Category: Blog

Organ-on-chip systems are promising new in vitro research tools in medical, pharmaceutical, and biological research. Their main benefit, compared to standard cell culture platforms, lies in the improved in vivo resemblance of the cell culture environment. A critical aspect of these systems is the ability to monitor both the cell culture conditions and biological responses of the cultured cells, such as proliferation and differentiation rates, release of signaling molecules, and metabolic activity. Today, this is mostly done using microscopy techniques and off-chip analytical techniques and assays. Integrating in situ analysis methods on-chip enables improved time resolution, continuous measurements, and a faster read-out; hence, more information can be obtained from the developed organ and disease models. Integrated electrical, electrochemical, and optical sensors have been developed and used for chemical analysis in lab-on-a-chip systems for many years, and recently some of these sensing principles have started to find use in organ-on-chip systems as well.

This perspective review describes the basic sensing principles, sensor fabrication, and sensor integration in organ-on-chip systems. The review also presents the current state of the art of integrated sensors and discusses future potential. We bring a technological perspective, with the aim of introducing in-line sensing and its promise to advance organ-on-chip systems and the challenges that lie in the integration to researchers without expertise in sensor technology.

You can access the full review here.

In 2022 the Annual EUROoCS Conference will be held in Grenoble in France on 4 and 5 July. Nathalie Picollet-D’hahan from CEA (Commissariat à l’énergie atomique et aux énergies alternatives) in Grenoble will be the Conference Chair and is looking forward to welcome you.

On 24 and 25 January 2022, the EUROoC-ITN met again for the biannual consortium meeting. The ESRs presented their progress and explained what the last few steps of their project would be. They also presented how collaborations with each other enabled better development of their systems.

With the end of their projects approaching, they had the chance to learn more about the different career paths available to them thanks to Q&A sessions with professionals from regulatory agencies (Frank Schulze from BfR and Susanne Brendler-Schwaab from BfArM), technology developing industries (Roland Thar from PyroScience) and pharmaceutical industries (Stefan Kauschke from Boehringer Ingelheim, Jean-Marc Balloul and Cecile Zaupa from Transgene, Christian Egler-Wedeking from Miltenyi).
They learnt what each different career path entails, from the demands and requirements, as well as benefits of each role. We hope that the session could help them in choosing the career path that best fits their goals.

The EUROoC validation workshop took place virtually from 17 to 19 January 2002. The focus of the workshop was to provide insights into the structure and functions of the main European regulatory agencies like Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM), Bundesinstitut für Risikobewertung (BfR), Rijksinstituut voor Volksgezondheid en Milieu (RIVM) and Medicines Evaluation Board (CBG-MEB).

The ESRs learnt about the processes for the assessment of human medicinal products, chemicals and oncology products within the European regulatory network. Particular importance was given to the aspects of drug metabolism and drug-drug interaction when investigating compounds. Moreover, they were offered an overview of the validation processes for in-vitro models, animal models and examples of validation of microphysiological systems.

The workshop was concluded with the validation procedure for vaccines and an intro to the Inno4Vac project which has the objective to validate organ-on-chip models for the testing of vaccines at the early developmental stage, a very relevant topic of today.

On 16-17 September the EUROoC ESRs were welcomed to Uppsala for their second training workshop, focused on microfabrication and scientific dissemination. Given the pandemic, this was a mammoth task to organize with travel restrictions and group size restrictions. Fortunately, all the ESRs and two PIs were able to attend the worskshop which spanned over two days.

The topic of microfabrication was first introduced with a lecture from Lena Klintberg (lecturer within the Division of Microsystems Technology at Uppsala University), before practical exercises related to four different methods were carried out. The participants were then split into groups led by Gabriel, Mara, and Tanvi to learn about microfabrication in the cleanroom. The fabrication techniques the students learnt about was laser cutting, UV lithography and metal deposition and afterwards they were all trained in the art of bonding and assembly of microfluidic chips using either heat or plasma treatments. In fact, such was the level of expertise amongst the ESRs that some of them were even able to take on the role of teacher! In the end, all participants had a realistic view of working in a cleanroom, the advantages and limitations of each process and the ability to select a process specific to their application for their specific chip design.

The scientific dissemination topic was introduced by Sarah Schwarz, a senior lecturer at Uppsala University who specialises in academic English and oral presentations. This was followed by group work in which the ESRs prepared and presented on one of the above microfabrication techniques. Each group did an excellent job and received constructive and positive feedback on their presentations. There was just time for cake and bubbly at the end, where Gabriel (ESR 8), Stefanie (ESR 14) and Anders (ESR 15) could jointly celebrate the publication of their review article “In-line analysis of organ-on-chip systems with sensors: Integration, fabrication, challenges and potentials” recently published in ACS Biomaterials Science & Engineering before it was time for the ESRs to head off for the weekend.

In addition to the workshop, the ESRs explored Uppsala with a walking tour, and a ferry trip to the nearby islands. A huge thank you is due to the organisers who ensured an interesting and enjoyable itinerary, and the ESRs, for their positive attitudes and excellent cooperation. We are unsure about the future travel, but we look forward to seeing each other nevertheless!

The 3rd edition of the Annual European Organ-on-Chip Society (EUROoCS) Conference took place online, and was organised by Uppsala University. With 442 attendees from many different countries, there were even more participants than in 2020. In toal, 129 Posters and 40 talks were presented by experts and junior scientists. The talks were divided in 4 parallel sessions revolving around the topics of Vasculature, Disease Models, Technology Platforms, Toxicity, Respiratory System, Immune System, and Gastrointestinal Tract. The ESRs of EUROoC actively participated in the conference by presenting their posters and talks. Moreover, Ulgu Arslan (ESR3) won the Best Presentation Award. We are looking forward to the next EUROoCS Conference, which will be held in person on 4 and 5 July 2022 in Grenoble, France.

Even though still online, the EUROoC-ITN met again from 28 to 30 June 2021 for the biannual consortium meeting, consisting of the project progress reports and the workshop on 3R Principles and Regulatory Requirements. Despite the COVID-19 pandemic, all ESRs managed to show substantial progress in their projects.

The workshop on 3R principles and regulatory requirements highlighted the use of animal testing with focus on the application of the 3Rs principles and the validation of alternative methods. During a morning session, speakers from regulatory agencies and experts from the field of 3Rs set the scene. This was complemented by 3 parallel session between Validation Board Members and ESRs in the afternoon. Each ESR received feedback from the experts and the next steps will be supervised by 1-2 experts per ESR. All information will be collated and shared within the project. The aim is to eventually make this information publicly available.

During the whole workshop, ESRs were involved in active discussions with regulatory experts about the purpose and potential validation of their own systems as models for drug testing and disease modelling. They were keen in understanding how to fill the gap between commonly used in-vitro model and humans and what regulatory procedures a new technology or model should go through to be accepted as a relevant testing tool. All ESRs found this very useful to look at their systems from an application perspective and hope there will be a chance to further discuss it with the experts at the end of their projects.

Regarding the secondments at the regulatory agencies, it is planned that all ESRs together, will physically visit each of the three regulatory agencies BfR (Berlin, Germany), BfArM (Bonn, Germany) and RIVM (Bilthoven, NL). This secondment will probably take place in January 2022. Whether the secondments will indeed be physical, depends on developments in the Covid-19 situation.

Our project partners, the German Federal Instiute for Risk Assessment (BFR) and the Dutch National Institute for Public Health and the Environment (RIVM), have published a paper on the “Applicability of organ-on-chip systems in toxicology and pharmacology”. The relative complexity of Organ-on-chip (OoC) over simple in vitro assays provides advantages and disadvantages in the context of compound testing. The broader biological domain of OoC potentially enhances their predictive value, whereas their complexity present issues with throughput, standardization and transferability. Using OoCs for regulatory purposes requires detailed and standardized protocols, providing reproducible results in an interlaboratory setting. The focus of applying OoCs in safety assessment is currently directed to characterization (the biology represented in the test) and qualification (the performance of the test). To this aim, OoCs are evaluated on a limited scale, especially in the pharmaceutical industry, with restricted sets of reference substances. Read more. M. R. Schneider, M. Oelgeschlaeger, T. Burgdorf, P. van Meer, P. Theunissen, A. S. Kienhuis, A. H. Piersma, R. J. Vandebriel. Applicability of organ-on-chip systems in toxicology and pharmacology. Publication: Critical Reviews in Toxicology, 2021. https://doi.org/10.1080/10408444.2021.1953439

Our project partners, the University of Luxembourg (UL) and the Jena University Hospital (JUH), have published a paper on the “Emulating the gut–liver axis: Dissecting the microbiome’s effect on drug metabolism using multiorgan-on-chip models”.

The homeostatic relationship between the gut, its microbiome, and the liver is crucial for the regulation of drug metabolism processes. Modeling the highly variable luminal gut environment and understanding how gut microbes can modulate drug availability or induce liver toxicity remains a challenge. However, microfluidics-based technologies such as organ-on-chips could overcome current challenges in drug toxicity assessment assays because these technologies are able to better recapitulate complex human responses. Read more (LINK).

M. Lucchetti, M. Kaminska, A. Kehinde Oluwasegun,Alexander S. Mosig, P. Wilmes.
Emulating the gut–liver axis: Dissecting the microbiome’s effecton drug metabolism using multiorgan-on-chip models.
Publication: Current Opinion in Endocrine and Metabolic Research, 2021, 18:94–101.
https://doi.org/10.1016/j.coemr.2021.03.003

The 5th edition of the EUROoC project newsletter has been published!

The fifth EUROoC project newsletter is now available for viewing.

It highlights EUROoC project activities over the last 6 months and provides you with news and events around the Organ-on-Chip technology. Furthermore, we inform you on the challenges posed to the project by the current SARS-CoV-2 outbreak.

Stay tuned and subscribe!

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