Microfluidic Generation of All‐Aqueous Double and Triple Emulsions

Higher order emulsions are used in a variety of different applications in biomedicine, biological studies, cosmetics, and the food industry. Conventional droplet generation platforms for making higher order emulsions use organic solvents as the continuous phase, which is not biocompatible and as a result, further washing steps are required to remove the toxic continuous phase. Recently, droplet generation based on aqueous two‐phase systems (ATPS) has emerged in the field of droplet microfluidics due to their intrinsic biocompatibility. Here, a platform to generate all‐aqueous double and triple emulsions by introducing pressure‐driven flows inside a microfluidic hybrid device is presented. This system uses a conventional microfluidic flow‐focusing geometry coupled with a coaxial microneedle and a glass capillary embedded in flow‐focusing junctions. The configuration of the hybrid device enables the focusing of two coaxial two‐phase streams, which helps to avoid commonly observed channel‐wetting problems. It is shown that this approach achieves the fabrication of higher‐order emulsions in a poly(dimethylsiloxane)‐based microfluidic device, and controls the structure of the all‐aqueous emulsions. This hybrid microfluidic approach allows for facile higher‐order biocompatible emulsion formation, and it is anticipated that this platform will find utility for generating biocompatible materials for various biotechnological applications.     

Microfluidic Synthesis of pH‐Sensitive Multicompartmental Microparticles for Multimodulated Drug Release

Stimuli‐responsive carriers releasing multiple drugs have been researched for synergistic combinatorial cancer treatment with reduced side‐effects. However, previously used drug carriers have limitations in encapsulating multiple drug components in a single carrier and releasing each drug independently. In this work, pH‐sensitive, multimodulated, anisotropic drug carrier particles are synthesized using an acid‐cleavable polymer and stop‐flow lithography. The particles exhibit a faster drug release rate at the acidic pH of tumors than at physiological pH, demonstrating their potential for tumor‐selective drug release. The drug release rate of the particles can be adjusted by controlling the monomer composition. To accomplish multimodulated drug release, multicompartmental particles are synthesized. The drug release profile of each compartment is programmed by tailoring the monomer composition. These pH‐sensitive, multicompartmental particles are promising drug carriers enabling tumor‐selective and multimodulated release of multiple drugs for synergistic combination cancer therapy.     

Preparation of Monodisperse Biodegradable Polymer Microparticles Using a Microfluidic Flow‐Focusing Device for Controlled Drug Delivery

Degradable microparticles have broad utility as vehicles for drug delivery and form the basis of several therapies approved by the US Food and Drug Administration. Conventional emulsion‐based methods of manufacturing produce particles with a wide range of diameters (and thus kinetics of release) in each batch. This paper describes the fabrication of monodisperse, drug‐loaded microparticles from biodegradable polymers using the microfluidic flow‐focusing (FF) devices and the drug‐delivery properties of those particles. Particles are engineered with defined sizes, ranging from 10 µm to 50 µm. These particles are nearly monodisperse (polydispersity index = 3.9%). A model amphiphilic drug (bupivacaine) is incorporated within the biodegradable matrix of the particles. Kinetic analysis shows that the release of the drug from these monodisperse particles is slower than that from conventional methods of the same average size but a broader distribution of sizes and, most importantly, exhibit a significantly lower initial burst than that observed with conventional particles. The difference in the initial kinetics of drug release is attributed to the uniform distribution of the drug inside the particles generated using the microfluidic methods. These results demonstrate the utility of microfluidic FF for the generation of homogenous systems of particles for the delivery of drugs.     

A New Approach to In‐Situ “Micromanufacturing”: Microfluidic Fabrication of Magnetic and Fluorescent Chains Using Chitosan Microparticles as Building Blocks

An in situ microfluidic assembly approach is described that can both produce microsized building blocks and assemble them into complex multiparticle configurations in the same microfluidic device. The building blocks are microparticles of the biopolymer chitosan, which is intentionally selected because its chemistry allows for simultaneous intraparticle and interparticle linking. Monodisperse chitosan‐bearing droplets are created by shearing off a chitosan solution at a microfluidic T‐junction with a stream of hexadecane containing a nonionic detergent. These droplets are then interfacially crosslinked into stable microparticles by a downstream flow of glutaraldehyde (GA). The functional properties of these robust microparticles can be easily varied by introducing various payloads, such as magnetic nanoparticles and/or fluorescent dyes, into the chitosan solution. The on‐chip connection of such individual particles into well‐defined microchains is demonstrated using GA again as the chemical “glue” and microchannel confinement as the spatial template. Chain flexibility can be tuned by adjusting the crosslinking conditions: both rigid chains and semiflexible chains are created. Additionally, the arrangement of particles within a chain can also be controlled, for example, to generate chains with alternating fluorescent and nonfluorescent microparticles. Such microassembled chains could find applications as microfluidic mixers, delivery vehicles, microscale sensors, or miniature biomimetic robots.     

Facile and High‐Throughput Synthesis of Functional Microparticles with Quick Response Codes

Encoded microparticles are high demand in multiplexed assays and labeling. However, the current methods for the synthesis and coding of microparticles either lack robustness and reliability, or possess limited coding capacity. Here, a massive coding of dissociated elements (MiCODE) technology based on innovation of a chemically reactive off‐stoichimetry thiol‐allyl photocurable polymer and standard lithography to produce a large number of quick response (QR) code microparticles is introduced. The coding process is performed by photobleaching the QR code patterns on microparticles when fluorophores are incorporated into the prepolymer formulation. The fabricated encoded microparticles can be released from a substrate without changing their features. Excess thiol functionality on the microparticle surface allows for grafting of amine groups and further DNA probes. A multiplexed assay is demonstrated using the DNA‐grafted QR code microparticles. The MiCODE technology is further characterized by showing the incorporation of BODIPY‐maleimide (BDP‐M) and Nile Red fluorophores for coding and the use of microcontact printing for immobilizing DNA probes on microparticle surfaces. This versatile technology leverages mature lithography facilities for fabrication and thus is amenable to scale‐up in the future, with potential applications in bioassays and in labeling consumer products.     

Rapid Production of Cell‐Laden Microspheres Using a Flexible Microfluidic Encapsulation Platform

This study establishes a novel microfluidic platform for rapid encapsulation of cells at high densities in photocrosslinkable microspherical hydrogels including poly(ethylene glycol)‐diacrylate, poly(ethylene glycol)‐fibrinogen, and gelatin methacrylate. Cell‐laden hydrogel microspheres are advantageous for many applications from drug screening to regenerative medicine. Employing microfluidic systems is considered the most efficient method for scale‐up production of uniform microspheres. However, existing platforms have been constrained by traditional microfabrication techniques for device fabrication, restricting microsphere diameter to below 200 µm and making iterative design changes time‐consuming and costly. Using a new molding technique, the microfluidic device employs a modified T‐junction design with readily adjustable channel sizes, enabling production of highly uniform microspheres with cell densities (10–60 million cells mL^?1) and a wide range of diameters (300–1100 µm), which are critical for realizing downstream applications, through rapid photocrosslinking (≈1 s per microsphere). Multiple cell types are encapsulated at rates of up to 1 million cells per min, are evenly distributed throughout the microspheres, and maintain high viability and appropriate cellular activities in long‐term culture. This microfluidic encapsulation platform is a valuable and readily adoptable tool for numerous applications, including supporting injectable cell therapy, bioreactor‐based cell expansion and differentiation, and high throughput tissue sphere‐based drug testing assays.     

Continuous Flow Deformability‐Based Separation of Circulating Tumor Cells Using Microfluidic Ratchets

Circulating tumor cells (CTCs) offer tremendous potential for the detection and characterization of cancer. A key challenge for their isolation and subsequent analysis is the extreme rarity of these cells in circulation. Here, a novel label‐free method is described to enrich viable CTCs directly from whole blood based on their distinct deformability relative to hematological cells. This mechanism leverages the deformation of single cells through tapered micrometer scale constrictions using oscillatory flow in order to generate a ratcheting effect that produces distinct flow paths for CTCs, leukocytes, and erythrocytes. A label‐free separation of circulating tumor cells from whole blood is demonstrated, where target cells can be separated from background cells based on deformability despite their nearly identical size. In doping experiments, this microfluidic device is able to capture >90% of cancer cells from unprocessed whole blood to achieve 10⁴‐fold enrichment of target cells relative to leukocytes. In patients with metastatic castration‐resistant prostate cancer, where CTCs are not significantly larger than leukocytes, CTCs can be captured based on deformability at 25× greater yield than with the conventional CellSearch system. Finally, the CTCs separated using this approach are collected in suspension and are available for downstream molecular characterization.     

Synergistic Impacts of Electrolyte Adsorption on the Thermoelectric Properties of Single‐Walled Carbon Nanotubes

Single‐walled carbon nanotubes are promising candidates for light‐weight and flexible energy materials. Recently, the thermoelectric properties of single‐walled carbon nanotubes have been dramatically improved by ionic liquid addition; however, controlling factors remain unsolved. Here the thermoelectric properties of single‐walled carbon nanotubes enhanced by electrolytes are investigated. Complementary characterization with absorption, Raman, and X‐ray photoelectron spectroscopy reveals that shallow hole doping plays a partial role in the enhanced electrical conductivity. The molecular factors controlling the thermoelectric properties of carbon nanotubes are systematically investigated in terms of the ionic functionalities of ionic liquids. It is revealed that appropriate ionic liquids show a synergistic enhancement in conductivity and the Seebeck coefficient. The discovery of significantly precise doping enables the generation of thermoelectric power factor exceeding 460 µW m^–1 K^–2.     

Impedance Spectroscopy of Ionic Ligand‐Modulated Charge Transport of Gold Nanoparticle Films

Assembled monolayer‐protected nanoparticles (NPs) possess unique electrical properties that are determined by the coupled effects of their nano‐sized electroactive inorganic cores that are capable of donating and accepting electrons and the organic shells. Core and ligand engineering for NP conductance modulation has been extensively explored; however, most studies focus on electron transport and not the interplay between the ion and electron transport processes. It is demonstrated here that electronic‐ and ionic‐conducting properties of nanoparticle assemblies can be controlled by engineering the charge and flexibility of the ligand shell. By using impedance spectroscopy, the electronic, mixed ionic and electronic, and responsive conductance of the nanoparticle film and structure‐function correlation are systematically investigated, and this correlation is used to provide a prototype volatile gas sensor based on the combined ionic and electronic conductance behavior of ionic ligand‐functionalized gold NPs.     

Ambient Protection of Few‐Layer Black Phosphorus via Sequestration of Reactive Oxygen Species

Few‐layer black phosphorous (BP) has emerged as a promising candidate for next‐generation nanophotonic and nanoelectronic devices. However, rapid ambient degradation of mechanically exfoliated BP poses challenges in its practical deployment in scalable devices. To date, the strategies employed to protect BP have relied upon preventing its exposure to atmospheric conditions. Here, an approach that allows this sensitive material to remain stable without requiring its isolation from the ambient environment is reported. The method draws inspiration from the unique ability of biological systems to avoid photo‐oxidative damage caused by reactive oxygen species. Since BP undergoes similar photo‐oxidative degradation, imidazolium‐based ionic liquids are employed as quenchers of these damaging species on the BP surface. This chemical sequestration strategy allows BP to remain stable for over 13 weeks, while retaining its key electronic characteristics. This study opens opportunities to practically implement BP and other environmentally sensitive 2D materials for electronic applications.