Particle manipulation using acoustophoresis has emerged as a pivotal technology in microsystems engineering, garnering significant attention across soft matter physics, biomedical diagnostics, and lab-on-a-chip applications. The operational efficacy of acoustofluidic tweezers platforms hinges on the precise control of the critical particle size threshold that governs the transition between radiation-force-dominated trapping and streaming-mediated transport. Through systematic numerical investigations in rectangular microchannels with two-dimensional (2D) confinement, this study establishes quantitative correlations between critical radius thresholds and geometric parameters in coupled standing-wave fields. The critical radius demarcates two distinct transport regimes: (i) Supercritical particles ( ) achieve stable nodal trapping via dominant radiation forces, independent of initial spatial distribution; (ii) subcritical particles ( ) undergo continuous advection through streaming vortices. Our multiphysics framework combines finite element modeling with analytical validation through boundary-layer force equilibrium analysis, revealing three key findings: First, geometric confinement induces characteristic scaling laws ( with being the channel size) for one-dimensional (1D) standing waves, confirmed through parametric studies ( : 0.1-5.1mm). Second, 1D models maintain predictive accuracy (with discrepancies ) for systems with wavelength ratios or , but fail in coupled-mode fields ( ) where maximum discrepancies reach . Third, orthogonal wave superposition in 2D configurations reduces by suppressing streaming velocities, particularly at . These insights advance fundamental understanding of size-selective acoustophoresis while providing engineering guidelines for performance optimization in acoustic tweezers design.

In diabetes management, oral formulation of insulin (INS) has the potential to improve safety, convenience, and patient-centered care compared to subcutaneous injections. However, its bioavailability remains limited, necessitating improved delivery strategies. Recent clinical trials indicate that taurocholic acid (TCA) can enhance the bioavailability of oral INS as an absorption enhancer. In this work, electrospray ionization mass spectrometry (ESI-MS) analysis revealed the formation of 1:1-1:4 INS-TCA complexes. MS/MS was used to explore the fragmentation pathway of complex ions and confirm binding stability in the gas phase. Circular dichroism spectra showed no clear conformational change in INS upon TCA binding, even though TCA enhanced INS's structural stability. Using Taylor dispersion analysis (TDA), we determined the diffusion coefficient and hydrodynamic radius of INS and its complexes. TCA binding was observed to increase INS size in both the 1:1 and 1:2 INS-TCA complexes. The binding constant of INS and TCA (1.3 × 103 L/mol) with approximately five binding sites was obtained via pressure-assisted capillary electrophoresis frontal analysis. Molecular docking simulations indicated that TCA binds to external binding sites on the INS B chain (near Ser-B9, Glu-B13, and Phe-B24 residues), consistent with ESI-MS and TDA results. These findings suggest that TCA binding may enhance INS absorption and increase the bioavailability of oral INS therapy.

Cancer cells that have separated from the main tumor and entered the bloodstream are known as circulating tumor cells (CTCs). Once there, they may spread to other parts of the body and cause metastases. This work proposes a novel inertial-based dielectrophoresis (DEP) device designed for the separation of CTCs from red blood cells (RBCs). The microchannel features a rectangular zigzag segment combined with a circular curved section, optimized to improve separation efficiency by integrating inertial and DEP forces. Numerical simulations are conducted to evaluate the effects of microchannel depth, applied voltage and frequency, and Reynolds number (Re) on the separation efficiency and trajectory of cells. The simulations identify four optimal scenarios that achieve 100% separation efficiency. Early cancer diagnosis and treatment may benefit from the use of the proposed device for CTC detection.

It is of fundamental importance to study and understand the behavior of falling droplets. External fields, such as electric and magnetic fields, are considered promising methods for controlling falling droplets, especially at small scales. Although some experimental and theoretical work on falling droplets in an electric field has been conducted, a fully numerical model for electrohydrodynamic falling droplets is still lacking. In this article, we proposed a phase field numerical model and studied the falling droplets in a vertical electric field. In particular, the influence of the electric field on the velocity and interfacial morphology of the falling droplets was investigated. It was found that the vertical electric field can elongate the droplet in the vertical direction and increase its falling velocity. With a weak or no electric field (the electrical capillary number CaE<1.0), an indentation appears on the top of the falling droplet, and the droplet evolves into a bowl-like structure. In contrast, a strong electric field (CaE≥1.0) causes a protrusion on the droplet, transforming it into a thumbtack-like shape. The numerical model and the obtained results can improve our understanding of falling droplets and highlight potential ways to regulate their behaviors.

9-Methylfascaplysin, a derivative of the marine natural product fascaplysin, has shown promising anti- Alzheimer's disease (AD) potential through its anti-β-amyloid (Aβ) neuroprotective effects. However, the pharmacokinetics (PK) of 9-methylfascaplysin, crucial for its preclinical evaluation, have not been thoroughly studied. In this study, we developed and validated a sensitive and accurate ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the quantification of 9-methylfascaplysin in rat plasma. The method demonstrated a lower limit of detection (LLOD) of 1ng/mL and a linear quantification range of 5-2000ng/mL. The PK study in rat plasma was conducted. After intragastric administration, the plasma concentration of 9-methylfascaplysin peaked at a maximum concentration (Cmax) of 193.4ng/m and an enterohepatic circulation (EHC) phenomenon was observed. By comparing the area under the plasma concentration-time curve (AUC) values obtained from intragastric and intravenous administrations, the absolute oral bioavailability (F) of 9-methylfascaplysin was determined as 18.3%. The tissue distribution study revealed that following a single intragastric administration, 9-methylfascaplysin was most concentrated in the stomach, followed by the small intestine, large intestine, liver, kidney, brain, lung, spleen, and heart in descending order. Furthermore, the excretion profiles of 9-methylfascaplysin in rat urine and feces were studied. The results of this study provide valuable insights into the PK behavior of 9-methylfascaplysin and serve as a foundation for its further preclinical evaluation and potential clinical application as an anti-AD agent.

Dielectrophoresis (DEP) has been extensively researched over the years for filtration, separation, detection, and collection of micro/nano/bioparticles. Numerical models have historically been employed to predict particle trajectories in three-dimensional (3D) DEP systems, but a common issue arises due to inherent noise near the edges of electrodes due to electric potential discontinuity, specifically when calculating electric field and gradient of electric field-squared, . This noise can be reduced to a certain extent with a finer mesh density but results near the electrode edge still have significant error. Realizing the importance of particle-electrode edge interactions prevalent in positive DEP systems, analytical solutionsgivenby Sun etal. was incorporated to demonstrate an improved 3D model of interdigitated electrodes. The results of electric field and gradient of electric field-squared of the numerical model and the improved analytical 3D model were compared, within a simulation space of 50 µm height, 10 µm width, and 50 µm length with interdigitated electrodes of the same width and gap of 10 µm. The DEP particle trajectory error due to the noise was quantified for different particle sizes at various heights above the electrode edge. For example, at 5 Vrms, a trapped 500nm particles exhibited a velocity error of 104 µm/s (it should have been zero).

A significant limitation of imaged capillary electric focusing (icIEF) is the inability to identify and characterize specific species in the electropherogram. This has led to the development of complementary ion-exchange chromatography (IEX)-based methods that are amenable to either fraction collection and subsequent characterization or online IEX coupled to mass spectrometry. To overcome this limitation while maintaining the use of icIEF, novel approaches, including an icIEF separation and fractionation technology (MauriceFlex, ProteinSimple), have been developed. This approach enables the fractionation of various icIEF peaks, which can then be characterized by mass spectrometry to confirm the identity of the separated charged species. Herein, the MauriceFlex technology was applied to adeno-associated viral (AAV) gene therapy products, which contain a DNA transgene packaged into a protein capsid and have shown tremendous therapeutic potential in recent years. Utilizing the MauriceFlex system, we developed an approach for the separation of charged species from AAV capsid viral proteins (VP) by icIEF and subsequent characterization by liquid chromatography and mass spectrometry (LC-MS). When applying the same sample preparation, charge profiles of AAV capsid proteins on the MauriceFlex instrument were demonstrated to be consistent with those from the original Maurice platform, the industrial gold standard. Optimization of the VP icIEF fractionation method required the development of a method for low concentration samples, optimization of mobilization conditions, enhancement of fraction recovery, and maintenance of protein stability post fractionation. Herein, we were able to successfully collect charge-separated VP fraction samples and subsequently analyze them by MS analysis. In addition, a workflow for AAV capsid protein characterization based on icIEF separation and fractionation coupled with downstream LC-MS has been established for the confirmation of VP identity and additional characterization of capsid protein heterogeneity.

Western flower thrips, Frankliniella occidentalis (Thysanoptera: Thripidae) is an invasive agricultural pest with developed resistance to abamectin in some strains due to frequent treatment with the pesticide. In this study, we examined differentially expressed proteins (DEPs) between abamectin-resistant (AbaR; under abamectin selective pressure) and susceptible strains (AbaS; without abamectin selective pressure) of F. occidentalis. Proteins were isolated from second instar larvae of both strains and separated via two-dimensional polyacrylamide gel electrophoresis. Nano-flow liquid chromatography-tandem mass spectrometry identified selected protein spot features. From 70 DEPs, 43 spot features were identified: A total of 23 showed an increase in abundance, and 20 were down-regulated in response to abamectin pressure. The enzymatic and structural proteins were classified into the functional groups of macromolecular metabolisms, signaling and cellular processes, immune system, genetic information processing, and exoskeleton-related proteins. The up-regulation of exoskeleton-related proteins may contribute to forming a thicker cuticle, potentially hindering abamectin penetration, which is an interesting finding that needs further investigation. Two novel proteins, triacylglycerol lipase and cuticle protein CPF 2, were only expressed in AbaR. This work provides insights into abamectin resistance mechanisms in F. occidentalis, which will provide important information for developing insecticide resistance management approaches for this pest.