Tecan Journal Edition 01/2016

Tecan Journal

Edition 1/2016

Life Sciences, Diagnostics and Partnering

Ramping up NGS in oncology: is sequencing tumor DNA enough?

A very short history of cancer research funding.

Darting from plate to plate.

Safety in extremes.

Pages 4-6

Pages 7-9

Pages 12-13

Pages 20-21

CEO WELCOME

Welcome Dear Reader, In 2015, we conducted a global survey of over 1,000 scientists to find out how Tecan adds value to their work. The resounding answer from the respondents was the solid reliability that Tecan stands for. Every day around the world, Tecan products are used in key studies in life science labs, as well as in diagnostic labs for daily operations that are critical to human lives. Tecan provides a high level of reliability and responsiveness that many people have come to depend upon.

For Tecan Partnering, scientists and engineers told us how they envision Tecan empowering their life sciences and diagnostic applications. And by working together with Tecan, they can launch new, innovative solutions faster to market and better than they could on their own.

As a consequence, we clearly formulated what we stand for and refreshed our brand.

We started by defining our new vision: Every Lab. Every Day. Empowered. The vision is not about us. It’s about empowering you, our customers and partners, wherever you are around the world, to achieve greater things than you could do before.

Next, we looked at what we need to commit to, in order to achieve our vision. Our promise to you is to be Always There For You. We strive to be closer to customers and partners, to be more responsive, and help you achieve your goals by contributing our expertise wherever we can. This issue of the Tecan Journal – in your hands or on your device – takes a closer look at some exciting stories of empowerment of our customers.

New to the Tecan Journal are in-depth stories on the trends that shape our industry, both today and in the past. We take a look at what might happen as next generation sequencing moves closer to the clinical lab, and at the fascinating story by Siddhartha Mukherjee of how cancer research funding took off through the efforts of a handful of committed individuals and the unlikeliest of circumstances. We also present product news about the Fluent™ laboratory automation solution and Spark™ reader that empower your work in drug discovery and cell-based assays respectively.

In October 2015, we were very excited to announce the acquisition of Sias by Tecan.

With Sias joining our family, this heralds the growth of Tecan Partnering, with a wider set of solutions for modular and complete systems. Sias customers will immediately benefit from Tecan’s global sales and support organization.

Please do send us your thoughts and opinions at hello@tecan.com. We’re always there for you.

Wishing you all the best in 2016.

Dr David Martyr CEO

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TECAN JOURNAL 1/2016

CONTENTS

Contents 2

CEO Welcome

4 - 6

Ramping up NGS in oncology:

is sequencing tumor DNA enough?

7 - 9 A very short history of cancer research funding 10 - 11 Liquid biopsies made easy 12 - 13 16 - 17 Faster food testing

Darting from plate to plate

14 - 15 Hands-free SPE method development in under two hours

16 - 17 Faster food testing 18 - 19 Fungal detection accelerated 20 - 21 Safety in extremes 22 - 23

Sensitive to light

24 - 25 Large molecule bioanalysis simplified 26 - 27 Step-by-step automation 28 New Fluent features increase speed and flexibility 29 Empower your research with the Spark 20M multimode reader

22 - 23

30 - 31 Sias joins Tecan Partnering

Sensitive to light

TECAN JOURNAL 1/2016

3

ONCOLOGY

Ramping up NGS in oncology: is sequencing tumor DNA enough?

Massively parallel sequencing has

Moreover, clinical oncologists are

rapidly become a must-have tool of the

recognizing the value of additional

trade in molecular biology and drug

information to be gained from RNA

discovery research. In recent years, the

sequencing (RNAseq) to define the

cost of next generation sequencing

tumor transcriptome. Perhaps a bit

(NGS) has declined exponentially, while

farther off in the future will be direct

throughput, accuracy and read lengths

clinical applications of sequencing data

have soared, and multiple regulatory-

derived from non-coding RNA species

compliant sequencing technologies

– such as microRNAs (miRNAs) and

have now achieved commercial

long non-coding RNAs (lncRNAs) – to

success. Advances in NGS – combined

detect aberrations that may affect

with global efforts to identify and

gene expression, and overarching

catalog genetic mutations in a range

gene regulatory networks that control

of cancer types and tumors, as well

biochemical pathways essential for

as to implement these discoveries in

tumorigenesis, malignant disease

diagnostic, therapeutic and prognostic

progression and metastasis. Furthermore,

applications – are driving the adoption

characterizing the epigenetic changes in

and, in the not-too-distant future, even

tumor DNA and determining how these

routine use of sequencing and related

might relate to cancer diagnostics, the

techniques in clinical laboratories.

monitoring of disease progression and drug response, and the prediction of

With the emergence of NGS in clinical

drug sensitivity and resistance, is an area

oncology have come abundant

still in its infancy.

examples in the literature of the value of tumor-derived DNA sequencing.

Immunotherapeutic strategies designed

These include identifying hotspots in

to stimulate the body’s immune system

cancer-predisposing genes, or specific

to recognize and destroy tumor cells

cancer-associated mutations in one

are increasingly being developed

or more genes that might contribute

to complement chemotherapeutic

valuable diagnostic or prognostic

regimens. The results of NGS can be

insights. This information could also help

used to predict patient response to

to guide clinicians in therapeutic decision

immunotherapy, as well as to inform the

making and drug selection to maximize

design of therapeutic cancer vaccines.

the efficacy of treatment, limit patient

Exome sequencing can reveal whether

exposure to toxic chemotherapeutic

a neoantigen – an antigen created

agents not likely to have a beneficial

by a somatic mutation in a tumor – is

effect on disease progression or patient

presented by the major histocompatibility

survival, and minimize the risk of

complex for recognition by sensitized

developing drug resistance.

T cells.1 The growing interest in clinical applications of NGS in oncology has also

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TECAN JOURNAL 1/2016

ONCOLOGY

recently spurred discussion and debate on what and how much sequence data is needed to ensure accurate interpretation and appropriate utilization of genomic

Sequencing overload – preparing for the future

for predicting cancer progression,

NGS-based diagnosis is specially promising for diseases that have a highly complex and heterogeneous genetic composition [such as oncology, which is] very well positioned to benefit greatly from such an approach.

metastatic potential and drug sensitivity

according to Pant and colleagues.4

An emerging trend towards sequencing

information in patients with cancer.

matched tumor and normal DNA samples

Too little information is not an option

and related sample extraction and library

One issue swirling around at present is

labs. The discovery of new tumor-specific

whether sequencing the DNA from a tumor biopsy is sufficient for diagnostic and therapeutic purposes, or if sequence data generated from a healthy sample from the same patient should serve as a matched control for comparison purposes. As noted in the article Cancer Sequencing Controls, sequencing a patient’s normal DNA is not common practice in clinical labs and would certainly add to the cost compared to analyzing only tumor DNA.2 However, the extra workload and cost must be weighed against the risk of basing treatment decisions on inaccurate information and an incomplete diagnosis.

The results of an analysis of 815 paired tumor-normal samples from patients with 15 different tumor types illustrated the potential to misinterpret somatic alterations identified in the tumor genome using NGS as tumor-specific mutations.3 Many of the same changes were shown to be present as germline variations in NGS analysis of the normal

would clearly increase the NGS volume preparation workflows in diagnostics genetic alterations that may be relevant

or resistance – and the eventual translation of these molecular tools to the bedside – would have an even greater impact on the demands placed on clinical labs.

The envisioned transition in healthcare to a more efficient and cost-effective strategy based on personalized medicine will require access to an abundance of genetic information for each and every patient, at various stages of health and disease. Thus, rapid, high throughput, massively parallel sequencing performed in a regulated environment will be the new norm for clinical labs. Clinical NGS

It is easy to imagine that soon every patient will have both their constitutional and cancer genomes sequenced, the latter perhaps multiple times in order to monitor disease progression, thus enabling an accurate molecular subtyping of disease and the rational use of molecularly guided therapies. state Meldrum et al.5

will become a commodity, essentially as it has in the research setting. This extensive application of NGS will be a reality across a broad range of diseases, but perhaps most acutely in cancer.

sample, and only about a third of the mutations found on sequencing of the tumor exome were tumor-specific.

The other two thirds were germline alterations, and would have led to false positive findings – including in cancerpredisposing (potentially actionable) genes – if only the tumor DNA had been sequenced, and that information alone used to inform therapeutic decisions.

TECAN JOURNAL 1/2016

5

ONCOLOGY

Regardless of the sequencing technology

The various trends described here –

sequencing activities in response to

used, the biggest bottleneck and

including advances in NGS technology

increasing demand for massively parallel

challenges lie in sample preparation.

and other factors driving personalized

sequencing capabilities – and transition

This involves the laborious and often

medicine – all point to a future on the

to automated systems to handle the

difficult process of DNA extraction,

horizon in which massively parallel

added volume of NGS and workload

especially when working with formalin-

sequencing will be routinely used

related sample prep functions – they are

fixed paraffin-embedded specimens.

for cancer diagnosis and to guide

likely to realize quite quickly that cost

Pant et al. contend that the current

therapeutic decision making. As clinical

need not be a barrier to meeting the

testing paradigm for precision medicine

labs begin to realize a dramatic increase

evolving needs of clinical oncology.

is unsustainable.

in demand for NGS, rapid adoption of high throughput solutions for upstream

Recent results from clinical studies support the emerging concept of the ‘mutation signature’ or spectrum of correlated mutations in cancer.

sample handling and library preparation in NGS workflows will be critical.

References 1) G agan, J; Van Allen, EM. Next-generation sequencing to guide cancer therapy.

Robotic systems that automate sample

Genome Medicine, 2015, 7, 80.

prep enable faster, more efficient and

2) W illiams, R. Cancer sequencing controls.

more secure sample processing, with

The Scientist, 2015, www.the-scientist.

better accuracy and consistency than

com/?articles.view/articleNo/42682/title/

manual techniques. They can also

Cancer-Sequencing-Controls/.

provide the flexibility to accommodate

3) J ones, S et al. Personalized genomic

In other words, combinations of

both commercial and customized,

analyses for cancer mutation discovery

mutations will be more predictive of

laboratory-developed diagnostic

and interpretation. Sci Transl Med, 2015, 7,

treatment response than individual

tests and sample prep protocols.

283RA53.

gene mutations. Therefore, physicians

In addition to improved speed and

will want to examine the tumor’s whole

productivity, automation and computer-

genome, both somatic mutations and

driven systems bring several crucial

transcriptional changes, to identify the

advantages to the clinical laboratory.

companion diagnostics. Front Oncol, 4(78).

most effective personalized therapy.

Not least of these is an emphasis on

doi: 10.3389/fonc.2014.00078

Thus, the use of RNAseq to analyze the

sample tracking and a secure chain-of-

transcriptome of tumor cells and assess

custody, as well as ensuring the quality

the relative expression of a mutated

controls, validation and documentation

gene will likely become a much more

required in a regulated environment.

common application. Rizzo and Buck

Furthermore, robotic liquid handling and

note that NGS-based RNAseq studies

sample processing minimize the risk of

continue “to identify and implicate key

contamination and maximize accuracy

somatic mutations in oncogenesis.”6

and reproducibility compared to manual

They point out that certain oncogenic

techniques.7

using RNAseq have also been shown to

With increased throughput, efficiency

alter gene function in vivo in a way that

and productivity typically comes cost

agrees with the tumor’s clinical behavior.

savings. Thus, as labs ramp up their

TECAN JOURNAL 1/2016

development of regulated next-generation sequencing-based clinical trial assays and

5) M eldrum, C et al. Next-generation sequencing for cancer diagnostics: A practical perspective. Clin Biochem Rev, 2011, 32(4), 177-195.

6) R izzo, JM; Buck, MJ. Key principles and clinical applications of “next-generation” DNA sequencing. Cancer Prev Res, 2012, 5(7), 887-900.

7) F assunke, J et al. Utility of different

mutations identified in tumor samples

6

4) P ant, S et al. Navigating the rapids: The

massive parallel sequencing platforms for mutation profiling in clinical samples and identification of pitfalls using FFPE tissue.

Internat J Mol Med, 2015, 36(5), 1233-1243.

ONCOLOGY

A very short history of cancer research funding In his book The Emperor of All Maladies, Siddhartha Mukherjee tells the story of one of the turning points in the history of cancer medicine. A turning point that he dates to May 1947.

At this time, cancer was a fatal disease and as a subject of discussion it was rarely mentioned among close friends, least of all at polite social gatherings. Cancer was an ugly disease that appeared to harvest lives regardless of the individual’s background, lifestyle or social stature. Its victims were carved up in radical surgical procedures or subjected to experimental chemical trials with little or no understanding of the underlying mechanisms.

After a brief period of remission, most patients succumbed to new tumors, some far more aggressive than their predecessors.

Research was performed by a handful of dedicated doctors who were nameless, faceless and relegated to the basements of hospitals to perform research with dubious outcomes.

If cancer was ever to have a future as a disease to be tackled seriously, it needed serious funding. Cancer had to become a disease that people were not afraid to talk about in public. And the focus had to be on a patient that nobody could deny deserved all the help in the world.

The story begins 19 years earlier, with a baby in a basket‌

TECAN JOURNAL 1/2016

7

ONCOLOGY

The baby girl was abandoned on a seat in the Sheridan Square Film Theater in Pittsburgh at the start of the Great Depression of 1928. The note attached to the baby read:

Please take care of my baby. Her name is Catherine. I can no longer take care of her. I have eight others. My husband is out of work. She was born on Thanksgiving Day. I have always heard of the goodness of show business and I pray to God that you will look after her. Signed, a heartbroken mother.

The baby was named Catherine Variety Sheridan, her surname after the theater where she was found, and her middle name after the Variety Club, an association of actors, producers, directors, writers and film theater owners that adopted Catherine as their ward.

The media exposure from the adoption of baby Catherine was far greater than the members of the Variety Club could ever have dreamed. During the war years, the entertainment industry had boomed and Hollywood realized that they had earned the adoring, if somewhat fickle, goodwill of the general public.

The Variety Club redefined itself as a philanthropic organization that was keen to reinforce the idea of ‘the goodness of show business’.

Every dime counts The Variety Club was inspired by the March of Dimes, a campaign initiated by the actor Eddie Cantor when Franklin D Roosevelt was re-elected President. In 1936, Roosevelt, himself a polio victim, established the National Foundation of Infantile Paralysis. Polio research and patient care received a massive boost in funding thanks to the nationwide campaigning efforts of the March of Dimes, which reached out through the radio waves into the living rooms of private homes across America. Dimes in envelopes flooded into the White House from factory workers, housewives, schoolchildren and Girl Scouts. In the first year alone, 2,680,000 dimes were collected. By the late 1940s, John Enders had succeeded in cultivating the first live poliovirus in the lab. The development of the polio vaccine was a direct result of the public funding initiative. In 1938, FDR focused on cancer, and signed legislation

TECAN JOURNAL 1/2016

experimenting with a new drug, an antifolate called aminopterin. Farber had demonstrated the first signs of partial remission of pediatric leukemia by aminopterin in a four year old girl.

Empowered by a rare positive result, Farber was now obsessed by his vision of a hospital dedicated to the research of childhood leukemia.

Koster had found his man. Together, Koster and Farber began to hatch plans to make the hospital a reality. In 1948, they launched the Children’s Cancer Research Fund. Their first raffle raised an impressive $45,456, but hardly enough to open a hospital. Koster recalled the success of the Catherine Sheridan campaign and convinced Farber that they needed a poster child, a mascot for childhood leukemia.

Jimmy gives cancer a voice

that gave birth to the National Cancer

The challenge was fraught by a

Institute. Its initial budget was $400,000.

seemingly intractable problem. Most of the children were extremely weak; far

Bill Koster of the Variety Club of New

too weak to appear on radio or make

England began the search for a new

public appearances. Most children

cause that his club could own. He had

died within months of their diagnosis.

visited many hospital labs and found

Finding a patient for the public to root

medical scientists buried under piles

for was not going to be easy. Scouring

of papers, but none of them had the

through all the patient lists, Koster

ambition to think big. Until he met

and Farber landed on Einar Gustafson.

Dr Sidney Farber.

Einar was not suffering from leukemia, rather he was being treated for a rare

Farber was at Children’s Hospital Boston

intestinal lymphoma. He was young,

working on childhood leukemia, a

fresh faced and radiated hope. Einar

disease that had confounded the medical

was the boy that the public would want

community – no treatment had been

to save from cancer.

identified that extended the

8

survival of patients. Farber had been

ONCOLOGY

Einar was renamed ‘Jimmy’ and, in 1948,

Albert Lasker was an advertising

cure cancer firmly in the public eye,

the Jimmy Fund was born. Using smart

executive at the firm Lord and Thomas,

millions of federal dollars have poured

PR moves, like recruiting the Boston

inventors of classic ads for Lucky Strike

into cancer research, so that the US

Braves to sing the team’s song with

and Sunkist. He famously said: “If a

today enjoys a dominant position and is a

Jimmy on the radio, the Jimmy Fund

toothpaste… deserved advertising at the

magnet for talent in cancer research.

attracted thousands of donors, many

rate of two or three or four million dollars

of whom queued in the lobby of the

a year, then research against diseases…

Children’s Hospital to personally hand

deserved hundreds of millions of dollars”.

in their donations so that Jimmy could

Further reading The Emperor of All Maladies -

watch the Braves on TV. The Jimmy

The self-styled group of ‘Laskerites’

Fund far surpassed its original target of

included action-oriented businessmen,

$20,000, raising $231,000 in its first year.

movie producers and lawyers. They

Since its foundation, the Jimmy Fund has

ousted the presiding scientific board of

raised $750 million for the Dana-Farber

the American Society for the Control

Cancer Institute using the tried and

of Cancer (ASCC) and renamed the

trusted method of fundraising through

organization the American Cancer

The Jimmy Fund

public engagement.

Society – the ACS. Their first move was

www.jimmyfund.org

to gain nationwide public awareness

Going to the country Farber learned that the fight against cancer was not just about science – it was as much about being seen and heard. He needed to understand the intricacies of political lobbying. He needed a clear strategy and a reason for people to believe in his cause.

Gaining and sustaining the public’s attention required the persuasive art of advertising. Enter Mary and Albert Lasker.

Mary Lasker was a star saleswoman, a long-time lobbyist and a political campaigner. A survivor of pneumonia and the Spanish flu of 1918, she became the most influential health activist of her day. Mary was horrified by the ravages of mastectomy operations, so she focused her keen mind on cancer. Mary’s husband

by publishing articles about cancer screening and detection in Reader’s

A Biography of Cancer. Siddhartha Mukherjee. ISBN 978-0-00-725092-9.

The Sheridan Square Theater on Cinema Treasures www.cinematreasures.org/theaters/16551

The Dana-Farber Cancer Institute www.dana-farber.org

Digest. Over the following years, the

The Lasker Foundation

results of their massive campaigns were

www.laskerfoundation.org

clearly evident. Donations rocketed from $832,000 in 1944 to over $12 million in 1947.

Farber’s coalition and friendship with Mary and Albert Lasker would transform the funding of cancer research. Farber had the scientific credentials needed to sway Congress, and the Laskers stood for constant lobbying ‘on the Hill’ and extremely effective advertising.

Most significantly, Mary Lasker’s work ultimately led to President Nixon famously declaring War on Cancer with the signing of the National Cancer Act of 1971. With the lobbying of the government, and with the urgency to

TECAN JOURNAL 1/2016

9

CLINICAL DIAGNOSTICS

Liquid biopsies made easy VolitionRx is using its

VolitionRx Ltd was established in 2010

Nucleosomics relies on the identification

proprietary Nucleosomics®

to combine established immunoassay

of characteristic epigenetic features

techniques with cutting-edge

which are present on the nucleosomes

nucleosome detection and analysis,

in cancerous cells. These uniquely

creating a revolutionary new approach

structured nucleosomes can be easily

to cancer diagnostics. Gaetan Michel,

detected in blood samples using

creating non-invasive tests

CEO of Belgian Volition SA – the parent

ELISA methods, reducing the cost of

that identify disease-specific

company’s operations organization in

testing for laboratories and providing a

nucleosome signatures

Namur, Belgium – explained: “Currently,

virtually pain free method of diagnosing

the only blood test routinely used for

various cancers. Gaetan continued:

cancer diagnostics is the PSA (prostate

“Nucleosomes are complexes composed

specific antigen) assay for prostate

of eight histone proteins plus 147 base

cancer. However, there are a number

pairs of double-stranded DNA, and

the company’s workflow, which

of other cancers which could benefit

their role is to package up the cell’s

it has chosen to automate using

from blood-based diagnostics, and

DNA into chromosomes. Each of the

four identical Freedom EVO®

our Nucleosomics technology has the

histone proteins has a number of

potential to detect early stage cancers

surface modifications – methylations,

and improve outcomes for many of

acetylations, etc. – depending on

these patients.”

the condition of the cell, which have

technology platform to develop a range of diagnostic assays for cancer and other conditions,

circulating in the blood.

High throughput biomarker validation is a crucial aspect of

200 workstations.

Brieuc Cuvelier and Dorian Pamart with one of VolitionRx’s four identical Freedom EVO platforms

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TECAN JOURNAL 1/2016

CLINICAL DIAGNOSTICS

an effect on transcription in the cell

operation in February 2015. Dorian

protocols we had already developed

nucleus. These patterns of epigenetic

Pamart, Research Associate and Manager

onto the new instruments. This was done

modifications are disrupted in many

of the Automated Platform, explained: “I

very quickly and efficiently, and all four

cancers, leading to uncontrolled cell

already had some limited experience with

systems were operational the following

proliferation and subsequent cell death.

Tecan liquid handling workstations from

week, minimizing disruption.”

Following cell death, the nucleosomes

a previous role, but had not performed

are released into the blood stream,

automated ELISA testing before. We

“Without automation, our biomarker

allowing us to detect them with our panel

outlined our workflow to the Tecan team,

validation workflow would be almost

of NuQ® immunoassays targeting specific

who then developed the instrument

impossible. There are two members

structural features of the nucleosome.”

configuration to meet our needs. Once

of staff responsible for the day-to-day

the system arrived, I worked closely

operation of the workstations, allowing

“Identifying and validating the

with a Tecan application specialist to

us to process around 3,200 samples

characteristic epigenetic nucleosome

design and test the protocols. This was

every day. This compares with just 120

profile associated with each cancer is

very easy, as the platform was already

samples per person manually, meaning

the main aim of our work here in Namur, collaborating with healthcare institutions across Europe and the USA to gather serum samples from clinically relevant patients. Once a candidate biomarker is selected, we begin by performing a proof-of-concept study with around 200 to 300 clinical samples. We then move

ur Nucleosomics technology has the O potential to detect early stage cancers and improve outcomes for many of these patients.

into the confirmatory phase, testing between 1,000 and 5,000 samples and, finally, we perform a regulatory validation

set up correctly for our workflow, but

we have increased our throughput

study on 5,000 to 15,000 samples from

by carefully optimizing the various plate

more than 13-fold while improving

a different patient cohort for regulatory

movements, pipetting actions and wash

reproducibility and process security,”

purposes. While the proof-of-concept

steps, we were able to dramatically ramp

Gaetan concluded.

experiments can easily be performed by

up throughput from 200 to 800 samples

hand, the confirmatory and validation

a day. Tecan also provided in-house

studies, which are often performed on

training for several of the laboratory

To find out more about Tecan’s

up to 30 candidate markers in parallel,

staff, allowing us to update or develop

clinical solutions, visit

would be virtually impossible to do

protocols as required.”

www.tecan.com/clinicalsolutions

manually. Inter-operator variability and the risk of handling errors would also

This set-up proved so successful that the

make analysis of results very difficult,

company soon ordered three additional

which is why we approached Tecan to

Freedom EVO 200 platforms with the

help us automate the workflow.”

same specifications. Gaetan continued:

To learn more about VolitionRx, go to www.volitionrx.com

“We carefully planned the installation Belgian Volition’s first Freedom EVO

and commissioning of the new platforms,

200 workstation was commissioned

so we knew exactly when they would

in September 2014 and, following

arrive on site. Because the systems were

transfer of the manual protocols onto

identical to our first platform, it was

the automated system, began routine

simply a case of copying the various

TECAN JOURNAL 1/2016

11

DRUG DISCOVERY

Darting from plate to plate Dart NeuroScience specializes

scientist at Dart NeuroScience, explained:

throughput necessary to keep pace with

in the development of novel

“Like any drug discovery company, we

our various drug development programs,

need the ability to test large numbers

generating hundreds of precisely filled

of compounds quickly and effectively.

assay plates a day.”

therapeutics targeting neurological disorders, with an emphasis on impairment

The advent of high density microplate formats – particularly 1,536-well plates –

of cognitive functions such

“We have been using Tecan liquid

has considerably increased our ability to

handling workstations since the company

as memory. The company

screen many compounds in parallel, but

was founded in 2007, and have over half

generates over a thousand new

this has created a number of logistical

a dozen Freedom EVO® workstations

challenges for compound management.”

performing a range of activities,” added

compounds every week to feed

Jose Quiroz, Manager of Laboratory

into its active drug discovery

Systems. “As the company has grown,

pipeline, creating a significant

the number of projects we have running

challenge for the compound

at any one time has obviously increased,

management team.

and so we were keen to purchase a new platform to increase the throughput of

Medical advances over the last century

assay plate generation. We evaluated

have dramatically increased life

several solution providers and decided

expectancies in developed countries,

to partner with Tecan, using the

placing ever-greater importance on

company’s Fluent™ platform. The huge

geriatric care. The aging process,

on-deck capacity offered by this system,

together with cognitive disorders such

combined with its high speed pipetting

as Alzheimer’s disease and Parkinson’s

capabilities, was very appealing to us.”

disease, can lead to significant loss of memory function, creating a niche for

Joe Zer, Research Scientist

Joe continued: “The only potential drawback was that we use a unique

therapeutic agents specifically targeting memory disorders. Dart NeuroScience

“Our synthesis group produces over

1,536-well microplate format. Although

– which recently moved to a new

1,000 new compounds every week

these plates conform to ANSI/SLAS

headquarters at Scripps Ranch in San

which need to be transferred to

standards, they have rounded flat-

Diego, California – is one of the few

compound plates for screening and

bottom wells to allow use of a pin tool

companies globally to be addressing

profiling. We also periodically buy in

in downstream operations. Our local

this largely unmet medical need, aiming

compound libraries from commercial

Tecan representative was confident that

to discover new technologies and

manufacturers – sometimes up to 30,000

this wouldn’t be an issue, so took one of

develop novel therapies to help maintain

compounds at a time – which need to

our plates to run on a demo system. He

cognitive vitality throughout life.

be accurately aliquoted and diluted

simply loaded the plate onto the system, and it ran perfectly

The company’s multidisciplinary strategy includes the identification of new therapeutic targets, the generation of closely-related compound libraries and

I t’s basically tripled the speed of most of our protocols.

first time using the standard 1,536-well microplate definitions pre-installed in the FluentControl™

the creation of novel functional assays, as well as the development of specialized

without introducing manual handling

software! Following that demonstration,

clinical therapies. This multi-faceted

errors that could affect downstream

we ordered our system straight away,

approach requires a large number of

processes. As a result, automated liquid

and it was installed in June 2015. After

compound plates to be generated for

handling has become an essential part of

a few weeks of familiarizing myself with

high throughput screening, as Joe Zer, a

our workflow, enabling us to achieve the

the new instrument, I went on the Tecan

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TECAN JOURNAL 1/2016

DRUG DISCOVERY

training course in North Carolina, and we have had the platform in routine operation since August.”

“The increased throughput the Fluent platform has already given us is fantastic.

Where we could previously generate 16 compound plates at a time, we can now produce 32 in parallel, and in a short time frame. And it’s even better for dilutions; where we could previously create about 20 single dilutions in parallel, we can now do 56 in duplicate. It’s basically tripled the speed of most of our protocols. We are also considering installing a bulk dispense module for DMSO below the workdeck to further increase throughput, as the system’s Robotic Gripper Arm can easily access this below-deck area without too much compromise in the instrument’s overall capacity.”

“Although our workstation is very simple in automation terms, the Fluent platform’s high definition liquid handling capabilities are still very impressive. The Multiple Channel Arm moves very quickly compared to most pipetting robots on the market, and the Path Finder™ feature means that it always takes the optimal route between plates. The Active Stop and Resume function – introduced with the latest software update – is also fantastic; if you see something wrong with the set-up on the workdeck, you can just open the door and it stops.

Once you’ve dealt with the problem, you just press ‘Retry’ and it picks up where it left off, avoiding the need for laborious resetting or reprogramming of the instrument. The software is also both powerful and very convenient to use; the Zero G teaching capability makes it extremely quick and easy to define plate positions, and almost every aspect of

“We are still in the process of learning the Fluent platform’s full capabilities and transferring existing protocols to the new system, but we are already very impressed with its performance. Once more of our staff have been trained on this instrument, we plan to consolidate

To find out more about Tecan’s Fluent laboratory automation solutions, visit www.tecan.com/fluent

as many of our standard compound

To learn more about

management functions as possible

Dart NeuroScience, go to

onto the system, providing a single

www.dartneuroscience.com

‘go to’ solution for plate generation,” Joe concluded.

instrument control can be adjusted to make operations faster and more robust.”

TECAN JOURNAL 1/2016

13

ANALYTICAL CHEMISTRY

Hands-free SPE method development in under two hours US-based PhenoLogix is offering a new paradigm in SPE method development for CROs and diagnostic labs. Combining the Freedom EVO® SPE workstation with the Phenomenex Strata™-X 96-Well SPE Method Development Plates, this approach reduces development time from six to seven days to under two hours.

To help address these issues,

prednisone (neutral) – allowing us to

Phenomenex has developed the Strata-X

identify the optimal sorbents and load/

96-Well SPE Method Development

wash conditions for good recovery of

Plate (MD Plate). Packed with four

all four analytes (Table 1). To reduce

unique polymer-based SPE sorbents

the background as much as possible

PhenoLogix, located in Torrance,

– reversed phase, mixed-mode strong

– maximizing column life – we used an

California, is a division of global

cation exchanger, mixed-mode weak

aggressive 70 % organic wash, however

separation sciences company

cation exchanger and mixed-mode weak

this caused some issues with the

Phenomenex. Initially part of the parent

anion exchanger – the MD Plate can be

moderately polar prednisone (logP =

company’s R&D department, it has grown

combined with the Freedom EVO SPE

2.07), leading to some loss of the drug

into a standalone analytical support

workstation to provide a faster, more

during washing. We are confident that,

service providing chromatography

structured approach to screening. Sean

by decreasing the organic content of

method development and optimization

continued: “Using the four different

the wash, the analyte recovery can be

support to customers around the world.

Strata-X sorbents, we have developed

improved further.”

SPE method development is an integral

a walkaway protocol to screen acidic,

part of LC-MS workflows for most CROs

basic and neutral conditions for each

“As a method development lab, the

and diagnostic labs, but is traditionally

step of the SPE process (load, wash

Freedom EVO’s versatility is another

extremely time consuming and error

and elution). This allows customers

major benefit to us. We implement

prone. Sean Orlowicz, PhenoLogix

to determine the best conditions for

different products on a regular basis –

Manager, explained: “SPE method

retention of the analyte of interest in a

switching between simple serial dilutions,

development is often the first and most

single hands-free SPE experiment lasting

protein precipitations, and liquid and

laborious step for CROs performing

under two hours. Processing the MD

solid phase extraction protocols – and it

studies on biological samples such as

plate is completely automated, requiring

is very easy to reconfigure the workdeck

plasma or serum. It involves careful

no analyst intervention, with all pipetting

for new applications. Programming the

screening of various SPE sorbents,

and vacuum steps controlled through the

instrument through Freedom EVOware

solvent concentrations and pH ranges –

platform’s Freedom EVOware® software.

is straightforward – it’s very easy to write

for both loading and elution – to ensure

We typically pipette volumes of between

new scripts or edit existing ones – and

maximum recoveries and clean samples

50 and 750 µl, and the platform’s

the TouchTools™ graphical user interface

ready for LC-MS analysis. Thorough

reproducibility in this range is excellent

is self-explanatory for selecting, setting

exploration of various conditions is

– in the region of 2-3 %. The flexibility

up and starting existing applications.”

crucial for the success of their client’s

of the Freedom EVO SPE workstation

studies, as well as ensuring maximum

also means that, once the most

“To date, our primary focus has been

lifetime for expensive analytical

appropriate sorbent has been identified,

on biological fluids – plasma, serum and

columns and minimizing the time and

you can quickly and easily switch to

urine – as well as some work with tissue

money spent on maintenance of mass

high throughput processing without

samples. Moving forward, we see the

spectrometers. Unfortunately, this

reconfiguring the workdeck, which is a

potential to develop environmental, waste

process usually takes around six or seven

real benefit for our customers.”

water and food applications, and there

days to complete, and so any reduction

is considerable demand for whole blood

in the SPE method development time

“We chose four structurally diverse

applications for forensic toxicology.

would offer savings in operational costs

analytes to test our assay set-up –

We also plan to develop applications

and reduce turnaround times.”

amitriptyline and metoprolol (both

in tube format, particularly for clinical

basic), diclofenac (acidic), and

diagnostics and clinical toxicology,

14

TECAN JOURNAL 1/2016

ANALYTICAL CHEMISTRY

his allows customers to determine the best T conditions… in a single hands-free SPE experiment lasting under two hours.

implementing positive pressure SPE on the Freedom EVO workstation. This will offer customers even more versatility, allowing them to choose between the 96-well format for maximum throughput and tube-based assays for lower sample numbers.”

“Overall, our automated approach offers CROs and diagnostic laboratories a rapid and systematic way of performing SPE method development. Working together with Tecan to demonstrate the potential gains in productivity and turnaround times – while reducing operational costs – has been a pleasure, creating the ideal basis for future collaborations,” Sean concluded.

To find out more about Tecan’s

The PhenoLogix team

Sorbent/ conditions

Recovery (%)

Reproducibility (%CV)

Amitriptyline

Strata-X-CW Loading – basic pH Elution – acidic pH

98.8

3.2

Metoprolol

Strata-X-CW Loading – basic pH Elution – acidic pH

98.5

9.6

Diclofenac

Strata-X-AW Loading – acidic pH Elution – basic pH

72

6.7

Prednisone

Strata-X Loading – basic pH Elution – acidic pH

50

1.8

Analyte

sample preparation solutions, visit www.tecan.com/analyticalchemistry To learn more about PhenoLogix, visit www.phenomenex.com/ home/phenologix

1) Phenomenex TN-0078. Automated SPE Method Development Using Strata™-X 96-Well SPE Method Development Plates In Conjunction with a Tecan Freedom EVO Liquid Handling System. Shahana Wahab Huq, Sean Orlowicz, and Matthew

Table 1: Example analyte recovery rates for four diverse drug analytes using polymer-based Strata-X sorbents (Strata-X, reversed phase; Strata-X-CW, mixed-mode weak cation exchanger; Strata-X-AW, mixed-mode weak anion exchanger).1

Brusius. Phenomenex, Inc., 411 Madrid Ave., Torrance, CA 90501 USA.

TECAN JOURNAL 1/2016

15

FOOD SCIENCE

Faster food testing The Institute for Product Quality, based in Berlin, has grown into a service laboratory that provides virtually any and every test required by the food market, from microbiology to pesticide testing. Using its expertise in food analytics and kit development, and with new, state-of-the-art equipment and facilities in the Berlin-Adlershof science park, ifp provides testing services and kits to the industry and public alike.

. .. ideal for food manufacturers who fortify their products with nutrients...

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TECAN JOURNAL 1/2016

FOOD SCIENCE

The Institute for Product Quality (ifp)

on automation to ensure both high

is an independent laboratory offering a

throughput and reliability for its kit

complete range of services and testing

manufacturing processes, and has used

products for the food, feed, water and

Tecan liquid handling systems since

pharmaceutical industries. Founded

operations began. Tobias Hein, head

in 2004 and now employing 230 staff

of marketing and sales at ifp, said:

in its purpose-built facilities in Berlin,

“We are producing large quantities of

Germany, ifp provides comprehensive

kits per lot, and automation is always

analysis of allergens, vitamins,

the better option than having to

genetically modified organisms,

produce thousands of kits manually.

pathogenic agents, mold toxins and

Reproducibility is very important for

pesticide residues to food producers and

us and for our customers; significant

caterers worldwide, as well as sterility

differences, either within or between

testing and other microbiological

kit lots, would be a serious issue, and

services for the pharmaceutical industry.

automation helps us to prevent this.”

In 2013, ifp hit the headlines after detecting non-declared horse meat in

ifp has a suite of Tecan equipment on

frozen ready meals, provoking a media

different production lines, including a

response that boosted its profile in the

HydroSpeed™ that washes microplates

public eye. Today, householders are

as part of the plate coating process

also turning to ifp to test the quality of

involved in the production of the

drinking water.

AgraQuant® Plus test kits for food allergens. Genesis™, Freedom EVO®

Alongside its extensive service portfolio,

and Fluent™ workstations are used to

ifp also develops and manufactures test

pipette reagents and controls as part of

kits for many food-related analytes,

the manufacturing process of various

based on techniques such as real-time

kits. The most recent addition, a Fluent

PCR, immunoassays, enzymatic

laboratory automation solution, was

assays and microbiological tests. The

chosen to increase production of ifp’s

production facility naturally relies

VitaFast® microbiological kits, as Victoria Bode, VitaFast production and R&D specialist, explained: “VitaFast is a ready-to-use test kit devised for the microbiological detection of all water-soluble vitamins and selected

From left to right, Nicole Menzel, Victoria Bode and Wiebke Hammers

current configuration – means that we have been able to more than double the number of plates per run. It is also very quick and intuitive to use; new operators find it incredibly easy to learn, and we were able to use it in production just a day after it was installed!”

“Thanks to the workstation’s rapid liquid handling capabilities, we can now dispense small volumes of bacterial solutions into each well of the test microplates much faster than was previously possible, saving up to 20 minutes per run. As it does not need to be monitored during operation, staff are also free to walk away while it is running.

This allows them to perform other work sooner than would otherwise be possible, further increasing productivity.”

amino acids. The test kit contains all the required reagents – standards, media, and a microplate containing

To find out more about Tecan’s

specific micro-organisms – making it

automation solutions, visit

remarkably easy to use. As it is

www.tecan.com/fluent

microplate-based, this fast microbiological method can be easily automated, and is ideal for food manufacturers who fortify their products with nutrients and need a precise

To learn more about the Institute for Product Quality, go to www.produktqualitaet.com

method for performing batch controls.”

“We chose the Fluent system for the production of VitaFast kits because we wanted to be able to increase our batch size. The high on-deck capacity of the platform – up to 47 microplates with our Reliable and reproducible liquid handling is vital for consistent assay kit manufacture

TECAN JOURNAL 1/2016

17

CLINICAL DIAGNOSTICS

Fungal detection accelerated Chinese IVD company Dynamiker has developed a range of rapid diagnostic kits to help address the rising problem of invasive fungal diseases in hospitals. Offering results in under two hours, these colorimetric and ELISA assays are designed to address the problems associated with traditional diagnostic techniques – poor sensitivity and slow turnaround times – allowing earlier implementation of antifungal treatments for better patient outcomes.

Dynamiker Biotechnology is an in

Jeffrey continued: “We offer a

clinical laboratories across China, and

vitro diagnostics kit manufacturer

range of immunodiagnostic assay

are expecting this number to rise to

based in Tianjin, China. Founded

kits allowing the detection of

between 100 and 150 this year alone.”

in early 2014, the company

both fungal antigens and specific

focuses on the development of

antibodies for Aspergillus, Candida

In addition to the genus-specific

immunodiagnostic assays for the

and Cryptococcus, representing

product range, Dynamiker also offers

rapid, early detection of invasive

the most comprehensive range on

a quantitative fungal infection assay

fungal diseases (IFDs). Jeffrey Lau,

the market. Working with serum,

based on the presence of the fungal

International Sales Manager at

cerebrospinal fluid (CSF) or broncho-

biomarker (1-3)-β-D-glucan, which is

Dynamiker, explained: “We specialize

alveolar lavage (BAL) samples, our

widely present in fungal cell walls. This

in the development and production

customers can perform a microplate-

kinetic assay is based on the binding

of IVD assay kits for the detection

based ‘panel’ test to rapidly determine

of the glucan to a proprietary reagent,

of the three main IFD-causing

the causative agent of an infection,

which activates a serine protease

fungi: Aspergillus, Candida and

getting accurate diagnostic results to

zymogen and causes a change in the

Cryptococcus. IFDs commonly cause

clinicians as quickly as possible and

OD. The Sunrise reader’s advanced

disease in immunocompromised

allowing targeted treatment to begin.”

temperature control – which heats the

patients, and can be particularly

microplate from both the top and the

problematic in the intensive care and

“A majority of our assays are based on

bottom – ensures consistent assay

respiratory wards of hospitals, where

colorimetric and ELISA technology,

performance. Jeffrey commented:

patients with primary pulmonary

making sensitive and reliable

“Thanks to its very uniform

infections or HIV are susceptible to

detection of changes in the optical

temperature control across the entire

secondary infections. Characterized

density (OD) of the reaction vital to

microplate, the Sunrise offers very

by very high mortality rates –

ensure accurate results. Although

good results for this assay, and has

sometimes 40 to 50 % – the major

most hospital laboratories already

effectively eliminated edge effects.

challenge of combatting IFDs is that

have microplate absorbance readers,

This is a huge advantage, providing

most traditional diagnostic methods –

the performance of these instruments

more reproducible results and

culture, microscopy and biopsy – are

is often not good enough to provide

allowing customers to use every well

either not sensitive enough or take a

reliable results in a clinical context.

of a plate, reducing the overall cost of

lot of time to get results. Our product

We tested a number of instruments,

testing. In addition, the Tecan China

range is designed to address this

and Tecan’s Sunrise™ offered the best

team helped us to develop a protocol

issue, providing positive pathogen

performance, which is why we have

to simplify the analysis of this assay

identification within just two hours

decided to recommend this reader to

using Magellan™ software, which has

and enabling antifungal treatment to

all our customers. We have already

made our customers very happy.”

be started as soon as possible.”

installed over 60 Sunrise readers in

18

TECAN JOURNAL 1/2016

CLINICAL DIAGNOSTICS

... providing positive pathogen identification within just two hours and enabling antifungal treatment to be started as soon as possible.

“As all our assays are performed in an automation-friendly 96-well microplate format, we have also begun evaluating the performance of our kits on the Freedom EVOlyzer® platform

The reader software makes it quick and easy to set up and run Dynamiker’s assays

for large hospital laboratories. This fully-automated workstation offers walkaway ELISA processing, using the same Sunrise reader and an integrated plate washer, providing the ideal solution when sample numbers are too high for manual processing. The system also has an eight-channel pipetting arm, which is a real advantage for kinetic assays, minimizing the amount of time required for pipetting operations.

Although our major market is currently in China, we are expanding towards Europe, the Middle East and Southeast Asia, and the greater reproducibility and process security offered by

Dynamiker’s assays are designed to provide positive pathogen identification within just two hours

automation will be a real advantage for approval of our IVD kits in these new markets,” Jeffrey concluded.

To find out more about Tecan’s Sunrise reader, visit www.tecan.com/sunrise To learn more about the Dynamiker range of fungal diagnostic products, go to www.dynamiker.com Local support is vital to the success of clinical diagnostic testing

TECAN JOURNAL 1/2016

19

APPLIED MARKETS

Safety in extremes German company ILS designs and builds custom chemical R&D testing units, primarily for customers in the petrochemical industry, integrating robotic components and reaction chambers into glove box set-ups that can withstand temperatures of 400 oC and conditions up to 100 times atmospheric pressure.

Integrated Lab Solutions (ILS), based

situation. This is one of the main

manufacturer working with moisture-

in Europe’s largest science park in

reasons we frequently choose Tecan

and air-sensitive catalysts. This module

Berlin, Germany, designs, develops

components. They are extremely robust

is effectively the heart of the system,

and constructs bespoke chemical R&D

and reliable, performing repetitive tasks

and everything else is parked around

testing units for its worldwide client

day after day; it’s obvious that they

it. You can think of it as the kitchen

base in the petrochemical, chemical

have been developed and perfected

that cooks the catalysts, shuffles

and pharmaceutical industries. Dr

over a long period of time. We tend to

around the different ingredients and,

Anton Nagy, founder and CEO of

do fairly unconventional things with

in the end, when the catalysts are

ILS, said: “We are a relatively low

them, but the way they have been

finished, it picks up the sample using

volume supplier of tailored solutions

made makes it easy for us to do that,

a Tecan Cavro syringe pump, and

to a niche market, integrating both

and the detailed product information,

injects it into the reactor. The robot

specialized and standard robotic

dimensions and diagrams really help us

does exactly what we need it to do; it is

components from various suppliers

as an OEM supplier.”

really fast, very accurate and excellent

into customized set-ups for our

from a safety point of view.”

clients. Our experienced engineers

“Controlling the units we assemble is

build and test all the units before they

a real challenge – all the systems we

“Tecan components also frequently

are sent out to customers, optimizing

deliver are fully automated, but we

have helpful add-on features – some of

the chemical processes here within

can’t simply direct actions from a PC.

which also have a significant impact on

our own laboratories. Based on the

Instead we operate on really robust,

safety – that you don’t tend to find on

expertise we have built in this area, we

industrial process control systems that

equipment from just any supplier. For

are also expanding our contract R&D

monitor around 200 sensors or control

example, if an obstacle gets in the way

services in catalyst testing, whether

points, constantly reading temperature

of an RSP, it recognizes its position,

that’s analyzing many different

and pressure and generating new set

always knows where it is and where to

compounds under similar operating

points to control parameters. The way

start again. You can demonstrate this

conditions, or looking at one or two

that the control systems of the Tecan

simply by putting your hand in the way

under different conditions in order to optimize a process.”

Safety is a major concern for all the units created by ILS, as Anton explained: “The systems we’re assembling tend to be for high pressure, high temperature applications, typical environments

of the arm, which gives our customers

ur engineers need O only write very simple scripts to get good, seamless integration.

for a refinery or a petrochemical

considerable confidence in the set-up.

This is really important, especially for our petrochemical clients, some of whom have a real aversion to having a fast-moving robotic arm in what is potentially a dangerous glove box environment. We’ve had situations in the past where somebody has accidentally put a bottle somewhere

R&D lab. These conditions can be

components are designed makes it

where it doesn’t belong, and this

quite demanding when it comes to

very easy to incorporate them into

simply is not an issue. Our Tecan

components, and we are looking for

these systems; our engineers need

representative is also extremely

robustness balanced with a good

only write very simple scripts to get

knowledgeable, multilingual and

product quality to cost ratio. Safety

good, seamless integration.”

pragmatic, guiding and supporting us

is understandably a very important

with his experience and knowledge of

issue for us and for our customers – if

“For example, we recently created a

products, applications and the market

a reactor containing hydrogen at 100

set-up using a Cavro® Robotic Sample

and, when I bounce ideas off him, he

bars pressure and at 300 oC vents

Processor (RSP) in an inert glove

comes back with very realistic solutions

by accident, it is a very dangerous

box atmosphere for a major catalyst

very quickly,” Anton concluded.

20

TECAN JOURNAL 1/2016

APPLIED MARKETS

ILS’ bespoke systems are designed specifically for high pressure,

Tecan Cavro robotic components offer fast, accurate and reliable

high temperature applications

automation

To find out more about Tecan Partnering, visit partnering.tecan.com To read more about ILS, www.integratedlabsolutions.com

TECAN JOURNAL 1/2016

21

CELL BIOLOGY

Sensitive to light The University of Salzburg’s Laboratory of Photodynamic Inactivation is exploring potential roles of photosensitizing agents in human health. With possible applications in areas as diverse as food decontamination and therapeutics, the lab is using a variety of photoactive compounds to generate reactive oxygen species which can kill key microbial pathogens or cancerous cells.

T his has effectively quadrupled the throughput of our investigations.

Dr Plaetzer and the Laboratory of Photodynamic Inactivation team

22

TECAN JOURNAL 1/2016

CELL BIOLOGY

Photodynamic inactivation (PDI) is a

system with bacteria, we then treated

experience outside of the human body

novel biophysical technique using light

the skin with a suitable photosensitizer

– for example on hospital equipment –

sensitive substances to disrupt biological

and, after just 5-10 minutes, exposed it

helping us to investigate how PDI could

activity. Following incubation with the

to a visible light source that is harmless

be used for surface decontamination.”

photosensitizing agent, exposure to a

to humans or the animal tissue. This

visible light source causes the formation

proved extremely successful in killing the

“The environmental regulation offered

of reactive oxygen species (ROS) that kill

bacterial cells, but the porcine tissue was

by the system is even more beneficial for

the target cells by oxidative processes.

completely unaffected.”

studying eukaryotic tumor cells. These

This mechanism is both highly effective

cells are affected by photosensitizers

and extremely fast-acting, offering

“We have used the same technique for

in a similar way to bacterial cells, and

possible new strategies for dealing with

the decontamination of plant materials.

the Spark allows us to study the in situ

multi-drug resistant pathogens – such

Pre-prepared salads are one of the most

formation of photoactive molecules over

as bacteria, yeasts and fungi – without

common sources of food contamination

time – up to 72 hours – under stable,

affecting the host tissue. Due to the

which affects human health, as

controlled conditions comparable to a

high proliferation rate of cancerous cells,

these foodstuffs are rarely heated or

CO2 incubator.2 The reader’s integrated

this approach has also been approved

cooked prior to consumption. Using

dispenser is an even greater benefit, as

by various national health institutions

photosensitive food additives which are

it uniquely offers continuous heating

for applications in oncology, allowing

already approved for other applications

and stirring of reagent flasks prior

malignant tumors to be specifically

– such as the yellow food coloring

to injection. This allows us to use the

targeted using suitable photosensitizers.

curcumin (E100) – we have demonstrated

module for automated seeding of cells

that we can effectively decontaminate

into assay plates, ensuring homogeneity

Dr Kristjan Plaetzer, Principal Investigator

these foodstuffs with a quick and easy

and maintaining the media at a constant

in the Laboratory of Photodynamic

light treatment.”

temperature to provide an even

Inactivation at the University of Salzburg’s

distribution of cells. This removes the need

Division of Physics and Biophysics,

Kristjan continued: “Characterizing the

for staff to sit and manually pipette cells

explained: “Antimicrobial resistance

uptake of the photosensitizing agents

into plates. It also means that we can move

is now a worldwide health problem,

into cells is obviously crucial to ensure

from a 96-well to a 384-well plate format,

threatening our ability to effectively treat

only the target is affected, and this is

which would be impossible to achieve

an ever-increasing range of infections

where our Spark™ 10M reader comes

manually, as the light sensitivity of the

caused by bacteria, viruses, fungi and

in. All photosensitive molecules are

chemicals we use means that all pipetting

other parasites. With very little progress

also fluorescent, so we can track the

and plate handling needs to be performed

in the development of new antibiotics,

intracellular concentration over time using

under very low light conditions. This has

there is now a real need for alternative

fluorescence measurements. The ability

effectively quadrupled the throughput of

treatment strategies which can bypass the

to incubate culture plates within the

our investigations – an experiment that

resistance mechanisms that have evolved

instrument’s environmentally-controlled

previously took 12 days to perform four

in organisms such as methicillin-resistant

measurement chamber is a real advantage

batches can now be achieved in a single

Staphylococcus aureus (MRSA), extended-

for this work, and we have even done

three-day study – which is vital for multi-

spectrum beta-lactamase (ESBL)

some preliminary studies with the new

parameter studies. It also saves reagents,

producing Escherichia coli and resistant

Te-Cool™ cooling module. This allows us to

lowering costs while producing the same

Candida albicans. The key advantage of

simulate the conditions micro-organisms

results in a shorter timeframe.”

PDI is that it has a non-specific mode of action – the resulting ROS disrupt cellular pathways in a random manner

To view a webinar on the role of

– and so pathogens cannot develop

laboratory automation in complex

resistance mechanisms. Our research is

translational research, go to

a curcumin derivate and a formulation on

focused on how we can translate this

www.tecan.com/spark10mwebinar

a porcine skin model. Photochemical &

approach from the research bench – where it is already well characterized and understood – to environments that can benefit human health.”

“Using S. aureus, E. coli and C. albicans

To find out more about Tecan’s Spark 10M reader, visit www.tecan.com/spark

1) T ortik, N et al. A comparative study on the antibacterial photodynamic efficiency of

Photobiological Sciences, 2015, DOI: 10.1039/ C5PP00393H.

2) K iesslich, T et al. Real-time analysis of endogenous protoporphyrin IX fluorescence from δ-aminolevulinic acid and its derivatives

as model organisms, we are looking at

To learn more about the University

reveals distinct time- and dose-dependent

various applications for PDI technology,

of Salzburg’s Laboratory of

characteristics in vitro. J Biomed Opt, 2014,

from food decontamination to chronic

Photodynamic Inactivation,

wound care. For example, in one

go to www.uni-salzburg.at/pdi

19(8), 085007.

recent study we used this approach to decontaminate porcine skin as a model of human tissue.1 After infecting the model TECAN JOURNAL 1/2016

23

ANALYTICAL CHEMISTRY

Large molecule bioanalysis simplified Thermo Fisher Scientific is helping to drive biotherapeutic research with the development of innovative sample processing tools designed to simplify and accelerate analytical workflows.

Offering automation-friendly affinity purification for proteins and antibodies, this provides a robust solution for high throughput preclinical research and development.

Biotherapeutics is now a key area

surface, allowing the target protein

Eric Niederkofler, Research &

of growth for the pharmaceutical

to be immobilized and purified

Development Manager at Thermo

sector, offering specificities and novel

with repeated wash cycles. This is

Fisher Scientific, explained: “In the

activities that cannot be achieved

commonly performed by fixing the

1990s, we began the development

with small molecule drugs. The

capture antibodies to a bead-based

of our MSIA™ (Mass Spectrometric

complex mode of action of many

support suitable for either magnetic or

Immunoassay) platform, which

biotherapeutics requires extensive

vacuum-based separation, but these

combined antibody capture of

preclinical testing and characterization

techniques can be time consuming

a protein of interest with mass

in cellular and animal models prior

– commonly taking seven to eight

spectrometric (MS) analysis. As

to clinical trials. Direct analysis of

hours – and offer poor recovery

antibody technologies and MS

antibody-based biotherapeutics in

rates, making quantitative analysis

instrumentation have developed, the

complex biological samples is virtually

difficult. This approach is also difficult

limitations of existing solid phase

impossible, due to the relatively low

to standardize or automate in a high

isolation techniques have become

abundance of these proteins and

throughput format, leading to higher

increasingly apparent, particularly

significant interference from other

costs for method development and

with regards to sensitivity. As a result,

macromolecules, requiring isolation

implementation.

we developed affinity microcolumns

of the antibody of interest prior to assessment.

Separation of these therapeutic molecules from complex media is generally performed using specific ‘capture’ antibodies affixed to a solid

– small volume, high surface area

his significantly T increases the rate of immobilization… allowing the incubation time to be reduced by up to 75 % in some cases.

supports mounted within pipette tips – as a way of improving both the ease of use and scalability of our MSIA technology. Each column is covalently derivatized with streptavidin, allowing straightforward immobilization of the user’s choice of biotinylated capture antibodies directly onto the inner surfaces of the microcolumn.”

“Initially developed for use in our in-house research activities, this system increases the rate and efficiency of target binding by using repeated

Each microcolumn is mounted within a pipette tip for simplified liquid handling

24

TECAN JOURNAL 1/2016

To overcome these limitations, Thermo

aspiration and dispense cycles. A

Fisher Scientific has developed a

key benefit of this ‘active’ incubation

solution which combines microfluidic

approach is that the microfluidic

principles with automated liquid

channels in the column repeatedly

handling to accelerate sample

bring the target molecule into close

preparation and improve recovery

proximity with the immobilized

rates for biological macromolecules.

capture antibody. This significantly

ANALYTICAL CHEMISTRY

increases the rate of immobilization

past, but selected the Freedom EVO®

the necessary devices and labware

compared to shaking with bead-based

workstation for the development of

onto the instrument’s large workdeck,

supports, allowing the incubation time

our latest product – MSIA Streptavidin

providing completely walkaway

to be reduced – by up to 75 % in some

EVO micro columns – due to the high

sample preparation. As we continue

cases – without affecting recovery

capacity, robustness and flexibility

to develop applications on the system,

rates. The capacity of these columns

this platform offers. In my mind,

we have also been impressed by the

is also very good, allowing the capture

Tecan is a company that really

versatility of the software – it has a lot

of target molecules across a broad

pushes the boundaries of laboratory

of built-in functionality – and we hope

dynamic range.”

automation and system integration,

to take advantage of this further in the

and the Freedom EVO is very easy to

future,” Eric concluded.

“As the microcolumns are housed

configure to your exact workflow.”

within pipette tips, this approach is ideally suited to automation with a

“The microcolumns are designed

liquid handling platform. When you

specifically to work with the platform’s

go down the automation route, there

MultiChannel Arm™ (MCA) 96,

is obviously a significant investment

allowing high throughput parallel

involved, so you want to be able to do

processing of up to 96 samples

everything in much higher throughput.

in under two hours, but it is the

We have worked with a number of

workstation’s versatility that is the

different liquid handling systems in the

real advantage. You can integrate all

To find out more about Tecan’s mass spectrometry sample preparation solutions, visit www.tecan.com/analyticalchemistry To learn more about the Thermo Scientific MSIA Streptavidin EVO micro columns, go to www.thermoscientific.com/en/products/ mass-spectrometric-immunoassay.html

The microcolumns are designed specifically to work with the MCA 96 for optimal performance

TECAN JOURNAL 1/2016

25

DRUG DISCOVERY

Step-by-step automation Antibody discovery and development company MorphoSys has a wealth of experience in designing novel assays for the screening and characterization of therapeutic antibodies. With active programs in oncology, inflammatory and autoimmune diseases, the company’s Discovery, Alliances and Technologies Department relies on a variety of automated solutions to provide the throughput necessary to support its pipeline.

Antibody technologies have a host

tumors), inflammatory and autoimmune

adopted, with a large number of small

of potential applications throughout

diseases – and have a very active

devices which perform individual steps of

medicine, from biomarker discovery and

research program designed to exploit

the overall workflow. This minimizes the

disease characterization in fundamental

our in-house technologies. For example,

amount of time each system is occupied

research to diagnostic devices and

our Ylanthia platform is the industry’s

for any given experiment, virtually

biological therapeutic agents in a clinical

largest known antibody Fab (fragment

eliminating the need for instruments

setting. Identifying and validating

antigen-binding) library – comprising

to sit idle during incubation steps and

antibodies with specificity for the

over 100 billion distinct, fully human

maximizing productivity.

epitope of interest is a laborious and

antibodies – and our HuCAL (Human

time-consuming process, requiring

Combinatorial Antibody Library)

Until recently, generating antibody

the screening of libraries consisting of

platform contains several billion distinct

predilutions for screening has been a

thousands or hundreds of thousands

fully human antibodies. This allows us

bottleneck in the workflow, as this has

of antibodies to select

always been performed

suitable candidates for

manually. Each antibody

further investigation. These candidates then need to be thoroughly characterized to establish their specificities and binding efficiencies, as well as to identify any potential off target effects.

I n just a few months since its introduction, the D300e really has become part of our routine workflow, with many project teams using it whenever possible.

MorphoSys AG, based in

is diluted in 96-well plates – usually creating between 8 and 16 different dilutions – then transferred to 384-well plates for testing, generally in duplicate or triplicate.

This is obviously prone to errors and very time consuming, so the team was

Munich, Germany, combines to perform rapid selection of antibodies

looking for ways to automate this step.

biology with its in-house antibody

targeting even the most difficult

Stephanie continued: “We already had a

technology platforms – HuCAL®,

disease-related epitopes.”

large number of Tecan devices in the lab,

an in-depth understanding of disease

including a Freedom EVO® workstation

Ylanthia® and Slonomics® – to provide high quality antibody generation and

The department has invested heavily in

for automated hit picking, plus various

optimization. Stephanie Patzelt, Principal

laboratory automation in order to achieve

readers and washers, so were keen to see

Technical Assistant in the Discovery,

a high throughput and make the most of

what the company could do to help us

Alliances and Technologies Department,

these technologies. As there are over 100

with this aspect of our workflow.”

explained: “We work across a range of

personnel working on a wide range of

disease areas – including oncology (both

different projects and diseases, a ‘modular’

She added: “Direct digital dispensing

hematological malignancies and solid

approach to automation has been

was a very appealing option – allowing

26

TECAN JOURNAL 1/2016

DRUG DISCOVERY

direct dispensing of the antibodies into the assay plates – but was originally only available for use with small molecules in DMSO. When Tecan advised us that the updated system capable of dispensing aqueous solutions was being launched, we immediately looked into this. As soon as we began testing the D300e in house, it was clear that this instrument was ideal for our needs, eliminating the cost and wastage associated with predilutions.”

Using the D300e has significantly reduced the amount of material required for each experiment, as well as minimizing the cost of consumables, and has proved very popular within the lab. It has also extended the experimental window for

Members of the MorphoSys Discovery, Alliances and Technologies Department

many investigations, as the increased dispensing accuracy – particularly at very low volumes – has improved data quality.

“In just a few months since its introduction, the D300e really has become part of our routine workflow, with most project teams using it whenever possible. The system’s licence-

To find out more about Tecan’s D300e, visit www.tecan.com/digitaltitration To learn more about MorphoSys, go to www.morphosys.com

free software is a real advantage for this, meaning that everyone can create their experimental designs on their own computer, without occupying the D300e’s dedicated workstation, and simply transfer the complete protocol to the device for processing. This is very important in such a busy lab, allowing numerous projects to use the device virtually in parallel,” Stephanie concluded.

TECAN JOURNAL 1/2016

27

PRODUCT NEWS

New Fluent features increase speed and flexibility TM

Spend more time doing the things that matter thanks to new Fluent laboratory automation solution* features designed to provide more streamlined and robust walkaway processing**. These latest additions further extend the flexibility of Fluent, maximizing productivity and ensuring a precise match for your laboratory’s automation needs.

The new Finger Exchange System allows

processing devices and the workdeck,

Customers can now opt to combine both

the workstation’s Robotic Gripper Arm

without the need for user intervention.

technologies on one platform, using air

to automatically switch between gripper

displacement for rapid pipetting with

options – including Centric Fingers,

The flexibility of Fluent’s high definition

disposable tips, and liquid displacement

Eccentric Fingers and Tube Fingers, plus

liquid handling has also been further

for reagent distribution or bulk

customized options available through

enhanced, with the option to mount

dispensing. This ensures you can always

the Tecan Integration Group – on the fly.

two Flexible Channel Arms on a single

select the most appropriate pipetting

This ensures secure transport for virtually

instrument. This pipetting option enables

technology for your application – offering

any automation-friendly plate or tube

access to virtually any tube or well

the best of all worlds – and gives you the

format, allowing straightforward sample

configuration, and provides a choice

option to increase throughput by using

reformatting and transfer of labware

of air or liquid displacement pipetting

both Flexible Channel Arms together to

between centrifuges, storage modules,

technologies to suit your application.

prepare a single plate or perform parallel analyses from common samples.

Understanding that confidence in workflow automation is critical to success, the Tecan team has also developed Method Recovery for FluentControl™.

This powerful yet simple feature helps to minimize the disruption caused by an unexpected event – such as a power loss or computer failure – providing a straightforward, user-friendly way of salvaging a run. Using the integrated touchscreen, Method Recovery guides the operator through the steps required to re-establish an interrupted protocol, minimizing potential loss of valuable samples and reagents.

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

* For research use only. Not for use in diagnostic procedures. ** N ew features due to be released soon.

The new Finger Exchange System allows on-the-fly switching between gripper heads

28

TECAN JOURNAL 1/2016

PRODUCT NEWS

Empower your research with the Spark 20M multimode reader ®

The new Spark 20M multimode microplate reader* offers tailor-made solutions to suit virtually any drug discovery or advanced life science research application. This freely configurable system gives researchers access to new techniques and features intended to enhance and streamline biochemical and cell-based workflows.

At the heart of the instrument are

cell-based assays.

Spark’s unique Fusion Optics and a

To complement

powerful, ultra-high frequency xenon

the existing cell

flash lamp. This advanced optical

counting and viability check functions,

system can be combined with your

a new automated cell imaging and

choice of high performance detection

confluence measurement feature allows

modules – from basic fluorescence

incubation and monitoring of cell culture

and DNA quantification to multi-color

microplates within the instrument’s

luminescence and TR-FRET – ensuring

environmentally-controlled chamber.

a perfect match for your workflow,

This allows the user to define the

with the option to upgrade as your

confluence at which the assay starts/

needs change.

ends or the substrate is injected, offering optimal assay results and greater

Understanding that throughput is

walkaway operation.

essential to drug discovery workflows, Tecan has introduced an enhanced

To ensure complete confidence in

Spark 20M offers fully automated cell

fluorescence module designed to

your data, the Spark 20M offers

counting, viability checks and confluence

improve sensitivity and increase the

complete control of the measurement

measurements

speed of high throughput screening.

environment, including the CO2 and

Combining dichroic mirrors with

O2 partial pressures, humidity and

the variable bandwidth selection

temperature. A newly developed

and full wavelength flexibility

Te-Cool™ cooling module now provides

offered by the latest generation

complete environmental independence,

QuadX Monochromators™, this set-

uniquely allowing the measurement

up allows on-the-fly measurements,

chamber temperature to be set below

providing exceptional performance

the ambient room temperature, offering

and speed – even for closely related

more precise control for more accurate

excitation and emission spectra –

and reliable results. These new options

without compromising on data quality.

– combined with the ability to read 6- to 1,536-well microplates – ensure there is a

Up to 1,536-well plate formats can be

The Spark 20M’s cell handling

Spark 20M configuration to increase the

accommodated

capabilities have also been enhanced to

productivity of your lab, both today and

provide greater workflow automation for

in the future.

To find out more about Tecan’s Spark 20M, visit

* Spark multimode reader is for research use only.

www.tecan.com/spark20m

TECAN JOURNAL 1/2016

29

CORPORATE NEWS

Sias joins Tecan Partnering Sias – a leading OEM supplier of laboratory automation solutions – has joined the Tecan Group, adding complementary new platforms, capabilities and expertise to customers of Tecan Partnering.

A dedicated OEM supplier, Sias is committed to the highest quality standards and building close relationships with its customers to ensure projects are delivered in the shortest possible time.

Complete automation of laboratory

and providing a healthy funnel for new

dedicated, highly trained team, innovative

workflows has become increasingly

development projects. Dr Achim von

technologies and leading products, as well

important over the last decade,

Leoprechting, Head of Tecan Partnering,

as a strong pipeline of new development

particularly in the in vitro diagnostics

explained: “Sias’ core expertise

projects and dedicated business

and contract research sectors.

in automating immunoassays and

partners all over the world. Tecan’s

The accuracy, reproducibility and

molecular diagnostics workflows – as

global presence will allow us to grow

comprehensive audit trails offered by

well as its strong client base in China –

even faster, leveraging local sales and

modern laboratory automation solutions

perfectly match our corporate strategy.

service organizations to the advantage

provide the high level of process security necessary to meet stringent quality control and regulatory standards.

Developing automation systems capable of delivering these features is both time consuming and complex, requiring extensive liquid handling expertise to ensure reliable, error-free processing. To overcome

of our customers. We will

We are pleased to have reached this agreement and look forward to welcoming the Sias team into Tecan. Sias will further extend our leading Partnering portfolio, providing access to complementary automation platforms which are particularly well suited to small to medium-sized OEM systems for diagnostic and research applications.

this issue, many leading

also greatly benefit from the combined capabilities of a larger development organization.”

Tecan CEO Dr David Martyr added: “We are pleased to have reached this agreement and look forward to welcoming the Sias team into Tecan.

Sias will further extend our leading Partnering portfolio, providing access to

providers choose to work

complementary automation

with a knowledgeable OEM laboratory

In addition, the close proximity of the

platforms which are particularly well suited

automation partner – such as Tecan

two Swiss facilities will allow synergies

to small to medium-sized OEM systems for

Partnering – to reduce both the time

to be implemented.”

diagnostic and research applications.”

and cost of developing new products.

Founded in 2000, Sias has grown into a

The company’s modular platforms and

leading supplier in the sector, combining

robotic components are ideally suited for

To find out more about Sias,

a flexible approach with open and

low- to medium-throughput applications,

visit www.sias.biz

efficient communication to establish

further extending Tecan’s capabilities

itself a reputation for exceptional

into new markets and applications. Sias’

customer satisfaction.

existing customers will also be able

The common history of a

to benefit from Tecan’s global sales

customer-focused approach, together

infrastructure and after-sales support

with its close proximity to Tecan’s

network. Andre Guenter, CEO of Sias,

Swiss facilities, make Sias an excellent

commented: “This agreement will be

fit with Tecan’s existing Partnering

mutually beneficial for both companies

portfolio, allowing close cooperation

and for our customers. Sias has a

30

TECAN JOURNAL 1/2016

To find out more about Tecan Partnering, visit partnering.tecan.com

CORPORATE NEWS

TECAN JOURNAL 1/2016

31

Every lab.

Every day.

Empowered.

Australia +61 3 9647 4100 Austria +43 62 46 89 33 Belgium +32 15 42 13 19 China +86 21 220 63 206 Denmark +45 70 23 44 50 France +33 4 72 76 04 80 Germany +49 79 51 94 170 Italy +39 02 92 44 790 Japan +81 44 556 73 11 Netherlands +31 18 34 48 17 4 Singapore +65 644 41 886 Spain +34 935 95 2531 Sweden +46 8 750 39 40 Switzerland +41 44 922 81 11 UK +44 118 9300 300 USA +1 919 361 5200 Other countries +43 62 46 89 33 Tecan Journal, Customer Magazine of Tecan Trading AG., ISSN 1660-5276 Design: OTM/London www.otmcreate.com Photography: Günter Bolzern/Zürich www.bolzern.tv Editor in Chief: Tecan Trading AG, Antonietta Allocca Editor: kdm/UK www.kdm-communications.com Editor: UP THERE, EVERYWHERE/Sweden upthereeverywhere.com Print: DAZ Druckerei Albisrieden AG/Zurich www.daz.ch Address: Tecan Trading AG, Marketing Communications, Seestrasse 103, CH-8708 Männedorf, Switzerland, hello@tecan.com, www.tecan.com To register for the Tecan Journal please go to www.tecan.com/journal © 2015 Tecan Trading AG, Switzerland, all rights reserved.

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

All mentioned trademarks are protected by law. In general, the trademarks and designs referenced herein are trademarks, or registered trademarks, of Tecan Group Ltd., Mannedorf, Switzerland. A complete list may be found at www.tecan.com/trademarks.

Product names and company names that are not contained in the list but are noted herein may be the trademarks of their respective owners. For technical details and detailed procedures of the specifications provided in this document please contact your Tecan representative.

This journal may contain reference to applications and products which are not available in all markets. Please check with your local sales representative: www.tecan.com/contact