Biopharma transformation: growing impact of automation 

The languages spoken by the 1,200 or so visitors to the 5^th SLAS Europe organised by the Society for Laboratory Automation and Screening (SLAS) in Barcelona could not have been more different. However, this was not because the specialists came from 40 countries, but because they are rooted in different research cultures: AI nerds, bioengineers and robotic specialists as well as big pharma managers speak and think differently tobiotech founders, biologists and medical serial entrepreneurs. 

Bridging the gap between these groups to accelerate the current data-driven transformation in the increasingly person­alised drug development is the mission of the 19,000-strong SLAS – also in Europe. It was not for nothing that SLAS CEO Vicki Loise called on the 1,185 registered visitors and 109 exhibitors at the start of SLAS Europe to join SLAS CONNECTED – an online network akin to LinkedIn that speeds up the confidential exchange of information, lab challenges, technology advice, and potentially technology transfer. Being the home for the European life sciences community to connect and collaborate with each other and colleagues across the globe is a declared goal of SLAS, Head of Communications Jill Hronek told Europe­an Biotechnology in the run-up to SLAS. 

Impressive market potential

The 5^th edition of SLAS Europe featured a striking number of product innovations and launches in the current growth markets of microfluidics (CGAR 9.4%, global turnover in 2023: US$16.94bn, organ-on-chip (CGAR: 11%; US$9.6bn, 10% of which in China), AI/bioinformatics (CGAR: 15.1%, US$2bn) and human cell, spheroid and organoid model (CGAR; 25.2%; US$1.5bn).

New drug delivery devices

In view of the lasting high failure rate of drug candidates (30%) due to adverse effects, mostly on the heart, drug developers are striving to develop drug candidates with less systemic effect, i.e. more precise local drug delivery and preclinically more predictable efficacy in humans, in addition to drug candidates that are as personalised as possible, i.e. tailored to patient groups. 

Right at the beginning of SLAS Europe, Catalonia’s flagship scientist Luis Serrano from the Centre of Genomic Regulation (CRB) in Barcelona presented a cutting-edge drug delivery approach. Using synthetic biology tools, Serrano engineered bacteria that show a natural tropism for the therapeutically targeted regions in such a way that they deliver their therapeutic cargo locally to the drug target. This helps to minimise adverse drug effects (ADEs) – at least in theory. 

Serrano is trying to do this in practice via his spin-out Pulmobiotics SL, founded in 2020, which uses engineered Mycoplasma pneumonia bacteria, which normally cause respiratory tract infections in infants, as an attenuated cell wall-free chassis organism to deliver an optimised version of the anti-inflammatory cytokine IL-10 or immunosuppressive nanobodies directly to the lung epithelium of patients with severe lung inflammation. Preclinical in vivo success has already been achieved with antibiotic-resistant ­Staphylococcus aureus and Pseudomonas aeruginosa biofilms. Serrano’s 2022 spin-out Orikine SL has the mission to design optimised anti-inflammatory cytokines.

The approach of using bacteria as a targeted drug delivery device is not limited to infectious diseases as demonstrated by the latest investment by Boehringer Ingelheim Venture Fund in August in the Chinese cancer specialist Shenzen Synthetica Pioneering Ltd, which exploits the natural cancer tropism of engineered Salmonella strains to trigger their multiplication exclusively in the tumour microenvironment and in metastases and to eliminate them preclinically in animal and organoid models for skin, kidney and colon cancer.

Automated safety prediction

The Viennese IMBA spin-off HeartBeat.Bio AG and the US automation specialist Molecular Devices in 2022 entered into a collaboration to develop a different approach to eliminate severe side effects of drug candidates on cardiac function during drug screening. The collab now resulted in a first product launch at SLAS Europe 2024. According to Florian Fuchs, CTO at HeartBeat.Bio, the company licensed a platform from IMBA in 2021 to differentiate induced human induced pluripotent stem cells (hiPSCs) into so-called cardiods that faithfully reproduce the physiology, electrical signalling and function of human heart chambers – unlike human cardiomyocyte-based cell or spheroid models. A miniature model of the automated cell, spheroid and organoid culture platform Cellexpress.ai, presented for the first time at SLAS-Europe by Molecular Devices LLC, now enables the reproducible and intervention-free culture of cardiods for drug screening. 

In Barcelona, ModDev‘s Senior Manager of Assay Development Oksana ­Sirenko presented the automated system that seeds, feeds and passages the cardiods that are in-line monitored by AI-guided image analysis. 

The co-development enables not only modelling of drug-induced cardiomyopathies but also genetic cardiomyopathies as well as myocardial infarction and fibrosis. Maja Hoi, Sales Commercial Product Expert and Account manager Drug Discovery – Nordics at Molecular Devices, told European Biotechnology that the fully automated system integrates Molecular Device’s first AI-supported optical cell recognition system to assure reproducible quality with a capacity for up to 154 plates at a time for 24h/7d cell or spheroid culture, standardised (stem) cell culture, from maintenance, monitoring, incubation through imaging, analysis and data processing to deliver unbiased results.

The system launched at SLAS demonstrates the general trend towards using generative AI for routine tasks in diagnostics or automated imaging in order to merge data for analysis. At SLAS Europe, Elyor Kodirov from modular liquid handling robot specialist Opentrons Labworks Inc. showed that this also works without special expertise. Generative AI tools can also be made available for protocol generation in plain language. They demonstrated that OpentronsAI is able to interpret language commands and to generate Python-based protocols such as PCR setup and on-deck thermocycling.

Organ on a chip

Microfluidic organ-on-chip systems are on the rise since the EMA and – thereafter – the FDA have created a regulatory framework that allows completely animal-free preclinical safety assessments. At SLAS Europe, Asli Akidil from Boston-based ­organ-on-a-chip market leader Emulate Inc pointed to the economic impact of the largest study conducted so far with ­organ-on-a-chip technology. Using 870 of their human Liver-Chips with a focus on drug-induced liver injury (DILI) prediction, the company assessed drug safety, toxicology, and efficacy of 27 small molecule drugs on liver cells of three donors with a sensitivity of 87% and a specificity of 100%. According to Akidil, compared to historical data from animal models and 3D spheroid cultures of primary human hepatocytes, the Liver-Chip performed significantly better. If widely adopted, she suggested an industry-wide $3bn increase in productivity. “This transformative approach ensures a more robust “fail early, fail fast” strategy, thereby increasing the likelihood of clinical success for candidate drugs“, she said. Just after the end of SLAS Europe, a German group led by Peter Loskill from NMI Reutlingen reported another revolution to the breast oncology field based on organoids: a patient-derived breast ­cancer ­organ-on-a-chip for the individualised safety assessment of CAR-T-cell therapy. The channels in this system are perfused with T- or CAR-T cells while the Chamber, which builds an endothelium-like barrier, contains the patient-derived breast cancer organoids in an extracellular matrix mimicking the tumour microenvironment. At the end of the chamber the researchers can measure the released cytokines and thus predict the strength of the immune response to be expected upon CAR-T cell therapy to inform individualised dosing. By addition of macrophages to the chamber, Loskill’s group next wants to add efficacy testing to the organ-on-a-chip. Another microfluidic device for early toxicity assessment was presented byMarie Pierron from EFPL spin out Nagi  Bio­science SA’s at SLAS Europe. The company’s Organism-on-a-Chip technology, however, uses C. elegans nematodes as an alternative high-content screening method that bridges the gap between in vitro data and vertebrate testing in early pipeline stages. Nagi’s robotic platform SydLab™ One can autonomously test 64 independent conditions on 1.000 organisms (nematodes) in one run. SydLab™ One combines advanced microfluidic technology, robotics, biology, and AI-based algorithms to automate the entire process of C. elegans culture, treatment administration, high-content imaging, data extraction, and phenotypic analysis. SydLab™ One is able to execute multiple toxicity and aging assays, including the possibility of using the exist-ing wide collection of reporter strains thanks to its fluorescent imaging capability. When blindly assessing the effects of 20 chemicals on development and reproduction, a balanced accuracy of 87.5% was reached (sensitivity: 75%, specificity: 100%) according to ECHA database. Thus the platform is qualified for rapid identification of toxic compounds and their mechanism of toxicity, effectively bridging the gap between in vitro and in vivo assays thanks to automation. According to Pierron, the platform allows not only endpoint measurements’ collection, but also the monitoring of biological responses’ dynamics.

Best teams in town

As every year, SLAS Europe honoured products and automation start-ups with the most impact on the sector. In Barcelona, Swiss Seed Biosciences SA (Epalinges) and UK-based CryoLogyx Ltd (Coventry) out of 13 applicants and six finalists won the SLAS Europe New Product Award 2024 for the development with “transformational potential” such as Seed Biosciences’ Dispen3D and Cyro­Logyx’ product PlateReady. According to SLAS CEO Vicki Loise at the award ceremony, the market opportunity, potential impact on the automation sector, originality of the product and the proof of concept of the products, which have been on the market for no more than a year, were assessed.

Dispen3D is a novel impedance-based single-cell dispensing and cell seeding system designed to handle 3D cell models that are sensitive to shear stress including spheroids, organoids and tumoroids with pressures below 0.2 psi, comparable to manual pipetting in high throughput. The DISPENCELL-derived new product assures monoclonality in emerging applications such as spheroid-based lead optimisation, personalised and regenerative medicine. Currently, the industry standard for handling cells, organoids and spheroids involves manual processes that are cumbersome and not very efficient in throughput, hardly reproducible and slow. On the other hand, more complex, specialised equipment may not be readily accessible and is highly expensive.

CryoLogyx PlateReady is set to revolutionise biobank analyses. It uses cryoprotectants branded Cryoshield to speed up research with cryopreserved cells significantly. Today, cells are stored frozen in suspension and must be cultured for days or weeks before they can be used in an experiment. As a result, a cell biologist has to devote significant time to cell preparation and the routine maintenance of cell lines rather than other valuable operations. CryoLogyx’s PlateReady™ featuring cryopreserved cell cultures is designed to simplify the freeze–thaw process while maintaining high cell viability and functionality post-thaw. PlateReady incorporates cryopreserved cells using Cryoshield™ that enable very high cell recoveries and cryopreservation of cells in non-standard formats. This approach ensures the cryopreserved cells work just as well as freshly cultured ones in terms of survival, function and response to drugs within 24 hours post-thaw. “Our PlateReady products enable a major shift in how cell biology and cell-based assays are approached in the lab, Dr Tom Congdon co-founder and CEO of CryoLogyx told European Biotechnology in Barcelona.

Finalists

Among the finalists were German LPKF AG with its product Arralyze that uses nanowells in glass to allow ­placing thousands of cells in a controlled manner onto a footprint of a ­microscope slide platform that physically immobilises cells, which is particularly beneficial for single-cell screening applications in the company’s CellShepard device. Further finalists included Italian CellDynamics isrl with its PL8 platform that allows accurate biophysical-based presorting of organoid subpopulations between 50µm and 500µm in diameter in terms of mass density, size and weight, and integrates label-free quantification of organoid structure with automated liquid handling processes, i.e. measurement of immune cell invasion into tumouroids; German CYTENA GmbH with the second generation of its product UP.SIGHT, a single-cell dispensing and imaging system with >97% single-cell dispensing efficiency >99.99% probability of clonal derivation, which eliminates the need for multiple devices, saving time and resources; and Yokogawa with its product CellVoyager CQ3000, a high-content analysis system that captures high-definition 3D microscopic images of live cell cultures at high speed over long periods, with minimal damage to cells.

Most innovative companies

Furthermore, UK-based Semarion Ltd (Cambridge) was was honoured with the Ignite Award for most innovative start-up company represented in the Innovation AveNEW section of the SLAS Europe exhibition. Not without reason, as the rush to the British company‘s stand, that has already a bunch of partners like AstraZeneca, continued unabated after co-founders Jeroen Verheyen (CEO) and Tarun Vemulkar (CTO) presented their Cavendish Lab’s spin-off‘s technology in Barcelona. The Semacyte platform enables adherent growing cells to be mobilised, magnetically aligned and tracked using microcarriers without losing the morphology and function of the cells, so that they can be handled and optically analysed using standard liquid handling tools used in drug development. According to Verheyen at the presentation of the finalists in Barcelona, this enables a significantly faster data generation than with high-throughput screening tools. “At the same time, around 100 times fewer cells are required for screenings and these can be stored frozen.

“Our SemaCyte^® cell assay microcarriers function as ultra-miniaturised, mobile, barcoded wells that carry small colonies of adherent cells. They can be moved with liquid handling tools, are magnetically steerable and can be frozen as assay-ready cells,” According to Semarion, the barcodes are viewed using bright-field microscopy and digitally deconvoluted using Semalyse software. Multiplexing and combining different barcoded adherent cell types in one well enables pooled cell screening, which accelerates discovery campaigns and reduces the resource burden of cell testing. After receiving the award Jeroen stated: “Receiving the SLAS Ignite Award is a tremendous honour. Our technology addresses fundamental bottlenecks in rapid data generation, offering a 10x increase in throughput and a 6x cost reduction to drug discovery workflows. We have recently launched the early adopter programme for our SemaCyte microcarrier platform and are already working on exciting projects with pharma companies and CROs. As we prepare for a full commercial rollout in the UK, EU, and aim to enter the US market, this award boosts our visibility and credibility among potential customers and investors. We are eager to continue our mission to accelerate drug discovery and deliver groundbreaking solutions to the biopharma industry.”

Together with Semarion, four companies with highly interesting platforms had qualified for the final of the Ignite Awards and presented their technologies at SLAS Europe:

Paris-based Oria Bioscience SA, led by CEO Alexandre Santinho, presented a microfluidic platform for the screening of whole organelles, which allows the testing of targets such as the lyso-resident protein for the treatment of lysosomal storage diseases in their native environment with a throughput of up to 50,000 compounds per week. The company, which has been financed with €800,000 to date, is building up its own pipeline in addition to the licensing business.

The Swedish company Lucero Bio A/S, which was founded in March 2020 through a matching programme of Chalmers E-School/Chalmers Ventures and is led by CEO Christopher Jacklin, presented a chip-based automated platform for cultivating, sorting and screening 3D spheroids/organoids. This promises to make the largely manual work involved in using human organoid models for lead optimisation and metabolic profiling more reproducible, cost-effective and manageable.

German University Ulm spin-off Sensific GmbH, combines microfluidics with image-based analysis, cell sorting and microscopy to enable assay-driven cell sorting. According to CEO Daniel Geiger, the flagship product ODIN adds high-speed and high-throughput real-time image processing capabilities to microscopes or customised setups. You can analyse your experiment label-free in brightfield or simultaneously with up to 3 additional fluorescence imaging channels. ODIN automatically measures particles, cells, droplets, algae, bacteria and droplets in microfluidic systems. Its intelligent algorithms provide more than 30 parameters of the object, including size, circumference, aspect ratio or brightness, and display them in a user-friendly interface.

Overcoming limits

Spanish Loop Diagnostics SL addresses the unmet need of early sepsis diagnosis. CEO and CSO Enrique Hernandez has invented a method to accurately diagnose sepsis 10 times faster and 3 times more effective than today’s culture-based methods that work with serum biomarkers or are based on pathogen detection through PCR. To do this, the company is using a new type of lateral flow assay for point-of-care testing called Septiloop with 90% sensitivity. In brief: Blood is incubated and then the immune response is measured. SeptiLoop can diagnose bacteraemia as early as one to three hours after infection and throughout all stages of sepsis, enabling emergency specialists an early detection and timely treatment initiation. The prognostic test could reduce sepsis mortality by 10-25%, said Hernández, and is to be commercialised in the UK from 2025, thereafter in the EU, said Hernández.

Researchers from South-Korean Incheon National University presented another rapid microfluidics-based culture method to detect sepsis-causing bacteria. It also can accelerate antibiotic susceptibility testing compared to standard blood culture, which takes 1-5 days depending on the pathogen but is not as fast as Loop Diagnostics‘ approach. While rapid DNA-based PCR tests (1-4 h detection time for microbes) can identify antibiotic resistance genes they do not allow to assess sensitivity for a specific antibiotic in sepsis patients. Using wide-field microscopy, with the DropVIST system, Sunghyun Hi and colleagues were able to detect living bacteria (100 per ml compared to 100.000 per ml required for other culture-based methods) after only 6 hours of incubation time, accelerating antibiotic susceptibility testing significantly. In pilot tests, the group used chlorinated medium to selectively kill bacteria from blood and identified five surviving bacterial strains by subsequent widefield imaging and dFinder software-based image analysis in a microfluidic device with up to 99.1% sensitivity. Limit of detection (LOD) was at 10CFU/ml. The system can theoretically analyse 3,103,377 droplets in real-time. Thus the platform is a potential tool for antibiotic susceptibility testing. 

In addition to the presentations, the international exhibition offered the opportunity to view new prototypes and exchange ideas – one more reason to fly to SLAS Europe‘s big brother, the SLAS2025 International Conference & Exhibition (25-29 January 2025) in San Diego – at least 7,500 visitors are expected. Before its EU and US launch in August, ThermoFisher Scientific’s Dr Andreas Koch presented prototype for cartridge-based plasmid preparation, which carries out a fully automated plasmid preparation in 75 minutes at SLAS Europe. All that is needed is the preculture, which is placed in a disposable cartridge which includes all required reagents. The system will be on display in full size in San Diego. 

Alternatively, SLAS Europe 2025 will take place in Hamburg from 20-22 May 2025.