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Creators/Authors contains: "Phillips, Gregory J."

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  1. 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. 
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  2. New combinations of existing antibiotics are being investigated to combat bacterial resilience. This requires detection technologies with reasonable cost, accuracy, resolution, and throughput. Here, we present a multi -drug screening platform for bacterial cultures by combining droplet microfluidics, search algorithms, and imaging with a wide field of view. We remotely alter the chemical microenvironment around cells and test 12 combinations of resistant cell types and chemicals. Fluorescence intensity readouts allow us to infer bacterial resistance to specific antibiotics within 8 hours. The platform has potential to detect and identify parameters of bacterial resilience in cell cultures, biofilms, and microbial aggregates. 
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