In cancer research and personalized medicine, new tissue culture models are needed to better predict the response of patients to therapies. With a concern for the small volume of tissue typically obtained through a biopsy, we describe a method to reproducibly section live tumor tissue to submillimeter sizes. These micro-dissected tissues (MDTs) share with spheroids the advantages of being easily manipulated on-chip and kept alive for periods extending over one week, while being biologically relevant for numerous assays. At dimensions below ~420 μm in diameter, as suggested by a simple metabolite transport model and confirmed experimentally, continuous perfusion is not required to keep samples alive, considerably simplifying the technical challenges. For the long-term culture of MDTs, we describe a simple microfluidic platform that can reliably trap samples in a low shear stress environment. We report the analysis of MDT viability for eight different types of tissues (four mouse xenografts derived from human cancer cell lines, three from ovarian and prostate cancer patients, and one from a patient with benign prostatic hyperplasia) analyzed by both confocal microscopy and flow cytometry over an 8-day incubation period. Finally, we provide a proof of principle for chemosensitivity testing of human tissue from a cancer patient performed using the described MDT chip method. This technology has the potential to improve treatment success rates by identifying potential responders earlier during the course of treatment and providing opportunities for direct drug testing on patient tissues in early drug development stages.

This work focuses on modelling design and operation of “microfluidic sample traps” (MSTs). MSTs regroup a widely used class of microdevices that incorporate wells, recesses or chambers adjacent to a channel to individually trap, culture and/or release submicroliter 3D tissue samples ranging from simple cell aggregates and spheroids, to ex vivo tissue samples and other submillimetre-scale tissue models. Numerous MST designs employing various trapping mechanisms have been proposed in the literature, spurring the development of 3D tissue models for drug discovery and personalized medicine. Yet, there lacks a general framework to optimize trapping stability, trapping time, shear stress, and sample metabolism. Herein, the effects of hydrodynamics and diffusion-reaction on tissue viability and device operation are investigated using analytical and finite element methods with systematic parametric sweeps over independent design variables chosen to correspond to the four design degrees of freedom. Combining different results, we show that, for a spherical tissue of diameter d < 500 μm, the simplest, closest to optimal trap shape is a cube of dimensions w equal to twice the tissue diameter: w = 2d. Furthermore, to sustain tissues without perfusion, available medium volume per trap needs to be 100× the tissue volume to ensure optimal metabolism for at least 24 hours.

Intra-arterial liver cancer therapies such as transarterial chemoembolization (TACE) are the preferred therapeutic approaches for advanced hepatocellular carcinoma (HCC). However, these palliative techniques are challenging for delivering therapeutic agents selectively in the tumor without real-time 3D visualization of the catheter within the hepatic arteries. The objective of this work is to develop and evaluate in preclinical tests an advanced interventional guidance platform using a distributed strain sensing device based on optical frequency domain reflectometry (OFDR) to track the tip and shape of a catheter. The scattering properties of a fiber triplet are enhanced by focusing an ultraviolet beam on these fibers, producing a fully-distributed strain sensor, which avoids interpolation errors observed with traditional shape tracking systems. A 3D roadmap of the hepatic arteries is obtained from a combined fully convolutional and residual networks trained on MR angiography, and combined with a 4D flow dynamic sequence enabling to map blood flow velocities. An anisotropic curvature matching method is proposed to map the sensed data onto pre-operative MR and using 3D ultrasound to correct for non-rigid deformations. Experiments were conducted in a controlled environment setting, as well as in both synthetic phantoms and in 5 porcine models to assess the performance for device navigation, yielding satisfactory tracking accuracy with 3D mean errors of 2.8 ± 0.9 mm. We present the first pilot study of MR-compatible UV-exposed OFDR optical fibers for non-ionizing device guidance in intra-arterial procedures, with the potential of avoiding multiple hospitalizations required to perform invasive selective chemoembolizations.

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We demonstrate laser induced cooling in ytterbium doped silica (SiO2) glass with alumina, yttria co-doping (GAYY-Aluminum: Yttrium: Ytterbium Glass) fabricated using the modified chemical vapour deposition (MCVD) technique. A maximum temperature reduction by − 0.9 K from room temperature (296 K) at atmospheric pressure was achieved using only 6.5 W of 1029 nm laser radiation. The developed fabrication process allows us to incorporate ytterbium at concentration of 4 × 1026 ions/m3 which is the highest value reported for laser cooling without clustering or lifetime shortening, as well as to reach a very low background absorptive loss of 10 dB/km. The numerical simulation of temperature change versus pump power well agrees with the observation and predicts, for the same conditions, a temperature reduction of 4 K from room temperature in a vacuum. This novel silica glass has a high potential for a vast number of applications in laser cooling such as radiation-balanced amplifiers and high-power lasers including fiber lasers.