Microfluidic fabrication of monodisperse microcapsules with gas cores.

A facile strategy for efficient and continuous fabrication of monodisperse gas-core microcapsules with controllable sizes and excellent ultrasound-induced burst performances is developed based on droplet microfluidics and interfacial polymerization. Monodisperse gas-in-oil-in-water (G/O/W) double emulsion droplets with a gas core and monomer-contained oil layer are fabricated in the upstream of a microfluidic device as templates, and then water-soluble monomers are added into the aqueous continuous phase in the downstream to initiate rapid interfacial polymerization at the O/W interfaces to prepare monodisperse gas-in-oil-in-solid (G/O/S) microcapsules with gas cores. The sizes of both microbubbles and G/O/W droplet templates can be precisely controlled by adjusting the gas supply pressure and the fluid flow rates. Due to the very thin shells of G/O/S microcapsules fabricated via interfacial polymerization, the sizes of the resultant G/O/S microcapsules are almost the same as those of the G/O/W droplet templates, and the microcapsules exhibit excellent deformable properties and ultrasound-induced burst performances. The proposed strategy provides a facile and efficient route for controllably and continuously fabricating monodisperse microcapsules with gas cores, which are highly desired for biomedical applications.

Dissolving microneedle system containing Ag nanoparticle-decorated silk fibroin microspheres and antibiotics for synergistic therapy of bacterial biofilm infection.

Most cases of delayed wound healing are associated with bacterial biofilm infections due to high antibiotic resistance. To improve patient compliance and recovery rates, it is critical to develop minimally invasive and efficient methods to eliminate bacterial biofilms as an alternative to clinical debridement techniques. Herein, we develop a dissolving microneedle system containing Ag nanoparticles (AgNPs)-decorated silk fibroin microspheres (SFM-AgNPs) and antibiotics for synergistic treatment of bacterial biofilm infection. Silk fibroin microspheres (SFM) are controllably prepared in an incompatible system formed by a mixture of protein and carbohydrate solutions by using a mild all-aqueous phase method and serve as biological templates for the synthesis of AgNPs. The SFM-AgNPs exert dose- and time-dependent broad-spectrum antibacterial effects by inducing bacterial adhesion. The combination of SFM-AgNPs with antibiotics breaks the limitation of the antibacterial spectrum and achieves better efficacy with reduced antibiotic dosage. Using hyaluronic acid (HA) as the soluble matrix, the microneedle system containing SFM-AgNPs and anti-Gram-positive coccus drug (Mupirocin) inserts into the bacterial biofilms with sufficient strength, thereby effectively delivering the antibacterial agents and realizing good antibiofilm effect on Staphylococcus aureus-infected wounds. This work demonstrates the great potential for the development of novel therapeutic systems for eradicating bacterial biofilm infections.

Microfluidic Controllable Preparation of Iodine-131-Labeled Microspheres for Radioembolization Therapy of Liver Tumors.

Transcatheter arterial radioembolization (TARE) is of great significance for the treatment of advanced hepatocellular carcinoma (HCC). However, the existing radioembolic microspheres still have problems such as non-degradability, non-uniform size, and inability to directly monitor in vivo, which hinders the development of TARE. In this paper, a novel radioembolic agent, 131 I-labeled methacrylated gelatin microspheres (131 I-GMs), is prepared for the treatment of HCC. Water-in-oil (W/O) emulsion templates are prepared by a simple one-step microfluidic method to obtain methacrylated gelatin microspheres (GMs) after UV irradiation. A series of GMs with uniform and controllable size is obtained by adjusting the flow rate of each fluid. Both air-dried and freeze-dried GMs can quickly restore their original shape and size, and still have good monodispersity, elasticity, and biocompatibility. The radiolabeling experiments show that 131 I can efficiently bind to GMs by chloramine-T method, and the obtained 131 I-GMs have good radioactive stability in vitro. The results of in vivo TARE treatment in rats show that 131 I-GMs can be well retained in the hepatic artery and have a good inhibitory effect on the progression of liver cancer, showing the potential for the treatment of HCC.

Ultrasensitive hydrogel grating detector for real-time continuous-flow detection of trace threat Pb2.

Ultrasensitive real-time detection of trace Pb2+ in continuous flow is vital to effectively and timely eliminate the potential hazards to ecosystem health and sustainability. This work reports on a micro-structured smart hydrogel grating with ultra-sensitivity, high selectivity, good transparency and mechanical property for real-time detection of Pb2+ in continuous flow. The hydrogel grating possesses uniform surface relief microstructures with periodic nano-height ridges made of poly(acrylamide-co-benzo-18-crown-6-acrylamide) networks that crosslinked by tetra-arm star poly(ethylene glycol)acrylamide. The hydrogel grating with good optical transparency and mechanical property can change its height via selective host-guest complexation with Pb2+ to output a changed diffraction efficiency. Meanwhile, the periodic nano-ridges with large specific area benefit the contact with Pb2+ for fast Pb2+-induced height change. Thus, with such rationally designed molecular structures and surface relief microstructures, the hydrogel grating integrated in a glass-based mini-chip allows real-time detection of Pb2+ in continuous flow with ultra-sensitivity and high selectivity. The hydrogel grating detector can achieve ultralow detection limit (10-9 M Pb2+), fast response (2 min), and selective detection of Pb2+ from dozens of interfering ions even with high concentrations. This high-performance hydrogel grating detector is general and can be extended to detect many analytes due to the wide choice of responsive hydrogels, thus opening new areas for creating advanced smart detectors in analytical science.

Designable microfluidic ladder networks from backstepping microflow analysis for mass production of monodisperse microdroplets.

Controllable mass production of monodisperse droplets plays a key role in numerous fields ranging from scientific research to industrial application. Microfluidic ladder networks show great potential in mass production of monodisperse droplets, but their design with uniform microflow distribution remains challenging due to the lack of a rational design strategy. Here an effective design strategy based on backstepping microflow analysis (BMA) is proposed for the rational development of microfluidic ladder networks for mass production of controllable monodisperse microdroplets. The performance of our BMA rule for rational microfluidic ladder network design is demonstrated by using an existing analogism-derived rule that is widely used for the design of microfluidic ladder networks as the control group. The microfluidic ladder network designed by the BMA rule shows a more uniform flow distribution in each branch microchannel than that designed by the existing rule, as confirmed by single-phase flow simulation. Meanwhile, the microfluidic ladder network designed by the BMA rule allows mass production of droplets with higher size monodispersity in a wider window of flow rates and mass production of polymeric microspheres from such highly monodisperse droplet templates. The proposed BMA rule provides new insights into the microflow distribution behaviors in microfluidic ladder networks based on backstepping microflow analysis and provides a rational guideline for the efficient development of microfluidic ladder networks with uniform flow distribution for mass production of highly monodisperse droplets. Moreover, the BMA method provides a general analysis strategy for microfluidic networks with parallel multiple microchannels for rational scale-up.

Mathematical modeling of sign-and-symptom-oriented diagnostic procedure in traditional Chinese medicine based on the analytic hierarchy process: indications of Guizhi Decoction and its varieties in the Shanghanlun.

OBJECTIVE: This study explores the applicability of a multi-attribute decision-making method in assessing Guizhi Decoction (GZD) and its varieties as noted in the Shanghanlun. METHODS: A known multi-attribute decision-making method, the analytic hierarchy process (AHP), was adopted to transform the clinical challenge of selecting optional decoction for a given combination of symptoms or signs into multiple criteria decision-making problem. RESULTS: A normative model based on the AHP was realized for indications of GZD and its varieties. The indications of sub-family GZD-f (indications of GZD itself) were exterior illness; the indications of GZD-vf1 (indications of GZD's variants which consist of fine adjustments to the ingredients or content on the basis of GZD) were exterior illness with interior excess, suggesting that GZD-vf1 consisted of most conservative variants of GZD; the indications of both GZD-vf2 (indications of Guizhi Qu Shaoyao Decoction and its derivative variants) and GZD-vf3 (indications of Guizhi Gancao Decoction and its derivative variants) showed evolution from exterior illness to interior deficiency in 2 directions. As to efficacy evaluation of the decoction, GZD and its varieties (restricted to those comparable ones) were of equal efficacy on 3 popular signs or symptoms indicating exterior illness: floating pulse, aversion to wind and spontaneous sweating, which were the common ground of indications for the GZD family. CONCLUSION: Modeling of diagnostic procedure based on the AHP is proved practicable to analyze the clinical judgment system of traditional Chinese medicine. Quantification research on syndrome differentiation and decoction evaluation system focused on signs and symptoms is suggested as a feasible and reliable model.

[Probing the cause on Wang Qingrens idea of "Fallacious theory, effective prescription" of Wang Qingren].

The theory of human body in Yilin Gaicuo (Correction on Errors in Medical Classics) by Wang Qingren in late Qing Dynasty is different from that of traditional Chinese Medicine and that of anatomy of western medicine. However, the prescriptions recorded in Yilin Gaicuo (Correction on Errors in Medical Classics) are indeed effective clinically. The paradox of "Fallacious theory, effective prescription" suggests that the theories of Wang Qingren are not superficial in anatomy. By carefully analyzing the concept of zang-fu organs and concept of qi and blood as well as the theory of human body in Yilin Gaicuo (Correction on Errors in Medical Classics), although many viewpoints of theories of Wang Qingren deviates from that of traditional Chinese Medicine, they inherits the qi and blood concept, the core theory of Chinese Medicine. Therefore, the theories belong to the theoretical scope of Chinese Medicine. The root of "Fallacious theory, effective prescription" is in the heritage of the qi and blood concept. The set view of Wang Qingren in criticizing the theories of traditional Chinese Medicine and establishing new theories revealed in this process possesses the significance of revelation to the contemporary Chinese Medicine.