Scientific Papers

Read About How Our Technology Has Been Used

Our patented technology has been utilised by scientists around the world. Take a look at some of the scientific papers published to date, which have utilised Sphere Fluidics’ picodroplet technology, microfluidic technology or specialist research chemicals.

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Published papers

Reviews and Guides

Craig F. F. et al. (2018a). Designing a CRISPR experiment. Gene Editing 101 (2018 edition). An introduction to gene editing. 18-26.

Craig, F. F. (2018b). Microfluidics driving innovation and streamlining single cell analysis. Drug Discovery World. Summer 2018: 61-66.

Craig, F. F. (2018c). The future of antibody discovery and cell line development. Gen. Eng. Biotech. News. December Issue. 18-19.

Craig, F. F. (2018d). Unlocking the potential of single cell analysis. Mednous. September 2018. 11.

Craig F. F. (2019). Single cell analysis in biopharmaceutical discovery. Innov. Pharm Tech. 67: 41-44

Rehak, M. et al. (2015). Use of standards for digital biological information in the design, construction and description of a synthetic biological system – guide. PAS: 246:2015.

Shembekar, N. et al. (2015). Droplet-based microfluidics in drug discovery, transcriptomics and high-throughput molecular genetics. Lab Chip. 16: 1314-1331.

Cellular Assays

Abalde-Cela, A. et. al. (2015). High-throughput detection of ethanol-producing cyanobacteria in a microdroplet platform. Interface. 12: 2015.0216.

Bai, Y. et al. (2013). Intra-species bacterial quorum sensing studied at single cell level in a double droplet trapping system. Int. J. Mol. Sci. 14: 10570-10581.

Best, R. J. et al. (2016). Label-free analysis and sorting of microalgae and cyanobacteria in microdroplets by intrinsic chlorophyll fluorescence for the identification of fast growing strains. Anal. Chem. 88:10445-10451.

Chan, H. F. et al. (2013). Rapid formation of multicellular spheroids in double-emulsion droplets with controllable microenvironment. Sci. Rep. 3: 3462.

Chokkalingam, V. et al. (2013). Probing cellular heterogeneity in cytokine-secreting immune cells using droplet-based microfluidics. Lab Chip. 13: 4740-4744.

Courtois, F. et al. (2009). Controlling the retention of small molecules in emulsion microdroplets for use in cell-based assays. Anal. Chem. 81: 3008-3016.

Del Ben, F. et al. (2016). A method for detecting circulating tumour cells based on the measurement of single-cell metabolism in droplet-based microfluidics. Angew. Chem. In. Ed. 55: 858108584.

Deng, N. -N. et al. (2017). Microfluidic assembly of monodisperse vesosomes as artificial cell models.  J. Am. Chem. Soc. 139: 587-590.

Hu, H. et al. (2015). Efficient cell pairing in droplets using dual-color sorting. Lab Chip. 15: 3989-3993.

Huebner, A. et al. (2007). Quantitative detection of protein expression in single cells using droplet microfluidics. Chem. Commun. 1218-1220.

Huebner, A. et al. (2008). Development of quantitative cell-based enzyme assays in microdroplets. Anal. Chem. 80: 3890-3896.

Huebner, A. et al. (2009). Static microdroplet arrays: a microfluidic device for droplet trapping, incubation and release for enzymatic and cell-based assays. Lab Chip. 9: 692-698.

Hufnagel, H. et al. (2009). An integrated cell culture lab on a chip: modular microdevices for cultivation of mammalian cells and delivery into microfluidic microdroplets. Lab Chip. 9: 1576-1582.

Kelley, et al. (2018). Rapid generation of high-producing clonal cell lines: using FRET-based microfluidic screening for analysis, screening, imaging, and dispensing. Bioprocess International (Sep 19).

Liu, X. et al. (2016). High-throughput screening of antibiotic-resistant bacteria in picodroplets. Lab Chip. 16: 1636-1643.

Ma, Y. et al.  (2013). Monodisperse collagen-gelatin beads as potential platforms for 3D cell culturing. J. Mater. Chem. B. 1: 5128-5136.

Ma, Y. et al. (2014). Artificial microniches for probing mesenchymal stem cell fate in 3D. Biomater. Sci. 2: 1661-1671.

Pan, J. et al. (2011). Quantitative tracking of the growth of individual algal cells in microdroplet compartments. Integr. Biol. 3: 1043-1041.

Sherwood et al (2014). Spatial Distributions of Red Blood Cells Significantly Alter Local Haemodynamics. PLOS ONE. 9:e100473. pmid:24950214

Shim, J. U. et al. (2009). Simultaneous determination of gene expression and enzymatic activity in individual bacterial cells in microdroplet compartments J. Am. Chem. Soc. 131: 15251-15256.

Yu et al (2018). Droplet-based microfluidic analysis and screening of single plant cells. PLOS ONE. 13(5): e0196810

Wimmers, F. et al. (2018). Single-cell analysis reveals that stochasticity and paracrine signaling control interferon-alpha production by plasmacytoid dendritic cells. Nature Comm. 9: DOI: 10.1038/s41467-018-05784-3.

Zang, E. et al. (2013). Real-time image processing for label-free enrichment of Actinobacteria cultivated in picolitre droplets. Lab Chip. 13: 3707-3713.

Chemical Synthesis and/or Analysis

Mellouli, S. et al. (2012). Investigation of “on water” conditions using a biphasic fluidic platform. Angewandte Chemie Int. Ed. 32: 7981-7984.

Theberge, A. B. et al. (2009). Suzuki-Miyaura coupling reactions in aqueous microdroplets with catalytically active fluorous interfaces. Chem. Commun. 6225-6227.

Theberge, A. B. et al. (2010). Generation of picoliter droplets with defined contents and concentration gradients from the separation of chemical mixtures. Anal. Chem. 82: 3449-3453.

Theberge, A. B. et al. (2012). Microfluidic platform for chemical synthesis in picolitre droplets. Lab Chip. 12: 1320-1326.

DNA Analysis

Morf, J. et al. (2017). Spatial RNA proximities reveal a bipartite nuclear transcriptome and territories of differential density and transcription. BioRxiv: doi: https://doi.org/10.1101/196147.

Scaherli, Y. et al. (2009). Continuous-flow polymerase chain reaction of single-copy DNA in microfluidic microdroplets. Anal. Chem. 81: 302-306.

Drug Screening

Theberge, A. B. et al. (2010). Generation of picoliter droplets with defined contents and concentration gradients from the separation of chemical mixtures. Anal. Chem. 82: 3449-3453.

Gene Expression

Courtois, F. et al. (2008). An integrated device for monitoring time-dependent in vitro expression from single genes in picolitre droplets. ChemBioChem. 9: 439-446.

Thiele, J. et al. (2014). DNA-functionalized hydrogels for confined membrane-free in vitro transcription/translation. Lab Chip. 14: 2651-2656.

Mass Spectrometry

Fidalgo, L. M., et al. (2009). Coupling microdroplet microreactors with mass spectrometry: reading the contents of single droplets online. Angew. Chem. Int. Ed. 48: 3665-3668.

Kempa, E.E. et al (2018) High throughput screening of complex biological samples with mass spectrometry – from bulk measurements to single cell analysis. Analyst. DOI: 10.1039/C8AN01448E

Smith, C. A. et al. (2013). Sensitive, high-throughput detection of proteins in individual surfactant-stabilised picoliter droplets using nanoelectrospray ionization mass spectrometry. Anal. Chem. 85: 3812-3816.

Microfluidic Technology

Abalde-Cela et al (2018). Droplet microfluidics for the highly controlled synthesis of branched gold nanoparticles. Nature Scientific Reports. 8: Article number 2440

Bakewell, D. J. et al. (2015a). Real-time dielectrophoretic signalling and image quantification methods for evaluating electrokinetic properties of nanoparticles. Electrophoresis. 36(13): 1443-1450.

Bakewell, D. J. et al. (2015b). Information processing tools for extracting the electrical properties of nanoparticles. AIP Conf. Proc. 1646: 17-24.

Bakewell, D. J. et al. (2016). Exploring and evaluating micro-environment and nanoparticle dielectrophoretic-induced interactions with image analysis methods.  Materials Today Proceedings: 3(3): 867-874.

Bauer, W-A. C. et al. (2010). Hydrophilic PDMS microchannels for high-throughput formation of oil-in-water microdroplets and water-in-oil-water double emulsions. Lab Chip. 10: 1814-1819.

Fidalgo, L. M. et al. (2007). Surface-induced droplet fusion in microfluidic devices. Lab Chip. 7: 984-986.

Fidalgo, L. M. et al. (2008). From microdroplets to microfluidics: selective emulsion separation in microfluidic devices. Angew. Chem. Int. Ed. 47: 2042-2045.

Huebner, A. et al. (2009). Static microdroplet arrays: a microfluidic device for droplet trapping, incubation and release for enzymatic and cell-based assays. Lab Chip. 9: 692-698.

Hufnagel, H. et al. (2009). An integrated cell culture lab on a chip: modular microdevices for cultivation of mammalian cells and delivery into microfluidic microdroplets. Lab Chip. 9: 1576-1582.

Li et al (2018). Size-based sorting of hydrogel droplets using inertial microfluidics. Lab Chip 18, 2575–2582

Liu, S. et al. (2008). The electrochemical detection of droplets in microfluidic devices. Lab Chip. 8: 1937-1942.

Ma, S. et al. (2014). On the flow topology inside droplets moving in rectangular microchannel. Lab Chip. 14: 3611-3620.

Ma, Y. et al. (2014). Biocompatible macro-initiators controlling radical retention in microfluidic on-chip photopolymerization of water-in-oil emulsions. Chem. Commun. 50: 112-114.

Shim, J. et al. (2011). Controlling the contents of microdroplets by exploiting the permeability of PDMS. Lab Chip. 11: 1132-1137.

Theberge, A. B. et al. (2010). Generation of picoliter droplets with defined contents and concentration gradients from the separation of chemical mixtures. Anal. Chem. 82: 3449-3453.

Theberge, A. B. et al. (2010). Microdroplets in microfluidics: an evolving platform for discoveries in chemistry and biology. Angew. Chem. Int. Ed. 49: 5846-5868.

Picodroplet Technology

Abalde-Cela, S. et al. (2011). Microdroplet fabrication of silver-agarose nanocomposite beads for SERS optical accumulations. Soft Matter. 7: 1321-1325.

Bai, Y. et al. (2010). A double droplet trap system for studying mass transport across a droplet-droplet interface. Lab Chip. 10: 1281-1285.

Bauer, W. -A. et al. (2011). Microfluidic production of monodisperse functional o/w droplets and study of their reversible pH dependent aggregation behaviour. Soft Matter. 7: 4214-4220.

Chokkalingam, V. et al. (2014). An electro-coalescence chip for effective emulsion breaking in droplet microfluidics. Lab Chip. 14: 2398-2402.

Courtois, F. et al. (2009). Controlling the retention of small molecules in emulsion microdroplets for use in cell-based assays. Anal. Chem. 81: 3008-3016.

Crawford et al. (2017). Image-based closed-loop feedback for highly mono-dispersed microdroplet production. Nature Scientific Reports. 7: Article number 10545 

Damean, N. et al. (2009). Simultaneous measurement of reactions in microdroplets filled by concentration gradients. Lab Chip. 9: 1707-1713.

Fidalgo, L. M. et al. (2007). Surface-induced droplet fusion in microfluidic devices. Lab Chip. 7: 984-986.

Fidalgo, L. M. et al. (2008). From microdroplets to microfluidics: selective emulsion separation in microfluidic devices. Angew. Chem. Int. Ed. 47: 2042-2045.

Holt, D. J. et al. (2010). Fluorosurfactants for microdroplets: interfacial tension analysis. J. Colloid and Interface Science. 350: 205-211.

Huebner, A. M. et al. (2011). Monitoring a reaction at submillisecond resolution in picoliter volumes. Anal. Chem. 83: 1462-1468.

Jan, Y. et al. (2013). Monodisperse Water-in-Oil-in-Water (W/O/W) Double Emulsion Droplets as Uniform Compartments for High-Throughput Analysis via Flow Cytometry. Micromachines. 4: 402-413.

Khooi, Y. T. et al. (2011). Island brushes to control adhesion of water in oil droplets on planar surfaces. Soft Matter. 7: 7013-7020.

Ma, S. et al. (2012). Fabrication of microgel particles with complex shape via selective polymerisation of aqueous two-phase systems. Small. 8: 2356-2360.

Ma, Y. et al. (2014). Biocompatible macro-initiators controlling radical retention in microfluidic on-chip photopolymerization of water-in-oil emulsions. Chem. Commun. 50: 112-114.

Ma, Y. et al. (2015). The microenvironment of double emulsions in rectangular microchannels. Lab Chip. 15: 2327-2334.

Mashaghi, S. et al. (2015). External control of reactions in microdroplets. Nature Scientific Reports. 5: Article number 11837.

Parker, R. M. et al. (2015). Electrostatically directed self-assembly of ultrathin supramolecular polymer microcapsules. Adv. Funct. Mater. 25: 4091-4100.

Rakszewska, J. et al. (2014). One drop at a time: toward droplet microfluidics as a versatile tool for single-cell analysis. NPG Asia Materials. 6: e133.

Salmon et al. (2016). Monitoring early-stage nanoparticle assembly in microdroplets by optical spectroscopy and SERS. Small DOI: 10.1002/smil.201503513.

Tan, K. Y. et al. (2012). Nonfouling capture-release substrates based on polymer brushes for separation of water-dispersed oil droplets. ACS Appl. Mater. Interfaces. 4: 6403-6409.

Theberge, A. B. et al. (2010). Generation of picoliter droplets with defined contents and concentration gradients from the separation of chemical mixtures. Anal. Chem. 82: 3449-3453.

Theberge, A. B. et al. (2010). Microdroplets in microfluidics: an evolving platform for discoveries in chemistry and biology. Angew. Chem. Int. Ed. 49: 5846-5868.

Thiele, J. et al. (2014). Vesicle budding from polymersomes templated by microfluidically prepared double emulsions. Mater. Horiz. 1: 96-101.

Wu, N. et al. (2010). Management of the diffusion of 4-methylumbelliferone across phases in microdropletbased systems for in vitro protein evolution. Electrophoresis. 31: 3121-3128.

Zhang, J. et al. (2012). One-step fabrication of supramolecular microcapsules from microfluidic droplets. Science. 335: 690-694.

Protein Analysis

Damean, N. et al. (2009). Simultaneous measurement of reactions in microdroplets filled by concentration gradients. Lab Chip. 9: 1707-1713.

Huebner, A. et al. (2007). Quantitative detection of protein expression in single cells using droplet microfluidics. Chem. Commun. 1218-1220.

Huebner, A. et al. (2008). Static microdroplet arrays: a microfluidic device for droplet trapping, incubation and release for enzymatic and cell-based assays. Lab Chip. 9: 692-698.

Jiao. Y. et al. (2018). Microfluidic-assisted fabrication of clay microgels for cell-free protein synthesis. ACS Applied Mater. Interfac. 10: 10.1021/acsami.8b09324.

Mellouli, S. et al. (2013). Self-organization of the bacterial cell-division protein FtsZ in confined environments. Soft Matter. Advance Article. Accepted June 27th 2013.

Shim, J. -U. et al. (2013). Ultrarapid generation of femtoliter microfluidic droplets for single molecule-counting immunoassays. ACS Nano, 7: 5955–5964.

Sokolova, E. et al. (2013). Enhanced transcription rates in membrane-free protocells formed by coacervation of cell lysate. PNAS. 110: 11692-11697.

Wu, N. et al. (2011). Enzyme synthesis and activity assay in microfluidic droplets on a chip. Eng. Life Sci. 11: 157-164.

Separations

Fidalgo, L. M. et al. (2008). From microdroplets to microfluidics: selective emulsion separation in microfluidic devices. Angew. Chem. Int. Ed. 47: 2042-2045.

Holmes, D. et. al. (2014). Separation of blood cells with differing deformability using deterministic lateral displacement.  Interface Focus. 4: 20140011.

Kruger, T. et. al. (2014). Deformability-based red blood cell separation in deterministic lateral displacement devices – a simulation study.  Biomicrofluidics. 8: 054114.

Theberge, A. B. et al. (2010). Generation of picoliter droplets with defined contents and concentration gradients from the separation of chemical mixtures. Anal. Chem. 82: 3449-3453.

Surfactants

Holt, D. J. et al. (2010). Fluorosurfactants for microdroplets: interfacial tension analysis. J. Colloid and Interface Science. 350: 205-211.

Holt, D. J. et al. (2010). Synthesis of novel fluorous surfactants for microdroplet stabilisation in fluorous oil streams. J. Fluorine Chem. 131: 398-407.

Wagner, O. et al. (2016). Biocompatible fluorinated polyglycerols for droplet microfluidics as an alternative to PEG-based copolymer surfactants. Lab. Chip. 16: 65-69.