We have designed, built, and tested microfluidic systems capable of transporting individual, preimplantation mouse embryos (100-microm to 150-microm diameter) through a network of channels. Typical channels are 160 to 200 microm deep, 250 to 400 microm wide at the top, and narrower at the bottom (0 to 250 microm wide) due to the fabrication process. In these channels, a pressure gradient of 1 Pa/mm causes the medium to flow on the order of 10(-10) m3/s (100 nl/s), with an average speed of 1 to 2 mm/s. Under these flow conditions the embryos roll along the bottoms of the channels, traveling at 1/2 the speed of the fluid. By manipulating the pressure at the wells connected to the ends of the channels, the embryos can be transported to (and retained at) specific locations including culture compartments and retrieval wells.
A fundamental maneuver in autonomous space operations is known as rendezvous, where a spacecraft navigates to and approaches another spacecraft. In this case study, we present linear and nonlinear benchmark models of an active chaser spacecraft performing rendezvous toward a passive, orbiting target. The system is modeled as a hybrid automaton, where the chaser must adhere to different sets of constraints in each discrete mode. A switched LQR controller is designed accordingly to meet this collection of physical and geometric safety constraints, while maintaining liveness in navigating toward the target spacecraft. We extend this benchmark problem to check for passive safety, which is collision avoidance along a passive, propulsion-free trajectory that may be followed in the event of system failures. We show that existing hybrid verification tools like SpaceEx, C2E2, and our own implementation of a simulation-driven verification tool can robustly verify this system with respect to the requirements, and a variety of relevant initial conditions.
We have developed a structurally-guided scaffold phage display strategy for identification of ligand mimetic bio-therapeutics. As a proof of concept we used the ligand of integrin αvβ6, a tumour cell surface receptor and a major new target for imaging and therapy of many types of solid cancer. NMR structure analysis showed that RGD-helix structures are optimal for αvβ6 ligand-interaction, so we designed novel algorithms to generate human single chain fragment variable (scFv) libraries with synthetic VH-CDR3 encoding RGD-helix hairpins with helices of differing pitch, length and amino acid composition. Study of the lead scFv clones D25scFv and D34scFv and their corresponding VH-CDR3 derived peptides, D25p and D34p, demonstrated: specific binding to recombinant and cellular αvβ6; inhibition of αvβ6-dependent cell and ligand adhesion, αvβ6-dependent cell internalisation; and selective retention by αvβ6-expressing, but not αvβ6-negative, human xenografts. NMR analysis established that both the D25p and D34p retained RGD-helix structures confirming the success of the algorithm. In conclusion, scFv libraries can be engineered based on ligand structural motifs to increase the likelihood of developing powerful bio-therapeutics.
The biosand filter is a household-level water treatment technology used globally in low-resource settings. As of December 2016, over 900,000 biosand filters had been implemented in 60 countries around the world. Local, decentralized production is one of the main advantages of this technology, but it also creates challenges, especially in regards to quality control. Using the current recommended proportions for the biosand filter concrete mix, slump was measured at water-tocement ratios of 0.51, 0.64 and 0.76, with two replicates for each level. Twenty-eight day strength was tested on four replicate cylinders, each at water-to-cement ratios of 0.51, 0.59, 0.67 and 0.76.Wet curing and dry curing were compared for 28-day strength and for their effect on shrinkage.Maximum strength occurred at water-to-cement ratios of 0.51-0.59, equivalent to 8-9.3 L water for a full scale filter assuming saturated media, corresponding to a slump class of S1 (10 mm to 40 mm).Wet curing significantly improved strength of the concrete mix and reduced shrinkage. Quality control measures such as the slump test can significantly improve the quality within decentralized production of biosand filters, despite localized differences in production conditions.
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