Benchmarking of X-Ray Fluorescence Microscopy with Ion Beam Implanted Samples Showing Detection Sensitivity of Hundreds of Atoms.

Single impurities in insulators are now often used for quantum sensors and single photon sources, while nanoscale semiconductor doping features are being constructed for electrical contacts in quantum technology devices, implying that new methods for sensitive, non-destructive imaging of single- or few-atom structures are needed. X-ray fluorescence (XRF) can provide nanoscale imaging with chemical specificity, and features comprising as few as 100 000 atoms have been detected without any need for specialized or destructive sample preparation. Presently, the ultimate limits of sensitivity of XRF are unknown - here, gallium dopants in silicon are investigated using a high brilliance, synchrotron source collimated to a small spot.

Brachytherapy on-a-chip: a clinically-relevant approach for radiotherapy testing in 3d biology.

We describe the first microfluidic device for testing of brachytherapy (BT), with applications in translational cancer research. Our PDMS-made BT-on-chip system allows highly precise manual insertion of clinical BT seeds, reliable dose calculation using standard clinically-used TG-43 formalism and easy culture of naturally hypoxic spheroids in less than 3 days, thereby increasing the translational potential of the device. As the BT-on-chip platform is designed to be versatile, we showcase three different gold-standard post-irradiation bioassays and recapitulate, for the first time on-chip, key clinical observations such as dose rate effect and hypoxia-induced radioresistance.

The enhancement of photosynthetic performance, water use efficiency and potato yield under elevated CO is cultivar dependent.

As a fourth major food crop, potato could fulfill the nutritional demand of the growing population. Understanding how potato plants respond to predicted increase in atmospheric CO at the physiological, biochemical and molecular level is therefore important to improve potato productivity. Thus, the main objectives of the present study are to investigate the effects of elevated CO on the photosynthetic performance, water use efficiency and tuber yield of various commercial potato cultivars combined with biochemical and molecular analyses.

Multiplexed Viability Assays for High-Throughput Screening of Spheroids of Multiple Sizes.

High-throughput (HT) drug screening is in high demand for successful drug discovery and personalized medicine. Spheroids act as a promising preclinical model for HT drug screening, which may decrease drug failures in clinical trials. Numerous spheroid-forming technological platforms are currently under development, which include synchronous, jumbo-sized, hanging drop, rotary, and nonadherent surface spheroid growth.

The 2D microfluidics cookbook - modeling convection and diffusion in plane flow devices.

A growing number of microfluidic systems operate not through networks of microchannels but instead through using 2D flow fields. While the design rules for channel networks are already well-known and exposed in microfluidics textbooks, the knowledge underlying transport in 2D microfluidics remains scattered piecemeal and is not easily accessible to experimentalists and engineers. In this tutorial review, we formulate a unified framework for understanding, analyzing and designing 2D microfluidic technologies.

Pixelated Microfluidics for Drug Screening on Tumour Spheroids and Ex Vivo Microdissected Tumour Explants.

Anticancer drugs have the lowest success rate of approval in drug development programs. Thus, preclinical assays that closely predict the clinical responses to drugs are of utmost importance in both clinical oncology and pharmaceutical research. 3D tumour models preserve the tumoral architecture and are cost- and time-efficient.

Cell Death Analysis in Cancer Spheroids from a Microfluidic Device.

Microfluidic technology facilitates the generation of 3D spheroids from cancer cells, a more suitable model for preclinical therapeutic studies. This system opens the possibility to test many drugs combination at a low cost. Here we describe the use of microfluidic devices for cytotoxicity evaluation on cancer spheroids for the discovery of drugs that could be used in combination with radiotherapy.

Radiotherapy on-chip: microfluidics for translational radiation oncology.

The clinical importance of radiotherapy in the treatment of cancer patients justifies the development and use of research tools at the fundamental, pre-clinical, and ultimately clinical levels, to investigate their toxicities and synergies with systemic agents on relevant biological samples. Although microfluidics has prompted a paradigm shift in drug discovery in the past two decades, it appears to have yet to translate to radiotherapy research. However, the materials, dimensions, design versatility and multiplexing capabilities of microfluidic devices make them well-suited to a variety of studies involving radiation physics, radiobiology and radiotherapy.

The expression of virulence genes increases membrane permeability and sensitivity to envelope stress in Salmonella Typhimurium.

Virulence gene expression can represent a substantial fitness cost to pathogenic bacteria. In the model entero-pathogen Salmonella Typhimurium (S.Tm), such cost favors emergence of attenuated variants during infections that harbor mutations in transcriptional activators of virulence genes (e.

Large-Scale Dried Reagent Reconstitution and Diffusion Control Using Microfluidic Self-Coalescence Modules.

The positioning and manipulation of large numbers of reagents in small aliquots are paramount to many fields in chemistry and the life sciences, such as combinatorial screening, enzyme activity assays, and point-of-care testing. Here, a capillary microfluidic architecture based on self-coalescence modules capable of storing thousands of dried reagent spots per square centimeter is reported, which can all be reconstituted independently without dispersion using a single pipetting step and ≤5 μL of a solution. A simple diffusion-based mathematical model is also provided to guide the spotting of reagents in this microfluidic architecture at the experimental design stage to enable either compartmentalization, mixing, or the generation of complex multi-reagent chemical patterns.

Potato Response to Drought Stress: Physiological and Growth Basis.

Drought poses a major challenge to the production of potatoes worldwide. Climate change is predicted to further aggravate this challenge by intensifying potato crop exposure to increased drought severity and frequency. There is an ongoing effort to adapt our production systems of potatoes through the development of drought-tolerant cultivars that are appropriately engineered for the changing environment.

Microdissected Tissue vs Tissue Slices-A Comparative Study of Tumor Explant Models Cultured On-Chip and Off-Chip.

Predicting patient responses to anticancer drugs is a major challenge both at the drug development stage and during cancer treatment. Tumor explant culture platforms (TECPs) preserve the native tissue architecture and are well-suited for drug response assays. However, tissue longevity in these models is relatively low.

Hypoxic Jumbo Spheroids On-A-Chip (HOnAChip): Insights into Treatment Efficacy.

Hypoxia is a key characteristic of the tumor microenvironment, too rarely considered during drug development due to the lack of a user-friendly method to culture naturally hypoxic 3D tumor models. In this study, we used soft lithography to engineer a microfluidic platform allowing the culture of up to 240 naturally hypoxic tumor spheroids within an 80 mm by 82.5 mm chip.

Rapid quantitative assays for glucose-6-phosphate dehydrogenase (G6PD) and hemoglobin combined on a capillary-driven microfluidic chip.

Rapid tests for glucose-6-phosphate dehydrogenase (G6PD) are extremely important for determining G6PD deficiency, a widespread metabolic disorder which triggers hemolytic anemia in response to primaquine and tafenoquine medication, the most effective drugs for the radical cure of malaria caused by parasites. Current point-of-care diagnostic devices for G6PD are either qualitative, do not normalize G6PD activity to the hemoglobin concentration, or are very expensive. In this work we developed a capillary-driven microfluidic chip to perform a quantitative G6PD test and a hemoglobin measurement within 2 minutes and using less than 2 μL of sample.

X-ray on chip: Quantifying therapeutic synergies between radiotherapy and anticancer drugs using soft tissue sarcoma tumor spheroids.

Purpose: Radioresistance, tumor microenvironment, and normal tissue toxicity from radiation limit the efficacy of radiotherapy in treating cancers. These challenges can be tackled by the discovery of new radiosensitizing and radioprotecting agents aimed at increasing the therapeutic efficacy of radiotherapy. The goal of this work was to develop a miniaturized microfluidic platform for the discovery of drugs that could be used in combination with radiotherapy.

Carboplatin sensitivity in epithelial ovarian cancer cell lines: The impact of model systems.

Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy in North America, underscoring the need for the development of new therapeutic strategies for the management of this disease. Although many drugs are pre-clinically tested every year, only a few are selected to be evaluated in clinical trials, and only a small number of these are successfully incorporated into standard care. Inaccuracies with the initial in vitro drug testing may be responsible for some of these failures.

Pixel-based open-space microfluidics for versatile surface processing.

An increasing number of applications in biology, chemistry, and material sciences require fluid manipulation beyond what is possible with current automated pipette handlers, such as gradient generation, interface reactions, reagent streaming, and reconfigurability. In this article, we introduce the pixelated chemical display (PCD), a scalable strategy for highly parallel, reconfigurable liquid handling on open surfaces. Microfluidic "pixels" are created when a fluid stream injected above a surface is confined by neighboring identical fluid streams, forming a repeatable flow unit that can be used to tesselate a surface.

Adsorption-Desorption Behavior of Polar Imidazolinone Herbicides in Tropical Paddy Fields Soils.

Analysis of herbicides sorption behavior in soil is critical in predicting their fate and possible harmful side effects in the environment. Application of polar imidazolinone herbicides is growing in tropical agricultural fields. Imidazolinones have high leaching potential and are persistent.

Additive manufacturing of resonant fluidic sensors based on photonic bandgap waveguides for terahertz applications.

A hollow-core Bragg waveguide-based resonant fluidic sensor operating in the terahertz frequency band is studied. A fused deposition modeling 3D printing technique with a Polylactic Acid filament is employed to fabricate the sensor where the liquid analyte is flowing in the microfluidic channel integrated into the waveguide cladding. The fluidic channel supports a resonant defect state which is probed spectrally using the core-guided mode of the Bragg waveguide.

Self-coalescing flows in microfluidics for pulse-shaped delivery of reagents.

Microfluidic systems can deliver portable point-of-care diagnostics without the need for external equipment or specialist operators, by integrating all reagents and manipulations required for a particular assay in one device. A key approach is to deposit picogram quantities of dried reagents in microchannels with micrometre precision using specialized inkjet plotters. This means that reagents can be stored for long periods of time and reconstituted spontaneously when adding a liquid sample.

Long-term fluorescence hyperspectral imaging of on-chip treated co-culture tumour spheroids to follow clonal evolution.

Multicellular tumour spheroids are an ideal in vitro tumour model to study clonal heterogeneity and drug resistance in cancer research because different cell types can be mixed at will. However, measuring the individual response of each cell population over time is challenging: current methods are either destructive, such as flow cytometry, or cannot image throughout a spheroid, such as confocal microscopy. Our group previously developed a wide-field fluorescence hyperspectral imaging system to study spheroids formed and cultured in microfluidic chips.

Microfluidic multipoles theory and applications.

Microfluidic multipoles (MFMs) have been realized experimentally and hold promise for "open-space" biological and chemical surface processing. Whereas convective flow can readily be predicted using hydraulic-electrical analogies, the design of advanced microfluidic multipole is constrained by the lack of simple, accurate models to predict mass transport within them. In this work, we introduce the complete solutions to mass transport in multipolar microfluidics based on the iterative conformal mapping of 2D advection-diffusion around a simple edge into dipoles and multipolar geometries, revealing a rich landscape of transport modes.

On-chip combined radiotherapy and chemotherapy testing on soft-tissue sarcoma spheroids to study cell death using flow cytometry and clonogenic assay.

Radiotherapy (RT) and chemotherapy (CT) are the major therapeutics to treat cancer patients. Conventional in vitro 2D models are insufficient to study the combined effects of RT and CT towards optimized dose selection or drug screening. Soft-tissue sarcomas (STS) are rare cancers with profound social impacts as they affect patients of all ages.

Paraffin-embedding lithography and micro-dissected tissue micro-arrays: tools for biological and pharmacological analysis of ex vivo solid tumors.

There is an urgent need and strong clinical and pharmaceutical interest in developing assays that allow for the direct testing of therapeutic agents on primary tissues. Current technologies fail to provide the required sample longevity, throughput, and integration with standard clinically proven assays to make the approach viable. Here we report a microfluidic micro-histological platform that enables ex vivo culture of a large array of prostate and ovarian cancer micro-dissected tissue (MDT) followed by direct on-chip fixation and paraffination, a process we term paraffin-embedding lithography (PEL).

3D Printed Microfluidic Probes.

In this work, we fabricate microfluidic probes (MFPs) in a single step by stereolithographic 3D printing and benchmark their performance with standard MFPs fabricated via glass or silicon micromachining. Two research teams join forces to introduce two independent designs and fabrication protocols, using different equipment. Both strategies adopted are inexpensive and simple (they only require a stereolithography printer) and are highly customizable.