Prof. Andrew deMello

Principal Investigator

Andrew is currently Professor of Biochemical Engineering in the Department of Chemistry and Applied Biosciences at ETH Zurich. Prior to his arrival in Zurich he was Professor of Chemical Nanosciences and Head of the Nanostructured Materials and Devices Section in the Chemistry Department at Imperial College London. 

He obtained a 1st Class Degree in Chemistry and PhD in Molecular Photophysics from Imperial College London in 1995 and subsequently held a Postdoctoral Fellowship in the Department of Chemistry at the University of California, Berkeley working with professor Richard Mathies.

His research interests cover a broad range of activities in the general area of microfluidics and nanoscale science. Primary specializations include the development of microfluidic devices for high-throughput biological and chemical analysis, ultra-sensitive optical detection techniques, nanofluidic reaction systems for chemical synthesis, novel methods for nanoparticle synthesis, the exploitation of semiconducting materials in diagnostic applications, the development of intelligent microfluidics and the processing of living organisms.

Andrew has given approximately 250 invited lectures at conferences and universities in North America, Europe, Africa and Asia (including 50 plenary or keynote lectures), has published 170 papers in refereed journals, and co-authored two books. He currently sits on the Editorial Boards of Chemistry World, The Journal of Flow Chemistry, Biomicrofluidics, BioChip journal and Imperial College Press. He is also co-founder of Molecular Vision Ltd, an Imperial College spin-out company developing low-cost diagnostic devices for use in the doctor's surgery and in the home.

Science originating from the deMello group has been recognized through the award of the 2002 SAC Silver Medal (Royal Society of Chemistry), the 2009 Clifford Paterson Medal from The Royal Society, the 2009 Corday Morgan Medal (Royal Society of Chemistry) and the 2007 Clark Memorial Lectureship (California State University).


Yun Ding, Xavier Casadevall i Solvas and Andrew deMello. The “V-junction”: a novel structure for high-speed generation of bespoke droplet flows. Analyst, 2014, Accepted Manuscript

We present the use of microfluidic “V-junctions” as a droplet generation strategy that incorporates enhanced performance characteristics when compared to more traditional “T-junction” formats. This includes the ability to generate target-sized droplets from the very first one, efficient switching between multiple input samples, the production of a wide range of droplet sizes (and size gradients) and the facile generation of droplets with residence time gradients. Additionally, the use of V-junction droplet generators enables the suspension and subsequent resumption of droplet flows at times defined by the user. The high degree of operational flexibility allows a wide range of droplet sizes, payloads, spacings and generation frequencies to be obtained, which in turn provides for an enhanced design space for droplet-based experimentation. We show that the V-junction retains the simplicity of operation associated with T-junction formats, whilst offering functionalities normally associated with droplet-on-demand technologies.

Chiara Martino, Simon Berger, Robert C. R. Wootton and Andrew J. deMello. A 3D-Printed Microcapillary Assembly for Facile Double Emulsion Generation. Lab Chip. 2014, 14, 4178-4182
Claire Stanley, Martina Stöckli, Dirk van Swaay, Jerica Sabotič, Pauli Kallio, Markus Kuenzler, Andrew deMello and Markus Aebi. Probing bacterial-fungal interactions at the single cell level. Integr. Biol., 2014, 6, 935-945

Interactions between fungi and prokaryotes are abundant in many ecological systems. A wide variety of biomolecules regulate such interactions and many of them have found medicinal or biotechnological applications. However, studying a fungal-bacterial system at a cellular level is technically challenging. New microfluidic devices provided a platform for microscopic studies and for long-term, time-lapse experiments. Application of these novel tools revealed insights into in the dynamic interactions between the basidiomycete Coprinopsis cinerea and Bacillus subtilis. Direct contact was mediated by polar attachment of bacteria to only a subset of fungal hyphae suggesting a differential competence of fungal hyphae and thus differentiation of hyphae within a mycelium. The fungicidal activity of Bacillus subtilis was monitored at a cellular level and showed a novel mode of action on fungal hyphae.

Richard M. Maceiczyk and Andrew J. deMello. Fast and Reliable Metamodeling of Complex Reaction Spaces Using Universal Kriging. J. Phys. Chem. C, 2014, 118, 20026–20033

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.

Thomas W. Phillips*, Ioannis G. Lignos*, Richard M. Maceiczyk*, Andrew J. deMello and John C. deMello. Nanocrystal synthesis in microfluidic reactors: where next?. Lab Chip. 2014, 14, 3172-3180

The past decade has seen a steady rise in the use of microfluidic reactors for nanocrystal synthesis, with numerous studies reporting improved reaction control relative to conventional batch chemistry. However, flow synthesis procedures continue to lag behind batch methods in terms of chemical sophistication and the range of accessible materials, with most reports having involved simple one- or two-step chemical procedures directly adapted from proven batch protocols. Here we examine the current status of microscale methods for nanocrystal synthesis, and consider what role microreactors might ultimately play in laboratory-scale research and industrial production.

Jae-Won Choi, Sangmin Lee, Dong-Hun Lee, Joonwon Kim, Andrew J. deMello and Soo-Ik Chang. Integrated pneumatic micro-pumps for high-throughput droplet-based microfluidics. RSC Adv., 2014, 4, 20341-20345

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.

Ioannis Lignos, Loredana Protesescu, Stavros Stavrakis, Laura Piveteau, Mark J. Speirs, Maria Antonietta Loi, Maksym V. Kovalenko, and Andrew J. deMello. Facile Droplet-based Microfluidic Synthesis of Monodisperse IV–VI Semiconductor Nanocrystals with Coupled In-Line NIR Fluorescence Detection. Chem. Mater., 2014, 26, 2975–2982

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.

Jin-young Kim, Soo-Ik Chang, Andrew J. deMello and Danny O’Hare. Integration of monolithic porous polymer with droplet-based microfluidics on a chip for nano/ picoliter volume sample analysis. Nano Convergence 2014, 1, 1-5

In this paper, a porous polymer nanostructure has been integrated with droplet-based microfluidics in a single planar format. Monolithic porous polymer (MPP) was formed selectively within a microfluidic channel. The resulting analyte bands were sequentially comartmentalised into droplets. This device reduces band broadening and the effects of post-column dead volume by the combination of the two techniques. Moreover it offers the precise control of nano/picoliter volume samples.

Simon Berger, Joanna Stawikowska, Dirk van Swaay, and Andrew deMello. Continuous Suspension of Lipids in Oil by the Selective Removal of Chloroform via Microfluidic Membrane Separation. Ind. Eng. Chem. Res., 2014, 53, 9256–9261

A continuous flow method for the suspension of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) lipids in oil using a microfluidic platform is presented. The system consists of a microfluidic device housing a semipermeable membrane, a vacuum pump, and a syringe pump. Separation is achieved using a counter current flow of chloroform and a lipid containing oil stream, driven by the syringe pump and vacuum. Using such a system, a high efficiency extraction method was realized through the use of a semipermeable polydimethylsiloxane (PDMS) membrane on an anodized aluminum oxide (AAO) support. For a liquid flow rate of 5 μL/min, an air flow rate of 100 mL/min, and initial chloroform concentrations between 0.245 and 1.619 M, extraction rates of 93.5% to 97.9% and a retentate stream purity of between 99.79% and 99.29% were achieved.

Yan Zhao, Fiona Pereira, Andrew J. deMello, Hywel Morgan and Xize Niu. Droplet-based in situ compartmentalization of chemically separated components after isoelectric focusing in a Slipchip. Lab Chip. 2014, 14, 555-561

Isoelectric focusing (IEF) is a powerful and widely used technique for protein separation and purification. There are many embodiments of microscale IEF that use capillary or microfluidic chips for the analysis of small sample volumes. Nevertheless, collecting the separated sample volumes without causing remixing remains a challenge. Herein, we describe a microfluidic Slipchip device that is able to efficiently compartmentalize focused analyte bands in situ into microdroplets. The device contains a microfluidic “zig-zag” separation channel that is composed of a sequence of wells formed in the two halves of the Slipchip. The analytes are focused in the channel and then compartmentalised into droplets by slipping the chip. Importantly, sample droplets can be analysed on chip or collected for subsequent analysis using electrophoresis or mass spectrometry for example. To demonstrate this approach, we perform IEF separation using standard markers and protein samples, with on-chip post-processing. Compared to alternative approaches for sample collection, the method avoids remixing, is scalable and is easily hyphenated with the other analytical methods.

Xiuqing Gong, Amol V. Patil, Aleksandar P. Ivanov, Qingyuan Kong, Thomas Gibb, Fatma Dogan, Andrew J. deMello, and Joshua B. Edel . Label-Free In-Flow Detection of Single DNA Molecules using Glass Nanopipettes. Anal. Chem., 2014, 86, 835–841

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.

Oliver J. Dressler, Richard M. Maceiczyk, Soo-Ik Chang, Andrew J. Demello. Droplet-Based Microfluidics: Enabling Impact on Drug Discovery. J. Biomol. Screen., 2014, 19, 483-496

Over the past two decades, the application of microengineered systems in the chemical and biological sciences has transformed the way in which high-throughput experimentation is performed. The ability to fabricate complex microfluidic architectures has allowed scientists to create new experimental formats for processing ultra-small analytical volumes in short periods and with high efficiency. The development of such microfluidic systems has been driven by a range of fundamental features that accompany miniaturization. These include the ability to handle small sample volumes, ultra-low fabrication costs, reduced analysis times, enhanced operational flexibility, facile automation, and the ability to integrate functional components within complex analytical schemes. Herein we discuss the impact of microfluidics in the area of high-throughput screening and drug discovery and highlight some of the most pertinent studies in the recent literature.

Katherine S. Elvira, Xavier Casadevall i Solvas, Robert C. R. Wootton and Andrew J. deMello. The past, present and potential for microfluidic reactor technology in chemical synthesis. Nat. Chem., 2013, 5, 905–915

The past two decades have seen far-reaching progress in the development of microfluidic systems for use in the chemical and biological sciences. Here we assess the utility of microfluidic reactor technology as a tool in chemical synthesis in both academic research and industrial applications. We highlight the successes and failures of past research in the field and provide a catalogue of chemistries performed in a microfluidic reactor. We then assess the current roadblocks hindering the widespread use of microfluidic reactors from the perspectives of both synthetic chemistry and industrial application. Finally, we set out seven challenges that we hope will inspire future research in this field.

Xize Niu, Fiona Pereira, Joshua B. Edel, and Andrew J. de Mello. Droplet-Interfaced Microchip and Capillary Electrophoretic Separations. Anal. Chem. 2013, 85, 8654–8660

Both capillary and chip-based electrophoresis are powerful separation methods widely used for the separation of complex analytical mixtures in the fields of genomics, proteomics, metabolomics, and cellular analysis. However their utility as basic tools in high-throughput analysis and multidimensional separations has been hampered by inefficient or biased sample injection methods. Herein, we address this problem through the development of a simple separation platform that incorporates droplet-based microfluidic module for the encapsulation of analytes prior to the analytical separation. This method allows for the precise and reproducible injection of pL to nL volume isolated plugs into an electrophoretic separation channel. The developed platform is free from inter sample contamination, allows for small sample size, high-throughput analysis, and can provide quantitative analytical information.

Soongwon Cho, Dong-Ku Kang, Steven Sim, Florian Geier, Jin-Young Kim, Xize Niu, Joshua B. Edel, Soo-Ik Chang, Robert C. R. Wootton, Katherine S. Elvira and Andrew J. deMello. Droplet-Based Microfluidic Platform for High-Throughput, Multi-Parameter Screening of Photosensitizer Activity. Anal. Chem. 2013, 85, 8866–8872

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.

Fiona Pereira, Xize Niu and Andrew J. deMello. A Nano LC-MALDI Mass Spectrometry Droplet Interface for the Analysis of Complex Protein Samples. PLoS ONE, 2013, 8, e63087

The integration of matrix-assisted laser desorption ionization (MALDI) mass spectrometry with an upstream analytical separations (such as liquid chromatography and electrophoresis) has opened up new opportunities for the automated investigation of complex protein and peptide mixtures. The ability to efficiently analyze complex proteomic mixtures in this manner is primarily determined by the ability to preserve spatial discrimination of sample components as they leave the separation column. Current interfacing methods are problematic in this respect since minimum fraction volumes are limited to several microliters. Herein we show for the first time an LC-MALDI interface based on the formation, processing and destruction of a segmented flow. The interface consists of a droplet-generator to fractionate LC effluent into nL-volume droplets and a deposition probe that transfers the sample (and MALDI matrix) onto a conventional MALDI-MS target. The efficacy of the method is demonstrated through the analysis of Trypsin digests of both BSA and Cytochrome C, with a 50% enhancement in analytical performance when compared to conventional interface technology.

Fabrice Gielen, Liisa Van Vliet, Bartosz T. Koprowski, Sean R.A. Devenish, Martin Fischlechner, Joshua B. Edel, Xize Niu, Andrew J. de Mello and Florian Hollfelder. A Fully Unsupervised Compartment-on-demand Platform for Precise Nanolitre Assays of Time-Dependent Steady-State Enzyme Kinetics and Inhibition. Anal. Chem., 2013, 85, 4761–4769

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 system results in a fully automated analytical platform. 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 minutes; droplet production (5 minutes), initial reading of the droplet sequence (5 minutes), droplet fusion to initiate the reaction and read-out over time (10 minutes). 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 by >104-fold volume reduction, from micro- to nanoliters.

Dirk van Swaay and Andrew deMello. Microfluidic methods for forming liposomes. Lab Chip, 2013, 13, 752-767

Liposome structures have a wide range of applications in biology, biochemistry, and biophysics. As a result, several methods for forming liposomes have been developed. This review provides a critical comparison of existing microfluidic technologies for forming liposomes and, when applicable, a comparison with their analogous macroscale counterparts. The properties of the generated liposomes, including size, size distribution, lamellarity, membrane composition, and encapsulation efficiency, form the basis for comparison. We hope that this critique will allow the reader to make an informed decision as to which method should be used for a given biological application.

Katherine S. Elvira, Robert C. R. Wootton, Nuno M. Reis, Malcolm R. Mackley and Andrew J. deMello. Through-Wall Mass Transport as a Modality for Safe Generation of Singlet Oxygen in Continuous Flows. ACS Sustainable Chem. Eng., 2013, 1, 209-213

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, allows for increased safety of operation, and provides for space–time yields over 20 times larger than the corresponding bulk synthesis.

Mikihide Yamazaki, Siva Krishnadasan, Andrew J. deMello and John C. deMello. Non-emissive plastic colour filters for fluorescence detection. Lab Chip, 2012,12, 4313-4320

We report the fabrication of non-emissive short- and long-pass filters on plastic for high sensitivity fluorescence detection. The filters were prepared by overnight immersion of titania-coated polyethylene terephthalate (PET) in an appropriate dye solution – xylene cyanol for short-pass filtering and fluorescein disodium salt for long-pass filtering – followed by repeated washing to remove excess dye. The interface between the titania and the dye molecule induces efficient quenching of photo-generated excitons in the dye molecule, reducing auto-fluorescence to negligible values and so overcoming the principal weakness of conventional colour filters. Using the filters in conjunction with a 505 nm cyan light-emitting diode and a Si photodiode, dose-response measurements were made for T8661 Transfluosphere beads in the concentration range 1 × 10^9 to 1 × 10^5 beads μL−1, yielding a limit of detection of 3 × 10^4 beads μL−1. The LED/short-pass filter/T8661/long-pass filter/Si-photodiode combination reported here offers an attractive solution for sensitive, low cost fluorescence detection that is readily applicable to a wide range of bead-based immunodiagnostic assays.

Miriam S. Goyder, Keith R. Willison, David R. Klug, Andrew J. deMello and Oscar Ces. Affinity chromatography and capillary electrophoresis for analysis of the yeast ribosomal proteins. BMB Reports, 2012, 45, 233-238

We present a top down separation platform for yeast ribosomal proteins using affinity chromatography and capillary electro- phoresis which is designed to allow deposition of proteins onto a substrate. FLAG tagged ribosomes were affinity purified, and rRNA acid precipitation was performed on the ribosomes fol- lowed by capillary electrophoresis to separate the ribosomal proteins. Over 26 peaks were detected with excellent reprodu- cibility (<0.5% RSD migration time). This is the first reported separation of eukaryotic ribosomal proteins using capillary electrophoresis. The two stages in this workflow, affinity chro- matography and capillary electrophoresis, share the advantages that they are fast, flexible and have small sample requirements in comparison to more commonly used techniques. This meth- od is a remarkably quick route from cell to separation that has the potential to be coupled to high throughput readout plat- forms for studies of the ribosomal proteome.

Alexandra Yashina, Fiona Meldrum and Andrew deMello. Calcium carbonate polymorph control using droplet-based microfluidics. Biomicrofluidics, 2012, 6, 022001

Calcium carbonate (CaCO3) is one of the most abundant minerals and of high importance in many areas of science including global CO2 exchange, industrial water treatment energy storage, and the formation of shells and skeletons. Industrially, calcium carbonate is also used in the production of cement, glasses, paints, plastics, rubbers, ceramics, and steel, as well as being a key material in oil refining and iron ore purification. CaCO3 displays a complex polymorphic behaviour which, despite numerous experiments, remains poorly characterised. In this paper, we report the use of a segmented-flow microfluidic reactor for the controlled precipitation of calcium carbonate and compare the resulting crystal properties with those obtained using both continuous flow microfluidic reactors and conventional bulk methods. Through combination of equal volumes of equimolar aqueous solutions of calcium chloride and sodium carbonate on the picoliter scale, it was possible to achieve excellent definition of both crystal size and size distribution. Furthermore, highly reproducible control over crystal polymorph could be realised, such that pure calcite, pure vaterite, or a mixture of calcite and vaterite could be precipitated depending on the reaction conditions and droplet-volumes employed. In contrast, the crystals precipitated in the continuous flow and bulk systems comprised of a mixture of calcite and vaterite and exhibited a broad distribution of sizes for all reaction conditions investigated.

Katherine S. Elvira, Robin Leatherbarrow, Joshua Edel and Andrew deMello. Droplet dispensing in digital microfluidic devices: Assessment of long-term reproducibility. Biomicrofluidics, 2012, 6, 022003

We report an in-depth study of the long-term reproducibility and reliability of droplet dispensing in digital microfluidic devices (DMF). This involved dispensing droplets from a reservoir, measuring the volume of both the droplet and the reservoir droplet and then returning the daughter droplet to the original reservoir. The repetition of this process over the course of several hundred iterations offers, for the first time, a long-term view of droplet dispensing in DMF devices. Results indicate that the ratio between the spacer thickness and the electrode size influences the reliability of droplet dispensing. In addition, when the separation between the plates is large, the volume of the reservoir greatly affects the reproducibility in the volume of the dispensed droplets, creating “reliability regimes.” We conclude that droplet dispensing exhibits superior reliability as inter-plate device spacing is decreased, and the daughter droplet volume is most consistent when the reservoir volume matches that of the reservoir electrode.

Jae-Won Choi, Dong-Ku Kang, Hyun Park, Andrew J. deMello & Soo-Ik Chang. High-Throughput Analysis of Protein–Protein Interactions in Picoliter-Volume Droplets Using Fluorescence Polarization. Anal. Chem., 2012, 84, 3849-3854

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 (KD = 10.4 ± 3.3 nM) within short time periods.

Claire E. Stanley, Robert C. R. Wootton and Andrew J. deMello. Continuous and Segmented Flow Microfluidics: Applications in High- throughput Chemistry and Biology. Chimia, 2012, 66, 88-98

This account highlights some of our recent activities focused on developing microfluidic technologies for application in high-throughput and high-information content chemical and biological analysis. Specifically, we discuss the use of continuous and segmented flow microfluidics for artificial membrane formation, the analysis of single cells and organisms, nanomaterial synthesis and DNA amplification via the polymerase chain reaction. In addition, we report on recent developments in small-volume detection technology that allow access to the vast amounts of chemical and biological information afforded by microfluidic systems.

Robert C.R. Wootton and Andrew J. deMello. Microfluidics: Analog-to-digital drug screening. Nature, 2012, 483, 43-44

Current methods for screening libraries of compounds for biological activity are rather cumbersome, slow and imprecise. A method that breaks up a continuous flow of a compound's solution into droplets offers radical improvements.

Xiuqing Gong, Philip W. Miller, Antony D. Gee, Nicholas J. Long, Andrew J. de Mello and Ramon Vilar. Gas–Liquid Segmented Flow Microfluidics for Screening Pd-Catalyzed Carbonylation Reactions. Chem. Eur. J., 2012, 18, 2768-2772

Go with the (segmented) flow: A gas–liquid microfluidic reactor system has been developed to study Pd-catalyzed carbonylation reactions over a range of flow regimes and reaction conditions (see picture). The segmented gas–liquid flow regime, in comparison to annular flow, enables reactions to be studied over longer reaction times and without the buildup of unwanted Pd particles.

Fabrice Gielen, Andrew J. deMello and Joshua B. Edel. Dielectric Cell Response in Highly Conductive Buffers. Anal. Chem., 2012, 84,1849-1853

We present a novel method for the identification of live and dead T-cells, dynamically flowing within highly conductive buffers. This technique discriminates between live and dead (heat treated) cells on the basis of dielectric properties variations. The key advantage of this technique lies in its operational simplicity, since cells do not have to be resuspended in isotonic low conductivity media. Herein, we demonstrate that at 40 MHz, we are able to statistically distinguish between live and dead cell populations.

Soongwon Cho, Dong-Ku Kang, Jaebum Choo, Andrew J. deMello and Soo-Ik Chang. Recent advances in microfluidic technologies for biochemistry and molecular biology. BMB Reports, 2011, 44, 705-712

Advances in the fields of proteomics and genomics have necessitated the development of high-throughput screening methods (HTS) for the systematic transformation of large amounts of biological/ chemical data into an organized database of knowledge. Microfluidic systems are ideally suited for high-throughput biochemical experimentation since they offer high analytical throughput, consume minute quantities of expensive biological reagents, exhibit superior sensitivity and functionality compared to traditional micro-array techniques and can be integrated within complex experimental work flows. A range of basic biochemical and molecular biological operations have been transferred to chipbased microfluidic formats over the last decade, including gene sequencing, emulsion PCR, immunoassays, electrophoresis, cellbased assays, expression cloning and macromolecule blotting. In this review, we highlight some of the recent advances in the application of microfluidics to biochemistry and molecular biology.

Xize Niu, Fabrice Gielen, Joshua B. Edel and Andrew J. deMello. A microdroplet dilutor for high-throughput screening. Nat. Chem., 2011, 3, 437-442

Pipetting and dilution are universal processes used in chemical and biological laboratories to assay and experiment. In microfluidics such operations are equally in demand, but difficult to implement. Recently, droplet-based microfluidics has emerged as an exciting new platform for high-throughput experimentation. However, it is challenging to vary the concentration of droplets rapidly and controllably. To this end, we developed a dilution module for high-throughput screening using droplet-based microfluidics. Briefly, a nanolitre-sized sample droplet of defined concentration is trapped within a microfluidic chamber. Through a process of droplet merging, mixing and re-splitting, this droplet is combined with a series of smaller buffer droplets to generate a sequence of output droplets that define a digital concentration gradient. Importantly, the formed droplets can be merged with other reagent droplets to enable rapid chemical and biological screens. As a proof of concept, we used the dilutor to perform a high-throughput homogeneous DNA-binding assay using only nanolitres of sample.
» A microfluidic droplet dilutor
» Nature Chemistry 2011 Cover

Robert C. R. Wootton and Andrew J. deMello. Microfluidics: Exploiting elephants in the room. Nature, 2010, 464, 839-840

Microfluidic devices have many applications in chemistry and biology, but practical hitches associated with their use are often overlooked. One such device that optimizes catalysts tackles these issues head-on.

Yolanda Schaerli, Robert C. Wootton, Tom Robinson, Viktor Stein, Christopher Dunsby, Mark A. A. Neil, Paul M. W. French, Andrew J. deMello, Chris Abell and Florian Hollfelder. Continuous-Flow Polymerase Chain Reaction of Single-Copy DNA in Microfluidic Microdroplets. Anal. Chem., 2009, 81, 302-306

We present a high throughput microfluidic device for continuous-flow polymerase chain reaction (PCR) in water-in-oil droplets of nanoliter volumes. The circular design of this device allows droplets to pass through alternating temperature zones and complete 34 cycles of PCR in only 17 min, avoiding temperature cycling of the entire device. The temperatures for the applied two-temperature PCR protocol can be adjusted according to requirements of template and primers. These temperatures were determined with fluorescence lifetime imaging (FLIM) inside the droplets, exploiting the temperature-dependent fluorescence lifetime of rhodamine B. The successful amplification of an 85 base-pair long template from four different start concentrations was demonstrated. Analysis of the product by gel-electrophoresis, sequencing, and real-time PCR showed that the amplification is specific and the amplification factors of up to 5 × 106-fold are comparable to amplification factors obtained in a benchtop PCR machine. The high efficiency allows amplification from a single molecule of DNA per droplet. This device holds promise for convenient integration with other microfluidic devices and adds a critical missing component to the laboratory-on-a-chip toolkit.
» Continuous flow PCR in droplets

Peter M.P. Lanigan, Karen Chan, Tanya Ninkovic, Richard H. Templer, P.M.W. French, A.J. deMello1,2, K. R. Willison, P.J. Parker, M.A.A. Neil, O. Ces and D.R. Klug. Spatially selective sampling of single cells using optically trapped fusogenic emulsion droplets: a new single-cell proteomic tool. J. R. Soc. Interface, 2008, 5, S161–S168

We present a platform for the spatially selective sampling of the plasma membrane of single cells. Optically trapped lipid-coated oil droplets (smart droplet microtools, SDMs), typically 0.5–5 mm in size, composed of a hexadecane hydrocarbon core and fusogenic lipid outer coating (mixture of 1,2-dioleoyl-phosphatidylethanolamine and 1,2-dioleoyl-sn-glycero-3- phosphatidylcholine) were brought into controlled contact with target colon cancer cells leading to the formation of connecting membrane tethers. Material transfer from the cell to the SDM across the membrane tether was monitored by tracking membrane-localized enhanced green fluorescent protein.

Alexander Iles, Matthew Habgood, Andrew J. de Mello and Robert C. R. Wootton. A Simple technique for microfluidic heterogeneous catalytic hydrogenation reactor fabrication. Catal. Lett., 2007, 114, 71-74

A simple process is described for the facile production of microfluidic reactors with built-in metallic catalysts. This approach provides considerable reductions in cost and complexity when compared to existing catalytic chip designs. The process involves the sputtering of catalytic metals into the channels of microfluidic reactors prior to device bonding. The utility of such microreactors as environments for heterogenous catalytic hydrogenations was tested and demonstrated by applying them to the on-chip reduction of butyraldehyde to butanol and benzyl alcohol to benzaldehyde. The use of such built-in systems as microreactors for specific processes was shown to have considerable potential for both fundamental research and industrial application.