Three organ-on-a-chip systems will be developed to study the biological aspects of ex vivo living tissue structures by taking our existing sensor and lab-on-a-chip technology and integrating and analyzing 3D cellular assemblies. The premise of the organ-on-a-chip is the re-creation of the biological niche on chip to study cellular responses and tissue dysfunctions under physiologically relevant conditions.

The aim of this project is to integrate a living tissue analogue that resembles the inner layer of a joint capsule into our complementary cell chip system. This WWTF-funded research project sets out to integrate a human synovial 3D-micromass onto a chip platform containing embedded electrical and optical microsensor arrays to analyze the interdependence of cellular reorganization and tissue function in an inflammatory microenvironment. Called “synovial organ-on-a-chip”, this lab-on-a-chip will be used to study the destructive inflammatory process of rheumatoid synovitis by investigating the dynamic structural changes of the organ model. Results are expected to yield substantial insight into rheumatoid arthritis pathogenesis and may open new ways to explore the mechanisms of inflammation-induced tissue fibrosis and organ failure.

The aim of this project is the development of a human placenta model to monitor the uptake and accumulation of nanomaterials at the placenta cell barrier. Particular emphasis is placed on the physicochemical properties that play a role in the uptake of nanomaterials because it is still unknown which nanoparticle properties affect barrier function and if they pose a risk to the fetus during pregnancy. The integration of a functional placenta cell barrier in a microdevice would shed light on the behavior of nanodrugs, nanosensors and environmental nanoparticles at this important biological barrier. This research activity is funded by H2020-NMP-2015 to evaluate the safety of engineered nanomaterials and is part of an international collaborative project involving 10 partners entitled HINSET: High level integrated Sensor for NanoToxcity Screening. Overall the establishment of a human placental cell barrier also aligns with the European Union mandate to replace animal testing as well as a recent initiative of the United States National Institute of Health (NIH) to establish a “Human Placenta Project”.

MIDBRAIN-ON-A-CHIP: Parkinson's disease model
One of the main limitations in neuroscience and in the modeling of neurodegenerative diseases is the lack of advanced experimental in vitro models that truly recapitulate the complexity of the human brain. Therefore, it is the aim of the here proposed research project to generate brain-like organoids that resemble the human midbrain and their integration into a multifunctional lab-on-a-chip device. We will focus on Parkinson’s disease, which is the second most common neurodegenerative disease. The objectives of the research is the development of a computer-controlled fully automated miniaturized 3D midbrain-on-a-chip system containing embedded optical and electrical microsensors to determine Parkinson’s disease specific phenotypes. The midbrains-on-a-chip project is funded by funded by EU Joint Programme for Neurodegenerative Research (JPND) and is conducted in collaboration with University of Luxembourg (lead) and four additional European partners.

All cell migration and wound healing assays are based on the inherent ability of adherent cells to move into adjacent cell-free areas, thus providing information on cell culture viability, cellular mechanisms and multicellular movements such as tumor invasions. It has been recently recognized that only a better understanding of the complex, dynamic processes that govern cell migration will foster the development of novel therapeutic strategies to combat these diseases. We have developed a lab-on-a-chip capable of mechanically inducing circular cell-free areas within confluent cell layers (see Figure), which will be used for early stage biopharmaceutical screening.

The aim of this FFG funded project is the development of microfluidic single cell microarray for medium and high-throughput toxicity screening of nanomaterials based on measuring the cell viability with integrated optical chemical sensors. The premise of the research is the ability to describe the heterogeneity within biological samples. In other words, differences in the ratio of responding and non-responding cells could lead to the development of personalized medical approaches. This project is jointly conducted with the Technical University Graz and Kdg Opticomp.

Another aspect of my research involves the development of smart implants that contain embedded passive microsensors to monitor dynamic tissue reconstruction and in situ bone formation. Monitoring bone healing at the titanium implant-tissue biointerface in vivo is crucial for determining the integration and stability of endosseous implants. We have already developed and evaluated a titanium dioxide-coated implantable biosensor for minimal-invasive and continuous monitoring of implant stability. Based on initial animal studies, we aim in future to implement a state-of-the-art wireless, passive sensing strategy in combination with custom electronics and readout (e.g. fully integrated PCB) to remotely operate the smart implant.

A relatively new aspect to my research is the development of integrated energy systems as bio-batteries capable of powering embedded biosensors using organic molecules, such as glucose, present in biofluids (e.g. human blood). The goal of the project is to develop microfluidic hydrogel-based biofuel cells for self-powered sensing applications. The research project sets out to create a point-of-care disposable diagnostic microsystem to detect the presence of biomarkers (e.g. proteins, toxins, hormones and viruses) in small blood samples without the need for external electronic components or read out. The entire system architecture would consist of: (a) the biofuel cell containing the enzyme-coupled hydrogels in combination with nanowire-coated electrodes and charge separators, (b) a sensing region based on a sandwich immunoassay, and (c) optical and/ or electric readout. Sensing will be accomplished using a simple antibody-antigen affinity assay followed by the addition of metallic nanoparticles functionalized with secondary antibodies to electrically shorten the interrupted leads. Large scale production of disposable microfluidic cartridges are envisioned to rapidly detect the onset and spread of infectious disease (e.g. malaria, Ebola, Zika and etc.), which is an increasing problem in the developing world.

In cooperation with Dr. Seta Küpcü (Department for Nanobiotechnology, BOKU Vienna) we are developing a microfluidic assay for on-chip phenotyping of human blood cells based on a nanoscale anti-fouling protein matrix that incorporates fusion tags for antibody immobilization.