Designing Semipermeable Hydrogel Shells with Controlled Thickness through Internal Osmosis in Triple-Emulsion Droplets

Hydrogel shells that compartmentalize the water core from the aqueous surrounding provide molecular selectivity on size and charge in transmembrane transport. It is highly demanding to produce thin hydrogel shells to minimize diffusion length and maximize core volume. Here, internal osmosis in water-in-oil-in-water-in-oil (W/O/W/O) triple-emulsion droplets is used to produce thin hydrogel shells enclosing a large water core. The triple-emulsion droplets are prepared to have an ultrathin middle oil layer using a capillary microfluidic device. The innermost water droplet has a higher osmolarity than the outer water layer containing photopolymerizable hydrogel precursors, which pumps water from the outer layer to the core through the ultrathin oil layer by the osmosis. Therefore, the outer layer gets thinner and hydrogel precursors are enriched while the size of the triple-emulsion droplets remains unchanged. Through photopolymerization of precursors and phase transfer from oil to water, hydrogel shells enclosing water core are produced in the water environment; the oil layer is ruptured for molecular exchange through the shells. The thickness and composition of the hydrogel shells are precisely controllable by the osmotic conditions. The shells show a high permeation rate due to the thinness as well as controlled cut-off threshold of permeation for neutral and charged molecules.     

Digital Microfluidics for Manipulation and Analysis of a Single Cell

The basic structural and functional unit of a living organism is a single cell. To understand the variability and to improve the biomedical requirement of a single cell, its analysis has become a key technique in biological and biomedical research. With a physical boundary of microchannels and microstructures, single cells are efficiently captured and analyzed, whereas electric forces sort and position single cells. Various microfluidic techniques have been exploited to manipulate single cells through hydrodynamic and electric forces. Digital microfluidics (DMF), the manipulation of individual droplets holding minute reagents and cells of interest by electric forces, has received more attention recently. Because of ease of fabrication, compactness and prospective automation, DMF has become a powerful approach for biological application. We review recent developments of various microfluidic chips for analysis of a single cell and for efficient genetic screening. In addition, perspectives to develop analysis of single cells based on DMF and emerging functionality with high throughput are discussed.     

Optimization of Pathogen Capture in Flowing Fluids with Magnetic Nanoparticles

Magnetic nanoparticles have been employed to capture pathogens for many biological applications; however, optimal particle sizes have been determined empirically in specific capturing protocols. Here, a theoretical model that simulates capture of bacteria is described and used to calculate bacterial collision frequencies and magnetophoretic properties for a range of particle sizes. The model predicts that particles with a diameter of 460 nm should produce optimal separation of bacteria in buffer flowing at 1 L h⁻¹. Validating the predictive power of the model, Staphylococcus aureus is separated from buffer and blood flowing through magnetic capture devices using six different sizes of magnetic particles. Experimental magnetic separation in buffer conditions confirms that particles with a diameter closest to the predicted optimal particle size provide the most effective capture. Modeling the capturing process in plasma and blood by introducing empirical constants (c_e), which integrate the interfering effects of biological components on the binding kinetics of magnetic beads to bacteria, smaller beads with 50 nm diameters are predicted that exhibit maximum magnetic separation of bacteria from blood and experimentally validated this trend. The predictive power of the model suggests its utility for the future design of magnetic separation for diagnostic and therapeutic applications.     

PCR芯片和生化微分析系统

介绍了PCR微芯片的最新研究进展,给出了不同结构的PCR芯片设计原理以及特点,介绍由PCR芯片为主要单元的集成微全分析系统的相关研究,同时简要介绍了对PCR的仿真模拟等。     

Glycyrrhetinic Acid Liposomes Encapsulated Microcapsules from Microfluidic Electrospray for Inflammatory Wound Healing

In diabetic wound healing, M1 macrophage accumulation and elevated inflammation are prevalent issues. Intelligent delivery systems that can sustainably release antioxidizing and anti-inflammatory ingredients are expected for effective wound healing. Herein, a novel glycyrrhetinic acid (GA) liposomes encapsulated microcapsules delivery system that has desired features for inflammatory wound repair is presented. As the bacteria could break down the alginate shells, the GA liposomes could be controllably released from the microcapsules, which promotes M2 macrophage polarization and regulate their responses in the inflammatory wound microenvironment. Based on these, it is demonstrated that the GA liposomes encapsulated microcapsules delivery system exhibits an anti-inflammatory and immunomodulatory effect for diabetic wound healing in a full-thickness defect model in diabetic rats. These results indicate that the immunomodulatory capabilities of the microcapsules can be unitized for efficient wound repair, and such a delivery system is valuable for clinical wound healing applications.     

Investigation on replication of microfluidic channels by hot embossing

In this study, effects of embossing temperature, time, and force on production of a microfluidic device were investigated. Polymethyl methacrylate (PMMA) substrates were hot embossed by using a micromilled aluminum mold. The process parameters were altered to observe the variation of replication rate in width and depth as well as symmetry of the replicated microfluidic channels. Analysis of variance (ANOVA) on the experimental results indicated that embossing temperature was the most important process parameter, whereas embossing time and force have less impact. One distinguishing aspect of this study is that, the channels were observed to be skewed to either side of the channel depending on the location of the protrusions on the mold. The mechanism of the skewness was investigated by finite element analysis and discussed in detail. Results showed that the skewness depends on the flow characteristics of the material and could be reduced by increasing the embossing temperature. The best replication rates were obtained at parameter settings of 115°C, 10?kN, and 8?min for the molds with minimum 56?µm wide features of 120?µm depth. We also showed that the fabricated channels could be successfully sealed by solvent-assisted thermo-compressive bonding at 85°C under 5.5?kN force.     

Fast Dynamic Visualizations in Microfluidics Enabled by Fluorescent Carbon Nanodots

Microfluidic systems have become a superior platform for explorations of fascinating fluidic physics at microscale as well as applications in biomedical devices, chemical reactions, drug delivery, etc. Exploitations of this platform are built upon the fundamental techniques of flow visualizations. However, the currently employed fluorescent materials for microfluidic visualization are far from satisfaction, which severely hinders their widespread applications. Here fluorescent carbon nanodots are documented as a game‐changer, applicable in versatile fluidic environment for the visualization in microfluidics with unprecedented advantages. One of the fastest fluorescent imaging speeds up to 2500 frames per second under a normal contionous wave (CW) laser line is achieved by adopting carbon nanodots in microfluidics. Besides better visualizations of the fluid or interface, fluorescent carbon nanodots‐based microparticles enable quantitative studies of high speed dynamics in fluids at microscale with a more than 90% lower cost, which is inaccessible by traditionally adopted fluorescent dye based seeding particles. The findings hold profound influences to microfluidic investigations and may even lead to revolutionary changes to the relevant industries.     

Passive Picoinjection Enables Controlled Crystallization in a Droplet Microfluidic Device

Segmented flow microfluidic devices offer an attractive means of studying crystallization processes. However, while they are widely employed for protein crystallization, there are few examples of their use for sparingly soluble compounds due to problems with rapid device fouling and irreproducibility over longer run‐times. This article presents a microfluidic device which overcomes these issues, as this is constructed around a novel design of “picoinjector” that facilitates direct injection into flowing droplets. Exploiting a Venturi junction to reduce the pressure within the droplet, it is shown that passive injection of solution from a side‐capillary can be achieved in the absence of an applied electric field. The operation of this device is demonstrated for calcium carbonate, where highly reproducible results are obtained over long run‐times at high supersaturations. This compares with conventional devices that use a Y‐junction to achieve solution loading, where in‐channel precipitation of calcium carbonate occurs even at low supersaturations. This work not only opens the door to the use of microfluidics to study the crystallization of low solubility compounds, but the simple design of a passive picoinjector will find wide utility in areas including multistep reactions and investigation of reaction dynamics.