Microsurgeons require dexterity to make precise and stable maneuvers to achieve surgical objectives and to minimize surgical risks during freehand procedures. This work presents a novel, common path, swept source optical coherence tomography-based "smart" micromanipulation aided robotic-surgical tool (SMART) that actively suppresses surgeon hand tremor. The tool allows enhanced tool tip stabilization, more accurate targeting and the potential to lower surgical risk. Freehand performance is compared to smart tool-assisted performance and includes assessment of the one-dimensional motion tremor in an active microsurgeon's hand. Surgeon hand tremor-the ability to accurately locate a surgical target and maintain tool tip offset distances-were all improved by smart tool assistance.

Human pluripotent stem cell-derived hepatocytes have the potential to provide in vitro model systems for drug discovery and hepatotoxicity testing. However, these cells are currently unsuitable for drug toxicity and efficacy testing because of their limited expression of genes encoding drug-metabolizing enzymes, especially cytochrome P450 (CYP) enzymes. Transcript levels of major CYP genes were much lower in human embryonic stem cell-derived hepatocytes (hESC-Hep) than in human primary hepatocytes (hPH). To verify the mechanism underlying this reduced expression of CYP genes, including CYP1A1, CYP1A2, CYP1B1, CYP2D6, and CYP2E1, we investigated their epigenetic regulation in terms of DNA methylation and histone modifications in hESC-Hep and hPH. CpG islands of CYP genes were hypermethylated in hESC-Hep, whereas they had an open chromatin structure, as represented by hypomethylation of CpG sites and permissive histone modifications, in hPH. Inhibition of DNA methyltransferases (DNMTs) during hepatic maturation induced demethylation of the CpG sites of CYP1A1 and CYP1A2, leading to the up-regulation of their transcription. Combinatorial inhibition of DNMTs and histone deacetylases (HDACs) increased the transcript levels of CYP1A1, CYP1A2, CYP1B1, and CYP2D6. Our findings suggest that limited expression of CYP genes in hESC-Hep is modulated by epigenetic regulatory factors such as DNMTs and HDACs.

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A two-tiered susceptibility monitoring strategy was developed that includes testing field populations at diagnostic concentrations and doses in first-tier vial LC bioassays and second-tier gel bait matrix LD bioassays. The vial method facilitates rapid identification of field strains with reduced susceptibility. The feeding bioassay effectively simulates field exposure to Advion(®) and therefore has utility for secondary confirmation of susceptibility shifts and identification of behavioral resistance (i.e. bait aversion).

This Letter reports a fully packaged microelectromechanical system (MEMS) endoscopic catheter for forward imaging optical coherence tomography (OCT). Two-dimensional optical scanning of Lissajous patterns was realized by the orthogonal movement of two commercial aspherical glass lenses laterally mounted on two resonating electrostatic MEMS microstages at low operating voltages. The MEMS lens scanner was integrated on a printed circuit board and packaged with an aluminum housing, a gradient index fiber collimator, and an objective lens. A home-built spectral-domain OCT system with 60 kHz A-line acquisition rate was combined with the endoscopic MEMS catheter. Three-dimensional images of 256×256×995 voxels were directly reconstructed by mapping the A-line datasets along the Lissajous patterns. The endoscopic catheter can provide a new direction for forward endoscopic OCT imaging.

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A handheld Smart Micromanipulation Aided Robotic-surgery Tool (SMART) micro-forceps guided by a fiber-optic common-path optical coherence tomography (CP-OCT) sensor is presented. A fiber-optic CP-OCT distance and motion sensor is integrated into the shaft of a micro-forceps. The tool tip position is manipulated longitudinally through a closed loop control using a piezoelectric motor. This novel forceps design could significantly enhance safety, efficiency and surgical outcomes. The basic grasping and peeling functions of the micro-forceps are evaluated in dry phantoms and in a biological tissue model. As compared to freehand use, targeted grasping and peeling performance assisted by active tremor compensation, significantly improves micro-forceps user performance.

A motion-compensated, hand-held, common-path, Fourier-domain optical coherence tomography imaging probe has been developed for image-guided intervention during microsurgery. A hand-held prototype instrument was achieved by integrating an imaging fiber probe inside a stainless steel needle and attached to the ceramic shaft of a piezoelectric motor housed in an aluminum handle. The fiber probe obtains A-scan images. The distance information was extracted from the A-scans to track the sample surface distance and a fixed distance was maintained by a feedback motor control which effectively compensated hand tremor and target movements in the axial direction. Real-time data acquisition, processing, motion compensation, and image visualization and saving were implemented on a custom CPU-GPU hybrid architecture. We performed 10× zero padding to the raw spectrum to obtain 0.16 µm position accuracy with a compensation rate of 460 Hz. The root-mean-square error of hand-held distance variation from target position was measured to be 2.93 µm. We used a cross-correlation maximization-based shift correction algorithm for topology correction. To validate the system, we performed free-hand OCT M-scan imaging using various samples.