A hydrogel-based optical fibre fluorescent pH sensor for observing lung tumor tissue acidity

Technologies for measuring physiological parameters in vivo offer the possibility of the detection of disease and its progression due to the resulting changes in tissue pH, or temperature, etc. Here, a compact hydrogel-based optical fibre pH sensor was fabricated, in which polymer microarrays were utilized for the high-throughput discovery of an optimal matrix for pH indicator immobilization. The fabricated hydrogel-based probe responded rapidly to pH changes and demonstrated a good linear correlation within the physiological pH range (from 5.5 to 8.0) with a precision of 0.10 pH units. This miniature probe was validated by measuring pH across a whole ovine lung and allowed discrimination of tumorous and normal tissue, thus offering the potential for the rapid and accurate observation of tissue pH changes.</p

Polymer Microarrays for the Discovery and Optimization of Robust Optical-Fiber-Based pH Sensors

Polymer microarrays were utilized for the high-throughput screening and discovery of optimal polymeric substrates capable of trapping functional ratiometric fluorescence-based pH sensors. This led to the identification of poly­(methyl methacrylate-<i>co</i>-2-(dimethylamino) ethyl acrylate) (<b>PA101</b>), which allowed, via dip coating, the attachment of fluorescent pH sensors onto the tips of optical fibers, resulting in robust, rapid, and reproducible sensing of physiological pHs

Rapid detection of major Gram-positive pathogens in ocular specimens using a novel fluorescent vancomycin-based probe

Bacterial infections of the eye are significant causes of morbidity that can lead to permanent visual loss without rapid and adequate treatment, with Gram-positive bacteria causing the majority of ocular infections. Here we report a novel probe, based on the reductive amination of vancomycin with a 4-nitrobenzoxadiazole (NBD)-based aldehyde, that rapidly and specifically detects Gram positive infections from ocular samples

Development of hydrogel-based standards and phantoms for non-linear imaging at depth

Significance: Rapid advances in medical imaging technology, particularly the development of optical systems with non-linear imaging modalities, are boosting deep tissue imaging. The development of reliable standards and phantoms is critical for validation and optimization of these cutting-edge imaging techniques. Aim: We aim to design and fabricate flexible, multi-layered hydrogel-based optical standards and evaluate advanced optical imaging techniques at depth. Approach: Standards were made using a robust double-network hydrogel matrix consisting of agarose and polyacrylamide. The materials generated ranged from single layers to more complex constructs consisting of up to seven layers, with modality-specific markers embedded between the layers. Results: These standards proved useful in the determination of the axial scaling factor for light microscopy and allowed for depth evaluation for different imaging modalities (conventional one-photon excitation fluorescence imaging, two-photon excitation fluorescence imaging, second harmonic generation imaging, and coherent anti-Stokes Raman scattering) achieving actual depths of 1550, 1550, 1240, and 1240 μm, respectively. Once fabricated, the phantoms were found to be stable for many months. Conclusions: The ability to image at depth, the phantom's robustness and flexible layered structure, and the ready incorporation of "optical markers" make these ideal depth standards for the validation of a variety of imaging modalities

Synthetic Polymers Provide a Robust Substrate for Functional Neuron Culture

Substrates for neuron culture and implantation are required to be both biocompatible and display surface compositions that support cell attachment, growth, differentiation, and neural activity. Laminin, a naturally occurring extracellular matrix protein is the most widely used substrate for neuron culture and fulfills some of these requirements, however, it is expensive, unstable (compared to synthetic materials), and prone to batch-to-batch variation. This study uses a high-throughput polymer screening approach to identify synthetic polymers that supports the in vitro culture of primary mouse cerebellar neurons. This allows the identification of materials that enable primary cell attachment with high viability even under “serum-free” conditions, with materials that support both primary cells and neural progenitor cell attachment with high levels of neuronal biomarker expression, while promoting progenitor cell maturation to neurons.Biomaterials & Tissue Biomechanic

Long-term feeder-free culture of human pancreatic progenitors on fibronectin or matrix-free polymer potentiates β cell differentiation

With the aim of producing β cells for replacement therapies to treat diabetes, several protocols have been developed to differentiate human pluripotent stem cells to β cells via pancreatic progenitors. While in&nbsp;vivo pancreatic progenitors expand throughout development, the in&nbsp;vitro protocols have been designed to make these cells progress as fast as possible to β cells. Here, we report on a protocol enabling a long-term expansion of human pancreatic progenitors in a defined medium on fibronectin, in the absence of feeder layers. Moreover, through a screening of a polymer library we identify a polymer that can replace fibronectin. Our experiments, comparing expanded progenitors to directly differentiated progenitors, show that the expanded progenitors differentiate more efficiently into glucose-responsive β cells and produce fewer glucagon-expressing cells. The ability to expand progenitors under defined conditions and cryopreserve them will provide flexibility in research and therapeutic production

Novel bead-based platform for direct detection of unlabelled nucleic acids through Single Nucleobase Labelling

Over the last decade, circulating microRNAs have received attention as diagnostic and prognostic biomarkers. In particular, microRNA122 has been demonstrated to be an early and more sensitive indicator of drug-induced liver injury than the widely used biomarkers such as alanine aminotransferase and aspartate aminotransferase. Recently, microRNA122 has been used in vitro to assess the cellular toxicity of new drugs and as a biomarker for the development of a rapid test for drug overdose/liver damage. In this proof-of-concept study, we report a PCR-free and label-free detection method that has a limit of detection (3 standard deviations) of 15 fmoles of microRNA122, by integrating a dynamic chemical approach for "Single Nucleobase Labelling" with a bead-based platform (Luminex®) thereby, in principle, demonstrating the exciting prospect of rapid and accurate profiling of any microRNAs related to diseases and toxicology

Polymer Microarrays for the Discovery and Optimization of Robust Optical-Fiber-Based pH Sensors

Polymer microarrays were utilized for the high-throughput screening and discovery of optimal polymeric substrates capable of trapping functional ratiometric fluorescence-based pH sensors. This led to the identification of poly(methyl methacrylate-co-2-(dimethylamino) ethyl acrylate) (PA101), which allowed, via dip coating, the attachment of fluorescent pH sensors onto the tips of optical fibers, resulting in robust, rapid, and reproducible sensing of physiological pHs.</p