Dielectric spectroscopy is a label-free, non-contact, real-time, multi-layer sensing technology, and has been used for identification and quantification of many biological materials. A combination of such sensing features is in demand for monitoring of organ-on-chip systems; however available sensing technologies have yet to address this need. In this work, we explore the possibility of leveraging the inherent features of dielectric spectroscopy for the application in organ-on-chip systems, by investigating three key technological developments using open-ended coaxial probes. Firstly, biocompatible non-contact sensing capabilities are proved by showing similar sensing performance of Parylene C-coated probes and uncoated probes. Secondly, a setup and methodology are developed for highly accurate and non-destructive height positioning of the probe to allow for precise extraction of intermediate sample layers. Finally, non-contact multi-layer sensing performance of the presented technology is successfully demonstrated by means of a biological phantom in a three-layered system. With further integration, dielectric spectroscopy can potentially become a cornerstone sensing technique for organ-on-chip by enabling real-time non-contact tracking of various tissue contents and properties.

In this work, we present a numerical testbench, realized in a circuit simulation environment, enabling a priori uncertainty evaluation of dielectric spectroscopy in the application field of organs-on-chip. This testbench evaluates the impact of noise, ambient temperature variation and impurity of liquid standards on the uncertainty of dielectric spectroscopy measurements. Moreover, the proposed approach allows to account for the impact on measurement sensitivity of system parameters such as probe dimensions and probe coatings. The estimated uncertainty contributions for the considered effects are compared and benchmarked experimentally. Finally, the testbench is employed to project the dielectric spectroscopy accuracy on a relevant biological application, namely monitoring the growth of a 7 μm-thick kidney cell monolayer.

Organ-on-chip (OoC) is emerging as a key technology for improved pre-clinical drug testing. Monitoring tissues and the artificial microenvironment in OoC devices is critical to recapitulate human physiology; however, sensing is often invasive, superficial, and not continuous over time. This work aims to overcome these issues by proposing dielectric spectroscopy as a non-invasive and time-continuous sensing technique capable of extracting information from multi-layer OoC devices, including distinguishable tissue layers. The presented results set the foundations for this goal by proving this technique’s feasibility, showing excellent correspondence between the experimental and modelled data, and providing design guidelines for application-tailored optimization.

Electronic implants are becoming a valuable tool to explore as well as regulate neural activity, potentially overcoming neural disabilities that are not yet curable. For effective exploration and regulation, it has become increasingly necessary to cover larger areas of neural tissue and to interact at a higher resolution by means of electrode arrays. Application specific integrated circuits (ASICs) are often employed to accommodate the interaction with these electrodes but these are limited in size, which consequently limits the amount of individual recording or stimulation channels. The de facto solution that allows for the connection of an electrode array to an ASIC is to multiplex high numbers of electrodes to a single ASIC channel. However, due to switching and signal latencies only a limited number of electrodes can be multiplexed per channel. Multiple channels on an ASIC are therefore desirable to accommodate implants with a high electrode count. Due to recent miniaturization advances, an ever-increasing number of channels can be made available on a single ASIC and the urgency arises to investigate technological complications of connecting these channels to electrodes. In this work we will investigate the technological complications of assembling a flexible electrode array substrate to an ASIC with a high number of independent channels. Our aim is to manufacture a biocompatible multi-layer substrate-ASIC assembly that can route 10.000 independent recording and/or stimulating sites to an array of electrodes covering a large area of the brain.