Shape sensing of miniature snake-like robots using optical fibers

Snake like continuum robots are increasingly used for minimally invasive surgery. Most robotic devices of this sort that have been reported to date are controlled in an open loop manner. Using shape sensing to provide closed loop feedback would allow for more accurate control of the robot's position and, hence, more precise surgery. Fiber Bragg Gratings, magnetic sensors and optical reflectance sensors have all been reported for this purpose but are often limited by their cost, size, stiffness or complexity of fabrication. To address this issue, we designed, manufactured and tested a prototype two-link robot with a built-in fiber-optic shape sensor that can deliver and control the position of a CO 2 -laser fiber for soft tissue ablation. The shape sensing is based on optical reflectance, and the device (which has a 4 mm outer diameter) is fabricated using 3D printing. Here we present proof-of-concept results demonstrating successful shape sensing - i.e. measurement of the angular displacement of the upper link of the robot relative to the lower link - in real time with a mean measurement error of only 0.7°

Integration of disease-specific single nucleotide polymorphisms, expression quantitative trait loci and coexpression networks reveal novel candidate genes for type 2 diabetes.

Aims/hypothesisWhile genome-wide association studies (GWASs) have been successful in identifying novel variants associated with various diseases, it has been much more difficult to determine the biological mechanisms underlying these associations. Expression quantitative trait loci (eQTL) provide another dimension to these data by associating single nucleotide polymorphisms (SNPs) with gene expression. We hypothesised that integrating SNPs known to be associated with type 2 diabetes with eQTLs and coexpression networks would enable the discovery of novel candidate genes for type 2 diabetes.MethodsWe selected 32 SNPs associated with type 2 diabetes in two or more independent GWASs. We used previously described eQTLs mapped from genotype and gene expression data collected from 1,008 morbidly obese patients to find genes with expression associated with these SNPs. We linked these genes to coexpression modules, and ranked the other genes in these modules using an inverse sum score.ResultsWe found 62 genes with expression associated with type 2 diabetes SNPs. We validated our method by linking highly ranked genes in the coexpression modules back to SNPs through a combined eQTL dataset. We showed that the eQTLs highlighted by this method are significantly enriched for association with type 2 diabetes in data from the Wellcome Trust Case Control Consortium (WTCCC, p = 0.026) and the Gene Environment Association Studies (GENEVA, p = 0.042), validating our approach. Many of the highly ranked genes are also involved in the regulation or metabolism of insulin, glucose or lipids.Conclusions/interpretationWe have devised a novel method, involving the integration of datasets of different modalities, to discover novel candidate genes for type 2 diabetes

Fluorescent Labeling of Collagen Production by Cells for Noninvasive Imaging of Extracellular Matrix Deposition.

Extracellular matrix (ECM) is an essential component of tissues and provides both integrity and biological cues for cells. Collagen is one of the major proteins found within the ECM and therefore is an essential component of all engineered tissues. Therefore, in this article, we present a method for the online real-time monitoring of collagen deposition in three-dimensional engineered constructs. This method revolves around modification of collagen through the addition of azide-L-proline to cell culture media. The incorporation of azide-L-proline into the neocollagen produced by cells can then be detected by reaction with 10 mM of a Click-IT Alexa Fluor 488 DIBO Alkyne. The reaction was shown as being specific to the collagen as little background staining was observed in cultures, which did not contain the modified proline, and the staining was also depleted after treatment with collagenase and colocalization of collagen type I staining by immunochemistry assay. Real-time online staining of collagen deposition was observed under different culture conditions without affecting proliferation. Collagen deposition was observed to be increased under mechanical stimulation; however, the localization varied across stimulation regimes. This is a new technique for real-time monitoring of cell-produced collagen and will be a valuable addition to the tissue engineering field

Differentiation of Human Embryonic Stem Cells into Cells with Corneal Keratocyte Phenotype

Corneal transparency depends on a unique extracellular matrix secreted by stromal keratocytes, mesenchymal cells of neural crest lineage. Derivation of keratocytes from human embryonic stem (hES) cells could elucidate the keratocyte developmental pathway and open a potential for cell-based therapy for corneal blindness. This study seeks to identify conditions inducing differentiation of pluripotent hES cells to the keratocyte lineage. Neural differentiation of hES cell line WA01(H1) was induced by co-culture with mouse PA6 fibroblasts. After 6 days of co-culture, hES cells expressing cell-surface NGFR protein (CD271, p75NTR) were isolated by immunoaffinity adsorption, and cultured as a monolayer for one week. Keratocyte phenotype was induced by substratum-independent pellet culture in serum-free medium containing ascorbate. Gene expression, examined by quantitative RT-PCR, found hES cells co-cultured with PA6 cells for 6 days to upregulate expression of neural crest genes including NGFR, SNAI1, NTRK3, SOX9, and MSX1. Isolated NGFR-expressing cells were free of PA6 feeder cells. After expansion as a monolayer, mRNAs typifying adult stromal stem cells were detected, including BMI1, KIT, NES, NOTCH1, and SIX2. When these cells were cultured as substratum-free pellets keratocyte markers AQP1, B3GNT7, PTDGS, and ALDH3A1 were upregulated. mRNA for keratocan (KERA), a cornea-specific proteoglycan, was upregulated more than 10,000 fold. Culture medium from pellets contained high molecular weight keratocan modified with keratan sulfate, a unique molecular component of corneal stroma. These results show hES cells can be induced to differentiate into keratocytes in vitro. Pluripotent stem cells, therefore, may provide a renewable source of material for development of treatment of corneal stromal opacities. © 2013 Chan et al

Modelling & characterization of a compliant tethered microgripper for microsurgical applications

The development of microscale surgical tools could pave the way for truly minimally invasive microsurgical procedures. This work demonstrates the application of direct laser writing (DLW) using two-photon polymerization (TPP), a rapid prototyping microfabrication technique, to create a tethered, passively actuated three-dimensional gripper with potential applications in microbiopsy. A microgripper design was devised, modelled and optimized. The gripper was then fabricated and characterized for validation of the theoretical model. The results demonstrate that modelling the behavior of compliant microtools provides a useful approximation for the observed trends and, thus, can be utilized in the design of TPP tools. Future work on the incorporation of viscoelastic material into the model will further improve agreement between the predicted and experimental performance

Kinetic studies of CO<inf>2</inf> methanation over a Ni/γ-Al<inf>2</inf>O<inf>3</inf> catalyst using a batch reactor

The methanation of CO₂ was investigated over a wide range of partial pressures of products and reactants using a gradientless, spinning-basket reactor operated in batch mode. The rate and selectivity of CO₂ methanation, using a 12 wt% Ni/γ-Al₂O₃ catalyst, were explored at temperatures 453 – 483 K and pressures up to 20 bar. The rate was found to increase with increasing partial pressures of H₂ and CO₂ when the partial pressures of these reactants were low; however, the rate of reaction was found to be insensitive to changes in the partial pressures of H₂ and CO₂ when their partial pressures were high. A convenient method of determining the effect of H₂O on the rate of reaction was also developed using the batch reactor and the inhibitory effect of H₂O on CO₂ methanation was quantified. The kinetic measurements were compared with a mathematical model of the reactor, in which different kinetic expressions were explored. The kinetics of the reaction were found to be consistent with a mechanism in which adsorbed CO₂ dissociated to adsorbed CO and O on the surface of the catalyst with the rate-limiting step being the subsequent dissociation of adsorbed CO.JYL was funded by the Cambridge International Scholarship Scheme. The Cambridge Philosophical Society, the Lundgren Research Award and Corpus Christi College are also gratefully thanked for contributing to the support of his PhD studies.This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.ces.2015.10.02

Flourescent, online monitoring of PLGA degradation for regenerative medicine applications

Degradable polymers such as poly(lactic-co-glycolic acid) (PLGA) are frequently chosen for tissue engineering, due to their ease of production, controllable degradation rates and Food and Drug Administration (FDA) approval. Within tissue engineering it is essential that the degradation profile of such biomaterials is understood and measured both in vitro and in vivo. The majority of techniques currently undertaken to study degradation are however destructive, leading to an over reliance on end point analysis. This study therefore defines a method of fluorescently tagging PLGA, via the addition of reactive amine groups and subsequent isothiocyanate reactions, with the purpose of monitoring degradation profiles through non-destructive techniques. The amine grafting and fluorescent labelling of the PLGA was confirmed using both X-ray photospectrometry and high performance liquid chromatography. The modification of the PLGA also had no significant effect on molecular weight or the hydrophilicity of the polymer. Both the release of fluorescent by-products and the changes in fluorescence retention within the modified PLGA were observed to be highly correlated to the changes in physical weight. This paper therefore demonstrates a novel method for the online and non-destructive monitoring of polymer degradation through the incorporation of a fluorescent marker, which can decrease the reliance on end point analysis and reduce the number of samples required both in vitro and in vivo