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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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Passive Control of Silane Diffusion for Gradient Application of Surface Properties
Liquid lithography represents a robust technique for fabricating three-dimensional (3D) microstructures on a two-dimensional template. Silanization of a surface is often a key step in the liquid lithography process and is used to alter the surface energy of the substrate and, consequently, the shape of the 3D microfeatures produced. In this work, we present a passive technique that allows for the generation of silane gradients along the length of a substrate. The technique relies on a secondary diffusion chamber with a single opening, leading to a directional introduction of silane to the substrate via passive diffusion. The secondary chamber geometry influences the deposited gradient, which is shown to be well captured by Monte Carlo simulations that incorporate the passive diffusion and grafting processes. The technique ultimately allows the user to generate a range of substrate wettabilities on a single chip, enhancing throughput for organ-on-a-chip applications by mimicking the spatial variability of tissue topographies present in vivo.
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- PAR ID:
- 10355872
- Date Published:
- Journal Name:
- Micromachines
- Volume:
- 12
- Issue:
- 11
- ISSN:
- 2072-666X
- Page Range / eLocation ID:
- 1360
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
-
Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.3390/mi12111360
