creating a software script to retrieve

explained: “The Superlab was designed

and compile the relevant data from

to be as efficient and high throughput

each platform but, after discussing the

as possible, while still offering us the

issue with our local Tecan

flexibility to run numerous different

representative, we discovered that the

assays and chemistries on each

Tecan software development team had

workstation. Being able to see when

Freedom EVO liquid handling

been exploring the same idea. We

and how effectively each system is

platforms to perform a wide range of

decided to collaborate and act as the

being used is therefore key to ensuring

assays, and the lab’s automation

we can maximize our throughput, and

portfolio has since grown to include

still have built-in redundancy to cope

almost the same number of Fluent

with peaks in sample numbers or

Automation Workstations.

instrument downtime for maintenance.”

built a state-of-the-art ‘Superlab’ designed to increase the efficiency, precision and quality of its testing workflows, while reducing the risk of human error. This CLIA/CAP-certified facility was initially equipped with 30

alpha user for this project, which later became Introspect.”

“Our primary requirement at the outset was to have a software tool that provided a visual representation of when we were using our various instruments,” Joy continued. “I’m a big advocate of color-coded graphical data, as it makes it much easier to understand and digest.

And once we began looking at that data, we started to notice patterns and pick up on all sorts of things we hadn’t even considered before. For example, we noticed that certain assays or times of day had higher error rates, prompting us to investigate and address the cause – from providing additional staff or training on a certain workflow to identifying bugs in our scripts. Regardless of the reason, resolving these issues has led to fewer errors and re-preps – which are both costly and time consuming – and has simultaneously increased staff confidence. We hadn’t even considered this as a potential benefit when we began the software development with Tecan.”

Members of the Ambry Genetics automation team

24

TECAN JOURNAL 2/2019

SOFTWARE

aving easy access to your instrument H data makes Introspect such a powerful lab management tool, allowing us to be proactive in our approach to resource utilization.

“Looking at the basic utilization data by instrument, Introspect obviously highlights which platforms are being used to capacity, and where we have redundancy. For example, if a system is being fully employed during the day, but not overnight, then there is potential for it to be used to perform a different assay in the evenings – as long as we have enough staff to run it. This level of visibility makes it very easy to build a business case for the purchase of new platforms, as we can clearly see how

Track utilization of an instrument on single days in the time-of-day chart

much instrument time and capacity is available relative to the number of tests we’re performing. It also makes it much easier to deal with fluctuations in sample numbers, allowing us to forecast how many consumables we are likely to need and ensure we have enough disposable tips and other labware in our inventory.”

“Another interesting aspect, which we hadn’t considered, was the software’s ability to track the amount of time we spend on research and development activities to validate newly commissioned assays or platforms.

This can have tax implications, so being

Identify low performing weekdays in Introspect dashboards

able to easily show when the platforms have been used for non-profit generating activities without having

To find out more about Tecan’s

to manually record hours is important.

Introspect service, visit

This is another example of how having

www.tecan.com/introspect

easy access to your instrument data makes Introspect such a powerful lab

To learn more about Ambry

management tool, allowing us to be

Genetics, go to

proactive in our approach to resource

www.ambrygen.com

utilization.”

TECAN JOURNAL 2/2019

25

LIQUID BIOPSIES

A step closer to simpler liquid biopsy screening Liquid biopsies offer the potential for the minimally-invasive detection of a growing number of cancers. Epigenomics is using its expertise in epigenetics to develop rapid tests for blood-borne cancer biomarkers, based on the unique DNA methylation fingerprint of cancerous cells.

DNA methylation is the process by

Epigenomics – which has sites in Berlin,

they require you to have access to the

which methyl groups are added to

Germany, and San Diego, California – has

tumor. If this is not possible, or the

cellular DNA, and it plays a key role in

over 20 years of expertise in the

patient is unwilling to undergo a biopsy

gene regulation throughout the lifecycle

development of DNA methylation-based

procedure, then a liquid biopsy may be

of cells. Aberrant methylation of cytosine

in vitro diagnostic tools, and aims to

the only solution. This technique also has

bases has been implicated in the

become a global leader in blood-based

significant potential for ongoing patient

pathogenesis of many genetic

cancer detection. Dr Gunter Weiss,

monitoring. For example, after surgery,

diseases – particularly cancers –

Senior Vice President of Product

when the primary tumor is no longer in

disrupting the normal gene regulation

Development at Epigenomics, explained

situ, a liquid biopsy can be used to

and cell proliferation. The unique

the advantages of this approach

detect any spread of the cancer.”

‘fingerprints’ created by these

compared to tissue biopsies: “The main

anomalous methylation patterns

benefit is that liquid biopsies are

Epigenomics’ approach relies on the use

provide potential biomarkers of

minimally invasive, requiring just a

of ammonium bisulfite to convert the

carcinogenesis, which can be detected

plasma sample from the patient. While

cytosine bases in denatured DNA to

in cell-free DNA circulating in the

cell- or tissue-based assays are still

uracil. This conversion is blocked by the

blood as part of a liquid biopsy.

considered the gold standard for

presence of methyl groups, so only

genotyping or diagnostic procedures,

unmethylated cytosines are affected,

Members of the Epigenomics team (left to right): Dr Gunter Weiss, Oliver Hasinger, Sebastian Rausch, Dr Anne Schlegel and Andreas Aurenz 26

TECAN JOURNAL 2/2019

LIQUID BIOPSIES

Despite these challenges and the complexity of the workflow, we were able to publicly unveil our automated solution within a year of beginning the project.

conditions and requires a constant 80 °C; too high and the DNA is destroyed, too low and the bisulfite conversion is inefficient. Our initial experiments highlighted that poor heat transfer between the heater and the plate surface led to very inconsistent heating, so we needed a solution that would improve this. We jointly found a form Epigenomics’ automated workflow requires integration of various labware formats and ancillary devices onto the workdeck

allowing methylation to be investigated

Rausch, a Scientist at Epigenomics,

by downstream applications such as PCR

described the start of the project: “We

or NGS. “High volume DNA extraction

started by visiting different customer

and bisulfite conversion have been core

laboratories to see what equipment they

competencies since the founding of the

were already using, but our previous

company,” commented Dr Anne Schlegel,

positive experiences of using Tecan

Senior Manager, Product Development.

instruments meant that the company

“We see ourselves as a provider of

was definitely our first choice. Once we

enabling technologies, and our Epi BiSKit

had made our decision, we worked

offers other laboratories the ability to

closely with the Tecan team to set up

prepare bisulfite-converted DNA

our protocols on a Freedom EVO 200

consistently and robustly from liquid

workstation, progressively optimizing

biopsy samples.”

the scripts and workdeck layout. The

®

high input sample volume required for “Preparation of DNA for epigenetic

our assay – 3.5 ml of plasma – ruled out

analysis requires relatively large amounts

the use of regular SLAS-format 96-well

of input material and is very time

plates, so we had to use high volume

consuming,” Anne continued. “It takes

24-well plates. Although these are twice

almost a full day to prepare a full run of 16

the height of standard plates, the

samples manually. This has been our

instrument’s Freedom EVOware

major challenge over the last decade, and

software makes it very easy to create

we have had several requests from

new labware templates with different

customer laboratories to provide an

dimensions. However, this created our

automated solution. This would not only

next challenge, as four 24-well plates

free up hands-on technician time, it would

would be needed to perform a full run of

also help to improve the reproducibility of

96 samples, requiring four shakers to be

the process by eliminating user-to-user

running in parallel.”

®

and special – to overcome this. Despite these challenges and the complexity of the workflow, we were able to publicly unveil our automated solution within a year of beginning the project.”

The outcome of this collaboration was an optimized and validated automated workflow with 87 major processing steps that takes 7.5 hours to extract 96 bisulfite converted samples, with equivalent results to manual processing.

Epigenomics is confident that this automated protocol will help to open up the world of liquid biopsy testing to more laboratories, by removing the considerable manpower and technical barriers to adoption. Gunter commented: “This type of protocol will certainly be of interest to large reference labs already performing large numbers of assays. These facilities have very high throughput capabilities, and can help to drive further development of liquid biopsy testing in both cancer screening and other disease areas.”

To find out more about Tecan’s

variability and the risk of human error from the workflow.”

fitting adapter – something quite unique

“We also needed a fifth shaker, one with

Freedom EVO workstation, visit

built-in heating, to perform the bisulfite

www.tecan.com/freedomevo

Epigenomics needed an automation

conversion on the smaller volumes of

partner capable of managing its

eluted DNA in a 96-well plate,”

To learn more about Epigenomics,

complex and delicate sample

Sebastian explained. “This conversion

go to www.epigenomics.com

preparation protocols. Sebastian

takes place under harsh chemical

TECAN JOURNAL 2/2019

27

DRUG DISCOVERY

Developing novel influenza inhibitors The VirPath laboratory is focused

Emerging strains of influenza and other

This integrated research program uses a

on the study of influenza and

respiratory viruses pose a significant

combination of in vitro, ex vivo and

other respiratory viruses to

threat to global health. They have great

animal models of infections, molecular

potential to spread around the world at

and cellular biology and ‘omics’

speed, creating a need for new and

approaches, and genetically engineered

rapid response containment and control

viruses. Olivier Terrier, a CNRS

vaccines. Digital dispensing

strategies. The VirPath laboratory – part

researcher in the Manuel Rosa-Calatrava

and luminescence-based assays

of the International Center for

team at VirPath, explained: “Our focus is

play an important role in the

Infectiology Research set up by the

mainly on respiratory viruses, such as

evaluation of viral growth in

French National Institute of Health and

human respiratory syncytial virus,

Medical Research (Inserm), the French

metapneumovirus and, in particular,

National Centre for Scientific Research

influenza, which are clinically prevalent

(CNRS), the École Normale Supérieure

and responsible for severe pathogenesis.

de Lyon (ENS) and the Claude Bernard

The aim of our research is to identify

Lyon 1 University – is studying viral

new antiviral molecules and develop

infections in classical cell lines and a

novel vaccines to combat these

reconstituted nasal epithelium model.

respiratory infections.”

identify new antiviral molecules and develop innovative

different experimental models.

The objective is to develop an understanding of the mechanisms

Postdoctoral researcher Andrés Pizzorno

driving virus pathogenesis and their

took up the story: “We have developed

functional interplays with the host

an innovative strategy of repositioning

cellular machineries.

drugs, targeting the host cell rather than

Members of the VirPath team with the lab’s Spark reader and D300e digital dispenser

28

TECAN JOURNAL 2/2019

DRUG DISCOVERY

specific viral molecular determinants. The

and were quickly able to operate the

use the Spark to certify the quality of its

objective is to identify broad spectrum

system independently. It also helps that

RNA-Seq libraries; high quality libraries

antiviral molecules that can be combined

the system is preprogrammed for

are essential for the determination of

with existing molecules that target the

commonly used microplate formats,

high RNA-Seq signatures of different

viruses, to improve performance and

which we can use as a starting point

respiratory viruses or bacteria in the

reduce viral resistance. We perform

for our assays.”

respiratory epithelium and at a treatment

transcriptome analysis of patient

level. Blandine commented: “Performing

samples, and experiment with various in

“We use the Spark’s luminescence

nucleic acid quantification using the

vitro and in vivo models to evaluate the

module a lot, as many of our

Spark and the NanoQuant Plate™ lets

effects of different treatments.” PhD

experiments depend on luciferase-

us collect information more quickly and

student Blandine Padey added: “One of

expressing reporter viruses. It allows us

easily than with other quantification

our main study models uses

to monitor the growth of viruses in

techniques.”

reconstituted human respiratory

different experimental models very

epithelium. Differentiated primary cells

precisely, and correctly evaluate the

“In addition to these applications, we

obtained from patient biopsies or healthy

effects new molecules have on the virus

perform drug combination studies. These

donors are cultivated at the air-liquid

reporters,” said Olivier. Andrés

can be quite complex and challenging to

interface, providing an organ-level

continued: “The reporter viruses enable

set up manually, and so we are also

imitation of human lung epithelium that

simultaneous monitoring of the infection

evaluating Tecan’s D300e Digital

is of great biological relevance.”

and rapid sampling, allowing us to

Dispenser. The D300e simplifies set-up

quickly discover how the virus evolves.

of a large number of drug combinations

The virology team takes a

Comparison of the differences between

in a microplate, which can then be read

multidisciplinary approach to its

treated and untreated cells then guides

very easily and effectively in the Spark,

research, and uses a Spark® multimode

decision-making on new molecules.”

allowing precise identification of the

reader for a range of applications,

synergies between the different

including absorbance, fluorescence and

VirPath performs library preparation

molecules. The combination of the

luminescence measurements, nucleic

using the Universal Plus mRNA-Seq kit

D300e and the Spark looks promising

acid quantification and cytotoxicity

with NuQuant™ technology, and plans to

for the future,” Andrés concluded.

assays. Olivier explained: “The Spark was a replacement for an older, lower performance luminometer. We wanted a reader that was versatile and robust, and could be used by all members of our team. Spark met that need, offering not only the luminescence module that we required, but also options such as absorbance and fluorescence, giving us the flexibility to use other techniques as

Performing nucleic acid quantification using the Spark and the NanoQuant Plate lets us collect information more quickly and easily than with other quantification techniques.

our needs change. This versatility, and the fact that we were already familiar with Tecan – we have a number of the company’s systems at the research center – was an important factor in choosing the reader, and meant that the Spark was quickly used for many more applications than luminescence.

To find out more about Tecan’s drug discovery solutions, visit www.tecan.com/drugdiscovery

Practically all our colleagues in the laboratory use it and find it very

To learn more about VirPath, go to

intuitive. After a short training session,

www.virpath.com

they found the Spark easy to understand

TECAN JOURNAL 2/2019

29

MASS SPEC SAMPLE PREP

Interfering with heart disease Developing drugs that are effective, with minimal side effects, is important to improve the lives of patients suffering from serious diseases. Leading biotechnology company Amgen focuses on producing therapies for a wide range of conditions, and is currently developing small interfering RNAs (siRNAs) as a method to treat patients with a genetic predisposition to heart disease.

Determining the distribution and

‘bad’ gene mutations, for instance, one

“I mainly study plasma samples to

breakdown of drugs after they enter the

that targets patients with a defective

analyze overall drug concentration, and

body is vital to understand a drug’s

lipoprotein(a) gene.”

liver samples to see if the siRNAs have

mechanism of action (MOA), any

made it to the target location. The

possible side effects it causes and the

Lp(a) is synthesized in the liver, and is

problem with these liver homogenate

effect of any metabolites. The

comprised of an LDL-like particle with

samples is that they cannot be directly

Pharmacokinetics and Drug Metabolism

an apolipoprotein(a) coiled around it.

injected into the mass spectrometer,

(PKDM) department at Amgen studies

Babak continued: “High levels of Lp(a)

and we need to use solid phase

the distribution of drugs in the body, as

have been identified as an independent

extraction (SPE) to clean up the sample

Babak Basiri, a scientist in the team,

risk factor in cardiovascular disease, yet

and concentrate the siRNA to a level

explained: “Our group looks at how

it is largely unknown how this particle

suitable for analysis. There are a

various classes of drugs affect animal

contributes to disease. Over one billion

number of different molecules in our

models. My focus is on the distribution

families globally are at risk or living with

sample that we need to wash away –

and MOA of siRNAs – double-stranded

heart disease due to high Lp(a) and, of

including hemoglobin, other proteins

oligonucleotides that can be used to

these cases, around 20 percent are due

and fat – as they could interfere with

‘interfere’ with the production of

to a genetic mutation. Patients with

our measurements.”

targeted proteins. They achieve this by

elevated levels may have a two- to

binding to, and promoting the

fourfold increased risk of heart attacks

“We use positively-charged SPE

degradation of, specific messenger RNAs

and other serious events, and our aim is

cartridges that the negatively-charged

(mRNAs), preventing the translation of

to develop siRNAs that limit the

siRNA can bind to, and use at least six

the associated protein. We produce a

production of this protein, reducing the

different solvents and wash buffers

number of synthetic siRNAs that we are

risk of heart disease.”

before we elute the final product.

testing to stop the expression of certain

Previously, we were performing the entire process manually and it was very laborious. We were simply waiting to add buffers at the correct time and, with the growing numbers of samples we were studying, it was becoming impossible to do by hand, as our maximum throughput was about two 96-well plates a day. We trialed a Resolvex® A200 system, which Tecan installed in our lab and helped us to set up. The platform allows us to automate the entire SPE process; I can simply hook up all of my different solvents, program it to perform the washes I need – selecting the buffer, the volume required and the order of the washes – and load my samples. I can then walk away and return a couple of hours later to my samples that are ready to analyze

Babak presenting a poster on the use of the Resolvex A200 for automated SPE sample preparation at ASMS

30

TECAN JOURNAL 2/2019

via mass spec straightaway.”

MASS SPEC SAMPLE PREP

Babak and his team enjoying a group lunch

“Over the course of our trial with the Resolvex A200, we ran a lot of samples and different experiments, such as stability studies or looking at metabolism profiles. Comparing the results to previous manually-generated results, we were happy with every experiment we ran; the data was more robust, with less variation and better consistency, and so

Overall, the system is very intuitive and user friendly, and has increased our throughput dramatically to double or triple what we were performing before. It’s not just the extra throughput that is amazing, but the time we are saving is huge.

we invested in our own system. Although there were other instruments out there with more ‘bells and whistles’, the A200 is perfect for our workflow. Its flexibility

“Overall, the system is very intuitive and

accommodates our varying workload,

user friendly, and has increased our

processing anything from a few to

throughput dramatically to double or

hundreds of samples a day. It’s also easy

triple what we were performing before.

to use and doesn’t require any

It’s not just the extra throughput that is

specialized programming, which is

amazing, but the time we are saving is

SPE solutions, visit

important in our busy lab, as multiple

huge. The ability to just set the system

www.tecan.com/ppspe

people from different projects are using

running is a godsend, as it frees our

the system. An added bonus is that it

hands for other work or data analysis,

To learn more about Amgen, go to

doesn’t take up any more space than the

and that alone is phenomenal,”

www.amgen.com

manual unit we had previously.”

concluded Babak.

To find out more about Tecan’s

TECAN JOURNAL 2/2019

31

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Tecan Journal, Customer Magazine of Tecan Trading AG., ISSN 1660-5276 Design: OTM/London www.otmcreate.com Photography: Günter Bolzern/Zürich www.bolzern.tv Editor in Chief: Tecan Trading AG, Antonietta Allocca Editor: kdm/UK www.kdm-communications.com Editor: UP THERE, EVERYWHERE/Sweden upthereeverywhere.com Print: DAZ Druckerei Albisrieden AG/Zurich www.daz.ch Address: Tecan Trading AG, Marketing Communications, Seestrasse 103, CH-8708 Männedorf, Switzerland, hello@tecan.com, www.tecan.com Images that are not owned by Tecan have been reproduced with permission.

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Tecan Group Ltd. makes every effort to include accurate and up-to-date information within this publication, however, it is possible that omissions or errors might have occurred. Tecan Group Ltd. cannot, therefore, make any representations or warranties, expressed or implied, as to the accuracy or completeness of the information provided in this publication. Changes in this publication can be made at any time without notice.

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