Transport of macromolecules across vascular endothelium and its modification by fluid mechanical forces are important for normal tissue function and in the development of atherosclerosis. However, the routes by which macromolecules cross endothelium, the hemodynamic stresses that maintain endothelial physiology or trigger disease, and the dependence of transendothelial transport on hemodynamic stresses are controversial. We visualized pathways for macromolecule transport and determined the effect on these pathways of different types of flow. Endothelial monolayers were cultured under static conditions or on an orbital shaker producing different flow profiles in different parts of the wells. Fluorescent tracers that bound to the substrate after crossing the endothelium were used to identify transport pathways. Maps of tracer distribution were compared with numerical simulations of flow to determine effects of different shear stress metrics on permeability. Albumin-sized tracers dominantly crossed the cultured endothelium via junctions between neighboring cells, high-density lipoprotein-sized tracers crossed at tricellular junctions, and low-density lipoprotein-sized tracers crossed through cells. Cells aligned close to the angle that minimized shear stresses across their long axis. The rate of paracellular transport under flow correlated with the magnitude of these minimized transverse stresses, whereas transport across cells was uniformly reduced by all types of flow. These results contradict the long-standing two-pore theory of solute transport across microvessel walls and the consensus view that endothelial cells align with the mean shear vector. They suggest that endothelial cells minimize transverse shear, supporting its postulated proatherogenic role. Preliminary data show that similar tracer techniques are practicable in vivo. Solutes of increasing size crossed cultured endothelium through intercellular junctions, through tricellular junctions, or transcellularly. Cells aligned to minimize the shear stress acting across their long axis. Paracellular transport correlated with the level of this minimized shear, but transcellular transport was reduced uniformly by flow regardless of the shear profile.

We developed a novel method to fabricate a crab-like microrobot that can actuate for a long period in a physiological condition. The microrobot backbone was built with a biocompatible and elastic material-polydimethylsiloxane (PDMS)-by using a specially designed 3D molding aligner, and consisted of three strips of PDMS "legs" connected across a "body." Cardiomyocytes were then plated on the grooved top surface of the backbone, resulting in a high concentration of pulsating cells. These key techniques enabled the microrobot to walk continuously for over ten days. The performance of our crab-like microrobot was measured at an average velocity of 100 microm s(-1), and the estimated total distance it travelled was 50 m over a one-week period. Thus, we have demonstrated for the first time a walking robot that exhibited reliable and long-term actuation performances.

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This paper presents the design and actuation of a six-degree-of-freedom (6-DOF) manipulator for a handheld instrument, known as “Micron,” which performs active tremor compensation during microsurgery. The design incorporates a Gough-Stewart platform based on piezoelectric linear motor, with a specified minimum workspace of a cylinder 4 mm long and 4 mm in diameter at the end-effector. Given the stall force of the motors and the loading typically encountered in vitreoretinal microsurgery, the dimensions of the manipulator are optimized to tolerate a transverse load of 0.2 N on a remote center of motion near the midpoint of the tool shaft. The optimization yields a base diameter of 23 mm and a height of 37 mm. The fully handheld instrument includes a custom-built optical tracking system for control feedback, and an ergonomic housing to serve as a handle. The manipulation performance was investigated in both clamped and handheld conditions. In positioning experiments with varying side loads, the manipulator tolerates side load up to 0.25 N while tracking a sinusoidal target trajectory with less than 20 μm error. Physiological hand tremor is reduced by about 90% in a pointing task, and error less than 25 μm is achieved in handheld circle-tracing.

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