Microwave-microfluidic devices (MMDs) have emerged as precision tools for the rapid, accurate, sensitive, and non-invasive characterisation of low-volume liquids. However, the fabrication of MMDs remains a significant challenge due to the complexities associated with integrating fluidic ducts and electronic components. Herein, we present a versatile and economical 3D-printing approach for MMD fabrication, using liquid metal as an electrical conductor. Cyclic olefin copolymer, polylactic acid and polypropylene were identified as potential printable dielectric materials for MMD fabrication. 3D-printed cyclic olefin copolymer substrates exhibited the lowest loss tangent of 0.002 at 2.7GHz, making it an ideal material for high frequency engineering. Liquid metal, specifically gallium indium eutectic, was injected into the printed ducts to form conductive microwave structures. Exemplar MMDs were fabricated to integrate split-ring type microwave resonators and droplet-forming fluidic junctions. These devices were applied in the formation and characterisation of water-in-oil emulsions for constructing definable lipid-segregated droplet interface bilayer (DIB) networks. This work not only indicates the feasibility of using 3D-printing for rapid prototyping of customised MMDs but also demonstrates the potential of MMDs as a new research tool for biochemistry and synthetic biology.### Competing Interest StatementThe authors have declared no competing interest.

Microfluidic-microwave devices (MMDs) have emerged as precision tools for the rapid, accurate, sensitive, and non-invasive characterisation of liquids in low-volumes. However, the fabrication of MMDs remains a significant challenge. This is due to the complexities associated with integrating fluidic ducts and electronic components. Herein, we present a versatile and economical 3D-printing approach using ducts filled with liquid metal as an electrical conductor. Cyclic olefin copolymer, polylactic acid, and polypropylene were identified as printable dielectric materials for MMD fabrication. Substrates of 3D-printed cyclic olefin copolymer exhibited the lowest loss tangent (0.002 at 2.7 GHz), making them suitable materials for high-frequency microwave devices. Liquid metal, specifically gallium-indium eutectic, was injected into the printed ducts to form electrically conductive microwave structures. Exemplary MMDs operating at 2 GHz integrated split-ring microwave resonators that serve as sensitive detection geometries able to measure changes in dielectric properties, with droplet-forming fluidic junctions and flow channels. The performance of 3D-printed MMDs for microwave droplet sensing was comprehensively evaluated. These devices were used in the formation and characterisation of water-in-oil emulsions, constructing definable lipid-segregated droplet interface bilayer (DIB) networks. This work indicates the feasibility of using 3D-printed manifolds for the rapid prototyping of customised MMDs, and also demonstrates the potential of MMDs as new analytical research tools in droplet-based materials and biochemistry studies. A 3D-printed microwave-microfluidic device using a liquid metal resonator for droplet network formation and characterisation.

Whilst it is highly desirable to produce artificial lipid bilayer arrays allowing for systematic high-content screening of membrane conditions, it remains a challenge due to the combined requirements of scaled membrane production, simple measurement access, and independent control over individual bilayer experimental conditions. Here, droplet bilayers encapsulated within a hydrogel shell are output individually into multi-well plates for simple, arrayed quantitative measurements. The afforded experimental throughput is used to conduct a 2D concentration screen characterising the synergistic pore-forming peptides Magainin2 and PGLa. Maximal enhanced activity is revealed at equimolar peptide concentrations via a membrane dye leakage assay, a finding consistent with models proposed from NMR data. The versatility of the platform is demonstrated by performing in situ electrophysiology, revealing low conductance pore activity (∼15 to 20 pA with 4.5 pA sub-states). In conclusion, this array platform addresses the aforementioned challenges and provides new and flexible opportunities for high-throughput membrane studies. Furthermore, the ability to engineer droplet networks within each construct paves the way for “lab-in-a-capsule” approaches accommodating multiple assays per construct and allowing for communicative reaction pathways.

Intracellular compartments are functional units that support the metabolism within living cells, through spatiotemporal regulation of chemical reactions and biological processes. Consequently, as a step forward in the bottom-up creation of artificial cells, building analogous intracellular architectures is essential for the expansion of cell-mimicking functionality. Herein, we report the development of a droplet laboratory platform to engineer complex emulsion-based, multicompartment artificial cells, using microfluidics and acoustic levitation. Such levitated models provide free-standing, dynamic, definable droplet networks for the compartmentalisation of chemical species. Equally, they can be remotely operated with pneumatic, heating, and magnetic elements for post-processing, including the incorporation of membrane proteins; alpha-hemolysin; and mechanosensitive channel of large-conductance. The assembly of droplet networks is three-dimensionally patterned with fluidic input configurations determining droplet contents and connectivity, whilst acoustic manipulation can be harnessed to reconfigure the droplet network in situ. The mechanosensitive channel can be repeatedly activated and deactivated in the levitated artificial cell by the application of acoustic and magnetic fields to modulate membrane tension on demand. This offers possibilities beyond one-time chemically mediated activation to provide repeated, non-contact, control of membrane protein function. Collectively, this expands our growing capability to program and operate increasingly sophisticated artificial cells as life-like materials.

Within the context of the European Horizon 2020 project ACDC

Anticancer drug development is a crucial step toward cancer treatment, that requires realistic predictions of malignant tissue development and sophisticated drug delivery. Tumors often acquire drug resistance and drug efficacy, hence cannot be accurately predicted in 2D tumor cell cultures. On the other hand, 3D cultures, including multicellular tumor spheroids (MCTSs), mimic the in vivo cellular arrangement and provide robust platforms for drug testing when grown in hydrogels with characteristics similar to the living body. Microparticles and liposomes are considered smart drug delivery vehicles, are able to target cancerous tissue, and can release entrapped drugs on demand. Microfluidics serve as a high-throughput tool for reproducible, flexible, and automated production of droplet-based microscale constructs, tailored to the desired final application. In this review, it is described how natural hydrogels in combination with droplet microfluidics can generate MCTSs, and the use of microfluidics to produce tumor targeting microparticles and liposomes. One of the highlights of the review documents the use of the bottom-up construction methodologies of synthetic biology for the formation of artificial cellular assemblies, which may additionally incorporate both target cancer cells and prospective drug candidates, as an integrated "droplet incubator" drug assay platform.

Microneedle technology offers a viable means of delivering biologically active pharmaceutical agents across the skin in a minimally invasive and virtually pain free manner. Previous work detailed the first successful transdermal delivery of a model peptide drug, polymyxin b, utilising a dissolving polymer-based microneedle system. The focus of this study was to examine the ability of a dissolving microneedle system to deliver a range of peptides of different sizes and properties. Analogue versions of 2 existing therapeutic peptides; pentagastrin and sincalide, were synthesised utilising Fmoc based solid phase peptide synthesis (SPPS) chemistry techniques and once successfully synthesised and purified, the peptide analogues were characterised using LC-MS. The peptide analogues were then incorporated into PVP/trehalose microneedle formulations. Skin permeation testing, in addition to skin penetration testing, was carried out to determine the effectiveness of the microneedle system to deliver the peptide analogues through porcine skin. The results obtained from these studies were then compared with the permeation results obtained utilising polymyxin B as the peptide drug cargo to evaluate the PVP/trehalose microneedle system’s suitability to successfully deliver therapeutic peptides. Results indicated that the microneedle system successfully systemically delivered a higher overall percentage of the encapsulated peptides at an initially faster rate than peptide loaded control discs and in therapeutically relevant concentrations.

Droplet interface bilayers (DIBs) represent a recently developed method of generating stable artificial lipid membranes suitable for electrophysiology and optical interrogation. Prepared from the contacting of two aqueous droplets in oil, in the presence of dissolved lipid, DIBs are usually confined to a hydrophobic medium. Recent advances have created freestanding, hydrogel-encapsulated droplet interface bilayers (eDIBs) that are aqueous compatible, self-supporting and can withstand mechanical handling. Microfluidic methods allow for their rapid generation, paving the way for high throughput measurements on individually addressable lipid bilayers. Here, we report on the mass preparation of eDIBs using a 3D-printed microfluidic device and the proof-of-principle demonstration of high-throughput optical membrane screening with single bilayer resolution. Individual eDIBs are produced and output into wells of a 96-well plate. Optical measurements are made reporting on membrane leakage to monitor membrane integrity by fluorescent measurement. Addition of bilayer disrupting agents, such as detergents, to individual wells enables parallel measurement of membrane activity using a standard fluorescent plate reader. This platform provides sufficient sensitivity to measure the leakage of dye through membrane spanning pores in otherwise intact bilayers, as well as direct detection of bilayer failure. This high-throughput, scalable and automatable approach to arrayed bilayer measurements offers exiting opportunities for application with further fluorescent-based membrane, or protein, assays. The segregated nature of each droplet allows for the separation of contents either side of the bilayer. Individual bilayers can easily be independently addressed, affording the opportunity to screen a wide parameter space with single bilayer resolution. The ability to reconstitute membrane proteins into DIBs and eDIBs creates many exciting opportunities for the optical screening of membrane proteins and high throughput biophysical measurements.

Aspheric astigmatic polymer micro-lenses were fabricated directly onto photonic integrated circuits using two-photon lithography. We observed a 12.6 dB improvement in the free space coupling efficiency between integrated ridge laser pairs with micro-lenses to those without. © 2018 Optical Society of America under the terms of the OSA Open Access Publishing Agreement OCIS codes: (250.5300) Photonic integrated circuits; (350.3950) Micro-optics; (220.3630) Lenses; (250.5960) Semiconductor lasers; (220.4000) Microstructure fabrication; (200.4650) Optical interconnects. References and links 1. S.E. Miller, “Integrated Optics – An Introduction,” Bell System Tech. J. 4 (7), 2059-2069 (1969). 2. L. M. Augustin, R. Santos, E. den Haan, S. Kleijn, P. J. A. Thijs, S. Latkowski, D. Zhao, W. Yao, J. Bolk, H. Ambrosius, S. Mingaleev, A. Richter, A. Bakker, T. Korthorst, “InP-Based Generic Foundry Platform for Photonic Integrated Circuits,” IEEE J. Sel. Top. Quantum Electron. 24(1), 1-10 (2018). 3. F. Kish, V. Lal, P. Evans, S. W. Corzine, M. Ziari, T. Butrie, M. Reffle, H-S. Tsai, A. Dentai, J. Pleumeekers, M. Missey, M. Fisher, S. Murthy, R. Salvatore, P. Samra, S. Demars, N. Kim, A. James, A. Hosseini, P. Studenkov, M. Lauermann, R. Going, M. Lu, J. Zhang, J. Tang, J. Bostak, T. Vallaitis, M. Kuntz, D. Pavinski, A. Karanicolas, B. Behnia, D. Engel, O. Khayam, N. Modi, M. R. Chitgarha, P. Mertz, W. Ko, R. Maher, J. Osenbach, J. T. Rahn, H. Sun, K-T Wu, M. Mitchell and D. Welch, “System-on-Chip Photonic Integrated Circuits,” IEEE J. Sel. Top. Quantum Electron. 24 (1), 6100120 (2018). 4. S. J. Ben Yoo, Binbin Guan and Ryan P. Scott, “Heterogeneous 2D/3D photonic integrated Microsystems,” Microsystems Nanoengineering 2, 16030 (2016). 5. N. Lindenmann, G. Balthasar, D. Hillerkuss, R. Schmogrow, M. Jordan, J. Leuthold, W. Freude, and C. Koos, “Photonic wire bonding: a novel concept for chipscale interconnects,” Opt. Express 20, 17667 (2012). 6. X. J. Liang, A. Q. Liu, C. S. Lim, T. C. Ayi and P. H. Yap, “Determining refractive index of single living cell using an integrated microchip,” Sensors Actuators A 133, 349–354 (2007). 7. S. Cran-McGreehin, T. F. Krauss K. Dholakia, “Integrated monolithic optical manipulation,” Lab Chip 6, 1122-

Stem cell encapsulation technology demonstrates much promise for the replacement of damaged tissue in several diseases, including spinal cord injury (SCI). The use of biocompatible microcapsules permits the control of stem cell fate in situ to facilitate the replacement of damaged/lost tissue. In this work, a novel customized microfluidic device was developed for the reproducible encapsulation of neural stem cells (NSCs) and dental pulp stem cells (DPSCs) within monodisperse, alginate-collagen microcapsules. Both cell types survived within the microcapsules for up to 21 days in culture. Stem cells demonstrated retention of their multipotency and neuronal differentiation properties upon selective release from the microcapsules, as demonstrated by high proliferation rates and the production of stem cell and neuronal lineage markers. When cell-laden microcapsules were transplanted into an organotypic SCI model, the microcapsules effectively retained the transplanted stem cells at the site of implantation. Implanted cells survived over a 10 day period in culture after transplantation and demonstrated commitment to a neural lineage. Our device provides a quick, effective, and aseptic method for the encapsulation of two different stem cell types (DPSCs and NSCs) within alginate-collagen microcapsules. Since stem cells were able to retain their viability and neural differentiation capacity within such microcapsules, this method provides a useful technique to study stem cell behavior within three-dimensional environments.

A new oscillatory microfluidic junction is described, which enables the consistent formation of highly uniform and complex double emulsions, and is demonstrated for the encapsulation of four different reagents within the inner droplets (called cores) of the double emulsion droplets. Once the double emulsion droplets had attained a spherical form, the cores assumed specific 3D arrangements, the orchestration of which appeared to depend upon the specific emulsion morphology. Such double emulsion droplets were used as templates to produce highly compartmentalised microcapsules and multisomes. Based on these construct models, we numerically demonstrated a model chemical reaction sequence between and within the liquid cores. This work could provide a platform to perform space/time-dependent applications, such as programmed experiments, synthesis, and delivery systems.

Chip based particle sensing using 3D capillary fill microfluidics integrated with monolithically integrated lasers and photodetectors is used to demonstrate the feasibility of true chip scale photonic measurements of fluids. The approach is scalable and manufactured using industry standard compound semiconductor fabrication tools. The need for fluid speed regulation via external pumps is removed by measuring local particle velocity at the point of interrogation and particle position within the fluid flow is derived from multiple time resolved forward scattered light signals. Particle size discrimination of 10 and 15 μm polystyrene microbeads is used as an example.

A new oscillatory microfluidic junction is described, which enables the consistent formation of highly uniform and complex double emulsions, and is demonstrated for the encapsulation of four different reagents within the inner droplets (called cores) of the double emulsion droplets. Once the double emulsion droplets had attained a spherical form, the cores assumed specific 3D arrangements, the orchestration of which appeared to depend upon the specific emulsion morphology. Such double emulsion droplets were used as templates to produce highly compartmentalised microcapsules and multisomes. Based on these construct models, we numerically demonstrated a model chemical reaction sequence between and within the liquid cores. This work could provide a platform to perform space/time-dependent applications, such as programmed experiments, synthesis, and delivery systems.

High specification, polymer capsules, to produce inertial fusion energy targets, were continuously fabricated using surfactant-free, inertial centralisation, and ultrafast polymerisation, in a scalable flow reactor. Laser-driven, inertial confinement fusion depends upon the interaction of high-energy lasers and hydrogen isotopes, contained within small, spherical and concentric target shells, causing a nuclear fusion reaction at ~150 M°C. Potentially, targets will be consumed at ~1 M per day per reactor, demanding a 5000x unit cost reduction to ~$0.20, and is a critical, key challenge. Experimentally, double emulsions were used as templates for capsule-shells, and were formed at 20 Hz, on a fluidic chip. Droplets were centralised in a dynamic flow, and their shapes both evaluated, and mathematically modeled, before subsequent shell solidification. The shells were photo-cured individually, on-the-fly, with precisely-actuated, millisecond-length (70 ms), uniform-intensity UV pulses, delivered through eight, radially orchestrated light-pipes. The near 100% yield rate of uniform shells had a minimum 99.0% concentricity and sphericity, and the solidification processing period was significantly reduced, over conventional batch methods. The data suggest the new possibility of a continuous, on-the-fly, IFE target fabrication process, employing sequential processing operations within a continuous enclosed duct system, which may include cryogenic fuel-filling, and shell curing, to produce ready-to-use IFE targets.

Computerized tomography scan (CT scan) imaging and finite element analysis were employed to investigate how the geometric composition of microneedles affects their mechanical strength and penetration characteristics. Simulations of microneedle arrays, comprising triangular, square and hexagonal microneedle base, revealed a linear dependence of the mechanical strength to the number of vertices in the polygon base. A laser-enabled, micromoulding technique was then used to fabricate 3×3 microneedle arrays, each individual microneedle having triangular, square or hexagonal base geometries. Their penetration characteristics into ex-vivo porcine skin, were investigated for the first time by CT scan imaging. This revealed greater penetration depths for the triangular and square-based microneedles, demonstrating CT scan as a powerful and reliable technique for studying microneedle skin penetration.

A fluidic one-bit half-adder is made of five channels which intersect at a junction. Two channels are inputs, two channels are outputs and one channel is the drain. The channels direct fluid from input fragments to output fragments and the streams of fluid interact at the junctions. Binary signals are represented by water droplets introduced in the input channels: presence of a droplet in an input or output segments symbolises logical {\sc True}, absence --- {\sc False}. The droplets travel along channels by following a path of least resistance unless deflected at the junction. We demonstrate the function of the half-adder in both computer modelling and laboratory experiments, and propose a design of a one-bit full adder based on simulation.

AbstractThe ability to make artificial lipid bilayers compatible with a wide range of environments, and with sufficient structural rigidity for manual handling, would open up a wealth of opportunities for their more routine use in real‐world applications. Although droplet interface bilayers (DIBs) have been demonstrated in a host of laboratory applications, from chemical logic to biosynthesis reaction vessels, their wider use is hampered by a lack of mechanical stability and the largely manual methods employed in their production. Multiphase microfluidics has enabled us to construct hierarchical triple emulsions with a semipermeable shell, in order to form robust, bilayer‐bound, droplet networks capable of communication with their external surroundings. These constructs are stable in air, water, and oil environments and overcome a critical obstacle of achieving structural rigidity without compromising environmental interaction. This paves the way for practical application of artificial membranes or droplet networks in diverse areas such as medical applications, drug testing, biophysical studies and their use as synthetic cells.

The uptake of microfluidics by the wider scientific community has been limited by the fabrication barrier created by the skills and equipment required for the production of traditional microfluidic devices. Here we present simple 3D printed microfluidic devices using an inexpensive and readily accessible printer with commercially available printer materials. We demonstrate that previously reported limitations of transparency and fidelity have been overcome, whilst devices capable of operating at pressures in excess of 2000 kPa illustrate that leakage issues have also been resolved. The utility of the 3D printed microfluidic devices is illustrated by encapsulating dental pulp stem cells within alginate droplets; cell viability assays show the vast majority of cells remain live, and device transparency is sufficient for single cell imaging. The accessibility of these devices is further enhanced through fabrication of integrated ports and by the introduction of a Lego®-like modular system facilitating rapid prototyping whilst offering the potential for novices to build microfluidic systems from a database of microfluidic components.

A novel microfluidic biosensing platform based on Bipolar-Complementary Oxide Semiconductor (BiCMOS) technology is presented. The device relies on a quadruple electrode system and a microfluidic channel that are directly integrated into the back-end-of-line (BEOL) of the BiCMOS stack. For proof of concept repeatable electrical trapping of single SW620 (colon cancer) cells in the quadruple electrode system is initially demonstrated. Additionally, for the first time a microwave intermodulation technique is used for high sensitivity dielectric spectroscopy, which could pave the way to label-free monitoring of intracellular processes and manipulation such as electroporation.

A new microwave microstrip sensor is presented in this paper for microsphere detection and dielectric characterization within a microfluidic channel. This comprises a 2.5 GHz split ring resonator with a 35 µm gap. To validate the sensor, two sizes of polystyrene microspheres (of diameters 15 and 25 µm) were tested. Measurements of changes in resonant frequency and insertion loss of the odd mode were related to the dielectric contrast provided by the microspheres and their host solvent, here water. COMSOL Multiphysics® was used to model the sensor, and good agreements were found between the simulated and measured results.