Edition 2 /2022 Tecan Journal Life Sciences, Diagnostics and Partnering A voyage of discovery: exploring the role of HMGB1 in trauma pathology A dream team for bioanalytical drug testing Fighting the opioid epidemic by reducing manual labor and increasing throughput Supporting Zika virus drug screening in Brazil Pages 18-19 Pages 26-27Pages 20-21 Pages 16-17
Driving the translation of research insights into compliant clinical solutions at scale is not ‘unprecedented’ for Tecan: it is our core business. I therefore invite you to join us on this path of discovery, as we work with our partners in research, drug development and discovery, diagnostics and clinical settings to confront the challenges we face with a common purpose. Tecan will continue to push the boundaries of research, the potential for discovery, and the promise of solutions and applications that scale healthcare innovation globally.
Beyond the pandemic, our customers are making exciting discoveries and developing novel therapeutics for improved patient outcomes across many areas, including oncology and metabolic disorders. They are taking innovative approaches to new therapeutic fields – like cell and gene therapies – advancing minimally invasive robotic surgery, facilitating novel insights in spatial biology, and expanding use of technologies like mass spectrometry and NGS. In combination with strong innovation in digital solutions, this is driving a whole new world of accelerated discovery, increasingly personalized diagnostics and enabling ever more tailored and effective treatments. As we did during the pandemic with scalable solutions for PCR testing, Tecan will continue to broaden the availability and adoption of further solutions for better diagnosis and treatment of patients around the world.
2 CEO WELCOME TECAN JOURNAL 2/2022
We have become accustomed to referring to the last couple of years as ‘unprecedented’. However, the life sciences, biomedical and healthcare communities have regularly bound together in common purpose to tackle the pressing issues of our times. Though the challenges we face are rarely as novel as the SARS-CoV-2 outbreak, those issues do have global impact on people’s lives and health. This is why, as the world emerges from the worst of the pandemic, we are accelerating our work at Tecan to make critical lab processes and medical procedures even more precise, reproducible and accessible. We are continuing to work arm-in-arm with our research and industry partners to find where collaboration accelerates innovation, not just to drive success in the market, but to create farreaching, scalable solutions that add value and improve people’s health.
A whole new world of discovery, diagnosis and treatment
Achim von Leoprechting CEO
18 - 19 A voyage of discovery: exploring the role of HMGB1 in trauma pathology
3
Contents
26 - 27 A dream team for bioanalytical drug testing 27 Leading the debate 18 - 19 A voyage of discovery: exploring the role of HMGB1 in trauma pathology Applications and platforms presented in the Tecan Journal may not be available in all markets. Please consult your local Tecan office for information.
20 - 21 Supporting Zika virus drug screening in Brazil
10 - 11 Revolutionizing long DNA synthesis by speeding up the process 12 - 13 Trust your gut – advances in microbiome DNA analysis
8 - 9 The truth about NGS and library prep: find out what is inflating your costs
Salivary stress biomarkers to nose out the benefits of healthcare clowning to children with psychiatric disorders
16 - 17 Fighting the opioid epidemic by reducing manual labor and increasing throughput
CONTENTS TECAN JOURNAL 2/2022
24 - 25 Salivary stress biomarkers to nose out the benefits of healthcare clowning to children with psychiatric disorders
Automated sample prep – bringing proteomics closer to the clinic
14 - 15 Quality food and feed enzyme development at the industrial scale
24 - 25
22 - 23 Improving speed and accuracy of biomanufacturing for more rapid and cost-effective therapies
2 Welcome 4 - 7
• achieving acceptable turnaround times from receiving samples to the generation of a complete proteome profile analysis
Increasing protein sample analysis throughput When considering sample prep, there are broadly two types of proteomics experiments that researchers might want to perform: discovery or targeted proteomics. Both types can have significantly different sample prep requirements, and any solutions that can mitigate the need for differences in sample prep would be helpful. For discovery proteomics, experiments are designed to identify as many proteins as possible across a broad dynamic range. For example, the complete measured range for the plasma proteome – from upper limits for albumin to lowest values for thyroid-stimulating hormone (TSH) –represents more than 10 logs of molar abundance.1 Discovery proteomics can be used to form an inventory of all detectable proteins in a given sample or to detect differences in the abundance of specific proteins amongst multiple samples. When it comes to sample prep, this intrinsic complexity means that we might require the concurrent depletion of highly abundant proteins and enrichment of less abundant proteins, plus fractionation – for example by SDS-PAGE – or liquid chromatography
• simplification of the workflow to remove the need for personnel with specific technical skills in proteomics
Automated sample prep –bringing proteomics closer to the clinic
To date, proteomics has not hit its stride for two reasons. Firstly, expectations were set unreasonably high, hot on the optimistic coat tails of the genomics revolution. Secondly, techniques have only recently been developed that allow reproducible sample processing for a large variety of samples without changes to the protocol. The obvious complexity and diverse physiochemical nature of the proteome has all but tripped us up, raising a frustrating list of ‘must haves’ for proteomics to be useful in clinical research and, eventually, in the clinic.
• the ability to analyze enough (possibly hundreds or thousands or more) samples to achieve statistically significant results in patient cohorts
TRENDS, NEWS, STORIES AND MUCH MORE! FROM THE EXPERTS TO YOU.The Blog BLOG 4 TECAN JOURNAL 2/2022
Successful implementation of proteomics in the clinical environment has still not materialized, and lags far behind genomics, even after decades of advances in protein sample preparation. The primary cause for this underwhelming performance lies in the diverse physiochemical properties of proteins and the complexity of the sample prep workflow itself. So what are the bottlenecks that prevent proteomics from entering clinical use?
Proteins – both the disease and the cure Proteins are the root cause of disease and represent a pathway to cures, whether we are looking at cancer or coronavirus.
• a cost-effective workflow Let us examine each of these in turn, as potential steps on our path to automated protein sample preparation.
Indeed, the vast majority of drugs hit protein targets. We have long anticipated that proteomics would deliver novel biomarkers to be used in the diagnosis, prognosis and therapeutic monitoring of disease. However, for this to happen, simple and efficient protein recovery and sample preparation must be reproducibly achieved from a broad range of sample types without significantly altering sample processing. Why hasn’t proteomics delivered yet?
At a bare minimum, these include:
Complex protein samples can be viscous, so automation is also likely to necessitate positive pressure or centrifugation – vacuum may not be enough. Positive pressure has been
Simplifying the protein sample prep workflow When it comes to preparing protein samples for downstream analysis, enzymatic digestion protocols can be extremely effective when working with protein suspensions. 4 This approach typically requires use of a lysis buffer with a high concentration of detergent, such as 5 % SDS. However, SDS is incompatible with downstream analytical instrumentation and assays, such as LC-MS/MS or ELISA. Wash or clean-up steps prior to analysis are therefore essential yet time consuming and possibly prone to human error when done Simplificationmanually.ofprotein sample prep workflows requires a robust protocol that can be automated for binding, washing and digestion steps. The ideal protocol should be identical for the different sample types of interest, or at least have as few variations as possible, because differences in the sample preparation are a major source of experimental variation. 5
www.tecan.com/blog BLOG TECAN JOURNAL 2/2022 5 prior to mass spectrometry. If quantitation is needed, this will add yet another layer of difficulty.
Whether considering discovery or targeted proteomics, sample preparation for bottom-up proteomics consists of several critical steps: 1) extraction and solubilization of protein 2) protein denaturation 3) removal of detergent and desalting 4) enzymatic digestion 5) separation of peptides 6) analysis by mass spectrometry, electrophoresis or immunoassay Detergents such as SDS are routinely used for solubilization and denaturation of proteins. However, these reagents can interfere with downstream protease digestion and MS analysis –even at low concentrations – and are notoriously hard to remove, creating a major barrier to increasing throughput. Throughput is further hampered if different sample types require different Anyprotocols.attempt to automate protein sample prep and still retain as complete as possible an inventory of the proteome – including membrane proteins – is likely to require some sort of solid support onto which the proteins can be captured so they can be rinsed free from substances that are incompatible with downstream processing. Such a protocol will need to remove all types of potential contaminants, including detergents (eg. up to 15 % SDS), salts, glycerol, PEG, Laemmli loading buffer and bile salts, among other contaminants.
Once proteins of interest have been identified and demonstrated to be biomarkers for a given disease state, targeted proteomics experiments can be considered. In contrast to discovery proteomics, targeted experiments might seek to quantify specific proteins with high precision, sensitivity, specificity and throughput. These proteins may become biomarkers for specific diseases. A targeted approach might decrease the complexity of sample preparation and will likely be far easier to implement when it comes to increasing throughput. Targeted proteomics is therefore the method of choice to quantify specific proteins and metabolites in complex samples in pharmaceutical and diagnostic applications. 2,3
Decreasing sample turnaround time
The ability to perform accurate, automated total protein sample prep in a 96-well plate format would be a game-changer when it comes to experimental design in proteomics. When done manually, total protein sample prep is tedious, as samples are handled and processed one by one, whereas automation allows the scalable analysis of proteomes, with multiple samples at multiple time points, giving researchers the potential to do infinitely more dynamic and complex sets of Achievingexperiments.anacceptable turnaround time from receiving samples to the generation of a complete proteome profile analysis will also depend on the technology used downstream. This may involve one or more of the following: mass spectrometry or LC-MS/MS, electrophoresis or, if specific proteins have already been identified, ELISA or other immunoassays.
To optimize sample turnaround times, one can either decrease the time it takes for an individual sample to be processed, process as many samples as possible in parallel, or both. If the upstream capture, clean-up and digestion is automated, the process is probably as optimized as it can be on the level of treatment of the individual sample, so then one can look towards parallel processing of multiple samples in order to decrease sample turnaround times overall.
Ensuring cost effectiveness of the workflow
Thus, if we want to be realistic about simplifying the protein sample prep workflow by automation, we will need to consider processing our captured protein samples using a positive pressure unit with a compatible liquid handling protocol for cleaning up and digesting samples prior to analysis.
Automation is often thought of as an expensive luxury in the lab. However, we cannot forget that the cost of repeating research can be massive, far dwarfing the cost of automation. Cost effectiveness will depend on the aim of a particular proteomics research project, as well as on the existing infrastructure. The streamlining of the protein sample prep workflow as described here will certainly help towards cost effectiveness, potentially saving time and money with fewer errors and less manual labor. In turn, a new, automated way of working will shift the bottlenecks and the questions that can be answered, allow new projects to be conceived and, ultimately, quicken scientific progress.
TRENDS, NEWS, STORIES AND MUCH MORE! FROM THE EXPERTS TO YOU.The Blog BLOG 6 TECAN JOURNAL 2/2022 shown to be more reproducible than vacuum.6 In addition, positive pressure units can generally operate at higher pressures than a vacuum is able to provide and can therefore more easily guarantee sufficient and constant pressure on all the columns in a parallel set-up of a matrix of samples, such as in a 96-well plate. This results in a steady pressure being applied over a specified time with a defined pressure-assisted sample processing (PASP) protocol.
4) Klont, F et al. Assessment of Sample Preparation Bias in Mass Spectrometry-Based Proteomics. Analytical Chemistry, 2018, 90 (8), 5405-5413.
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1) Hortin, GL & Sviridov, D. The dynamic range problem in the analysis of the plasma proteome. Journal of Proteomics, 2010, 73(3), 629-636.
References
2) Thakur, S. Proteomics and Its Application in Pandemic Diseases. Journal of Proteome Research, 2020, 19 (11), 4215-4218.
5) Piehowski, PD et al. Sources of technical variability in quantitative LC-MS proteomics: human brain tissue sample analysis. Journal of Proteome Research, 2013, 12(5), 2128-2137.
3) Faria, SS et al. A Timely Shift from Shotgun to Targeted Proteomics and How It Can Be Groundbreaking for Cancer Research. Frontiers in Oncology, 2017, 7, 13.
6) PressureExtraction-Method-Using-Positive-of-an-Automated-Solid-Phase-Application-Notes/172423-Evaluation-www.americanlaboratory.com/914-
TRENDS, NEWS, STORIES AND MUCH MORE! FROM THE EXPERTS TO YOU.The Blog BLOG 8 TECAN JOURNAL 2/2022
The truth about NGS and library prep: find out what is inflating your costs
Even when library prep is automated, it can take far too long to set up and optimize the scripts Many automated workflows still involve a lot of time-consuming activities that could be further simplified and streamlined. For example, how much time are your lab members spending making up master mixes, ensuring the workdeck is configured properly and reconfiguring protocols for their specific applications? Do you need to get help from a programmer every time a new application comes along or even to make a simple script change? This is not uncommon. 2. Library reproducibility issues may be arising more frequently than necessary Manual processing increases the risk of variability In particular, library prep involves numerous pipetting steps, which increases the likelihood of errors, sample carry-over, contamination and operator variability.
Training is a hassle Whether preparing libraries manually or with an automated system, an excessive amount of time is often spent on training. This can have a big negative impact on productivity, especially in labs where there is a high staff turnover. In cases where automated library prep is not user friendly, or requires some level of programming skills, many labs will hand over day-to-day management and running of the system to a dedicated expert. However, this can be a costly option, not to mention a waste of valuable expertise. Errors are more likely Any steps that require manual intervention are opportunities for human error, and potential sources of variability. Lots of replicates and boring, repetitive tasks like pipetting are a recipe for mistakes because it’s easy to lose concentration. Errors and variability often translate into poor quality or invalid results, in which case the experiment must be repeated. Not only can this cause an expensive delay, there may not even be enough sample remaining to enable a repeat experiment, for example, if it was a very rare patient sample, you might only have one shot.
Should you be concerned about that? Absolutely. Here’s why: 1. Valuable time is being wasted on NGS library preparation Typical manual library prep workflows require a lot of hands-on time Since the majority of library prep workflows can now be automated, too much time is spent doing manual work. This time could and should be better spent on more intellectually demanding tasks, like results interpretation or planning the next important experiment. Other wastes of time in the lab include, for example, the need to order reagents and consumables from multiple vendors and having to find the correct reagents and consumables in the lab before starting library preparation.
Isn’t it time we spoke the truth about the toll next generation sequencing (NGS) is taking on your lab? Yes, NGS is a revolutionary technology that can help you break new ground in your research, but when you get right down to it, how much time is actually spent making the big breakthroughs versus generating the raw sequencing data? If your lab is like most, the answer is surprisingly little. Why? Because most of your team’s time is probably spent on tedious, labor-intensive tasks like library prep.
Conclusion – the cost of ignoring these issues may be higher than you think
Lack of standardization can have a big impact Use of standardized procedures and protocols is essential to ensure consistent results, yet this is a source of variability that is often overlooked. Problems can arise when there are inconsistencies or unplanned changes in the library prep kits and protocols being used, the quality or source of reagents, the standard to which incoming staff are trained and so on. Variability in the amount of input DNA or RNA Nucleic acid variability is another common culprit that can affect NGS library reproducibility, particularly if the kit you are using is not designed to tolerate a broad input range or variable sample volumes.
3. Your lab staff are getting burned out Lab work is demanding at the best of times, but stress levels can go through the roof when staff are burdened with many mind-numbing and time-consuming tasks that don’t seem to add much value. In addition to compromising the quality of their work, this situation can cause ill health, job dissatisfaction and, ultimately, a higher than average attrition rate. Don’t let it get to that point!
The bottom line is that while the cost of sequencing has plummeted over the years, a lot of labs are still spending far more than they should on NGS. Many hidden costs of NGS can be traced back to the upstream steps of sample and library prep. Over time, the cost of errors or poor quality in library prep is often higher than investing in a streamlined library prep workflow. Any time spent doing something a robot could do or figuring out how to operate the robot – if there is one – is a total waste of resources. Likewise, having to hire or train dedicated experts is an unnecessary expense if you can source equipment and reagents designed to minimize complexity and maximize ease of use.
Until recently, labs running NGS at low throughput, or only infrequently, have tended to suffer the most from these sorts of issues because library prep solutions are typically designed with higher throughputs in mind. Fortunately, for labs such as these, Tecan is working with them to uncover hidden costs that make NGS and automated library prep a more feasible solution even at low throughputs.
www.tecan.com/blog BLOG TECAN JOURNAL 2/2022 9
Dr Marc J Brehme, Chief Technology Officer at Ribbon Biolabs, explained: “Our mission is to make long DNA accessible at a scale previously unseen in the industry, driving the development of scientific and translational research across all fields of biotechnology. We focus on the synthesis of complex products, providing long, subgenomic DNA strands – 10,000 base pairs or longer – and entire libraries containing multiple variations of a molecule. Traditionally, this is something that has been expensive and difficult to obtain, with very little guarantee of success. Equally important, researchers often had to wait weeks or even months before receiving their materials, which is a long time to wait for any project in the pharmaceutical industry. At Ribbon Biolabs, we have combined automation with an innovative enzymatic approach to speed up this process, providing accurate, fast and affordable DNA synthesis, to empower biopharmaceutical and biotechnology customers across academia and industry.” Harold, Ribbon Biolabs’ Founder and CEO, said: “We are bringing the Ford model to the automated synthesis of long DNA, at a scale that is unprecedented in the Marcindustry.”continued:
quickly and at an affordable price.
Revolutionizing long DNA synthesis by speeding up the process
“Coming from a systems biology and biotech background, I joined the company in 2019 to oversee tech development and workflow automation. We initially began by creating a concept process and developing a proprietary algorithm-based pipeline that would enable us to synthesize bespoke DNA sequences for each customer. This was combined with customized automation platforms to help increase the throughput, multiplexing and robustness of the workflow. We procured a
10 TECAN JOURNAL 2/2022 SYNTHETIC BIOLOGY
Ribbon Biolabs is revolutionizing the production of long and complex DNA, using cutting-edge technologies to rapidly synthesize long, subgenomic polynucleotides at an affordable rate.
Founded in 2018, the company is the result of geneticist and mathematician Dr Harold P de Vladar’s frustrations at the prohibitive cost and slow turnaround he encountered when procuring libraries of viral DNA variants for his own evolutionary genetics studies. Based in the Vienna region of Austria, Ribbon Biolabs is streamlining and automating the synthesis of DNA, and specializes in providing long DNA molecules or complex libraries of high fidelity variants, Synthetic DNA has become the central component of countless scientific and technological innovations across many applications, from biopharmaceuticals to biofuels.
Dr Marc Brehme, CTO, and Dr Harold P de Vladar, CEO, of Ribbon Biolabs
However, research and drug development pipelines are often hindered by the cost and the length of time that it takes to obtain long sequences of DNA or multiple DNA variants. Ribbon Biolabs, based in Vienna, is addressing this issue by combining automation and adaptive algorithmic control with highly precise, optimized enzymatic synthesis.
To find out more about Tecan’s Frida Reader, Totecan.com/fridareadervisitfindoutmoreabout Tecan’s Fluent Automation Workstation, visit tecan.com/fluent helping to streamline parts of our workflow and enabling successful automation of our core processes. Automating every step of this pipeline without the need for manual interaction differentiates us from competing technologies and has been a key part of our success. It avoids human errors and increases walkaway times, freeing up laboratory technicians and reducing costs. This also helps to significantly improve our turnaround times to offer fast and accurate long DNA products at a highly competitive price. Recently, we were excited to announce a significant milestone for the company, underlining our technology’s capability and potential. Using our proprietary FullGenes platform, the team produced a linear, synthetic double-stranded DNA product with a record length of 10kbp. This technological breakthrough will help us to provide our customers with faster access to synthetic long DNA, boosting future scientific developments and accelerating the research of novel products, such as next generation
TECANbiopharmaceuticals.”JOURNAL2/2022
Fluent® Automation Workstation to fit into this workflow because we needed a robust multifunctional liquid handling solution that was both convenient and affordable. The set-up process in cooperation with Tecan was smooth and efficient, and the company was very helpful in providing custom drivers for the integration of other modules with the platform.”
“As the evolution of our automated workflow progressed, we decided to join the beta testing team for the Frida Reader™. We were interested in the possibility of incorporating a spectrophotometric reader with a small footprint into our instrument because we wanted to have real-time measurements of our synthesis process to enable full use of adaptive control and feed data back to our algorithms. This newly developed system offered the capability to perform the necessary absorbance measurements without sample loss. This is an important consideration for us, as the long DNA products we generate are valuable, so it is highly desirable that we avoid sample loss throughout the process. The principle of obtaining measurements from a hanging drop – while keeping our sample volume unchanged – was therefore extremely appealing. Furthermore, the Frida Reader has a very small footprint for ease of integration, offering us a fully automated workflow that combines standard liquid handling functions with the measurement and processing of samples – such as concentration adjustments – in a seamless manner. This is simply unachievable with conventional lab robotics.”
TECAN JOURNAL 2/2022 11 SYNTHETIC BIOLOGY
To learn more about Ribbon Biolabs, go to ribbonbiolabs.com
“Our Tecan instruments have been crucial additions to our platform, Our Tecan instruments have been crucial additions to our platform, helping to streamline parts of our workflow and enabling successful automation of our core process.
For Research Use Only. Not for use in diagnostic procedures.
Ortho-Analytic extracts bacterial, fungal and parasite nucleic acids from stool specimens using the DreamPrep™ NAP workstation and the ZymoBIOMICS™ 96 MagBead DNA Kit from Zymo Research, minimizing contact time with the samples and reducing the likelihood of introducing manual errors. The system also incorporates the Frida Reader™ module for built-in quantification and normalization. Dr Philipp Lemal, deputy laboratory manager at Ortho-Analytic, explained: “We tested several DNA extraction kits, and found that the one from Zymo Research was the best for our application. Tecan had already automated this kit for use on its DreamPrep NAP system, so we could purchase the whole package and save ourselves a lot of time in the validation process.”
12 TECAN JOURNAL 2/2022 GENOMICS
The demand for gut microflora analysis has been growing rapidly over the last few years due to recent discoveries that bacteria in the digestive tract can have significant impacts on our general health. However, many smaller facilities are now struggling to keep up with the increased workflow. One solution that addresses this challenge is the automation of DNA extraction from stool samples, which represents an important step towards increasing lab throughput and reducing costs, and offers the potential to open up the medical benefits of microbiome profiling to greater segments of the general public. This approach was the one taken by Ortho-Analytic for its specialist service providing the detection and analysis of bacterial DNA present in patients’ stool samples.
Trust your gut – advances in microbiome DNA analysis
Members of the microbiome project team at Ortho-Analytic The human gut microbiome has been found to affect metabolic health and nutrient absorption, and preliminary research also suggests that it contributes to the development of the immune response, food allergies and intolerances, obesity, and a wide range of other conditions. This field is the focus of Ortho-Analytic, an integrative medicine laboratory based in Wallisellen, Switzerland, that identifies bacterial, fungal and parasite DNA found in stool samples. The company uses molecular genetic analyses to build a detailed picture of a patient’s gut microbiome, aiding practitioners in formulating specific treatment plans.
TECANforward.”JOURNAL
TECAN JOURNAL 2/2022 13 GENOMICS
To learn more about OrthoAnalytic, visit orthoanalytic.ch
Philipp spoke about the team’s current and upcoming research projects: “At the moment we are collaborating with several universities all over the world that are using our technical platform for their research. We also hope to be involved in a greater number of long-term studies in the near future, which will help the research community to be able to clearly associate the microbiome with many conditions, including cancers and inflammatory bowel disease.”
2/2022
It took under two weeks for the system to be fully calibrated and adjusted in the lab, and it has proven to be very robust and reliable, allowing staff to perform other tasks while the machine runs in the background. The team has found the workstation itself to be very flexible, enabling employees to easily add or change scripts as necessary to fine-tune the extraction process.
The DreamPrep NAP now automates most of our workflow, which has increased throughput more than fivefold to around 200 samples per day. The Frida Reader module also allows us to measure DNA concentration straight after we extract it, all on the same machine, and that’s very convenient.
Philipp described how the move towards automation has had a positive impact on the lab’s productivity: “Before we had the DreamPrep NAP workstation, we did all of our extractions manually, and could only process a maximum of 40 samples per day. The DreamPrep NAP now automates most of our workflow, which has increased throughput more than fivefold to around 200 samples per day. The Frida Reader module also allows us to measure DNA concentration straight after we extract it, all on the same machine, and that’s very convenient.”
For Research Use Only. Not for use in clinical diagnostics.
For more information about Tecan’s genomics applications, visit genomicsapplications_and_solutions/lifesciences.tecan.com/
To further improve the quality of microbial DNA extraction, Ortho-Analytic has collaborated with BÜHLMANN Laboratories to develop its own sample tube, the Calex NGS. The tube contains a special stabilization buffer that kills bacteria, viruses and fungi and hinders biological activity inside the tube to stabilize DNA prior to extraction. This ultimately produces a more accurate and realistic representation of microbiome composition for each sample. Until recently, the lab was sending the samples to an external partner laboratory for DNA extraction and molecular genetic analysis. However, the team was concerned about sample stability during transport due to the long transit times and inconsistent storage conditions. This limitation motivated staff to begin performing microbial DNA analysis themselves, with the aim of preserving their specimens and providing faster, more reliable results. These workflow adjustments promise to enhance the speed and quality of both DNA extraction and analysis, increasing the lab’s capacity to meet the demand for microbiome profiling well into the future. Philipp concluded: “We are really happy that we can finally do all our DNA extraction and analysis in house, and we hope that this will greatly benefit our clients and their patients going
The use of enzymes as biocatalysts in industrial applications has steadily gained popularity, as it offers an efficient way to use raw materials while minimizing waste. This approach has been successfully scaled for commercial processes in the pharmaceutical, food and beverage industries, largely thanks to the use of automation to screen, optimize and produce suitable enzymes. Roal Oy in Rajamäki, Finland – a leading producer of industrial enzymes – has automated large parts of its enzyme discovery and screening activities to accelerate product development and optimization.
Quality food and feed enzyme development at the industrial scale
Roal relies on a number of Tecan automation workstations across its R&D and QC departments to ensure accuracy
14 TECAN JOURNAL 2/2022 INDUSTRIAL ENZYMES
For Research Use Only. Not for use in clinical diagnostics. We originally chose to purchase instruments from Tecan because we needed to increase our liquid handling capabilities and throughput in R&D, and the best way to do that was by investing in an automated system.
automated quantitative analyses to assess the individual activities of libraries of variants. Each of our systems also has a Pickolo™ Colony-Picker from SciRobotics for hit-picking and cultivation, and both the hardware and software of this device integrate seamlessly into the Fluent.”
Roal’s Research and Development Department uses automation extensively in its workflows, enabling efficient molecule screening and enzyme development, as well as quality control activities. The company has a long experience using Tecan’s
“The Fluent is user friendly and offers a sterile and safe work environment, minimizing the strain of repetitive pipetting. I really like that you can tune the set-up of the system to suit different purposes, and that it is possible to add on modules, such as integrated readers and heaters. The FluentControl® software makes it easy to implement new features and devices. Just as importantly, we have a good relationship with Tecan’s local distributor here in Finland – Triolab Oy – so we are confident that we will receive good technical and service support,” concluded Kari.
TECAN JOURNAL 2/2022 15 INDUSTRIAL ENZYMES
The main benefit of enzyme-catalyzed processes over chemical reactions is that they are more efficient and better controlled, enabling very costeffective development of specific final products while minimizing raw material use.
Roal Oy – a subsidiary of Associated British Foods and Anora – is one of the world’s largest enzyme companies, creating a wide range of products for different applications across the food, technical and feed industries, specializing in Trichoderma, Aspergillus and Bacillus fermentations. Dr Kari Juntunen, Senior Research Scientist at Roal, explained: “Our main markets are the feed industry – predominantly producing xylanases and phytases –and the food sector, including amylases, proteases and pectinases. In addition, we make cellulases and xylanases for the paper and pulp industry, and enzymes for detergent applications, as well as a number of products for other industries.”
For more information about Roal Oy, visit www.roal.fi
To find out more about Tecan’s Fluent Automation Workstation, visit tecan.com/fluent
Enzymes have become increasingly common in industrial applications of the past century and are now widely used in the food, agricultural, pharmaceutical and cosmetics sectors.
products. Dr Janne Wallenius, Senior Research Scientist, commented: “We originally chose to purchase instruments from Tecan because we needed to increase our liquid handling capabilities and throughput in R&D, and the best way to do that was by investing in an automated system. We started with a Freedom EVO® liquid handling workstation and, when even better pipetting capabilities and more flexibility were required, we purchased two Fluent® Automation Workstations. This was an easy choice, since we were already accustomed with the brand, and intuitively knew how to use the “Wesystems.”now have a number of Tecan platforms here in Rajamäki, in both R&D and QC,” Kari added. “The QC team uses its system for routine activity analysis of products, whereas our instruments in R&D are mainly used for new enzyme discovery and screening, meaning they need to be much more flexible for developing new methods. In addition, our sister company AB Enzymes GmbH in Darmstadt, Germany – which sells many of our products –also has a number of Tecan platforms, allowing smooth transfer of protocols between sites.”
Janne continued: “We use the Fluent systems extensively for cloning and screening, providing consistency for our analyses and increasing our throughput for enzyme discovery and screening, while also reducing monotonous manual work. We also have Spark® and Infinite® 200 PRO M Plex plate readers integrated into our platforms for measurements,absorbanceallowingfully
Fighting the opioid epidemic by reducing manual labor and increasing throughput Automation helps the small Ideal Option team to efficiently process samples from 75 clinics across 10 states
“We have two different aspects to the lab,” David added. “The biggest part is our toxicology screening, but we also have a medical lab, as some patients come to us with other health problems, such as sexually transmitted infections. In the toxicology lab, sample preparation begins with solid phase extraction – primarily from urine samples, but also from oral fluid collections. These samples are then analyzed using LC-MS. When I first
Opioid addiction, alongside addiction to other substances, is a significant public health, social and economic challenge in the US. In 2017, the opioid epidemic was declared a public health emergency by the Department of Health and Human Services, with one of its aims to improve access to treatment and recovery services. Despite this, over 100,000 US lives were lost to opioid overdoses in the year to April 2021. Increasingly, outpatient centers such as Ideal Option are providing medication-assisted treatment (MAT) – combining approved medications with counseling and support therapy – to offer a ‘whole-patient’ approach to treatment of, and sustained recovery from, these addictions. Ideal Option was established in 2012 by two emergency medicine physicians, with a mission to provide underserved populations with low-barrier access to evidence-based addiction treatment. Since then, the company has undergone rapid expansion and is now one of the largest outpatient providers of MAT for addiction to opioids, alcohol, methamphetamine and other substances in the US. Dr David Newcombe, Laboratory Director, explained: “The company started with one clinic in Kennewick, Washington. Since then, it has expanded to more than 75 clinics in 10 states, as well as laboratory services to support the clinics with toxicology and medical screening. Since 2017, we have more than tripled the number of patient samples that we process every day –we now run around 17,000 each month – and this growth has required a substantial increase in our infrastructure. For example, we originally had just one LC-MS/MS instrument, and we now have 10.”
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Dave concluded: “Automation has helped us tremendously during our organization’s growth phase. We’ve been able to absorb a lot more work than if we were still doing things manually. We always run on the thinnest margins of capacity, but automation has offered a buffer so, for example, if we get a big sample surge, we’re able to work through it faster. I honestly couldn’t see us doing it any other way now.”
To find out more about Tecan’s solutions for solid phase extraction workflows, visit tecan.com/spe For Research Use Only. Not for use in clinical diagnostics. started at the company in 2017, our technicians were pipetting every single sample by hand. In the morning, one technician would sit down with their 100 samples, and they would spend the next four hours doing nothing but pipetting, performing the hydrolysis, then transferring the samples to vials for the instruments. Every vial was also having to be labeled by hand, and it was just not sustainable, as well as being easily open to mistakes.” With the throughput requirements of the lab increasing quickly, it became clear that a new solution had to be found.
TECAN JOURNAL 2/2022
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Automation has helped us tremendously during our organization’s growth phase…. I honestly couldn’t see us doing it any other way now.
“The Tecan team helped to set up the protocols in the very beginning, and then anything we’ve had to modify, we’ve done ourselves. Anytime we’ve had issues, we’ve easily been able to talk to an applications specialist or an engineer, which has been great. We’ve had the instruments in place since 2018, and we’ve found them to be very robust considering we use them heavily.”
to load 10 plates it would take 10 people. Now, two people can carry out all the extractions for the day, freeing up the others to review data and carry out other tasks. Using the Resolvex to clean the samples has also allowed us to go for a more aggressive gradient on the LC portion, so we have reduced our run time from 9.5 to 6.5 minutes. Because of the quality of the samples, it’s also easier to review the data, and we’ve found it much easier to maintain the mass spec equipment, so it’s been completely win-win for us.”
To learn more about Ideal Option, go to www.idealoption.com
David continued: “We knew we had to find a way to automate the whole process, and Tecan offered an ideal solution. We now use a Freedom EVO® 100 liquid handling workstation to pipette our samples and reagents, then move on to a Resolvex® A200 positive pressure processor to carry out the extractions. The Freedom EVO has a barcode reader, so all of the tubes are scanned automatically, which has eliminated the tedious manual labeling and made samples much easier to track. We also use disposable tips on the platform, which removes the risk of “Before,cross-contamination.”ifwewanted
TraumaIMMUNOASSAYSisthemain cause of premature death internationally, resulting in more deaths in people under 40 years old than all other causes combined. Even trauma victims receiving hospital care have a high mortality rate, in part due to massive systemic inflammatory reactions leading to the dysfunction of organs that were not initially injured. A team at Oslo University Hospital in Norway has been investigating the role of the protein HMGB1 (High Mobility Group Box 1) in the development of trauma pathologies and its potential as a clinical biomarker or therapeutic target in these cases.
HMGB1 is a nuclear protein that, under normal physiological conditions, binds and bends DNA strands as part of the normal process of DNA organization and transcription. However, cells release HMGB1 into the extracellular environment when exposed to stress factors such as hypoxia, contributing to disease pathogenesis and inflammation. HMGB1 is also released passively from damaged cells, serving as a necrosis marker. Consequently, HMGB1 has gained attention as a potentially important marker for the progress of organ failure after trauma and as a predictor of clinical outcomes over recent years. Torsten’s aim was to capture the dynamics of HMGB1 release from as early on as possible and throughout a patient’s illness, ideally establishing HMGB1 as a prognostic marker for trauma pathology and preparing for the development of HMGB1 antagonist-based therapy. In 2011, the critical care team began to assemble a biobank, initially collecting
Oslo University Hospital, Ullevål (OUHU) is the major trauma center for half of Norway. Affiliated with the University of Oslo, OUHU is also a large research institution, conducting lab-based research in fields such as cancer, cell biology and cardiovascular disease. Dr Torsten Eken is a Senior Consultant Anesthesiologist in the Department of Anesthesia and Intensive Care at OUHU – as well as Professor at the Institute of Clinical Medicine at the University of Oslo –and has a long history of working with trauma patients. He explained his interest in HMGB1: “Over the first few days in intensive care, critically injured patients may begin to exhibit symptoms similar to sepsis, experiencing remote organ failure in areas of the body that had not originally been damaged. I began investigating the possible underlying causes of these pathologies, leading me to look at HMGB1 as a possible driving force behind remote organ failure and delayed mortality.”
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A voyage of discovery: exploring the role of HMGB1 in trauma pathology
blood samples from around 150 trauma patients. For each individual, they took samples upon arrival in the emergency room, then at two-hour intervals for the first eight hours, and every morning in the ICU. The team then performed quantitative analyses using Tecan’s HMGB1 ELISA Kit to examine fluctuations in HMGB1 levels during illness. “We began using the Tecan HMGB1 ELISA Kit from the very beginning of our research,” Torsten continued. “[The Tecan kit] was the de facto standard for HMGB1 analysis and had previously been validated for a number of diseases and
Dr Torsten Eken and his research team at Oslo University Hospital, Ullevål
Torsten outlined the next steps on their journey: “This discovery holds a lot of promise because it’s highly predictive, For more information about Torsten Eken’s research, tecan.com/hmgb1-express-elisaHMGB1Toindex.htmlenglish/people/aca/torsten/www.med.uio.no/klinmed/visitfindoutmoreaboutTecan’sExpressELISA,visit and it seems we can influence the outcome in some experiments. There appears to be a small but clinically accessible time window where it may be possible to limit progression of the disease. So far, most of the research has been carried out with rat and mouse models, but it is challenging to extend these models to prolonged intensive care in humans. We are therefore refining a large-animal model in deeply anesthetized pigs with multiple injuries, including femur fracture and lung contusion, as well as hemorrhagic shock. We want to explore the HMGB1 kinetics in this model to see if we can reproduce the second wave that we have seen in our human patient population. If we succeed, we would like to go on and introduce HMGB1 antagonism as well, paving the way for future clinical trials.” Tecan HMGB1 Express ELISA is CE-IVD marked in Europe, and may not be available in all countries. Please contact your local Tecan office.
[The Tecan kit] was the de facto standard for HMGB1 analysis and had previously been validated for a number of diseases and sample types, so it was an obvious choice. sample types, so it was an obvious choice. It was already in use in other labs in our hospital and allowed us to compare the results of our research with other studies on trauma and sepsis.” Screening the biobank with the HMGB1 ELISA Kit produced surprising results for the team. All patients showed high initial HMGB1 levels at admission, but HMGB1 had a half-life of only 26 minutes, and was cleared from their systems extremely quickly. What’s more, the most severely injured patients displayed a second wave of HMGB1 – a biphasic release – peaking three to six hours after the initial trauma. Injury severity and the level of physiological derangement are classical predictors of disease outcome, but the second HMGB1 wave rendered them statistically insignificant in multivariable analyses. The researchers therefore speculated that the second wave of HMGB1 release could be a mediator of the combined detrimental effects of anatomical injury and physiological derangement after trauma, making it a predictor of delayed mortality.
William Ottestad is a Consultant Anesthesiologist at OUHU and works within the Air Ambulance Department for the Helicopter Emergency Medical Service. He completed his PhD in 2020, and is part of the team studying the links between trauma pathology and HMGB1. He added: “We think that the second wave is not just a delayed release, but that it has a different biology, so it’s probably a distinct HMGB1 isoform. The next logical step is therefore to perform isoform analysis on both the first and second wave proteins. Unfortunately, this is very difficult to achieve using mass spectrometry, but we hope for the development of high throughput immunoassays for HMGB1 isoforms in the future. We believe that such an assay would give us clinically relevant results far sooner, which could have a large influence on the treatment of trauma patients, as well as allowing us to track the impact of different treatment options on the patient’s condition.”
TECAN JOURNAL 2/2022 19 IMMUNOASSAYS
Professor Martin Würtele from the DCT explained: “The core of our research here is drug design, structural biological and molecular modeling, with the overarching aim of finding lead compounds for the development of new antiviral drugs.”
Professor Martin Würtele and his team use a Freedom EVO workstation to automate library screening for new antivirals
Several outbreaks of the Zika virus have been reported around the world since its discovery in 1947, but a commercially available treatment for the disease is still not available, and scientists continue to search for the best antiviral agent.
Professor Martin Würtele and his colleagues in the Department of Science and Technology at the Federal University of São Paulo recently published a study identifying several natural substances that showed potent antiviral activity against the Zika virus protease.
Supporting Zika virus drug screening in Brazil
20 TECAN JOURNAL 2/2022 DRUG DISCOVERY
“Recently, our research has focused on finding novel antiviral agents to treat the Zika virus, which currently has no commercially available treatment,” Martin elaborated. “We carried out high throughput screening on a library consisting of 2,400 approved drugs, drug-like molecules and natural products in a bid to identify potent Zika virus protease inhibitors.1 Zika virus protease is a well-established and essential target for antiviral agents, so we began by purifying recombinantlyexpressed protease from the virus, before screening libraries of compounds against the enzyme using biochemical assays. Our study showed that several of the natural compounds – most of which were flavonoids – could successfully inhibit the activity of this
The Federal University of São Paulo (UNIFESP) is a well-ranked, government-led academic institution in the vibrant financial center of Brazil. Its Department of Science and Technology (DCT), located on the outskirts of São Paulo state, carries out drug development for various infectious diseases, including the Zika virus and COVID-19, performing large-scale screening and forming important collaborations with other national and international universities.
“We opted for this set-up because many members of our team had enjoyed working with Tecan instruments in the past, and in much larger diagnostic or drug development laboratories, which we believe is always the best reference when buying new equipment. Once you start working with a company that meets all of your needs, there is very little reason to change! Crucially for us, Tecan is also one of the few leading providers that has a good, local service organization in Brazil – RChisto Soluções LTDA. This was a huge deciding factor for our team, as we were able to work closely alongside the Tecan representatives, who demonstrated how to use the equipment and made model calculations for how accurate our pipetting would be. We had the whole workflow planned before even buying the devices, and the Brazilian representatives made sure that we had everything we needed. Since then, they have continued to be fantastic, training all of our team members on the equipment and answering any questions that we may have. I cannot express how helpful this was.”
1) Coelho, C et al. Biochemical Screening of Potent Zika Virus Protease Inhibitors. Chem Med Chem, 2022, 17(8), e202100695. For more information about the Department of Science and Technology at the Federal University of São Paulo, tecan.com/drugdiscoverdrugTowww.unifesp.br/campus/sjc/dctvisitfindoutmoreaboutTecan’sdiscoverysolutions,gotoy For Research Use Only. Not for use in clinical diagnostics.
“In our line of research, establishing a good biochemical assay and purifying high grade recombinant proteins –proteases in this instance – sets the stage for obtaining accurate results,” Martin continued. “That’s why we decided to automate all of our production and screening protocol with a Freedom EVO® 150 to guarantee pipetting accuracy. This instrument is coupled with the Infinite® M200 PRO multimode microplate reader, which offers accurate readings for the fluorescent marker peptides used in our assays, giving us a good indication of reaction kinetics, even at below micromolar affinity.”
TECAN JOURNAL 2/2022 21 DRUG DISCOVERY
Once you start working with a company that meets all of your needs, there is very little reason to change! protease, even at nanomolar levels, making them promising starting points for the development of future antivirals.”
“Introducing these instruments has been really great for the whole team, but especially for the students. Learning to work with automation is crucial for their career progression in drug discovery, as this is where the whole industry is headed. Equally, we can attract more students by offering them the chance to work with top-of-the-range equipment. Prior to this, the team was having to pipette 384-well plates manually, which was tedious and really took the enjoyment and precision out of our work. These systems have truly revolutionized our individual assay productivity, and the rate at which we can produce research papers. The open nature of the Freedom EVO platform, and resulting potential for upgrades, also unlocks further possibilities for us in the future, which is very exciting for academia.”
Improving speed and accuracy of biomanufacturing for more rapid and cost-effective therapies
Scientists working in the biopharmaceutical industry are constantly seeking novel drugs to advance human healthcare. However, despite the introduction of a steady stream of innovative technologies, the time and costs associated with the manufacture of biologics and cell therapies is still very high. ValitaCell, headquartered in Dublin, Ireland, is tackling this issue by developing pioneering analytical technologies and quality control tools to improve the performance, speed and accuracy of biomanufacturing, helping to bring novel therapies to market more rapidly and cost effectively.
Following the discovery of an antibody candidate, many clones must be screened to identify the best-producing cell line for downstream development.
The ValitaCell team is revolutionizing QC for biomanufacturing
Dr Eligio Iannetti, Business Development Manager at ValitaCell, explained: “IgG quantification has applications all the way through the biomanufacturing process, including in antibody discovery, cell line and process development, and manufacturing.
It is critical to know how much of a potential therapeutic the cell lines are producing over time, as well as the stability of the clone, which requires high throughput quantification of IgG.
“In contrast, ValitaTiter is a straightforward add-mix-read assay completed in three steps,” Eligio continued. “This fluorescence polarization (FP) assay is supplied in a microplate format, with the bottom of each well coated with a fluorescentlylabeled IgG-binding peptide. When this peptide binds to the IgG of interest, quantification can be quickly and easily performed by measuring FP in a microplate reader. An entire 96- or 384-well plate can be read in just 10 minutes. It’s fast, easy to use, convenient and cost effective – all you need is a plate reader with FP capabilities. Tecan’s Infinite® and Spark® readers are excellent examples of compatible systems, and the company also supplies liquid handling platforms for those labs wanting to automate the process.”
22 TECAN JOURNAL 2/2022 CELL BIOLOGY
The company’s flagship product, Valita®Titer, is a high throughput tool for quantification of IgG in monoclonal antibody development and manufacturing.
While this can be done by HPLC, analysis is slow and usually involves an overnight run. ELISA is another option, but it has multiple complex washing and blocking steps and can take up to five hours to complete.”
The biomanufacturing industry is constantly on the lookout for new technologies to improve the speed, accuracy and performance of its processes, particularly in the biologics arena. Biotechnology company ValitaCell has embraced this challenge, developing novel assays and label-free bright field imaging approaches employing artificial intelligence to complement fluorescence-based cell monitoring techniques.
“One of the first CellAi applications was developed using Chinese hamster ovary (CHO) cells and the Spark Cyto’s bright field imaging capability with a 10x objective. The benefit of this label-free technology is that we can predict cell viability without the need for staining, which can overestimate viability and has relatively low throughput. Moreover, trypan blue –the gold standard method to measure cell viability – has been identified as toxic. In addition, this technique generally uses cassettes containing the cells and the stain, which limits the number of samples that can be measured at any one time, while producing substantial waste in the process. Our approach is a safe, non-destructive, accurate and costeffective way of measuring cell viability from an entire 96- or 384-well plate without staining, and produces zero waste. You simply put the plate in the Spark Cyto and use bright field imaging to predict cell viability using the CellAi software. The 10x magnification produces excellent image quality and, since the reader also includes FP capabilities, it has everything needed for CellAi and ValitaTiter assays in a single small footprint, relatively cost-effective device that can quickly acquire data from an entire plate.”
To learn more about ValitaCell, visit valitacell.com To find out more about Tecan’s cell biology solutions, go lifesciences.tecan.com/cellbiologyto For Research Use Only. Not for use in clinical diagnostics.
TECAN JOURNAL 2/2022 23 CELL BIOLOGY
Artificial intelligence is increasingly being employed across the scientific community, and ValitaCell has developed an image analysis software – CellAi® – to extract information from label-free microscopy images, such as those obtained using bright field techniques. This game-changing technology, based on both deep and machine learning, has a wide range of image analysis applications.
There is a strong commercial synergy between ValitaCell and Tecan, and a good technological fit; we supply innovative analytical technologies, and Tecan provides high quality hardware.
“Typically, a lab carrying out this type of work will have a plate reader and a microscope. The automated microscopes used for high content screening are excellent for microscopy but can cost as much as one million euros, and don’t have an integrated plate reader. The Spark Cyto is ideal for this application, as it combines bright field and fluorescence imaging with conventional detection technologies for real-time cytometry.”
Eligio concluded.
ValitaCell has made extensive use of Tecan instruments during the development of its products, and this has led to a strong collaboration with Tecan’s global distributor network, partnering to combine and integrate both companies’ technologies into customers’ labs. “There is a strong commercial synergy between ValitaCell and Tecan, and a good technological fit; we supply innovative analytical technologies, and Tecan provides high quality hardware. Some customers already have suitable instrumentation in their labs and just require our reagents, software or service, so we help them set up and optimize the assay on their existing equipment. Others want to use our technology but don’t have a suitable plate reader or an automated microscope. We can talk to these customers and their distributors and suggest an appropriate system for their specific application, such as the Infinite reader for labs that only perform IgG quantification or the Spark Cyto for those that also require whole-well imaging for cell line development. The collaboration with Tecan is a clear win-win situation,”
shown that healthcare clowning has a strong positive effect on pediatric patients in general, but there is limited research into its impact on those with psychological disorders. RED NOSES Clowndoctors Austria – an organization with decades of experience in healthcare clowning – is addressing this issue through a collaboration with the Department of Clinical and Health Psychology at the University of Vienna. A joint study is currently being conducted in several psychiatric in-patient wards across Austria, using salivary stress biomarkers to assess whether clown visits are really benefitting patients.
24 TECAN JOURNAL 2/2022
medical procedures. This requires a lot of understanding and acceptance of our work from the healthcare staff and a good partnership with the hospital in Drgeneral.”Martina Zemp, Deputy Head at the Department of Clinical and Health Psychology at the University of Vienna, described the collaboration: “RED NOSES approached our department suggesting a study to evaluate the impact of clown visits on children and adolescents in a psychiatric setting, which is something that we found very interesting. There is a significant amount of evidence proving that healthcare clowning has a positive effect on stress, mood, anxiety and pain for non-psychiatric pediatric patients. However, there is not enough research that really quantifies its success in psychiatric care, and this information might be particularly relevant for the care of patients who experience symptoms associated with stress and mood disorders.”
Salivary stress biomarkers to nose out the benefits of healthcare clowning to children with psychiatric disorders
Amos Friedrich, a PhD student at the Department of Clinical and Health Psychology, continued: “The study is being performed in different psychiatric facilities for child andRED NOSES Clowndoctors has been bringing joy to hospital patients since 1994 (© NikoHavranek)
SeveralIMMUNOASSAYSstudieshave
RED NOSES Clowndoctors is an Austrian organization – founded in 1994 – that specializes in healthcare clowning, bringing joy to those in need. The clowns are professional performance artists who undergo specialist training and visit in-patients in various healthcare settings – including pediatrics, palliative care and psychiatric wards, as well as care homes for the elderly. Simone Seebacher from the Department of Research and Learning at RED NOSES, explained: “Initially, the RED NOSES were focusing on children’s wards but, over time, new target groups have been identified, including the elderly, people with disabilities, and refugees. Our visits are carefully planned, and we work closely with the healthcare staff to gather the necessary information regarding an individual patient’s condition. In the psychiatric wards, we visit the patients in their rooms but, in other hospitals, we also accompany the patients during
Although the subjective observations from both patients and staff are, of course, of great value, the unique approach of this study is to couple these with clear biochemical values from salivary stress biomarkers analyzed by the University of Vienna’s Biochemical Laboratory. Dr Urs Nater, Head of the Department of Clinical and Health Psychology and Co-director of the Biochemical Laboratory, added: “We are especially interested in alpha-amylase as an indirect marker of autonomic nervous system activity and cortisol as a marker of regulation,hypothalamic-pituitary-adrenalbothofwhichareamong the most often used salivary biomarkers. We are screening patients using Tecan’s Cortisol Saliva ELISA, which we chose partly because we have used this assay in the past, and we will be able to compare the results from this study with previous projects. A clear advantage of this assay is that it is calibrated using isotope dilution LC-MS as a reference method, which is considered to be the gold standard approach. The assay therefore yields reliable results, as demonstrated by low intra- and inter-assay CVs.”
TECAN JOURNAL 2/2022 25 IMMUNOASSAYS 2/2022
Martina continued: “This study is important because, as far as we know, it is the first one to examine the stress-reducing and mood-improving effects of clown visits on in-patients in child and adolescent psychiatry. The results could be used to design even larger-scale trials and show whether healthcare clowning can help to reduce stress and improve mood in children and adolescents in psychiatric care.”
adolescent in-patients in Austria, where clown visits have become a part of the clinical routine. We have implemented a non-controlled, repeated pre-post design, assessing the changes through self-reported data on stress and mood, as well as salivary cortisol values.1 The data is being collected before and after the clown visits – which occur once a week – over the course of four consecutive weeks. The healthcare staff are also reporting on the effects of clown visits, for themselves as well as for their patients’ wellbeing.”
To find out more about Tecan’s Cortisol Saliva ELISA, laboratoryac.at/en/research/biochemical-klinische-gesundheit-psy.univie.UniversityBiochemicalToclinical-and-health-psychologyunivie.ac.at/department-of-Vienna,PsychologyDepartmentTowww.rotenasen.atClowndoctorsTosaliva-elisaibl-international.com/cortisol-visitlearnmoreaboutREDNOSESAustria,visitlearnmoreabouttheofClinicalandHealthatUniversityofgotolearnmoreabouttheLaboratoryoftheofVienna,goto
The study is currently in the final phase of the data collection, but there are already subjective indications that the healthcare clowning had a positive effect on the children and adolescents.
Karoline Gans, a clown at RED NOSES, said: “When I go into the patient’s room, I always look at the child’s face, trying to assess the stress level and, as I leave, I turn around to see if there is any difference in the facial expression. I often see that the face has become more relaxed, there might be a smile, and sometimes I even get a ‘thank you for bringing me joy’. I believe that clown visits can help the children feel in control of their situation; it empowers them since every child is smarter than a clown could ever be!”
1) Zemp, M et al. Effects of clown visits on stress and mood in children and adolescents in psychiatric care –Protocol for a pilot study. PLoS One, 2022, 17(2), e0264012.
Clown visits can help children feel in control of their situation; it empowers them since every child is smarter than a clown could ever be!
9-Delta Analytical was founded in the midst of a global pandemic to offer research groups and industry partners a reliable service for drug testing at a time when a majority of laboratory resources were dedicated to tackling COVID-19. Co-founders Dr Christine Moore and Cindy Coulter used their many years of expertise to design the company’s state-of-the-art facility in Ontario, California, drawing on numerous industry contacts to build a thriving bioanalytical laboratory from scratch in a very short timeframe. Christine explained: “Prior to establishing 9-Delta, I was the Chief Toxicologist in the rapid diagnostics division of a major industry player and had extensive experience in coordinating laboratory tests for drugs in blood and oral fluid specimens, including from multiple roadside surveys. I was therefore very aware that, tragically, the opioid and cannabinoid crises are still very much present in the USA but have somewhat slipped under the radar over the last couple of years due to the COVID-19 pandemic.”
TOXICOLOGY
Cindy, a former toxicology laboratory manager, highlighted the unforeseen benefits to starting up a new facility during the COVID-19 pandemic: “It was actually a good time for us to launch our new laboratory, because we had the opportunity to find an investor and focus on the infrastructure of our business, without having the pressure of any specific projects looming over us. We were able to devote our time to completing the laboratory build, setting up the instrumentation and validating our methods. We could also reach out to our existing industry contacts and make connections with potential clients. For a long time, funding for many research projects was held back due to the pandemic. But now these funds are finally starting to be released, so researchers are ready to go, and we’re perfectly poised to help them hit the ground running.”
The semi-automated Resolvex instrument gives us more flexibility... removing the human error and producing extremely reproducible results.
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“Despite this global emergency, many research groups still needed to track substance abuse, primarily opioids and cannabinoids, and how these drugs interact with prescribed medications and treatments. These groups often do not have sufficient facilities or manpower to perform their own sample screening, instead relying on private bioanalytical companies to conduct bodily fluids testing. What makes 9-Delta unique is that we focus on human biological samples, using cutting-edge techniques – such as headspace gas chromatography with flame ionization detection (HS-GC-FID) and LC-MS/MS –to screen oral fluid and whole blood for drugs and alcohol in a collaborative process. Our aim is to work in partnership with academic researchers, running long-term bioanalytical projects and providing reliable and verified results to support their in-house projects.”
A dream team for bioanalytical drug testing
9-Delta has already racked up an impressive list of completed projects and is currently embarking upon product performance, recovery and stability studies for industrial clients. The analytical workflow for each 9-Delta co-founders Christine Moore and Cindy Coulter
9-Delta Analytical LLC in California provides independent forensic and clinical toxicology testing services for academic research groups, non-profit organizations and governmental agencies across the USA and Canada. Focusing mainly on human samples, the company uses numerous analytical techniques to screen for a wide range of legal and illicit drugs.
At the end of the day, the products that result from the partnership will have your company name on them and your reputation attached, so it is imperative that you find a partner that aligns with your values, is communicative and listens to your organization’s needs. The partnership needs to be built on a strong foundation of technical expertise, application knowledge and manufacturing capabilities, but also on trust and transparent communication, which are soft traits much more difficult to measure.
Resolvex positive pressure workstations, go to pressure-processorspreparation-resolvex-positive-tecan.com/sampleFor Research Use Only. Not for use in diagnostic procedures. The importance of trust in OEM partnerships
Ralf Griebel, Head of the Partnering Business Division project typically begins with a solid phase extraction of the samples, which is currently performed with a Resolvex® A100 positive pressure workstation. Christine continued: “We had both used Tecan products for over 16 years in our previous roles, and they are the best ones that we have found. The semi-automated Resolvex instrument gives us more flexibility, and allows us to process smaller sample sets to match project requirements. We really appreciate that you can program all the flow, pressure and column settings to your needs, removing the human error and producing extremely reproducible results. Because it’s semi-automated, it also increases our workflow by enabling us to maximize our time; you can go and do something else while it’s running, and that’s really handy when you’re a small company. It was a good decision to go with Tecan.”
“The sales and technical teams were great in helping us to get set up, they really went above and beyond,” Christine added. “Tecan was very keen to help out a small, women-owned start-up, and did everything it could to get our business in the door and off the ground. The Resolvex has been very reliable, and whenever we have a query or an issue, the staff are quick to respond and always know exactly how to fix it.” For more information about 9-Delta Analytical, visit Towww.9-delta.comfindoutmoreabout
Crucially, we believe that a partnership does not end at the launch of a product, and we aim to continually support the success of our partners’ businesses. This includes ongoing support throughout a product’s lifetime, from training and comprehensive lifecycle management to expert regulatory support and field servicing that exceeds your customers’ expectations. Our goal is to lead the way in automation, and we back this up with our core values – ambition, highest standards and trust – that are not necessarily written into contracts. This is why so many companies in the IVD sector choose to have long-term partnerships with Tecan.
Choosing a partner that offers comprehensive OEM services opens up a whole new world of possibilities for healthcare companies planning their next complex development. Partnering is an opportunity to consolidate knowledge and resources, combining the industry experience and capabilities of both companies to facilitate entry into a new market, support the growth of an existing business or gain market share in an emerging sector.
Leading the debate
Tecan’s Synergence™ OEM services bring together the expertise, technologies and scalability that customers need to fulfill their lab automation requirements.
Share your thoughts by emailing empowered@tecan.com
TECAN JOURNAL 2/2022 27 LEADING THE DEBATE
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