Compliant microelectrodes have been designed in a microcable geometry that can be used individually or in an array and either as a shank-style electrode or as a string-like electrode that can be threaded around features such as the peripheral nerve. The fabrication process, using spin-cast micromolding (SCuM), is simple and adaptable to different patterns. The microcables were fabricated using polydimethyl siloxane (PDMS) for the insulating substrate and thin-film gold for the conductive element. The thin, metal film and the low tensile modulus of the PDMS substrate created an electrode with a composite tensile modulus lower than other compliant electrodes described in the literature. The gold film increased the composite modulus approximately three-fold compared to the unaltered PDMS. The durability of the electrodes and tolerance for stretch was also tested. The microcables were found to be conductive up to 6% strain and to regain conductivity after release from multiple applications of 200% strain. The tolerance for high-strain shows that the electrodes can be deployed for use and stretched or pulled into place as needed without damaging the conductivity. The microcable electrode recording sites were electrically characterized using frequency-based impedance modeling and were tested for electrophysiological recording using a peripheral nerve preparation. A suitable insertion mechanism was designed to use the microcables as shank-style cortical electrodes. The microcables were coated on one side with fibrin, which, when dry, stiffens the microcables for insertion into cortical tissue. A 28-day implant study testing the inflammatory response to fibrin coated PDMS microcable electrodes showed a positive, but relatively low inflammatory response, as measured by glial fibrillary astrocytic protein (GFAP; indicating activated astrocytes) immediately at the tissue edge of the implant site. The response of the control, silicon shank-style electrodes, was varied, but also trended toward low levels of GFAP expression. The GFAP staining was possibly due to the clearance of the fibrin from the implant site in addition to the presence of the PDMS-based electrode. Implant studies extending beyond 28 days are necessary to determine whether and to what degree the inflammation persists at the implant site of PDMS-based electrodes.

Steigende Zahlen von Patienten mit neurodegenerativen Erkrankungen sind ein überzeugender Grund, das menschliche Gehirn und seinen fortschreitenden Verfall zu untersuchen, wobei aber viele essenzielle biochemische Funktionen bisher noch nicht vollends geklärt sind. In vitro Forschung zur Hirnfunktion auf geeigneten Plattformen ist ein vielversprechender Weg, diese Lücke zu schließen. Eigenschaften der brain-machine Grenzfläche müssen erforscht werden, um neue Biomaterialien effektiv für lab-on-a-chip Anwendungen wie bspw. Multielektrodenarrays (MEAs) einzusetzen. Diese brain-on-a-chip Anwendungen können dazu dienen, die Zahl der Tierexperimente zu reduzieren, damit Forschung zu beschleunigen und Kosten zu senken. In dieser Hinsicht erfordert die Miniaturisierung von MEAs für eine detailliertere Messung von neuronalen Funktionen die Entwicklung von neuen Biomaterialien mit vorteilhaften elektrischen Eigenschaften. Die Wechselwirkung dieser Biomaterialien mit Zellen muss untersucht werden, um gute Zelladhäsion, Proliferation und elektrische Kopplung zu gewährleisten. Die vorliegende Arbeit dient der Charakterisierung der Wechselwirkung von humanen neuronalen Zellen und Gliazellen (neuronenartige SH-SY5Y und gliaartige U-87 MG Zellen) mit dem Elektrodenmaterial Titannitrid mit nanokolumnarer Oberfläche (TiN nano) und dessen Vorteile bezüglich elektrischer und bioaktiver Eigenschaften im Vergleich mit Gold (Au) und Indiumzinnoxid (ITO), welche derzeit für MEAs und Neuroelektroden verwendet werden. Das Ziel der Arbeit ist die Implementierung neuer aus der theoretischen Physik, Mathematik und Computerwissenschaft entlehnten Techniken, um eine bildbasierte Methode zu entwickeln, die auf minimalen Experimenten beruht und trotzdem wichtige Hinweise zur Biokompatibiliät eines Materials liefert. Das schließt die Analyse von Zellnetzwerken, Zellverteilung, Adhäsion und elektrochemischer Eigenschaften in mono- und co-Kultur ein. Dazu werden Autokorrelation, selbstlernende Algorithmen und die Analyse nächstgelegener Nachbarn eingesetzt, um einen Weg von klassischen biochemischen Assays weg zu einem rechnerischen Ansatz zu finden. Die Ergebnisse zeigen eine Überlegenheit von Tin nano als potenzielles Biomaterial für lab-on-a-chip Anwendungen und in vivo neuraler Stimulation. Die präsentierte bildbasierte Analysemethode für die Untersuchung von Zellverteilungen erweist sich als wertvolles Werkzeug für die Bewertung von Biokompatibilität. Sie ist universell einsetzbar für verschiedene Zelltypen und quantifiziert die Wechselwirkung von Zellen mit Biomaterialien. / Rising numbers of patients with neurodegenerative diseases are a compelling reason to study the human brain and its progressive deterioration but many essential biochemical functions are still under investigation. Conducting research on brain function in vitro with suitable platforms is a promising solution to close these gaps. Characteristics of the brain-machine interface need to be investigated to effectively employ new biomaterials for lab-on-a-chip devices, such as multielectrode arrays (MEAs) for example. These brain-on-a-chip devices will potentially reduce the number of conducted animal experiments and therewith accelerate future research and reduce costs. In this context, miniaturization of MEAs for more detailed measurements of neuronal function calls for new biomaterials with advantageous electrical characteristics. The interaction of these biomaterials with cells needs to be investigated to ensure good cell adhesion, proliferation, and electrical coupling. This thesis aims to study and characterize the interaction of human neuronal and glial cells (neuron-like SH-SY5Y and glia-like U-87 MG cells) with the electrode material titanium nitride with nanocolumnar surface topography (TiN nano) and its advantages in terms of electric and bioactive properties compared to gold (Au) and indium tin oxide (ITO) which are currently employed for MEAs and neuroelectrodes. The overall goal of this study is the implementation of new techniques drawn from theoretical physics, mathematics, and computer science to establish an image-based method that relies on minimal experimental effort but nevertheless yields important evidence of biocompatibility of the material. Analysis includes the investigation of cellular networks, cell distribution, adhesion, and electrochemical properties in mono- and co-culture experiments. To this end, autocorrelation function, self-learning algorithms, and nearest neighbor analysis are deployed to move away from classical biochemical assays toward a more computational approach. Results show the superiority of TiN nano as a potential biomaterial employed for lab-on-a-chip designs as well as for in vivo neural stimulation. The proposed image-based analysis method for the investigation of cellular distribution turns out to be a valuable tool for the assessment of biocompatibility. It is universally applicable to cell types other than neuronal and quantifies the interaction of cells with biomaterials.

Coupling of cells to biomaterials is a prerequisite for most biomedical applications; e.g., neuroelectrodes can only stimulate brain tissue in vivo if the electric signal is transferred to neurons attached to the electrodes’ surface. Besides, cell survival in vitro also depends on the interaction of cells with the underlying substrate materials; in vitro assays such as multielectrode arrays determine cellular behavior by electrical coupling to the adherent cells. In our study, we investigated the interaction of neurons and glial cells with different electrode materials such as TiN and nanocolumnar TiN surfaces in contrast to gold and ITO substrates. Employing single-cell force spectroscopy, we quantified short-term interaction forces between neuron-like cells (SH-SY5Y cells) and glial cells (U-87 MG cells) for the different materials and contact times. Additionally, results were compared to the spreading dynamics of cells for different culture times as a function of the underlying substrate. The adhesion behavior of glial cells was almost independent of the biomaterial and the maximum growth areas were already seen after one day; however, adhesion dynamics of neurons relied on culture material and time. Neurons spread much better on TiN and nanocolumnar TiN and also formed more neurites after three days in culture. Our designed nanocolumnar TiN offers the possibility for building miniaturized microelectrode arrays for impedance spectroscopy without losing detection sensitivity due to a lowered self-impedance of the electrode. Hence, our results show that this biomaterial promotes adhesion and spreading of neurons and glial cells, which are important for many biomedical applications in vitro and in vivo.