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Physics and Astronomy

Photo of Dr Fabrice Gielen

Dr Fabrice Gielen

Senior Lecturer

 F.Gielen@exeter.ac.uk

 (Streatham) 7457

 01392 727457

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Overview

Research specialisms:

  • microfluidics
  • high-throughput screening
  • bacteriophage/AMR
  • directed evolution of enzymes
  • 3D cell cultures

Qualifications:

2008-2011 Ph.D. in Chemistry, Imperial College London, UK.
2007-2008 MRes in protein membrane chemical biology, Imperial College London, UK    
2004-2006 MEng. in Micro and Nanotechnology for Integrated Systems, Phelma, Grenoble, FR

Biography:

Fabrice holds an MEng degree in micro and nanotechnology for integrated systems and an MRes degree in protein and membrane chemical biology. His PhD at Imperial College London in the laboratory of Prof. Joshua Edel focussed on the study of cellular membrane dynamics by developing microfluidic cell trapping platforms using dielectrophoresis and high-resolution fluorescence spectroscopy.

He joined Prof. Florian Hollfelder’s lab as a post-doc in 2011 with a view to applying microfluidic tools to important biological questions such as the interrogation of protein-protein interactions, the evolution and discovery of enzymes (e.g. from the metagenome), or the discovery of novel small molecule drugs.

He is co-founder of Drop-Tech Ltd, a start-up that develops and help commercialize droplet-on-demand products (e.g. the Mitos Dropix, sold by Dolomite Microfluidics).

Research interests:

The trend towards ever faster, cheaper and more efficient ways of discovering drugs or catalysts has been concomitant with miniaturization of assay volumes. One direction of research is the encapsulation of reagents with volumes down to picoliters using water-in-oil microemulsions.

My research focuses on the development of high-throughput screening platforms for molecular and cellular assays with special emphasis on drug screening and directed evolution. We use droplet microfluidics to rapidly encapsulate thousands to millions of (single) cells before rapidly identifying improved phenotypes with bespoke high-throughput optical tools.

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Publications

Copyright Notice: Any articles made available for download are for personal use only. Any other use requires prior permission of the author and the copyright holder.

| 2024 | 2023 | 2022 | 2021 | 2020 | 2019 | 2018 | 2017 | 2016 | 2015 | 2014 | 2013 | 2012 | 2011 | 2010 | 2009 |

2024

2023

2022

2021

2020

2019

  • Anagnostidis V, Sherlock B, Metz J, Mair P, Hollfelder F, Gielen F. (2019) Deep learning guided image-based droplet sorting for on-demand selection and analysis of single cells and 3D cell cultures, DOI:10.48550/arxiv.1912.05490.
  • Gerstmans H, Gielen F, van Hileghem L, Lavigne R, Hollfelder F, Lammertyn J, Briers Y. (2019) Versatile engineering of lysins: One drop to kill, 23rd International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2019, pages 180-181.
  • Anagnostidis V, Sherlock B, Metz J, Mair P, Hollfelder F, Gielen F. (2019) Deep learning guided image-based droplet sorting for biological screenings, 23rd International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2019, pages 945-946.
  • Vasina M, Buryska T, Vanacek P, Gielen F, van Vliet L, Pilat Z, Jezek J, Zemanek P, Damborsky J, Hollfelder F. (2019) Oil/water partitioning and microdialysis for controlled delivery of hydrophobic compounds in droplet-based microfluidic systems, 23rd International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2019, pages 1654-1655.
  • Anagnostidis V, Sherlock B, Metz J, Mair P, Hollfelder F, Gielen F. (2019) Deep learning guided image-based droplet sorting for on-demand selection and analysis of single cells and 3D cell cultures. [PDF]
  • Buryska T, Vasina M, Gielen F, Vanacek P, van Vliet L, Jezek J, Pilat Z, Zemanek P, Damborsky J, Hollfelder F. (2019) Controlled Oil/Water Partitioning of Hydrophobic Substrates Extending the Bioanalytical Applications of Droplet-Based Microfluidics, Anal Chem, volume 91, no. 15, pages 10008-10015, DOI:10.1021/acs.analchem.9b01839. [PDF]
  • Kleine-Brüggeney H, van Vliet LD, Mulas C, Gielen F, Agley CC, Silva JCR, Smith A, Chalut K, Hollfelder F. (2019) Long-Term Perfusion Culture of Monoclonal Embryonic Stem Cells in 3D Hydrogel Beads for Continuous Optical Analysis of Differentiation, Small, volume 15, no. 5, DOI:10.1002/smll.201804576.

2018

2017

2016

2015

2014

  • Crowther DC, van Vliet L, Kuhaudomlarp S, Gielen F, Yan J, Azhar M, Hinault M, Hollfelder F. (2014) O4‐10‐03: AN ASSAY FOR SEEDED PROTEIN AGGREGATION DETECTS ABETA SEEDS IN SERUM, Alzheimer's & Dementia, volume 10, no. 4S_Part_5, pages p271-p271, DOI:10.1016/j.jalz.2014.04.441.
  • Van Vliet LD, Gielen F, Sinha A, Koprowski BT, Edel JB, Niu X, De Mello AJ, Hollfelder F. (2014) Droplet-on-demand platform for biochemical screening and drug discovery, 18th International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2014, pages 1214-1216.

2013

2012

2011

2010

2009

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Further information

Personal Homepage

The overarching theme of our research is the development of novel high-throughput technologies for molecular and cellular screens, including directed enzyme evolution and single cell -omic assays. We are combining microfluidic tools with optical read-outs and state-of-the-art data analysis methods including machine learning to interrogate protein function or decipher cell population heterogeneities.

● Ultra-high-throughput screening tools

We are working on the development of microdroplet sorters for the screening of mutant protein libraries. For instance, we developed absorbance read-outs and applied it to the directed evolution of industrially relevant biocatalysts. We are exploring other types of read-outs and assess their potential to screen antimicrobial libraries, which constitute promising alternatives/complements to antibiotics.

● Multicellular Spheroid screens

 In-vitro cultured cancer cells can serve as important models for preclinical testing of anti-cancer compounds. 3D cell culture formats have emerged as powerful paradigms that can closely mimic in-vivo culture conditions.[4] However, finding optimal conditions that allow the retention of original tumor features during in vitro 3D culturing of cancer cells is challenging. This is because of the high number of individual environmental cues (biochemical, mechanical, etc) present in each cellular culture, representing a high-dimensional combinatorics problem (each cellular culture generates many variables that can be controlled precisely).[5] A promising development in the field of 3D cell cultures is the use of microfluidic technologies which can be used to produce ultra-large numbers (up to millions) of individual cultures starting from single cells encapsulated into monodisperse hydrogel beads.

Selected publications:

(1) Colin, P. Y., Kintses, B., Gielen, F., Miton, C. M., Fischer, G., Mohamed, M. F., Hyvonen, M., Morgavi, D. P., Janssen, D. B., Hollfelder, F., Nature Communications. 2015, 6. .

(2) Gielen, F., Hours, R., Emond, S., Fischlechner, M., Schell, U., Hollfelder, F., Proceedings of the National Academy of Sciences. 2016, 113. E7383-E7389.

(3) Gielen, F., Buryska, T., Van Vliet, L., Butz, M., Damborsky, J., Prokop, Z., Hollfelder, F., Analytical Chemistry. 2015, 87. 624-632.

(4) Kleine-Bruggeney, H., van Vliet, L. D., Mulas, C., Gielen, F., Agley, C. C., Silva, J. C. R., Smith, A., Chalut, K., Hollfelder, F., Small. 2019, 15. .

(5) Allazetta, S., Lutolf, M. P., Curr. Opin. Biotechnol. 2015, 35. 86-93.

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