Functionalized copolymers offer the opportunity for tailored biology, where specific functionalities within these materials can be rapidly engineered on demand. Embedding effector molecules, for example, into these copolymers transforms an otherwise inactive component into a functional matrix for envisioned in vivo applications such as suppression of cellular inflammation/stress or immuno-regulatory implant coating, etc. Furthermore, our ability to utilize these copolymers in both a vesicular/planar configuration, coupled with their versatility in block composition empowers opportunities of utilizing vesicle-encapsulated effector molecules as dedicated drug delivery vehicles with targeting capabilities, or as modalities to replenish exhausted effector molecule stores within planar copolymer thin films. As such, these copolymeric membrane materials may potentially impact multiple medically-relevant fields in both scientific and technological contexts.

An important element empowering this transition is the examination of the bio-inert properties of these materials. This includes the interrogation of the stress response of macrophages to the chemical/topographical stimuli presented by these materials. We have previously developed copolymers as neural implant coatings functionalized with a glucocorticoid anti-inflammatory Dexamethasone (Dex) using Langmuir-Blodgett deposition. This technology successfully suppressed, to a significant degree, RAW264.7 macrophage transcriptional machinery of several cytokines including TNFα, Il-6, and Il-12 analyzed using real time PCR (RT-PCR). These findings offered insight into both bio-abio material fabrication, as well as analysis of stress specific gene program activation which may be used to generate principles for optimizing neural implant biocompatibility and chronicity by attenuating innate immune responses.

This study has broadened the range of applications of this material via its integration with a combination of intracellular signaling agonists (e.g. Liver X receptor-α/β (LXR α/β)) that function as non-steroidal anti-inflammatories to block transcriptional machinery associated with cell stress among other disorders. Here we demonstrate both planar encapsulation of an additional effector in the form of a robust, cell permeable LXRα/β agonist 3-((4-Methoxyphenyl)amino)-4-phenyl-1-(phenylmethyl)-1H-pyrrole-2, 5-dione using a crosslinked copolymer thin film. In addition, we investigated the underlying mechanisms of the attenuation of cellular inflammation via RT-PCR analysis of the resultant inhibition of lipopolysaccharide (LPS)-stimulated secretion of proinflammatory cytokine in murine macrophages. These advancements may potentially result in multi-functional nanoscale thin films that are chronically active, and can suppress cellular inflammation as implant coatings or bio-inert vesicular carriers of a non-steroidal pharmacological system.

This paper reports our effort to develop amorphous silicon carbide (a-SiC) films for use as hermetic thin film coatings for mechanically-flexible neural electrodes. In our work, the a-SiC films were deposited by plasma enhanced chemical vapor deposition (PECVD) using two distinct methods, namely a single precursor approach using trimethylsilane, and a dual precursor approach using methane (CH4) and silane (SiH4). The mechanical properties of films deposited on Si substrates were characterized using the wafer curvature and load-deflection methods. The effectiveness of the films as moisture barriers for polyimide substrates was characterized by measuring the leakage currents of SiC-coated interdigitated electrode structures soaked in PBS. A microfabricated prototype of the flat interface nerve electrode (FINE) based on a flexible polyimide substrate and a PECVD SiC capping layer was fabricated using a monolithic process based on conventional micromachining techniques. To facilitate this approach, a reactive ion etching process was developed that exhibited high etch rates and high selectively to the SiC films.

Among the variety of applications for biosensorsone of the exciting frontiers is to utilize those devices as post-synaptic sensing elements in chemical coupling between neurons and solid-state systems. The first necessary step to attain this challenge is to realize highly efficient detector for neurotransmitter acetylcholine (ACh). Herein, we demonstrate that the combination of floating gate configuration of ion-sensitive field effect transistor (ISFET) together with diluted covalent anchoring of enzyme acetylcholinesterase (AChE) onto device sensing area reveals a remarkable improvement of a four orders of magnitude in dose response to ACh. This high range sensitivity in addition to the benefits of peculiar microelectronic design show, that the presented hybrid provides a competent platform for assembly of artificial chemical synapse junction. Furthermore, our system exhibits clear response to eserine, a competitive inhibitor of AChE, and therefore it can be implemented as an effective sensor of pharmacological reagents, organophosphates, and nerve gases as well.

Understanding the nature of specific neural activity is essential to the progression of research in the field of brain disorders and diseases, as well as neuroprosthetics. Microelectrodes are the primary measurement devices used to transduce neural activity into electrical signals to help neuroscientists study dynamic brain function. Advances in signal processing and packaging currently allow neural recording for periods as long as a year by use of chronically implanted electrodes in freely behaving animals. Stability of the electrode impedance is required for optimum signal recording over the length of the recording interval. While electrode–tissue interaction plays a major role in the quality of the recorded signal, delamination or degradation of the dielectric coating also interferes with signal recording. Therefore, to improve the signal recording process, it is useful to understand how the electrode design and component materials affect the signal over the course of time.

Multielectrode arrays create the interfaces between nerves and technical systems in neuroprosthetic devices. MEMS (microelectromechanical systems) technologies offer opportunities to develop high density arrays with large numbers of electrodes and smallest dimensions of electrode site area and pitch. Polymers are promising candidates for flexible substrates of these electrode arrays to meet the requirements of structural biocompatibility. In addition, these substrates must be biostable and should be non-toxic. From an engineering point of view, material processing should be feasible with standard MEMS process technology. Fail-safe integration of electronic circuitry, encapsulation of the systems with substrate-integrated electrodes and connection to cables and connectors is of great importance for reliable (micro-) implants.

A comprehensive overview of the application of polymers like silicone rubber, polyimide, and parylene C as substrate, insulation and encapsulation material for multielectrode arrays will be given. Assembling techniques for system integration and encapsulation concepts will be discussed with a special attention on the adhesion properties between substrate, interconnects and insulation and possible failure mechanisms. Application scenarios include peripheral nerve interfaces like cuff and sieve electrodes as well as multielectrode arrays for retinal vision prostheses and shaft and grid arrays for the central nervous system interfaces.

Fabrication of biomedical devices and components on soft, elastomeric substrates is a promising step toward mechanically-matched and conformal biological-electrical interfaces. However, while polymeric substrates are extremely deformable, electronic materials typically are not. To explore this convergence of stiff electronic materials and compliant elastomers, we prepare thin film gold conductors on polydimethylsiloxane (PDMS) membranes (Fig. 1), which have Young's modulus, E ~ 2 MPa. The gold conductors have the property of remaining electrically conducting while stretched uni-axially to 20% strain and more [1]. Varying the fabrication methods affects the initial microstucture and morphology of the metal films, which in turn determine stretchability. To examine this effect, tensile tests are performed to measure electro-mechanical behavior, and scanning electron microscopy is used to observe the morphology of the films. In this study, we compare metal deposition techniques as well as samples of various metal thicknesses, linking resulting film morphologies to stretchability.

Neuronal research requires to efficiently perform long-time experiments on large-scale neuronal networks in a minimally invasive way. Such experiments imply stimulation and measurements of electrical activity on a large number of neurons. This could be achieved by on-chip integration of actuators, sensors and readout electronics with dimensions comparable to the sizes of neurons. Integration of biosensors at this scale creates new challenges: the processing of the sensors must be compatible with state-of-the art CMOS technology, the system must be biocompatible, and the down-scaled technology imposes restrictions on the applicable stimulation voltages and increases the electrical noise.

Recently it has been demonstrated that biological phenomena can be exploited in order to achieve the best coupling between cells and sub-micron scale electronics. Engulfment of sub-micron nail structures by the cell membrane minimizes the distance between the sensor and the cell [1], [2].

This paper presents two methods to produce nails with sizes from sub-micrometer to micrometer scales, on top of a CMOS chip. Prototype chips have been fabricated, and cells have been cultured to examine the in-vitro bio-compatibility of the chip.

Stretchable microelectrode arrays (SMEAs) that are fabricated on the compliant silicone poly dimethyl siloxane (PDMS) have potential applications for research on traumatic brain injury (TBI). Increasing the number of electrodes in the array improves the accuracy in assessing the effects of traumatic injury to cell tissue cultures. The currently available encapsulation process with a photopatternable silicone limits the electrode density on the array. The present research examines four factors in the encapsulation process: exposure dose, scattered and reflected light as well as hard bake time. Careful optimization of these four factors leads to a significant reduction of the minimum feature size of a contact via patterned into the encapsulation layer, thus enabling an increase of the electrode density on the array.

A process to fabricate stretchable and adherent gold tracks on flat silicone rubber substrates is studied by X-ray photoelectron spectroscopy (XPS), static water contact angle measurement, atomic force microscopy (AFM) and scanning electron microscopy (SEM). The process involves several steps: curing flat silicone substrate; removing uncured oligomers by hexane Soxhlet extraction; pre-stretching the substrate; activating the strained silicone surface by an oxygen plasma treatment; coating the strained substrate with 5nm titanium and 80nm gold layers by e-beam evaporation; and finally releasing the sample. The plasma treatment creates a thin brittle silica-like layer that temporarily increases the substrate's surface energy. Indeed the plasma treatment is followed by a hydrophobic recovery. As a consequence, the delay between plasma treatment and metal deposition has to be reduced as much as possible. The silica-like layer can be nicely observed after release. Its thickness is estimated to be around 20nm to 50nm. The entire process allows us to obtain stretchable metallized samples that remain conductive even after an excessive deformation leading to electrical failure.