Arteriovenous malformations (AVMs) are fragile direct connections between arteries and veins that arise during times of active angiogenesis. To understand the etiology of AVMs and the role of blood flow in their development, we analyzed AVM development in zebrafish embryos harboring a mutation in activin receptor-like kinase I (alk1), which encodes a TGFβ family type I receptor implicated in the human vascular disorder hereditary hemorrhagic telangiectasia type 2 (HHT2). Our analyses demonstrate that increases in arterial caliber, which stem in part from increased cell number and in part from decreased cell density, precede AVM development, and that AVMs represent enlargement and stabilization of normally transient arteriovenous connections. Whereas initial increases in endothelial cell number are independent of blood flow, later increases, as well as AVMs, are dependent on flow. Furthermore, we demonstrate that alk1 expression requires blood flow, and despite normal levels of shear stress, some flow-responsive genes are dysregulated in alk1 mutant arterial endothelial cells. Taken together, our results suggest that Alk1 plays a role in transducing hemodynamic forces into a biochemical signal required to limit nascent vessel caliber, and support a novel two-step model for HHT-associated AVM development in which pathological arterial enlargement and consequent altered blood flow precipitate a flow-dependent adaptive response involving retention of normally transient arteriovenous connections, thereby generating AVMs.

Contemporary lab-chip devices require efficient, high-performance mixing capability. A series of artificial cilia with embedded magnetic particles was fabricated to achieve precise flow manipulation through magnetically driven control. These fabricated structures were actuated in a homogeneous magnetic field generated by a built-in magnetic coil system for various beating cycles inside a microchannel. Three representative trajectories, namely, circular motion, back-and-forth oscillation, and a figure-of-eight pattern, of artificial cilia were designed and generated to mimic the motion of actual cilia. Homogeneous mixing of two highly viscous (>25 centipoise) dyed solutions by using the figure-of-eight trajectory achieved a mixing efficiency of approximately 86%. The underlying relationship between ciliated structures and the induced flow fields was further elucidated by performing a hydrodynamic analysis with micro-particle image velocimetry. In addition, a numerical modeling method which used a fluid structure interaction module was applied to provide quantitative 3D illustrations of induced flow patterns, including vortical structures and vortex core locations. The results reveal that both the magnitude and distribution of induced vortices primarily affect the mixing performance of two viscous flow streams. By using magnetically controlled artificial cilia along with the presented analytical paradigms, a new active flow mixing strategy was suggested to efficiently transport/agitate flows for microfluidics and biomedical applications.

Artificial cilia-based microfluidics is a promising alternative in lab-on-a-chip applications which provides an efficient way to manipulate fluid flow in a microfluidic environment with high precision. Additionally, it can induce favorable local flows toward practical biomedical applications. The endowment of artificial cilia with their anatomy and capabilities such as mixing, pumping, transporting, and sensing lead to advance next-generation applications including precision medicine, digital nanofluidics, and lab-on-chip systems. This review summarizes the importance and significance of the artificial cilia, delineates the recent progress in artificial cilia-based microfluidics toward microfluidic application, and provides future perspectives. The presented knowledge and insights are envisaged to pave the way for innovative advances for the research communities in miniaturization.

The pathology of the human abdominal aortic aneurysm (AAA) and its relationship to the later complication of intraluminal thrombus (ILT) formation remains unclear. The hemodynamics in the diseased abdominal aorta are hypothesized to be a key contributor to the formation and growth of ILT. The objective of this investigation is to establish a reliable 3D flow visualization method with corresponding validation tests with high confidence in order to provide insight into the basic hemodynamic features for a better understanding of hemodynamics in AAA pathology and seek potential treatment for AAA diseases. A stereoscopic particle image velocity (PIV) experiment was conducted using transparent patient-specific experimental AAA models (with and without ILT) at three axial planes. Results show that before ILT formation, a 3D vortex was generated in the AAA phantom. This geometry-related vortex was not observed after the formation of ILT, indicating its possible role in the subsequent appearance of ILT in this patient. It may indicate that a longer residence time of recirculated blood flow in the aortic lumen due to this vortex caused sufficient shear-induced platelet activation to develop ILT and maintain uniform flow conditions. Additionally, two computational fluid dynamics (CFD) modeling codes (Fluent and an in-house cardiovascular CFD code) were compared with the two-dimensional, three-component velocity stereoscopic PIV data. Results showed that correlation coefficients of the out-of-plane velocity data between PIV and both CFD methods are greater than 0.85, demonstrating good quantitative agreement. The stereoscopic PIV study can be utilized as test case templates for ongoing efforts in cardiovascular CFD solver development. Likewise, it is envisaged that the patient-specific data may provide a benchmark for further studying hemodynamics of actual AAA, ILT, and their convolution effects under physiological conditions for clinical applications.

Hydrofluoric (HF)/nitric (HNO₃)/acetic (CH₃COOH) acid, normally referred to as the HNA method, is a widely utilized technique for performing isotropic etching on silicon (Si) in industrial Si-based processing and device construction. Here, we reported a novel etching strategy based on a HF/HNO₃ process with the assistance of silver (Ag) nano-seeds, offering good controllability in preparing diversified Si nanostructure arrays with particularly smooth top surfaces. The involved mechanism was visualized by systematically investigating both the time and temperature dependencies on the etching kinetics with various ratios of HF to HNO₃. Moreover, by testing different Ag⁺-ion containing oxidants on Si etching, we have re-examined the state-of-the-art metal-assisted chemical etching (MaCE) using HF/AgNO₃ etchants. In contrast with previous reports, we found that the interplay of hole injections from Ag⁺ and NO₃ ⁻ ions to the valence band of Si collectively contributes to the unidirectional dissolution of Si. Finally, we explored the engineering of the Ag nano-seeds to regularize the orientation of the etched nanowires formed on non-Si (100) wafers, which further provides a reliable pathway for constructing the desired morphologies of one-dimensional Si nanostructures regardless of wafer orientation.