Tecan Journal Edition 01/2017

Tecan Journal

Edition 1/2017

Life Sciences, Diagnostics and Partnering

Synthetic biology in the real world

A smarter approach to LC-MS sample prep

Finding the perfect match

Designed for exibility, built for speed

Pages 4-5

Pages 8-9

Pages 16-17

Pages 30-31

CEO WELCOME

Welcome Dear Reader, I would like to begin by welcoming SPEware Corporation to the Tecan family. SPEware is a leading US provider of mass spectrometry sample preparation products, and offers a range of smart consumables and instrumentation designed to simplify customer workflows in this rapidly expanding field. SPEware’s portfolio is a perfect match for the Tecan range of automation workstations, and this innovative technology enables our global customer base to benefit from walkaway SPE-based sample preparation for a variety of MS applications.

As the laboratory automation sector becomes increasingly focused on applicationdriven solutions, it is more important than ever to work with knowledgeable providers with an in-depth understanding of laboratories’ needs, both today and in the future.

This acquisition reflects our ongoing commitment to providing customers with complete, end-to-end solutions to simplify laboratory workflows, and complements our existing MS sample prep consumables, including the AC Extraction Plate™. Full integration of the SPEware technology and product range with Tecan workstations will provide unrivalled throughput and flexibility for laboratories looking to automate MS workflows, as well as helping to improve the consistency and reliability of results.

More on this topic, along with our customary mix of customer stories and novel applications, can be found in this issue of the Tecan Journal.

Dr David Martyr CEO

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TECAN JOURNAL 1/2017

CONTENTS

Contents 2

CEO Welcome

4 - 5 Synthetic biology in the real world – automating the creation of new lifeforms

10 - 11 Putting the pieces together

6 - 7

How to reliably get more data from less volume

8 - 9

A smarter approach to LC-MS sample prep

10 - 11

Putting the pieces together

12 - 13

Vectoring in on success

14 - 15 Putting milk to the test 16 - 17 Finding the perfect match 18 - 19

A (cyto)genetic revelation

20 - 21 Effective sample preparation minimizes mass spectrometry maintenance

22 - 23

Lighter work for many hands

24 - 25 A natural affinity 26 - 27 Faster processing for biosimilars 28 - 29 Time saved in diagnostic vitamin B testing 30 - 31 Designed for flexibility, built for speed 14 - 15 Putting milk to the test

TECAN JOURNAL 1/2017

3

SYNTHETIC BIOLOGY

Synthetic biology in the real world – automating the creation of new lifeforms Synthetic biology is, quite literally, the creation of new genetic constructs and novel micro-organisms with innovative functions. Together with systems biology, it provides a platform for translating advances in genomics, proteomics and molecular biology into real-world applications.

Automating DNA synthesis Recent advances in robotics and liquid handling technologies are enabling synthetic and systems biologists to fully automate the design and production of the basic components of life. This ability to define and control the various steps involved in synthesizing genes,

more quickly and efficiently, with

commented Almer van der Sloot, a Senior

uncompromised accuracy. The various

Research Associate in the Institute’s

applications and collaborative ventures

Systems Biology and Synthetic Biology

described below give a taste of the

Research Unit. “We can now routinely

scope and commercial implications

perform 48 or even 96 DNA assembly

of the field at present, as well as the

reactions from start to finish in the time it

directions in which it could develop.

used to take us to do about 12 manually.

Importantly, automation has also

promoters and other genomic control

An assembly line for life

regions with increasingly high precision

One need look no further than the

is making it possible for scientists to

Massachusetts Institute of Technology’s

reprogram the activities and capabilities

Synthetic Biology Center to get a sense

of bacterial, yeast and mammalian cells.

Automated instruments and computer-controlled robotic systems have propelled synthetic biology from the research and development laboratory to commercial-scale, real-world industrial applications.

This approach allows many of the time-consuming and labor-intensive tasks intrinsic to synthetic biology workflows – such as colony picking and liquid dispensing – to be performed

improved accuracy and reproducibility.”

Producing drugs, chemicals, biofuels and more

of the breadth of applications being

Synthetic biology approaches are

investigated. Researchers at MIT are

also being widely explored for

developing genetic circuits capable of

biomanufacturing processes. For

regulating numerous cellular functions,1

example, Elanco Animal Health, a

with potential uses in areas as diverse as

division of Eli Lilly, is using Enbiotix’s

biofuel development and drug discovery.

engineered phage technology to develop

By automating specific protocols and

bacteriophage-based antimicrobial

processes within their workflow, the

therapies targeting specific infectious

MIT team has been able to fabricate

veterinary diseases. This type of ‘phage

plasmid constructs encoding these novel

therapy’ represents a complementary

biological circuits on a much larger scale.

antibacterial strategy to help reduce the

“Scaling up this process on a robotic

use of antibiotics.

system gives us higher throughput and repeatability, without the variability

Another example of synthetic

inherent in manual procedures,” said

biology-based production is Amyris’

researcher Dr Jonathan Babb.

use of microbial engineering to develop plant-derived ingredients for cosmetics

The Blog 4

Similarly, scientists at the University

and lubricants. The company uses its

of Montreal’s Institute for Research in

µPharm™ discovery and production

Immunology and Cancer have used

platform to create stable libraries of

automation to streamline the cloning

analogs of natural compounds. This

and DNA assembly workflow they use

technology offers rapid design and

to design artificial cell signaling circuits

scale-up of fermentation processes for

and sensors.2 “Automation has given

the production of target molecules in

us a dramatically higher throughput,”

engineered yeast strains.

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

TECAN JOURNAL 1/2017

SYNTHETIC BIOLOGY

Global energy company Repsol is also applying synthetic biology technology to bioproduction, in this case for the development of micro-organisms capable of generating advanced biofuels via novel metabolic routes.3 Jose Miguel Seoane, a researcher in the biotechnology department at Repsol’s Madrid Technology Center, explained: “The investigation of new biological applications involves screening large numbers of mutants of different micro-organisms, enabling the best performing candidates to be selected for further studies. As we test thousands of different mutations, automated high throughput screening is the key to our success.”

Building in flexibility Computer-controlled robotic systems can be used to automate virtually all aspects of the synthetic biology workflow, including next generation sequencing, DNA extraction, PCR set-up and clean-up, cell transformation and transfection, colony picking, biochemical and cell-based assays, and protein purification and expression screening.

The flexibility and open architecture of

1) Reprogramming nature.

Tecan Journal 3 2012, 22-23.

2) Designer proteins.

Tecan Journal 3 2015, 20-21.

3) Developing the fuels of the future.

Tecan Journal 2 2015, 20-21.

the Freedom EVO® workstation make it ideal for these applications, offering a complete solution for accelerating

For more information on Tecan’s

workflows and improving productivity

synthetic biology solutions, visit

for virtually any laboratory.

lifesciences.tecan.com/ syntheticbiology

www.tecan.com/blog TECAN JOURNAL 1/2017

5

LOW VOLUME PIPETTING

How to reliably get more data from less volume

The industrialization of biology

The industry-wide drive to generate

has become possible thanks to

more data has also created a demand

the automation of repetitive tasks – such as liquid handling – making 24/7 operation feasible.

for reliable assay miniaturization.

Moving manual steps, such as pipetting, onto automated liquid handling solutions enables the reliable

This cost-saving automation

dispensing of lower volumes, which can

addresses several major

result in both reagent and sample cost

concerns for biology workflows.

Firstly, automation brings consistency that reduces the risk of expensive errors that

savings. This is especially true when increasingly sensitive assays are used to screen libraries of potential drug candidates that are available in very limited amounts.

can, for example, delay the publication of your paper in a respected peer-reviewed journal, or hold up the development of a drug. The ability to implement

Dispensing at the lower specified limits of liquid handling platforms – in the microliter or sub-microliter range – can pose particular challenges for the manufacture of low volume disposable

low-error automation may

tips. This is especially true for highly

even be critical for regulatory

sensitive techniques, such as next

acceptance in clinical applications. Secondly, automation enables personnel to concentrate on key competencies and be more productive.

generation sequencing (NGS), where it is advisable to use high quality disposable tips from the manufacturer of the liquid handling instrument, as these issues are addressed during development.

Achieving economy of scale Massive technological advances have reduced the cost of sequencing the human genome from $10M to under $1,000 in less than 10 years, with NGS being the major driver. As a result, the bottlenecks have shifted from sequencing to library preparation. This process can be tedious and error prone when performed manually, as each library must be carefully prepared using time-consuming and resource-intensive processes (see further reading).

Automation of library preparation minimizes errors, reduces hands-on time and increases throughput. It can, for example, ramp up the efficiency of NGS for monitoring clinical trials, helping to accelerate clinical development projects.

Success in many NGS protocols relies on accurate and reproducible dispensing of carefully quantified library samples to ensure optimal cluster generation, and also carefully controlled dispensing of small volumes of expensive reagents.

Failure can result in time-consuming and expensive resequencing. To meet these needs, automated library preparation is now available to the majority of labs interested in streamlining NGS processes.

The Blog 6

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

TECAN JOURNAL 1/2017

LOW VOLUME PIPETTING

More with less – low volume pipette

trays, ANSI/SLAS format trays and

tips for high precision sub-microliter

nested trays, which improves throughput

dispensing

and lengthens walkaway times. Tecan’s 10 µl disposable tip can be used with

Consistently generating more data

the Liquid Handling Arm™ or Flexible

from lower reaction volumes relies on

Channel Arm™ of Freedom EVO® and

dispensing small volumes accurately

Fluent® liquid handling platforms

and reproducibly. This is why Tecan

respectively. The 10 µl disposable tips

has developed a portfolio of new 10 µl

are available in non-filtered and filtered

disposable pipette tips that increase

formats, and at two purity levels:

Further reading Baym M et al. Inexpensive multiplexed library preparation for megabase-sized genomes.

PLoS One, 22 May 2015, 10(5).

Lamble S et al. Improved workflows for high throughput

the precision of sub-microliter liquid handling. The result is improved success

• Tecan Pure has been developed

library preparation using the

rates in a number of applications,

for genomics research, forensics and

transposome-based Nextera®

including genomics research, cell-based

molecular diagnostics. These tips are

assays, forensics, molecular diagnostics

guaranteed to be free from human DNA,

system. BMC Biotechnol.

and microbiology.

PCR inhibitors, RNase and DNase.

The new 10 µl tips enable you to pipette

• Tecan Sterile is intended for cell-based

as little as 0.5 µl with confidence. This

assays and screens, and microbiology

gives an important advantage in

applications. These tips are guaranteed

applications that require low volume

to be sterile and free from human DNA,

pipetting due to high assay sensitivity,

RNase, DNase, pyrogens and endotoxins.

20 Nov 2013, 13, 104.

the expense of the reagent or the scarcity of the sample.

These tips, combined with the precision of automated liquid handling, will provide

An added benefit is that the new 10 µl

you with a reliable platform on which

tips are longer, enabling you to use a

to develop robust assay protocols

wider range of labware with deeper

that help you consistently generate

wells, such as PCR and 384-well plates.

more data from lower dispensed

The carrier choice is flexible, with a

volume.

range of formats including standard

www.tecan.com/blog TECAN JOURNAL 1/2017

7

MASS SPEC SAMPLE PREP

A smarter approach to LC-MS sample prep SPEware is the latest member

Routine analysis by mass spectrometry

and support of SPE consumables from

of the Tecan Group, providing

(MS) is now commonplace in a variety

a range of suppliers. Today it has grown

of sectors, including toxicology, drug

into a complete SPE solution provider,

discovery, forensics and hospital

as founder and CEO Phil Dimson

medicine. Despite this, sample clean-up

explained: “We started out very

and pre-analytical processing is still the

simply, working as a distributor and

analysis. The company

major challenge for these laboratories,

demonstrating the benefits of SPE

combines its proprietary smart

as traditional liquid-liquid extractions are

sample prep to our customers. We sold

chemistry consumables and

time consuming, difficult to automate

consumables from a variety of sources,

and don’t provide sufficient selectivity

and used our knowledge and

for more complex samples, creating a

understanding to show customers how

significant bottleneck. To overcome

SPE-based sample clean-up could

these issues, many laboratories have

increase the quality and reproducibility

help them achieve efficient

turned to solid phase extraction (SPE)

of their data, as well as reduce

laboratory workflows.

techniques, which not only represent a

maintenance requirements for

more time- and cost-effective approach

expensive MS instrumentation. As the

to sample clean-up, they are also more

popularity of this technology grew,

automation friendly, helping to increase

we found that more and more of our

throughput and improve reproducibility.

customers were not only looking to

However, a majority of companies

improve their data, they also wanted

advanced sample preparation solutions for laboratories performing mass spectrometry

positive pressure processors with an in-depth understanding of customers’ needs to

This application-focused approach is completely unique in the market, providing customers with a one-stop shop to support everything from sample reception to mass spec analysis.

Jim Leontis and Phil Dimson, SPEware

offering SPE sample preparation

help streamlining their workflows.

solutions simply provide the chemistry

More laboratories were using MS to test

and consumables required to perform

more analytes, and so they needed

the extraction, with little consideration

systems capable of processing hundreds

of how this can be practically

of samples a day, which naturally led to

implemented in the laboratory workflow

automation. We launched our first

or the impact of varying sample

automated processor in 2000, and this

processing parameters on downstream

proved to be the big breakthrough

analytical results.

for us, as nobody else was offering a combination of chemistry, automation

SPEware Corporation, founded in 1997,

and workflow expertise.”

was originally created to serve the

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TECAN JOURNAL 1/2017

emerging MS sample preparation

Jim Leontis, Director of Sales, took up

market, offering independent supply

the story: “Our understanding of this

MASS SPEC SAMPLE PREP

synergy between efficient workflows

last five percent that helps them to

and clean analytical results has been

achieve reliable, high quality sample

the foundation of our growth, and

preparation and reproducible results.”

today we offer a wide range of solutions that combine proprietary

Phil continued: “Until now, we have only

SPE consumables – using our high

been able to offer the benefits of this

performance CEREX® microparticulate

comprehensive service to the North

chemistry – with dedicated automated

American market, and so becoming part

processors and application support.

of the Tecan Group was a logical next

This application-focused approach is

step for the business. By combining our

completely unique in the market,

smart consumables and existing

providing customers with a one-stop

automated processors with Tecan’s

shop to support everything from

liquid handling and workflow automation

David Martyr, CEO of Tecan,

sample reception to mass spec analysis.”

expertise and worldwide support

commented: “We are excited to

network, we now have the opportunity

welcome SPEware to the Tecan Group.

“Our technical expertise is what really

to offer complete SPE sample

The company’s range of market-leading

sets SPEware apart. We have a

preparation solutions to the global

smart consumables and automated

dedicated laboratory with a team of

market. Integration of our consumables

processors is a natural fit for our

application scientists – a mix of

and processing options onto the

advanced liquid handling platforms,

automation specialists, chemists and

company’s liquid handling workstations

offering customers a real advantage

mass spectrometry experts – who work

will not only enable us to provide truly

for MS sample prep. This will allow us

directly with customers to assist them

turnkey solutions – including all the

to provide fully integrated solutions

in tailoring our solutions to their exact

hardware, software, consumables and

that offer exceptional time- and

workflow needs. While it may be

technical support required for successful

cost-savings for laboratories large and

possible for a customer to perform a lot

automation of MS sample preparation

small, anywhere in the world.”

of this work themselves, our in-depth

– it will also allow us to further increase

understanding of their processes can

throughput and better serve highly

make a big difference – providing that

regulated environments.”

To find out more about the SPEware range of sample preparation products, visit www.spewarecorporation.com

SPEware can provide assistance and advice on every step of the MS workflow TECAN JOURNAL 1/2017

9

DRUG DISCOVERY

Putting the pieces together Biomolecular interaction analysis plays an important role in the pharmaceutical industry. SensiQ Technologies has optimized surface plasmon resonance technology for drug discovery applications, developing an automated system that can provide rapid affinity data for prompt identification of candidate fragment activities.

Early stage drug discovery is a numbers

explore, as well as identifying technology

game, often requiring hundreds or

partners we can collaborate with to

thousands of compounds to be

move this field forward.”

screened to identify potential drug

Tom Jobe, Chief Operating Officer, SensiQ Technologies, Inc.

candidates that interact with the

Over the past decade, SensiQ has

therapeutic target of interest.

established a broad range of SPR-based

Biomolecular interaction analysis (BIA)

instruments to streamline BIA, including

using label-free surface plasmon

the SensiQ Pioneer family of fully

resonance (SPR) is regarded as the gold

automated benchtop systems. Tom

standard approach for the binding

continued: “We first introduced the

affinity and kinetic studies performed as

Pioneer platform around six years ago

part of this process. SensiQ

and, over time, this system has been

Technologies, Inc. in Oklahoma City,

updated and enhanced, and new

USA, has developed a portfolio of

versions introduced for specific

label-free SPR devices for the life

applications. We currently offer a choice

sciences market, enabling the

of three systems, including the latest

generation of real-time data on the

addition to the range, the Pioneer FE for

interactions between molecules. Tom

fragment screening. This is a cutting-edge

Jobe, the company’s Chief Operating

area of pharma research, where large

Officer, explained: “SensiQ was founded

libraries of protein fragments are used to

12 years ago, with a focus on developing

create molecules so small that the body’s

new SPR-based tools for life scientists.

immune system does not attack them.

It is this combination of pinpoint positioning accuracy and very high resolution liquid handling that has enabled us to create the extremely sensitive Pioneer FE system.

Our main market is pharma research,

The Pioneer FE has been developed in

principally early stage drug discovery

collaboration with a leading biotech

applications, where scientists are

company to optimize this process; it’s

looking for molecules that fit together

very much a case of fine-tuning our

very well and could eventually be

automated platform to offer superior

developed into novel therapeutics. We

throughput and sensitivity for binding

keep a very close eye on ongoing

affinity studies. The system uses our

developments in this sector, using

patented OneStep® gradient injection

feedback from both our customers and

technology, which helps to accelerate

key opinion leaders to enhance our

library screening by uniquely offering

products and develop new solutions

the ability to determine full kinetics and

that will streamline BIA studies. This

affinity from a single SPR injection.”

helps us to decide which areas to

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TECAN JOURNAL 1/2017

DRUG DISCOVERY

“When you design a new system, you

accuracy and very high resolution liquid

have a choice between developing all

handling that has enabled us to create the

the components in house, or using

extremely sensitive Pioneer FE system.”

established OEM solutions. We considered the in-house option but, as

“With any OEM product, it is also vital that

OEM components that suited our needs

system support will be available for a long

were already available, it made more

period, and Tecan’s history and reputation

sense to go down this route. We looked

were definitely an advantage. The local

at the various options available on the

Tecan team has been very supportive, and

market, and the resolution and accuracy

we have been able to work with Tecan on

offered by the Tecan Cavro® range was

a number of innovations for SPR

very compelling. We looked to the Tecan

automation. This partnership has also

team to recommend the most

given us greater insight into the direction

appropriate automation solutions for our

markets and technology are taking, which

purposes, and they suggested the Cavro

helps to guide our next generation of

Robotic Sample Processor (RSP) and

instruments. Working with Tecan to plan

Cavro Centris pumps. It is this set-up’s

where we are going next is very helpful,”

combination of pinpoint positioning

Tom concluded.

To find out more about Tecan Cavro components, visit partnering.tecan.com To learn more about SensiQ Technologies, go to www.sensiqtech.com

The Pioneer FE has been developed to simplify fragment analysis experiments TECAN JOURNAL 1/2017

11

CELL BIOLOGY

Vectoring in on success Genetic modification of mammalian cells is now a routine daily activity in academic and industrial R&D laboratories around the world, with viral vectors – such as lentivirus – commonly used to create new cellular models for a wide range of applications. SIRION Biotech specializes in the development of innovative gene delivery systems, helping to improve transduction and performance for both basic research and preclinical studies.

Viral vectors allow the efficient delivery

at SIRION, explained: “Our work centers

adeno-associated virus – offering

of genetic material into mammalian cells.

on providing individually engineered

methods suitable for both in vitro and in

This technology is now commonly used

genetic tools to modify mammalian cell

vivo applications. For many clients, we

in basic and medical research, enabling

lines. A majority of our business is in the

produce small to medium-sized batches

cell and molecular biologists to develop

preclinical sector, and ranges from

of vectors for use in their own

cellular models of healthy and diseased

designing and supplying viruses for use

laboratories, but we can also build full

tissues. SIRION Biotech, on the outskirts

in external laboratories, to partnerships

cellular models to over express, knock

of Munich, Germany, specializes in the

and collaborations aiming to develop

down or otherwise regulate one or more

creation of custom viral vectors for a

new vector technologies which will later

genes of interest.”

range of industrial and academic

be used in clinical applications, such as

research fields, including oncology,

gene therapies or the creation of

Silke Schrödel, Laboratory Head for Cell

neuroscience, regenerative medicine,

alternative vaccines.”

Culture, took up the story: “To build a

gene therapy, CAR-T cell therapy and

cellular model, we generally start by

vaccine development. Dr Carl Christel,

“We work with all the major viral vector

generating the viral vectors encoding

Senior Manager of Sales and Marketing

systems – adenovirus, lentivirus and

the gene of interest. We use lentiviral

The SIRION Biotech laboratory team

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TECAN JOURNAL 1/2017

CELL BIOLOGY

vectors 95 percent of the time, because

consistent results, even for cell lines with

this allows stable integration of genetic

low contrast. Just like the cell counting

material into the genome of most

algorithm, confluence measurements

dividing and non-dividing cells. We then

can be performed without the need for

transduce the target cell line using these

any complex adjustments.”

viral carriers, followed by extensive characterization – including various QC

“The system provides a standardized

checks and functional assays, depending

environment for our cells; we have full

on the project – and this is the stage

control over the temperature, humidity

where the Tecan reader comes into play.”

and gas partial pressures within the

To find out more about Tecan’s Spark reader, visit www.tecan.com/spark To learn more about SIRION Biotech go to www.sirion-biotech.com

reader chamber. This allows longer “We have used an Infinite® 200 PRO to

in-reader incubations without affecting

perform functional assays for a number

the consistency of results. The ability to

of years now, and have recently begun

incubate our cells in the reader also

evaluating the Spark® 10M for several

allows longer-term studies to be

applications. The Spark represents an

performed, without the operator needing

‘all-in-one’ system that is very well suited

to shuttle the plate back-and-forth

to our needs, and we have already

between the reader and a standard

tested the cell counting, luminescence

microplate incubator.”

and confluence modes for the assessment of our cellular models. It is

“We pride ourselves on the exceptional

very intuitive, and doesn’t require any

quality standards we adhere to for all our

complex adjustments between cell lines,

viral vectors and cellular models; we feel

helping us to accelerate and standardize

that this is what sets us apart from our

our processes, as well as ensuring that

competition internationally. We are trying

we meet the highest quality standards.”

to stay ahead of the game in terms of quality, and the Spark reader fits well

“The automated cell counting feature is

with this high standard. It provides us

a particularly interesting option, as

with a lot of flexibility for different

nearly every new project requires us to

experimental set-ups, helping us to

handle a new cell line. So far we have

deliver reliable and reproducible genetic

worked with over 200 different cell

tools to our clients,” Carl concluded.

types, and the instrument’s cell counting algorithm makes analyzing such a broad spectrum of cell types very straightforward; it is much easier and more reliable than manual cell counting methods. We are also using the cell confluence tool to monitor how specific genetic modifications influence cell

This allows longer in-reader incubations without affecting the consistency of results.

growth. This module offers very

TECAN JOURNAL 1/2017

13

FOOD SCIENCE

Putting milk to the test Milk testing plays an essential role in the dairy industry, ensuring the quality and safety of the end product. RAUDSZUS Electronic in Bavaria provides customized front-end sample preparation solutions to help laboratories cope with the high throughput demands of this work, enabling complete automation of the testing process, and has also recently introduced automated ELISA testing of milk for disease and pregnancy.

To accommodate wide-ranging throughput demands, RAUDSZUS systems incorporate Sias® Xantus® pipetting solutions from Tecan which can be tailored to individual needs. Michaela continued: “Each of our customers has specific demands and requires a different degree of automation. A small laboratory may only need to integrate a single sample preparation solution and analyzer, while a larger organization might connect several analyzers via a track system. It is important that our systems can be customized to provide exactly what the customer needs, and partnering with Tecan allows us to do this.”

Several of RAUDSZUS’ automated systems are based on the Sias Xantus instrument

Dairy products depend on high quality

laboratories with front-end sample

raw materials. Milk testing is therefore

preparation solutions for integration with

essential, and so samples are collected

laboratory analyzers, and works with

from dairy farms and transported to

Tecan to provide tailored systems for

specialist laboratories to ensure the

its customers. Michaela Raudszus-

quality of the product. Typically, this

Weidenschlager, Head of Sales and

involves high throughput analysis of

Project Management, explained: “Some

various milk constituents, including

routine sample preparation is required

inhibitor testing, spore analysis and

before any testing can take place,

disease screening. More recently, there

including warming and mixing samples,

has been growing demand for ELISA

uncapping and recapping vials, and

testing for various analytes in milk, further

sub-sampling for further analysis. When

increasing throughput needs. Automation

this is done manually, it is time consuming

is essential for efficient, cost-effective

and there is always the potential for

sample processing, offering labor savings

human errors and inconsistencies. Over

and ensuring reproducibility, and a

the last few years, we have seen more

growing number of companies are turning

and more laboratories – even small ones

to laboratory automation solutions that

– wanting to automate their analyses, not

include liquid handling stations, track

only to reduce costs, but also to ensure

systems and RFID traceability.

that every sample is treated identically.

“Our automation solutions handle all the sample preparation steps required for fully automated milk analysis. This

Our role is to provide automated RAUDSZUS Electronic, based near

solutions that can be integrated with

Munich in Germany’s Bavarian forest, is

existing laboratory analyzers to eliminate

focused on supplying milk testing

manual processing.”

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TECAN JOURNAL 1/2017

Michaela Raudszus-Weidenschlager, Head of Sales and Project Management

FOOD SCIENCE

It is important that our systems can be customized to provide exactly what the customer needs, and partnering with Tecan allows us to do this.

standardizes procedures, enhancing

– with no user-to-user variation – the

reproducibility and eliminating manual

process is full traceable as every action

handling errors. One big advantage of

is logged, and staff are freed up for

the Sias Xantus systems is the ability

other activities.”

to cherry-pick samples. Each customer uses vials with different dimensions,

“We have worked successfully with the

and the distance between them varies.

Sias Xantus for over a decade now. Our

The pipetting arm can be set up to

own in-house knowledge and experience

accommodate these differences, allowing

is perfect for installations using existing

multiple samples to be transferred

applications or equipment, and is

directly into a microplate in one step

complemented by support from Tecan

using a multi-channel pipetting arm. This

when designing a bespoke system for a

is much quicker than sample-by-sample

specialist process. In just a few hours we

transfer, and is a big improvement.

can visit the company and discuss every

Equally important is the option to choose

detail of the project, using our combined

disposable or washable fixed tips;

expertise to devise a solution that

although the majority of customers

simplifies the customer’s workflow,”

choose fixed tips, there are occasions

Michaela concluded.

To find out more about the Sias Xantus, visit partnering.tecan.com/products/sias To learn more about RAUDSZUS Electronic, go to www.raudszus.de

when disposable tips are a necessity.”

“Recently, there has been a surge in ELISA testing, particularly for pregnancy markers, as this is much cheaper for farmers than a veterinary call-out. When milk samples are sent to the laboratory, they simply request this additional test on an ad hoc basis, and the result is delivered via an online database. This is a huge benefit for farmers and has led to a large increase in ELISA sample numbers, with some laboratories now running as many as 50 microplates a day. Larger platforms are needed to cope with this demand, and we are currently installing a fully automated solution with two pipettors and an integrated plate reader at a customer site, enabling end-to-end processing from receipt of the initial sample to result readout. This offers several advantages; each step is perfectly timed and performed in the correct order

Several analyzers can be connected via a track system

TECAN JOURNAL 1/2017

15

MOLECULAR GENETICS

Finding the perfect match The success of hematopoietic stem cell donation is highly dependent on a close match between the donor and recipient human leukocyte antigen (HLA) alleles. DKMS Life Science Lab performs HLA typing of over a million potential donors a year, relying on automation to provide a cost-effective, high quality solution that delivers reliable high sample throughput.

Johanna Andreas, Automation Specialist

rejection. Some patients are fortunate

of samples are screened each week, which

enough to find a donor within their own

would be difficult – if not impossible – to

family, but the majority will depend on a

do manually. Automation is the obvious

donation from a completely unrelated

solution, allowing procedures to be

person. However, the likelihood of

standardized and more samples

finding a suitable donor outside the

processed, more rapidly and with greater

family is very low. To maximize the

reliability, helping to reduce the number of

chances of finding a match in as short a

repeat analyses required. This saves both

time as possible, donor registries have

staff time and reagent costs, ensuring that

been established around the world.

analytical workflows are as efficient and cost effective as possible. Johanna

With over six million registered donors,

Andreas, Automation Specialist in the

DKMS is the world’s largest bone marrow

Laboratory Technology Department,

Hematopoietic stem cell transplantation

donor center, and its Life Science Lab in

explained: “Our laboratory types around

is a treatment option for patients

Dresden, Germany, is one of the most

1.3 million samples a year – 25,000 a

suffering from certain cancers of the

advanced genotyping service providers

week! To cope with this workload, we use

blood, such as multiple myeloma or

globally. Rapid, reliable HLA typing of

liquid handling workstations to automate

leukemia. For the transplant to be

potential donors is essential, requiring the

our protocols, helping to streamline the

successful, it is essential that the donor’s

extraction of DNA from blood or buccal

various workflows.”

HLA type closely matches the recipient’s

swab samples to determine the exact

HLA type, minimizing the potential for

genetic profile of the donor. Vast numbers

Johanna continued: “When blood samples arrive at the laboratory, they are automatically aliquoted from blood collection tubes into 96-well plates, ready for DNA isolation. Until recently, this was performed on an older Tecan liquid handling platform which, after nearly 10 years of service, has been replaced by a Freedom EVO® 150. With just a single Liquid Handling Arm™ (LiHa), this is the most basic Tecan platform in our lab, but it offers straightforward, robust performance for this simple, highly repetitive task.”

“Once the DNA has been isolated, it is quantified by fluorescence measurements using an Infinite® 200 PRO reader. This was originally a standalone instrument, which in 2016 was integrated into an additional new Freedom EVO 150; the fifth of its kind in our lab. Prior to this, DNA

Automation on a Freedom EVO platform enables cost-effective, high throughput HLA typing 16

TECAN JOURNAL 1/2017

MOLECULAR GENETICS

quantification was a tedious job for the

ready for HLA amplicon sequencing and

lab personnel, as each plate had to be

analysis using Illumina next generation

measured independently. This new

sequencing technology.”

platform also features a plate storage carousel – based on a LiCONiC LPX220 –

In addition to offering higher throughput

as well as a refillable trough for SYBR®

capabilities, automation helps to enhance

Green dye reagent. This set-up enables the

the quality and reliability of analytical

quantification of 70 plates in a single

protocols. This is reflected by the low

run, a real time and workload saver.”

number of repeat analyses performed by the laboratory. “Despite an ever-increasing

“The samples are then reformatted on

workload – we are now typing tens of

a Freedom EVO 200 workstation,

thousands of samples each week – the

sorting them into 384-well plates

number of repeat measurements we

containing either low or high

perform is steadily decreasing. Our PCR

concentrations of DNA in preparation

assays look at 12 different loci and, even if

for the next stage of the typing process,

an analysis is inconclusive and needs to be

PCR. This workstation uses two LiHas

repeated, we still save time by performing

to reformat two separate panels in

automated cherry-picking overnight – also

To find out more about Tecan’s

parallel, helping us to manage our high

on Tecan platforms.”

molecular diagnostics solutions,

throughput requirements.”

The Freedom EVO offers straightforward, robust pipetting of samples

visit www.tecan.com/genomics “We have been using our Tecan liquid

“We have successfully automated both

handling workstations for almost 10 years

To learn more about DKMS, visit

microplate- and microfluidics-based PCR

now, and are very happy with them. The

protocols on two additional liquid handling

large workdecks have space for a selection

www.dkms-lab.de

platforms – a Freedom EVO 150 and a

of different carriers, making the systems

Freedom EVO 200. The PCR method of

very versatile and giving us the flexibility

choice is dependent on the DNA

to use them for a range of assays. Most

concentration of the sample. For high

importantly, they are reliable systems and,

concentration samples, we use the

in the case of any issues, we receive good

microfluidics-based assay. The samples,

support. This is absolutely essential when

molecular identifiers and master mixes are

you have such a high sample throughput,

transferred to the sample inlets of a 192.24

as any unplanned downtime can cause a

Dynamic Array™ IFC (Fluidigm), and

huge backlog to build up very quickly,”

target-specific primers are added. The

concluded Johanna.

entire reaction takes place within the chip, and so the reagent volumes used are really small – the total assay volume is less than 10 nanoliters – which helps reduce the cost of the assay. For low concentration DNA samples, PCR is performed in 384-well plates. Finally the PCR products are harvested, pooled, purified and quantified,

Most importantly, they are very reliable, [which] is absolutely essential when you have such a high sample throughput.

TECAN JOURNAL 1/2017

17

MEDICAL GENETICS

A (cyto)genetic revelation Specialist laboratories engaged in molecular genetics and cytogenetics are turning to automation to cope with ever-increasing sample numbers, implementing tailored solutions designed to handle a range of materials and meet specific testing needs.

Dr Sarah Volpert, Head of Cytogenetics & Cancer Cytogenetics Laboratories, amedes-group

y implementing B automated protocols, we have standardized quality and improved reproducibility.

18

TECAN JOURNAL 1/2017

The amedes group is a network of 60

wagnerstibbe of Laboratory Medicine,

laboratories and medical practices

Hemostasis, Human Genetics and

located across Germany and Belgium

Microbiology in Hannover – focus chiefly

that provides interdisciplinary medical

on genetic analyses, employing state-of-

diagnostic services for patients, doctors

the-art technologies for molecular

and hospitals, as well as delivering

genetics and cytogenetic investigations.

specialist laboratory management

To cope with ever-increasing sample

services to more than 40 hospital

numbers and standardize procedures,

laboratories. The laboratories offer a

the laboratories have implemented

wide range of tests, including standard

identical automation solutions tailored

and specialist laboratory medicine,

to their workflows, helping to ensure the

microbiology, gynecology, oncology,

quality and reliability of these complex

pathology, endocrinology, cytology,

processes within each lab and between

hemostasis, dysplasia, prenatal medicine

the two sites. Dr Sarah Volpert, Head of

and genetics, processing more than

Cytogenetics & Cancer Cytogenetics

150,000 samples per day.

Laboratories, amedes-group, explained: “Our main focus is on human genetics,

Two of the group’s German laboratories

particularly prenatal screening and

– the MVZ Department of Laboratory

diagnosis, and oncology. We use a

Medicine and Clinical Genetics Rhein/

variety of molecular genetic techniques

Ruhr in Essen and the amedes MVZ

– Sanger and next generation

The Tecan Integration Group customized the Freedom EVO to fit amedes’ exact needs

MEDICAL GENETICS

The amedes team

sequencing, and array technologies – as

the company as the instruments are high

results of genetic analyses to decide on

well as cytogenetics by routine analysis

quality and we are familiar with their

the most appropriate course of

of G-banded chromosomes and

operation. We also set great store by

treatment. Not only is the system time

fluorescence in situ hybridization (FISH).

good service and know from past

and cost efficient, but there are benefits

In the past, this work has been done

experience that the company responds

for staff too; as much less hands-on

manually. However, with sample numbers

quickly if we need help, which is essential

time is required, highly qualified,

continually rising and a need to reduce

to avoid any delays in sample analysis.”

experienced members of staff now have

the time to results without compromising

extra time to focus on more interesting,

on quality, optimizing our processes to

“With the help of the Tecan Integration

make the workflow as efficient as

Group (TIG), we transferred our manual

possible was essential. Automation was

processes onto a Freedom EVO®*

“We have a very good relationship with

the logical way forward.”

platform adapted to our needs, and are

Tecan. It is a well-known brand that we

reaping the benefits. However good

have faith in, and the company gives us

Sarah continued: “As one of the largest

scientists are, there will always be

very good support. We have local

cytogenetic laboratories in Germany, we

individual differences in manual

representatives who we know, and the

handle a wide range of materials,

techniques; by implementing automated

central hotlines always guarantee quick

including chorion and amniotic cells,

protocols, we have standardized quality

communication, which is important for

fetal and peripheral blood, and bone

and improved reproducibility.

us. We really appreciate the company’s

marrow aspirates and tumor tissues from

Turnaround times are also increasingly

personal approach,” Sarah concluded.

cancer patients. It is really important to

important. Automating our processes as

have the flexibility to adapt our sample

much as possible enables us to operate

preparation processes to the individual

for 12 hours, six days a week, starting

requirements of each specimen type,

earlier and taking advantage of the

To find out more about

and also to be able to expand to

system’s huge capacity to run larger,

Tecan’s clinical diagnostics

accommodate more samples in the

48-sample batches when we need to.

future, if necessary. We needed a

This is particularly beneficial at peak

solutions, visit www.tecan.com/

bespoke automated platform tailored to

periods, helping to reduce the

meet the specific demands of our

underlying run times and allowing

workflows. We have used Tecan

results to be reported more rapidly,

platforms in our clinical laboratories for a

which is especially important in prenatal

long time and so, although we looked at

diagnostics and oncology, where

other systems, it made sense to stay with

clinicians increasingly depend on the

less routine tasks.”

clinicaldiagnostics To learn more about amedes, go to www.amedes-group.com

*Not for clinical use in the USA

TECAN JOURNAL 1/2017

19

CLINICAL DIAGNOSTICS

Effective sample preparation minimizes mass spectrometry maintenance Testosterone levels are typically determined using automated immunoassay analyzers, but this has limitations. Liquid chromatography-tandem mass spectrometry (LC-MSMS) offers a selective and accurate alternative, and the Center for Advanced Laboratory Medicine at the University of California San Diego is using a novel extraction technology to automate sample preparation for this technique.

Senior CLS Specialist Judy Stone

Judy continued: “Reliable, accurate

“When I moved to UCSD-CALM,

results must also be cost effective to

I approached Tecan about doing some

be useful for patient care. In terms of

collaborative studies using a

materials, analytes such as testosterone

Freedom EVO® workstation and the

can often be measured at a lower cost

AC Extraction Plate, starting with

using LC-MSMS compared to an

testosterone analysis. Most clinical

automated immunoassay analyzer.

laboratories do these tests on an

However, the trade-off is that LC-MSMS

automated immunoassay instrument,

is labor intensive; sample preparation

which works well for samples from men

involves a great deal of pipetting, and

with normal testosterone levels, but is

there is always concern about the risk of

not always the best technique for

mixing up samples. In addition, there are

samples from women, children or men

ergonomic considerations associated

with low serum testosterone. LC-MSMS

with manual processes. Automating

offers better accuracy and selectivity,

sample preparation on a liquid handling

but robust and reliable preparation of

workstation can help with these issues.”

large sample numbers is difficult using

The University of California San Diego Center for Advanced Laboratory Medicine (UCSD-CALM) uses state-ofthe-art technologies to provide diagnostic medicine and pathology services, as well as developing new

ith cleaner extracted samples, instruments W need maintenance less often, minimizing unplanned downtime and sample backlogs.

diagnostic assays for therapeutic applications. Mass spectrometry (MS)

“I was working at another laboratory

manual liquid-liquid extraction. This

is an important analytical tool in the

when Tecan launched the

process can be tedious and hard to

laboratory, but the challenge is

AC Extraction Plate™ for MS sample

automate, and requires some expertise

developing and validating reliable,

preparation. I tried it, and found it so

to use routinely with acceptable

reproducible sample preparation

simple to use; I just manually pipetted

performance. In contrast, the

methods suited to a clinical setting.

the samples into the plate and used the

AC Extraction Plate is extremely simple,

Judy Stone, Senior CLS Specialist in the

existing instrument parameters, and it

requiring just a plate shaker and

Toxicology Laboratory, explained: “I’ve

worked the first time, which was very

accurate pipetting, which can be

been working with MS for about 25

impressive. However, we had just

reproducibly performed by the

years, initially with gas chromatography-

invested a huge amount of time and

Freedom EVO. We can prepare a batch

mass spectrometry. More recently, the

resources in validating a different

of samples on the liquid handling

focus has been on LC-MSMS. This has

sample preparation method and,

platform with as little as 15 minutes of

become the technique of choice for

as this process was almost complete,

hands-on time, or from start to finish in

many applications, with laboratories

it simply wasn’t realistic to change

about 90 minutes, which is a significant

developing and validating new methods

direction at that point.”

labor savings. Manual preparation can

for testing patient samples.”

20

TECAN JOURNAL 1/2017

CLINICAL DIAGNOSTICS

take from 30 minutes of hands-on time

“Ultimately, our goal is to increase

unplanned downtime and sample

for a small batch to two and a half hours

both our test menu and the number

backlogs. When it comes to MS

for larger numbers of samples. The

of samples performed per test on a

sample preparation, I firmly believe

results after using the AC Extraction Plate

daily basis. We already perform

that clean-up is worth the time,”

for sample preparation were so

25-hydroxyvitamin D testing by mass

Judy concluded.

reproducible during validation that we

spectrometry, and plan to automate

are considering whether we actually

the manual pipetting steps of this

need to run a full set of 11 calibration

process on the Freedom EVO in the

standards with each batch of samples.

future. We are also developing an

AC Extraction Plate visit

If comparable results can be obtained

AC Extraction Plate method for

www.tecan.com/acplate

with just two standards per batch –

1,25-dihydroxyvitamin D, which will be

the highest and lowest concentration

challenging as it is present at much

To learn more about UCSD-

calibrators – or using a standard curve

lower levels than 25-hydroxyvitamin D.

CALM, go to pathology.ucsd.

from another day updated with a couple

In the long term, investment in sample

of key calibrators, this is a clear benefit

preparation techniques such as the

edu/ucsd_center_for_advanced_

to the laboratory. We are retrospectively

AC Extraction Plate makes sense as, with

studying our data to see if this is viable,

cleaner extracted samples, instruments

and it looks very promising so far.”

need maintenance less often, minimizing

To find out more about Tecan’s

laboratory_medicine.htm

Automation helps eliminate tedious manual pipetting TECAN JOURNAL 1/2017

21

DRUG DISCOVERY

Lighter work for many hands Drug development pipelines are under ever-increasing pressure to deliver more comprehensive data in a shorter timeframe, while reducing costs and making in vitro assay results more relevant to in vivo drug behavior. Assay automation and miniaturization has become essential for the oncology research team in Bayer’s Pharmaceuticals Division.

Knowledge of the relationship between

Recent trends towards assay

technologies – such as Tecan’s D300e

the dose, bioavailability and clinical

miniaturization have significantly

Digital Dispenser – capable of

effects of a drug candidate are

reduced the cost and effort for drug

reproducible dispensing in the nano- to

fundamental to the development of new

titration studies, with a shift towards

picoliter range. The ability to dispense

therapeutics. Without in-depth

performing these experiments earlier on

drug candidates directly into assay plates

characterization of the effects of a

in the drug development workflow.

has transformed the workflows of the

compound at a biochemical and cellular

Collecting more comprehensive data on

oncology research laboratories at Bayer,

level, it would be impossible to safely

early compounds supports the process

as Carmen Wegner, biology lab assistant,

progress drug candidates to the clinical

of compound optimization and

explained: “We have three teams in

phases of development. Drug titration

identification of the most promising

oncology research, more than 60 people

studies are, therefore, at the heart of the

candidates for the next steps of

overall, and we perform a wide range of

drug development process, with many

investigation. The reduction in assay

different activities on a daily basis. Our

hundreds of dose-response curves

volumes has been driven by the

group is primarily responsible for

generated each day across the globe.

development of novel liquid handling

performing functional assays, testing

The D300 has changed the way Bayer’s Pharmaceuticals Division approaches many assays

22

TECAN JOURNAL 1/2017

DRUG DISCOVERY

compounds from our chemical department against human or animal cellular models of various cancers.”

“The timescales for our development projects have become much shorter,

The way our laboratory approaches many assays has really changed.

so anything that helps to accelerate research is much appreciated. We acquired the first D300 Digital Dispenser in 2013 and, since then, the way our laboratory approaches many assays has really changed. The Tecan D300s are very easy to use, and only require a brief introduction. After loading the assay plate and the Dispensehead cartridge containing the compound, the instrument takes care of everything else. This saves a great amount of staff time in planning and setting up experiments. There is no need for manual pipetting anymore, and the D300 performs calculations automatically – based on your target final concentrations.”

“Direct digital dispensing allows nanoliters – or even picoliters – of compound to be reliably added to a microplate well, which we couldn’t achieve manually. This eliminates the need for serial dilutions – as well as media changes for many cell-based assays – which also saves a lot of staff time, and reduces the amount of compound, reagent and consumables waste.”

To find out more about Tecan’s

“We now have five D300 instruments

D300e Digital Dispenser, visit

in the department – with more than

www.tecan.com/d300e

60 users. We find the software intuitive, and the systems are usually maintenance

To learn more about the

free. We only need Tecan’s technical

Pharmaceuticals Division of

support to help us program special

Bayer go to

applications. Overall, we are very excited about the instruments.”

www.pharma.bayer.com

TECAN JOURNAL 1/2017

23

DRUG DISCOVERY

A natural affinity Receptor binding assays form an integral part of the preclinical screening service provided by Eurofins Pharma Discovery Services division. The first stage of the protocol is the transfer of tissue samples to a 96-well plate, a process that must be carefully performed to avoid any cross-contamination.

Pharma Discovery Services Receptor binding assays are a key tool in

liquid handling platform. This has a

third workstation – a Freedom EVO 100

the pharma industry, enabling scientists

number of benefits: it is highly flexible –

– customized for our tissue dispensing

to study a compound’s affinity for a

allowing a variety of sample transfer

protocols.”

chosen receptor. Compounds are

requirements to be accommodated –

dispensed into a microplate, then

assay plate preparation is consistent,

The tissue dispensing process begins with

membrane receptors and the

and cross-contamination is virtually

uploading the assay plate preparation

radiolabeled ligands are added. This is

eliminated compared to manual

requirements to the LIMS. Barcoded low

followed by an incubation step, after

processes. In addition, the automated

residual volume troughs containing the

which the radioligand-receptor complex

tissue dispensing platform provides

tissue preparations – five tissue types per

is harvested, and the amount of

full sample traceability, which is

batch – are loaded onto the workstation

radioactivity is determined to

increasingly being demanded by

and scanned by a PosID™ Positive

calculate the degree of binding

customers in this sector. Scientists gain

Identification System. Information

that has occurred.

too, as they have extra time to devote

corresponding to the barcode

to other tasks. Andy Chou, an associate Eurofins Pharma Discovery Services division, based in Taipei, Taiwan, is a contract

scientist in the Molecular Operation Department, explained: “Our department mainly performs

identification is extracted from the LIMS and a Freedom EVOware® worklist is created for the preparation of 96-well assay plates. Up to six 96-well assay

research organization with a

receptor binding assays, which

plates per batch are placed on the carrier,

worldwide customer base of

involve several liquid handling

and the preparations are transferred into

pharmaceutical companies

steps. These include dispensing

the plates via a MultiChannel Arm™ 96

engaged in drug discovery.

of test compounds and tissue

(MCA96) using disposable tips. Once the

The company has several

preparations, as well as the

transfer is complete, a report is generated

decades of experience in

addition of radioligands. More

for each assay plate and exported to the

preclinical screening and

than 10 years ago, we automated

LIMS, ensuring sample traceability.

offers a comprehensive

our compound dilutions on a

Downstream processing – incubation,

service portfolio. To help

Freedom EVO® platform,

harvesting and radioactivity

with its radioligand receptor

followed a few years later by the

measurements – then takes place.

binding assays, Eurofins

installation of a second system

has automated its tissue

for addition of the radioligands.

Phyllis Tsai, also an associate scientist in

dispensing process on a

More recently, we have added a

the Molecular Operation Department,

The risk of cross-contamination was always a big concern, but automated pipetting using disposable tips eliminates this problem.

24

TECAN JOURNAL 1/2017

DRUG DISCOVERY

The Eurofins team

continued: “With a diverse range of

consistency of the assay plates prepared

requests from our customers, we need

is good too, with the inter-plate variation

To find out more about

to be extremely flexible in terms of the

around 2 % CV. Implementing automated

Tecan’s molecular diagnostics

assays we perform, and the Freedom EVO

procedures that employ barcode reading

solutions, visit

helps us to achieve this. Of all the systems

– importing and exporting data directly

www.tecan.com/cellbiology

we assessed, it was the platform best

from and to the LIMS – is another key

suited to our needs, enabling us to pipette

benefit, linking each tissue preparation to

by row or column – 8- and 12-channel

a specific position in the microplate. This

dispensing – using the MCA96. It also

ensures we maintain the sample

allows us to pipette into two rows of a

traceability that is vital to our customers,”

microplate simultaneously, a functionality

Andy concluded.

To learn more about Eurofins Pharma Discovery Services, go to www.eurofinspanlabs.com

that is not available on other liquid handling workstations. Another important feature of the system is its ability to incorporate our customized 24-well troughs, which have a low residual volume

The Freedom EVO offers flexibility and sample traceability for receptor binding assays

Dispensing compounds Adding membrane receptor

of less than 0.8 ml, on a Te-Shake™ shaker.

Tissue preparations are very precious, and

Adding radiolabeled ligand

it is important to minimize any waste as far as possible; the customized troughs significantly reduce the tissue volume

Incubation

required for our assays.”

Harvesting

“Previously, the risk of cross-conta mination was always a big concern, but

Counting on the reader

automated pipetting using disposable tips eliminates this problem, increasing the robustness of our assay results. The

Radioligand binding assay workflow

TECAN JOURNAL 1/2017

25

BIOPROCESSING

Faster processing for biosimilars The biosimilars market is expanding rapidly as the patents expire for an increasing number of high profile biopharmaceutical agents. The complex nature of biologics requires extensive characterization of the production techniques and in vivo effects of new biosimilars before they can be released onto the market. Coherus Biosciences is using advanced laboratory automation to help screen chromatography conditions as part of its downstream purification processes for new biosimilars.

The importance of biologically-derived therapeutics is of ever growing importance to the pharmaceutical sector, offering more specific and targeted therapies for the treatment of a wide range of conditions and diseases. Unlike generic versions of small molecule drugs, which have chemically identical active ingredients to marketed products, most biologics are heterogeneous preparations composed of multiple protein or antibody subspecies, as well as a variety of other closely associated biomolecules. They are therefore complex to both manufacture and purify, and this presents a major challenge for follow-on manufacturing of generic versions of these medicines – known as biosimilars – once their patents expire.

Coherus Biosciences – based in Redwood City, California – develops, manufactures and markets high quality biosimilar therapeutics with the aim of reducing healthcare costs for treating chronic or life threatening diseases. Founded in 2010 by a group of like-minded industry veterans with extensive experience in the biopharmaceutical industry, the company focuses on inflammatory diseases and

Brian Williamson with Coherus’ Fluent Laboratory Automation Solution

cancers, aiming to expand access to biologically-derived medicines.

biologic. Chromatography is commonly

downstream laboratory, explained: “In

used to separate target molecules from

our development program, we screen

Downstream processing is an essential

the rest of the production cell culture,

many different chromatography

element of the biosimilar workflow,

requiring rigorous screening of

conditions and media to identify

ensuring reliable and reproducible

chromatography conditions to enable

protocols capable of separating out

manufacture of a product showing the

efficient extraction and recovery. Brian

various proteins of interest from all the

same in vivo effect as the original

Williamson, a senior scientist in Coherus’

other cell culture components, such as

26

TECAN JOURNAL 1/2017

BIOPROCESSING

Our Tecan systems are enabling us to run new types of experiments that were not previously possible, generating much more data and making it much easier to answer questions and find solutions for our manufacturing environment. degraded proteins and product-related

the lab, as this frees up the Freedom EVO

contaminants. We built up our

platform for large-scale screening of

laboratory from scratch on a limited

chromatography conditions,” Brian

budget, but I requested automated

continued. “The Fluent has an eight-

equipment to help accelerate the whole

channel Flexible Channel Arm™ with

downstream development cycle. It’s

disposable tips, which not only allows us

obviously a commitment on my part, as

to quickly perform repetitive liquid

there’s a significant learning curve with

handling tasks – such as preparing

any advanced laboratory equipment, but

cultures and batching plates – it also

being able to automate chromatography

gives us the flexibility to run PhyTip®

experiments is very helpful; it allows us

columns (PhyNexus) for small-scale

to very quickly screen conditions to find

and lower-fidelity separations. This

a protocol that is suitable for use in a

technology is ideally suited to sample

manufacturing environment.”

preparation applications, offering rapid clean-up of eight samples in parallel for

“I was already familiar with the various

our analytical laboratory.”

options on the market, and chose Tecan liquid handling platforms because I had

“Our Tecan systems are enabling us to

some limited experience of using the

run new types of experiments that were

company’s instruments in a previous role,

not previously possible, generating

and I could see how well they would fit

much more data and making it much

into our whole development workflow.

easier to answer questions and find

A lot of work has been done in this field

solutions that are appropriate to

with Atoll MediaScout® RoboColumns® –

implement in a manufacturing

it’s clearly a front runner in the sector –

environment. Both systems, each with

and combining this technology with the

a different focus, are great time savers

Freedom EVO® platform is ideal, allowing

and really benefit our workflow; the

us to run eight chromatography

Freedom EVO/RoboColumns

separation experiments in parallel. There

combination is clearly the way to go for

are other systems on the market that

large-scale chromatography condition

offer a similar approach, but they just

screening, and the Fluent offers more

don’t have the degree of fidelity that this

advanced automation, with higher

combination does.”

precision and reproducibility. The

The Freedom EVO allows complete automation of the Atoll MediaScout RoboColumns workflow

support we receive from Tecan is also “We are now running about 16 columns

fantastic; we always get a quick reply to

every day, with each cycle of eight

any questions we have, which is a really

experiments taking six to 10 hours. This

good way to resolve issues that come

gives us an eight-fold increase in

up,” Brian concluded.

Up to eight chromatography experiments can be run in parallel

throughput compared to manual methods, as a researcher could only run two or three columns a day. The samples collected from the MediaScout

To learn more about Tecan’s

columns are then either analyzed in our

bioprocessing solutions, visit

laboratory to find chromatography

www.tecan.com/bioprocessing

conditions that can be scaled up for manufacturing purposes, or by our

For more information on

analytical laboratory to support other

Coherus Biosciences, go to

studies or regulatory filings.”

www.coherus.com

“We have also purchased a Fluent® 480 Laboratory Automation Solution to perform general liquid handling tasks in

TECAN JOURNAL 1/2017

27

CLINICAL DIAGNOSTICS

Time saved in diagnostic vitamin B testing Mass spectrometry is rapidly becoming the method of choice for quantitative analysis of micronutrients such as vitamins B1, B6, B12 and D, as well as for steroids, hormones and many other drugs. For clinical laboratories, the bottleneck of MS-based techniques is not the analysis, but the pre-processing of the samples to remove proteins and other biological molecules that could interfere with the results.

The role of micronutrients in maintaining

Holland. It is a very busy laboratory,

platform following a demonstration in

good health and well-being in an aging

reporting over 10,000 patient results

Amsterdam. Our aim was to completely

population has become increasingly well

every day, so we need rapid and

automate the LC-MS sample preparation

understood over the past 30 years, but it

efficient analytical processes to ensure

and so, based on Tecan’s advice,

is only in the last decade or so that reliable

we can manage this workload.”

we purchased a Freedom EVO 150

assays to effectively detect dietary or

workstation.”

metabolic deficiencies of many of these

“We originally began quantifying

nutrients have become common. This

vitamins B1 and B6 over 20 years

The laboratory’s Freedom EVO was

combination of better understanding and

ago on a HPLC system, however, the

commissioned in the summer of 2016,

more effective testing has seen a huge

assay involves a derivatization step

and has been optimized to work in

increase in the number of requests clinical

followed by a lengthy analysis time. It

a 96-well microplate format. Plates

laboratories receive from both primary

also requires a lot of manual pipetting

containing patients’ hemolyzed whole

and secondary care, requiring a change

– technicians needed to spend several

blood samples, calibrators and quality

in working practices to accommodate

hours at a time performing very

control samples are placed on the deck

their growing workloads.

repetitive tasks – and so we recently

of the instrument, and trichloroacetic

looked into automating the sample

acid (TCA) is added to each well to

Requests for vitamins B1 (thiamine)

preparation to increase throughput,

precipitate out the plasma proteins.

and B6 (pyridoxine) – which play roles

reduce variability and eliminate pipetting

The plate is then sealed and spun down

in energy uptake from carbohydrates

errors. Instead of simply automating

in a centrifuge, and the supernatant

and fats respectively, as well as being

our existing protocol, we chose to

from each well is transferred to a fresh

involved in many other metabolic

switch to an ultra high performance

96-well plate using the Tecan system.

pathways – are among those that have

liquid chromatography with tandem

This analysis-ready plate is then

seen a large increase. The Clinical

MS (UHPLC-MSMS) technique, using

re-sealed and transferred to a

Chemistry Department at Noordwest

an automation-friendly protein

standalone UHPLC-MSMS system.

Ziekenhuisgroep (Northwest Clinics)

precipitation step for pre-analytical

Edwin continued: “Although we did not

Alkmaar in the

have any previous

Netherlands now

experience with

processes over 19,000 assays a year for each of these metabolites alone. Edwin ten Boekel, a Clinical Chemist in the

Most importantly, automation of sample preparation on the Freedom EVO has halved the time required for processing the same number of samples.

department,

Tecan platforms, once you familiarize yourself with the Freedom EVO, the system is very easy to use. The customer support from Tecan has also

explained: “Our

been good; they

department is one of two laboratories

sample processing. We investigated

are friendly and we never have to wait

that are part of the Northwest Clinics,

several systems to automate this

long for replies to our queries. We have

serving a population of around 600,000

sample preparation, and I was very

now implemented several protocols on

people across the province of North

impressed with the Freedom EVO®

the instrument, and the reproducibility

28

TECAN JOURNAL 1/2017

CLINICAL DIAGNOSTICS

and repeatability of the automated

to increase traceability, which is obviously

procedure is improved compared to our

very important in a diagnostics lab.

prior pipetting procedures. We carried

Most importantly, automation of sample

out a control experiment by repeatedly

preparation on the Freedom EVO has

processing different batches of the same

halved the time required for processing

samples, and obtained a CV of less than

the same number of samples. This not

five percent, which is well within our

only eliminates the need for staff to

acceptable limits. By using a handheld

repetitively pipette samples, it also

barcode scanner and barcoded

releases them for other tasks,”

microplates, we have also been able

Edwin concluded.

To find out more on Tecan’s clinical solutions, visit diagnostics.tecan.com For more information on Noordwest Ziekenhuisgroep, go to www.nwz.nl/English/About-us

NWZ’s Freedom EVO offers fully automated pre-analytical processing

TECAN JOURNAL 1/2017

29

BIOMEDICAL ENGINEERING

Designed for flexibility, built for speed Multidisciplinary research calls for multifunctional laboratory equipment capable of rapidly switching between applications.

Staff in the Department of Biomedical Engineering at the TU Eindhoven understand that having the right instruments for your workflow can allow more users to benefit and help to accelerate research.

– despite the age of our Safire2 reader – but the growing number of bioluminescence studies we are now performing, as well as an increase in students in the lab, means that we had effectively run out of instrument capacity. We looked at the various systems on the market, and the Spark® was an excellent match for our needs.

The ability to switch between filter- and monochromator-based measurements is ideal for a multidisciplinary group, and the Spark’s bioluminescence module has a 40 filter set that enables you to perform complete luminescence scans, which is a huge advantage for assay development. Having all three readers from the same manufacturer also simplifies staff training and equipment maintenance.”

Members of the Chemical Biology Group

“One of the biggest advantages for our lab is the system’s Te-Cool™ option,

Biomedical engineering is a broad

antibody-based sensors to DNA-based

which was launched just before we

field, with scientists from numerous

reaction networks, nuclear receptors

purchased our Spark reader. Because

disciplines coming together to develop

and supramolecular architectures.

we’re such a big lab, our readers are

innovative solutions to challenges in

It’s a very busy environment.”

in high demand and constant use.

the pharmaceutical, diagnostic and

Being able to accurately set the assay

healthcare sectors. The Chemical

This multidisciplinary team requires

temperature and actively cool the

Biology Group in Eindhoven University

laboratory equipment that is equally

measurement chamber is therefore

of Technology’s Department of

versatile, enabling a wide range of

a real boost to our productivity. For

Biomedical Engineering is even more

activities to be performed quickly and

example, one user’s assay may require

diverse than most, as it was formed by

easily. “All our instruments need to

the measurement temperature to be

merging together three existing research

be both robust and flexible,” Anniek

fixed at 37 °C, while the next user

groups. The laboratory is now home to

continued. “We have had two Tecan

may want to perform an experiment

over 120 researchers, with a wide range

multimode readers – a Safire2™ and

at 20 °C. Previously, this could lead to

of research interests. Anniek den Hamer,

an Infinite® F500 – in the laboratory

long delays while waiting for the reader

a PhD student in the group, explained:

since the group was created, and

to cool and equilibrate to the correct

“We’re a big lab with a lot people – not

perform a variety of measurements,

temperature, with this time effectively

just PhD students and postdocs, but also

including absorbance, fluorescence

‘lost’. To speed up this process for our

undergraduate and masters students

intensity, fluorescence polarization

Infinite and Safire readers, we have

– working on different biotechnologies

and bioluminescence. We have always

resorted to opening the measurement

and applications; everything from

been very happy with the reliability

chamber and using a fan to accelerate

protein-protein interactions and

and performance of these instruments

cooling, but this is far from ideal, and is

30

TECAN JOURNAL 1/2017

BIOMEDICAL ENGINEERING

not particularly effective on a warm day.

This issue is completely eliminated by the Spark’s Te-Cool module. You simply set it to the temperature you want, and it quickly and efficiently heats or cools the measurement chamber to the target value. This saves a huge amount of time, and allows us to perform more experiments on any given day.”

“The SparkControl™ software is also very intuitive to use. Anyone who has experience with the Infinite’s iControl™ software can use the new system with virtually no training, and it’s very easy to explain to new users, which is particularly useful for teaching undergraduate or masters students with limited lab experience. Each user can also save and share their individual protocols – which saves a lot of time when switching between measurement modes or assay types – and if we have any queries, the Tecan helpdesk is always very quick to respond. Overall, we’re very pleased with the Spark system and the Te-Cool module, it’s proving to be a very versatile instrument.”

One of the biggest advantages for our lab is the system’s Te-Cool option.

To find out more about Tecan’s Spark multimode reader, visit www.tecan.com/spark To learn more about TU Eindhoven’s Department of Biomedical Engineering, go to www.tue.nl/en/university/ departments/biomedicalengineering/

The Spark reader was purchased to help cope with the lab’s increasing number of students

The lab’s Safire2 reader has performed reliably for many years

TECAN JOURNAL 1/2017

31

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

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