Liquid biopsy, as a minimally invasive method of gleaning insight into the dynamics of diseases through a patient fluid sample, has been growing in popularity for cancer diagnosis, prognosis, and monitoring. While many technologies have been developed and validated in research laboratories, there has also been a push to expand these technologies into other clinical settings and as point of-care devices. In this review we discuss and evaluate microchip-based technologies for circulating tumor cell (CTC), exosome, and circulating tumor nucleic acid (ctNA) capture, detection, and analysis. Such integrated systems streamline otherwise multiple-step, manual operations to get a sample-to-answer quantitation. In addition, analysis of disease biomarkers is suited to point of care settings because of ease of use, low consumption of sample and reagents, and high throughput. We also cover the basics of biomarkers and their detection in biological fluid samples suitable for liquid biopsy on-chip. We focus on emerging technologies that process a small patient sample with high spatial-temporal resolution and derive clinically meaningful results through on-chip biomarker sensing and downstream molecular analysis in a simple workflow. This critical review is meant as a resource for those interested in developing technologies for capture, detection, and analysis platforms for liquid biopsy in a variety of settings.
Abstract. We employed direct numerical simulations to estimate the error on chemical calculation in simulations with regional chemical-transport models induced by neglecting subgrid chemical segregation due to inefficient turbulent mixing in an urban boundary layer with strong and heterogeneously distributed surface emissions. In simulations of initially segregated reactive species with an entrainment-emission configuration with an A–B–C second-order chemical scheme, urban surface emission fluxes of the homogeneously emitted tracer A result in a very large segregation between the tracers and hence a very large overestimation of the effective chemical reaction rate in a complete-mixing model. This large effect can be indicated by a large Damköhler number (Da) of the limiting reactant. With heterogeneous surface emissions of the two reactants, the resultant normalised boundary-layer-averaged effective chemical reaction rate is found to be in a Gaussian function of Da, and it is increasingly overestimated by the imposed rate with an increased horizontal scale of emission heterogeneity. Coarse-grid models with resolutions commensurable to regional models give reduced yet still significant errors for all simulations with homogeneous emissions. Such model improvement is more sensitive to the increased vertical resolution. However, such improvement cannot be seen for simulations with heterogeneous emissions when the horizontal resolution of the model cannot resolve emission heterogeneity. This work highlights particular conditions in which the ability to resolve chemical segregation is especially important when modelling urban environments.
Abstract. Global and regional chemical transport models of the atmosphere are based on the assumption that chemical species are completely mixed within each model grid box. However, in reality, these species are often segregated due to localized sources and the influence of topography. In order to investigate the degree to which the rates of chemical reactions between two reactive species are reduced due to the possible segregation of species within the convective boundary layer, we perform large-eddy simulations (LESs) in the mountainous region of Hong Kong Island. We adopt a simple chemical scheme with 15 primary and secondary chemical species, including ozone and its precursors. We calculate the segregation intensity due to inhomogeneity in the surface emissions of primary pollutants and due to turbulent motions related to topography. We show that the inhomogeneity in the emissions increases the segregation intensity by a factor of 2–5 relative to a case in which the emissions are assumed to be uniformly distributed. Topography has an important effect on the segregation locally, but this influence is relatively limited when considering the spatial domain as a whole. In the particular setting of our model, segregation reduces the ozone formation by 8 %–12 % compared to the case with complete mixing, implying that the coarse-resolution models may overestimate the surface ozone when ignoring the segregation effect.
Abstract. We employed direct numerical simulations to estimate the error on chemical calculation in simulations with regional chemical-transport models induced by neglecting subgrid chemical segregation due to inefficient turbulent mixing in an urban boundary layer with strong and heterogeneously-distributed surface emissions. In simulations of initially-segregated reactive species with an entrainment-emission configuration with an A–B–C second-order chemical scheme, urban surface emission fluxes of the homogeneously-emitted Tracer A result in a very large segregation between the tracers and hence a very large overestimation of the effective chemical reaction rate in a complete-mixing model. This large effect can be indicated by a large Damköhler number (Da) of the limiting reactant. With heterogeneous surface emissions of the two reactants, the resultant normalised boundary layer-averaged effective chemical reaction rate is found to be in a Gaussian function of Da, and is increasingly overestimated by the imposed rate with an increased horizontal scale of emission heterogeneity. Coarse-grid models with resolutions commensurable to regional models give reduced yet still significant errors for all simulations with homogeneous emissions. Such model improvement is more sensitive to the increased vertical resolution. However, such improvement cannot be seen for simulations with heterogeneous emissions when the horizontal resolution of the model cannot resolve emission heterogeneity. This work highlights particular conditions in which the ability to resolve chemical segregation is especially important when modelling urban environments.
Previously compound I showed great anti-glioblastoma activity without toxicity in a mouse xenograft study. In this study, a sensitive and rapid high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed and validated to investigate the pharmacokinetics and brain distribution of compound I in mice. The protein precipitation method was applied to extract the compound from mouse plasma and brain homogenates, and it was then separated
Abstract. To perform realistic high-resolution air quality modeling in a polluted urban area, the WRF (Weather Research and Forecasting) model is used with an embedded large-eddy simulation (LES) module and with online chemistry. As an illustration, a numerical experiment is conducted in the megacity Hong Kong, which is characterized by multi-type pollution sources as well as complex topography. The multi-resolution simulations from mesoscale to LES scales are evaluated by comparing to ozone sounding profiles and surface observations. The comparisons show that both mesoscale and LES simulations reproduce well the mean concentrations of the chemical species and their diurnal variations at the background stations. However, the mesoscale simulations largely underestimate the NOX concentrations and overestimate O3 at the roadside stations due to the coarse representation of the traffic emissions. The LES simulations improve the agreement with the measurements near the road traffic, and the LES with the highest spatial resolution (33.3 m) provides the best results. The LES simulations show more detailed structures in the spatial distributions of chemical species than the mesoscale simulations, highlighting the capability of LES to resolve high-resolution photochemical transformations in urban areas. Compared to the mesoscale model results, the LES simulations show similar evolutions in the profiles of the chemical species as a function of the boundary layer development over a diurnal cycle.
Abstract. To perform realistic high-resolution air quality modeling in a polluted urban area, the Weather Research and Forecasting (WRF) model is used with an embedded large-eddy simulation (LES) module and online chemistry. As an illustration, a numerical experiment is conducted in the megacity of Hong Kong, which is characterized by multi-type inhomogeneous pollution sources and complex topography. The results from the multi-resolution simulations at mesoscale and LES scales are evaluated by comparing them with ozone sounding profiles and surface observations. The comparisons show that both mesoscale and LES simulations reproduce the mean concentrations of the chemical species and their diurnal variations at the background stations well. However, the mesoscale simulations largely underestimate the NOx concentrations and overestimate O3 at the roadside stations due to the coarse representation of the traffic emissions. The LES simulations improve the agreement with the measurements near the road traffic, and the LES with the highest spatial resolution (33.3 m) provides the best results. The large-eddy simulations show more detailed structures in the spatial distributions of chemical species than the mesoscale simulations, highlighting the capability of LES to resolve high-resolution photochemical transformations in urban areas. Compared to the mesoscale model results, the LES simulations show similar evolutions in the profiles of the chemical species as a function of the boundary layer development over a diurnal cycle.
Abstract. Global and regional chemical transport models of the atmosphere are based on the assumption that chemical species are completely mixed within each model grid box. However, in reality, these species are often segregated due to localized sources and the influence of the topography. In order to investigate the degree to which the rates of chemical reactions between two reactive species are reduced due to the possible segregation of species within the convective boundary layer, we perform large-eddy simulations (LES) in the mountainous region of the Hong Kong island. We adopt a simple chemical scheme with 15 primary and secondary chemical species including ozone and its precursors. We calculate the segregation intensity due to inhomogeneity in the surface emissions of primary pollutants and due to turbulent motions related to topography. We show that the inhomogeneity in the emissions increases the segregation intensity by a factor 2–5 relative to a case in which the emissions are assumed to be uniformly distributed. Topography has an important effect on the segregation locally, but this influence is relatively limited when considering the spatial domain as a whole.
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