An official website of the United States government
Engineered living materials (ELMs) are an emerging class of biohybrid materials that have shown great promise with advanced capabilities unachievable by conventional materials. However, application of ELMs outside of the laboratory has been limited due to the need for periodic media replenishment or complete media immersion. We herein demonstrated the integration of capillary microfluidics for the autonomous and pump-free hydration of ELM hydrogels. We optimized 3D printing parameters, including exposure time and build plate lift and retract distances, to obtain microchannel dimensions capable of spontaneous capillary flow using a low-cost liquid crystal display stereolithographic apparatus (LCD-SLA) 3D printer and two hydrogel resins that are suitable for ELMs. Microchannel dimensions were accurate with ≤ 10% deviation between designed and measured widths and precise with coefficients of variation (CVs) <5% for microchannels ≥ 206.4 µm. We demonstrated proof-of-concept spontaneous capillary flow in 3D printed microfluidic devices using dye-incorporated lysogeny broth (LB). Snapshots of the devices captured up to 24 hours showed the diffusion of dye-incorporated LB throughout the bulk material. Through this proof-of-concept study, we have showcased the feasibility of integrating capillary microfluidics with ELMs for the autonomous and pump-free flow of fluids towards self-sustaining and long-term hydration.
more »
« less
Influence of microchannel geometry on device performance and electrophysiological recording fidelity during long-term studies of connected neural populations
Compartmentalized microfluidic neural cell culture platforms, which physically separate axons from the neural soma using a series of microchannels, have been used for studying a wide range of pathological conditions and basic neuroscience questions. While each study has different experimental needs, the fundamental design of these devices has largely remained unchanged and a systematic study to establish long-term neural cultures in this format is lacking. Here, we investigate the influence of microchannel geometry and cell seeding density on device performance particularly in the context of long-term studies of synaptically-connected, yet fluidically-isolated neural populations of neurons and glia. Of the different experimental parameters, the microchannel height was the principal determinant of device performance, where the other parameters offer additional degrees of freedom in customizing such devices for specific applications. We condense the effects of these parameters into design rules and demonstrate their utility in engineering a microfluidic neural culture platform with integrated microelectrode arrays. The engineered device successfully recorded from primary rat cortical cells for 59 days in vitro with more than on order of magnitude enhancement in signal-to-noise ratio in the microchannels.
more »
« less
- PAR ID:
- 10426125
- Date Published:
- Journal Name:
- Lab on a Chip
- Volume:
- 22
- Issue:
- 20
- ISSN:
- 1473-0197
- Page Range / eLocation ID:
- 3961 to 3975
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Focusing particles into a tight stream is critical for many microfluidic particle-handling devices such as flow cytometers and particle sorters. This work presents a fundamental study of the passive focusing of polystyrene particles in ratchet microchannels via direct current dielectrophoresis (DC DEP). We demonstrate using both experiments and simulation that particles achieve better focusing in a symmetric ratchet microchannel than in an asymmetric one, regardless of the particle movement direction in the latter. The particle focusing ratio, which is defined as the microchannel width over the particle stream width, is found to increase with an increase in particle size or electric field in the symmetric ratchet microchannel. Moreover, it exhibits an almost linear correlation with the number of ratchets, which can be explained by a theoretical formula that is obtained from a scaling analysis. In addition, we have demonstrated a DC dielectrophoretic focusing of yeast cells in the symmetric ratchet microchannel with minimal impact on the cell viability.more » « less
-
null (Ed.)Acoustofluidics, by combining acoustics and microfluidics, provides a unique means to manipulate cells and liquids for broad applications in biomedical sciences and translational medicine. However, it is challenging to standardize and maintain excellent performance of current acoustofluidic devices and systems due to a multiplicity of factors including device-to-device variation, manual operation, environmental factors, sample variability, etc. Herein, to address these challenges, we propose “intelligent acoustofluidics” – an automated system that involves acoustofluidic device design, sensor fusion, and intelligent controller integration. As a proof-of-concept, we developed intelligent acoustofluidics based mini-bioreactors for human brain organoid culture. Our mini-bioreactors consist of three components: (1) rotors for contact-free rotation via an acoustic spiral phase vortex approach, (2) a camera for real-time tracking of rotational actions, and (3) a reinforcement learning-based controller for closed-loop regulation of rotational manipulation. After training the reinforcement learning-based controller in simulation and experimental environments, our mini-bioreactors can achieve the automated rotation of rotors in well-plates. Importantly, our mini-bioreactors can enable excellent control over rotational mode, direction, and speed of rotors, regardless of fluctuations of rotor weight, liquid volume, and operating temperature. Moreover, we demonstrated our mini-bioreactors can stably maintain the rotational speed of organoids during long-term culture, and enhance neural differentiation and uniformity of organoids. Comparing with current acoustofluidics, our intelligent system has a superior performance in terms of automation, robustness, and accuracy, highlighting the potential of novel intelligent systems in microfluidic experimentation.more » « less
-
Abstract Microfluidic devices that combine an extracellular matrix environment, cells, and physiologically relevant perfusion, are advantageous as cell culture platforms. We developed a hydrogel-based, microfluidic cell culture platform by loading polyethylene glycol (PEG) hydrogel-encapsulated U87 glioblastoma cells into membrane-capped wells in polydimethyl siloxane (PDMS). The multilayer microfluidic cell culture system combines previously reported design features in a configuration that loads and biomimetically perfuses a 2D array of cell culture chambers. One dimension of the array is fed by a microfluidic concentration gradient generator (MCGG) while the orthogonal dimension provides loading channels that fill rows of cell culture chambers in a separate layer. In contrast to typical tree-like MCGG mixers, a fractional serial dilution of 1, ½, ¼, and 0 of the initial solute concentration is achieved by tailoring the input microchannel widths. Hydrogels are efficiently and reproducibly loaded in all wells and cells are evenly distributed throughout the hydrogel, maintaining > 90% viability for up to 4 days. In a drug screening assay, diffusion of temozolomide and carmustine to hydrogel-encapsulated U87 cells from the perfusion solution is measured, and dose–response curves are generated, demonstrating utility as an in vitro mimic of the glioblastoma microenvironment.more » « less
-
Miniaturization of microelectronic components comes at a price of high heat flux density. By adopting liquid cooling, the rising demand of high heat flux devices can be met while the reliability of the microelectronic devices can also be improved to a greater extent. Liquid cooled cold plates are largely replacing air based heat sinks for electronics in data center applications, thanks to its large heat carrying capacity. A bench level study was carried out to characterize the thermohydraulic performance of two microchannel cold plates which uses warm DI water for cooling Multi Chip Server Modules (MCM). A laboratory built mock package housing mock dies and a heat spreader was employed while assessing the thermal performance of two different cold plate designs at varying coolant flow rate and temperature. The case temperature measured at the heat spreader for varying flow rates and input power were essential in identifying the convective resistance. The flow performance was evaluated by measuring the pressure drop across cold plate module at varying flow rates. Cold plate with the enhanced microchannel design yielded better results compared to a traditional parallel microchannel design. The study conducted at higher coolant temperatures yielded lower pressure drop values with no apparent change in the thermal behavior using different cold plates. The tests conducted after reversing the flow direction in microchannels provide an insight at the effect of neighboring dies on each other and reveal the importance of package specific cold plate designs for top performance. The experimental results were validated using a numerical model which are further optimized for improved geometric designs.more » « less
- Free Publicly Accessible Full Text
-
Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1039/d2lc00683a
