Health Technologies

11.40 – 13.00 | Room ..
Chairs: Loes Segerink & Andries van der Meer

  • Organs-on-chip are microengineered in vitro models that recapitulate aspects of human tissue physiology for disease research and drug testing. For excitable tissues such as the heart, electrical stimulation is essential to enhance physiological relevance and to gain deeper insight into tissue function and disease mechanisms. Conventional electrode fabrication, however, typically relies on cleanroom-based lithography, which increases costs and limits use as a consumable. Alternatively, electrodes are often inserted manually into microscale systems, but this approach is time-consuming, technically cumbersome, and lacks reproducibility. In this work, we present an alternative approach based on extrusion printing of conductive pastes, enabling rapid, low-cost fabrication of integrated electrodes without the need for cleanroom facilities.

    Silver paste was employed for conductive traces to ensure low-resistance signal delivery, while carbon paste was used for electrode sites interfacing with cells or culture medium, offering biocompatibility and stability. The method supports printing on diverse substrates, including glass, PDMS, and flexible tapes, with precise spatial alignment to microengineered tissue compartments.

    We demonstrate three use cases: (i) stimulation of microscale engineered heart tissues (µEHTs), highlighting the advantage of a low-cost, disposable format; (ii) integration into geometrically defined tissue structures, where accurate electrode placement enables targeted excitation; and (iii) adaptation to a 12-well plate platform using flexible printed electrodes on a sticky tape substrate, demonstrating the unique advantage of electrode systems that can be directly integrated into existing culture setups in a conformal and adaptable manner.

    Together, these results position extrusion-printed electrodes as a practical and versatile solution for electrical stimulation in organ-on-chip systems, reducing fabrication costs while maintaining precision and reproducibility.

  • Organ-on-chip (OOC) devices replicate key aspects of human physiology by combining human stem cells with three-dimensional constructs, fluid flow, and mechanical cues. While these systems provide powerful opportunities to study inter-organ communication and provide insights into disease predisposition and progression, their impact is limited by the lack of reliable, real-time biochemical sensing. This challenge stems from difficulties in achieving sensor stability, sensitivity, and compatibility with complex physiological media.

    The gut–brain axis (GBA) is a particularly compelling application, as its communication relies on small-molecule signalling through systemic circulation and the vagus nerve. An OOC model of the GBA therefore offers multiple microenvironments in which real-time monitoring could reveal mechanisms of gut–brain signalling and dysregulation.

    Here, we introduce an enzymatic, fluorescence-based approach to continuously monitor the neurotransmitter l-glutamate, enabling real-time detection of cellular and inter-organ communication at time scales previously inaccessible. This strategy leverages the intrinsic fluorescence of tryptophan residues in enzymes, thereby bypassing conventional indirect sensing methods that rely on redox activity, hydrogen peroxide, oxygen, or pH.

    Our findings demonstrate substrate-sensitive spectral peaks from glutamate oxidase and glutamate dehydrogenase at 340 nm, and explore the integration of optical sensors using solid-state matrices such as gelatine and UV-curable poly(ethylene glycol) diacrylate (PEG-DA). Ongoing work focuses on engineered enzyme variants and antenna dye coupling, with the potential of extending these techniques to other neurotransmitters, such as serotonin and acetylcholine, thereby laying the foundation for comprehensive, label-free monitoring of biochemical signals within organ-on-chip systems.

  • Retinal diseases affect millions of people worldwide and may lead to irreversible blindness. Many retinal diseases, such as diabetic retinopathy and age-related macular degeneration, originate from or have its effect on the tissue of the outer blood-retinal barrier (oBRB). The oBRB is essential for regulating transport of nutrients, ions, drugs and other molecules in the retina. To improve understanding of disease mechanisms and to develop new therapeutic strategies, there is a need for controlled, human tissue-based, biologically relevant models. We have demonstrated that using (patient-derived) induced pluripotent stem cells (iPSCs) and organ-on-chip technology, we can create relevant and patient-specific models of the oBRB. Organ-on-chip technology combines culturing of living cells with their environmental cues, such as fluidic shear stress, in a microfluidic device to model specific organ systems. In such models, assessing barrier integrity is of vital importance to oBRB function and disease. Measuring trans-epithelial electrical resistance (TEER) is a quantitative method to asses barrier integrity and is already implemented in many simple cell culture models. However, combining TEER measurements with organ-on-chip devices is a relatively experimental and new field.
    Here, we showcase our collaboration with high-tech sensing company LocSense (Enschede, The Netherlands) in which we are developing a tailored solution for our standardized oBRB-on-chip to measure TEER using impedance spectroscopy. We demonstrate the versatility and sensitivity of the system and provide an first proof-of-concept by monitoring our oBRB-on-chip for 8 consecutive weeks.

  • Several flu pandemics recorded in the history of humankind were originated from the infections of influenza viruses. The infection is initiated by virus attachment to cell surface. Influenza viruses are known to bind to glycan receptors at a cell membrane by multivalent interactions. A 100-nm virus particle may vary in the number of hemagglutinins (HAs) and neuraminidases (NAs) on the viral capsid, so estimating the valency of the interactions required to achieve the apparent avidity requires assumptions. In this work, a protein assembly based on the two-component I53 architecture is employed to arrange a well-defined number of HAs in an icosahedral nanoparticle presentation. A platform composed of supported lipid bilayers (SLBs) functions as a cell membrane mimic and enables the tuning of the glycan surface density and provides antifouling properties. This HA presentation results in a nanomolar affinity between the nanoparticle and glycan-SLB, whereas individual HA-glycan interactions are in the millimolar range. Due to the multivalent binding, the HA nanoparticle shows superselective binding, i.e., a non-linear increase in binding with respect to the glycan density. Moreover, varying the distribution of functional and non-functional HAs during the mixing at the protein assembly step can result in binding differences compared to fully functional nanoparticles due to a distribution of displayed valencies. With multivalency theory, we aim to elucidate how the affinity of HA-glycan binding scales from a single HA to multivalent HAs presented in particles and full viruses. This knowledge may be used in the surveillance of influenza and in the design of new antiviral drugs.