Applications of Knudsen compressors as both microscale and macroscale vacuum pumps have been investigated. The study is based on a cascade analysis incorporating available transitional thermal transpiration and Poiseuille flow results for slender channels. It was found that the Knudsen compressor is an attractive possibility for microscale pumps down to a pressure of about 1 mTorr and for macroscale pumps to about 0.1 mTorr. A microscale pump for a micromass spectrometer providing a molecule flow rate of 5×1014 molecules/s results in the following pump characteristics: energy use of 2.4 W, pump volume of 13.9 mℓ at an inlet pressure of 1 mTorr and an energy use of 28.5 mW, and pump volume of 0.16 mℓ at an inlet pressure of 10 mTorr. A macroscale pump providing a pumping speed of 103 ℓ/s results in a pump with an energy use of 1786 W, and pump volume of 1695 ℓ at an inlet pressure of 0.1 mTorr. Several Knudsen compressor characteristics such as pressure rise, pumping speed, volume, energy use and mass flow are presented.

Retinal degeneration is a leading cause of vision impairment and blindness worldwide and medical care for advanced disease does not exist. Stem cell-derived retinal organoids (RtOgs) became an emerging tool for tissue replacement therapy. However, existing RtOg production methods are highly heterogeneous. Controlled and predictable methodology and tools are needed to standardize RtOg production and maintenance. In this study, we designed a shear stress-free micro-millifluidic bioreactor for nearly labor-free retinal organoid maintenance. We used a stereolithography (SLA) 3D printer to fabricate a mold from which Polydimethylsiloxane (PDMS) was cast. We optimized the chip design using in silico simulations and in vitro evaluation to optimize mass transfer efficiency and concentration uniformity in each culture chamber. We successfully cultured RtOgs at three different differentiation stages (day 41, 88, and 128) on an optimized bioreactor chip for more than 1 month. We used different quantitative and qualitative techniques to fully characterize the RtOgs produced by static dish culture and bioreactor culture methods. By analyzing the results from phase contrast microscopy, single-cell RNA sequencing (scRNA seq), quantitative polymerase chain reaction (qPCR), immunohistology, and electron microscopy, we found that bioreactor-cultured RtOgs developed cell types and morphology comparable to static cultured ones and exhibited similar retinal genes expression levels. We also evaluated the metabolic activity of RtOgs in both groups using fluorescence lifetime imaging (FLIM), and found that the outer surface region of bioreactor cultured RtOgs had a comparable free/bound NADH ratio and overall lower long lifetime species (LLS) ratio than static cultured RtOgs during imaging. To summarize, we validated an automated micro-millifluidic device with significantly reduced shear stress to produce RtOgs of comparable quality to those maintained in conventional static culture.