Microfluidics and Nanofluidics最新文献

Imaging of chemical composition in microfluidic chips is addressed using Surface Enhanced Raman Spectroscopy (SERS). The Y-shaped SERS microfluidic chip used is fabricated by xurography and an electrodeposition method is employed to form a thin nanostructured silver layer over the bottom glass wall of the main microchannel. Used as an immobilized SERS substrate, this layer of silver nanocrystals exhibits an analytical enhancement factor of 5.10(^4) uniformly distributed over its surface (RSD < 7%). These good performances allow the quantitative imaging of transverse diffusion profiles of Crystal Violet (CV) at low concentrations ((10^{-8}-10^{-6}) mol/L). The SERS measurement turns out to be reversible at high laser power and this is explained by the thermal desorption of adsorbed CV (photothermal effect). However, too high heating leads to a low amount of adsorbed species and a low SERS signal. This effect is limited by using a fast enough flow inducing a cooling effect. A compromise must be found between laser power and liquid flow rate to enable a reversible and sensitive SERS measurement in the chip. These findings should contribute to the development of imaging, in microfluidic conditions, of the spatiotemporal dynamics of weakly concentrated key molecules involved in chemical, biochemical or biological processes.

A new fabrication of micro-nano fluidic chips by thermal nanoimprint and multilayer compositing is proposed. The nano-channels with different aspect ratios were first manufactured by thermal nanoimprinting and Parylene layer coating, and the effect of parylene layer thickness on aspect ratio is studied. Then SU-8 layers with the micro channels and liquid reservoirs were superposed by ultraviolet exposure and secondary bonding to form a multilayer micro-nano fluidic chip. By optimizing the bonding parameters, a Parylene-SU-8 micro-nano fluidic chip with 200 μm wide and 8 μm deep micro-channels, cross-linked with 78 nm wide and 288 nm deep nano-channels was constructed, of which the maximum bonding strength is 0.92 MPa. This method has the advantages of simple process and low cost, which is suitable for mass manufacturing of micro-nano fluidic chips.

The physiological function of lung is strongly correlated with its unique structural microenvironment and mechanical stimulation. Most existing lung-on-a-chips (LOCs) do not replicate the key physiological structure and stimulation of human lung, reducing their reliability in application. In this study, a scaffold structure of a styrene-butadiene-styrene (SBS) nanofiber and porous honeycomb polydime-thylsiloxane (PDMS) composite membrane was developed to construct an alveolar air-blood barrier that mimics the alveolar characteristics of flexibility, cross-scale structure, and triaxial mechanical stimulation. By combining micro-fluidic and electrospinning technology, a biomimetic LOC with dynamic triaxial cyclic strain was realized. The composite membrane had a Young’s modulus of 0.54 ± 0.05 MPa and was capable of 8–12% strain at 1 kPa air pressure. We monocultured and co-cultured human non-small cell lung cancer cells stably expressing red fluorescent protein (A549-RFP) with human umbilical vein endothelial cell stably expressing green fluorescent protein (HUVECs-GFP) within the chip. A multi-layered structure of epithelial cell layer-basal layer-endothelial cell layer, similar to the air-blood barrier in vivo, was constructed. The LOC was proved to be an initial foundation for creating in vitro alveolar physiological models, and could be a potential platform for application in physiology, pathology, toxicology, drug screening, and customized medicine.

The blood-brain barrier (BBB) protects the brain by actively allowing the entry of ions and nutrients while limiting the passage of from toxins and pathogens. A healthy BBB has low permeability and high selectivity to maintain normal brain functions. Increased BBB permeability can result from neurological diseases and traumatic injuries. Modern engineering technologies such as microfluidics and fabrication techniques have advanced the development of BBB models to simulate the basic functions of BBB. However, the intrinsic BBB properties are difficult to replicate. Existing in vitro BBB models demonstrate inconsistent BBB permeability and selectivity due to variations in microfluidic design, cell types and arrangement, expression of tight junction (TJ) proteins, and use of shear stress. Specifically, microfluidic designs have flow channels of different sizes, complexity, topology, and modular structure. Different cell types are selected to mimic various physiological conditions. These factors make it challenging to compare results obtained using different experimental setups. This paper highlights key factors that play important roles in influencing microfluidic models and discusses how these factors contribute to permeability and selectivity of the BBB models.

Microfluidic preparation of nanoparticles (NPs) offers many advantages over traditional bench-top preparation techniques, including better control over particle size and higher uniformity. Although many studies have reported the use of low-cost microfluidic chips for nanoparticle synthesis, the technology is still expensive due to the high cost of the pumps needed to generate the required flows inside microchannels. Here, we present a low-cost finger-operated constant-pressure pumping platform capable of generating pressures as high as 120 kPa using finger-operated pumping caps that can be attached to any pop bottle. The platform costs around $208 and enables the generation of flow rate ratios (FRR) of up to 47:1 for the continuous flow synthesis of NPs. The pump has a resolution of 500 Pa per stroke and exhibits stable pressures for up to a few hours. To show the functionality of the proposed pump, we used it to prepare pegylated liposomes and poly lactic-co-glycolic acid (PLGA) nanoparticles with sizes ranging from 47 nm to 250 nm with an average polydispersity of 20% using commercially available micromixer chips and in-house made hydrodynamic flow focusing devices. We believe this platform will render microfluidic preparation of NPs accessible to any laboratory with minimal capabilities.

Here, a PLLCL-on-chip platform was developed by direct electrospinning of poly (L-lactide-co-ε-caprolactone) (PLLCL) on polymethyl methacrylate (PMMA) microfluidic chips. Designed microchip provides the electrospinning of free-standing aligned PLLCL fibers which eliminates limitations of conventional electrospinning. Besides, aligned fiber structure favors cell alignment through contactless manipulation. Average fiber diameter, and fiber alignment was evaluated by SEM analyses, then, leakage profile of microchip was investigated. 3D cell culture studies were conducted using HeLa and NIH-3T3 cells, and nearly 85% cell viability was observed in PLLCL-on-chip for 15 days, while cell viability of 2D control started to decrease after 7 days based on Live dead and Alamar Blue analyses. These findings emphasize biocompatibility of PLLCL-on-chip platform for 3D cell culture and its ability to mimic extracellular matrix (ECM). Immunostaining results prove that PLLCL-on-chip platform favors the secretion of ECM proteins compared to control groups, and cytoskeletons of cells were in aligned orientation in PLLCL-on-chip, while they were in random orientation in control groups. Overall, these results demonstrate that the developed platform is suitable for the formation of various 3D cell culture models and a potential candidate for cell alignment studies.

Graphical Abstract

In order to reduce the influence of the thermal conductivity of the digital polymerase chain reaction (dPCR) chip material and the temperature distribution of the droplet collection chamber on the amplification effect, an optimized integrated dPCR chip was designed. The heat conduction of the designed dPCR gene chip was simulated by COMSOL finite element model, which provided theoretical basis for the design and fabrication of the chip. Three-dimensional ht models of dPCR microarray under steady state and transient conditions were established. The thermodynamic simulation of dPCR gene chip was carried out by changing the material, thickness, structure and width of droplet collection chamber. During the high temperature denaturation stage of amplification, the temperature characteristics were analyzed, and the surface temperature, heating curve, isotherm, thermal expansion and other results of the dPCR gene chip were obtained, and the structural parameters of the chip design were optimized to provide guidance for the subsequent chip design. The results showed that the internal temperature uniformity of the COC sample was higher than other materials. The chip has a thickness of 2 mm and the collection chamber has a width of 4 mm, which was better suited to meet the requirements of PCR reaction. The PCR amplification device was established, and the uniformity of temperature distribution of the fabricatedchip was verified by thermal imager. The results showed that the heat conduction speed was fast, the heat conduction was uniform, and the uniformity was less than ± 0.5 °C. Therefore, under the premise of meeting the quantity of microdroplet generation, the chip designed in this paper has excellent heat conduction performance.

The current research focuses on investigating the influence of magnetic forces and differently shaped nanoparticles within diverging tapering arteries afflicted with stenoses, utilizing a blood flow model. A notable aspect of this study is the exploration of metallic nanoparticles of various shapes within a water-based fluid medium, a research area that remains largely unexplored. To simulate blood flow dynamics, a radially symmetric yet axially non-symmetric stenosis configuration is employed, providing insights into the complex flow patterns within diseased arteries. A significant contribution of our research lies in the analysis of the symmetrical distribution of wall shearing stresses and their correlation with resistive impedance. Moreover, we investigate the progressive rise of these quantities in tandem with stenosis severity. Through numerical simulations, we evaluate several flow parameters, including velocity, temperature, resistance impedance, boundary shear stress, and shearing stress at the stenosis throat. These assessments provide a comprehensive understanding of the multifaceted effects of nanoparticle shape and magnetic forces on blood flow characteristics within tapered arteries. Furthermore, our study explores the graphical representation of various flow quantities across a spectrum of relevant parameters for Cu-blood systems. By examining different types of tapered arteries, particularly diverging tapering configurations, we gain insights into the intricate interplay between arterial geometry, fluid rheology, and nanoparticle behavior.

With developments of nanofluidics, understanding the behavior of fluids confined in nanospaces becomes important. Particle tracking is an efficient approach, but in nanospaces, it often suffers from the finite temporal resolution, which causes the Brownian displacement of nanoparticles, and the finite spatial resolution due to the decreased signal-to-noise ratio of nanoparticle images, both of which are factors that can cause artifacts. Therefore, in the present study, we simulated nanoparticle tracking velocimetry based on the particle dynamics given by the Langevin equation to evaluate the artifacts. The results revealed that for measurement of the velocity distribution of pressure-driven flow in a 400 nm nanochannel utilizing 60 nm tracer nanoparticles, high-speed (temporal resolution: Δt ≤ 360 µs) and super-resolution (spatial resolution: Δz ≤ 25 nm) measurement is required for errors less than 10%, while insufficient resolution causes an artifact that results in a flattened velocity distribution compared with the original flow profile. The proposed resolutions were experimentally verified by defocusing nanoparticle tracking velocimetry developed by our group. As the simulation predicted, at longer temporal resolution and larger spatial resolution, the measured nanoparticle velocity distribution in the nanochannel indicated a parabolic flow profile but became flattened because of the artifacts. In contrast, at measurement resolutions within the proposed range, the velocity distribution close to the profile given by the Hagen-Poiseuille equation, which was considered to be the actual flow profile, was successfully obtained. This work provides a guideline for nanoscale flow measurements and will accelerate the understanding of specific transport phenomena in nanospaces.

Single-cell analysis provides a groundbreaking avenue for exploring cell-to-cell variation, the heterogeneity of cell responses to stimuli, and the impact of DNA sequence variations on cell phenotypes. A crucial facet of this analytical approach involves the refinement of techniques for effective single-cell trapping and sustained culture. This study introduces a microfluidic platform based on micropillars for hydrodynamic trapping and prolonged cultivation of individual cells. The proposed biochip design, termed three-micropillars based microfluidic (3µPF) structure, incorporates interleaved trap units, each featuring three-micropillars based microfluidic structure strategically designated to trap single cells, enhance the surface area of cells exposed to the culture medium, and enable dynamic culture, continuous waste removal. This configuration aims to mitigate adverse effects associated with bioparticle collisions compared to conventional trap units. The study employs finite element method to conduct a comprehensive numerical investigation into the operational mechanism of the microfluidic device. The simulation results show that the filled trap unit demonstrates a low-velocity magnitude, reducing shear stress on cells and facilitating extended culture. The hydrodynamic single-cell trap mechanism of the proposed device was also verified. The insights derived from this work are pivotal for optimizing the device and guiding future experimental examinations, thus contributing significantly to the progression of single-cell analysis techniques.