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Herein we report the assessment of the effects of shockwave (SW) impacts on adult rat hippocampal progenitor cell (AHPC) neurospheres (NSs), which are used as in vitro brain models, for enhancing our understanding of the mechanisms of traumatic brain injury (TBI). The assessment has been achieved by using culture dishes and a new microchip. The microchip allows the chemicals released from the brain models cultured inside the cell culture chamber under SW impacts to diffuse to the nano sensors in adjacent sensor chambers through built-in diffusion barriers, which are used to prevent the cells from entering the sensor chambers, thereby mitigating the biofouling issues of the sensor surface. Experiments showed the negative impact of the SW on the viability, proliferation, and differentiation of the cells within the NSs. A qPCR gene expression analysis was performed and appeared to confirm some of the immunocytochemistry (ICC) results. Finally, we demonstrated that the microchip can be used to monitor lactate dehydrogenase (LDH) released from the AHPC-NSs subjected to SW impacts. As expected, LDH levels changed when AHPC-NSs were injured by SW impacts, verifying this chip can be used for assessing the degrees of injuries of AHPC-NSs by monitoring LDH levels. Taken together, these results suggest the feasibility of using the chip to better understand the interactions between SW impacts and in vitro brain models, paving a way for potentially establishing in vitro TBI models on a chip. 

Neurotransmitters are used by the nervous system to transmit messages between neurons. The abnormal levels of the neurotransmitters may lead to neurological disorders. It is very important to monitor their levels in patients. Herein, we report a polymer nanostructured electrode-enabled electrochemical sensing microchip for detecting dopamine and serotonin. The nanostructures on the electrode can enhance the surface area of the electrode dramatically. As a result, the measured electrical signals increased in comparison with those of an electrochemical sensor with an electrode of a flat surface. It has been found that this microchip can detect neurotransmitters with a level as low as ~120 nM with high specificity and can be used to monitor the dopamine and serotonin in a mixed sample successfully in both static and dynamic conditions. Finally, the real-time measurements of dopamine released from N27-A dopaminergic neural cells using the microchip have been demonstrated. 

We report a method to fabricate silicon micro–nanostructures of different shapes by tuning the number of layers and the sizes of self-assembled polystyrene beads, which serve as the mask, and by tuning the reactive ion etching (RIE) time. This process is simple, scalable, and inexpensive without using any sophisticated nanomanufacturing equipment. Specifically, in this work, we demonstrate the proposed process by fabricating silicon micro- or nanoflowers, micro- or nanobells, nanopyramids, and nanotriangles using a self-assembled monolayer or bilayer of polystyrene beads as the mask. We also fabricate flexible micro–nanostructures by using silicon molds with micro–nanostructures. Finally, we demonstrate the fabrication of bandage-type electrochemical sensors with micro–nanostructured working electrodes for detecting dopamine, a neurotransmitter related to stress and neurodegenerative diseases in artificial sweat. All these demonstrations indicate that the proposed process provides a low-cost, easy-to-use approach for fabricating silicon micro–nanostructures and flexible micro–nanostructures, thus paving a way for developing wearable micro–nanostructures enabled sensors for a variety of applications in an efficient manner. 

To improve our understanding of how the central nervous system functions in health and disease, we report the development of an integrated chip for studying the effects of the neurotransmitters dopamine and serotonin on adult rat hippocampal progenitor cell (AHPC) neurospheroids. This chip allows dopamine or serotonin located in one chamber to diffuse to AHPC neurospheroids cultured in an adjacent chamber through a built-in diffusion barrier created by an array of intentionally misaligned micropillars. The gaps among the micropillars are filled with porous poly(ethylene glycol) (PEG) gel to tune the permeability of the diffusion barrier. An electrochemical sensor is also integrated within the chamber where the neurospheroids can be cultured, thereby allowing monitoring of the concentrations of dopamine or serotonin. Experiments show that concentrations of the neurotransmitters inside the neurospheroid chamber can be increased over a period of several hours to over 10 days by controlling the compositions of the PEG gel inside the diffusion barrier. The AHPC neurospheroids cultured in the chip remain highly viable following dopamine or serotonin treatment. Cell proliferation and neuronal differentiation have also been observed following treatment, revealing that the AHPC neurospheroids are a valuable in vitro brain model for neurogenesis research. Finally, we show that by tuning the permeability of diffusion barrier, we can block transfer of Escherichia coli cells across the diffusion barrier, while allowing dopamine or serotonin to pass through. These results suggest the feasibility of using the chip to better understand the interactions between microbiota and brain via the gut–brain axis.