Myocardial ischaemia induced by cardioplegia is the most prominent risk during open-heart surgery. To achieve adequate protection of the cardiomyocytes during surgery, the cardioplegia must arrive at all cardiomyocytes. Local obstruction can lead to regional ischaemia. For surgeons and perfusionist, the arrested heart is a black box. They know how much cardioplegia they are administering to the heart. However, they do not know if cardioplegia is reaching all cells. This work describes which parameters can be measured during cardioplegia induced cardiac arrest and compares the methods used in the literature to detect these parameters. Following this, it is the goal to create a proof-­of-­concept sensor for the detection of myocardial ischaemia. A literature review indicated that a fluorescent optochemical pH sensor has the most potential. To be able to develop a proof-­of-­concept, optical, chemical, and medical knowledge needs to be combined. This is necessary to map what is required and what is possible for optochemical in vivo sensing. First, a framework is designed and used to select the best technique and material suited for this project. In this framework, the medical requirements and the resources available are combined. As a result, this thesis work will use a dual wavelength pH­-sensitive fluorescent dye encapsulated in a biocompatible hydrogel. In preparation for the proof-­of-­conceptsensor, multiple samples are fabricated and extensively tested to achieve the optimal sensing layer. Using the optimised concentrations, a proof-­of-­conceptsensor is created using a miniature reflection probe and an USB spectrometer. This proof-­of-­conceptsensor shows that it can measure the changes in pH and can be corrected for multiple interferences. It also shows the potential to be further miniaturised and to be used during cardiac surgery. Before this can happen, chemical optimisation of the sensing layer is needed, and the consistency of the sensing layer needs to be improved. However, besides this, the work succeeded in selecting an optochemical sensing technique and material which shows the potential to be used in cardiac surgery

Organ-on-chip (OOC) devices are micro-engineered three-dimensional (3D) biomimetic systems that can be used to create in vitro models of human tissue. They provide an alternative for conventional cell culture tools in pharmaceutical R&D. Moreover, these devices can contribute in research focused on understanding complex disease processes. OOC often includes porous membranes made of polydimethylsiloxane. The conventional method to create these membranes has drawbacks such as a limited achievable porosity. A novel approach to create porous PDMS membranes is to use micro-electro-mechanical systems (MEMS)-based fabrication technologies such as etching. With this method, the porosity of the membranes can be finely tuned. Quirós-solano et al.1 used this method and created a thin (>10 m) highly porous membrane and 3D scaffolds. Furthermore, their membrane could be easily transferred from its substrate to an OOC. In order to achieve this transfer, they incorporated a sacrificial layer of poly acrylic acid (PAA). The high porosity of the scaffold was created by introducing lateral gaps between the vertical pores of the scaffold. The dimensions of the gaps can be tuned by changing the etching time. However, this resulted in complete etching of the underlying layer. In order to reduce the etching time, this project is focused on the mechanism that created the lateral gaps. The contribution of bias power, chamber pressure and chuck temperature to that mechanism are investigated. With the knowledge gained from these experiments, the dimensions of the gaps were tuned by changing the aforementioned parameters.Furthermore, in this work the fabrication process of Quirós-Solano et al. is adapted to create thick (>20 m) PDMS membranes. These membranes were successfully fabricated and employed by researchers at the University of Technology in Eindhoven.

The Flex-to-Rigid (F2R) platform is a generic IC-based technology platform that allows flexible sensors and electronics to be fabricated and integrated onto the catheters or guidewires of minimally invasive medical instruments. In this thesis, a process flow was developed for the fabrication of flexible metal interconnects based on the F2R platform using materials that are biocompatible for neural implants, namely parylene and titanium nitride. A “parylene last” process flow was developed that allows a higher temperature budget of up to 400°C for IC fabrication, and enabled the addition of a ceramic encapsulation layer beneath the parylene encapsulation for improved adhesion and decreased permeability to moisture. For this process flow, two new technology modules were developed: the titanium buried mask and the aluminium etch stop layer. A device with working flexible interconnects connected to bond pads on a rigid silicon island was fabricated. Evaluation testing showed that the interconnects were able to function after four weeks at accelerated aging conditions corresponding to four months in human body conditions, and were able to be bent to a diameter of less than 0.25 mm before device failure.

One of the most widely used structural Organ-on-Chip industry is Polydimethylsiloxane (PDMS). This material offers desirable features such as customizable mechanical properties, patterning , biocompatibility, optical transparency, permeability to gasses, viscoelasticity and hydrophicity. One example of OoC, the Cytostretch platform proposed at TU Delft, where different tissues can be cultured in one single OoC platform. Its PDMS membrane can inflate and deflate in a cyclic and controlled matter, introducing mechanical cues to the cell substrate, and cell-cell interactions. 3D stimulation and custom patterning of the surface has shown to affect cells fate, this network gives both mechanical support and optimal cues for a more accurate cell formation. A new material appeared in literature as a substitute for PDMS: a formulation of off-stoichiometry-thiol-ene PDMS (OSTE-PDMS) is a proposed as a substitute material for PDMS as it features similar characteristics as PDMS but without known issues such as absorption of molecules, swelling and gas leakage. This material offers a surface modified to allow a specific functional group to covalently bond with it. This physical bond between the layer ensures a transfer of the stimuli produced by the device directly into the cell culture inside the hydrogel. Hydrogels are widely used in the cell culturing industry, this material offers a 3D interface for biochemical and mechanical cues as well as a optimal environment for the cells to survive. The goal of this project is to integrate an ECM supporting platform to a porous membrane made of OSTE-PDMS ensuring local adherence between layers. During this project a new material has been used to obtain a microporous thin membrane which has its surface modified to bond with thiol reactive hydrogels. Samples of PDMS, OSTE-PDMS and OSTE-PDMS+Hydrogels underwent tensile tests and were analyzed and compared to literature showing results to be not similar in value but same behavior as in literature.UV cured and chemically induced hydrogels were tested during this project to physically bond with the modified OSTE-PDMS surface, both of the hydrogels proved to be possible candidates as both were successfully bonded to a OSTE-PDMS substrate in a petri dish. During the project the chemically induced hydrogel was prefered out of the two hydrogels due the its success in bonding to a OSTE-PDMS patterned and suspended membrane. This hydrogel has better mechanical properties, not UV dependant and has a quicker curation time making it a great option for future projects.