Dr Fabrice Gielen
Senior Lecturer
(Streatham) 7457
01392 727457
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.
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
- Ribeiro ALJL, Pérez-Arnaiz P, Sánchez-Costa M, Pérez L, Almendros M, van Vliet L, Gielen F, Lim J, Charnock S, Hollfelder F. (2024) Thermostable in vitro transcription-translation for enzyme screening in microdroplets, DOI:10.1101/2024.02.22.580490.
2023
- Tiwari A, Nikolic N, Anagnostidis V, Gielen F. (2023) Label-free analysis of bacterial growth and lysis at the single-cell level using droplet microfluidics and object detection-oriented deep learning, Frontiers in Lab on a Chip Technologies, volume 2, DOI:10.3389/frlct.2023.1258155. [PDF]
- Nikolic N, Anagnostidis V, Tiwari A, Chait R, Gielen F. (2023) Droplet-based methodology for investigating bacterial population dynamics in response to phage exposure, Frontiers in Microbiology, volume 14, DOI:10.3389/fmicb.2023.1260196. [PDF]
- Rogers S, Zhang C, Anagnostidis V, Liddle C, Fishel ML, Gielen F, Scholpp S. (2023) Cancer-associated fibroblasts influence Wnt/PCP signaling in gastric cancer cells by cytoneme-based dissemination of ROR2, Proceedings of the National Academy of Sciences, volume 120, no. 39, DOI:10.1073/pnas.2217612120. [PDF]
- Tiwari A, Anagnostidis V, Nikolic N, Gielen F. (2023) Droplet microfluidics and deep learning for label-free analysis of single-cell bacterial growth and lysis, EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS, volume 52, no. SUPPL 1, pages S110-S110. [PDF]
- Anagnostidis V. (2023) Enabling microfluidic technologies for real-time imaging and single cell sorting.
- Tiwari A, Nikolic N, Anagnostidis V, Gielen F. (2023) Label-free analysis of bacterial growth and lysis at the single-cell level using droplet microfluidics and object detection-oriented deep learning, DOI:10.1101/2023.06.27.546533.
- Nikolic N, Anagnostidis V, Tiwari A, Chait R, Gielen F. (2023) Investigating bacteria-phage interaction dynamics using droplet-based technology, DOI:10.1101/2023.07.14.549014. [PDF]
2022
- Bentley S, Laeverenz Schlogelhofer H, Anagnostidis V, Cammann J, Mazza M, Gielen F, Wan Y. (2022) Dataset: Phenotyping single cell motility in microfluidic confinement, DOI:10.5281/zenodo.7226288. [PDF]
- Neun S, van Vliet L, Hollfelder F, Gielen F. (2022) High-Throughput Steady-State Enzyme Kinetics Measured in a Parallel Droplet Generation and Absorbance Detection Platform, Anal Chem, volume 94, no. 48, pages 16701-16710, DOI:10.1021/acs.analchem.2c03164. [PDF]
- Bentley SA, Laeverenz-Schlogelhofer H, Anagnostidis V, Cammann J, Mazza MG, Gielen F, Wan KY. (2022) Phenotyping single-cell motility in microfluidic confinement, eLife, volume 11, DOI:10.7554/elife.76519. [PDF]
- Neun S, van Vliet L, Hollfelder F, Gielen F. (2022) High throughput steady-state enzyme kinetics measured in a parallel droplet generation and absorbance detection platform, DOI:10.1101/2022.07.28.500969.
- Collins S, Vliet LV, Gielen F, Janeček M, Valladolid SW, Poudel C, Fusco G, De Simone A, Michel C, Kaminski C. (2022) A unified in vitro to in vivo fluorescence lifetime screening platform yields amyloid β aggregation inhibitors, DOI:10.21203/rs.3.rs-1478521/v1.
- Rogers S, Zhang C, Anagnostidis V, Fishel M, Gielen F, Scholpp S. (2022) Cancer-associated fibroblast-derived ROR2 induces WNT/PCP activation and polarized migration in receiving gastric cancer cells, DOI:10.1101/2022.04.07.487474.
- Collins S, van Vliet L, Gielen F, Janeček M, Valladolid SW, Poudel C, Fusco G, De Simone A, Michel C, Kaminski CF. (2022) A unified in vitro to in vivo fluorescence lifetime screening platform yields amyloid β aggregation inhibitors, DOI:10.1101/2022.03.28.485913.
- Elvira KS, Gielen F, Tsai SSH, Nightingale AM. (2022) Materials and methods for droplet microfluidic device fabrication, Lab Chip, volume 22, no. 5, pages 859-875, DOI:10.1039/d1lc00836f. [PDF]
- Howell L, Anagnostidis V, Gielen F. (2022) Multi-Object Detector YOLOv4-Tiny Enables High-Throughput Combinatorial and Spatially-Resolved Sorting of Cells in Microdroplets, ADVANCED MATERIALS TECHNOLOGIES, volume 7, no. 5, article no. ARTN 2101053, DOI:10.1002/admt.202101053. [PDF]
2021
- Bentley SA, Anagnostidis V, Schlogelhofer HL, Gielen F, Wan KY. (2021) Phenotyping single-cell motility in microfluidic confinement, DOI:10.1101/2021.12.24.474109.
- Gielen F. (2021) Single-Cell Microencapsulation for Evolution and Discovery of Biocatalysts, Handbook of Single-Cell Technologies, Springer Nature, 673-694, DOI:10.1007/978-981-10-8953-4_47.
- Gielen F. (2021) Micro Fishing in Microdroplets: Phenotyping Single Cell Motility, Proceedings of the Emerging Investigators in Microfluidics Conference, DOI:10.29363/nanoge.eimc.2021.008.
- Lindenburg LH, Pantelejevs T, Gielen F, Zuazua-Villar P, Butz M, Rees E, Kaminski CF, Downs JA, Hyvönen M, Hollfelder F. (2021) Improved RAD51 binders through motif shuffling based on the modularity of BRC repeats, Proc Natl Acad Sci U S A, volume 118, no. 46, DOI:10.1073/pnas.2017708118. [PDF]
- Nikiforov PO, Hejja B, Chahwan R, Soeller C, Gielen F, Chimerel C. (2021) Functional Phenotype Flow Cytometry: On Chip Sorting of Individual Cells According to Responses to Stimuli, Advanced Biology, volume 5, no. 8, DOI:10.1002/adbi.202100220. [PDF]
2020
- Lindenburg LH, Pantelejevs T, Gielen F, Zuazua-Villar P, Butz M, Rees E, Kaminski CF, Downs JA, Hyvönen M, Hollfelder F. (2020) Improved RAD51 binders through motif shuffling based on the modularity of BRC repeats, DOI:10.1101/2020.05.14.097071.
- Gielen F. (2020) Single-Cell Microencapsulation for Evolution and Discovery of Biocatalysts, Handbook of Single Cell Technologies, Springer Nature, 1-22, DOI:10.1007/978-981-10-4857-9_47-1.
- Anagnostidis V, Al-Saadi D, Gielen F. (2020) Ai-assisted microfluidic stiffness gradient for analysis of 3d cell cultures in hydrogel beads, MicroTAS 2020 - 24th International Conference on Miniaturized Systems for Chemistry and Life Sciences, pages 1292-1293.
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
- Gielen F, Colin P-Y, Mair P, Hollfelder F. (2018) Ultrahigh-Throughput Screening of Single-Cell Lysates for Directed Evolution and Functional Metagenomics, Methods Mol Biol, volume 1685, pages 297-309, DOI:10.1007/978-1-4939-7366-8_18. [PDF]
2017
- Collins S, Gielen F, van Vliet L, Kaminski G, Hollfelder F, Spring D. (2017) Identification and development of small molecule inhibitors of the aggregation of amyloid β, ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, volume 253. [PDF]
- Mair P, Gielen F, Hollfelder F. (2017) Exploring sequence space in search of functional enzymes using microfluidic droplets, Curr Opin Chem Biol, volume 37, pages 137-144, DOI:10.1016/j.cbpa.2017.02.018. [PDF]
- Gielen F, Butz M, Rees EJ, Erdelyi M, Moschetti T, Hyvonen M, Edel JB, Kaminski CF, Hollfelder F. (2017) Quantitative Affinity Determination by Fluorescence Anisotropy Measurements of Individual Nanoliter Droplets, ANALYTICAL CHEMISTRY, volume 89, no. 2, pages 1092-1101, DOI:10.1021/acs.analchem.6b02528. [PDF]
2016
- Gielen F, Hours R, Emond S, Fischlechner M, Schell U, Hollfelder F. (2016) Ultrahigh-throughput-directed enzyme evolution by absorbance-activated droplet sorting (AADS), Proc Natl Acad Sci U S A, volume 113, no. 47, pages E7383-E7389, DOI:10.1073/pnas.1606927113. [PDF]
2015
- Gielen F, Buryska T, Van Vliet L, Butz M, Damborsky J, Prokop Z, Hollfelder F. (2015) Interfacing microwells with nanoliter compartments: a sampler generating high-resolution concentration gradients for quantitative biochemical analyses in droplets, Anal Chem, volume 87, no. 1, pages 624-632, DOI:10.1021/ac503336g. [PDF]
- Chen W, Avezov E, Schlachter SC, Gielen F, Laine RF, Harding HP, Hollfelder F, Ron D, Kaminski CF. (2015) A method to quantify FRET stoichiometry with phasor plot analysis and acceptor lifetime ingrowth, Biophys J, volume 108, no. 5, pages 999-1002, DOI:10.1016/j.bpj.2015.01.012. [PDF]
- Colin P-Y, Kintses B, Gielen F, Miton CM, Fischer G, Mohamed MF, Hyvönen M, Morgavi DP, Janssen DB, Hollfelder F. (2015) Ultrahigh-throughput discovery of promiscuous enzymes by picodroplet functional metagenomics, Nat Commun, volume 6, DOI:10.1038/ncomms10008. [PDF]
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
- Gielen F, van Vliet L, Koprowski BT, Devenish SRA, Fischlechner M, Edel JB, Niu X, deMello AJ, Hollfelder F. (2013) A fully unsupervised compartment-on-demand platform for precise nanoliter assays of time-dependent steady-state enzyme kinetics and inhibition, Anal Chem, volume 85, no. 9, pages 4761-4769, DOI:10.1021/ac400480z. [PDF]
2012
- Hassan SU, Gielen F, Niu X, Edel JB. (2012) Controlled one dimensional oscillation of the Belousov-Zhabotinsky reaction confined within microchannels, RSC Advances, volume 2, no. 16, pages 6408-6410, DOI:10.1039/c2ra21019c.
- Gielen F, deMello AJ, Edel JB. (2012) Dielectric cell response in highly conductive buffers, Anal Chem, volume 84, no. 4, pages 1849-1853, DOI:10.1021/ac2022103. [PDF]
2011
- Niu X, Gielen F, Edel JB, deMello AJ. (2011) A microdroplet dilutor for high-throughput screening, Nat Chem, volume 3, no. 6, pages 437-442, DOI:10.1038/nchem.1046. [PDF]
2010
- Gielen F, Pereira F, Demello AJ, Edel JB. (2010) High-resolution local imaging of temperature in dielectrophoretic platforms, Anal Chem, volume 82, no. 17, pages 7509-7514, DOI:10.1021/ac101557g. [PDF]
2009
- Niu X, Gielen F, DeMello AJ, Edel JB. (2009) A hybrid microfluidic chip for digital electro-coalescence of droplets, Proceedings of Conference, MicroTAS 2009 - The 13th International Conference on Miniaturized Systems for Chemistry and Life Sciences, pages 94-96.
- Gielen F, deMello AJ, Cass T, Edel JB. (2009) Increasing the trapping efficiency of particles in microfluidic planar platforms by means of negative dielectrophoresis, J Phys Chem B, volume 113, no. 5, pages 1493-1500, DOI:10.1021/jp808897g. [PDF]
- Niu X, Gielen F, deMello AJ, Edel JB. (2009) Electro-coalescence of digitally controlled droplets, Anal Chem, volume 81, no. 17, pages 7321-7325, DOI:10.1021/ac901188n. [PDF]
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.