Speeding up OoC-development
by integrating electronics

By integrating electronics with organ-on-chip-related technologies the development of new medicines, such as those for neurodegenerative and cardiovascular diseases, can be accelerated. At Holst Centre we contribute to the OoC-ecosystem with our flexible electronics and large-area manufacturing expertise.

Organ on chip (OoC) technology holds promise to reduce animal testing and establish more efficient drug-discovery processes. Over the past decade, OoC technology is becoming prominent in the world of drug development, with initial OoCs application already on the market. The technology may also prove useful for nutritional, diagnostic, cosmetic, chemical and environmental industries. The future wave of OoC modalities is expected to integrate electronics and sensors, which helps to develop better medicines, such as those for neurodegenerative and cardiovascular diseases, with brain and heart on chip devices. Involvement of all stakeholders is essential to realize the full potential of OoC-related devices, to which Holst Centre looks to contribute its flexible electronics and manufacturing expertise.

Closing the gap

Within the realm of pharmaceutical research, more humanspecific compounds are being developed. This means that traditional preclinical models, such as murine and other animal models, are not suitable for use with these compounds. Human cells must be used to test, validate and regulate said compounds; therefore, new tools are needed. Organoid, organ and lab on chip, and other in vitro devices, like smart multiwell plates (microplates), can close the gap between the findings of preclinical and clinical studies. There is an increased need for such devices as human-specific compounds become commonplace in the pharmaceutical world. Pharmaceutical companies are already working alongside regulatory agencies, to establish a bigger role for in vitro technologies in validation, safety and toxicology processes. Collaborations are also in place between OoC manufacturers and pharmaceutical companies, where both sides see an integral role for in vitro devices in the coming years

Next level OoC platform

There are a few frontrunners with products currently on the market that include integrated electronics. These products include wellplate-compatible TEER accessories, integrated multi-electrode arrays (MEA) for stimulation and electrophysiological readout, as well as others. If categorized based on three main attributes: multiwell format, containing microfluidics, and possessing integrated electrodes, most devices would include two of three attributes, but no device has yet integrated all three attributes altogether. We would like to help the pioneers creating these products take the next step, in order to fabricate OoC-related devices using industry-proven manufacturing techniques from the world of flexible, printed circuit boards and displays. The field would benefit from economies of scale, and an institute familiar with the scale up of R&D to higher technology-readiness levels (TRL).

Breakthrough technologies

In the realm of OoC, Holst Centre is working towards the acceleration of drug screening with the development of autonomous, connected OoC platforms and has begun to develop a number of technologies:

• One of the first steps, is an integrated transepithelial electrical resistance (TEER) device. Holst Centre is exploring the use of thin-film electrodes, spatially dispersed over large area on ultrathin substrates. Regardless of the implementation method, the desired result is unique in-well TEER measurements continuously provided throughout an experiment.

• We have developed a transparent, flexible, active-matrix mesh-electrode arrays, which would allow for the diffusion of molecules to be unobstructed by the array.

• Additional sensors, such as temperature and oxgen, are also sought after for cell-culture experiments. Increasing the precision and capabilities of in vitro devices and cell-culture setups, will provide increased insight regarding the state of cells.

Boosting the OoC ecosystem

At Holst Centre we look to contribute expertise in the domain of flexible electronics and manufacturing to the OoC ecosystem, while also leveraging the vast realm of OoC knowledge within the Netherlands. This will also require the involvement of multiple stakeholders such as OoC companies, electronics and sensor technology enterprises, partnerships such as hDMT and EUROoCS, pharmaceutical companies, and preclinical research organizations. We believe that Holst Centre can play a crucial role, as an internationally renowned independent research institute, in bringing these various stakeholders together.