Tecan Journal Edition 01/2020

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

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

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,

2

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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