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Over the past decades, microfluidics has emerged as an increasingly important tool to perform biochemical assays for diagnosis and healthcare. The precise fluid control and molecule manipulation within microfluidics greatly contribute to developing assays with simplicity and convenience. The advantages of microfluidics, including decreased consumption of reagents and samples, lower operating and analysis time, much lower cost, and higher integration and automation over traditional systems, offer a great platform to meet the needs of point-of-care applications. In this Review, versatile strategies are outlined and recent advances in microfluidics-implemented assays are discussed from the perspective of readout, because a convenient and straightforward readout is what a biochemical assay requires and the end user desires. Functions and properties arising from each readout are reviewed and the advantages and limitations of each readout are discussed together with current challenges and future perspectives., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Microfluidics-based microfibers have been widely used as bottom-up scaffolds for tissue engineering applications. Different forms of microfibers with certain thickness of shell have been developed during the past decade. Ultra-thin microfiber, as a special and promising carrier of cells, was less explored. In this work, by using the interfacial ionic interaction between sodium alginate (NaA) and chitosan (CS), a novel ultra-thin polyelectrolyte hollow microfiber with the diameter of ~200 μm and the shell thickness of 1.3 ± 0.3 μm was fabricated via a microfluidic device for liver tissue engineering. The fluorescence of FITC labeled CS confirmed the inner CS layer of the fabricated microfiber and the SEM results illustrated its ultra-thin characteristic. Although there are only two layers in the ultra-thin polyelectrolyte hollow microfiber, the following cells encapsulation experiments indicated that it could bear cells loading and the hollow space of the microfibers could encapsulate sufficient number of cells for tissue engineering applications. The presence of inner CS layer in the microfiber promoted cell adhesion and ultra-thin shell characteristic facilitated the exchange of nutrient substance and O 2 and thus promoted cell proliferation. HepG2 cells encapsulated in the microfibers maintained favorable viability, proliferation ability and hepatic specific functions during 10 days' culture. These results suggest that the established polyelectrolyte microfibers hold great potential applications in the field of liver tissue engineering. We believe this work will lead to the development of innovative methodologies and materials for both cell culture and biomedical application., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Integrated device with high purity for circulating tumor cell (CTC) identification has been regarded as a key goal to make CTC analysis a "bench-to-bedside" technology. Here, we have developed a novel integrated microfluidic device that can enrich and identify the CTCs from the blood of patients with colorectal cancer. To enrich CTCs from whole blood, microfabricated trapping chambers were included in the miniaturized device, allowing for the isolation of tumor cells based on differences in size and deformability between tumor and normal blood cells. Microvalves were also introduced sequentially in the device, enabling automatic CTC enrichment as well as immunostaining reagent delivery. Under optimized conditions, the whole blood spiked with caco-2 cells passing through the microfluidic device after leukocyte depletion and approximately 73% of caco-2 cells were identified by epithelial cell adhesion molecule (EpCAM) staining. In clinical samples, CTCs were detectable from all patients with advanced colorectal cancer within 3 h. In contrast, the number of CTCs captured on the device from the blood of healthy donors was significantly lower than that from the patients, suggesting the utilization of the integrated device for further molecular analyses of CTCs.

Multiplexed assay of analytes is of great importance for clinical diagnostics and other analytical applications. Barcode-based bioassays with the ability to encode and decode may realize this goal in a straightforward and consistent manner. We present here a microfluidic barcoded chip containing several sets of microchannels with different widths, imitating the commonly used barcode. A single barcoded microchip can carry out tens of individual protein/nucleic acid assays (encode) and immediately yield all assay results by a portable barcode reader or a smartphone (decode). The applicability of a barcoded microchip is demonstrated by human immunodeficiency virus (HIV) immunoassays for simultaneous detection of three targets (anti-gp41 antibody, anti-gp120 antibody, and anti-gp36 antibody) from six human serum samples. We can also determine seven pathogen-specific oligonucleotides by a single chip containing both positive and negative controls.

The rapid development of smart wearable microdevices has stimulated the urgent demand for micro‐supercapacitors (MSCs) with multiple form factors, however, several factors like conventional bulky stacked geometries, rigid substrates, and complex manufacturing processes have blocked their path toward practical application. Herein, a microfluidics‐assisted fabrication strategy is demonstrated which utilizes capillary action for precisely customising planar MSCs, showing substrate‐free configuration attributed to the use of polyvinyl alcohol hydrogel in both electrolytes and transfer template. Remarkably, the resulting MSCs with highly conductive polymer (PEDOT:PSS)‐based active materials as microelectrodes, exhibit excellent areal capacitance of 21.4 mF cm−2 and noticeable capacitance retention of 88% after 10000 cycles. Furthermore, the substrate‐free MSCs display extraordinary flexibility and remarkable stretchability of 640% strain. Significant serial and parallel integration is demonstrated for boosting voltage and capacitance output, demonstrative of impressive performance uniformity and applicability for different scenarios. Therefore, the exploration of microfluidics‐assisted fabrication is shown to be a reliable strategy for high performance standalone microelectronics with in‐plane configuration. [ABSTRACT FROM AUTHOR]

Bacterial adhesion and colonization can result in chronic non‐healing wounds. Current hydrophilic wound dressings can release antibacterial agents into the wound exudate, but may result in overhydrated wounds, bacterial overgrowth, and even tissue maceration. Hydrophobic dressings are anti‐fouling, though ineffective to encapsulate and release bactericidal agents. Combining the advantages of hydrophilic and hydrophobic dressings seems difficult, until the development of superwettability surfaces offers an opportunity for omniphobic dressings from intrinsic hydrophilic polymers. Herein, omniphobic porous hydrogel wound dressings loaded with a zinc imidazolate framework 8 (ZIF‐8) are fabricated by a microfluidic‐emulsion‐templating method. The fabricated porous hydrogel membrane with its reentrant architecture is repellent to blood and body fluids, though intrinsically hydrophilic. This unique combination not only reduces the adhesion of harmful microbes, but also enables the encapsulation and release of antibacterial ingredients to wounded sites from hydrophilic polymer networks. As such, the omniphobic metal‐organic frameworks (MOFs)@hydrogel porous wound dressing can inhibit bacteria invasion and enable the controlled release of the bactericidal, anti‐inflammatory, and nontoxic zinc ions. Furthermore, in vivo study of infected full‐thickness skin defect models demonstrates that the dressing also accelerates wound closure by promoting angiogenesis and collagen deposition. Therefore, the omniphobic MOFs@hydrogel porous wound dressings are potentially useful for clinical application. [ABSTRACT FROM AUTHOR]

Sodium alginate (NaA) has been widely used as microfiber‐based scaffold material. However, Ca‐alginate microfiber might disintegrate in the physiological environment due to the loss of calcium ions, which will limit its long‐term application in tissue engineering. In this work, to enhance the stability of Ca‐alginate microfiber in the physiological environment, an inner chitosan coating was introduced to Ca‐alginate hollow microfiber by one step via a microfluidic device. A more stable composite microfiber with double cross‐linking layers was generated. The stability of the microfiber was studied in the PBS solution (pH 7.4) to identify the coating effect on the hollow structure. The results revealed that chitosan component bonded an NaA layer to form a stable polyelectrolyte complex membrane in the inner wall of the microfiber, which stabilized the hollow region even though the Ca‐alginate shell was disintegrated by PBS solution. In addition, the introduction of chitosan coating improved the inner environment of the low affinity of alginate to cell surfaces and facilitated the cell adhesion and culture in the microfiber. HepG2 cells in the microfibers displayed favorable cell viability and proliferation ability. We believe that this work will lead to the development of innovative methodologies and materials for both cell culture and tissue engineering application. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B:2527–2536, 2019. [ABSTRACT FROM AUTHOR]

This report describes a straightforward but robust tubing method for connecting polydimethylsiloxane (PDMS) microfluidic devices to external equipment. The interconnection is irreversible and can sustain a pressure of up to 4.5 MPa that is characterized experimentally and theoretically. To demonstrate applications of this high-pressure tubing technique, we fabricate a semicircular microfluidic channel to implement a high-throughput, size-controlled synthesis of poly(lactic-co-glycolic acid) (PLGA) nanoparticles ranging from 55 to 135 nm in diameter. This microfluidic device allows for a total flow rate of 410 mL h−1, resulting in enhanced convective mixing which can be utilized to precipitate small size nanoparticles with a good dispersion. We expect that this tubing technique would be widely used in microfluidic chips for nanoparticle synthesis, cell manipulation, and potentially nanofluidic applications. [ABSTRACT FROM AUTHOR]

We have developed a microfluidic chip for colorimetric Cu2+ detection. In this chip, it is facile to do colorimetric Cu2+ detection based on gold nanoparticles. This method has a dynamic detection range from 0.75 to 50 µmol/L with only 20 µL solution including detection reagents and sample. The result can be readout by naked eye and photographed by digital cameras. With the help of image processing software, we could measure the RGB value and calculate the Blue/Red ratio for more accurate quantification. Tap water could be detected in this portable chip. [ABSTRACT FROM AUTHOR]

The pharmacokinetic (PK) properties of drug, which include drug absorption and excretion, play an important role in determining the in vivo pharmaceutical activity. However, current in vitro systems that model PK profiles are often limited by the in vivo-like concentration profile of a drug. Herein, we present a perfused and multi-layered microfluidic chip system to model the PK profile of anti-cancer drug 5-FU in vitro. The chip device contains two layers of culture channels sandwiched by a porous membrane, which allows for drug exposure and diffusion between the two channels. The integration of upper intestine cells (Caco-2) and bottom targeted cells within the device enables the generation of loading and clearance portions of a PK curve under peristaltic flow. Fluorescein as a test molecule was initially used to generate a concentration-time curve, investigating the effects of parameters of flow rate, administration time, and initial concentration on dynamic drug concentration profiles. Furthermore, anti-cancer drug 5-FU was performed to assess its pharmaceutical activity on target cells (human lung adenocarcinoma cells or human pulmonary alveolar epithelial cells) using different drug administration regimens. A dynamic, in vivo-like 5-FU exposure refers to PK profile regimen, led to generate a lower drug concentration (dynamically fluctuate from 0 to 1 μg/mL affected by absorption) compared to the constant exposure. Moreover, the PK profile regimen alleviates the drug-induced cytotoxicity on target cells. These results demonstrate the feasibility of determining the PK profiles using this microfluidic system with in vivo-like drug administration regimens. This established system may provide a powerful platform for the prediction of drug safety and effectiveness in the pharmaceutical research. [ABSTRACT FROM AUTHOR]

Exosomes are nanoscale membrane vesicles (∼30–150 nm) actively released by most types of cells, which has great potential for non-invasive disease diagnostics. Current isolation techniques such as ultracentrifugation face a number of drawbacks including low integrity, low purity and long processing times. This represents an interesting challenge for microfluidic technologies, from integrity perspective as well as for enhanced purity capabilities, point-of-care acquisition and diagnosis. In this review, we highlight the label-free microfluidic advances for isolation and analysis of exosomes based on their size, deformability and electrical characteristics. These new capabilities are expected to advance fundamental research while paving the way for routine exosome-based personalized medicine. • Microfluidic strategies for label-free exosome isolation and analysis are elucidated. • Integrating exosomes detection on the microfluidic platforms are introduced. • Current challenges to practical concerns for exosome-based fundamental research and disease diagnostics are discussed. [ABSTRACT FROM AUTHOR]