Lab on a Chip最新文献

Glioblastoma is one of the most malignant tumors in the world, but the development of its therapies remains limited. Herein, a microfluidic chip that mimics the cerebrospinal fluid (CSF) circulation microenvironment is proposed to study the migration characteristics of glioblastoma U87-MG cells and U251 cells in complex environments where glioblastoma coexists with diseases that elevate CSF levels. In the presence of interstitial flow (IF), changing both cell densities and the cellular environment results in increased cell motility, including an increase in the number of migrating cells, the mean displacement of the top 30% fastest-moving cells, and the overall mean displacement. Then, through dynamic migration characterization analysis, it was found that IF enhances cell velocity and speed. Importantly, cells exposed to IF tend to migrate in directions with smaller angles of deviation from the opposite direction of IF. Finally, cytoskeleton inhibitors and decreased expressions of focal adhesion proteins, such as cytochalasin D, FAK inhibitors (VS-6063 and PF-573228), and FAK siRNA, were both proved to decrease the cells' response to IF. This work not only demonstrates the effect of IF on glioblastoma cell migration, but also indicates the reliability of microfluidic chips for modeling complex physiological environments, which is expected to be further developed for drug screening.

This study introduces a modular centrifugal platform developed for stepwise gradient elution in reversed-phase liquid chromatography, featuring adjustable mixing and automated position-switching mechanisms. Traditional methods of gradient elution rely on precision syringes and mixers to control eluent composition, but incorporating external pumping systems into centrifugal platforms presents substantial technical and economic challenges. To overcome these limitations, an adjustable eluent mixer was designed to generate concentration gradients by utilizing Coriolis-induced metering and shake-mode mixing processes. The eluent composition was controlled by varying the platform's rotational speed, with the effects of geometric and operational parameters on liquid distribution thoroughly analyzed. An operating curve was established to correlate methanol–water eluent compositions with rotational speed. Furthermore, a switchable fraction collector capable of automated position switching was developed to collect eluates from each elution step. By synchronizing rotational speed with ratchet-driven movements, the outer ring containing multiple fraction collectors rotates relative to the inner disk, enabling efficient replacement of filled collectors. Experimental results demonstrated the successful separation and collection of water-soluble dyes, highlighting the platform's potential as a cost-effective and precise solution for chromatographic applications.

Rapid, efficient, simple approaches for biological nanoparticle recovery from bodily fluids are required for translating detection strategies from lab diagnostics to low-resource settings, where expensive sample processing instruments such as an ultracentrifuge are not accessible. In this work, we characterize an alternative approach in which intact nanoparticles are filtered from plasma with a nanoporous filtration device that separates particulates within a 100–200 nm diameter range followed by detection on a photonic crystal (PC) biosensor with a portable photonic resonator interferometric scattering microscopy (PRISM) instrument. The biosensor-integrated recovery device's (BIRD) collection efficiency is initially characterized using gold nanoparticles and fluorescent nanobeads suspended in buffer solution and plasma, followed by spiking intact HIV pseudovirus into the same media. We demonstrate a recovery rate of 55.0% for 100 nm diameter AuNP and HIV spiked into the buffer and 11.9% for 100 nm diameter FluoSpheres spiked in human plasma. Using PRISM, we observed the Brownian motion of filtered nanoparticles and virions eluted into the detection compartment, with concentration-dependent counting of transient contact events between the nanoparticles and the PC surface.

In response to mechanical cues, endothelial cells elicit highly sensitive cellular response pathways that contribute to the regulation of the physiology and disorders of the vascular system. However, it remains relatively unexplored how endothelial tissues process and integrate the intraluminal pressure, and in turn regulate the permeation flow across the vessel wall. Leveraging a tissue engineering approach to create microvessels (MVs), we measured real-time permeation flow induced by intraluminal pressures ranging from 0.1 to 2.0 kPa. Our findings reveal that mechanically stimulated MVs strengthen their barrier function within seconds of exposure to pressures below 1 kPa, with this enhanced barrier function persisting for 30 minutes. We demonstrate that this barrier reinforcement is linked to the closure of paracellular gaps. Additionally, we observe that it is associated with, and depends on, actin cytoskeleton reorganization, including the accumulation of stress fibers near intercellular junctions and the broadening of adherence junction protein localization. These findings provide insights into the ability of endothelial tissues to regulate interstitial fluid flow in response to sudden increases in blood pressure.

Soft micropillar arrays enable detailed studies of cellular mechanotransduction and biomechanics using traditional beam-bending models. However, they often rely on simplified assumptions, leading to significant errors in force estimation. We present MechanoBioCAD (MBC), a finite element method (FEM)-based tool designed specifically for micropillar research and error estimation. Unlike traditional methods, MBC leverages the principle of minimizing total potential energy, avoiding errors associated with beam bending assumptions. MBC automates FEM model generation, analysis, and post-processing, providing accurate force quantification based on deflection input. The tool addresses critical issues such as substrate deformation, interpillar interactions, improper load application heights, and nonlinear effects. Applied to fibroblast cell traction and Caenorhabditis elegans (C. elegans) thrashing cases, MBC recorded 23% and 34% errors in the estimated forces, respectively, compared to traditional methods. As an open-access tool with the Abaqus Student Edition, MBC democratizes rational design, analysis, and error estimation for researchers who are not subject matter experts in FEM.

Microvessels (e.g., capillaries) are ubiquitous throughout human anatomy, yet recreating their three-dimensional (3D) microfluidic and architectural sophistication at biologically accurate length scales has remained a critical challenge. To overcome this barrier, here we report a hybrid additive manufacturing—or “3D printing”—strategy in which “Two-Photon Direct Laser Writing (DLW)” is used to nanoprint microvessels of arbitrary design directly atop “Liquid-Crystal Display (LCD)” 3D-printed microfluidic chips. Fabrication results indicated effective production of 100 μm-diameter 3D polydimethylsiloxane (PDMS) microfluidic vessels with 5 μm-thick walls—featuring arrays of pre-designed 5 μm-diameter micropores—as well as three discrete spiralled, intertwined microvessels. Experimental results with MDA-MB-231 epithelial breast cancer cells revealed the ability for the 3D PDMS microvessels to support cell culture. In combination, these results suggest that the presented strategy for 3D nanoprinting PDMS microvessels with custom-designed architectures and microporosity offers a promising pathway to enable new classes of “organ-on-a-chip (OOC)” systems for wide-ranging biomedical applications.

Atmospheric pressure plasma conversion of methane is usually addressed in gas-only systems, such as dry reforming of methane. Introducing a liquid in such a system enables direct utilization of plasma-produced radicals, such as methyl (CH₃), as a reactant in the liquid. Methylation of organic liquids by this technique can lead to the sustainable production of high-value products. A dielectric-barrier-discharge (DBD) microfluidic reactor having a 500 μm × 500 μm cross-section was developed to investigate the characteristics of methane-containing atmospheric pressure plasmas in contact with organic solvents. The sensors included optical emission spectroscopy and chip surface temperature measurement to estimate and predict plasma initiation in these methane-containing systems and provide insights into the plasma-liquid interfacial behavior. Fluids having high liquid hold-up, low boiling point, and low dielectric constant have been found to have adverse effects on non-equilibrium DBD methane plasma ignition.

Bioinspired ionic power devices have been investigated due to their high biocompatibility and potential for sustainable energy conversion through ion concentration gradients. However, recent research into portable ionic power devices has primarily focused on hydrogel-based stacking elements, such as ion-selective gels and ionic reservoirs, to enhance productivity. However, this approach results in ionic resource consumption for the operating time. In this study, we propose a portable ionic power generator that provides continuous electricity by integrating multi-ionic reverse electrodialysis (MRED) with a passive capillary micropump for electrolyte absorption. The integrated MRED system was fabricated on a portable fluidic chip with optimizations of absorbing performance, electrolyte concentration, and shortcut current regulation attaining maximum potential of 267.45 mV and current of 4.42 mA. Furthermore, consistent and continuous performance for 25 min was achieved by incorporating cotton flow resistors, which modulate the electrolyte absorbing rate at the electrolyte contact region of the pumps. The electric potential was controlled by adjusting the cotton mass inspiring controllable drug release via iontophoresis where high voltage enhances charged drug penetration. This study paves the way for a new form of ionic power supply for patch-type wearable health devices.

Human circulation exhibits significant diversity and heterogeneity of blood vessel shapes. The complex architecture of these vessels may be physiological or pathological resulting in unique hemodynamics and endothelial cell phenotypes that may determine the regulation and alteration of cell signaling pathways and vascular function. While human microphysiological systems of blood vessels (vessel-chips) have mimicked several aspects of vascular pathophysiology, engineering of these tools is still limited to the fabrication of homogeneous tubular structures, especially when living endothelial cell culture is also included. Here, a common unifying approach based on gravitational lumen patterning (GLP) is presented to create non-uniform, living 3D and closed vascular lumens embedded in a collagen matrix and lined with endothelial cells, resulting in reproduction of the architecture of straight vessels, stenosis, bifurcations, aneurysms and tortuous vessels. Upon blood perfusion, these systems reveal the nature of altered flow dynamics and corresponding endothelial cell morphology. These vessel-chips closely mimic the structural variations and resulting endothelial responses often observed in vivo and may be used to investigate vascular complications like aortic and cerebral aneurysm, arterial tortuosity syndrome, atherosclerosis, carotid artery disease, etc., where architecture plays a crucial role in disease onset and progression.

Azobenzene mesogen, as a typical photo-responsive material, has potential possibility in the field of soft robots based on its trans–cis isomerization. The alignment of the azobenzene mesogen in a polymer network has a decisive impact on the photo-actuation behavior of the membrane. However, the alignment of mesogens is difficult to change after being determined, which limits the diversity of actuation modes. To solve this problem, this paper proposes a facile solvent treatment approach to reversibly change the alignment of mesogens in the polymer network. The as-prepared membrane demonstrates reversible photo-actuation behavior under UV-vis irradiation based on the strong penetration of the solvent into the polymer network, leading to disruption of the original ordered alignment of the mesogen. Promising application of a photo-driven membrane floating and sinking in the liquid phase is demonstrated. The results of this study are of great significance for the design and fabrication of a novel-type azobenzene actuator in the liquid phase.