Abstract:We introduce a new class of neural implants with the topology and compliance of dura mater, the protective membrane of the brain and spinal cord. These neural interfaces, which we called e-dura, achieve chronic bio-integration within the subdural space where they conform to the statics and dynamics of neural tissue. e-dura embeds interconnects, electrodes and chemotrodes that sustain millions of mechanical stretch cycles, electrical stimulation pulses, and chemical injections. These integrated modalities enable multiple neuroprosthetic applications. e-dura extracted cortical states in freely behaving animals for brain machine interface, and delivered electrochemical spinal neuromodulation that restored locomotion after paralyzing spinal cord injury. e-dura offers a novel platform for chronic multimodal neural interfaces in basic research and neuroprosthetics.3 Neuroprosthetic medicine is improving the lives of countless individuals. Cochlear implants restore hearing in deaf children, deep brain stimulation alleviates Parkinsonian symptoms, and spinal cord neuromodulation attenuates chronic neuropathic pain (1). These interventions rely on implants developed in the 1980s (2, 3). Since then, advances in electroceutical, pharmaceutical, and more recently optogenetic treatments triggered development of myriad neural interfaces that combine multiple modalities (4-9). However, the conversion of these sophisticated technologies into chronic implants mediating long-lasting functional benefits has yet to be achieved. A recurring challenge restricting chronic bio-integration is the substantial biomechanical mismatch between implants and neural tissues (10-13). Here, we introduce a new class of soft multimodal neural interfaces that achieve chronic bio-integration, and we demonstrate their long-term efficacy in clinically relevant applications. e-dura fabrication. We designed and engineered soft interfaces that mimic the topology and mechanical behavior of the dura mater (Fig. 1A-B). The implant, which we called electronic dura mater or e-dura, integrates a transparent silicone substrate (120µm in thickness), stretchable gold interconnects (35nm in thickness), soft electrodes coated with a novel platinum-silicone composite (300µm in diameter), and a compliant fluidic microchannel (100µm x 50µm in crosssection) (Fig. 1C-D, fig. S1-S2-S3). The interconnects and electrodes transmit electrical excitation and transfer electrophysiological signals.The microfluidic channel, termed chemotrode (14), delivers drugs locally (Fig. 1C, fig. S3). Microcracks in the gold interconnects (15) and the newly developed soft platinum-silicone composite electrodes confer exceptional stretchability to the entire implant (Fig. 1B, Movie S1). The patterning techniques of metallization and microfluidics support rapid manufacturing of customized neuroprostheses.4 e-dura implantation. Most implants used experimentally or clinically to assess and treat neurological disorders are placed above the dura mater (3,(16)(17)(18). The compliance of e-...

The generation of surfaces and interfaces that are able to withstand protein adsorption is a major challenge in the design of blood-contacting materials for both medical implants and bioaffinity sensors. Poly(ethylene glycol)-derived materials are generally considered to be particularly effective candidates for the fabrication of protein-resistant materials. Most metallic biomaterials are covered by a protective, stable oxide film; converting such oxide surfaces, which are known to strongly interact with proteins, into noninteractive surfaces requires a specific design of the surface/interface architecture. A class of copolymers based on poly(L-lysine)g-poly(ethylene glycol) (PLL-g-PEG) was found to spontaneously adsorb from aqueous solutions onto several metal oxide surfaces, such as TiO 2 , Si 0.4 Ti 0.6 O 2 , and Nb 2 O 5 , as measured by the in situ optical waveguide lightmode spectroscopy technique and by ex situ X-ray photoelectron spectroscopy. The resulting adsorbed layers are highly effective in reducing the adsorption both of blood serum and of individual proteins such as fibrinogen, which is known to play a major role in the cascade of events that lead to biomaterial-surfaceinduced blood coagulation and thrombosis. Adsorbed protein levels as low as <5 ng/cm 2 could be achieved for an optimized polymer architecture. The modified surfaces are stable to desorption under flow conditions at 37 °C and pH 7.4 in HEPES [4-(2-hydroxyethyl)piperazine-1-ethanesulfonic acid] and PBS (phosphatebuffered saline) buffers. The adsorbed layer of copolymer is thought to form a comblike structure at the surface, with positively charged primary amine groups of the PLL bound to the negatively charged metal oxide surface, while the hydrophilic and uncharged PEG side chains are exposed to the solution phase.Copolymer architecture is an important factor in the resulting protein resistance; it is discussed on the basis of packing-density considerations and the corresponding radii of gyration of the different PEG chain lengths studied. This surface functionalization technology is believed to be of value for use in both the biomaterial and biosensor areas, as the chosen macromolecules are biocompatible and the application is straightforward and cost-effective. † Part of the special issue "Gabor Somorjai Festschrift".

Quantification of biological or biochemical processes are of utmost importance for medical, biological and biotechnological applications. However, converting the biological information to an easily processed electronic signal is challenging due to the complexity of connecting an electronic device directly to a biological environment. Electrochemical biosensors provide an attractive means to analyze the content of a biological sample due to the direct conversion of a biological event to an electronic signal. Over the past decades several sensing concepts and related devices have been developed. In this review, the most common traditional techniques, such as cyclic voltammetry, chronoamperometry, chronopotentiometry, impedance spectroscopy, and various field-effect transistor based methods are presented along with selected promising novel approaches, such as nanowire or magnetic nanoparticle-based biosensing. Additional measurement techniques, which have been shown useful in combination with electrochemical detection, are also summarized, such as the electrochemical versions of surface plasmon resonance, optical waveguide lightmode spectroscopy, ellipsometry, quartz crystal microbalance, and scanning probe microscopy. The signal transduction and the general performance of electrochemical sensors are often determined by the surface architectures that connect the sensing element to the biological sample at the nanometer scale. The most common surface modification techniques, the various electrochemical transduction mechanisms, and the choice of the recognition receptor molecules all influence the ultimate sensitivity of the sensor. New nanotechnology-based approaches, such as the use of engineered ion-channels in lipid bilayers, the encapsulation of enzymes into vesicles, polymersomes, or polyelectrolyte capsules provide additional possibilities for signal amplification. In particular, this review highlights the importance of the precise control over the delicate interplay between surface nano-architectures, surface functionalization and the chosen sensor transducer principle, as well as the usefulness of complementary characterization tools to interpret and to optimize the sensor response.