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Most mental disorders, such as addictive diseases or schizophrenia, are characterized by impaired cognitive function and behavior control originating from disturbances within prefrontal neural networks. Their often chronic reoccurring nature and the lack of efficient therapies necessitate the development of new treatment strategies. Brain-computer interfaces, equipped with multiple sensing and stimulation abilities, offer a new toolbox whose suitability for diagnosis and therapy of mental disorders has not yet been explored. This study, therefore, aimed to develop a biocompatible and multimodal neuroprosthesis to measure and modulate prefrontal neurophysiological features of neuropsychiatric symptoms. We used a 3D-printing technology to rapidly prototype customized bioelectronic implants through robot-controlled deposition of soft silicones and a conductive platinum ink. We implanted the device epidurally above the medial prefrontal cortex of rats and obtained auditory event-related brain potentials in treatment-naïve animals, after alcohol administration and following neuromodulation through implant-driven electrical brain stimulation and cortical delivery of the anti-relapse medication naltrexone. Towards smart neuroprosthetic interfaces, we furthermore developed machine learning algorithms to autonomously classify treatment effects within the neural recordings. The neuroprosthesis successfully captured neural activity patterns reflecting intact stimulus processing and alcohol-induced neural depression. Moreover, implant-driven electrical and pharmacological stimulation enabled successful enhancement of neural activity. A machine learning approach based on stepwise linear discriminant analysis was able to deal with sparsity in the data and distinguished treatments with high accuracy. Our work demonstrates the feasibility of multimodal bioelectronic systems to monitor, modulate and identify healthy and affected brain states with potential use in a personalized and optimized therapy of neuropsychiatric disorders.

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This study introduces a thermophoretic lab-on-a-chip device to measure the Soret coefficient. We use resistive heating of a microwire on the chip to induce a temperature gradient, which is measured by fluorescence lifetime imaging microscopy (FLIM). To verify the functionality of the device, we used dyed polystyrene particles with a diameter of 25 nm. A confocal microscope is utilized to monitor the concentration profile of colloidal particles in the temperature field. Based on the measured temperature and concentration differences, we calculate the corresponding Soret coefficient. The same particles have been recently investigated with thermal diffusion forced Rayleigh scattering (TDFRS) and we find that the obtained Soret coefficients agree with literature results. This chip offers a simple way to study the thermophoretic behavior of biological systems in multicomponent buffer solutions quantitatively, which are difficult to study with optical methods solely relying on the refractive index contrast.

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Neuromuscular interfaces are required to translate bioelectronic technologies for application in clinical medicine. Here, by leveraging the robotically controlled ink-jet deposition of low-viscosity conductive inks, extrusion of insulating silicone pastes and in situ activation of electrode surfaces via cold-air plasma, we show that soft biocompatible materials can be rapidly printed for the on-demand prototyping of customized electrode arrays well adjusted to specific anatomical environments, functions and experimental models. We also show, with the monitoring and activation of neuronal pathways in the brain, spinal cord and neuromuscular system of cats, rats and zebrafish, that the printed bioelectronic interfaces allow for long-term integration and functional stability. This technology might enable personalized bioelectronics for neuroprosthetic applications.

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We study the thermodiffusion behavior of spherical polystyrene beads with a diameter of 25 nm by infrared thermal diffusion Forced Rayleigh Scattering (IR-TDFRS). Similar beads were used to investigate the radial dependence of the Soret coefficient by different authors. While Duhr and Braun (Proc. Natl. Acad. Sci. U.S.A. 104, 9346 (2007)) observed a quadratic radial dependence Braibanti et al. (Phys. Rev. Lett. 100, 108303 (2008)) found a linear radial dependence of the Soret coefficient. We demonstrated that special care needs to be taken to obtain reliable thermophoretic data, because the measurements are very sensitive to surface properties. The colloidal particles were characterized by transmission electron microscopy and dynamic light scattering (DLS) experiments were performed. We carried out systematic thermophoretic measurements as a function of temperature, buffer and surfactant concentration. The temperature dependence was analyzed using an empirical formula. To describe the Debye length dependence we used a theoretical model by Dhont. The resulting surface charge density is in agreement with previous literature results. Finally, we analyze the dependence of the Soret coefficient on the concentration of the anionic surfactant sodium dodecyl sulfate (SDS), applying an empirical thermodynamic approach accounting for chemical contributions.

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Formamide is one of the important compounds from which prebiotic molecules can be synthesized, provided that its concentration is sufficiently high. For nucleotides and short DNA strands, it has been shown that a high degree of accumulation in hydrothermal pores occurs, so that temperature gradients might play a role in the origin of life [Baaske P, et al. (2007)Proc Natl Acad Sci USA104(22):9346-9351]. We show that the same combination of thermophoresis and convection in hydrothermal pores leads to accumulation of formamide up to concentrations where nucleobases are formed. The thermophoretic properties of aqueous formamide solutions are studied by means of Infrared Thermal Diffusion Forced Rayleigh Scattering. These data are used in numerical finite element calculations in hydrothermal pores for various initial concentrations, ambient temperatures, and pore sizes. The high degree of formamide accumulation is due to an unusual temperature and concentration dependence of the thermophoretic behavior of formamide. The accumulation fold in part of the pores increases strongly with increasing aspect ratio of the pores, and saturates to highly concentrated aqueous formamide solutions of ∼85 wt% at large aspect ratios. Time-dependent studies show that these high concentrations are reached after 45-90 d, starting with an initial formamide weight fraction of[Formula: see text]wt % that is typical for concentrations in shallow lakes on early Earth.

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We present a versatile chip-based method to inflict microscopic lesions on cellular networks or tissue models. Our approach relies on resistive heating of microstructured conductors to impose highly localized thermal stress on specific regions of a cell network. We show that networks can be precisely dissected into individual subnetworks using a microwire crossbar array. To this end, we pattern a network of actively beating cardiomyocyte-like cells into smaller subunits by inflicting thermal damage along selected wires of the array. We then investigate the activity and functional connectivity of the individual subnetworks using a Ca(2+) imaging-based signal propagation analysis. Our results demonstrate the efficient separation of functional activity between individual subnetworks on a microscopic level. We believe that the presented technique may become a powerful tool for investigating lesion and regeneration models in cellular networks.

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In this work, we study the molar mass dependence of the thermodiffusion of polyethylene oxide at different temperatures in ethanol, water/ethanol mixture (c(water) = 0.7), and water in a molar mass range up to M(w) = 180,000 g/mol. Due to the low solubility of polyethylene oxide oligomers in ethanol the measurements are limited up to M(w) = 2200 g/mol. The specific water/ethanol concentration 0.7 has been chosen, because at this weight fraction the thermal diffusion coefficient, D(T), of water/ethanol vanishes so that the system can be treated as a pseudo binary mixture. The addition of ethanol will degrade the solvent quality, so that we expect a change of the interaction energies between polymer and solvent. The analysis of the experimental data within a theoretical model shows the need of a refined model, which takes specific interactions into account.

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The supported lipid bilayer (SLB) is a well-known system for studying the cell membrane and membrane proteins. It is also promising as a platform for studying cell processes: the cell adhesion, the cell membrane receptors, and the intercellular signaling processes. SLBs made of natural lipids appeared to be protein and cell repellent. Thus, to use the SLB as a substrate for cells, one should functionalize them to provide adhesion. In the present paper, we describe a simple approach to promote adhesion of neuronal cells to the SLB without using proteins or peptides, by introducing positively charged lipids 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) into the SLB made of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC). We show that neurons adhere to these bilayers and grow for at least 10 days. The SLBs themselves were found to degrade with time in cell culture conditions, but maintained fluidity (as revealed by fluorescence recovery after photobleaching), demonstrating the possibility of using SLBs for studying neuronal cells in culture.

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It is still incompletely known how NMDA receptors (NMDA-R) regulate bidirectional synaptic plasticity. We examined this issue by an experimental protocol in which paired pulse stimulation (PPS) with 50ms interstimulus interval and basal frequency of 0.1Hz was applied to CA1 area of rat hippocampal slices during low Mg(2+) perfusion. Under blockade of NMDA-Rs by AP5, PPS for 12-60min led to only a minor depression. In contrast, when PPS was applied in the absence of AP5, there was a prominent short-term potentiation (STP), mainly of AMPA-R mediated responses, with peak at 1min and lasting 10-15min. The STP was followed by a slowly developing long-term depression (LTD). Applying AP5 during the STP, converted it to a stable increase relative to the control pathway. Following peak STP, plasticity was controlled in a composite manner. Whereas the initial decay was counteracted by NMDA-R activation, the following LTD was dependent on such activation. Our data suggest that synaptic changes do not only depend on the instantaneous, NMDA-dependent Ca(2+) concentration in the dendritic spine, but are also influenced by prior induction events. In addition to NMDA-R driven processes, passive relaxation contributes to the synaptic plasticity and in some cases outbalances the active control.

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