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Small extracellular vesicles (sEVs) are membranous vesicles released from cellular structures through plasma membrane budding. These vesicles contain cellular components such as proteins, lipids, mRNAs, microRNAs, long-noncoding RNA, circular RNA, and double-stranded DNA, originating from the cells they are shed from. Ranging in size from ≈25 to 300 nm and play critical roles in facilitating cell-to-cell communication by transporting signaling molecules. The discovery of sEVs in bodily fluids and their involvement in intercellular communication has revolutionized the fields of diagnosis, prognosis, and treatment, particularly in diseases like cancer. Conventional methods for isolating and analyzing sEVs, particularly their nucleic acid content face challenges including high costs, low purity, time-consuming processes, limited standardization, and inconsistent yield. The development of microfluidic devices, enables improved precision in sorting, isolating, and molecular-level separation using small sample volumes, and offers significant potential for the enhanced detection and monitoring of sEVs associated with cancer. These advanced techniques hold great promise for creating next-generation diagnostic and prognostic tools given their possibility of being cost-effective, simple to operate, etc. This comprehensive review explores the current state of research on microfluidic devices for the detection of sEV-derived nucleic acids as biomarkers and their translation into practical point-of-care and clinical applications., (© 2024 Wiley‐VCH GmbH.)

There is a recent resurgence of interest in phage therapy (the therapeutic use of bacterial viruses) as an approach to eliminating difficult-to-treat infections. However, existing approaches for therapeutic phage selection and virulence testing are time-consuming, host-dependent, and facing reproducibility issues. Here, this study presents an innovative approach wherein integrated resonant photonic crystal (PhC) cavities in silicon are used as optical nanotweezers for probing and manipulating single bacteria and single virions with low optical power. This study demonstrates that these nanocavities differentiate between a bacterium and a phage without labeling or specific surface bioreceptors. Furthermore, by tailoring the spatial extent of the resonant optical mode in the low-index medium, phage distinction across phenotypically distinct phage families is demonstrated. The work paves the road to the implementation of optical nanotweezers in phage therapy protocols., (© 2024 The Authors. Small published by Wiley‐VCH GmbH.)

A novel class of diazonium salts is introduced for the photochemical aryl-aryl coupling to produce (substituted) biphenyls. As common diazonium tetrafluoroborate salts fail, soluble and safe aryl diazonium trifluoroacetates are applied. In this mild synthesis route no catalysts are required to generate an aryl-radical by irradiation with UV-A light (365 nm). This reactive species undergoes direct C-H arylation at an arene, forming the product in reasonable reaction times. With the implementation of a continuous flow setup in a capillary photoreactor 13 different biphenyl derivatives are successfully synthesized. By integrating an inline 19 F-NMR benchtop spectrometer, samples are reliably quantified as the fluorine-substituents act as a probe. Here, real-time NMR spectroscopy is a perfect tool to monitor the continuously operated system, which produces fine chemicals of industrial relevance even in a multigram scale., (© 2024 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Although hypodermic needles are a "gold standard" for transdermal drug delivery (TDD), microneedle (MN)-mediated TDD denotes an unconventional approach in which drug compounds are delivered via micron-size needles. Herein, an isotropic XeF 2 dry etching process is explored to fabricate silicon-based solid MNs. A photolithographic process, including mask writing, UV exposure, and dry etching with XeF 2 is employed, and the MN fabrication is successfully customized by modifying the CAD designs, photolithographic process, and etching conditions. This study enables fabrication of a very dense MNs (up to 1452 MNs cm -2 ) with height varying between 80 and 300 µm. Geometrical features are also assessed using scanning electron microscopy (SEM) and 3D laser scanning microscope. Roughness of the MNs are improved from 0.71 to 0.35 µm after titanium and chromium coating. Mechanical failure test is conducted using dynamic mechanical analyzer to determine displacement and stress/strain values. The coated MNs are subjected to less displacement (≈15 µm) upon the applied force. COMSOL Multiphysics analysis indicates that MNs are safe to use in real-life applications with no fracture. This technique also enables the production of MNs with distinct shape and dimensions. The optimized process provides a wide range of solid MN types to be utilized for epidermis targeting., (© 2023 The Authors. Small published by Wiley-VCH GmbH.)

A Teflon AF-2400 based tube-in-tube device was used to generate flow streams of CO 2 in acetonitrile and a computer-vision based 'bubble counting' technique was used to estimate the amount of CO 2 that had passed into solution whilst in the tube-in-tube device by quantifying the amount of CO 2 that left solution (forming separate gas-phase segments) downstream of the back-pressure regulator. For both CO 2 pressures used, there appeared to be a minimum residence time below which no CO 2 was observed to leave solution. This was assumed to be due to residual CO 2 below (or close to) the saturation concentration at atmospheric pressure and, by taking this into account, we were able to fit curves corresponding to simple gradient-driven diffusion and which closely matched previously obtained colorimetric titration data for the same system. The estimated value for the residual concentration of CO 2 (0.37 M) is higher than, but in reasonable general correspondence with, saturation concentrations previously reported for CO 2 in acetonitrile (0.27 M)., (© 2022 The Authors. ChemPlusChem published by Wiley-VCH GmbH.)

Nanoparticles (NPs) have attracted tremendous interest in drug delivery in the past decades. Microfluidics offers a promising strategy for making NPs for drug delivery due to its capability in precisely controlling NP properties. The recent success of mRNA vaccines using microfluidics represents a big milestone for microfluidic NPs for pharmaceutical applications, and its rapid scaling up demonstrates the feasibility of using microfluidics for industrial-scale manufacturing. This article provides a critical review of recent progress in microfluidic NPs for drug delivery. First, the synthesis of organic NPs using microfluidics focusing on typical microfluidic methods and their applications in making popular and clinically relevant NPs, such as liposomes, lipid NPs, and polymer NPs, as well as their synthesis mechanisms are summarized. Then, the microfluidic synthesis of several representative inorganic NPs (e.g., silica, metal, metal oxide, and quantum dots), and hybrid NPs is discussed. Lastly, the applications of microfluidic NPs for various drug delivery applications are presented., (© 2022 The Authors. Small published by Wiley-VCH GmbH.)

Intracellular delivery is considered an indispensable process for various studies, ranging from medical applications (cell-based therapy) to fundamental (genome-editing) and industrial (biomanufacture) approaches. Conventional macroscale delivery systems critically suffer from such issues as low cell viability, cytotoxicity, and inconsistent material delivery, which have opened up an interest in the development of more efficient intracellular delivery systems. In line with the advances in microfluidics and nanotechnology, intracellular delivery based on micro- and nanoengineered platforms has progressed rapidly and held great promises owing to their unique features. These approaches have been advanced to introduce a smorgasbord of diverse cargoes into various cell types with the maximum efficiency and the highest precision. This review differentiates macro-, micro-, and nanoengineered approaches for intracellular delivery. The macroengineered delivery platforms are first summarized and then each method is categorized based on whether it employs a carrier- or membrane-disruption-mediated mechanism to load cargoes inside the cells. Second, particular emphasis is placed on the micro- and nanoengineered advances in the delivery of biomolecules inside the cells. Furthermore, the applications and challenges of the established and emerging delivery approaches are summarized. The topic is concluded by evaluating the future perspective of intracellular delivery toward the micro- and nanoengineered approaches., (© 2021 Wiley-VCH GmbH.)

Continuous flow reactors form part of a rapidly growing research area that has changed the way synthetic chemistry is performed not only in academia but also at the industrial level. This Review highlights the most recent advances in cycloaddition reactions performed in flow systems. Cycloadditions are atom-efficient transformations for the synthesis of carbo- and heterocycles, involved in the construction of challenging skeletons of complex molecules. The main advantages of translating these processes into flow include using intensified conditions, safer handling of hazardous reagents and gases, easy tuning of reaction conditions, and straightforward scaling up. These benefits are especially important in cycloadditions such as the copper(I)-catalyzed azide alkyne cycloaddition (CuAAC), Diels-Alder reaction, ozonolysis and [2+2] photocycloadditions. Some of these transformations are key reactions in the industrial synthesis of pharmaceuticals., (© 2020 Wiley-VCH GmbH.)

Robotics and automation provide potentially paradigm shifting improvements in the way materials are synthesized and characterized, generating large, complex data sets that are ideal for modeling and analysis by modern machine learning (ML) methods. Nanomaterials have not yet fully captured the benefits of automation, so lag behind in the application of ML methods of data analysis. Here, some key developments in, and roadblocks to the application of ML methods are reviewed to model and predict potentially adverse biological and environmental effects of nanomaterials. This work focuses on the diverse ways a range of ML algorithms are applied to understand and predict nanomaterials properties, provides examples of the application of traditional ML and deep learning methods to nanosafety, and provides context and future perspectives on developments that are likely to occur, or need to occur in the near future that allow artificial intelligence to make a deeper contribution to nanosafety., (© 2020 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The optimal synthesis of advanced nanomaterials with numerous reaction parameters, stages, and routes, poses one of the most complex challenges of modern colloidal science, and current strategies often fail to meet the demands of these combinatorially large systems. In response, an Artificial Chemist is presented: the integration of machine-learning-based experiment selection and high-efficiency autonomous flow chemistry. With the self-driving Artificial Chemist, made-to-measure inorganic perovskite quantum dots (QDs) in flow are autonomously synthesized, and their quantum yield and composition polydispersity at target bandgaps, spanning 1.9 to 2.9 eV, are simultaneously tuned. Utilizing the Artificial Chemist, eleven precision-tailored QD synthesis compositions are obtained without any prior knowledge, within 30 h, using less than 210 mL of total starting QD solutions, and without user selection of experiments. Using the knowledge generated from these studies, the Artificial Chemist is pre-trained to use a new batch of precursors and further accelerate the synthetic path discovery of QD compositions, by at least twofold. The knowledge-transfer strategy further enhances the optoelectronic properties of the in-flow synthesized QDs (within the same resources as the no-prior-knowledge experiments) and mitigates the issues of batch-to-batch precursor variability, resulting in QDs averaging within 1 meV from their target peak emission energy., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Modern nanotechnologies bring humanity to a new age, and advanced methods for preparing functional nanocrystals are cornerstones. A considerable variety of nanomaterials has been created over the past decades, but few were prepared on the macro scale, even fewer making it to the stage of industrial production. The gap between academic research and engineering production is expected to be filled by flow chemistry technology, which relies on microreactors. Microreaction devices and technologies for synthesizing different kinds of nanocrystals are discussed from an engineering point of view. The advantages of microreactors, the important features of flow chemistry systems, and methods to apply them in the syntheses of salt, oxide, metal, alloy, and quantum dot nanomaterials are summarized. To further exhibit the scaling-up of nanocrystal synthesis, recent reports on using microreactors with gram per hour and larger production rates are highlighted. Finally, an industrial example for preparing 10 tons of CaCO 3 nanoparticles per day is introduced, which shows the great potential for flow chemistry processes to transfer lab research to industry., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Colloidal crystals are of great interest to researchers because of their excellent optical properties and broad applications in barcodes, sensors, displays, drug delivery, and other fields. Therefore, the preparation of high quality colloidal crystals in large quantities with high speed is worth investigating. After decades of development, microfluidics have been developed that provide new choices for many fields, especially for the generation of functional materials in microscale. Through the design of microfluidic chips, colloidal crystals can be prepared controllably with the advantages of fast speed and low cost. In this Review, research progress on colloidal crystals from microfluidics is discussed. After summarizing the classifications, the generation of colloidal crystals from microfluidics is discussed, including basic colloidal particles preparation, and their assembly inside or outside of microfluidic devices. Then, applications of the achieved colloidal crystals from microfluidics are illustrated. Finally, the future development and prospects of microfluidic-based colloidal crystals are summarized., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Fluidic flow behaviors in microfluidics are dominated by the interfaces created between the fluids and the inner surface walls of microchannels. Microchannel inner surface designs, including the surface chemical modification, and the construction of micro-/nanostructures, are good examples of manipulating those interfaces between liquids and surfaces through tuning the chemical and physical properties of the inner walls of the microchannel. Therefore, the microchannel inner surface design plays critical roles in regulating microflows to enhance the capabilities of microfluidic systems for various applications. Most recently, the rapid progresses in micro-/nanofabrication technologies and fundamental materials have also made it possible to integrate increasingly complex chemical and physical surface modification strategies with the preparation of microchannels in microfluidics. Besides, a wave of researches focusing on the ideas of using liquids as dynamic surface materials is identified, and the unique characteristics endowed with liquid-liquid interfaces have revealed that the interesting phenomena can extend the scope of interfacial interactions determining microflow behaviors. This review extensively discusses the microchannel inner surface designs for microflow control, especially evaluates them from the perspectives of the interfaces resulting from the inner surface designs. In addition, prospective opportunities for the development of surface designs of microchannels, and their applications are provided with the potential to attract scientific interest in areas related to the rapid development and applications of various microchannel systems., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)