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The assembly of nanomaterials into suprastructures offers the possibility to fabricate larger scale functional materials, whose inner structure strongly influences their functionality for a vast range of applications. In spite of the many current strategies, achieving multi-compartment structures in a targeted and versatile way remains highly challenging. Here, we describe a controllable and straightforward route to create uniform suprastructured materials with a multi-compartmentalized architecture by confining primary nanocapsules into droplets using a cross-junction microfluidic device. Following solvent evaporation from the droplets, the nanocapsules spontaneously assemble into precisely sized multi-compartment particles, which we term supracapsules. Thanks to the process, each spatially separated nanocapsule unit retains its cargo and functionalities within the resulting supracapsules. However, new collective properties emerge, and, particularly, programmable release profiles that are distinct from those of single-compartment capsules. Finally, the suprastructures can be disassembled into single-compartment units by applying ultra-sonication, switching their release to a burst-release mode. These findings open up exciting opportunities to fabricate multi-compartment suprastructures incorporating diverse functionalities for materials with emerging properties., Materials Horizons, 9 (6), ISSN:2051-6347, ISSN:2051-6355

Microfluidics enables selection of different pathways in self-assembly processes, while allowing for an exquisite control over the processing of self-assembled materials., Self-assembly is a crucial component in the bottom-up fabrication of hierarchical supramolecular structures and advanced functional materials. Control has traditionally relied on the use of encoded building blocks bearing suitable moieties for recognition and interaction, with targeting of the thermodynamic equilibrium state. On the other hand, nature leverages the control of reaction–diffusion processes to create hierarchically organized materials with surprisingly complex biological functions. Indeed, under non-equilibrium conditions (kinetic control), the spatio-temporal command of chemical gradients and reactant mixing during self-assembly (the creation of non-uniform chemical environments for example) can strongly affect the outcome of the self-assembly process. This directly enables a precise control over material properties and functions. In this tutorial review, we show how the unique physical conditions offered by microfluidic technologies can be advantageously used to control the self-assembly of materials and of supramolecular aggregates in solution, making possible the isolation of intermediate states and unprecedented non-equilibrium structures, as well as the emergence of novel functions. Selected examples from the literature will be used to confirm that microfluidic devices are an invaluable toolbox technology for unveiling, understanding and steering self-assembly pathways to desired structures, properties and functions, as well as advanced processing tools for device fabrication and integration.

Live-imaging of C. elegans is essential for the study of conserved cellular pathways (e.g. EGFR/Wnt signaling) and morphogenesis in vivo. However, the usefulness of live imaging as a research tool has been severely limited by the need to immobilize worms prior to and during imaging. Conventionally, immobilization is achieved by employing both physical and chemical interventions. These are known to significantly affect many physiological processes, and thus limit our understanding of dynamic developmental processes. Herein we present a novel, easy-to-use microfluidic platform for the long-term immobilization of viable, normally developing C. elegans, compatible with image acquisition at high resolution, thereby overcoming the limitations associated with conventional worm immobilization. The capabilities of the platform are demonstrated through the continuous assessment of anchor cell (AC) invasion and distal tip cell (DTC) migration in larval C. elegans and germ cell apoptosis in adult C. elegans in vivo for the first time. ispartof: LAB ON A CHIP vol:18 issue:9 pages:1359-1368 ispartof: location:England status: published

In recent years, high-speed imaging has become increasingly effective for the rapid analysis of single cells in flowing environments. Single cell imaging methods typically incorporate a minimum magnification of 10× when extracting sizing and morphological information. Although information content may be significantly enhanced by increasing magnification, this is accompanied by a corresponding reduction in field of view, and thus a decrease in the number of cells assayed per unit time. Accordingly, the acquisition of high resolution data from wide field views remains an unsolved challenge. To address this issue, we present an optofluidic flow cytometer integrating a refractive, microlens array (MLA) for imaging cells at high linear velocities, whilst maximizing the number of cells per field of view. To achieve this, we adopt an elasto-inertial approach for cell focusing within an array of parallel microfluidic channels, each equipped with a microlens. We characterize the optical performance of the microlenses in terms of image formation, magnification and resolution using both ray-tracing simulations and experimental measurements. Results demonstrate that the optofluidic platform can efficiently count and magnify micron-sized objects up to 4 times. Finally, we demonstrate the capabilities of the platform as an imaging flow cyclometer, demonstrating the efficient discrimination of hB and Jurkat cells at throughputs up to 50 000 cells per second.

Despite the growing importance of droplet-based microfluidics in high-throughput experimentation, few current methods allow the sensitive measurement of absorbance within rapidly moving droplets. To address this significant limitation, we herein present the application of differential detection photothermal interferometry (DDPI) for single-point absorbance quantification in pL- and fL-volume droplets. To assess the efficacy of our approach, we initially measure absorbance in 100 pL droplets at frequencies in excess of 1 kHz and determine a detection limit of 1.4 μmol L-1 for Erythrosin B (A = 3.8 × 10-4). Subsequently, we apply the method to the analysis of fL-volume droplets and droplets generated at frequencies in excess of 10 kHz. Finally, we demonstrate the utility of DDPI as a detection scheme for colorimetric assays. Specifically, we extract the Michaelis-Menten constant for the reaction of β-galactosidase and chlorophenol-red-β-d-galactopyranoside and monitor the metabolomic activity of a population of HL-60 cells at the single cell level. Results establish single-point absorbance detection as a powerful, sensitive and rapid alternative to fluorescence for a wide range of assays within segmented flows.

The processes occurring during nanocrystal nucleation and growth are currently not well understood. Herein, we theoretically and experimentally investigate the growth kinetics in colloidal nanocrystal synthesis. Using a novel microfluidic reactor integrating independent modules for nucleation and growth, we demonstrate the controlled, direct synthesis of high quality nanocrystals in high yield. For CdSe nanocrystals, we find that size tuning solely by variation of the reaction time and temperature does not yield product populations of optimal size dispersion or yield. Instead, we present an improved method for the synthesis of bespoke nanocrystals that relies on the controlled addition of precise amounts of additional precursor subsequent to nucleation and fine tuning of the reaction time and temperature in the second stage. Real-time spectroscopic monitoring of the produced crystals in conjunction with kinetic simulations confirms the close correspondence between the model and the experiment and elegantly quantifies the effects of temperature, concentration, additives and surfactants on conversion, growth and diffusion rates within the model framework. We show that the conversion of the precursor to a monomer follows a first order rate law and that the growth rate has a stronger temperature dependence than the conversion rate. Moreover, the surfactant concentration retards the reaction by inhibiting diffusion to the growing crystals whilst maintaining a uniform conversion rate. Finally, we demonstrate that diphenylphosphine, a common additive in CdSe synthesis, enhances the reaction rate by accelerating precursor conversion.

Centrifugal microfluidic platforms have significant potential in commercial applications because of their operational flexibility and minimal external infrastructure requirements. However, the dynamic and real-time control of fluid flow within traditional centrifugal microfluidic platforms is problematic. To address this significant limitation, we propose a two degrees of freedom platform, in which a digital servo is located at each end of an arm driven by a motor. This allows for reversible inward pumping between multiple chambers with perfect efficiency. Furthermore, the addition of a second degree of freedom allows position-based pressure controlled burst valves to be accessed and operated in an independent fashion. To demonstrate the efficacy of this technical innovation, we show rapid and configurable flow switching between three target chambers within a centrifugal microfluidic device., Lab on a Chip, 16 (7), ISSN:1473-0197, ISSN:1473-0189

Fluorescence polarization (FP) is a sensitive, robust, and homogeneous assay format, able to probe a diversity of biological molecules and their interactions. Herein, we describe a new FP strategy based on the use of streptavidin as a signal amplifier. Such signal amplified fluorescence polarization (SAFP) was used to monitor the binding affinity of human angiogenin and a single-stranded DNA aptamer. Streptavidin was bound to a biotinylated single-stranded DNA aptamer and the interaction between this complex and Alexa Fluor 488 labelled human angiogenin was measured. A dissociation constant of 135.3 ± 32.9 nM and a limit of detection of 6.3 nM were successfully extracted only when the FP signal was increased (without binding hindrance) via streptavidin. Moreover, the demonstrated approach was specific to target molecules without any non-specific binding. The streptavidin-triggered SAFP method unlike amplification strategies that utilize nanomaterials (such as graphene oxides, carbon nanotubes, and metal nanoparticles) is not compromised by fluorescence quenching, and it is able to operate within nanomolar concentration regimes. Furthermore, unlike the other FP signal amplification strategies that use dual binding DNA probes, the presented method is simple to implement with signal amplification only requiring the binding of streptavidin with biotinylated DNA. This method could be expanded to analyze molecular interactions and it may be a useful tool for FP measurement by reducing the concentration of rare and expensive protein samples.

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.

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 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 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.

Correction for ‘Long-term C. elegans immobilization enables high resolution developmental studies in vivo’ by Simon Berger et al., Lab Chip, 2018, 18, 1359–1368.

Correction for ‘Soil-on-a-Chip: microfluidic platforms for environmental organismal studies’ by Claire E. Stanley et al., Lab Chip, 2016, 16, 228–241.

This paper presents a micromixer for the laminar flow regime based on the principle of flow lamination. The structure is made up from a glass/silicon/glass sandwich, has a total internal volume of ≡600 nL and measures 5 mm × 10 mm. Flow rates between 1–200 µL min–1 have successfully been used. Fluorescence quenching experiments were carried out for quantification and showed 95% mixing within 15 ms.

We describe the controlled synthesis of dextran-coated superparamagnetic iron oxide nanoparticles (SPIONs) using a stable passively-driven capillary-based droplet reactor. High quality highly crystalline particles were obtained with a narrow size distribution of mean diameter 3.6 nm and standard deviation 0.8 nm. The particles were evaluated for use in MRI, and found to exhibit a large saturation magnetisation of 58 emu/g and a high T2 relaxivity of 66 mM−1s−1 at 4.7 T, signifying good MRI contrast enhancement properties.

We demonstrate the integration of a droplet-based microfluidic device with high performance liquid chromatography (HPLC) in a monolithic format. Sequential operations of separation, compartmentalisation and concentration counter were conducted on a monolithic chip. This describes the use of droplet-based microfluidics for the preservation of chromatographic separations, and its potential application as a high frequency fraction collector.

Droplet interface bilayer (DIB) networks have vast potential in the field of membrane biophysics, synthetic biology, and functional bio-electronics. However a technological bottleneck exists in network fabrication: existing methods are limited in terms of their automation, throughput, versatility, and ability to form well-defined 3-D networks. We have developed a series of novel and low-cost methodologies which address these limitations. The first involves building DIB networks around the contours of a microfluidic chip. The second uses flow rate and droplet size control to influence droplet packing geometries within a microfluidic chamber. The latter method enables the controlled formation of various 3-D network arrays consisting of thousands of interconnected symmetric and asymmetric lipid bilayers for the first time. Both approaches allow individual droplet position and composition to be controlled, paving the way for complex on-chip functional network synthesis.

A microfluidic procedure for the controlled production of cadmium sulfide nanoparticles is described

We present a passive microfluidic strategy for sorting adult C. elegans nematodes on the basis of age and size. The separation mechanism takes advantage of phenotypic differences between 'adult' and 'juvenile' organisms and their behaviour in microfluidic architectures. In brief, the microfluidic device allows worms to sort themselves in a passive manner.

We describe a simple technique for fabricating non-emissive colour filters based on the sensitisation of a highly porous nanostructured metal-oxide film with a monolayer of dye molecules. Ultrafast electron transfer at the oxide/dye interface induces efficient quenching of photogenerated excitons in the dye, reducing the photoluminescence quantum yield by many orders of magnitude. The resultant filters exhibit much less autofluorescence than conventional colour filters (where the chromophore is dispersed in a glass or polymer host), and are a viable low cost alternative to interference filters for microfluidic devices and other applications requiring non-emissive filtering.

We report recent progress in the development of surface-enhanced Raman scattering (SERS)-based optofluidic platforms for the fast and sensitive detection of chemical and biological analytes. In the current context, a SERS-based optofluidic platform is defined as an integrated analytical device composed of a microfluidic element and a sensitive Raman spectrometer. Optofluidic devices for SERS detection normally involve nanocolloid-based microfluidic systems or metal nanostructure-embedded microfluidic systems. In the current review, recent advances in both approaches are surveyed and assessed. Additionally, integrated real-time sensing systems that combine portable Raman spectrometers with microfluidic devices are also reviewed. Such real-time sensing systems have significant utility in environmental monitoring, forensic science and homeland defense applications.

Distinguishing specific cells is an essential technique in cell research and clinical diagnostics. We report a novel method to passively isolate and extract cells in a microfluidic device. We utilise a droplet-based microfluidic system to generate an aqueous two phase system in which aqueous droplets consist of two phases in the form of a double emulsion. Specifically, we generate PEG droplets that completely encapsulate DEX droplets within a microfluidic channel. Target cells can be introduced directly into the droplets and driven to partition to the more favourable phase, whilst still being contained within the aqueous droplet. Human T lymphoma cells, with diameters in the range of 10–15 μm, are chosen as a model cell line to demonstrate the partitioning.

A novel method is presented for controllably merging aqueous microdroplets within segmented flow microfluidic devices. Our approach involves exploiting the difference in hydrodynamic resistance of the continuous phase and the surface tension of the discrete phase through the use of passive structures contained within a microfluidic channel. Rows of pillars separated by distances smaller than the representative droplet dimension are installed within the fluidic network and define passive merging elements or chambers. Initial experiments demonstrate that such a merging element can controllably adjust the distance between adjacent droplets. In a typical scenario, a droplet will enter the chamber, slow down and stop. It will wait and then merge with the succeeding droplets until the surface tension is overwhelmed by the hydraulic pressure. We show that such a merging process is independent of the inter-droplet separation but rather dependent on the droplet size. Moreover, the number of droplets that can be merged at any time is also dependent on the mass flow rate and volume ratio between the droplets and the merging chamber. Finally, we note that the merging of droplet interfaces occurs within both compressing and the decompressing regimes.

We report polymer light emitting diodes fabricated on flexible poly(ethyleneterephthalate) substrates coated with a layer of poly(3,4-ethylene-dioxythiophene) : poly(styrenesulfonate) that was lithographically patterned to define the anode structure. A blend of poly(9,9-dioctylfluorene-co-benzothiadiazole) and poly(9,9-dioctylfluorene-co-N-(4-butylphenyl)diphenylamine) was then spin-coated on top as the emissive layer and the device was completed by vacuum deposition of a LiF/Al bilayer cathode. The resulting yellow light emitting diodes had typical peak power and current efficiencies of 13.7 lm W−1 and 8.8 cd A−1 respectively, which compare well with values for similar devices fabricated on ITO-coated rigid glass substrates. A maximum luminance in excess of 7300 cd m−2 was achieved.

We report the fabrication of high quality monolithically integrated optical long-pass filters, for use in disposable diagnostic microchips. The filters were prepared by incorporating dye molecules directly into the microfluidic chip substrate, thereby providing a fully integrated solution that removes the usual need for discrete optical filters. In brief, lysochrome dyes were added to a poly(dimethylsiloxane) (PDMS) monomer prior to moulding of the microchip from a structured SU-8 master. Optimum results were obtained using 1 mm layers of PDMS doped with 1200 microg mL(-1) Sudan II, which resulted in less than 0.01% transmittance below 500 nm (OD 4),80% above 570 nm, and negligible autofluorescence. These spectral characteristics compare favourably with commercially available Schott-glass long-pass filters, indicating that high quality optical filters can be straightforwardly integrated into the form of PDMS microfluidic chips. The filters were found to be robust in use, showing only slight degradation after extended illumination and negligible dye leaching after prolonged exposure to aqueous solutions. The provision of low cost high quality integrated filters represents a key step towards the development of high-sensitivity disposable microfluidic devices for point-of-care diagnostics.

A simple and robust derivatisation system for glass and silica microdevices is described. The device surface is coated in a one-step treatment with a highly cross-linked polystyrene/divinylbenzene/allylsiloxane copolymer. The surface derivatisation is highly resistant to solvents, acids, bases and oxidising or reducing agents.

An extremely rapid tool for continuous flow synthetic process optimisation is described. A microfluidic reaction system operating in continuous flow is used in conjunction with confocal Raman microscopy to afford rapid molecule synthesis and product quantitation. Accordingly, the approach allows for rapid reaction optimisation within a continuous flow system. Specifically, the catalytic oxidation of isopropyl alcohol (IPA) to acetone using tetra-N-propylammonium perruthanate (TPAP)/N-methylmorpholine N-oxide (NMO) in a radial interdigitated micromixer is studied as a model reaction system. The composition of the reaction effluent can be determined with great facility and information relating to catalyst/co-oxidant ratios, catalyst turnovers and reaction endpoints extracted. Specifically, variation of catalyst and co-oxidant volumetric flow rates between 0 and 50 microL min(-1) is used to vary reactant concentrations, define reaction residence times and control product conversions between 0 and 100%. The rapid nature of the system allows chemical information to be gathered and utilised on a sub-minute timescale.

The online analysis of cadmium selenide nanoparticle formation in continuous-flow microfluidic reactors is described. The as-produced particles exhibit sharp excitonic absorption and emission peaks (∼30–40 nm) with relatively high quantum efficiencies (∼10%). The mean size and dispersity of the particles, determined using on-line fluorescence detection, may be controlled by varying the reaction temperature and/or the flow rate. The microfluidic approach provides considerable control over nucleation/growth processes and is a promising strategy for the direct production of near-monodisperse nanoparticles without recourse to further size selection.

The application of micro total analysis systems has grown exponentially over the past few years, particularly diversifying in disciplines related to bioassays. The primary focus of this review is to detail recent new approaches to sample preparation, nucleic acid amplification and detection within microfluidic devices or at the microscale level. We also introduce some applications that have as yet to be explored in a miniaturised environment, but should benefit from improvements in analytical efficiency and functionality when transferred to planar-chip formats. The studies described in this review were published in commonly available journals as well as in the proceedings of three major conferences relevant to microfluidics (Micro Total Analysis Systems, Transducers and The Nanotechnology Conference and Trade Show). Although an emphasis has been placed on papers published since 2002, pertinent articles preceding this publication year have also been included.

A procedure for the continuous purification of volatile liquids within microfluidic systems is reported.