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Soil is the habitat of countless organisms and encompasses an enormous variety of dynamic environmental conditions. While it is evident that a thorough understanding of how organisms interact with the soil environment may have substantial ecological and economical impact, current laboratory-based methods depend on reductionist approaches that are incapable of simulating natural diversity. The application of Lab-on-a-Chip or microfluidic technologies to organismal studies is an emerging field, where the unique benefits afforded by system miniaturisation offer new opportunities for the experimentalist. Indeed, precise spatiotemporal control over the microenvironments of soil organisms in combination with high-resolution imaging has the potential to provide an unprecedented view of biological events at the single-organism or single-cell level, which in turn opens up new avenues for environmental and organismal studies. Herein we review some of the most recent and interesting developments in microfluidic technologies for the study of soil organisms and their interactions with the environment. We discuss how so-called "Soil-on-a-Chip" technology has already contributed significantly to the study of bacteria, nematodes, fungi and plants, as well as inter-organismal interactions, by advancing experimental access and environmental control. Most crucially, we highlight where distinct advantages over traditional approaches exist and where novel biological insights will ensue.

We report the scalable formation of CuInS2/ZnS nanocrystals using a two-stage microfluidic reactor integrated with a real-time optical detection system, which is able to monitor reaction parameters prior and subsequent to the addition of the shell material. By injecting a ZnS single source precursor in droplets containing CuInS2 cores and without the need of purification steps, we are able to obtain core–shell nanocrystal populations emitting between 580 and 760 nm with significant narrower size distributions (90–95 nm) than for the same material systems synthesized on the macroscale. In-line monitoring allowed for rapid assessment of optimum reaction parameters (Cu/In, S/(Cu + In), Zn/(Cu + In) molar ratios, temperatures and reaction time) and enabled the formation of CuInS2/ZnS nanocrystals with high photoluminescence quantum yields (∼55%) within a few seconds. We believe that this synthetic methodology will be of significant utility in controllable production of ternary and quaternary metal chalcogenides, complex core–shell and doped nanostructures.

Thin‐film supercapacitors are promising candidates for energy storage in wearable electronics due to their mechanical flexibility, high power density, long cycling life, and fast‐charging capability. In addition to all of these features, device transparency would open up completely new opportunities in wearable devices, virtual reality or in heads‐up displays for vehicle navigation. Here a method is introduced for micromolding Ag/porous carbon and Ag/NixFeyOz@reduced graphene oxide (rGO) into grid‐like patterns on polyethylene terephthalate foils to produce transparent thin‐film supercapacitors and hybrid supercapacitors. The supercapacitor delivers a high areal capacitance of 226.8 µF cm−2 at a current density of 3 µA cm−2 and with a transparency of 70.6%. The cycling stability is preserved even after 1000 cycles under intense bending. A hybrid supercapacitor is additionally fabricated by integrating two electrodes of Ag/porous carbon and Ag/NixFeyOz@rGO. It offers an areal capacitance of 282.1 µF cm−2 at a current density of 3 µA cm−2, a transparency of 73.3% and the areal capacitance only decreases slightly under bending. This work indicates that micromolding of nano‐ and micro‐sized powders represents a powerful method for preparing regular electrode patterns, which are fundamental for the development of transparent energy storage devices.

Can controlled diffusion of reagents together with micro‐shielding features enable the regioselective localization of different chemical processes? In article number 1903172, Josep Puigmarti‐Luis and co‐workers present a method for the in‐situ fabrication of custom designed surface‐enhanced Raman spectroscopy (SERS) substrates as well as for the selective localization of multiple chemical reactions onto surfaces. [Image: see text]

The acoustic compressibility of Caenorhabditis elegans is a necessary parameter for further understanding the underlying physics of acoustic manipulation techniques of this widely used model organism in biological sciences. In this work, numerical simulations were combined with experimental trajectory velocimetry of L1 C. elegans larvae to estimate the acoustic compressibility of C. elegans. A method based on bulk acoustic wave acoustophoresis was used for trajectory velocimetry experiments in a microfluidic channel. The model-based data analysis took into account the different sizes and shapes of L1 C. elegans larvae (255 ± 26 μm in length and 15 ± 2 μm in diameter). Moreover, the top and bottom walls of the microfluidic channel were considered in the hydrodynamic drag coefficient calculations, for both the C. elegans and the calibration particles. The hydrodynamic interaction between the specimen and the channel walls was further minimized by acoustically levitating the C. elegans and the particles to the middle of the measurement channel. Our data suggest an acoustic compressibility κCe of 430 TPa-1 with an uncertainty range of ±20 TPa-1 for C. elegans, a much lower value than what was previously reported for adult C. elegans using static methods. Our estimated compressibility is consistent with the relative volume fraction of lipids and proteins that would mainly make up for the body of C. elegans. This work is a departing point for practical engineering and design criteria for integrated acoustofluidic devices for biological applications. ispartof: BIOPHYSICAL JOURNAL vol:115 issue:9 pages:1817-1825 ispartof: location:United States status: published

Recently, microfluidic technologies have attracted an enormous amount of interest as potential new tools for a large range of applications including materials synthesis, chemical and biological detection, drug delivery and screening, point-of-care diagnostics, and in-the-field analysis. Their ability to handle extremely small volumes of fluids is accompanied by additional benefits, most notably, rapid and efficient mass and heat transfer. In addition, reactions performed within microfluidic systems are highly controlled, meaning that many advanced materials, with uniform and bespoke properties, can be synthesized in a direct and rapid manner. In this review, we discuss the utility of microfluidic systems in the synthesis of materials for a variety of biological applications. Such materials include microparticles or microcapsules for drug delivery, nanoscale materials for medicine or cellular assays, and micro- or nanofibers for tissue engineering., Genes, 9 (6)

Recent advances in the development of hybrid organic-inorganic lead halide perovskite (LHP) nanocrystals (NCs) have demonstrated their versatility and potential application in photovoltaics and as light sources through compositional tuning of optical properties. That said, due to their compositional complexity, the targeted synthesis of mixed-cation and/or mixed-halide LHP NCs still represents an immense challenge for traditional batch-scale chemistry. To address this limitation, we herein report the integration of a high-throughput segmented-flow microfluidic reactor and a self-optimizing algorithm for the synthesis of NCs with defined emission properties. The algorithm, named Multiparametric Automated Regression Kriging Interpolation and Adaptive Sampling (MARIA), iteratively computes optimal sampling points at each stage of an experimental sequence to reach a target emission peak wavelength based on spectroscopic measurements. We demonstrate the efficacy of the method through the synthesis of multinary LHP NCs, (Cs/FA)Pb(I/Br)

Hybrid organic–inorganic perovskites and in particular formamidinium lead halide (FAPbX3, X = Cl, Br, I) perovskite nanocrystals (NCs) have shown great promise for their implementation in optoelectronic devices. Specifically, the Br and I counterparts have shown unprecedented photoluminescence properties, including precise wavelength tuning (530–790 nm), narrow emission linewidths (, Nano Letters, 18 (2), ISSN:1530-6984, ISSN:1530-6992

We report the use of inverse supercritical fluid extraction (SFE) and miniaturized asymmetrical flow field-flow fractionation (mAF4) for the preparation and subsequent analysis of titanium dioxide nanoparticles in model and commercial sunscreens. The approach allows for the fast and reliable fractionation and sizing of TiO2 nanoparticles and their quantitation in commercial products. This new method represents a powerful and efficient tool for the verification of nanoparticle content in a wide range of matrixes, as demanded by recently introduced regulatory requirements. Furthermore, the use of carbon dioxide as an environmentally friendly solvent is in line with the increasing need for ecologically compatible analytical techniques.

Hybrid organic-inorganic and fully inorganic lead halide perovskite nanocrystals (NCs) have recently emerged as versatile solution-processable light-emitting and light-harvesting optoelectronic materials. A particularly difficult challenge lies in warranting the practical utility of such semiconductor NCs in the red and infrared spectral regions. In this context, all three archetypal A-site monocationic perovskites-CH3NH3PbI3, CH(NH2)(2)PbI3, and CsPbI3-suffer from either chemical or thermodynamic instabilities in their bulk form. A promising approach toward the mitigation of these challenges lies in the formation of multinary compositions (mixed cation and mixed anion). In the case of multinary colloidal NCs, such as quinary Cs(x)FA(1-x)Pb-(Br1-yIy)(3) NCs, the outcome of the synthesis is defined by a complex interplay between the bulk thermodynamics of the solid solutions, crystal surface energies, energetics, dynamics of capping ligands, and the multiple effects of the reagents in solution. Accordingly, the rational synthesis of such NCs is a formidable challenge. Herein, we show that droplet-based microfluidics can successfully tackle this problem and synthesize Cs(x)FA(1-x)PbI(3) and Cs(x)FA(1-x)Pb(Br1-yIy)(3) NCs in both a time- and cost-efficient manner. Rapid in situ photoluminescence and absorption measurements allow for thorough parametric screening, thereby permitting precise optical engineering of these NCs. In this showcase study, we fine-tune the photoluminescence maxima of such multinary NCs between 700 and 800 nm, minimize their emission line widths (to below 40 nm), and maximize their photoluminescence quantum efficiencies (up to 89%) and phase/chemical stabilities. Detailed structural analysis revealed that the Cs(x)FA(1-x)Pb(Br1-yIy)(3) NCs adopt a cubic perovskite structure of FAPbI(3), with iodide anions partially substituted by bromide ions. Most importantly, we demonstrate the excellent transference of reaction parameters from microfluidics to a conventional flask based environment, thereby enabling up-scaling and further implementation in optoelectronic devices. As an example, Cs(x)FA(1-x)Pb(Br1-yIy)(3) NCs with an emission maximum at 735 nm were integrated into light-emitting diodes, exhibiting a high external quantum efficiency of 5.9% and a very narrow electroluminescence spectral bandwidth of 27 nm.

Herein we describe a novel microfluidic method for the generation of proteinosome micro-droplets, based on bovine serum albumin and glucose oxidase conjugated to PNIPAAm chains. The size of such water-in-oil droplets is regulated via control of the input reagent flow rate, with generated proteinosome populations exhibiting narrower size distributions than those observed when using standard bulk methodologies. Importantly, proteinosomes transferred from an oil to an aqueous-environment remain intact, become fully hydrated and exhibit an increase in average size. Moreover, functional proteinosomes prepared via microfluidics exhibit lower Km values and higher enzymatic activities than proteinosomes produced by bulk methodologies., Chemical Communications, 54 (3), ISSN:1359-7345, ISSN:1364-548X

Herein, we describe the development of a multilayer droplet microfluidic system for creating concentration gradients and generating microdroplets of varying composition for high-throughput biochemical and cell-based screening applications. The 3D droplet-based microfluidic device consists of multiple PDMS layers, which are used to generate logarithmic concentration gradient reagent profiles. Parallel flow focusing structures are used to form picoliter-sized droplets of defined volumes but of varying composition. As proof of concept, we demonstrate rapid enzymatic activity assays and drug cytotoxicity assays on bacteria. The 3D droplet-based microfluidic platform has the potential to allow for high-efficiency and high-throughput analysis, overcoming the structural limitations of single layer microfluidic systems.

We report the application of a fully automated surface-enhanced Raman scattering (SERS)-based solenoid-embedded microfluidic device to the quantitative and sensitive detection of anthrax biomarker poly-γ-D-glutamic acid (PGA) in solution. Analysis is based on the competitive reaction between PGA and PGA-conjugated gold nanoparticles with anti-PGA-immobilized magnetic beads within a microfluidic environment. Magnetic immunocomplexes are trapped by yoke-type solenoids embedded within the device, and their SERS signals were directly measured and analyzed. To improve the accuracy of measurement process, external standard values for PGA-free serum were also measured through use of a control channel. This additional measurement greatly improves the reliability of the assay by minimizing the influence of extraneous experimental variables. The limit of detection (LOD) of PGA in serum, determined by our SERS-based microfluidic sensor, is estimated to be 100 pg/mL. We believe that the defined method represents a valuable analytical tool for the detection of anthrax-related aqueous samples.

Cellular fusion is a key process in many fields ranging from historical gene mapping studies and monoclonal antibody production, through to cell reprogramming. Traditional methodologies for cell fusion rely on the random pairing of different cell types and generally result in low and variable fusion efficiencies. These approaches become particularly limiting where substantial numbers of bespoke one-to-one fusions are required, for example, for in-depth studies of nuclear reprogramming mechanisms. In recent years, microfluidic technologies have proven valuable in creating platforms where the manipulation of single cells is highly efficient, rapid and controllable. These technologies also allow the integration of different experimental steps and characterisation processes into a single platform. Although the application of microfluidic methodologies to cell fusion studies is promising, current technologies that rely on static trapping are limited both in terms of the overall number of fused cells produced and their experimental accessibility. Here we review some of the most exciting breakthroughs in core microfluidic technologies that will allow the creation of integrated platforms for controlled cell fusion at high throughput. © 2015 Society of Chemical Industry

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Microfluidic reactors are increasingly being recognized as a promising tool for the synthesis of bespoke and high quality nanomaterials. Herein, we discuss currently available methods for interfacing microfluidic reactors with online analysis systems such as photothermal, fluorescence, absorbance, X-ray, backscattering and correlation spectroscopies. Integration of appropriate on-line detection methods enables the facile extraction of information relating to size, shape and chemical composition of the formed nanoparticles, thus greatly enhancing control over the synthetic process. Furthermore, we discuss recent approaches aimed at implementing ‘intelligent’ algorithms that use such extracted information for optimization and parameter space evaluation. Lastly, we provide brief opinion about future directions of this emerging field.

Droplet-based microfluidic systems offer a range of advantageous features for the investigation of enzyme kinetics, including high time resolution and the ability to probe extremely large numbers of discrete reactions while consuming low sample volumes. Kinetic measurements within droplet-based microfluidic systems are conventionally performed using single point detection schemes. Unfortunately, such an approach prohibits the measurement of an individual droplet over an extended period of time. Accordingly, we present a novel approach for the extensive characterization of enzyme-inhibitor reaction kinetics within a single experiment by tracking individual and rapidly moving droplets as they pass through an extended microfluidic channel. A series of heterogeneous and pL-volume droplets, containing varying concentrations of the fluorogenic substrate resorufin β-d-galactopyranoside and a constant amount of the enzyme β-galactosidase, is produced at frequencies in excess of 150 Hz. By stroboscopic manipulation of the excitation laser light and adoption of a dual view detection system, "blur-free" images containing up to 150 clearly distinguishable droplets per frame are extracted, which allow extraction of kinetic data from all formed droplets. The efficiency of this approach is demonstrated via a Michaelis-Menten analysis which yields a Michaelis constant, Km, of 353 μM. Additionally, the dissociation constant for the competitive inhibitor isopropyl β-d-1-thiogalactopyranoside is extracted using the same method.

There is a recognized and growing need for rapid and efficient cell assays, where the size of microfluidic devices lend themselves to the manipulation of cellular populations down to the single cell level. An exceptional way to analyze cells independently is to encapsulate them within aqueous droplets surrounded by an immiscible fluid, so that reagents and reaction products are contained within a controlled microenvironment. Most cell encapsulation work has focused on the development and use of passive methods, where droplets are produced continuously at high rates by pumping fluids from external pressure-driven reservoirs through defined microfluidic geometries. With limited exceptions, the number of cells encapsulated per droplet in these systems is dictated by Poisson statistics, reducing the proportion of droplets that contain the desired number of cells and thus the effective rate at which single cells can be encapsulated. Nevertheless, a number of recently developed actively-controlled droplet production methods present an alternative route to the production of droplets at similar rates and with the potential to improve the efficiency of single-cell encapsulation. In this critical review, we examine both passive and active methods for droplet production and explore how these can be used to deterministically and non-deterministically encapsulate cells.

Droplet-based microfluidic systems that incorporate flowing streams of pL-volume droplets surrounded by a continuous and immiscible carrier phase have attracted significant recent attention due to their utility in complex chemical and biological experimentation. Analysis of pL droplets, generated at kHz frequencies and moving at high linear velocities, is almost exclusively achieved using fluorescence-based detection schemes. To extend the applicability of such optical detection schemes, we herein report the development of a simple and cost-effective optofluidic platform, integrating liquid-core PDMS waveguides, that allows the accurate measurement of absorbance within individual pL-volume droplets moving within segmented flows. Using such an approach, differential measurements of "sample "and "reference" droplets can be acquired at 1 kHz and yield detection limits of 400 nM for fluorescein in water. Significantly, the presented technique enables simultaneous fluorescence and absorbance interrogation of rapidly moving droplets in a fully automated manner. Proof of principle is demonstrated through the titration and monitoring of pH gradients in real time.

The ability to manipulate biological cells is critical in a diversity of biomedical and industrial applications. Microfluidic-based cell manipulations provide unique opportunities for sophisticated and high-throughput biological assays such as cell sorting, rare cell detection, and imaging flow cytometry. In this respect, cell focusing is an extremely useful functional operation preceding downstream biological analysis, since it allows the accurate lateral and axial positioning of cells moving through microfluidic channels, and thus enables sophisticated cell manipulations in a passive manner. Herein, we explore the utility of viscoelastic carrier fluids for enhanced elasto-inertial focusing of biological species within straight, rectangular cross section microfluidic channels. Since the investigated polymer solutions possess viscosities close to that of water and exhibit negligible shear thinning, focusing occurs over a wide range of elasticity numbers and a large range of Reynolds numbers. With a view to applications in the robust focusing of cells and bacteria, we assess and characterize the influence of accessible focusing parameters, including blockage ratio, volumetric flow rate, cell concentration, and polymer chain length.

Covalent Organic Frameworks (COFs) are a class of porous covalent materials which are frequently synthesized as unprocessable crystalline powders. The first COF was reported in 2005 with much effort centered on the establishment of new synthetic routes for its preparation. To date, most available synthetic methods for COF synthesis are based on bulk mixing under solvothermal conditions. Therefore, there is increasing interest in developing systematic protocols for COF synthesis that provide for fine control over reaction conditions and improve COF processability on surfaces, which is essential for their use in practical applications. Herein, we present a novel microfluidic-based method for COF synthesis where the reaction between two constituent building blocks, 1,3,5-benzenetricarbaldehyde (BTCA) and 1,3,5-tris(4-aminophenyl)benzene (TAPB), takes place under controlled diffusion conditions and at room temperature. Using such an approach yields sponge-like, crystalline fibers of a COF material, hereafter called MF-COF. The mechanical properties of MF-COF and the dynamic nature of the approach allow the continuous production of MF-COF fibers and their direct printing onto surfaces. The general method opens new potential applications requiring advanced printing of 2D or 3D COF structures on flexible or rigid surfaces.

The fabrication of functional 3D tissues is a major goal in tissue engineering. While electrospinning is a promising technique to manufacture a structure mimicking the extracellular matrix, cell infiltration into electrospun scaffolds remains challenging. The robust and in situ delivery of cells into such biomimetic scaffolds would potentially enable the design of tissue engineered constructs with spatial control over cellular distribution but often solvents employed in the spinning process are problematic due to their high cytotoxicity. Herein, microfluidic cell encapsulation is used to establish a temporary protection vehicle for the in situ delivery of cells for the development of a fibrous, cell-laden hybrid biograft. Therefore a layer-by-layer process is used by alternating fiber electrospinning and cell spraying procedures. Both encapsulation and subsequent electrospraying of capsules has no negative effect on the viability and myogenic differentiation of murine myoblast cells. Propidium iodide positive stained cells were analyzed to quantify the amount of dead cells and the presence of myosin heavy chain positive cells after the processes was shown. Furthermore, encapsulation successfully protects cells from cytotoxic solvents (such as dimethylformamide) during in situ delivery of the cells into electrospun poly(vinylidene fluoride-co-hexafluoropropylene) scaffolds. The resulting cell-populated biografts demonstrate the clear potential of this approach in the creation of viable tissue engineering constructs. Statement of Significance Infiltration of cells and their controlled spatial distribution within fibrous electrospun membranes is a challenging task but allows for the development of functional highly organized 3D hybrid tissues. Combining polymer electrospinning and cell electrospraying in a layer-by-layer approach is expected to overcome current limitations of reduced cell infiltration after traditional static seeding. However, organic solvents, used during the electrospinning process, impede often major issues due to their high cytotoxicity. Utilizing microfluidic encapsulation as a mean to embed cells within a protective polymer casing enables the controlled deposition of viable cells without interfering with the cellular phenotype. The presented techniques allow for novel cell manipulation approaches being significant for enhanced 3D tissue engineering based on its versatility in terms of material and cell selection.

The isotropic and nematic (I + N) coexistence for rod-like colloids is a signature of the first-order thermodynamics nature of this phase transition. However, in the case of amyloid fibrils, the biphasic region is too small to be experimentally detected, due to their extremely high aspect ratio. Herein, we study the thermophoretic behaviour of fluorescently labelled β-lactoglobulin amyloid fibrils by inducing a temperature gradient across a microfluidic channel. We discover that fibrils accumulate towards the hot side of the channel at the temperature range studied, thus presenting a negative Soret coefficient. By exploiting this thermophoretic behaviour, we show that it becomes possible to induce a continuous I-N transition with the I and N phases at the extremities of the channel, starting from an initially single N phase, by generating an appropriate concentration gradient along the width of the microchannel. Accordingly, we introduce a new methodology to control liquid crystal phase transitions in anisotropic colloidal suspensions. Because the induced order-order transitions are achieved under stationary conditions, this may have important implications in both applied colloidal science, such as in separation and fractionation of colloids, as well as in fundamental soft condensed matter, by widening the accessibility of target regions in the phase diagrams., Scientific Reports, 7, ISSN:2045-2322

Recent years have witnessed an increased use of droplet-based microfluidic techniques in a wide variety of chemical and biological assays. Nevertheless, obtaining dynamic data from these platforms has remained challenging, as this often requires reading the same droplets (possibly thousands of them) multiple times over a wide range of intervals (from milliseconds to hours). In this review, we introduce the elemental techniques for the formation and manipulation of microfluidic droplets, together with the most recent developments in these areas. We then discuss a wide range of analytical methods that have been successfully adapted for analyte detection in droplets. Finally, we highlight a diversity of studies where droplet-based microfluidic strategies have enabled the characterization of dynamic systems that would otherwise have remained unexplorable.

Droplet-based microfluidic technologies have proved themselves to be of significant utility in the performance of high-throughput chemical and biological experiments. By encapsulating and isolating reagents within femtoliter-nanoliter droplet, millions of (bio) chemical reactions can be processed in a parallel fashion and on ultra-short timescales. Recent applications of such technologies to genetic analysis have suggested significant utility in low-cost, efficient and rapid workflows for DNA amplification, rare mutation detection, antibody screening and next-generation sequencing. To this end, we describe and highlight some of the most interesting recent developments and applications of droplet-based microfluidics in the broad area of nucleic acid analysis. In addition, we also present a cursory description of some of the most essential functional components, which allow the creation of integrated and complex workflows based on flowing streams of droplets.

We describe the realization of a droplet-based microfluidic platform for the controlled and reproducible synthesis of lead chalcogenide (PbS, PbSe) nanocrystal quantum dots (QDs). Monodisperse nanocrystals were synthesized over a wide range of experimental conditions, with real-time assessment and fine-tuning of material properties being achieved using NIR fluorescence spectroscopy. Importantly, we show for the first time that real-time monitoring of the synthetic process allows for rapid optimization of reaction conditions and the synthesis of high quality PbS nanocrystals, emitting in the range of 765–1600 nm, without any post-synthetic processing. The segmented-flow capillary reactor exhibits stable droplet generation and reproducible synthesis of PbS nanocrystals with high photoluminescence quantum yields (28%) over extended periods of time (3–6 h). Furthermore, the produced NIR-emitting nanoparticles were successfully used in the fabrication of Schottky solar cells, exhibiting a power conversion efficiency of 3.4% under simulated AM 1.5 illumination. Finally, the droplet-based microfluidic platform was used to synthesize PbSe nanocrystals having photoluminescence peaks in the range of 860–1600 nm, showing the exceptional control and stability of the reactor., Chemistry of Materials, 26 (9), ISSN:0897-4756

Droplet-based microfluidic systems have recently emerged as powerful experimental tools in the chemical and biological sciences. In conventional droplet-based microfluidics, controlled droplet generation is normally achieved using precision syringe pumps, where the sample is delivered to the microdevice using external tubing that possesses an appreciable dead volume. Accordingly, there is an unmet need for a droplet generation system that does not require the use of syringe pumps. Herein, we report the integration of pneumatic micro-pumps with droplet-based microfluidic systems and their subsequent use in high-throughput biological experimentation. The efficacy of the system is demonstrated by investigating the interaction and the binding inhibition between angiogenin and the anti-angiogenin antibody with a dissociation constant (KD) value of 9.1 ± 3.5 nM and a half maximal inhibitory concentration (IC50) value of 12.2 ± 2.5 nM, respectively.

The design, fabrication and testing of facile microcapillary device assembly, suitable for monodisperse double emulsion production is reported. The interface is fabricated in a direct and rapid manner via 3D printing and shown to be robust in the controllable generation of both single and double emulsions at high generation frequencies.

We report the application of metamodeling algorithms based on Universal Kriging for the controlled synthesis of compound semiconductor nanoparticles. Application of such a metamodel allows the prediction of reaction outcomes at arbitrary points within sparsely sampled parameter spaces as a function of reaction conditions. To demonstrate the applicability of Universal Kriging to chemical reaction screening within microfluidic reaction systems CdSe and CdSeTe quantum dots were synthesized by using a segmented flow capillary reactor. Variation of input reagent flows (to control reagent concentrations and reaction residence times) and online spectroscopic monitoring of product characteristics was achieved in a fully automated manner. The resulting fluorescence spectra are analyzed to extract the fwhm wavelength maximum and intensity of the band edge emission. These values are subsequently used as inputs for the Universal Kriging metamodeling algorithm to predict the reactor output at arbitrary points within accessible parameter space. Results demonstrate that the algorithm can predict reaction outcomes with high accuracy and reliability.

We present a novel connector that allows for easy handling and injection of sample volumes between 1 and 20 μl. All tubing connections between external pumps and the microfluidic device are established before the sample is introduced into a sealable reservoir built into the connector. This approach allows for multiple injections of small sample volumes without the need to dismantle the chip-tubing assembly. We demonstrate that the connector reservoir seal can withstand pressures of up to 6 bar, that opening or closing the reservoir does not dislocate the sample by more than 35 nl, and that the connector can be used for injecting samples into both miscible and immiscible carrier fluids.

Advanced Materials Technologies, 4 (6), ISSN:2365-709X

With the view of enhancing the functionality of label-free single molecule nanopore-based detection, we have designed and developed a highly robust, mechanically stable, integrated nanopipette-microfluidic device which combines the recognized advantages of microfluidic systems and the unique properties/advantages of nanopipettes. Unlike more typical planar solid-state nanopores, which have inherent geometrical constraints, nanopipettes can be easily positioned at any point within a microfluidic channel. This is highly advantageous, especially when taking into account fluid flow properties. We show that we are able to detect and discriminate between DNA molecules of varying lengths when motivated through a microfluidic channel, upon the application of appropriate voltage bias across the nanopipette. The effects of applied voltage and volumetric flow rates have been studied to ascertain translocation event frequency and capture rate. Additionally, by exploiting the advantages associated with microfluidic systems (such as flow control and concomitant control over analyte concentration/presence), we show that the technology offers a new opportunity for single molecule detection and recognition in microfluidic devices.

We present a fully integrated droplet-based microfluidic platform for the high-throughput assessment of photodynamic therapy photosensitizer (PDT) efficacy on Escherichia coli. The described platform is able to controllably encapsulate cells and photosensitizer within pL-volume droplets, incubate the droplets over the course of several days, add predetermined concentrations of viability assay agents, expose droplets to varying doses of electromagnetic radiation, and detect both live and dead cells online to score cell viability. The viability of cells after encapsulation and incubation is assessed in a direct fashion, and the viability scoring method is compared to model live/dead systems for calibration. Final results are validated against conventional colony forming unit assays. In addition, we show that the platform can be used to perform concurrent measurements of light and dark toxicity of the PDT agents and that the platform allows simultaneous measurement of experimental parameters that include dark toxicity, photosensitizer concentration, light dose, and oxygenation levels for the development and testing of PDT agents.

The ability to miniaturize biochemical assays in water-in-oil emulsion droplets allows a massive scale-down of reaction volumes, so that high-throughput experimentation can be performed more economically and more efficiently. Generating such droplets in compartment-on-demand (COD) platforms is the basis for rapid, automated screening of chemical and biological libraries with minimal volume consumption. Herein, we describe the implementation of such a COD platform to perform high precision nanoliter assays. The coupling of a COD platform to a droplet absorbance detection set-up results in a fully automated analytical system. Michaelis–Menten parameters of 4-nitrophenyl glucopyranoside hydrolysis by sweet almond β-glucosidase can be generated based on 24 time-courses taken at different substrate concentrations with a total volume consumption of only 1.4 μL. Importantly, kinetic parameters can be derived in a fully unsupervised manner within 20 min: droplet production (5 min), initial reading of the droplet sequence (5 min), and droplet fusion to initiate the reaction and read-out over time (10 min). Similarly, the inhibition of the enzymatic reaction by conduritol B epoxide and 1-deoxynojirimycin was measured, and Ki values were determined. In both cases, the kinetic parameters obtained in droplets were identical within error to values obtained in titer plates, despite a >104-fold volume reduction, from micro- to nanoliters., Analytical Chemistry, 85 (9), ISSN:1520-6882, ISSN:0003-2700

Singlet oxygen, a reactive oxygen species, has been a basic synthetic tool in the laboratory for many years. It can be generated either through a chemical process or most commonly via a photochemical process mediated by a sensitizing dye. The relative paucity of singlet oxygen employment in fine chemical industrial settings can be attributed to many factors, not least the requirement for excessive quantities of oxygenated organic solvents and the dangers that these represent. Microcapillary films (MCFs) are comprised of multiple parallel channels embedded in a plastic film. In this study, MCFs are employed as flow reactor systems for the singlet oxygen mediated synthesis of ascaridole. No gaseous oxygen is supplied directly to the reaction, rather mass transport occurs exclusively through the reactor walls. The rate of production of ascaridole was found to be strongly dependent on the partial pressure of oxygen present within the reaction system. This methodology significantly simplifies reactor design, a...

Multiorifice Flow Fractionation (MOFF) devices have been used for the separation of microparticles and cells according to their size and the degree of inertia (i.e. Re number). Herein an additional parameter, particle concentration, is reported to affect the performance of MOFF when the remaining conditions are unchanged. Particularly, at low concentrations focusing occurs efficiently at the center of these devices, while at higher concentrations particles tend to accumulate near the channel walls. This indicates that particle-particle interactions are a key component in the performances of these devices. ispartof: Matters pages:1-7 status: Published online

We report a novel wash-free magnetic immunoassay technique for prostate-specific antigen (PSA) that uses a surface-enhanced Raman scattering (SERS)-based microdroplet sensor. The magnetic bar embedded in a droplet-based microfluidic system segregates the free and bound SERS tags by splitting the droplets into two smaller parts. The presence of PSA targets leads more SERS tags to immunocomplex in one droplet so that fewer SERS tags remain in another supernatant solution droplet. Thus, SERS signal measurement enables the quantitative evaluation of PSA markers. This approach can provide a rapid and sensitive assay that is applicable for PSA cancer markers in serum without any washing. Specifically, SERS signals were measured at 174 droplets per minute and averaged for quantitative evaluation of PSA. The limit of detection (LOD) determined by our SERS-based microdroplet sensor was estimated to be below 0.1 ng mL(-1), which is significantly below the clinical cut-off value for the diagnosis of prostate cancer. In addition, because the entire assay can be carried out automatically, only a minimal amount of sample is needed. Accordingly, the approach is expected to be useful as a potential clinical tool for the early diagnosis of prostate cancer.

Prior to this work, fully inorganic nanocrystals of cesium lead halide perovskite (CsPbX3, X = Br, I, Cl and Cl/Br and Br/I mixed halide systems), exhibiting bright and tunable photoluminescence, have been synthesized using conventional batch (flask-based) reactions. Unfortunately, our understanding of the parameters governing the formation of these nanocrystals is still very limited due to extremely fast reaction kinetics and multiple variables involved in ion-metathesis-based synthesis of such multinary halide systems. Herein, we report the use of a droplet-based microfluidic platform for the synthesis of CsPbX3 nanocrystals. The combination of online photoluminescence and absorption measurements and the fast mixing of reagents within such a platform allows the rigorous and rapid mapping of the reaction parameters, including molar ratios of Cs, Pb, and halide precursors, reaction temperatures, and reaction times. This translates into enormous savings in reagent usage and screening times when compared to analogous batch synthetic approaches. The early-stage insight into the mechanism of nucleation of metal halide nanocrystals suggests similarities with multinary metal chalcogenide systems, albeit with much faster reaction kinetics in the case of halides. Furthermore, we show that microfluidics-optimized synthesis parameters are also directly transferrable to the conventional flask-based reaction.

Herein, we assess the functionality of magnetic helical microswimmers as basic tools for the manipulation of soft materials, including microdroplets and single cells. Their ability to perform a range of unit operations is evaluated and the operational challenges associated with their use are established. In addition, we also report on interactions observed between the head of such helical swimmers and the boundaries of droplets and cells and discuss the possibilities of assembling an artificial swimming microorganism or a motorized cell., Micromachines, 7 (2), ISSN:2072-666X

Droplet-based microfluidic systems have emerged as a powerful platform for performing high-throughput biological experimentation. In addition, fluorescence polarization has been shown to be effective in reporting a diversity of bimolecular events such as protein-protein, DNA-protein, DNA-DNA, receptor-ligand, enzyme-substrate, and protein-drug interactions. Herein, we report the use of fluorescence polarization for high-throughput protein-protein interaction analysis in a droplet-based microfluidic system. To demonstrate the efficacy of the approach, we investigate the interaction between angiogenin (ANG) and antiangiogenin antibody (anti-ANG Ab) and demonstrate the efficient extraction of dissociation constants (K(D) = 10.4 ± 3.3 nM) within short time periods.

A methodology that can be efficiently used to synthesize, isolate, and study out-of-equilibrium crystal structures employing controlled and diffusion-limited microfluidic environments is demonstrated. Unlike studies conducted with conventional mixing procedures in a flask, it is proven experimentally and with numerical simulations that microfluidic technologies can undoubtedly fine-tune reaction times and reagents concentration profiles; factors that enable out-of-equilibrium crystal forms to be obtained., The authors acknowledge the financial support from MINECO-Spain, under projects MAT2012-30994 and CTQ2011-16009-E, the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007-2013)/ERC Grant agreement no 615954 and from the Swiss National Science Foundation (SNF) through the project no 200021_160174. The authors thank the Microscopy Service of the UAB. M.R.-M. and C.C. thank the ICN2 for their research fellowship, I.I., N.D., and J.P.-L. thank the MINECO for RyC contracts. ICN2 acknowledges the support of the Spanish MINECO through the Severo Ochoa Centers of Excellence Program, under Grant SEV-2013-0295.

Electron beam-induced shrinkage provides a convenient way of resizing solid-state nanopores in Si(3) N(4) membranes. Here, a scanning electron microscope (SEM) has been used to resize a range of different focussed ion beam-milled nanopores in Al-coated Si(3) N(4) membranes. Energy-dispersive X-ray spectra and SEM images acquired during resizing highlight that a time-variant carbon deposition process is the dominant mechanism of pore shrinkage, although granular structures on the membrane surface in the vicinity of the pores suggest that competing processes may occur. Shrinkage is observed on the Al side of the pore as well as on the Si(3) N(4) side, while the shrinkage rate is observed to be dependent on a variety of factors.

The development of ultrafast Raman-based detection is one of the most interesting challenges underpinning the application of droplet-based microfluidics. Herein, we describe the use of surface-enhanced resonance Raman spectroscopy (SERRS) with submillisecond time resolution as a powerful detection tool in microdroplet reactors. Individual droplets containing silver nanoparticle aggregates functionalized with Raman reporters are interrogated and characterized by full spectra acquisitions with high spatial resolution in real time. Whereas previous works coupling SERRS with droplet-based microfluidics acquire a single spectrum over single or multiple droplets, we build upon these results by increasing our temporal resolution by 2 orders of magnitude. This allows us to interrogate multiple points within one individual droplet. The SERRS signals emitted from the aggregates are utilized to access the influence of flow rate on droplet size and throughput. Accordingly, our approach allows for high-throughput analysis that facilitates the study of other biological assays or molecular interactions.

Aqueous droplets were used as a tool to confine a molecular population and enable highly efficient detection at the single-molecule level. Picoliter-sized aqueous droplets were generated using classical multiphase microfluidics with an aqueous stream containing the analyte under investigation and an oil carrier phase. The droplets were then localized and isolated in specially designed trapping areas within the microfluidic channel to provide a static environment for detection of the encapsulated molecules. We show that by continuously flowing the carrier oil phase while holding the aqueous stationary, we can significantly improve on measuring repeat single-molecule events. Further, we find that the flowing oil stream induces a circulation within the trapped droplets which is proportional to the volumetric flow velocity. This circulation phenomenon allows a given molecule to be detected multiple times during an experiment and can therefore be used for performing time-dependent single-molecule analysis.

The use of dielectrophoretic forces is crucially tied to the knowledge of Joule heating within a fluid, since the use of planar microelectrodes creates a temperature gradient within which the particle of interest is manipulated. Mapping temperature with sufficient spatial resolution within a dielectrophoretic trap is recognized to be of high importance. Herein, we demonstrate local temperature measurements in the vicinity of a trapped micrometer-size particle using confocal fluorescence spectroscopy. Such measurements are shown to provide a novel calibration tool for screening temperature-mediated processes with high resolution.