Tecan Journal Edition 01/2018

Tecan Journal

Edition 1/2018

Life Sciences, Diagnostics and Partnering

A flexible lab for the future

Stem cell research offers muscular dystrophy hope

Effortless integration

Accessible automation for the novice

Pages 8-9

Pages 16-17

Pages 18-19

Pages 24-25

CEO WELCOME

Welcome Dear Reader, When it was launched in 2014, the Fluent® Automation Workstation represented a step-change in laboratory automation, offering a unique concept built around the application-specific needs of laboratories.

From its inception, Fluent was designed to offer more capacity and greater speed while simplifying day-to-day activities. Looking back, we’re pleased to say that it has certainly succeeded, with major industry players such as Roche (pages 8-9) and Ambry Genetics (pages 12-13) embracing the benefits of this powerful platform.

As a pioneer of laboratory automation, Tecan continues to push the boundaries with new hardware and software options to suit an ever-expanding range of applications. We will soon be launching the Fluent Gx Automation Workstation to bring the speed and capabilities of the Fluent to regulated laboratories. The platform’s Fluent Gx Assurance Software will provide full sample tracking, electronic records, multi-level user management and a host of other features and utilities to simplify clinical, GCP, GLP, GMP and QC activities. We are excited to be opening up Fluent’s advanced liquid handling capabilities to customers in these regulated environments – complementing our existing offerings for this sector – and hope they enjoy the increased speed and productivity on offer. But the story doesn’t end there.

This powerful workstation has also come to the attention of diagnostic instrument manufacturers, and Tecan Partnering recently began its first project using the Fluent platform, collaborating with DiaSorin to develop a complete sample-to-result system for molecular diagnostics. Here at Tecan, we can’t wait to see what comes next.

I hope you enjoy the issue, Dr David Martyr CEO

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TECAN JOURNAL 1/2018

CONTENTS

Contents 2

CEO Welcome

4 - 5 The rise of live cell assays 6 - 7 Faster, error-free sample archiving and retrieval for clinical virology

10 - 11 Integrated knowhow

8 - 9

A flexible lab for the future

10 - 11

Integrated knowhow

12 - 13

Taking a Fluent approach to genetic screening

14 - 15 Automation dispenses with time-consuming calculations and preparation

16 - 17 Stem cell research offers muscular dystrophy hope 18 - 19

Effortless integration

20 - 21 More than skin deep 22 - 23

Harnessing the power of ‘friendly’ bacteria

24 - 25 Accessible automation for the novice 16 - 17

26 - 27 Targeting the treatment of solid tumors

Stem cell research offers muscular dystrophy hope

TECAN JOURNAL 1/2018

3

CELL BIOLOGY

The rise of live cell assays Cell-based assays are a core research tool, offering an informative and cost-effective counterpart to

in vitro and animal testing. Where destructive methods involving cell lysis once predominated, live cell assays are now commonplace, with measurements collected in real time, either at a single time point (end-point assays) or repeatedly over the course of minutes, hours or even days (kinetic assays).

Compare a movie to a still image, and it is easy to appreciate the added value of kinetic assays, in contrast to the more conventional end-point formats, which capture only a snapshot of the cells’ complex story. Knowing precisely when an event occurred, and how long it lasted, can add a vital dimension to the understanding of dynamic cell behaviors and responses.

Six things your cells would tell you

3) “I need some stability.”

if they could talk:

Random fluctuations in temperature,

kinetic assays, live cell experiments

1) “I can’t breathe.”

gas concentrations and humidity during

can offer more physiologically relevant

Cells depend on accurate and tightly

Environment matters Whether formatted as end-point or

and contextual information than their in vitro cousins, at a fraction of the cost of animal models. However, cell-based experiments that fail to mimic physiological conditions can be meaningless at best and, at worst, misleading. A fundamental factor for success is therefore the ability to maintain an optimal environment throughout the experiment. The importance of adequate environmental control is easy to overlook, because cells can sustain significant stress and damage without any overt changes in assay metrics. If only those cells could talk!

controlled gas and humidity levels to maintain metabolic and respiratory function. Common bicarbonate-buffered culture media require five to 10 percent CO2 to maintain pH between 7.2 and 7.4.

the course of an assay can trigger stress responses, changes in proliferation rates, and other unexpected behaviors – all without you even being aware of it.

4) “The grass is greener next door.”

It can also be advantageous to actively

Reliable and robust results depend on

regulate O2 levels to mimic physiological

consistent environmental conditions

conditions of different cell types or

from well to well, across the entire

tissues. High humidity is also essential

microplate. Variations in humidity can

to prevent evaporation, which can alter

lead to uneven evaporation across the

media salt and nutrient concentrations.

plate, a common source of confounding edge effects. Uneven temperature or

2) “It’s too hot (or too cold).”

Strict temperature control is critical for cell health and homeostasis. Even a few degrees of deviation from physiological temperatures can induce heat- or cold-shock responses. Active cooling may be just

gas distribution can be disastrous for cell growth and function, leading to unacceptably large variation across replicates.

5) “Please protect me.”

as important as heating for robust

Contamination is a risk in any live cell

temperature control, particularly when

assay, particularly during experimental

the desired set point is close to ambient.

manipulations. Minimizing human intervention – for example, with automated lid lifting and reagent dispensing – can go a long way to ensuring there are no mishaps.

The Blog 4

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

TECAN JOURNAL 1/2018

CELL BIOLOGY

6) “Look at me now!”

As automation and imaging

Monitoring even relatively basic aspects

Your cells are about to do something

technologies continue to break new

of cell health – such as proliferation,

ground, it may be tempting to believe

viability and apoptosis – can provide

the hype that cell-based assays require

significant biological insights. For

expensive high resolution imaging

results that are even more information

equipment. Without a doubt, these

rich, specific biological markers can be

systems have their place in cell biology

simultaneously monitored alongside

research but, in many cases, they

these general cell health indicators. And

are overkill. On the other hand, low

systems with a cell imaging option can

budget solutions like cell counters

extend the application range still further.

simply aren’t sophisticated enough to

Live cell analysis can open up the door

opportunity.

address complex biological questions.

to a wealth of new insights. With the

A multimode microplate reader with

latest advances in multimode kinetic

Finding the sweet spot

kinetic capabilities might just hit the

microplate readers, the possibilities for new discoveries seem almost unlimited.

Fortunately, the technology to maintain

sweet spot in such cases, handling a wide selection of in vitro and live cell

phenomenal, maybe even something that you couldn’t have predicted. To respond at the right time or capture the unexpected, careful experimental design is required to establish appropriate read intervals, timing of stimuli and reagent additions. Automation, remote control and conditional responsiveness can help ensure that you catch the window of

cell health and run long-term kinetic studies continues to improve and keep pace with evolving needs. Better environmental control – combined with kinetic capabilities, sensitive detection and high throughput automation – is

assays without a high price tag. Modular systems can also provide the flexibility to start with more basic applications, and build in additional functionality as needs evolve.

paving the way for new applications.

Larger scale studies and phenotypic screens are becoming more accessible than ever before.

www.tecan.com/blog TECAN JOURNAL 1/2018

5

BIOBANKING

Faster, error-free sample archiving and retrieval for clinical virology Virology testing at a molecular

The San Raffaele Hospital is one of the

“A good example of this is HHV-6,”

level is crucial for a fast and

largest hospitals in Italy, with over 1,300

Dr Racca continued. “The frequent

beds, and is internationally recognized

reactivation of HHV-6 following

as a leading center for clinical research.

transplants has recently been associated

Its research hospital (IRCCS, Istituto di

with neurological complications and

Ricovero e Cura a Carattere Scientifico)

even organ rejection but, until this link

request retrospective analysis,

status and close affiliation with the

was made, it was not included in the

sometimes as a means of

neighboring Vita-Salute San Raffaele

viral test panel. San Raffaele Hospital

monitoring drug response or

University and science park have kept

performs a large number of transplants,

the hospital at the vanguard of

predominantly bone marrow, and

molecular medicine for almost two

although it is now tested for routinely,

decades. The hospital’s laboratory of

clinicians have asked us to look at many

microbiology, serology and virology is at

samples retrospectively to assess the

that lead to, for example, organ

the forefront of these efforts, relying on

HHV-6 status of some patients. Our

rejection. The San Raffaele

cutting-edge technologies to enable

extensive knowledge of clinical testing

Hospital in Milan has developed

routine clinical testing and research

workflows, particularly in molecular

activities to run side by side. Dr Sara

diagnostics, means that we are also

Racca, head of the clinical virology

involved in a variety of research and

department, explained: “We are part of a

clinical studies, including the

large group of hospitals – one of 18 sites

development and validation of

sensitive initial diagnosis, but its role doesn’t stop there. Clinicians frequently

identifying drug resistance, and also increasingly to understand the underlying mechanisms

an automated archiving system that allows safe and accurate collection of clinical samples, as well as easy access and retrieval when further testing is required.

The Freedom EVO streamlines post-analytical sample preparation, simplifying the biobanking workflow

Automating our laboratory procedures as much as possible minimizes the infection risk to our staff, as well as saving them time, and has really helped us to avoid errors incurred from repeated manual pipetting. across Lombardy – and we receive over

laboratory instruments and tests. An

250 potentially infectious samples each

efficient biobanking system is essential

day from a large area of Northern Italy,

for this work, enabling us to properly

including the neighboring Emilia-Romagna

manage all our clinical samples and

region. It is very important for us to

patient details.”

store our samples, because clinicians often come back and ask for further

The lab originally archived samples

tests, whether this is in relation to drug

manually, transferring plasma directly

resistance, monitoring therapy, or simply

from primary tubes to cryostorage

asking for a test that wasn’t initially

tubes. In 2014, as part of the laboratory’s

requested.”

collaboration with Abbott Molecular, a Freedom EVO® 100 platform was

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TECAN JOURNAL 1/2018

BIOBANKING

acquired to improve the efficiency of

Following semi-automated real-time

sample collection, processing and

PCR analysis, the original patient

storage – as well as to help the team

samples are transferred onto the

gain better scientific insights from

Freedom EVO workstation, where 900 µl

banked samples. Dr Roee Dvir, a clinical

aliquots of plasma are pipetted into

microbiologist in the department,

small 2D barcoded cryovials. They are

explained: “We chose the Tecan system

then stored in the laboratory’s offline

to automate our post-analytical

-80 oC freezer, which has capacity for

aliquoting and sample archiving

more than 60,000 samples. Dr Dvir

because these tasks were extremely

added: “The Freedom EVOware®

slow and time consuming, occupying

software stores all the data on our

one member of staff full-time, and there

archived samples, allowing us to trace

was a very high potential for pipetting

any sample right back to when we

or labeling errors. We needed a compact

started the biobank in 2014. The

Dr Racca concluded: “The Freedom EVO

and easy-to-use system that was

software automatically matches up the

biobanking workstation has now been in

compatible with the primary sample

barcodes of original samples with the

routine use for three years, and it’s so

tubes taken directly from our clinical

corresponding stored aliquots; we

convenient, allowing us to get on with

analyzers, and that effectively

simply input the patient’s name and

other things while it just runs unattended.

eliminated the need for staff to handle

receive information on where each

The most important thing is that it gives

potentially infectious viruses. We also

sample is stored, and the dates on which

us the option to perform additional

decided to integrate a 2D barcode

they were collected. This enables us to

repetitive liquid handling tasks in the

reader onto the platform to optimize

further investigate key dates in the

future. For example, we are currently

cataloging and retrieval of clinical

patient’s care, such as when medication

planning to automate archiving of CSF

samples, and developed a custom

was changed. We now retrieve cryovials

samples, as there are a number of add-on

software interface that allows the

from storage several times a week for

tests under development in this field, and

Freedom EVO platform to communicate

additional testing.”

the intuitive user interface makes this easy

directly with the LIMS.”

Plasma samples are stored in 2D barcoded cryovials

to achieve. Automating our laboratory procedures as much as possible minimizes the infection risk to our staff, as well as saving them time, and has really helped us to avoid errors incurred from repeated manual pipetting.”

To find out more about Tecan’s biobanking solutions, visit lifesciences.tecan.com/biobanking For more information on the San Raffaele Scientific Institute, go to www.hsr.it/research/about-us

Dr Sara Racca, head of the clinical virology department

TECAN JOURNAL 1/2018

7

DRUG DEVELOPMENT

A flexible lab for the future Automated laboratory workflows are commonplace in the pharmaceutical sector, offering increased throughput and process security throughout the drug discovery process. Most of these systems are dedicated to a specific task or assay, and have been optimized to streamline these repetitive tasks.

Roche has taken a different approach for drug metabolism work, creating a centralized automation facility that is agile enough to respond to the changing demands of R&D.

As one of the world’s largest biotech

company is asking for our input on how

“In the drug disposition and safety

companies, Roche develops diagnostic

to redesign labs to encourage flexibility

department, we work closely with

tests and pharmaceutical drugs, from

and support increased collaboration. We

our modeling and clinical colleagues

initial discovery through to clinical trials

are drawing upon our past experience

to design in vivo pharmacokinetics

and commercialization. In 2014, Roche

in former companies and other Roche

studies, predict the potential drug-drug

announced a decade-long venture

labs to help us plan for the future.

interaction liabilities of a compound,

investing three billion Swiss francs in

People are spending less time in the lab

and investigate the enzymes involved

a new Basel research center, with an

than before, as automation frees us to

in the clearance of our compounds.

emphasis on improving sustainability

focus on the areas where we add most

We work across the entire spectrum of

and strengthening communication

value – analyzing data and designing

the process; there is no split between

between research staff. Dr Stephen

experiments to answer specific project

discovery and development as there is

Fowler, who heads up the automation

questions. We continually ask ourselves

in many drug metabolism departments,

team within the drug disposition and

how we can make the most of our

and we are responsible for collating the

safety department, said: “Our current

knowledge and expertise. And how our

information for new drug applications to

way of working has evolved both

familiarity and proximity to the projects

bring to the regulatory authorities.”

naturally and intentionally. Right now,

offer something that we cannot buy

in preparation for the new center, the

externally.”

“Our automated systems are centralized in a core facility with dedicated technicians to organize and program them, providing a service for all 80 researchers in the department. As most of the assays don’t require a high throughput approach, we have decided to use each instrument for multiple assays. We operate nine Tecan instruments – seven Freedom EVO® and two Fluent® instruments – and the two identical Fluent systems can each run 16 or 17 different assay scripts. Different people from the department use the instruments on a weekly or fortnightly basis, and they can book either system using an electronic calendar when a slot is available; one person can run one assay in the morning, and someone else an entirely different assay in the afternoon. Researchers are responsible for running their assays, but we help the process along by hosting the equipment and supporting them to optimize the

Two Fluent workstations are the latest additions to Roche’s core automation facility For research use only. Not for use in clinical diagnostics.

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TECAN JOURNAL 1/2018

DRUG DEVELOPMENT

utomation frees A us to focus on the areas where we add most value – analyzing data and designing experiments to answer specific project questions. automation and gather good quality data. They don’t need to reconfigure the Tecan instruments; they simply load up the experimental protocol, import their variables, add reagents, and set it running.”

Stephen continued: “The Tecan devices are well suited to running multiple different assays. We were fortunate enough to work with the Fluent during its development, and we’ve been involved throughout the planning phases of the system. Tecan has developed the software in line with some functionality we desired, and they’re very open to hearing our ideas. For example, we work with lots of different users and every so often an experiment will be set up with a reagent in the wrong place or with a misaligned plate, which disrupts the assay. We inserted a simple step into the software that brought up a screenshot of a correctly prepared assay for comparison, prior to the user pressing ‘Start’. If one in 20 assays now works where it would have failed, it’s a

Roche’s Stephen Fowler, Pascal Schenk and NaHong Qiu are ‘looking to the future of automation’ to meet the company’s changing R&D needs

worthwhile intervention. It’s great to see Tecan build on this idea, and you can now import JPEGs, videos and different

systems can be used for multiple tasks,

file formats.”

and reconfigured and reprogrammed quite easily. Tecan has provided very

“The future demands flexibility and the

good support whenever we have

ability to quickly adapt to embrace new

questions or encounter programming

opportunities – we can’t simply go out

problems, and has been willing to adapt

and buy a new instrument for every

software and hardware to suit our needs.

new assay that we need to run. If one

We’re really happy with improvements

of our assays is no longer needed, there

that Tecan has made to the software

is always another awaiting automation.

system, so much so, that we have just

We’ve been able to demonstrate that the

bought a third Fluent.”

To find out more about Tecan’s Fluent systems, visit www.tecan.com/fluent To learn more about Roche, visit www.roche.com

TECAN JOURNAL 1/2018

9

CELL BIOLOGY

Integrated knowhow Cell separation has become instrumental in many areas of medical research over the last two decades, and Miltenyi Biotec’s MACS® Technology has become the gold standard technique, having been cited in over 20,000 publications. Combining superparamagnetic microparticles conjugated to specific antibodies with proprietary columns, this technology uses strong magnetic fields to separate specific cell types, allowing retention of both labeled and unlabeled cells for downstream analysis.

Miltenyi Biotec has been helping to

approach: “Cell separation is probably

systems offering high throughput,

advance biomedical research and

the technology that we are best known

more automated cell separation. Our

cellular therapies since 1989, providing

for, but we aim to provide our customers

MultiMACS Cell Separation System is

equipment and instrumentation based

with a one-stop shop for everything to

available as a standalone instrument, but

on its core MACS Technology. Founded

do with cells – from sample preparation

the possibility of integrating it with a

and headquartered in Bergisch Gladbach

through cell separation using our MACS

liquid handling platform was considered

near Cologne, Germany, the company

Technology to analysis, as well as cell

from its inception. Prior to the

now offers solutions to cover the entire

culturing.”

development of the MultiMACS X,

cell processing workflow. Miltenyi Biotec

customers looking for a higher

provides cell biology equipment to both

Miltenyi Biotec has partnered with Tecan

throughput set-up needed to combine

academia and industry, and its

to develop a high throughput cell

our instrument with their own liquid

technology is used for fundamental

separation system, the MultiMACS™ X.

handling system. However, this is a

research, pre-diagnostics and in clinical

Lotta explained the history of the

complex undertaking, and requires a

settings. Lotta Räty, Global Product

partnership: “We started working with

large investment of time and manpower

Manager for Cell Separation Instruments

Tecan a number of years ago, when we

to ensure an optimal workflow and

at Miltenyi Biotec, outlined the company’s

first identified the market for integrated

achieve the desired biological results.”

Lotta Räty demonstrates the MultiMACS X cell separation system

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TECAN JOURNAL 1/2018

CELL BIOLOGY

Ultimately, you’re going to have far more dependable results with automation.

The MultiMACS X combines Miltenyi’s and Tecan’s expertise to offer high throughput cell separation

“Customers expect speed, high

incubation steps, the logistics of moving

entire time whereas, with the MultiMACS X,

throughput and quality results from our

labware around the workdeck, and

it takes five minutes to load, another five

systems, and so they don’t want to have

keeping track of all the samples. One

minutes to unload, and that’s it.”

to invest their time doing this

customer may want to have an additional

optimization and validation. It was

washing step, or separate several

“Another major benefit of automation is

therefore a logical next step for us to

different cell types from one sample, or

the reproducibility that can be achieved.

do this on behalf of our customers and

use a different starting material, and so

This should be a consideration when

create a fully-integrated platform. When

on. There are multiple interdependent

using any set-up, and reducing the

we set about designing the MultiMACS X,

processes, and so the challenge is to

number of hands-on steps minimizes the

we decided that combining our

establish a workflow that produces the

risk of human errors, lowering the overall

instrument with a Tecan Freedom EVO® 100

optimal final result. This is something

variability of your experiment. Ultimately,

liquid handling workstation was the best

specific to each customer, and we don’t

you’re going to have far more dependable

choice, bringing together two systems

leave their lab until they are happy with

results with automation, and partnering

that are well established in the

the system performance, which is

with Tecan has allowed us to meet the

marketplace. But it’s about more than

something that they really appreciate.”

needs of these higher throughput

simply integrating our instrument into a

applications while maintaining the quality

liquid handling system. This blend of our

“The MultiMACS X with the Multi-24

cell biology knowhow and Tecan’s liquid

Column Block allows the separation of

handling and automation expertise

up to 24 samples in parallel. This can be

enables us to offer a complete, validated

numerous different samples or, for very

solution, removing the onus of

large sample volumes, multiple aliquots

equipment assembly and workflow

of the same sample. The system takes

optimization from the customer.”

approximately 45 minutes to process

To find out more about

24 samples, including loading and

partnering with Tecan,

As well as providing a fully validated

unloading the instrument, whereas

hardware solution, Miltenyi Biotec also

processing that many samples manually

visit partnering.tecan.com

tailors the software and workflow to

could take three to five hours. But it isn’t

meet individual customers’ specific

just the total time that should be

needs. Lotta continued: “There are

considered, you also need to factor in

multiple steps to be considered in any

how much hands-on time is involved;

cell-based workflow; dispensing of

processing 24 samples manually requires

samples, reagents and buffers,

the technician to sit at the bench for the

our customers expect,” Lotta concluded.

To learn more about Miltenyi Biotec’s MultiMACS X, go to www.miltenyibiotec.com/ multimacsx

TECAN JOURNAL 1/2018

11

CLINICAL DIAGNOSTICS

Taking a Fluent approach to genetic screening ®

Clinical diagnostics company Ambry Genetics focuses on the identification of germline mutations, detecting large deletions and duplications primarily by next generation sequencing. Automation holds the key to efficient high throughput assays, ensuring optimum productivity.

Ambry Genetics, based in Aliso Viejo,

With the business growing rapidly,

capabilities of the Fluent quickly

California, specializes in genetic clinical

we recently expanded into the adjacent

became clear. As we were already using

diagnostics, offering services such as

building, known as the Ambry Superlab,

the Freedom EVO platform, we were

screening for familial cancers and exome

and this led to the acquisition of 16

also familiar with the liquid classes,

testing to identify previously undetected

Fluent Automation Workstations to

making the transition to the Fluent

mutations. In addition, the company

increase our capacity, speed and

easier. Validation of our workflow scripts

collaborates with universities and other

flexibility.”

was quicker and simpler too, as the

research groups via the AmbryShare™

systems use the same worklist file

program, sharing its large disease

Joy continued: “The Superlab was

database of aggregated anonymous

designed to be as efficient and high

formats.”

data from 11,400+ human genomes. Fast

throughput as possible, with a capacity

“Each of our systems has been tailored

and flexible liquid handling workstations

of thousands of samples per run, and

to our specific requirements, whether it

are essential in this high throughput

the flexibility to swap out different

is a large Fluent 1080 with a carousel

environment, as Director of Assay

assays and chemistries. I looked at a

and stacker, or a medium-sized, dual

Automation Joy Rae-Radecki Crandall

range of liquid handling platforms for

arm Fluent 780 platform. We

explained: “Automation is vital for our

the new facility, evaluating them for their

customized every system for an

work, and we are long-term users of

speed, capacity and flexibility – we

individual assay, with different liquid

Tecan’s liquid handling platforms, with

wanted to be able to customize the

handling arms and integrated third-party

more than 30 Freedom EVO® systems.

systems – and the outstanding

devices where necessary, and took advantage of the Multiple Channel Arm’s capability to switch pipetting heads on-the-fly, changing between 96- and 384-channel formats depending on the assay. Combined with the large deck capacity, this tripled our throughput for these assays. Fluent’s ‘teach-free’ feature also proved very useful with so many workstations to set up, and within six months we had transferred all of our current methods and completed the validation. Critically, the Fluent system’s design gives us the flexibility to easily change the deck layout. Not only does this provide built-in redundancy – switching from a layout customized for NGS to a microarray set-up is quite straightforward – it also allows new chemistries and assays coming onto the

Members of the Ambry Genetics automation team (left to right): Omar Alwatter, Chris Ramirez, Muaeen Obadi, Parker Sankey, Chris Yenzer, Emily Greene, Joy Rae-Radecki Crandall, Nina Do, Andrew Haling, Aarani Arulmoli and Sinead Hawker For research use only. Not for use in clinical diagnostics.

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TECAN JOURNAL 1/2018

market to be explored without major time and cost implications.”

CLINICAL DIAGNOSTICS

“We are benefitting from time and cost

to include a ‘Confirm’ button on the

savings as well as the increased capacity.

opposite side of the screen to the rest of

We run numerous hit-picking scripts for

the commands. It’s a small thing, but it’s

PCRs, and a 96-well plate that previously

had a big impact. The video feature is

took around eight minutes to complete can

useful too; we can make instructional

be done in about five minutes on the Fluent,

videos showing the user how to set up

trimming at least an hour off our overall

the deck, troubleshoot a run, and

preparation time for that step. The parallel

perform infrequently used protocols,

arm movements are a great advantage,

avoiding the need for hands-on

allowing the Robotic Gripper Arm™ to

refresher training.”

dispose of a used tip box while the Multiple Channel Arm simultaneously picks up new tips, saving about 15 seconds of time, which adds up when you are running numerous plates per day.

We have also been able to miniaturize some assays, changing from a 96- to a 384-well format, reducing the amount of sample and reagent used and decreasing the number of tip mounting and disposal movements from four to one. This saves

I looked at a range of liquid handling platforms for the new facility, evaluating them for their speed, capacity and flexibility… the outstanding capabilities of the Fluent quickly became clear.

time and decreases waste, providing considerable additional cost savings.”

“FluentControl™, with its TouchTools™

“We write all our scripts in house, and

interface and ‘wizard-like’ guidance,

people really like using the

simplifies user management and the

FluentControl software. They find it

day-to-day operation of the systems.

logical and easy to use, and can usually

Sample security and integrity is our

start writing scripts after about a week’s

number one priority and, with more than

worth of training. There are a lot of

30 users per instrument, we rely on the

variables to set for each script, and the

To learn more about

user management feature to assign

way that they are displayed makes

Ambry Genetics, go to

individual permissions and access to

troubleshooting very easy. It’s a clear,

www.ambrygen.com

scripts. Operators can only see and run

linear thought process, which makes the

those scripts that they have been

software very powerful. Operators also

certified competent for. Automated

enjoy having the option to personalize

barcode reading enables sample tracking

scripts, changing the color of the

and eliminates the potential for human

indicator lights, and even including

error, identifying plate loading errors and

background music to indicate which

notifying the user to take corrective

step of the protocol is being performed!

action. To help avoid accidental click-

They are really engaged with the

through errors, we even have the option

system,” Joy concluded.

To find out more about Tecan’s Fluent Automation Workstation, visit www.tecan.com/fluent

TECAN JOURNAL 1/2018

13

DRUG DISCOVERY

Automation dispenses with time-consuming calculations and preparation Automation brings more than simply speed to the laboratory.

Modern software is taking the headache out of serial dilution and normalization calculations, supporting assay development and delivering reliable results for international healthcare company Merck.

Merck KGaA is a global science

“My lab is currently working on a

and technology company working

number of projects in the areas of

in the healthcare, life sciences and

oncology and immuno-oncology, developing

performance materials sectors. The

assays for different targets, such as specific

company – which celebrates its 350th

protein-protein interactions and protein

anniversary in 2018 – operates in over

kinase assays. In March 2017, we

65 countries with approximately 50,000

developed an homogeneous time-

employees. This year, Merck received

resolved fluorescence (HTRF®) assay for

FDA approval for its immune checkpoint

protein-protein interaction studies, and

inhibitor, BAVENCIO® (avelumab),

we wanted to purchase an instrument to

used to treat metastatic Merkel cell

support our assay development and

carcinoma, a rare and aggressive skin

manage the large number of enzyme

cancer. Dr Nina Grossmann, a laboratory

and antibody titrations. We looked at

head within the discovery

the various dispensers on the market

pharmacology department in

before deciding on the Tecan D300e

Darmstadt, Germany, explained: “Our

Digital Dispenser. We really appreciated

department is primarily focused on

the instrument’s ability to work across

small molecule drug discovery, split

a broad volume range – from picoliters

across two sub-departments: cellular

to microliters – as there are not many

and molecular pharmacology. We

dispensers that can do this. We also

handle all kinds of biochemical assays,

use the instrument to support regular

which we miniaturize for high

compound titration testing.”

throughput screening and mode of action studies.”

The main benefits of the D300e have been the increased accuracy and time savings… we probably save ourselves one day per run.

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

14

TECAN JOURNAL 1/2018

DRUG DISCOVERY

Dr Nina Grossmann and lab technician Adrian Schoen with the D300e

“The main benefits of the D300e have

“We use 384-well plates for our assay

been the increased accuracy and time

development and, even though our

savings; assay development is now

technicians are very experienced with

much faster. We really appreciate the

this format, the error rate of the Tecan

reduction in preparation time, which

system is still much lower. The D300e

people often overlook. We simply set up

also helps us prepare for high

the metrics on the instrument – such as

throughput screening using 1,536-well

the titrations we want to carry out – and

plates – which we simply could not

the system does the rest, calculating

pipette by hand – saving us valuable

everything, including the normalization.

reagents.”

To find out more about Tecan’s D300e Digital Dispenser, visit www.tecan.com/D300e To learn more about Merck, go to www.merckgroup.com

If we were to do this by hand, we would have to create different stock solutions

“Whenever we have contacted Tecan

of the buffers, and we simply don’t have

support with questions, we get the

to do this anymore. Preparing a plate

answers we need quickly. For example,

only takes about half an hour on the

we’ve had some queries about using

D300e whereas, previously, doing the

the software and about which

calculations and pipetting by hand took

detergents were most suitable for use

a long time. We also had to use a series

with the digital dispenser. We also had

of titrations to narrow down the

a concern that using automation may

concentration range for further

damage or destroy the protein in some

investigation. The D300e allows us to

way, but we are currently using the

carry out these multiple steps in one

D300e in five different projects and

experiment, and we probably save

have not encountered any problems,”

ourselves one day per run. In addition,

Nina concluded.

the error rate is now much smaller, and the data is more reliable.”

TECAN JOURNAL 1/2018

15

DRUG DEVELOPMENT

Stem cell research offers muscular dystrophy hope Access to human pluripotent embryonic stem cells is enabling Genea Biocells to pioneer novel therapies to treat a number of neuromuscular diseases. Drawing on almost 30 years of research heritage, the company is using its expertise to model spinal muscular atrophy and facioscapulohumeral muscular dystrophy to identify potential therapies.

Cullen Pivaroff and Charles Martin with the Fluent Automation Workstation

Genea Biocells was established in 2017 as

with over 150 cell lines representing more

Genea is primarily focused on two

an independent company born out of the

than 30 diseases.”

conditions; spinal muscular atrophy

R&D arm of Genea Fertility – a world-leading

(SMA) and facioscapulohumeral

IVF clinic in Australia. The team

Monica continued: “We are in our early

muscular dystrophy (FSHD). SMA affects

of 20 scientists based in San Diego,

days as a drug discovery company, and

one in 10,000 people, with a carrier

California, specializes in drug discovery

have three main facets to our

frequency of one in 40 in the general

and therapy development to treat

organization. Firstly, we supply stem cells

population. FSHD is another of the most

neuromuscular diseases. Monica Hayhurst

and media reagents to strategic academic

common muscular dystrophies –

Bennett, director of preclinical research at

partners. We also carry out CRO work in

affecting one in 20,000 – and causes

Genea Biocells, explained: “In the early

collaboration with pharma companies

progressive loss of muscle strength.

days, the IVF clinic made a concerted

that want to focus on muscular

Genea has used its expertise to develop

effort to collect pluripotent embryonic

dystrophies we are not actively pursuing

the world’s first human stem cell model

stem cells that were excluded as part of

ourselves, such as Duchenne. Finally, we

of FSHD, and is using this platform to

preimplantation genetic screening.

have our scalable discovery platform that

search for therapeutic drug candidates.

Patients were asked if they wanted to

differentiates skeletal muscle cells from

“SMA and FSHD are monogenic diseases,

donate these cells for research and, over

human pluripotent stem cells and

which makes them good candidates for

time, we’ve created one of the world’s

supports our in-house assay

screening,” Monica added. “This has

largest and most varied private banks,

development.”

resulted in an abundance of stems cells

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

16

TECAN JOURNAL 1/2018

DRUG DEVELOPMENT

to work with, and has naturally focused

contamination issues. For cell-based

Cullen Pivaroff, a scientist at Genea

our research efforts. We primarily

assays, we manually create the cell

Biocells, added: “I’m fairly new to

concentrate on generating phenotypic

suspension, then the Fluent transfers this

laboratory automation and I have

assays for screening, elucidating

to either 96- or 384-well culture plates. All

discovered that, in addition to eliminating

different metabolic pathways in cells and

downstream manipulations are scheduled

manual work and improving the accuracy,

understanding pretranslational gene

through FluentControl™, from basic media

there are things the system can do that

expression. Once the team has

changes to more complex liquid handling

I simply can’t do manually. I have a

consolidated an assay, it can be passed

procedures involving the dilution of stock

background in cell culture and handling

on to the automation team.”

compounds to biologically relevant

fragile cell types, but the Fluent is so much

concentrations. In addition, we use the

gentler than working by hand; it’s a

Charles Martin, an automation scientist,

system for non-sterile applications,

well-configured and well-built system.”

continued: “Our Fluent® Automation

including immunocytochemistry for high

Workstation is central to everything that

content phenotypic analysis. We process

Charles continued: “There are so many

we do; it’s our workhorse system and is an

around 1,000 compounds – taken from

diverse applications for the Fluent, and

essential part of the screening process,

our small to medium-sized library – per

Tecan really values its working relationships

carrying out all the liquid handling and

screen, and the 384-channel pipetting

with people who are using the system.

supporting our analyzers and imaging

arm is very practical for this work; it’s

I recently went to a users’ round table

platforms. The Fluent system is equipped

obviously faster than an eight-channel

meeting, and it was great to see the

with a Multiple Channel Arm, an

option. I worked with a Freedom EVO®

Tecan engineers and software developers

integrated incubator and a laminar flow

platform in a previous job, so there wasn’t

responding to our suggestions. They

HEPA hood to run our cell-based assays.

a huge learning curve moving to the

seemed really keen to hear our feedback,

The HEPA hood creates a sterile, positive

Fluent, as there are enough similarities

and I’m sure a number of the ideas

pressure environment inside the

between Freedom EVOware® and

discussed will make it into future software

enclosure, and so we have very few

FluentControl.”

updates; they are always looking for ways to keep developing the platform.”

There are things the system can do that I simply can’t do manually.

To find out more about Tecan’s drug discovery solutions, visit www.tecan.com/drugdiscovery To learn more about Genea Biocells, go to www.geneabiocells.com

TECAN JOURNAL 1/2018

17

BIOPROCESSING

Effortless integration Microbioreactors are a convenient research tool, enabling cost-effective screening of a variety of fermentation parameters prior to scale-up and manufacturing of biological products. m2p-labs’ proprietary bioreactor technology offers automated, parallel monitoring of multiple micro-fermentations, and has been proven in applications such as clone screening, media optimization and synthetic biology.

m2p-labs, formed at the end of 2005 as a

extremely important for microbial

“We began the RoboLector project in

spin-off from RWTH Aachen University, is

applications. Most pertinent data for

2009,” commented Sebastian Blum,

a leading international supplier of

fermentations is, in some way, connected

European Sales Director. “We started by

microbioreactor systems for fermentation,

to biomass, and the BioLector offers the

speaking to customers, to get an idea of

screening and bioprocess development.

capacity to do this non-invasively.”

what they wanted from a fully automated

Octavia Deufel, Marketing and

system. We already knew that we wanted

Communications Manager at m2p-labs,

Product Manager Sebastian Hofzumahaus

to go from batch fermentations to

explained: “Our products are mainly used

added: “We have since expanded the range

fed-batch fermentations, as well as

for R&D applications, particularly in the

with a number of additional features and

offering automatic sampling and

chemical, biotechnology and

options, but all of our systems are capable

adjustments, but it became clear that

pharmaceutical sectors. We also have a

of doing 48-well plate fermentation –

users want a very flexible system capable

number of customers in the cosmetics

effectively 48 parallel microbioreactors

of fitting seamlessly into their workflows.

industry and, of course, we supply

– and measuring these key fermentation

We therefore looked for an OEM robotics

equipment to a lot of academic labs. Our

parameters. The difference between the

original benchtop system – the BioLector®

supplier that could provide a modular

models is the level of automation they

I – was designed to allow high throughput

liquid handling option that would be easy

provide. The RoboLector® is therefore

micro-fermentation experiments, with

to integrate with our BioLector systems.

the natural extension of the BioLector

real-time monitoring of important

The Xantus® was the only solution on the

range, enabling full bioprocess control –

parameters, such as biomass, pH value,

making pH adjustments, adding inducers

market with the level of flexibility we

oxygen saturation and fluorescence. The

and feed solutions, etc. – based on the

ability to optically measure biomass is

real-time data or a pre-programmed

unique to our reactors, and this is

schedule, or a combination of both.”

The RoboLector enables full bioprocess control For research use only. Not for use in clinical diagnostics.

18

TECAN JOURNAL 1/2018

wanted to offer to end users – it was a perfect fit.”

BIOPROCESSING

sers want a very U flexible system capable of fitting seamlessly into their workflows.

A variety of labware formats can be accommodated

The development of the RoboLector

by ourselves. We have a really good

had recently purchased a RoboLector

proceeded quickly. In just nine months,

relationship with the Tecan team

platform, and we were able to work

m2p-labs moved from initial planning to

as well and, if we encounter a new

together with them to develop this

shipping the first systems to customers.

problem that we don’t really know

option in just a few weeks. It’s a

Sebastian Hofzumahaus described the

how to solve immediately, we can

testament to the flexibility of the Xantus

process: “Most of the Xantus hardware

always get really quick and very solid

robot that we were able to so easily

could be used off-the-shelf, but we

support from Tecan’s personnel and

integrate this new module into our

required a number of small

the expert helpline.”

existing automated platform,” Sebastian

modifications to simplify integration,

Blum concluded.

such as an extended X-axis to enable full

“We are continually honing our software

access to the BioLector system. These

and modules to meet our customers’

adjustments were undertaken quickly

evolving needs. This year, for example,

and efficiently, and we are now able to

we have developed a new pre-culture

To find out more partnering with

offer customers a choice of three

module for the RoboLector. This allows

Tecan, visit partnering.tecan.com

options depending on their throughput.

us to reliably induce all 48 fermentations

The basic model has two pipetting

with the same quantity of cells, further

To learn more about m2p-labs

channels, one with a washable fixed tip,

reducing hands-on time and greatly

and the RoboLector, go to

and the other using disposable tips. We

increasing reproducibility. This module

then offer a four-channel version – again

www.m2p-labs.com

was suggested to us by a customer who

with a single channel using disposable tips – and an eight-channel model, using two channels with disposables tips for maximum throughput.”

“The software programming was done almost entirely by us in house, with a little bit of help and support from the Sias software development team,” Sebastian continued. “An important consideration, which influenced our initial decision to choose the Xantus, was the availability of a number of standard software drivers and interfaces.

This was a huge benefit, and the support we received during development was great. A number of our service technicians and application specialists have also been on Tecan’s training courses, allowing us to take on most customer service and technical support The RoboLector integrates a number of modules for true walkaway operation

TECAN JOURNAL 1/2018

19

CELL BIOLOGY

More than skin deep LMSM studies the effects of changing environmental parameters on the physiology of bacteria, and has recently began using this expertise to help the cosmetics industry. Many of these investigations involve absorbance-, luminescence- and fluorescence-based assays, requiring strict control of the temperature inside the microplate measurement chamber for reliable results.

The Laboratory of Microbiology Signals

fluorescence in this format but, equally

and Microenvironments (Laboratoire

importantly, we wanted to be able to

de Microbiologie Signaux et

precisely regulate the temperature

Microenvironnement, LMSM) is part

within the measurement chamber.

of the University of Rouen, France.

The Spark reader’s integrated Te-Cool™

First established in 1986, this specialist

module gives us complete control of

microbiology laboratory is home to

the temperature in the measurement

a team of university professors and

chamber, enabling us to perform

assistant professors, engineers, technicians and students engaged in projects investigating how microbiota interact with their environment.

LMSM focuses on three particular research areas – sensor systems and transducers, communication in human microbiota, and communication in plant microbiota – and works with a wide range of industrial partners, predominantly in the cosmetics and pharmaceutical industries. Assistant Professor Emeline Bouffartigues explained: “We use a variety of different approaches – including molecular and

microbiological studies within the reader. It also opens the door to new FRET-based applications, and will allow us to broaden our skills in interatomic characterization of protein-protein interactions. Choosing the Spark reader also futureproofs the laboratory to some extent, giving us the capabilities to perform, for example, time-resolved fluorescence and luciferase assays if we have a need to use these assay formats.”

Emeline continued: “We have been using the Spark for about six months now, and are pleased with its performance.

biochemical assays and cell cultures –

It offers everything we need in one

to carry out research into the physiology

instrument and has proved efficient

of bacteria in both human and plant

and reliable; our results have been very

hosts, looking at how micro-organisms

reproducible. One of the main uses

adapt to the environment. Many of our

of our Spark reader is for the study of

assays are carried out in a microplate

membrane fluidity in bacteria, which

format to increase throughput and save

employs a fluorescent diphenylhexatriene

reagents, and so we recently invested

(DPH) probe. The Te-Cool module is

in a Spark® multimode reader to assist

invaluable for these experiments, as

with this work.”

membrane fluidity is affected by temperature. Strict control of the

“We needed a reader that could

temperature in the measurement

accurately and reproducibly measure

chamber is therefore essential for

absorbance, luminescence and

reliable and reproducible results,

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

20

TECAN JOURNAL 1/2018

CELL BIOLOGY

Left to right: Ali Tahrioui, Emeline Bouffartigues and Olivier Maillot with LMSM’s Spark readers

and the Spark has made a big difference to our work. It enables us to obtain physiological measurements to help answer important questions about membrane fluidity, complementing the available genetic information.”

“We routinely monitor bacterial growth

The Spark reader’s integrated Te-Cool module gives us complete control of the temperature in the measurement chamber.

under different conditions while simultaneously following the expression of reporter genes. Again, the Spark and Te-Cool combination make these studies, which are also affected by

Senior Microbiology Technician

temperature, a lot easier to perform.

Olivier Maillot concluded: “We carefully

The user interface is quite intuitive too,

evaluated the Spark before purchase,

which is a real advantage for us, as a lot

to ensure that it would meet our needs,

of students use the system. They find

and it has exceeded our expectations

To find out more about Tecan’s

the reader easy to use and can work

and helped us to achieve a lot of success

cell biology solutions, visit

independently without the need for

in our investigations. Tecan’s customer

www.tecan.com/cellbiology

in-depth training. Another benefit is for

services are very responsive if we have

fluorescence anisotropy studies, where

any questions, and we have found the

To learn more about LMSM, go to

the Spark allows us to export raw data

Spark so useful that we have just bought

and perform the calculations ourselves.”

a second instrument for the laboratory.”

www.lmsm-lab.fr

TECAN JOURNAL 1/2018

21

FOOD SCIENCES

Harnessing the power of ‘friendly’ bacteria The rising global problem of antimicrobial resistance has led to growing pressure on food producers to eliminate the use of prophylactic antibiotics as an additive in livestock feeds. To help combat the potential risk this poses to animal health, Agro BioSciences is harnessing the power of the microbiota present in the gut of chickens, pigs and cows to try and eliminate the growth of pathogens.

All multicellular organisms – plants and

subsidiary of Arm & Hammer Animal

of livestock microbiota. This ‘Microbial

animals alike – are host to a variety

Nutrition – is harnessing the power of

Terroir™’ affects animals’ health in a

of bacteria, fungi and other microbial

the microbiota to enhance the health

variety of ways, including their growth

organisms. This ‘microbiota’ is essential

and production of livestock. Josh

rates and resistance to pathogens, and

to their survival, and can have a

Rehberger, Molecular Biologist at Agro

so we are adding probiotic bacteria to

significant effect on the health and

BioSciences, explained: “The local

feedstuffs in order to enhance these

taste of plants and animals destined for

environment around livestock can have

beneficial aspects of the microbiota.

the food chain. Agro BioSciences – a

a significant impact on the composition

The current push to eliminate the use of

Left to right: Evan Hutchison, Jesse Thompson, Josh Rehberger and Justin Sawall with Agro BioSciences Fluent platforms For research use only. Not for use in clinical diagnostics.

22

TECAN JOURNAL 1/2018

FOOD SCIENCES

growth-promoting antibiotics in poultry

such a major consideration, we

“A specialist from SciRobotics initially

production in the USA means that one

eventually chose the greater on-deck

helped us to develop the picking

area that we are particularly focusing on

capacity and speed offered by the

profiles during installation, and we

is the ability of the microbiota to help

Fluent® Automation Workstation. The

have since developed these further

reduce pathogen loads in these animals.”

SciRobotics modules hadn’t yet been

ourselves, resulting in huge time savings.

integrated into this system, but it was

The relationship between Tecan and

“One of the key features of our approach

a very smooth process, as I think the

SciRobotics is very beneficial from a

is that the nutritional supplements are

SciRobotics team had already done a

customer’s perspective, ensuring that

specific to each Microbial Terroir, which

lot of the background work.”

we can always get the answers to any queries we have,” Josh concluded.

means that we receive a lot of samples from farms across the country. These

“We now have two Fluent workstations

can be intestinal samples for poultry

in the lab: one equipped with a

but, due to the economic value of the

PetriPlater spiral plater and a high

animals, are more commonly fecal swabs or rumen samples for cattle, and a mix of fecal and intestinal samples for pigs. On average, we receive around 100 samples a day for poultry, and 60 each for cows and pigs. Each sample then needs to be plated on a number of different media –

What really set Tecan apart was the ability to perform automated plating as part of a liquid handling workstation.

usually around three per sample – ready for colony picking and downstream applications. This quickly adds up to

capacity PetriSel™ carousel – as well as two

somewhere in the region of 2,000 colonies

KingFisher™ Presto Purification Systems

To find out more on Tecan’s food

a week that need isolating, so in 2016 we

(Thermo Fisher) – and the other with a

sciences solutions, visit

looked for an automated solution that

Pickolo colony-picker. Both instruments

www.tecan.com/food

would perform the plating, colony picking

are capable of performing fully automated

and some of the downstream sample

plating, freeing up staff, then the plates

To learn more about Agro

preparation steps, allowing laboratory

are moved to an offline incubator to grow

staff to perform other activities.”

overnight. The plates are then loaded onto

BioSciences, go to

the platform equipped with the Pickolo “We looked at the various options on

for automated colony counting and picking.

offer, and what really set Tecan apart was

This system can count and transfer the

the ability to perform automated plating

colonies to 96-well plates far faster than we

as part of a liquid handling workstation;

could achieve by hand, and it’s more accurate

nobody else seemed to be offering that

too, eliminating some of the ‘guesswork’

capability at the time. We were initially

associated with the process. Plates are then

interested in Freedom EVO® platforms, as

split, with one portion archived in our offline

the SciRobotics modules – the PetriPlater™

freezers, and the system with the integrated

and Pickolo™ – were already integrated

KingFisher™ Prestos performs automated

into this system but, as throughput was

DNA isolation on the other.”

www.agro-biosciences.com

TECAN JOURNAL 1/2018

23

CHROMATOGRAPHY

Accessible automation for the novice High throughput bioprocess development is essential for optimizing run parameters prior to scale-up. University College London’s Advanced Centre for Biochemical Engineering is harnessing the possibilities afforded by automation, using custom-built scripts and programs to make its liquid handling platforms accessible to inexperienced users.

University College London’s

“A key step in many of our processes

previously run this type of experiment

interdisciplinary Advanced Centre for

is the development of effective

with the RoboColumns, and identified

Biochemical Engineering (ACBE) is a

separations of the biomolecules

early on that users would need intensive

world leader in the development of novel

of interest from other matrix and

training on the instrument to make the

bioprocesses and, in 2013, was awarded

cellular components, and we use*

most of its capabilities. The RoboColumn

a Queen’s Anniversary Prize for Higher

OPUS® RoboColumns® (Repligen) in

experiments are not simple to automate,

and Further Education in recognition of

combination with a Freedom EVO 200

as there is so much movement of labware

its ‘outstanding excellence’. Automation

to support these studies. This approach

and numerous aspirations from different

is at the very heart of its success, and

is highly regarded in both industrial

locations; everything needs to be

the department uses six Freedom EVO®

and academic environments, allowing

coordinated. Working competently with

platforms to accelerate its research. Dr

eight columns to be run in parallel

robotics often requires programming

Spyridon Konstantinidis, a postdoctoral

using the platform’s eight-channel

skills and, as the person with the most

research associate, explained: “We

Liquid Handling Arm™. This enables us

experience in this in the lab, I was having

apply quality by design to bioprocess

to collect more than 70 fractions per

to spend quite a lot of time helping

development, using high throughput

column in 96-well microplates over an

casual users and overseeing their

automation to screen out unfavorable

eight hour run, followed by analysis

programming. We therefore needed to

conditions and determine the ‘sweet

using an Infinite® M200 PRO multimode

find a way to make the automation easily

spot’ for each process through efficient

reader for absorbance and fluorescence

accessible to non-experts. The solution lay

and effective experimentation. This

measurements.”

in developing a custom Freedom EVOware® script to guide end-user inputs, deploy

maximizes the amount of knowledge we have about a process in early

“We purchased the Freedom EVO

compiled applications, generate

development stages, simplifying further

workstation to run these studies in

worklists, and execute common and

downstream activities and scale-up.”

2015,” Spyridon continued. “We had not

advanced commands.”

“This ‘scaffolding’ script takes the user though everything step-by-step. The script is divided into five parts, and the first phase asks the user to define the inputs and prepare the system. Custom screens guide the users through the available options, such as the number of columns, fraction size, etc. The software also guides them through preparing the system – putting the columns on the platform, loading solutions, etc. – and this whole process takes approximately 30 minutes. After this initial input phase – which takes only five to 10 minutes – calculations are performed automatically, and worklists are generated. The process does not require any end-user intervention after this point, as the remaining stages –

Spyridon Konstantinidis, postdoctoral research associate at the ACBE *For research use only. Not for use in clinical diagnostics.

24

TECAN JOURNAL 1/2018

CHROMATOGRAPHY

Freedom EVOware allows us to create these custom scripts and access advanced commands to unlock the potential of the system – it’s a very powerful tool.

The platform’s LiHa Arm can process eight RoboColumns in parallel

chromatography, fraction collection,

“Freedom EVOware allows us to

users, and we’ve benefitted from these

measurement and volume determination

create these custom scripts and

sessions; bouncing ideas off them and

of fractions and blanks, and results

access advanced commands to unlock

seeking their advice when it comes to

processing and reporting – are fully

the potential of the system – it’s a

implementing certain commands or

automated.”

very powerful tool. With most other

functions. The driving force behind our

platforms, you never even get to see

custom script was making automation

“There are a total of 165 inputs to manage,

this software architecture, and so the

more readily available, and we now

due to the high levels of flexibility that

options are limited. But Tecan’s software

have seven students who have used the

we need. However, the beauty of this

gives developers these tools and allows

platform unsupervised to complete their

method is that we can carry out many

them to innovate. As a result, we’ve been

investigations – it’s been a real success.”

different separations using one deck

able to generate a lot of commands

configuration, and so a majority of these

with our own custom programs; it’s a

inputs are classed as ‘defaults’, avoiding

massive step forward for our work and

any alterations to the script. One of the

enables the platforms to carry out very

benefits of developing our own script is

sophisticated actions.”

that we can also program the platform to perform separations in parallel with

“The support from Tecan has also

different durations, and this additional

been helpful. Every January, Tecan

functionality is a real bonus.”

runs a training course for first-time

To find out more about Tecan’s liquid handling solutions, visit www.tecan.com/ parallelchromatography To learn more about ACBE’s work, go to www.ucl.ac.uk/ biochemeng/research

TECAN JOURNAL 1/2018

25

BIOTECHNOLOGY

Targeting the treatment of solid tumors Tessa Therapeutics has developed a virus-specific T cell therapy for the treatment of solid tumors, which has shown promising results in early trials. Stringent quality control, including time-resolved fluorescence cytotoxicity assays performed on a multimode reader, is essential for this work.

S park offers the best of both worlds, combining the sensitivity of filters with the flexibility of monochromators in one reader.

Singapore-based Tessa Therapeutics

advanced nasopharyngeal carcinoma

is a clinical stage biopharmaceutical

therapy, which is currently undergoing

company aiming to revolutionize cancer

an international multi-center Phase III

treatment by redirecting the body’s

trial. In addition, we are conducting

anti-viral immune response to recognize

a Phase I trial of therapies for HPV-

and kill malignant cells. The company

associated malignancies – cervical and

is working with a growing network of

oropharyngeal cancers – and hope to

commercial and academic partners –

start Phase II trials soon.”

including the Baylor College of Medicine, the Parker Institute for Cancer

Working with partners across the globe

Immunotherapy, and the National

means that Tessa has had to build robust

Cancer Centre Singapore – to jointly

operational, quality control and supply

advance cancer immunotherapy

chain capabilities to allow it to

research and develop a portfolio of

successfully deliver VST therapies to

virus-specific T cell (VST) combination

a large patient pool internationally.

therapies to address a wide range of tumors.

Ruijuan continued: “Before any of our products enter a clinical trial they must

Unlike many other cell therapies, Tessa’s

undergo stringent QC testing. As part of

proprietary VSTs have the ability to

this process, we perform time-resolved

infiltrate and survive within solid tumors.

fluorescence cytotoxicity assays to

This allows them to migrate to the tumor

determine the cell-killing efficiency of

site and kill malignant cells with minimal

the VSTs prior to batch release of the

side effects. These VSTs can also

product for clinical trials. About two

self-renew, re-activate and expand when

years ago, we decided to upgrade our

encountering a virus-associated cancer

old fluorescence microplate reader to a

antigen, leading to a sustained and

multimode instrument, and looked at the

durable anti-tumor response in patients.

various systems available on the market.

This approach has already shown

We chose the Spark® for a number of

exciting results in the treatment of

reasons, including previous positive

advanced nasopharyngeal carcinoma,

experience of Tecan readers,

leading to the world’s largest Phase III

competitive pricing and the company’s

trial of a T cell immunotherapy for any

reputation in the field. Sensitivity was

cancer indication. Ruijuan Du, head of

another important consideration; Spark

quality control at Tessa Therapeutics,

offers the best of both worlds,

explained: “The company is involved

combining the sensitivity of filters with

in all stages of immunotherapy

the flexibility of monochromators in one

development, from fundamental

reader. We use the filter-based optics for

research to the co­ordination of late

our cytotoxicity assay because it offers

stage, multi-center clinical trials.

extra sensitivity, but we also have the

We are already dedicating resources to

option to use monochromators if we

planning scale-up and commercialization

need to.”

strategies, most notably for our

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

26

TECAN JOURNAL 1/2018

BIOTECHNOLOGY

Tessa Therapeutics is researching the use of its proprietary VSTs for a wide range of solid tumor indications

“We are really pleased with our Spark

“We work closely with specialists from

reader, and use it several times a week

our local distributor, SciMed, who provide

for QC batch testing. It allows us to

after-sales services, training and support

rapidly and accurately acquire specific

for our Spark reader. This includes

fluorescence read-outs, and is easy

preventive maintenance and periodic QC

to use, accurate and reliable. The

checks using Tecan’s MultiCheck™ plate

SparkControl™ dashboard is very user

and software – which has a useful

friendly, with straightforward, icon-driven

Pass/Fail feature – to quickly and easily

operation; we can store our methods on

check that the reader is operating on the

the instrument and then start a run with

basis of the determined parameters with

the click of a button. Operators need

defined limits. The company’s engineers

hardly any training, which is ideal, and

also help with troubleshooting if

the assay reproducibility from week to

necessary, and work flexibly to meet our

week is excellent.”

needs. It’s good to have local support to

To find out more about the Spark reader’s capabilities, visit www.tecan.com/spark-fluorescence To learn more about Tessa Therapeutics, go to www.tessatherapeutics.com

rely on,” Ruijuan concluded.

TECAN JOURNAL 1/2018

27

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