Typical in vitro barrier and co-culture models rely upon thick semi-permeable polymeric membranes that physically separate two compartments. Polymeric track-etched membranes, while permeable to small molecules, are far from physiological with respect to physical interactions with co-cultured cells and are not compatible with high-resolution imaging due to light scattering and autofluorescence. Here we report on an optically transparent ultrathin membrane with porosity exceeding 20%. We optimize deposition and annealing conditions to create a tensile and robust porous silicon dioxide membrane that is comparable in thickness to the vascular basement membrane (100–300 nm). We demonstrate that human umbilical vein endothelial cells (HUVECs) spread and proliferate on these membranes similarly to control substrates. Additionally, HUVECs are able to transfer cytoplasmic cargo to adipose-derived stem cells when they are co-cultured on opposite sides of the membrane, demonstrating its thickness supports physiologically relevant cellular interactions. Lastly, we confirm that these porous glass membranes are compatible with lift-off processes yielding membrane sheets with an active area of many square centimeters. We believe that these membranes will enable new in vitro barrier and co-culture models while offering dramatically improved visualization compared to conventional alternatives.
Ultrathin silicon-based nanomembranes hold significant promise for advancements in applications ranging from separations to tissue engineering. Widespread application of these membranes has been hindered by their small active area, which typically ranges from square micrometers to square millimeters. These membranes are typically supported on silicon chips as small windows as a result of a time-consuming through-wafer etch process. This approach results in a relatively low active area and can be challenging to integrate into devices because of the rigid silicon support. In this paper, a lift-off approach is demonstrated wherein the membrane is supported by a polymeric scaffold and separated from the wafer to enable fabrication of membrane sheets (>75 cm 2 ) with >80% active area. The wafer-scale lift-off process is demonstrated with 50 nm thick microporous and nanoporous silicon nitride (SiN) membranes. Release of large-scale SiN membranes is accomplished with both wet and dry lift-off techniques. The dry approach uses XeF 2 gas to etch a sacrificial silicon film, while the wet etch uses buffered oxide etchant to remove a silicon dioxide sacrificial layer. Finally, it is demonstrated that lift-off membranes have excellent optical properties and can be used to support cell culture on a conventional scale.
Conventional hemodialysis (HD) uses floor‐standing instruments and bulky dialysis cartridges containing ≈2 m2 of 10 micrometer thick, tortuous‐path membranes. Portable and wearable HD systems can improve outcomes for patients with end‐stage renal disease by facilitating more frequent, longer dialysis at home, providing more physiological toxin clearance. Developing devices with these benefits requires highly efficient membranes to clear clinically relevant toxins in small formats. Here, the ability of ultrathin (<100 nm) silicon‐nitride‐based membranes to reduce the membrane area required to clear toxins by orders of magnitude is shown. Advanced fabrication methods are introduced that produce nanoporous silicon nitride membranes (NPN‐O) that are two times stronger than the original nanoporous nitride materials (NPN) and feature pore sizes appropriate for middle‐weight serum toxin removal. Single‐pass benchtop studies with NPN‐O (1.4 mm2) demonstrate the extraordinary clearance potential of these membranes (105 mL min−1 m−2), and their intrinsic hemocompatibility. Results of benchtop studies with nanomembranes, and 4 h dialysis of uremic rats, indicate that NPN‐O can reduce the membrane area required for hemodialysis by two orders of magnitude, suggesting the performance and robustness needed to enable small‐format hemodialysis, a milestone in the development of small‐format hemodialysis systems.
Developing highly-efficient membranes for toxin clearance in small-format hemodialysis presents a fabrication challenge. The miniaturization of fluidics and controls has been the focus of current work on hemodialysis (HD) devices. This approach has not addressed the membrane efficiency needed for toxin clearance in small-format hemodialysis devices. Dr. Willem Kolff built the first dialyzer in 1943 and many changes have been made to HD technology since then. However, conventional HD still uses large instruments with bulky dialysis cartridges made of ~2 m2 of 10 micron thick, tortuous-path membrane material. Portable, wearable, and implantable HD systems may improve clinical outcomes for patients with end-stage renal disease by increasing the frequency of dialysis. The ability of ultrathin silicon-based sheet membranes to clear toxins is tested along with an analytical model predicting long-term multi-pass experiments from single-pass clearance experiments. Advanced fabrication methods are introduced that produce a new type of nanoporous silicon nitride sheet membrane that features the pore sizes needed for middle-weight toxin removal. Benchtop clearance results with sheet membranes (~3 cm2) match a theoretical model and indicate that sheet membranes can reduce (by orders of magnitude) the amount of membrane material required for hemodialysis. This provides the performance needed for small-format hemodialysis.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.