Evaluation of peristaltic micromixers for highly integrated microfluidic systems

Microfluidic devices based on the multilayer soft lithography allow accurate manipulation of liquids, handling reagents at the sub-nanoliter level, and performing multiple reactions in parallel processors by adapting micromixers. Here, we have experimentally evaluated and compared several designs of micromixers and operating conditions to find design guidelines for the micromixers. We tested circular, triangular, and rectangular mixing loops and measured mixing performance according to the position and the width of the valves that drive nanoliters of fluids in the micrometer scale mixing loop. We found that the rectangular mixer is best for the applications of highly integrated microfluidic platforms in terms of the mixing performance and the space utilization. This study provides an improved understanding of the flow behaviors inside micromixers and design guidelines for micromixers that are critical to build higher order fluidic systems for the complicated parallel bio/chemical processes on a chip

In Situ Self-Cross-Linkable, Long-Term Stable Hyaluronic Acid Filler by Gallol Autoxidation for Tissue Augmentation and Wrinkle Correction

Copyright © 2019 American Chemical Society.Injectable fillers mainly aim to augment tissue volume and correct wrinkles in cosmetic and plastic reconstructions. However, the development of long-lasting, injectable fillers with minimal complications of pain, toxicity, and displacement has been challenging because of the absence of reliable cross-linking chemistry. Here, we report a novel cross-linker-free injectable hydrogel formulated by autoxidation as a highly biocompatible, easily injectable, and long-term volumetrically stable filler agent. Self-cross-linkable hyaluronic acid (SC-HA) with gallol moieties could form a hydrogel via autoxidation of gallols in vivo without additional cross-linking agents. The gelation of SC-HA in situ after injection is accelerated by the self-production of oxygen species and endogenous peroxidase in vivo. The SC-HA filler does not require a high injection force, thus minimizing pain, bleeding, and tissue damage-associated complications. In addition, improved tissue adhesiveness of the SC-HA hydrogel by oxidized gallols (shear strength; 2 kPa) prevented displacement of the filler constructs from the injection site. The SC-HA filler retained its mechanical properties in vivo (600-700 Pa) for wrinkle correction and volumetric augmentation up to 1 year after injection. Overall, the performance of the SC-HA hydrogel as an injectable dermal filler was superior to that of commercially available, chemically cross-linked biphasic HA filler composites in terms of injectability, tissue adhesiveness, and long-term volumetric augmentation. Our injectable HA hydrogel with no need of cross-linkers provides a long-lasting filler that has clinical utility for cosmetic applications11sciescopu

Empagliflozin Contributes to Polyuria via Regulation of Sodium Transporters and Water Channels in Diabetic Rat Kidneys

Besides lowering glucose, empagliflozin, a selective sodium-glucose cotransporter-2 (SGLT2) inhibitor, have been known to provide cardiovascular and renal protection due to effects on diuresis and natriuresis. However, the natriuretic effect of SGLT2 inhibitors has been reported to be transient, and long-term data related to diuretic change are sparse. This study was performed to assess the renal effects of a 12-week treatment with empagliflozin (3 mg/kg) in diabetic OLETF rats by comparing it with other antihyperglycemic agents including lixisenatide (10 μg/kg), a glucagon-like peptide receptor-1 agonist, and voglibose (0.6 mg/kg), an α-glucosidase inhibitor. At 12 weeks of treatment, empagliflozin-treated diabetic rats produced still high urine volume and glycosuria, and showed significantly higher electrolyte-free water clearance than lixisenatide or voglibose-treated diabetic rats without significant change of serum sodium level and fractional excretion of sodium. In empagliflozin-treated rats, renal expression of Na+-Cl- cotransporter was unaltered, and expressions of Na+/H+ exchanger isoform 3, Na+-K+-2Cl- cotransporter, and epithelial Na+ channel were decreased compared with control diabetic rats. Empagliflozin increased an expression of aquaporin (AQP)7 but did not affect AQP3 and AQP1 protein expressions in diabetic kidneys. Despite the increased expression in vasopressin V2 receptor, protein and mRNA levels of AQP2 in empagliflozin-treated diabetic kidneys were significantly decreased compared to control diabetic kidneys. In addition, empagliflozin resulted in the increased phosphorylation of AQP2 at S261 through the increased cyclin-dependent kinases 1 and 5 and protein phosphatase 2B. These results suggest that empagliflozin may contribute in part to polyuria via its regulation of sodium channels and AQP2 in diabetic kidneys

Exploring Membrane-tethering Technology for Proteins as a Versatile Tool for Uncovering Novel Disease Targets and Advancing Biotherapeutic Development

Membrane-tethering technology for proteins (MTFP) is a promising approach for the development of therapeutic agents that display bioactive proteins, such as antibodies and cytokines, on the cell surface, resulting in the induction of autocrine signalling. In this review article, we provide a comprehensive overview of the MTFP, including its basic principles, selection of agonist antibodies and peptides, and the identification of novel functions of natural cytokines. Furthermore, we discuss the potential of increasing the therapeutic efficacy of existing treatments by engineering active proteins to the cell and extracellular vesicle surfaces. We suggest that the MTFP has the potential to maximize efficiency in drug discovery by identifying proteins with regulatory functions and engineering existing treatments. Our review highlights the importance of MTFP in basic research and translational research, and its potential to apply the development of biotherapeutics. © 2023 Wiley-VCH GmbH.FALS

Ferritin Nanoshuttle for Long-Lasting Self-Healing of Phenolic Hydrogels

Herein,we highlight a novel finding that ferritin can play a crucialrole in the "self-healing lifetime" of soft phenolicmaterials. Ferritin interacts with a catechol-functionalized polymerto form a self-healable and adhesive hydrogel bidirectionally by providingand retrieving Fe3+. As a result of its unique role asa nanoshuttle to store and release iron, ferritin significantly increasesthe self-healing lifetime of the hydrogel compared with that affordedby catechol-Fe3+ coordination through direct Fe3+ addition without ferritin. Ferritin also induces stableoxidative coupling between catechol moieties following metal coordination,which contributes to double cross-linking networks of catechol-catecholadducts and catechol-Fe3+ coordination. Thus, ferritin-mediatedcross-linking can provide phenolic hydrogels with the advantages ofhydrogels prepared by both metal coordination and oxidative coupling,thereby overcoming the limitations of the current cross-linking methodsof phenolic hydrogels and broadening their versatility in biomedicalapplications.11Nsciescopu

A Microfluidic Approach to Investigating a Synergistic Effect of Tobramycin and Sodium Dodecyl Sulfate on Pseudomonas aeruginosa Biofilms

In recent years, a microfluidic technology has contributed a significant role in biological research, specifically for the study of biofilms. Bacterial biofilms are a source of infections and contamination in the environment due to an extra polymeric matrix. Inadequate uses of antibiotics make the bacterial biofilms antibiotic resistant. Therefore, it is important to determine the effective concentration of antibiotics in order to eliminate bacterial biofilms. The present microfluidic study was carried out to analyze the activities of tobramycin and sodium dodecyl sulfate (SDS) against Pseudomonas aeruginosa biofilms with a continuous flow in order to achieve a greater delivery of the agents. The results show that a co-treatment of tobramycin and SDS significantly reduced the biomass of biofilms (by more than 99%) after 24 h. Tobramycin and SDS killed and detached bacteria in the cores of biofilms. Evidently, our data suggest that a microchannel would be effective for both quantitative and qualitative evaluations in order to test combinatorial effect of drugs and chemicals on a complexed biological system including biofilm. © 2016 The Japan Society for Analytical Chemistry.FALS

Quantitative analysis of pneumatically driven biomimetic micro peristalsis

A pneumatically operated peristaltic micro pump can play an important role in nanoliter or picoliter scale fluid handling and delivery for biomimetic micro-scale peristalsis system as well as biological and chemical applications. Here, we first investigate the performance of peristaltic micro peristaltic system that are composed of pneumatically operated micrometer scale mechanical valve. We examined the effect of the number of pumping valves, from two to six, with variations of the operating frequency. The micro pumps with 200×100 μm2 of valve area in 100 μm wide and 10 μm deep microchannels were mechanically actuated using a pneumatic pressure source and the optimum valve number and efficient operating frequency were found. This study provides an improved understanding of the working mechanism of microfabricated peristaltic pumps and delivers practical information for the design of robust and efficient peristaltic fluid manipulation systems with nanoliter or picoliter volumes of target samples

Plant-inspired quercetin thin films: universal coatings and their postfunctionalization for non-biofouling applications

Polyphenols containing catechol (1,2-dihydroxyphenyl)/pyrogallol (1,2,3-trihydroxyphenyl) groups have been employed as precursors to prepare substrate-independent (i.e., universal) coatings. However, quercetin, an interesting flavonol due to its unique biological properties, was previously found to be an inefficient compound for substrate coatings after screening polyphenolic compounds. We report that quercetin-based thin films could be formed on various substrates, including titanium dioxide, silicon wafers, gold, nylon, and glass, when diethylenetriamine (DETA) was used as an additive. DETA acted as a cross-linker to facilitate conjugate addition and imine formation with the catechol in quercetin. The film thickness was controllable by changing the quercetin concentration. Static water contact angles for all examined substrates converged to 25° regardless of the vastly different static water contact angles of the bare substrates, showing the universal coating capability of quercetin and DETA. Importantly, the films formed with quercetin and DETA were chemically modifiable; thus, specific functions on the surface could be introduced. α-Bromoisobutyryl bromide was immobilized on the films via esterification, and then a zwitterionic sulfobetaine polymer was subsequently grafted. Compared to the controls, the polymer-grafted surface effectively suppressed the adsorption of fibrinogen and platelets, demonstrating its non-biofouling effect. Considering its universal coating and postfunctionalization capabilities, this quercetin-based film provides a route for the preparation of functional organic coatings. This journal is © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique.1