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Precise prediction of the hindered diffusion behavior of electroneutral particles in fibrous media plays a critical role in the development of drugs, polymer membranes, and porous electrodes. However, the random microstructure and unknown coupling relationship of multiple resistance mechanisms lead to the lack of a universal prediction model. In this work, a dual-resistance model is proposed by reconstructed pore-scale simulations, which presents the coexistence of steric and hydrodynamic resistances in the multiplication form. The simulation results show that the relationship between steric resistance and structural parameters (porosity, fiber radius, and particle radius) is exponential, while that for hydrodynamic resistance is polynomial. The dominant diffusion resistance is found to change from hydrodynamic to steric resistance with a decrease in porosity. The fluorescent polystyrene microsphere diffusivity in a series of SiO2 fibrous media is determined by single-particle tracking experiments, quantitatively confirming the dual-resistance model. The present model can be used for rapid diffusivity prediction and fibrous membrane and drug design. [ABSTRACT FROM AUTHOR]

Lateral flow assays (LFAs) are promising candidates in biomedical diagnosis fields due to their rapid, low-cost, and portable features. However, improving their sensitivity remains challenging due to the unclear roles of capture probes with different distribution formats on the particle transfer and capturing in the test line. Therefore, we designed experiments and observed an asymmetrical U-shaped distribution of control probes throughout the NC membrane thickness. Based on this outcome, a two-dimensional mathematical model based on the Langmuir surface reaction kinetics was developed to investigate the effect of capture probe distributions on LFA performance. A two-dimensional model was qualitatively validated by comparing with the experimental results and the simulations of the reported one-dimensional model. Then, a higher detection signal was achieved by using the U-shaped distribution of capture probes throughout the NC membrane thickness instead of a uniform distribution. Furthermore, when the NC membrane thickness was less than 110 μm, the ratio of the detection signal in the visible region to the signal in the total section at the test line was above 13%. A thin NC membrane will produce a strong detection signal in the visible region at the test line. The developed model is capable of providing direct predictions in designing highly sensitive LFAs. [ABSTRACT FROM AUTHOR]

Lateral flow assays (LFAs) have attracted considerable attention in biomedical diagnostics. However, it's still challenging to achieve a high detection sensitivity and extensive working range, mainly because the underlying mechanism of complex reaction processes in LFAs remains unclear. Many mathematical models have been developed to analyze the complex reaction processes, which are only qualitative with limited guidance for LFA design. Now, a semi-quantitative convection-diffusion-reaction model is developed by considering the kinetics of renaturation of nucleic acids and the model is validated by our experiments. We established a method to convert the LFA design parameters between the simulation and experiment (i.e., inlet reporter particle concentration, initial capture probe concentration, and association rate constant), with which we achieved a semi-quantitative comparison of the detection limit and working range between simulations and experiments. Based on our model, we have improved the detection sensitivity and working range by using high concentrations of the inlet reporter particles and initial capture probe. Besides, we also found that target nucleic acid sequences with a high association rate constant are beneficial to improve the LFA performance. The developed model can predict the detection limit and working range and would be helpful to optimize the design of LFAs. [ABSTRACT FROM AUTHOR]

Nucleic acid testing (NAT) has been widely used for disease diagnosis, food safety control and environmental monitoring. At present, NAT mainly involves nucleic acid extraction, amplification and detection steps that heavily rely on large equipment and skilled workers, making the test expensive, time-consuming, and thus less suitable for point-of-care (POC) applications. With advances in paper-based microfluidic technologies, various integrated paper-based devices have recently been developed for NAT, which however require off-chip reagent storage, complex operation steps and equipment-dependent nucleic acid amplification, restricting their use for POC testing. To overcome these challenges, we demonstrate a fully disposable and integrated paper-based sample-in-answer-out device for NAT by integrating nucleic acid extraction, helicase-dependent isothermal amplification and lateral flow assay detection into one paper device. This simple device allows on-chip dried reagent storage and equipment-free nucleic acid amplification with simple operation steps, which could be performed by untrained users in remote settings. The proposed device consists of a sponge-based reservoir and a paper-based valve for nucleic acid extraction, an integrated battery, a PTC ultrathin heater, temperature control switch and on-chip dried enzyme mix storage for isothermal amplification, and a lateral flow test strip for naked-eye detection. It can sensitively detect Salmonella typhimurium, as a model target, with a detection limit of as low as 102 CFU ml−1 in wastewater and egg, and 103 CFU ml−1 in milk and juice in about an hour. This fully disposable and integrated paper-based device has great potential for future POC applications in resource-limited settings. [ABSTRACT FROM AUTHOR]

Understanding the underlying mechanism of nanomedicine–biomembrane interactions is important for the design and optimization of payload delivery systems. This study investigates the interactions between polyamidoamine (PAMAM) dendrimer–paclitaxel conjugates and biomembranes using coarse-grained molecular dynamics simulations. We found that acidic conditions (e.g., pH ∼ 5) and membrane asymmetry can improve the conjugate penetration. Paclitaxel (PTX) distributions on a G4 PAMAM dendrimer can affect interactions via the penetration mechanism, although they have no significant effect on interactions via the adsorption mechanism. The random distribution of PTX can enhance the ability of PTX molecules to pass through asymmetric membranes. Furthermore, the penetration process becomes more difficult with increasing paclitaxel loading ratios. These results provide molecular insights into the precise translocation mechanism of dendrimer–drug conjugates and thus provide suggestions for drug design and delivery. [ABSTRACT FROM AUTHOR]