Organ-on-Chip Systems Enable Personalized Medicine

Healthcare has traditionally focused on one-size fits-all medication to treat populations instead of tailoring treatments to individual patients. Recent advances in stem cell technology allow researchers to create disease models for personalized medicine. SEMI spoke with Thomas Pauwelyn, Postdoctoral Researcher at imec, about trends in medical technology innovation such as organ-on-chip devices and their applications.

SEMI: What triggered the healthcare move from a one-size fits-all medication to treat populations to tailored treatments? What advancements allowed researchers to create models for personalized medicine?

Pauwelyn: One of the main triggers for this transition is the inefficiency of the current healthcare system. The top 10 highest grossing drugs in the U.S. are effective for only between 1 in 25 to 1 in 4 patients. Not only do most medicines only help a small share of the patients, but they are often developed in classical clinical trials with predominantly western or male participants.

Recent advances in stem cell technology allow researchers to create disease models for individual patients. In other words, researchers can reprogram cells from a patient’s skin or blood sample to various cell types, including cardiac or neuronal cells, through stem cell techniques. These samples reflect the traits that make a patient unique.

However, patient-in-a-dish models expose cells to very artificial environments. So these models look very different from their counterparts in the body. Organ-on-chip systems address these issues by exposing cells to physiologically relevant conditions and create more mature models.

SEMI: What is exactly an organ-on-chip? 

Pauwelyn: Organ-on-chip devices are microfluidic cell culture chips that can revolutionize the development of drugs and personalized treatments. These devices model the pathophysiological behavior of organs and tissues. Inside these chips, cell cultures are grown and exposed to conditions that better resemble in vivo microenvironment. Different organ models can be created by exposing different cell types to an engineered microenvironment. Common examples are the heart-on-chip, lung-on-chip, gut-on-chip or brain-on-chip.

SEMI: Medical technology has made astonishing advances over the years. As new medical devices emerge, what are the main challenges?

Pauwelyn: Meeting stringent regulatory requirements is one of the main challenges for medical devices. Technologies related to personalized medicine do not neatly fit in existing health technology assessments and reimbursement processes.

In the case of organ-on-chip devices, there are challenges related to production, qualification and adoption. Increased standardization will also help scientists compare and interpret their findings. Currently, various research groups obtain different results from own organ-on-chip systems. These systems may be fabricated from different or exotic materials, expose cells to different microenvironments or rely on other cell models. Often, only a few devices are available for testing due to limited fabrication scalability.

SEMI: What did imec do to overcome those challenges?

Pauwelyn: imec turned to its expertise in chip design and technology to develop a novel organ-on-chip platform in close collaboration with Micronit Microtechnologies in the InForMed project funded by the ECSEL Joint Undertaking (ECSEL2014-2-662155). The platform’s main requirements were that it could reduce handling variability by microfluidic automation, be fabricated with conventional materials compatible with production upscaling, and produce high-quality electrical recordings of cellular activity. Another essential requirement was the compatibility of the device to the standard workflow of pharmaceutical research. The user interface is based a conventional 96-well plate, and peristaltic pumps are integrated into the device.

SEMI: How does the CMOS-based microelectrode array work and where do you see potential for applications in the field of personalized medicine?

The imec-developed CMOS-based microelectrode array is the sensor in our organ-on-chip system that monitors the cell culture. The sensor consists of 16,384 electrodes distributed over 16 independent microfluidic wells. It detects cellular activity down to the single-cell level, including intracellular action potentials or extracellular signals from electrically active cells or impedance caused by cells growing directly over the electrode.

We believe this technology has great potential for developing miniaturized patient models in the lab. By using patient cells reprogrammed to the desired cell types through stem cell technologies, we can develop patient-on-chip systems. These systems would be able to predict which treatment is best suited for a specific patient or how drugs affect certain subpopulations.

SEMI: What are your expectations for the SMART MedTech Forum at SEMICON Europa 2019 in Munich?

Pauwelyn: The SMART MedTech Forum brings together an interesting mixture of researchers, entrepreneurs and stakeholders in the future of healthcare. I look forward to hearing their perspectives and to discuss how personalized medicine and MedTech will help tackle current challenges.

SEMI: Can you share one prediction for the future of MedTech?

Pauwelyn:  I believe that MedTech in the future will help us tailor treatments to each patient. Doctors will have a wide arsenal of tools available to predict which treatment will deliver both the highest chance of success and the lowest chance of adverse reactions. One of these tools could be a human-patient-on-chip system. It would consist of interlinked organ-on-chip modules with patient-derived cell models. In this way, the reaction of patients to specific treatments could be predicted without ever exposing them to potentially harmful compounds.

Dr. Thomas Pauwelyn currently is a post-doctoral researcher with an Innovation Mandate grant from VLAIO, investigating strategies to valorize the results from his research. Pauwelyn’s research focuses on developing novel organ-on-chip systems for predictive toxicology and drug development. He also investigates how organ-on-chip devices may help stratify patients and help enable personalized medicine. Pauwelyn has studied at KU Leuven, Belgium, since 2008. He earned his BSc in Bioscience Engineering specializing in Catalytic Technologies in 2011 and a Master’s in Nanoscience and Nanotechnology with the Bioscience Engineering option in 2013. He completed an IWT fellowship for a PhD at KU Leuven and imec’s Life Science Technologies group in 2018.