DNA probe detection within 3D hydrogel matrix in a hollow core photonic crystal fibre

In this paper, we report for the first time the detection of a Cy5-labelled DNA probe immobilised within a 3D hydrogel matrix formed, inside a hollow core Photonic Crystal Fibre (HC-PCF). We show both the sensitivity of fluorescence detection inside the HC-PCF using a supercontinuum light source and of the variation of the luminescence intensity with the concentration DNA probe within the hydrogel. The 3D hydrogel matrix is a network of polymer chains, which is expected to provide highly sensitive detection and selection of bio-molecules, in comparison with 2D coverage. The biocompatibility of hydrogel in the HC-PCF suggests numerous applications associated with immobilised DNA probe detection for point-of-care or remote systems

Toward accurate cerebral blood flow estimation in mice after accounting for anesthesia

Purpose: To improve the accuracy of cerebral blood flow (CBF) measurement in mice by accounting for the anesthesia effects.Methods: The dependence of CBF on anesthesia dose and time was investigated by simultaneously measuring respiration rate (RR) and heart rate (HR) under four different anesthetic regimens. Quantitative CBF was measured by a phase-contrast (PC) MRI technique. RR was evaluated with a mouse monitoring system (MouseOX) while HR was determined using an ultrashort-TE MRI sequence. CBF, RR, and HR were recorded dynamically with a temporal resolution of 1 min in a total of 19 mice. Linear regression models were used to investigate the relationships among CBF, anesthesia dose, RR, and HR.Results: CBF, RR, and HR all showed a significant dependence on anesthesia dose (p < 0.0001). However, the dose in itself was insufficient to account for the variations in physiological parameters, in that they showed a time-dependent change even for a constant dose. RR and HR together can explain 52.6% of the variations in CBF measurements, which is greater than the amount of variance explained by anesthesia dose (32.4%). Based on the multi-parametric regression results, a model was proposed to correct the anesthesia effects in mouse CBF measurements, specifically CBFcorrected=CBF+0.58RR−0.41HR−32.66Dose. We also reported awake-state CBF in mice to be 142.0 ± 8.8 mL/100 g/min, which is consistent with the model-predicted value.Conclusion: The accuracy of CBF measurement in mice can be improved by using a correction model that accounts for respiration rate, heart rate, and anesthesia dose

Designing Artificial Two-Dimensional Landscapes via Room-Temperature Atomic-Layer Substitution

Manipulating materials with atomic-scale precision is essential for the development of next-generation material design toolbox. Tremendous efforts have been made to advance the compositional, structural, and spatial accuracy of material deposition and patterning. The family of 2D materials provides an ideal platform to realize atomic-level material architectures. The wide and rich physics of these materials have led to fabrication of heterostructures, superlattices, and twisted structures with breakthrough discoveries and applications. Here, we report a novel atomic-scale material design tool that selectively breaks and forms chemical bonds of 2D materials at room temperature, called atomic-layer substitution (ALS), through which we can substitute the top layer chalcogen atoms within the 3-atom-thick transition-metal dichalcogenides using arbitrary patterns. Flipping the layer via transfer allows us to perform the same procedure on the other side, yielding programmable in-plane multi-heterostructures with different out-of-plane crystal symmetry and electric polarization. First-principle calculations elucidate how the ALS process is overall exothermic in energy and only has a small reaction barrier, facilitating the reaction to occur at room temperature. Optical characterizations confirm the fidelity of this design approach, while TEM shows the direct evidence of Janus structure and suggests the atomic transition at the interface of designed heterostructure. Finally, transport and Kelvin probe measurements on MoXY (X,Y=S,Se; X and Y corresponding to the bottom and top layers) lateral multi-heterostructures reveal the surface potential and dipole orientation of each region, and the barrier height between them. Our approach for designing artificial 2D landscape down to a single layer of atoms can lead to unique electronic, photonic and mechanical properties previously not found in nature

A Fast Assay to Determine Infliximab Trough Level using Fiber-Optic Surface Plasmon Resonance Sensor

Therapeutic monoclonal antibodies, such as Infliximab (IFX) are highly effective for treating inflammatory bowel disease patients. It is recommended to monitor the trough level of IFX for improving therapeutic outcome of the bimonthly treatment [1]. The conventionally used ELISA assay is time-consuming and not optimal for single patient testing. Here, we present a fiber-optic surface plasmon resonance (FO-SPR) sensor [2] as a potential point-of-care diagnostic tool (Figure 1). On this platform, surface plasmon waves are generated at the interface of an optical fiber/gold layer (50 nm). On top of this gold layer through a self-assembly monolayer (SAM), an in-house developed IFX-specific monoclonal antibody is immobilized to establish a sandwich immunoassay. Analysis was performed on IFX spiked serum using 100 fold diluted serum obtained from healthy volunteers. The signal was specifically amplified by a second IFX-specific detection antibody conjugated to 20 nm gold nanoparticles. An IFX calibration curve in 100-fold diluted serum was made, ranging from 0 to 75 ng/ml, using a single fiber with surface regeneration in between measurements. The limit of detection from 6 calibration curves (Figure 2) was 2.17 ng/ml, corresponding to 0.22 g/ml in the whole serum. This bio-assay was further validated with 5 patient samples and corresponding IFX concentrations were determined based on the FO-SPR calibration curves. This work demonstrates the potential of the FO-SPR platform to be used at the point-of-care for improving the therapeutic outcome of patients treated with IFX.status: publishe

Development and validation of an optical biosensor for rapid monitoring of adalimumab in serum of patients with Crohn's disease

Therapeutic drug monitoring of adalimumab is recommended to improve therapeutic outcome in patients with Crohn's disease. Performing an ELISA requires a rather long time-to-result and the necessity of collecting multiple samples to decrease the cost per adalimumab determination. In this study, we aim to develop and validate a rapid assay suitable for measuring a single adalimumab serum sample using a fiber-optic surface plasmon resonance (FO-SPR) based sensor. Therefore, we have immobilized MA-ADM28B8 as capture antibody on an FO-probe and conjugated MA-ADM40D8 as detecting antibody to gold nanoparticles. A dose-response curve ranging from 2.5 to 40 ng/mL adalimumab was obtained in 1/400 diluted serum. Serum samples of patients with adalimumab concentrations between 1 and 16 μg/mL were measured whereas the negative control, a sample spiked with infliximab at a concentration of 16 μg/mL, showed no significant signal. Using a pre-functionalized FO-probe, the technology requires less than 45 minutes for measuring a single sample. Comparison of measurements between the biosensor and the ELISA revealed an excellent agreement with a Pearson r coefficient of 0.99 and an intra-class coefficient of 0.99. The reduced assay time and the possibility of measuring a single sample are major advantages compared to the ELISA. The developed and validated optical adalimumab biosensor could be a valuable point-of-care diagnostic tool for adalimumab quantification in patients with Crohn's disease.status: publishe

The roles of tumor-derived exosomes in non-small cell lung cancer and their clinical implications

Abstract Non-small cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer cases, and it is one of the leading causes of cancer death in both men and women worldwide due to diagnosis in the advanced stage, rapid metastasis, and recurrence. At present, precision molecular targeted therapeutics directed toward NSCLC driven genes has made great progress and significantly improved the overall survival of patients with NSCLC, but can easily lead to acquired drug resistance. New methods are needed to develop real-time monitoring of drug efficacy and drug resistance, such as new molecular markers for more effective early detection and prediction of prognosis. Exosomes are nano-sized extracellular vesicles, containing proteins, nucleic acids and lipids, which are secreted by various cells, and they play an important role in the development of lung cancer by controlling a wide range of pathways. Tumor-derived exosomes are of great significance for guiding the targeted therapy of NSCLC and exosomes themselves can be a target for treatment. In this review, we describe the potential roles of tumor-derived exosomes and their clinical significance in NSCLC