Edition 1/2020
Tecan Journal Life Sciences, Diagnostics and Partnering
A SparkÂŽ of hope for nerve damage repair
Food for thought
Capturing the IVD market in China
Artificial intelligence – the hero drug discovery needs
Pages 18-19
Pages 22-23
Pages 24-25
Pages 26-27
CEO WELCOME
Welcome to the Tecan Journal As Tecan enters its 40th year, I would like to begin by thanking you all – customers, partners, investors, suppliers and employees – for your ongoing commitment, professionalism and passion. Your insights drive us to continue to push the boundaries of laboratory automation to even better serve our clients. As such, you have all contributed to our success, so it seems only fitting that we want to celebrate this landmark occasion with you. We will be hosting a whole year of events – both scientific and social – around the world, and I’d like to cordially invite you to join us. This anniversary provides an excellent opportunity to celebrate Tecan’s past, and look to its future. Our heritage is in automation but, over the decades, we have accumulated an enormous depth of understanding in research and diagnostics – in areas such as cancers, infectious diseases, and hereditary and metabolic disorders – through our partners and customers. Increasingly, we’re moving towards offering more complete solutions – for genomics, proteomics, and cell and tissue analysis – that consist not only of automation, but also include software to enhance data analysis and usability, and reagents and consumables that target laboratory productivity and help accelerate developments and discoveries. Whether it’s supporting biological research, drug development and clinical labs through our Life Sciences business, or enabling precision medicine via our Synergence™ and Cavro® OEM solutions, our aim is to further our understanding of the world around us and make our contribution to a healthier global population. I hope you enjoy reading this issue, Achim von Leoprechting CEO
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TECAN JOURNAL 1/2020
CONTENTS
Contents 2
Welcome
4 - 6 Live cell imaging: how to gain more control 7 SparkÂŽ Cyto to empower CORE oncology research 8 - 9 Precision pipetting and perfect plates 10 - 11 Driving the development of novel 3D cell-based assays
8-9 Precision pipetting and perfect plates
12 - 13
Traditional Chinese medicine for the 21st century
14 - 15 Positive pressure proteomics 16 - 17
Sensing success
18 - 19 A Spark of hope for nerve damage repair 20 - 21
Streamlining genomics workflows
22 - 23
Food for thought
24 - 25 Capturing the IVD market in China 18 - 19
26 - 27 Artificial intelligence – the hero drug discovery needs
A Spark of hope for nerve damage repair
Applications and platforms presented in the Tecan Journal may not be available in all markets. Please consult your local Tecan office for information.
TECAN JOURNAL 1/2020
3
CELL BIOLOGY
Live cell imaging: how to gain more control Christian Oberdanner, Marketing Application Specialist Live cell imaging is one of the most important techniques in life sciences today. But behind every great imaging assay, pity the poor scientist grappling with the demands of biological variability and complex kinetic assays. Live cell experiments are often synonymous with unsociable working hours, tedious protocols and unrepeatable results. In this blog, we explore what it takes to tame automated cell imaging assays, and take back control of kinetic experiments to get reliable results more quickly, with fewer errors and less aggravation.
Real-time cytometry is empowering
giving you misleading results. Here are
help us accommodate the necessary
life science exploration
six common pitfalls that can send your
complexity, rather than avoid it.
The popularity of imaging living cells
live cell experiments spinning out of
continues to grow year on year. In the
control::
3) Failing to adapt to biological
nearly 8,000 scientific publications
1) Starting with unhappy cells
Living cells are inherently variable, which
on live cell imaging – more than in the
Many live cell assays are doomed to
means that, to obtain consistent assay
preceding 40 years combined. Why?
fail before they even start, because the
results from day-to-day or lab-to-lab,
Because the old adage ‘seeing is believing’
cells are not in the exponential growth
you may need to adjust experimental
is actually true: images convincingly
phase, or have been subjected to stress
protocols and timings on the fly. For
capture aspects of living cells’ behavior
prior to the experiment – for example,
example, rather than always starting
and function that are otherwise difficult
when transferring from the tissue
your assay a fixed number of hours after
or impossible to detect.
culture incubator to the slightly different
seeding, you may get more consistent
environment in the imager or plate
results if you wait a variable time
reader.
period until the cells reach their optimal
variability
last five years alone, there have been
Today’s cell imaging platforms enable
confluence – say 80 percent. But what
real-time, non-destructive capture of
2) Experimental complexity
do you do if the cells reach 80 percent
individual cellular events, in multi-well
Kinetic live cell assays can get very
confluence when you aren’t in the lab?
formats that support higher throughputs
complex, very quickly. That’s because
Quite often, we compromise and start
and robust, cell-by-cell statistical
you need to factor in many different
the assay at the wrong confluence,
analyses. When image-based cytometry
fluorescent probes, time points, dose
rather than go back to the drawing
is combined with the capabilities of
concentrations, replicates, control
board and rework the timings.
a multimode plate reader, even more
wells, cell types, and so on. The more
insights are possible. With multiple
elaborate the experiment, the more
When you compromise protocol timings
detection modalities, including both top-
chances there are for variability to
to fit your schedule, the assay may
and bottom-reading configurations, you
creep in and mistakes to be made. To
still work, but reviewers may question
can multiplex more types of assays and
make matters worse, manual steps
whether your results are biologically
make use of novel fluorescent probes to
and complicated instrument control
relevant. In the example discussed
quantify complex dynamic events.
software can significantly increase the
later, we see how variable factors like
likelihood of human error. Unfortunately,
percentage cell viability and fluorescent
Why live cell experiments get out of hand
some experimental complexity is
signal may dictate the most appropriate
Real-time live cell assays often involve
often unavoidable – you really do need
times to add various stimuli or probes,
sensitive cell types and complex
all those concentrations, replicates
or when to start and stop imaging to
protocols that can easily go awry,
and time points! Fortunately, cell
ensure you capture the full response.
wasting valuable resources and possibly
imaging platforms are advancing to
The Blog 4
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TECAN JOURNAL 1/2020
CELL BIOLOGY
4) Disturbances and disruptions
When a simple assay isn’t so simple
two fluorescent dyes: calcein AM to
Mechanical or environmental
Live cell imaging assays require a high
identify live (metabolically active) cells,
disturbances can trigger cellular stress
degree of responsive control; the person
and propidium iodide (PI) to detect
responses that will alter cell behaviors
running the experiment typically needs
dead cells (loss of plasma membrane
and responses to stimuli, and may even
to monitor conditions frequently, and
integrity).
activate cell death pathways. Common
take action based on cell appearance
culprits include lid lifting, harsh addition
or some other biological cue, such as
Seems pretty straightforward, right?
of reagents or compounds, wash steps
intensity of a fluorescent indicator.
But take another look at the assay schematic. There are several key
and transfer of plates from one device to another.
To illustrate the challenges of live
points in the protocol when biological
cell imaging assays, and the level of
conditions trigger a particular action.
5) Scale-up and miniaturization
experimental control needed to avoid
Kinetic assays may work fine at the
the pitfalls discussed above, let’s take a
prototype stage, only to fall prey to
look at a relatively simple ‘live/dead’ cell
mistakes when scale-up suddenly
viability assay.
If you are running the assay without full automation, you will need to assess the cells periodically on a manual microscope to monitor confluence and
amplifies the number of replicates, pipetting steps, samples and compounds. In addition, scale-up often entails miniaturization, which means dealing with very small liquid volumes.
STOP IMAGING @10 % viability
1
7
SEED CELLS
Incubate to 80 % confluence
In such cases, evaporation – and, by extension, assay duration – becomes a significant concern. At the same time, liquid handling accuracy and precision become even more critical, and the chances of mistakes and crosscontamination are further magnified. 6) Image management challenges Depending on the assay complexity, a live cell imaging experiment may
CELL VIABILITY ASSAY 6
Calcein AM = live Propidium iodide = dead
TIME COURSE 4 5
ADD COMPOUND 4h incubation
3
Image every hour and analyze in real time
ADD DYES (@~16h) 1h incubation
START BOTTOM READS Red fluorescence = dead cells
generate thousands – or even hundreds
START IMAGING
of thousands – of images per run. Data
Dead cell intensity threshold reached
storage and archiving can be expensive,
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and servers quickly become filled to capacity. If storage space runs out in the middle of a critical run, you risk losing the cells and the entire data set – a big toll in terms of the cost, time and labor
The goal of this assay is to monitor changes in percentage cell viability
you put into your experiment. For all
in response to varying doses of test
these reasons, limiting the number of
compounds, generating a dose response
images you need to acquire can be a
curve and half maximal viability (IC50)
smart move.
for each. To assess viability, we are using a conventional combination of
decide when to add compounds. The timings for compound addition, dye addition and PI fluorescence recording are all dictated by the confluence of the cells. Likewise, the ideal imaging start and stop times depend on when the cells start to be affected by each
www.tecan.com/blog TECAN JOURNAL 1/2020
5
CELL BIOLOGY
compound, and when the percentage
subsequent steps. An automated
imaging to start from that point onward.
cell viability bottoms out. Orchestrating
multimode reader and cell imaging
Similarly, if we can calculate percent
all these actions manually or across
platform with this sort of conditional
viability by analyzing the image data in
multiple detection platforms without
real-time experimental control can
real time, we can set a second threshold
making any mistakes is not easy. Maybe
minimize the amount of manual
that will trigger the imaging to stop
this ‘simple’ live/dead assay is not so
intervention needed, while eliminating
when viability bottoms out, in this case
simple after all!
subjective assessments – triggering
at 10 percent. With both thresholds
additions and reads at the right
applied, imaging is performed only from
How to take back control of your live
times, based on accurate quantitative
hours 20 to 44. The result? Automated
cell experiments
measurements.
real-time experimental control reduces
Let’s take a look at some improvements we can make to gain more control and eliminate errors.
the number of acquired images by 5,376 3) Reduce the number of images acquired As shown in the schematic, the assay
1) Get on-board environmental control At the start of the experiment, cells are seeded into a 384-well plate, and left to incubate until they have recovered and reached 80 percent confluence. Crucially, you need to avoid shocking the cells when transferring them from the tissue culture incubator to the liquid handling workstation or detection system. This means providing the cells with a stable, humidified on-board environment (typically 37 oC and 5 % CO2), where they can equilibrate for a sufficient amount of time before compounds are added and measurements are taken. 2) Automatically trigger actions using thresholds
is configured to run for approximately 48 hours from start to finish. If we run
– over 20 percent! That’s a major saving in terms of both experiment time and storage space. 4) Create a walkaway process
the assay in just one 384-well plate,
A final consideration is the amount
collecting a single whole-well image for
of hands-on time needed to run the
both the red and green channels every
assay from start to finish. As mentioned
hour from the point that the dyes have
earlier, the more manual steps you can
been equilibrated (ie. hours 17 through
eliminate the better. Automating as
48), we’ll need to collect a jaw-dropping
much of the assay protocol as possible
24,576 images.
will significantly improve accuracy, decrease variability, reduce the chance
Can we do better? Of course. It turns
of errors and free up valuable staff for
out that we are collecting many images
more important, less tedious tasks.
that are not needed, namely those at the very top and bottom of the dose
The answer? A multimode imager with
response curves. The key to reducing
real-time experimental control
the image number is to use threshold-
The best way to achieve hands-free,
based conditional programming to
error-proof kinetic cell assays is with a
collect only the images that are actually
multimode reader that includes on-
needed to generate a reliable curve.
board environmental control and lets
Here’s how it works...
you perform image-based confluence assessment, intensity measurements,
Depending on the health of the cells at the time of seeding, the length of time
After the cells have been equilibrated
fluorescence imaging and real-time
needed to reach 80 percent confluence
with the dye mix, we start continuously
image analysis – all on the same system.
can vary unpredictably. To avoid the
recording PI intensity using bottom
And crucially, you need a system that
hassle of having to adapt your protocol
reading (no images required!). We can
allows you to set up threshold-based
and working hours to suit the cells, the
then automatically detect an increase
conditional responses easily and with
smart solution is to automate confluence
in fluorescence when dead cells first
no need for programming skills.
determination, and set up a confluence
start appearing, and use an intensity
threshold that will automatically trigger
threshold to trigger the two-color
The Blog 6
TRENDS, NEWS, STORIES AND MUCH MORE! FROM THE EXPERTS TO YOU.
TECAN JOURNAL 1/2020
CELL BIOLOGY
Spark Cyto to empower CORE oncology research ®
Congratulations to Christophe Deben
the unique features of the Spark Cyto
and the team at the University of
could contribute to the growing field
Antwerp’s Center for Oncological
of immuno-oncology.
Research (CORE) on winning a fullyloaded Spark Cyto plate reader with live
Christophe commented: “I’m very
cell imaging and real-time cytometry!
pleased to have been selected as the
This competition, which ran from April
winner of this competition. When
to September 2019, required labs to
writing the project proposal, I let my
submit a written proposal explaining
imagination run wild in creating the
how they would use the system to
experimental set-up, and it amazes
further their research and advance
me that nearly everything I thought of
scientific understanding. A shortlist
is possible with the Spark Cyto! The
was selected from a strong field of over
versatility of the instrument means that
100 entries by a panel of expert judges,
we will be able to use it for nearly every
and each finalist was invited to give a
line of research running at CORE, and
short webinar presentation providing
I can’t wait to start working with it and
further details of their planned research.
discover all of its capabilities.”
Christophe’s winning proposal described how he would use the Spark Cyto to
Look out for details of Christophe’s work
investigate the influence of oxygen
in a future issue of the Tecan Journal.
levels on chemotherapy-induced CD70 expression and antibody-dependent cellular cytotoxicity in non-small cell lung cancer cells. The judges were impressed by both the scope of this
To find out more about the Spark Cyto, visit www.tecan.com/sparkcyto
proposal and Christophe’s vision of how
CORE received its Spark Cyto system in early December
www.tecan.com/blog TECAN JOURNAL 1/2020
7
CELL BIOLOGY
Precision pipetting and perfect plates Probiotics play an important role in animal nutrition, ensuring a healthy balance of gut microbiota to improve performance or productivity. Scientists at Christian Hansen are using high throughput liquid handling systems to fully automate sample inoculation and plating for research into novel bacteria for animal feed supplements.
‘Good’ bacteria are increasingly being
and cattle: “We use both spore-forming
different pipetting technique or they
added to foodstuffs such as yogurt and
bacilli – which are very robust and
hold the tube in a different way when
dairy products to improve nutrition and
hardy – and lactic acid bacteria, that
vortexing the sample, and this can
human health, and the agricultural
are more sensitive to stress in the form
affect the results. As all our products
sector is using the same approach to
of heat or moisture. Our work involves
must adhere to strict quality control
boost the health and productivity of
growing up the different bacterial
standards and meet the criteria of
livestock. Animal wellbeing is incredibly
strains on agar plates and counting the
relevant regulatory authorities, all of
important to many farmers, who strive
successful colonies that form, before
our work must be consistent and
to produce food that is both high
selecting strains for further testing.”
replicable, which was a huge
quality and sustainable. Christian
contributing factor to deciding to
Hansen (Chr. Hansen), a global
“As some of our cultures have up to a
bioscience company based in Denmark,
hundred billion bacteria per gram, the
has been committed to using natural
samples need to be diluted significantly
Following a recommendation from
ingredients for improved food and
before plating. If this was being carried
another group at Chr. Hansen, Christel
health for more than 140 years. Christel
out manually, it would mean performing
got in touch with Tecan to discuss
Galschiøt, senior laboratory technician
8-10 serial dilutions before spreading
liquid handling automation. She
in Stability, Formulation and Analysis
the bacteria onto the agar, which is
continued: “We needed a system that
(SFA) in the company’s Animal Health
incredibly laborious. In addition to the
Innovation Division, discussed how they
time factor, we also found that there
are developing beneficial bacterial
was substantial variation between
strains as probiotics for poultry, swine
technicians; everyone has a slightly
automate our workflow.”
could not only perform reliable plating, but that also had precision pipetting capability for our serial dilutions. The Freedom EVO ® 200 was the best system for our workflow, as we could easily integrate a SciRobotics PetriPlater™ into the system. Our set-up can accommodate up to 60 standard plates at a time, which is fantastic, as it allows full automation of both the serial dilution steps and the plating of the samples. An integrated barcode reader also allows us to track the samples through each stage of the workflow, before transferring them to an external colony counter to avoid a backlog and keep the process running smoothly.” “We purchased two Freedom EVO platforms in 2015 and, since automating our workflow, we can run significantly more plates than we could have done manually,” Christel added. “In 2018, we
Freedom EVO platforms allow scientists at Christian Hansen to automate their inoculation and plating protocols
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TECAN JOURNAL 1/2020
prepared around 25,000 plates; achieving this high throughput by hand
CELL BIOLOGY
he automated solution not only saves T time, it has also increased our consistency between plates. would have required several
as we don’t have to worry about
Freedom EVOware ® script and some
technicians, which isn’t cost effective
keeping an eye on the system while it’s
visual basic programs that were needed
and is not the best use of our time. The
running, or interrupt the workflow.
to create the worklists. They also
automated solution not only saves time,
We’ve also noticed that we are now
supplied us with a template that helped
it has also increased our consistency
using less plastic, as we are using the
us to adapt our scripts to incorporate
between plates. We have also
smaller volume tips where possible and,
the nested tips. This was slightly
introduced nested tips into one of our
as the nested tips are sterile, this
complicated, as we had to do some
platforms, which gives us a very high
reduces packaging waste as well.”
local optimization, but we also got very good advice from the helpline and
on-deck tip capacity. This means that we need to refill the tips a lot less
“When it came to setting up the
technical staff. All in all, it was a smooth
frequently, and we no longer need to
system, Tecan offered very valuable
transition to automation, and we are
either reset the tip position or replace
assistance. The company’s application
very impressed with the service that
the tips during a run. This is fantastic,
specialists helped us set up both the
Tecan has provided us with over the years,” Christel concluded.
To find out more about Tecan’s cell biology solutions, visit www.tecan.com/cellbiology To learn more about Christian Hansen, go to www.chr-hansen.com/en An integrated SciRobotics PetriPlater supports this high throughput workflow
TECAN JOURNAL 1/2020
9
DRUG DISCOVERY
Driving the development of novel 3D cell-based assays 3D cell culture is an area of
Cell-based assays are integral to drug
see what’s going on in the cells.
great interest in the drug
development, helping to speed up the
Although we use both 2D and 3D cell
time taken for pharmaceuticals to go
models, our attention is increasingly
from bench to market. Researchers in
focusing on the 3D format, as this
the Cellular Pharmacology Department
provides a more physiologically-
– part of Discovery and Development
relevant representation of how cells
act in response to compounds
Technologies at Merck’s facility in
behave in vivo. 3D models can also
in vivo. Merck’s Cellular
Darmstadt, Germany – are exploring
successfully mimic the complex
Pharmacology Department
novel cell-based assays for high
microenvironment of a variety of
throughput screening methods.
tissues, assisting research into
Dr Sakshi Garg, head of the laboratory,
different disease areas.”
development industry, as 3D models give a more accurate representation of how cells
specializes in the use of spheroid cell cultures to test various conditions and
explained: “High throughput screening platforms are essential for many drug
Jasmin Hunsrucker, a PhD student in
compounds of interest, and
discovery programs, in order to
the lab, continued: “To create 3D
identify candidate drugs.
generate as much data as possible from
spheroids, we generally use coated
Automation plays a vital role
the compounds of interest. We perform
384-well plates with round-bottom
a variety of target- and phenotypic-
wells to prevent the cells from sticking
based studies, using a combination of
to the plastic. Once cell density has
image-based and enzymatic assays to
been optimized, we leave the cells to
allow multivariate analysis and actually
float in the media to form spheroids
in this process, enabling high throughput screening of cellbased assays.
Left to right: Bianca Roth, Jasmin Hunsrucker and Sakshi Garg in the cellular pharmacology lab at Merck
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TECAN JOURNAL 1/2020
DRUG DISCOVERY
e easily save about half a day per plate W in time since adopting this automated approach.
which, depending on the cell line, can
dispenser allows us to work with
take anywhere between one to three
smaller liquid volumes without the risk
To find out more about Tecan’s
days. Once the spheroids are visible, we
of pipetting errors and, as we need to
inspect them to make sure that they are
perform fewer dilutions, we use less
D300e Digital Dispenser, visit
intact and that they don’t easily
starting material, which is great. We
disperse, then go ahead and treat them
used to carry out all of the dilutions by
with candidate compounds; this is
hand, which was incredibly time
where Tecan comes in. We add
consuming, so we were really happy
compounds to the spheroids and then
when we started using the D300e, as
incubate the plates for two to four days
we saved so much time. There’s a huge
before performing a viability assay to
improvement in accuracy since we
see the effects.”
started direct dispensing into the
www.tecan.com/d300e To learn more about the Merck group, go to www.merckgroup.com/en
plates, and it has improved the Jasmin continued: “We’ve been using
workflow of the lab significantly; we
Tecan’s D300e Digital Dispenser since
easily save about half a day per plate in
around late 2016, as a solution for
time since adopting this automated
automated and reliable low volume
approach. Previously, when pipetting
liquid handling. We aim to automate
manually, we would use 96-well plates,
our processes where we can because,
which limited the number of
ultimately, when we go into high
compounds or different conditions we
throughput screening, a manual
could test. But now, as automated
workflow just isn’t viable. Automation
pipetting is so much quicker, we can
of these set-ups provides our
perform more tests at once in 384-well
laboratory with a solution that not only
plates. We can generate data much
saves time and increases productivity,
faster now, and that helps us to make
but also improves the reproducibility
decisions on whether or not to continue
and accuracy of our results. We first
with certain compounds or projects –
started using the D300e when we
the process is much more streamlined
initiated our 3D cell work, as our
and efficient.”
acoustic dispenser required us to flip the plate when adding various
“Another huge benefit of the D300e is
compounds, which is not possible with
how intuitive it is; it was very easy and
spheroids, as they would fall out of the
self-explanatory to set up, and the
wells. We needed a contactless system
interface is extremely clear. Having this
capable of picoliter dispensing, and
capability in a compact system on the
Tecan gave us this solution.”
benchtop really does simplify our workflow, increasing throughput and
Bianca Roth, a technician in the
helping to advance our 3D cell
laboratory, added: “The digital
research,” Sakshi concluded.
TECAN JOURNAL 1/2020
11
DRUG DISCOVERY
Traditional Chinese st medicine for the 21 century Recent viral outbreaks have alerted the world to the serious consequences of viral disease, yet the development of new antiviral drugs is challenging because of problems such as resistance or lack of molecular targets. Researchers at Zhejiang University’s College of Pharmaceutical Sciences are seeking to identify new antiviral drugs by combining insights from traditional Chinese medicine with modern high throughput technologies to discover novel lead compounds.
Infectious diseases have become one of
These challenges have led Professor Yi
the greatest global public health threats.
Wang and his group at Zhejiang
stimulation of the immune system.
The rise of antibiotic resistance, and
University to explore a novel source for
Our methodology is not focused on a
search for new drug targets and
new antiviral compounds – the ancient
specific virus or bacterium, but instead
candidates, has been well publicized for
Zhongjing formulae. Written almost
uses a cell-based luciferase reporter
a number of years, but recent major
2,000 years ago – sometime between
assay that determines the ability of the
outbreaks of highly contagious viral
150 and 200 AD – this collection of
formulae to activate interferon-
infections – such as Ebola, Zika and
more than 200 traditional Chinese
stimulated response elements (ISRE) –
Dengue – have highlighted the need for
remedies is well known throughout Asia,
a key element of the antiviral interferon
more effective antiviral drugs. These
and is the origin of many modern
signaling pathway.”
viral infections accounted for over one
Chinese medicines today. Professor
million deaths worldwide annually in
Wang outlined how his group has gone
2016, yet the development of new
about investigating this unconventional
antiviral drugs has seen little progress
source: “In ancient times, people knew
due to a number of challenges. The lack
nothing of viruses or bacteria; they only
of viral molecular targets impedes viral
knew that one of the Zhongjing
drug discovery, as does the high rate of
formulae would be effective against
genetic mutation in some viruses, which
certain symptoms. We therefore needed
drives the development of new drug
to develop an approach which was not
resistance mechanisms.
dependent on understanding the
molecular target, but rather the
This joint facility is shared between Tecan and the Zhejiang University College of Pharmaceutical Sciences
Traditional Chinese medicine is considered a valuable resource for drug innovation, but blind screening models result in high rates of rediscovery, and low probabilities of hit compounds. To counteract this, Professor Wang and his group developed a knowledge-based high throughput screening platform which combines information already known about ancient healing practices with high throughput screening. He explained: “We identified the herbs that appear most frequently in the Zhongjing formulary, then focused on formulae that not only contain these herbs, but are also suggested for treating influenza-like symptoms as an indicator of possible antiviral activity. Aqueous Professor Wang and his group in the joint laboratory
12
TECAN JOURNAL 1/2020
DRUG DISCOVERY
utomation allows you to easily investigate A more than 1,000 compounds at a time, and the stability and reproducibility of the Fluent system results in very linear data. The Fluent Automation Workstation is at the heart of the lab’s workflow
extracts of the most promising formulae
The luciferase signal is detected with an
now been published in Pharmacological
are prepared and fractionated to
Infinite M1000® PRO. Professor Wang
Research,1 and we are preparing two
construct a library of 1,306 different
continued: “This instrument is very
further manuscripts for submission in
fractions or components.”
sensitive, and we haven’t found any
the coming months. We are very happy
analyses we can’t handle. It can do
with our successful collaboration with
To examine the antiviral activity of the
everything – luminescence readouts,
Tecan, and look forward to working
compounds, HEK293T cells transfected
protein quantification, testing
together more in the future,” Professor
with pISRE luciferase are seeded into
fluorescent probes – so it gets a lot of
Wang concluded.
96-well microplates and cultured for 24
use by everyone in the lab. We have
hours. They are then treated with
another reader downstairs but it’s not as
components – or IFN-β as a positive
nice to use as the Tecan.”
control – and incubated for a further 24 hours before measurement of the
This screening study identified several
luciferase signal as an indicator of ISRE
hits – from the components of seven of
activity. “We are very lucky to have a joint
the Zhongjing formulae – which were
laboratory with Tecan here at the
further characterized using LC-MS. 11
university, and use a Fluent® 780
compounds were tentatively identified,
Automation Workstation to manage all the
five of which were unambiguously
pipetting steps, including the initial dilution
identified with chemical standards.
of the fractions. The system works very
The group then went on to confirm the
quickly, allowing us to test three biological
antiviral function of each compound
replicates of each cell-based assay plate.
using ISRE activity.
Previously, we would have had to perform
1) Yu, Y; Li, Z; et al. Ononin, sec-O-β-Dglucosylhamaudol and astragaloside I: antiviral lead compounds identified via high throughput screening and biological validation from traditional Chinese medicine Zhongjing formulary. Pharmacol Res, 2019, 145, 104248.
To find out more about Tecan’s drug discovery solutions, visit
all the pipetting manually, but could handle
“Using the Tecan equipment, we’ve
no more than 300 compounds in a study.
been able to screen more than 1,000
Automation allows you to easily investigate
components from traditional Chinese
more than 1,000 compounds at a time, and
medicine and found not just one, but
the stability and reproducibility of the
three novel compounds that led to a
Fluent system results in very linear data,
significant increase in ISRE activity that
Pharmaceutical Sciences, go to
with small standard deviations.”
had not previously been reported in the
www.cps.zju.edu.cn
www.tecan.com/drugdiscovery To learn more about Zhejiang University’s College of
literature. The results of the study have
TECAN JOURNAL 1/2020
13
PROTEOMICS
Positive pressure proteomics Proteomics studies using mass spectrometry have an important role to play in understanding tumor cell biology and the impact of novel therapeutics. Sample clean-up prior to analysis is an essential part of these workflows, and researchers at Pfizer are performing this on a positive pressure workstation to save time and enhance reproducibility.
Pfizer is a leading pharmaceutical
understanding of the mechanism of
a principal scientist specializing in
company with sites across the globe.
action of drugs. A crucial part of these
chemical proteomics and mass
One of its main areas of interest is
studies is mass spectrometry analysis
spectrometry, explained: “I joined the
oncology, and scientists in the Tumor
of peptides, which depends on
Tumor Cell Biology group about 18
Cell Biology group at the company’s La
thorough sample clean-up to remove
months ago, having spent 10 years
Jolla facility in California are engaged
unwanted components that could
working in proteomics, including
in proteomics studies to gain a better
interfere with the results. John Lapek,
postdoctoral positions at the University
The Tumor Cell Biology group taking a well-earned break from the laboratory
14
TECAN JOURNAL 1/2020
PROTEOMICS
of California, San Diego, and the
exactly the same rate or dry them to
process a 96-well plate in about an
Massachusetts General Hospital Cancer
the same extent, and this affects the
hour and a half. As we typically run
Center at Harvard Medical School. My
final analytical results. Automation was
three or four 96-well plates a week, it’s
focus is on chemical biology, which
the way forward, as it would overcome
a huge time saver. And if we have fewer
involves target deconvolution,
these issues, allowing us to save time,
samples to process, we also have the
engagement and occupancy studies,
increase throughput and improve
option to use individual columns.
along with some broader mechanism of
reproducibility.”
Another noticeable difference is the improvement in reproducibility, as
action investigations looking at global proteomic profiling to get a better
“I had been looking for an automated
automating our procedures has
understanding of how drugs work.”
system for some time when I came
eliminated inter-operator variation. We
across the Resolvex ® A200 positive
have standard protocols set up on the
John continued: “Our proteomics
pressure SPE workstation at an
system, which makes everything
workflows involve a complex digestion
American Society for Mass
straightforward to operate and ensures
process, where cell lysates are typically
Spectrometry exhibition. Until then,
that everyone uses the same method. It
treated with trypsin to break the
I had only seen low throughput
also means that if there is a query with
proteins down into smaller, easier to
platforms that processed about eight
a result, it is unlikely to have arisen due
analyze peptides, and a tandem mass
samples at a time, and so my interest
to variations in sample preparation.”
tag (TMT) strategy that allows
was immediately captured by this
multiplexing of 11 samples. Before we
system’s flexibility and potential to
“We’ve had the Resolvex A200 for over
can analyze the samples by mass
enable automated sample preparation
a year now, and find it easy to program
spectrometry, we have to perform a
in 96-well plates. We arranged a
and operate. It only took a couple of
couple of clean-up steps to remove
demo, and shortly afterwards a
hours to show people how to use it, and we now have eight members of the
Desalting used to be our biggest bottleneck; manually desalting 96 samples took two people dedicated to the task two days…the Resolvex A200 can process a 96-well plate in about an hour and a half.
group trained to run and program the system. Building on the success of automating our desalting protocols, we are considering using the system for simple fractionations – such as immunoprecipitation – in the future. This would remove the need to use spin columns. In addition, another one of our research groups has used the
urea and any other salts remaining after
Resolvex A200 was set up in our lab
Resolvex A200 to investigate various
digestion, and excess, unreacted TMT
for a one week trial. This allowed us to
metabolites. It lends itself to so many
reagents. This is done by solid phase
perform manual and automated
different applications,” concluded
extraction (SPE).”
sample preparation in parallel and
John.
compare the results.” Manual SPE procedures tend to be time consuming and subject to operator-to-
“While the results of the manual and
To find out more about Tecan’s
operator variation, which can be
automated sample preparation were
mass spectrometry sample
eliminated by automation. “In the past,
comparable, we found that the big
preparation solutions, visit
sample clean-up was performed
advantage of using the Resolvex A200
manually on a 16-place vacuum
was the amount of time we saved.
www.tecan.com/resolvex
manifold. Not only is it very time
Desalting used to be our biggest
consuming to pipette everything
bottleneck; manually desalting 96
manually, but there will always be
samples took two people dedicated to
differences between the various users,
the task two days to complete. In
as people don’t load the columns at
contrast, the Resolvex A200 can
To learn more about Pfizer’s Tumor Cell Biology Group, go to www.pfizer.com/partners/ candidate/oncology
TECAN JOURNAL 1/2020
15
OEM COMPONENTS
Sensing success Spanish company Advanced Wave Sensors (AWSensors) is playing a key role in the pan-European Horizon 2020 LiqBiopSens and Catch-U-DNA projects to develop a new liquid biopsy platform for the early detection of colorectal and lung cancers. An important part of this process was the creation of a liquid handling platform incorporating an acoustic wave sensor array and microfluidic technology for the analysis of biomarkers in blood.
Colorectal cancer is the third most
crucially, allows tumor dynamics to be
research in the field of piezoelectrics
common cancer worldwide according
monitored in real time. The Horizon
to produce acoustic sensors and
to World Cancer Research Fund data,
2020 LiqBiopSens and Catch-U-DNA
complementary electronic
making it an important diagnostic
projects aim to replace the labor-
instrumentation. The company’s focus
target. Currently, tissue biopsy is the
intensive, costly and occasionally
is on high frequency, quartz crystal
conventional cancer identification
biased PCR-based approach currently
microbalance with dissipation
technique. However, this is an invasive
used for the detection of genetic
measurement (QCMD) sensors and
procedure that only delivers a snapshot
markers with a liquid biopsy platform
sensor arrays – as well as control
of the patient’s condition at a specific
that uses acoustic wave sensing to
electronics and software – and
moment in time. An alternative method
deliver precise, real-time and robust
microfluidics to allow miniaturization
is the use of liquid biopsies, where
DNA quantification.
of the systems and sample volumes
biomarkers are monitored in body
for specific analyte detection. Maribel
fluids, such as blood, saliva and urine.
AWSensors was spun out from the
Rocha, an application scientist at
Liquid biopsy is a far less invasive
Polytechnic University of Valencia a
AWSensors, explained: “Our company
process than tissue biopsy and,
decade ago, building on years of
was founded to make advanced
The AWSensors team
16
TECAN JOURNAL 1/2020
OEM COMPONENTS
Workflow automation is therefore key; it is much less laborious and time consuming than manual pipetting, and enables accurate and precise transfer of samples to the sensing device. The Cavro XMP’s six-channel syringe pump manifold is used to provide a steady flow of fluids across the sensors
QCMD-based technology available to
we chose the Omni Flex, as Cavro is a
“We have successfully developed a
the wider community, by developing
brand that offers good value and high
prototype automated platform based
and manufacturing high precision
quality. We also knew that, as a
on the Cavro Omni Flex robot,
sensing instrumentation for basic and
complete liquid handling system, the
combining our technology and the
preclinical research and industrial
Cavro Omni Flex would significantly
DestiNA chemistry to offer faster
applications. This technology has
reduce the time taken to develop the
detection of oncogenic mutations than
many potential applications, with
liquid biopsy platform,” said Maribel.
is possible with currently available
biosensors proving to be one of the
“The project development team
enzyme-based assays, with fewer false
most important sectors.”
integrated our sensor array technology
positive results. This straightforward
onto the system, allowing automation
technique is now being evaluated by
A particularly important use for this
of the highly selective DestiNA reaction
our Horizon 2020 partners, using
technology is the development of
and detection of any biomarker targets
patient samples in a ‘real world’
biosensors for the detection of cancer
using the acoustic transducers.”
environment. Once fully validated, the
biomarkers, and AWSensors is working
system is set to deliver low cost,
with its Horizon 2020 partners across
“Samples and reagents are delivered to
real-time detection of cancer markers
Europe to develop a novel early
the six independent channels of the
in blood samples, benefitting both
detection system. Maribel continued:
sensing cartridge using the Cavro ADP,
patients and healthcare providers,”
“As part of the LiqBiopSens and
then the Cavro XMP’s six-channel
said Maribel.
Catch-U-DNA projects, we are
syringe pump manifold is used to
developing a reliable, rapid, non-
provide a steady flow of fluids across
invasive liquid biopsy assay to detect
the sensors during the reactions. By
colon and lung cancer. The aim is to
including a 24-sensor array rather than
combine our ultrasensitive acoustic
the more commonly used single sensor,
wave sensors, microfluidic cartridge
we have increased the throughput and
technology and engineering
number of analytes that can be
capabilities with novel chemical
simultaneously detected in a run.
reagents from DestiNA Genomics,
Accurate and precise pipetting
creating an automated platform for the
throughout the process is essential for
analysis of liquid biopsies for circulating
reliable, consistent results, as any
tumor DNA. To do this, we needed to
variation in the volumes pipetted will
develop a liquid handling platform that
have an impact on the reproducibility
could accommodate a microfluidic
and quantitative accuracy of the
device and a 24-sensor array for
experiments. Workflow automation is
simultaneous monitoring of multiple
therefore key; it is much less laborious
biomarkers.”
and time consuming than manual
To find out more about Tecan’s
pipetting, and enables accurate and
Cavro Omni Flex, visit
AWSensors looked at the different
precise transfer of samples to the
www.tecan.com/omniflex
options available on the market, and
sensing device, eliminating the
chose the Cavro® Omni Flex robot,
potential for human errors. The
To learn more about AWSensors,
equipped with a Cavro XMP 6000
end-user simply has to load the
go to www.awsensors.com
Pump and Cavro Air Displacement
workdeck and start the run.”
Pipettor (ADP). “After talking to Tecan,
TECAN JOURNAL 1/2020
17
DRUG DISCOVERY
A Spark of hope for nerve damage repair ®
Damage to the brain or spinal cord can be life changing for affected individuals, and it was historically thought that these injuries would not heal and could not be repaired. However, since the discovery of neurite growth inhibitors by Professor Martin E. Schwab at the University of Zurich, clinical researchers have been exploring new therapeutic approaches to treat cerebral stroke and spinal cord injury. The Wyss Zurich/University of Zurich CeNeReg project and NovaGo Therapeutics Inc. – co-founded by Professor Schwab – are at the forefront of this exciting field, and are dedicated to the development of human antibody therapeutics to stimulate nerve repair and regeneration.
The concept of neurite growth
potential therapeutic target that could
potential of anti-Nogo-A antibodies as
inhibitors as the key reason for the lack
be inhibited to allow neurons damaged
a new therapeutic approach. Start-up
of regeneration in the central nervous
by cerebral stroke or spinal cord injury
biotech NovaGo Therapeutics and
system was first proposed by Professor
to regrow and form new networks.
Wyss Zurich – a foundation supporting
Schwab in the early 1990s. His team at
Since this time, a large number of
translational medicine within the
the University of Zurich then went on to
preclinical studies have been
University of Zurich and ETH Zurich –
discover a key inhibitory factor –
performed by independent laboratories
are determined to translate this
Nogo-A – which it identified as a
around the world, validating the unique
knowledge from a research to a clinical
Michael Maurer (back row, second from right) and the NovaGo team relaxing away from the lab
18
TECAN JOURNAL 1/2020
DRUG DISCOVERY
I t’s very easy to develop new methods; everything is very intuitive and self-explanatory – I’ve never even opened the manual!
environment, with the aim of
the first things we used the system for
they are performed. It’s very easy to
developing novel immunotherapies that
was to take pictures of our cultures
develop new methods; everything is
would enable the regeneration of
during cell-based assays, and this
very intuitive and self-explanatory – I’ve
disrupted nerve tissue.
worked really well straightaway. We
never even opened the manual! And if
also use this function to perform cell
we need any support from Tecan, we
Dr Michael Maurer, a former senior
adhesion assays, as Nogo-A – either
get it within a day, which is great. I’ve
scientist at Wyss Zurich and currently a
fragments or total protein from tissue
never heard any complaints about the
senior scientist at NovaGo, explained:
samples – blocks cell adhesion.”
Spark, and everybody is happy with it;
“We are developing and characterizing
it’s fast, easy to use and works like a
an anti-Nogo-A antibody for health
Most multimode readers can be
authorities, and needed a system that
equipped with either filters or
would allow in-depth characterization
monochromators (MCRs) to define
of these complex macromolecules.
excitation and emission wavelengths in
Many of our assays are cell- or ELISA-
fluorescence applications, but Spark is
based, making a high performance
equipped with both, allowing the user
plate reader essential. I initially began
to independently choose between
looking for a system to perform ELISAs,
filters and MCRs for both excitation and
but quickly realized that a multimode
emission. Michael illustrated the value
system that could also quantify DNA,
of this: “All the assays we run on the
perform fluorescence measurements,
Spark are developed and validated in
and count and image cells, would be
house, and the flexibility of the MCRs is
the best solution. The Spark seemed
ideal for the development of
ideal, as it could do everything, so I
fluorescence-based methods, speeding
asked Tecan for a demonstration, and
up the whole process. To have them for
was really surprised at just how good
both excitation and emission is really
this system is.”
awesome, because you are not limited
charm,” Michael concluded.
by the filters that you have available.
To find out more about Tecan’s
“Before getting the Spark, we had a
Then, once you’ve optimized your
Spark reader, visit
number of benchtop instruments in the
assay, you can switch to the more
www.tecan.com/spark
lab, but it has now replaced all of them.
sensitive filters and create a standard
The space-saving is not so important
curve to check the limits of detection
To learn more about the Wyss
for us, but only having a single
and maximum quantification.”
Zurich CeNeReg project, go to
instrument to maintain is an important saving. The only downside of having an
“Each validated method is turned into
instrument that does everything well is
an SOP using the method development
that a lot of people want to use it!
tool in the Magellan™ software.
Fluorescence and absorbance
Everyone in the lab can then simply
measurements are very easy, and the
click on and use the assays – but not
imaging capabilities are good. One of
modify them – standardizing the way
www.wysszurich.uzh.ch To learn more about NovaGo Therapeutics, go to www.novagotherapeutics.com
TECAN JOURNAL 1/2020
19
GENOMICS
Streamlining genomics workflows DNA isolation and PCR
medical microbiology laboratory,
set-up can be laborious
based in Veldhoven, offers a broad range of bacteriology, virology and
and time consuming when
serology testing, working with blood,
performed manually. Dutch
sputum, urine, feces, hair, biopsy and
pathology and microbiology
smear samples. With the growth of
services provider PAMM
molecular diagnostics, PAMM now
has overcome this issue by
PAMM is an independent, non-profit
performs a large number of PCR-
automating its molecular
diagnostics laboratory company in
based tests for the identification of
testing protocols for sexually
the Netherlands. With facilities in
both sexually transmitted infections
Veldhoven and Eindhoven, it offers
(STIs) – including Chlamydia
clinical microbiology and pathology
trachomatis, Neisseria gonorrhoeae,
services to general practitioners and
Trichomonas vaginalis and Mycoplasma
five hospitals in the southeastern area
genitalium – and gastrointestinal (GI)
of North Brabant province. The
disorders leading to vomiting, diarrhea
transmitted infections and gastrointestinal conditions, freeing up staff to perform other tasks.
Lieke Donders (left), Jeroen van de Bovenkamp (center) and Inge Briels are reaping the benefits of automated genomics workflows
20
TECAN JOURNAL 1/2020
GENOMICS
or gastroenteritis, for example GI bacteria or parasites. Senior technician Inge Briels explained: “Typically, we receive almost 100 STI samples a day – 80 percent of them swabs, the rest urine – plus another 60 fecal samples. Isolating DNA from these samples, then setting up the subsequent PCR amplification, can be time consuming
ll we have to do is load fresh PCR master A mix onto the workdeck, start the run and walk away, and two hours later the extraction is complete and the plate is ready for PCR amplification.
when performed manually.” To streamline the workflow and free
Inge continued: “We have been using
and incubation steps. All we have to do
staff for other tasks, the laboratory has
the Freedom EVOs for DNA isolation
is load fresh PCR master mix onto the
automated its isolation and PCR set-up
and set-up of PCR reactions for around
workdeck, start the run and walk away,
protocols on two Freedom EVO ®
two years now. Generally, we use one
and two hours later the extraction is
platforms. Inge continued:
of the workstations for the detection of
complete and the plate is ready for PCR
“Automation plays an important role in
STIs and the other for processing fecal
amplification.”
our laboratory and, as our molecular
samples, although we can switch
testing workload increased, it became
between the platforms if necessary for
“Automating our DNA isolation and
obvious that we needed another
maintenance or to accommodate
PCR protocols on the Freedom EVO
workstation to perform this work. We
additional samples, as the set-up is the
has made a big difference to the
already had one Freedom EVO
same. The Freedom EVOs
laboratory, and we are thinking about
platform in the lab and, after looking
communicate with our LIMS via a
automating other assays – such as
at different systems available, we
middleware solution, automatically
vancomycin-resistant enterococci
decided that this was the best option
generating worklists to fully automate
(VRE) and possibly hepatitis B and C –
for our intended use.”
these protocols.”
in the future, to free up even more staff
Lieke Donders, also a senior
“Sample preparation before DNA
technician, added: “Together with our
isolation is minimal,” said Lieke.
time,” Inge concluded.
clinical molecular biologist, Dr Jeroen
“We just add 10 µl of fecal matter to
van de Bovenkamp from the medical
1 ml of lysis buffer – STI tubes simply
staff, we discussed our existing
need to be uncapped – and load the
manual workflows with Tecan, and
sample tubes onto the workdeck. All of
explained what we needed. We have
the samples, as well as the PCR
developed a number of in-house PCR
reagents, are barcoded, minimizing the
To learn more about PAMM,
assays for both STI and GI samples,
risk of errors and providing full
go to www.pamm.nl
based on the CE-IVD compliant
traceability. The platforms perform all
VERSANT® CT/GC DNA 1.0 Assay
the required pipetting tasks using an
(kPCR) (Siemens), and the company
eight-channel Liquid Handling Arm™
was able to set up the workstation
with disposable filtered tips, and a
according to our exact needs, making
Robotic Manipulator Arm™ moves the
it easy to transfer our manual
microplates to the correct station on
protocols directly to the system.”
the workdeck for the shaking, washing
To find out more about Tecan’s genomics solutions, visit www.tecan.com/genomics
TECAN JOURNAL 1/2020
21
CLINICAL DIAGNOSTICS
Food for thought Patients suffering from a number of different chronic diseases are turning to holistic healthcare provider RP Sanitas Humanus in the Netherlands for answers, frequently after conventional medicine has been unsuccessful. Food intolerances often lie at the root of the problem, and can be evaluated using automated analysis of IgG and IgG4 antibodies to isolate the true causes.
The name RP Sanitas Humanus, derived
The laboratory offers a range of
conventional medical approaches have
from Latin, means to ‘improve health
analytical services – including fecal
been exhausted to no avail.”
with natural interventions’, a
analysis and food intolerance testing
description that perfectly sums up the
– to doctors and recognized therapists,
Ralf continued: “The crucial thing for
activities of this Kamperland-based
to help them make a more informed
these patients is to identify the trigger
company. The company was
diagnosis in patients suffering from
that is causing their health problem. We
established two decades ago to
chronic diseases. Ralf Abels, CEO and
take a holistic approach to diagnosis,
provide holistic healthcare services,
co-founder of RP Sanitas Humanus,
looking at the big picture and not just
and comprises a diagnostic laboratory,
explained: “The majority of our work is
isolated symptoms. To begin with, we
RP Analytic, complemented by RP
focused on chronically ill patients
look at the patient’s general condition
Supplements, which supplies nutritional
suffering from a broad spectrum of
– the gut microbiota, inflammatory
supplements to naturopath
conditions – for example, chronic bowel
state, immune system and potential
professionals, and educational services
disease, rheumatic patients and
pathogens – and run blood tests to
delivered through the RP Academy.
behavioral disorders – where
check liver and kidney function. These
IgG and IgG4 Food Screen ELISAs and Freedom EVOlyzer workstations are helping RP Sanitas Humanus take a targeted approach to food intolerance testing
22
TECAN JOURNAL 1/2020
CLINICAL DIAGNOSTICS
results help direct any further
complete automation solution tailored
system to run overnight. The results
diagnostic tests that may be necessary,
to our needs, allowing us to take a
are transferred directly to the LIMS
such as screening for food intolerances,
targeted approach,” said Ralf.
and all we need to do is review them in the morning and send the report to the
which are surprisingly often a contributory factor in chronic
“Initially, we run a base panel of seven
conditions. The involvement of IgG and
core allergens from the most common
IgG4 antibodies is well known, and
food groups – fruits, vegetables, fish,
“Testing for food intolerance is just the
testing for these gives us more specific
meat – which gives us an indication of
start; once we have determined the
insight into the cause of the patient’s
total IgG (types IgG1-4) and also IgG4,
cause of the problem and made dietary
problem, taking the guesswork out of
which is indicative of more severe
recommendations, success lies in the
advising which foods they need to
reactions. Based on these results, we
hands of the patient. Recovery can
avoid consuming. Instead of simply
then go on to run a more specialized
take months but, when the patient is
suggesting they try eliminating a
follow-up screen of a further 24
motivated and prepared to act on the
particular foodstuff and see what
allergens tailored to the individual
results of the test, adjusting their diet
happens, we can identify the specific
patient. For example, if the patient
accordingly, we have seen success
cause of the patient’s reaction.”
follows a vegetarian diet, there will be
rates of between 70 and 80 percent for
more focus on fruit and vegetables,
some chronic diseases. The challenge
RP Sanitas Humanus receives in the
while animal products will not be
for the patient is to continue to follow
region of 100,000 samples a year for
included in the screen. In all, we can
the recommendations months down
food intolerance testing, many of
test 280 foods from 16 product groups,
the line, even when they feel as if they
which will undergo more than one level
which gives us a very good chance of
have recovered,” Ralf concluded.
of screening. Previously, these samples
identifying the specific food the
were sent to another laboratory for
patient cannot tolerate and should
testing but then, two years ago, the
eliminate from their diet.”
company brought the service in house,
referring practitioner.”
To find out more about food intolerance testing, visit
running Tecan’s IgG and IgG4 Food
“The implementation of a complete
Screen ELISAs on two Freedom
automated food intolerance testing
EVOlyzer ® workstations. “When we
solution has really benefitted the
decided to bring this testing in house,
laboratory. The combination of
the biggest consideration was to find a
Tecan’s IgG and IgG4 Food Screen
company offering assays that would
ELISAs and the Freedom EVOlyzer
RP Sanitas Humanus, go to
allow us to screen in a structured way;
workstations has given us the
www.rpsanitashumanus.com
we wanted to be able to run a
throughput we need and made the
preliminary screen that would direct
entire workflow less labor intensive. All
further in-depth testing if necessary.
the modules we need to process the
This keeps costs to a minimum for our
assays are integrated onto the
patients – they don’t end up paying for
Freedom EVOlyzers, which are linked
unnecessary tests. Tecan was the only
to our LIMS. We simply set up a
supplier that could provide us with a
worklist, press start and leave the
www.food-intolerancediagnostics.com To learn more about
ecan was the only supplier that could T provide us with a complete automation solution tailored to our needs, allowing us to take a targeted approach.
TECAN JOURNAL 1/2020
23
CLINICAL DIAGNOSTICS
Capturing the IVD market in China In vitro diagnostics (IVD) is central to the provision of healthcare globally, and is estimated to be worth in excess of $8.2 billion (â‚Ź7.3 billion) a year in China alone.1 Despite this, the Chinese IVD landscape has historically been controlled by large international providers, with few domestic instrumentation and assay suppliers. Start-up company Shenzen AiTe is looking to change this, with the development of diagnostic platforms and assays offering rapid detection for a wide range of blood-based markers.
Blood-based testing is at the heart of
Over the last decade or so, Chinese
pathology services, and accounts for a
companies and investors have become
large proportion of the total diagnostic
increasingly interested in this sector,
workload in almost every hospital lab
looking to expand the proportion of the
and independent facility around the
market controlled by domestic
world. Shenzen AiTe is looking to break
providers. This has had the ripple effect
into the vast testing market in China by
of more people studying the necessary
developing its own range of fully-
biomedical and engineering disciplines
automated IVD platforms. Peter Peng,
at university, providing a rich pool of
CEO and founder of Shenzen AiTe,
talent locally. I founded Shenzen AiTe
explained: “Blood-based diagnostics is
to tap into this potential and develop a
a huge industry here in China but, at
range of chemiluminescence-based
present, it is dominated by just a few
diagnostic assays and instruments for
big international companies, which
hospital laboratories.�
have around 85 percent of the market.
The systems fully automate the analytical workflow
24
TECAN JOURNAL 1/2020
CLINICAL DIAGNOSTICS
“The basic principle of our instruments
pipetting parameters to ensure
is to fully automate the entire analytical
accurate and reliable liquid transfers,
process; the operator simply loads the
even for complex fluids such as blood.”
blood sample tube onto the platform. A
This module provides advanced pipetting parameters to ensure accurate and reliable liquid transfers, even for complex fluids such as blood.
built-in barcode reader then identifies
“Integration of the Cavro ADP into our
the sample and, by connecting to the
platform was easy, and we have had
hospital or laboratory information
ongoing support from the Tecan Cavro
system, determines which assays need
team in California to ensure optimal
to be performed. Parallel testing of all
pipetting performance. We have also
samples takes approximately 15
chosen the Cavro Pulssar PBC Pump for
minutes using our proprietary
distribution of our chemiluminescent
chemiluminescence-based assay
reporter reagent, as we need to
chemistries. We are developing two
accurately dispense 5 μl of reagent into
instruments – with capacities of 30 or
each reaction vessel to ensure
60 tubes – to cater for different sized
reproducible quantitative results. This
laboratories, giving a maximum
piston pump is very accurate and
To find out more about Tecan
throughput of 180 tests per hour.”
reliable, and has an ultra-low
Cavro components, visit
maintenance design, making it ideal for
partnering.tecan.com/cavro
“To perform each assay, the system
our needs.”
transfers 5-50 μl of blood into a ‘cup’ containing the target-specific reagents.
“Both components have been
The reaction vessel is then incubated
straightforward to integrate into our
and washed several times, before being
system design in terms of the hardware
analyzed with a built-in luminescence
and the software, which has helped us
reader. Since these tests could include
to speed up instrument development.
infectious samples, we wanted to avoid
Although we are currently still in the
the use of washable fixed tips for liquid
development and validation phase, our
handling, which increases the risk of
aim is to achieve national certification
cross-contamination. We therefore
for the instruments towards the end of
wanted a pipetting system that used
2020, and release the systems into the
disposable tips as, although this
market in early 2021. Using validated
increases the cost slightly, it eliminates
liquid handling components with
the contamination risk. Rather than
certified performance will certainly
design our own liquid handling module,
help with this process, and we are very
we looked at the solutions already on
happy with our choice of Tecan Cavro
the market that used disposable tips,
components,” Peter concluded.
and chose the Cavro® Air Displacement Pipettor (ADP) and Tecan disposable tips. This module provides advanced
1) www.prnewswire.com/news-releases/ china-in-vitro-diagnostic-ivd-industryreport-2019-2025-300880671.html
TECAN JOURNAL 1/2020
25
DRUG DISCOVERY
Artificial intelligence – the hero drug discovery needs Drug discovery is a lengthy and expensive process, particularly in the early candidate identification stages, where screening of large numbers of compounds is required. Researchers at the University of Central Florida are using artificial intelligence (AI) to aid candidate selection for antimalarial drugs, making this selection process more efficient and cost effective, as well as increasing the likelihood of success.
Malaria is one of the biggest challenges
in terms of time and cost savings,
Milad Salem, an AI scientist in the
facing the world today. Not only does it
allowing researchers to be far more
Department of Computer Engineering,
affect a considerable proportion of the
selective when choosing compound
took up the story: “This work involves
world’s population, but the prevalence
libraries to study. For example, the
using a deep learning approach, finding
of drug-resistant parasites is causing
time and cost involved in physically
and adapting computer models to
the limited number of treatments
screening a library of 250,000
predict the potential efficacy of drug
available to become less effective.
compounds is simply prohibitive.
candidates. We initially chose to study
Researchers in the Burnett School of
However, using AI, we can screen all
malaria, looking for novel candidates to
Biomedical Sciences at the University
250,000 compounds in silico to
overcome the growing issue of drug
of Central Florida, Orlando, have turned
identify potential antimalarials – such
resistance. The idea was to establish a
to AI to assist in the discovery of new
as macrocyclic scaffolds – while
model that could successfully predict
candidate drugs, initially focusing on
excluding compounds that would
antimalarial candidates, before using
malaria. Arash Keshavarzi Arshadi, a
definitely not be effective. This
this model to develop further
computational biotechnology PhD
approach saves us time and money,
algorithms for other diseases. From a
student, explained: “AI offers
as we only need to buy and screen
computational standpoint, having the
considerable benefits for drug discovery
the ‘hits’ identified by AI.”
correct data to make the model is essential. Finding that data can be really challenging – sometimes impossible – but in this case we were lucky enough to have publicly available data from a major pharmaceutical company that had identified around 13,000 compounds active for a specific malarial strain. We used this dataset to train our algorithm to find hidden patterns in those compounds.” Once the in silico model – known as DeepMalaria1 – had been trained, the next step was to test the accuracy of the algorithm using macrocyclic compound libraries. With large numbers of compounds to screen, turning to automation was an obvious decision. Arash continued: “We bought a number of compound libraries to test the algorithm, comparing the theoretical results predicted by AI
Milad Salem (left) and Arash Keshavarzi Arshadi
26
TECAN JOURNAL 1/2020
DRUG DISCOVERY
with those observed during practical
format has made our workflow more
high throughput screening on a
efficient and economical, reducing
Freedom EVO ® workstation in Dr
costs by over 50 percent.”
Debopam Chakrabarti’s laboratory. This involved single-point screening of
Milad added: “Normally, data that has
one micromolar solutions of 2,500
already been physically screened is
compounds, and confirmed that our
given to an AI model to see how good
algorithm predicted hits with an overall
it is at predicting what has already
accuracy of about 87.5 percent for
happened. However, we wanted to save
those that inhibited growth by
time by working prospectively, using
50 percent. This rose to 100 percent
our model to predict which compounds
for nanomolar active compounds. In
would be active against malaria, and
other words, DeepMalaria did not
we were really pleased with how well
miss any highly potent macrocyclic
our AI performed. These results have
antimalarials.”
given us hope that deep learning models can find patterns that humans
“We then went on to determine the half
can’t, and may be able to work in a
maximal inhibitory concentration (IC 50)
more abstract way than was previously
of the hits we had identified, using the
thought possible.”
Freedom EVO to perform serial dilutions and transfer them to a black plate for
“Moving forward, we plan to continue
SYBR® Green screening to assess cell
this work by developing more
viability of malaria parasites.
algorithms targeting other diseases,
Automating this high throughput
such as cancer and HIV, which Dr Jiann
screening is a very efficient way to
Shiun Yuan’s laboratory is studying. AI
perform our workflow; it would take so
has huge potential to aid drug
much time to do manually. I had no
discovery, and having publicly available
previous experience with this type of
data for malaria really helped us to
system, but found it straightforward to
drive our research forward. We would
work with. I quickly learnt the basics,
encourage all researchers in this sector
and it is easy to write scripts for our
to take an open source approach to
screening and toxicity assays in
data sharing, allowing more diseases to
Freedom EVOware®. I also attended a
benefit from AI,” Arash concluded.
Tecan workshop, where I picked up some useful tips, particularly for working with 384-well plates. Previously, we did everything in 96-well plates, but switching to a 384-well
1) Arshadi, A; Salem, M; et al. DeepMalaria: Artificial Intelligence Driven Discovery of Potent Antiplasmodials. Frontiers in Pharmacol, January 2020, DOI: 10.3389/ fphar.2019.01526
Automating this high throughput screening is a very efficient way to perform our workflow; it would take so much time to do manually.
To find out more about Tecan’s hit screening and lead optimization solutions, visit lifesciences. tecan.com/screening_and_lead_ optimization To learn more about AI and nontarget drug discovery, go to www.transilico.com
TECAN JOURNAL 1/2020
27
Empowering you. Join us as we celebrate 40 years of
and partners’ research is changing
supplying cutting-edge technologies to
the world for the better, furthering
the life sciences and clinical
our understanding of our
communities! In marking this milestone,
surroundings, from fundamental
we celebrate the employees, investors,
science to the prevention, diagnosis
suppliers, clinicians and – most
and treatment of disease. So what
importantly – customers who have made
better way to celebrate your
Tecan into the leading laboratory
achievements than to host a series
automation solutions provider it is today.
of genomics, proteomics and cellomics events – including
One of our greatest pleasures here at
symposia, podcasts and workshops
Tecan is seeing how our customers’
– across the globe.
Keep an eye on www.tecan.com/40years where details of these events will be announced soon.
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