Miniaturized metachronal magnetic artificial cilia.

Biological cilia, hairlike organelles on cell surfaces, often exhibit collective wavelike motion known as metachrony, which helps generating fluid flow. Inspired by nature, researchers have developed artificial cilia as microfluidic actuators, exploring several methods to mimic the metachrony. However, reported methods are difficult to miniaturize because they require either control of individual cilia properties or the generation of a complex external magnetic field. We introduce a concept that generates metachronal motion of magnetic artificial cilia (MAC), even though the MAC are all identical, and the applied external magnetic field is uniform. This is achieved by integrating a paramagnetic substructure in the substrate underneath the MAC. Uniquely, we can create both symplectic and antiplectic metachrony by changing the relative positions of MAC and substructure. We demonstrate the flow generation of the two metachronal motions in both high and low Reynolds number conditions. Our research marks a significant milestone by breaking the size limitation barrier in metachronal artificial cilia. This achievement not only showcases the potential of nature-inspired engineering but also opens up a host of exciting opportunities for designing and optimizing microsystems with enhanced fluid manipulation capabilities.

Actuation-enhanced multifunctional sensing and information recognition by magnetic artificial cilia arrays.

Artificial cilia integrating both actuation and sensing functions allow simultaneously sensing environmental properties and manipulating fluids in situ, which are promising for environment monitoring and fluidic applications. However, existing artificial cilia have limited ability to sense environmental cues in fluid flows that have versatile information encoded. This limits their potential to work in complex and dynamic fluid-filled environments. Here, we propose a generic actuation-enhanced sensing mechanism to sense complex environmental cues through the active interaction between artificial cilia and the surrounding fluidic environments. The proposed mechanism is based on fluid-cilia interaction by integrating soft robotic artificial cilia with flexible sensors. With a machine learning-based approach, complex environmental cues such as liquid viscosity, environment boundaries, and distributed fluid flows of a wide range of velocities can be sensed, which is beyond the capability of existing artificial cilia. As a proof of concept, we implement this mechanism on magnetically actuated cilia with integrated laser-induced graphene-based sensors and demonstrate sensing fluid apparent viscosity, environment boundaries, and fluid flow speed with a reconfigurable sensitivity and range. The same principle could be potentially applied to other soft robotic systems integrating other actuation and sensing modalities for diverse environmental and fluidic applications.

Enhancement of microalgae growth using magnetic artificial cilia.

Microalgae have shown great potential as a source of biofuels, food, and other bioproducts. More recently, microfluidic devices have been employed in microalgae-related studies. However, at small fluid volumes, the options for controlling flow conditions are more limited and mixing becomes largely reliant on diffusion. In this study, we fabricated magnetic artificial cilia (MAC) and implemented them in millimeter scale culture wells and conducted growth experiments with Scenedesmus subspicatus while actuating the MAC in a rotating magnetic field to create flow and mixing. In addition, surface of MAC was made hydrophilic using plasma treatment and its effect on growth was compared with untreated, hydrophobic MAC. The experiments showed that the growth was enhanced by ten and two times with hydrophobic and hydrophilic MAC, respectively, compared with control groups which contain no MAC. This technique can be used to investigate mixing and flow in small sample volumes, and the enhancement in growth can be beneficial for the throughput of screening studies. Moreover, the methods used for creating and controlling MAC can be easily adopted in labs without microfabrication infrastructures, and they can be mastered by people with little prior experience in microfluidics.

Engineered modular microphysiological models of the human airway clearance phenomena.

Mucociliary clearance is a crucial mechanism that supports the elimination of inhaled particles, bacteria, pollution, and hazardous agents from the human airways, and it also limits the diffusion of aerosolized drugs into the airway epithelium. In spite of its relevance, few in vitro models sufficiently address the cumulative effect of the steric and interactive barrier function of mucus on the one hand, and the dynamic mucus transport imposed by ciliary mucus propulsion on the other hand. Here, ad hoc mucus models of physiological and pathological mucus are combined with magnetic artificial cilia to model mucociliary transport in both physiological and pathological states. The modular concept adopted in this study enables the development of mucociliary clearance models with high versatility since these can be easily modified to reproduce phenomena characteristic of healthy and diseased human airways while allowing to determine the effect of each parameter and/or structure separately on the overall mucociliary transport. These modular airway models can be available off-the-shelf because they are exclusively made of readily available materials, thus ensuring reproducibility across different laboratories.

A stirring system using suspended magnetically-actuated pillars for controlled cell clustering.

Controlled stirring of a solution is a household task in most laboratories. However, most stirring methods are perturbative or require vessels with predefined shapes and sizes. Here we propose a novel stirring system based on suspended magnetically-actuated pillars (SMAPs), inspired by the ability of biological flagella and cilia to generate flow. We fabricated flexible, millimeter-scale magnetic pillars grafted on transparent polydimethylsiloxane (PDMS) substrates and built a simple actuation setup to control the motion of the pillars remotely. We tested the system with a standard 24-well plate routinely used in most research laboratories and demonstrate that the magnetic actuation results in robust bending of the pillars and large-scale fluid flow in the wells. Quantitative analysis using computational fluid dynamics modeling indicates that the flow profile in the well can be tuned by modulating the applied magnetic field and the geometries of the well and the pillar. Finally, we show that, by employing the stirring system in a standard cell culture plate, we were able to obtain controlled clustering of cells. The SMAP stirring system is therefore a promising cost-effective and scalable stirring approach for various types of studies involving colloids as well as soft and biological materials.

Effect of tea polyphenols on chitosan packaging for food preservation: Physicochemical properties, bioactivity, and nutrition.

Chitosan packaging has been widely studied for food preservation, the application of which is expanded by the incorporation of tea polyphenols. This paper reviews the influence of tea polyphenols incorporation on chitosan-based packaging from the perspectives of physicochemical properties, bioactivity used for food preservation, and nutritional value. The physicochemical properties included optical properties, mechanical properties, water solubility, moisture content, and water vapor barrier property, concluding that the addition of tea polyphenols improved the opacity, water solubility, and water vapor barrier property of chitosan packaging, and the mechanical properties and water content were decreased. The bioactivity used for food preservation, that is antioxidant and antimicrobial properties, is enhanced by tea polyphenols, improving the preservation of food like meat, fruits, and vegetables. In the future, efforts will be needed to improve the mechanical properties of composite film and adjust the formula of tea polyphenols/chitosan composite film to apply to different foods. Besides, the identification and development of high nutritional value tea polyphenol/chitosan composite film is a valuable but challenging task. This review is expected to scientifically guide the application of tea polyphenols in chitosan packaging.

Recent advances in delivery systems of fucoxanthin.

Fucoxanthin is a carotenoid derived from marine algae/microalgae, which has wide application in the food industry. This review first proposes the promotion development of fucoxanthin delivery systems from the perspective of diverse biological activities, extraction complexity, instability, poor aqueous solubility, and low bioavailability. The materials for the delivery systems of fucoxanthin mainly include protein, polysaccharide, and lipid. Colloidal structures include nanoparticles, microcapsules, emulsions, gels, coacervates, and nanofibers. Delivery systems exhibited positive effects on the stability, release, bioavailability, and bioactivity of fucoxanthin. Currently, the reported applications of fucoxanthin in food are limited. A variety of colloidal structures should be constructed to provide options for fucoxanthin applications in different foods, and the applicability of fucoxanthin colloidal structures in commercial products should be advanced. Additionally, a set of internationally unified evaluation criteria for fucoxanthin stability and bioavailability should be established.

Pd-Catalyzed TBHP-Mediated Selective Wacker-Type Oxidation and Oxo-acyloxylation of Olefins Using a 2-(1H-Indazol-1-yl)quinoline Ligand.

Pd(II)-catalyzed oxidation of terminal olefins to methyl ketones has emerged as an attractive strategy for organic synthesis. Here we report the Pd(II)-catalyzed selective oxidation of olefins using tert-butyl hydroperoxide as the oxidant and 2-(1H-indazol-1-yl)quinoline as the ligand. A wide range of olefins were well tolerated in this reaction system to provide methyl ketones, whereas the presence of Ac2O initiated the oxo-acyloxylation to afford the α-acetoxyacetone products. Isotope labeling studies and active-intermediate-capture experiments were performed to elucidate the underlying selective reaction mechanism. Notably, the generation of α-acetoxyacetone products involves the palladium enolate intermediate while the methyl ketone products were generated through the most commonly proposed alkylperoxide intermediates, followed by 1,2-hydride migration.

Rh(III)-catalyzed regioselective versatile indole derivatization: delivering potential of rare ß-(1H-indol-2-yl)-ß-amino acids in one pot.

Rh-catalyzed selective C-H functionalization of indoles with two routes was developed: an alkenylation-annulation with the addition of KHSO4 and alkenylation-elimination in the presence of CsOAc to the corresponding products, respectively. Notably, one-pot hydrolysis and benzoylation of the annulation products successfully afforded easily separable ß-(1H-indol-2-yl)-ß-amino acid derivatives.

Efficient Utilization of Tea Resources through Encapsulation: Dual Perspectives from Core Material to Wall Material.

With the high production and consumption of tea around the world, efficient utilization of tea byproducts (tea pruning, tea residues after production, and drinking) is the focus of improving the economy of the tea industry. This review comprehensively discusses the efficient utilization of tea resources by encapsulation from the dual perspectives of core material and wall material. The core material is mainly tea polyphenols, followed by tea oils. The encapsulation system for tea polyphenols includes microcapsules, nanoparticles, emulsions, gels, conjugates, metal-organic frameworks, liposomes, and nanofibers. In addition, it is also diversified for the encapsulation of tea oils. Tea resources as wall materials refer to tea saponins, tea polyphenols, tea proteins, and tea polysaccharides. The application of the tea-based delivery system widely involves functionally fortified food, meat preservation, film, medical treatment, wastewater treatment, and plant protection. In the future, the coencapsulation of tea resources as core materials and other functional ingredients, the precise targeting of these tea resources, and the wide application of tea resources in wall materials need to be focused on. In conclusion, the described technofunctional properties and future research challenges in this review should be followed.

3D-printed micrometer-scale wireless magnetic cilia with metachronal programmability.

Biological cilia play essential roles in self-propulsion, food capture, and cell transportation by performing coordinated metachronal motions. Experimental studies to emulate the biological cilia metachronal coordination are challenging at the micrometer length scale because of current limitations in fabrication methods and materials. We report on the creation of wirelessly actuated magnetic artificial cilia with biocompatibility and metachronal programmability at the micrometer length scale. Each cilium is fabricated by direct laser printing a silk fibroin hydrogel beam affixed to a hard magnetic FePt Janus microparticle. The 3D-printed cilia show stable actuation performance, high temperature resistance, and high mechanical endurance. Programmable metachronal coordination can be achieved by programming the orientation of the identically magnetized FePt Janus microparticles, which enables the generation of versatile microfluidic patterns. Our platform offers an unprecedented solution to create bioinspired microcilia for programmable microfluidic systems, biomedical engineering, and biocompatible implants.

C(sp3)-H oxygenation via alkoxypalladium(ii) species: an update for the mechanism.

Pd-catalyzed C(sp3)-H oxygenation has emerged as an attractive strategy for organic synthesis. The most commonly proposed mechanism involves C(sp3)-H activation followed by oxidative addition of an oxygen electrophile to give an alkylpalladium(iv) species and further C(sp3)-O reductive elimination. In the present study of γ-C(sp3)-H acyloxylation of amine derivatives, we show a different mechanism when tert-butyl hydroperoxide (TBHP) is used as an oxidant-namely, a bimetallic oxidative addition-oxo-insertion process. This catalytic model results in an alkoxypalladium(ii) intermediate from which acyloxylation and alkoxylation products are formed. Experimental and computational studies, including isolation of the putative post-oxo-insertion alkoxypalladium(ii) intermediates, support this mechanistic model. Density functional theory reveals that the classical alkylpalladium(iv) oxidative addition pathway is higher in energy than the bimetallic oxo-insertion pathway. Further kinetic studies revealed second-order dependence on [Pd] and first-order on [TBHP], which is consistent with DFT analysis. This procedure is compatible with a wide range of acids and alcohols for γ-C(sp3)-H oxygenation. Preliminary functional group transformations of the products underscore the great potential of this protocol for structural manipulation.

Delivery of curcumin by shellac encapsulation: Stability, bioaccessibility, freeze-dried redispersibility, and solubilization.

Curcumin is an active ingredient with multiple functions, however, its application is limited by its low stability, bioaccessibility, freeze-dried redispersibility, and solubilization. The work aims to improve the application of curcumin (Cur) by encapsulation. Shellac was the wall material inspired by its pH-dependent deprotonation and amphiphilic nature to form nanoparticles. The curcumin/shellac nanoparticles (S/Cur) exhibited a bright spot of high loading capacity (the maximum of higher than 70 %), while still having high encapsulation efficiency (the minimum of higher than 85 %). Transmission electron microscopy showed that S/Cur was a spherical structure. It exhibited good physical stability, including pH (4.0-8.0), ionic strength (NaCl, < 900 mM), thermo stability (80 â„ƒ, 180 min), and storage stability (light and dark, 4 and 25 â„ƒ, 20 days). Meanwhile, the chemical stability was increased by encapsulation. Furthermore, the bioaccessibility of Cur was improved to 75.95 %, which is attributed to the pH response of shellac. Additionally, S/Cur had freeze-dried redispersibility and solubilization, which is proportional to the mass ratio of shellac-to-Cur. The mechanism of S/Cur formation involved hydrophobic interaction and hydrogen bonds, and the nanoconfined Cur was amorphous.

pH-driven self-assembly of alcohol-free curcumin-loaded propylene glycol alginate nanoparticles.

The purpose of this paper was to explore the application of propylene glycol alginate (PGA) alone in alcohol-free curcumin-loaded nanoparticles (PGA/Cur) prepared by a pH-driven method to solve the curcumin shortcomings of low water solubility, stability and bioavailability. One of the bright spots of PGA/Cur was its extremely high loading capacity. PGA/Cur formed a spherical structure mainly by hydrophobic interaction and hydrogen bonding, making curcumin amorphous. PGA/Cur exhibited stability at pH 4.0-8.0 due to its high surface charges. PGA/Cur still showed a unimodal size distribution even under 3000 mM ionic strength. Heating caused uneven size distribution, but the smaller size still presented its thermostability. PGA/Cur exhibited good physical stability and slowed down the curcumin degradation with t1/2 of 37.47 days during storage. PGA/Cur could maintain structural integrity in gastric acid and released curcumin in the intestine, thus improving the bioaccessibility of curcumin. Additionally, PGA/Cur displayed the solubilization after lyophilization.

Microscopic artificial cilia - a review.

Cilia are microscopic hair-like external cell organelles that are ubiquitously present in nature, also within the human body. They fulfill crucial biological functions: motile cilia provide transportation of fluids and cells, and immotile cilia sense shear stress and concentrations of chemical species. Inspired by nature, scientists have developed artificial cilia mimicking the functions of biological cilia, aiming at application in microfluidic devices like lab-on-chip or organ-on-chip. By actuating the artificial cilia, for example by a magnetic field, an electric field, or pneumatics, microfluidic flow can be generated and particles can be transported. Other functions that have been explored are anti-biofouling and flow sensing. We provide a critical review of the progress in artificial cilia research and development as well as an evaluation of its future potential. We cover all aspects from fabrication approaches, actuation principles, artificial cilia functions - flow generation, particle transport and flow sensing - to applications. In addition to in-depth analyses of the current state of knowledge, we provide classifications of the different approaches and quantitative comparisons of the results obtained. We conclude that artificial cilia research is very much alive, with some concepts close to industrial implementation, and other developments just starting to open novel scientific opportunities.

Direct Transition-Metal Free Benzene C-H Functionalization by Intramolecular Non-Nitroarene Nucleophilic Aromatic Substitution of Hydrogen to Diverse AIEgens.

Direct C(sp2 )-H functionalization through nitroarene-triggered nucleophilic aromatic substitution of hydrogen (SNArH ) has attracted growing attention, owing to its high efficiency and low carbon footprint. In this study, non-nitro-group-assisted SN ArH has been developed for direct benzene functionalization in one pot under mild conditions. The electron-withdrawing carbonyl group and the halide or trifluoromethyl group on the phenyl ring enable the σH adduct formation to fulfill the intramolecular C(sp2 )-C(sp3 ) bond construction. Notably, the cyano group serves as both the electron-withdrawing group to activate the C(sp3 )-H bond and the leaving group to fulfill the ß-elimination. Three series of pyrrolo[1,2-b]isoquinolinones, as well as unexpected rearrangement products 3-(1H-pyrrol-2-yl)-1H-inden-1-ones are regioselectively obtained through a simple and efficient base-catalyzed one-pot strategy. Mechanistic studies indicate that the σH adduct from carbanion addition to hydrogen serves as the sole intermediate for all of the aforementioned transformations. These molecules show intense luminescence and the subsequent one-step structural modification results in the aggregation-induced emission (AIE) derivatives with redshifted full-color tunable fluorescence, large Stokes shifts, and good quantum yields. Further living cell imaging investigations suggest their potential application as specific bioprobes for lipid droplet localization and visualization.

Acid- and Base-Switched Palladium-Catalyzed γ-C(sp3)-H Alkylation and Alkenylation of Neopentylamine.

The functionalization of remote unactivated C(sp3)-H and the reaction selectivity are among the core pursuits for transition-metal catalytic system development. Herein, we report Pd-catalyzed γ-C(sp3)-H-selective alkylation and alkenylation with removable 7-azaindole as a directing group. Acid and base were found to be the decisive regulators for the selective alkylation and alkenylation, respectively, on the same single substrate under otherwise the same reaction conditions. Various acrylates were compatible for the formation of C(sp3)-C(sp3) and C(sp3)-C(sp2) bonds. The alkenylation protocol could be further extended to acrylates with natural product units and α,ß-unsaturated ketones. The preliminary synthetic manipulation of the alkylation and alkenylation products demonstrates the potential of this strategy for structurally diverse aliphatic chain extension and functionalization. Mechanistic experimental studies showed that the acidic and basic catalytic transformations shared the same six-membered dimer palladacycle.

Metachronal µ-Cilia for On-Chip Integrated Pumps and Climbing Robots.

Biological cilia often perform metachronal motion, that is, neighboring cilia move out of phase creating a travelling wave, which enables highly efficient fluid pumping and body locomotion. Current methods for creating metachronal artificial cilia suffer from the complex design and sophisticated actuation schemes. This paper demonstrates a simple method to realize metachronal microscopic magnetic artificial cilia (µMAC) through control over the paramagnetic particle distribution within the µMAC based on their tendency to align with an applied magnetic field. Actuated by a 2D rotating uniform magnetic field, the metachronal µMAC enable strong microfluidic pumping and soft robot locomotion. The metachronal µMAC induce twice the pumping efficiency and 3 times the locomotion speed of synchronously moving µMAC. The ciliated soft robots show an unprecedented slope climbing ability (0 to 180°), and they display strong cargo-carrying capacity (>10 times their own weight) in both dry and wet conditions. These findings advance the design of on-chip integrated pumps and versatile soft robots, among others.

Controlled Multidirectional Particle Transportation by Magnetic Artificial Cilia.

Manipulation of particles in a controllable manner is highly desirable in many applications. Inspired by biological cilia, this article experimentally and numerically demonstrates a versatile particle transportation platform consisting of arrays of magnetic artificial cilia (MAC) actuated by a rotating magnet. By performing a tilted conical motion, the MAC are capable of transporting particles on their tips, along designated directions that can be fully controlled by the externally applied magnetic field, in both liquid and air, at high resolution (particle precision), with varying speeds and for a range of particle sizes. Moreover, the underlying mechanism of the controlled particle transportation is studied in depth by combining experiments with numerical simulations. The results show that the adhesion and friction between the particle and the cilia are essential ingredients of the mechanism underlying the multidirectional transportation. This work offers an advanced solution to controllably transport particles along designated paths in any direction over a surface, which has potential applications in diverse fields including lab-on-a-chip devices, in vitro biomedical sciences, and self-cleaning and antifouling.

Metachronal actuation of microscopic magnetic artificial cilia generates strong microfluidic pumping.

Biological cilia that generate fluid flow or propulsion are often found to exhibit a collective wavelike metachronal motion, i.e. neighboring cilia beat slightly out-of-phase rather than synchronously. Inspired by this observation, this article experimentally demonstrates that microscopic magnetic artificial cilia (µMAC) performing a metachronal motion can generate strong microfluidic flows, though, interestingly, the mechanism is different from that in biological cilia, as is found through a systematic experimental study. The µMAC are actuated by a facile magnetic setup, consisting of an array of rod-shaped magnets. This arrangement imposes a time-dependent non-uniform magnetic field on the µMAC array, resulting in a phase difference between the beatings of adjacent µMAC, while each cilium exhibits a two-dimensional whip-like motion. By performing the metachronal 2D motion, the µMAC are able to generate a strong flow in a microfluidic chip, with velocities of up to 3000 µm s-1 in water, which, different from biological cilia, is found to be a result of combined metachronal and inertial effects, in addition to the effect of asymmetric beating. The pumping performance of the metachronal µMAC outperforms all previously reported microscopic artificial cilia, and is competitive with that of most of the existing microfluidic pumping methods, while the proposed platform requires no physical connection to peripheral equipment, reduces the usage of reagents by minimizing "dead volumes", avoids undesirable electrical effects, and accommodates a wide range of different fluids. The 2D metachronal motion can also generate a flow with velocities up to 60 µm s-1 in pure glycerol, where Reynolds number is less than 0.05 and the flow is primarily caused by the metachronal motion of the µMAC. These findings offer a novel solution to not only create on-chip integrated micropumps, but also design swimming and walking microrobots, as well as self-cleaning and antifouling surfaces.