Publications by authors named "Philippe Renaud"

231 Publications

Dielectrophoretic Traps for Efficient Bead and Cell Trapping and Formation of Aggregates of Controlled Size and Composition.

Front Bioeng Biotechnol 2022 14;10:910578. Epub 2022 Jul 14.

Laboratory of Microsystems LMIS4, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.

We present a microfluidic dielectrophoretic-actuated system designed to trap chosen single-cell and form controlled cell aggregates. A novel method is proposed to characterize the efficiency of the dielectrophoretic trapping, considering the flow speed but also the heat generated by the traps as limiting criteria in cell-safe manipulation. Two original designs with different manufacturing processes are experimentally compared. The most efficient design is selected and the cell membrane integrity is monitored by fluorescence imaging to guarantee a safe-cell trapping. Design rules are suggested to adapt the traps to multiple-cells trapping and are experimentally validated as we formed aggregates of controlled size and composition with two different types of cells. We provide hereby a simple manufactured tool allowing the controlled manipulation of particles for the composition of multicellular assemblies.
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http://dx.doi.org/10.3389/fbioe.2022.910578DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9333130PMC
July 2022

On-Demand Nanoliter Sampling Probe for the Collection of Brain Fluid.

Anal Chem 2022 07 5;94(29):10415-10426. Epub 2022 Jul 5.

Microsystems Laboratory 4 (STI-IEM-LMIS4), École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.

Continuous fluidic sampling systems allow collection of brain biomarkers . Here, we propose a new sequential and intermittent sampling paradigm using droplets, called Droplet on Demand (DoD). It is implemented in a microfabricated neural probe and alternates phases of analyte removal from the tissue and phases of equilibration of the concentration in the tissue. It allows sampling droplets loaded with molecules from the brain extracellular fluid punctually, without the long transient equilibration periods typical of continuous methods. It uses an accurately defined fluidic sequence with controlled timings, volumes, and flow rates, and correct operation is verified by the embedded electrodes and a flow sensor. As a proof of concept, we demonstrated the application of this novel approach and , to collect glucose in the brain of mice, with a temporal resolution of 1-2 min and without transient regime. Absolute quantification of the glucose level in the samples was performed by direct infusion nanoelectrospray ionization Fourier transform mass spectrometry (nanoESI-FTMS). By adjusting the diffusion time and the perfusion volume of DoD, the fraction of molecules recovered in the samples can be tuned to mirror the tissue concentration at accurate points in time. Moreover, this makes quantification of biomarkers in the brain possible within acute experiments of only 20-120 min. DoD provides a complementary tool to continuous microdialysis and push-pull sampling probes. Thus, the advances allowed by DoD will benefit quantitative molecular studies in the brain, i.e., for molecules involved in volume transmission or for protein aggregates that form in neurodegenerative diseases over long periods.
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http://dx.doi.org/10.1021/acs.analchem.2c01577DOI Listing
July 2022

Pilot Study of Embedded IMU Sensors and Machine Learning Algorithms for Automated Ice Hockey Stick Fitting.

Sensors (Basel) 2022 Apr 29;22(9). Epub 2022 Apr 29.

Department of Kinesiology and Physical Education, McGill Research Centre for Physical Activity and Health, McGill University, 475 Pine Avenue West, Montreal, QC H2W 1S4, Canada.

The aims of this study were to evaluate the feasibility of using IMU sensors and machine learning algorithms for the instantaneous fitting of ice hockey sticks. Ten experienced hockey players performed 80 shots using four sticks of differing constructions (i.e., each stick differed in stiffness, blade pattern, or kick point). Custom IMUs were embedded in a pair of hockey gloves to capture resultant linear acceleration and angular velocity of the hands during shooting while an 18-camera optical motion capture system and retroreflective markers were used to identify key shot events and measure puck speed, accuracy, and contact time with the stick blade. MATLAB R2020a's Machine Learning Toolbox was used to build and evaluate the performance of machine learning algorithms using principal components of the resultant hand kinematic signals using principal components accounting for 95% of the variability and a five-fold cross validation. Fine k-nearest neighbors algorithms were found to be highly accurate, correctly classifying players by optimal stick flex, blade pattern, and kick point with 90-98% accuracy for slap shots and 93-97% accuracy for wrist shots in fractions of a second. Based on these findings, it appears promising that wearable sensors and machine learning algorithms can be used for reliable, rapid, and portable hockey stick fitting.
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http://dx.doi.org/10.3390/s22093419DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9105185PMC
April 2022

Microscale hydrodynamic confinements: shaping liquids across length scales as a toolbox in life sciences.

Lab Chip 2022 04 12;22(8):1415-1437. Epub 2022 Apr 12.

IBM Research - Europe, Säumerstrasse 4, 8803 Rüschlikon, Switzerland.

Hydrodynamic phenomena can be leveraged to confine a range of biological and chemical species without needing physical walls. In this review, we list methods for the generation and manipulation of microfluidic hydrodynamic confinements in free-flowing liquids and near surfaces, and elucidate the associated underlying theory and discuss their utility in the emerging area of open space microfluidics applied to life-sciences. Microscale hydrodynamic confinements are already starting to transform approaches in fundamental and applied life-sciences research from precise separation and sorting of individual cells, allowing localized bio-printing to multiplexing for clinical diagnosis. Through the choice of specific flow regimes and geometrical boundary conditions, hydrodynamic confinements can confine species across different length scales from small molecules to large cells, and thus be applied to a wide range of functionalities. We here provide practical examples and implementations for the formation of these confinements in different boundary conditions - within closed channels, in between parallel plates and in an open liquid volume. Further, to enable non-microfluidics researchers to apply hydrodynamic flow confinements in their work, we provide simplified instructions pertaining to their design and modelling, as well as to the formation of hydrodynamic flow confinements in the form of step-by-step tutorials and analytical toolbox software. This review is written with the idea to lower the barrier towards the use of hydrodynamic flow confinements in life sciences research.
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http://dx.doi.org/10.1039/d1lc01101dDOI Listing
April 2022

Traceable impedance-based single-cell pipetting, from a research set-up to a robust and fast automated robot: DispenCell-S1.

SLAS Technol 2022 04 17;27(2):121-129. Epub 2021 Dec 17.

SEED Biosciences SA, Épalinges, Switzerland. Electronic address:

Single-cell isolation is a truly transformative tool for the understanding of biological systems. It allows single-cell molecular analyses and considers the heterogeneity of cell populations, which is of particular relevance for the diagnosis and treatment of evolving diseases and for personalized medicine. Single-cell isolation is also a key process in cell line development, where it is used to obtain stable and high producing clonally-derived cell lines, thus contributing to the efficiency, safety and reproducible quality of the drug produced. High producing clonally-derived cell lines are however rare events and their identification is a time-consuming process that requires the screening of thousands of clones. Therefore, there is an unmet need for a device that would allow the fast and efficient isolation of single cells, while preserving their integrity and providing an insurance of their clonality. We proposed earlier an impedance based pipetting technology for isolation of single cells (Bonzon et al., 2020), with initial validations for state-of-the-art stem cell in-vitro and in-vivo assays (Muller et al., 2020). Here, we present the transition from this pioneering technology developed in an academic setting into an automated instrument, called DispenCell-S1, allowing for traceable isolation of single cells. We developed and validated models predicting the performances for 96-well plates single-cell isolation. This resulted in a time of dispense down to 3 min and a plate filling rate up to 96%. Finally, we obtained an impedance signal reliability for proof of single particle isolation of 99% with beads and ranging from 93 to 95% with CHO cells.
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http://dx.doi.org/10.1016/j.slast.2021.12.003DOI Listing
April 2022

Radical chain monoalkylation of pyridines.

Chem Sci 2021 Dec 3;12(46):15362-15373. Epub 2021 Nov 3.

Department of Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern Freiestrasse 3 CH-3012 Bern Switzerland

The monoalkylation of -methoxypyridinium salts with alkyl radicals generated from alkenes ( hydroboration with catecholborane), alkyl iodides ( iodine atom transfer) and xanthates is reported. The reaction proceeds under neutral conditions since no acid is needed to activate the heterocycle and no external oxidant is required. A rate constant for the addition of a primary radical to -methoxylepidinium >10 M s was experimentally determined. This rate constant is more than one order of magnitude larger than the one measured for the addition of primary alkyl radicals to protonated lepidine demonstrating the remarkable reactivity of methoxypyridinium salts towards radicals. The reaction has been used for the preparation of unique pyridinylated terpenoids and was extended to a three-component carbopyridinylation of electron-rich alkenes including enol esters, enol ethers and enamides.
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http://dx.doi.org/10.1039/d1sc02748dDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8635225PMC
December 2021

Europe-Wide Atmospheric Radionuclide Dispersion by Unprecedented Wildfires in the Chernobyl Exclusion Zone, April 2020.

Environ Sci Technol 2021 10 29;55(20):13834-13848. Epub 2021 Sep 29.

The Henryk Nievodniczanski Institute of Nuclear Physics (IFJ), Polish Academy of Sciences, Kraków 31-342,Poland.

From early April 2020, wildfires raged in the highly contaminated areas around the Chernobyl nuclear power plant (CNPP), Ukraine. For about 4 weeks, the fires spread around and into the Chernobyl exclusion zone (CEZ) and came within a few kilometers of both the CNPP and radioactive waste storage facilities. Wildfires occurred on several occasions throughout the month of April. They were extinguished, but weather conditions and the spread of fires by airborne embers and smoldering fires led to new fires starting at different locations of the CEZ. The forest fires were only completely under control at the beginning of May, thanks to the tireless and incessant work of the firefighters and a period of sustained precipitation. In total, 0.7-1.2 TBq Cs were released into the atmosphere. Smoke plumes partly spread south and west and contributed to the detection of airborne Cs over the Ukrainian territory and as far away as Western Europe. The increase in airborne Cs ranged from several hundred μBq·m in northern Ukraine to trace levels of a few μBq·m or even within the usual background level in other European countries. Dispersion modeling determined the plume arrival time and was helpful in the assessment of the possible increase in airborne Cs concentrations in Europe. Detections of airborne Sr (emission estimate 345-612 GBq) and Pu (up to 75 GBq, mostly Pu) were reported from the CEZ. Americium-241 represented only 1.4% of the total source term corresponding to the studied anthropogenic radionuclides but would have contributed up to 80% of the inhalation dose.
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http://dx.doi.org/10.1021/acs.est.1c03314DOI Listing
October 2021

Microfluidic Device for Droplet Pairing by Combining Droplet Railing and Floating Trap Arrays.

Micromachines (Basel) 2021 Sep 6;12(9). Epub 2021 Sep 6.

Laboratory of Microsystems LMIS4, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1011 Lausanne, Switzerland.

Droplet microfluidics are characterized by the generation and manipulation of discrete volumes of solutions, generated with the use of immiscible phases. Those droplets can then be controlled, transported, analyzed or their content modified. In this wide droplet microfluidic toolbox, no means are available to generate, in a controlled manner, droplets co-encapsulating to aqueous phases. Indeed, current methods rely on random co-encapsulation of two aqueous phases during droplet generation or the merging of two random droplets containing different aqueous phases. In this study, we present a novel droplet microfluidic device to reliably and efficiently co-encapsulate two different aqueous phases in micro-droplets. In order to achieve this, we combined existing droplet microfluidic modules in a novel way. The different aqueous phases are individually encapsulated in droplets of different sizes. Those droplet populations are then filtered in order to position each droplet type towards its adequate trapping compartment in traps of a floating trap array. Single droplets, each containing a different aqueous phase, are thus paired and then merged. This pairing at high efficiency is achieved thanks to a unique combination of floating trap arrays, a droplet railing system and a droplet size-based filtering mechanism. The microfluidic chip design presented here provides a filtering threshold with droplets larger than 35 μm (big droplets) being deviated to the lower rail while droplets smaller than 20 μm (small droplets) remain on the upper rail. The effects of the rail height and the distance between the two (upper and lower) rails were investigated. The optimal trap dimensions provide a trapping efficiency of 100% for small and big droplets with a limited double trapping (both compartments of the traps filled with the same droplet type) of 5%. The use of electrocoalescence enables the generation of a droplet while co-encapsulating two aqueous phases. Using the presented microfluidic device libraries of 300 droplets, dual aqueous content can be generated in less than 30 min.
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http://dx.doi.org/10.3390/mi12091076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8470175PMC
September 2021

Nanovolcano microelectrode arrays: toward long-term on-demand registration of transmembrane action potentials by controlled electroporation.

Microsyst Nanoeng 2020 24;6:67. Epub 2020 Aug 24.

Laboratory of Microsystems LMIS4, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.

Volcano-shaped microelectrodes (nanovolcanoes) functionalized with nanopatterned self-assembled monolayers have recently been demonstrated to report cardiomyocyte action potentials after gaining spontaneous intracellular access. These nanovolcanoes exhibit recording characteristics similar to those of state-of-the-art micro-nanoelectrode arrays that use electroporation as an insertion mechanism. In this study, we investigated whether the use of electroporation improves the performance of nanovolcano arrays in terms of action potential amplitudes, recording durations, and yield. Experiments with neonatal rat cardiomyocyte monolayers grown on nanovolcano arrays demonstrated that electroporation pulses with characteristics derived from analytical models increased the efficiency of nanovolcano recordings, as they enabled multiple on-demand registration of intracellular action potentials with amplitudes as high as 62 mV and parallel recordings in up to ~76% of the available channels. The performance of nanovolcanoes showed no dependence on the presence of functionalized nanopatterns, indicating that the tip geometry itself is instrumental for establishing a tight seal at the cell-electrode interface, which ultimately determines the quality of recordings. Importantly, the use of electroporation permitted the recording of attenuated cardiomyocyte action potentials during consecutive days at identical sites, indicating that nanovolcano recordings are nondestructive and permit long-term on-demand recordings from excitable cardiac tissues. Apart from demonstrating that less complex manufacturing processes can be used for next-generation nanovolcano arrays, the finding that the devices are suitable for performing on-demand recordings of electrical activity from multiple sites of excitable cardiac tissues over extended periods of time opens the possibility of using the devices not only in basic research but also in the context of comprehensive drug testing.
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http://dx.doi.org/10.1038/s41378-020-0178-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8433144PMC
August 2020

Planar hydrodynamic traps and buried channels for bead and cell trapping and releasing.

Lab Chip 2021 09 28;21(19):3686-3694. Epub 2021 Sep 28.

Laboratory of Microsystems LMIS4, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.

We present a novel concept for the controlled trapping and releasing of beads and cells in a PDMS microfluidic channel without obstacles present around the particle or in the channel. The trapping principle relies on a two-level microfluidic configuration: a top main PDMS channel interconnected to a buried glass microchannel using round vias. As the fluidic resistances rule the way the liquid flows inside the channels, particles located in the streamlines passing inside the buried level are immobilized by the round with a smaller diameter, leaving the object motionless in the upper PDMS channel. The particle is maintained by the difference of pressure established across its interface and acts as an infinite fluidic resistance, virtually cancelling the subsequent buried fluidic path. The pressure is controlled at the outlet of the buried path and three modes of operation of a trap are defined: idle, trapping and releasing. The pressure conditions for each mode are defined based on the hydraulic-electrical circuit equivalence. The trapping of polystyrene beads in a compact array of 522 parallel traps controlled by a single pressure was demonstrated with a trapping efficiency of 94%. Pressure conditions necessary to safely trap cells in holes of different diameters were determined and demonstrated in an array of 25 traps, establishing the design and operation rules for the use of planar hydrodynamic traps for biological assays.
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http://dx.doi.org/10.1039/d1lc00463hDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8477447PMC
September 2021

Preparation of Antiproliferative Terpene-Alkaloid Hybrids by Free Radical-Mediated Modification of -Kauranic Derivatives.

Molecules 2021 Jul 28;26(15). Epub 2021 Jul 28.

Institute of Chemistry (MECC), Str. Academiei, 3, MD-2028 Chișinău, Moldova.

A convenient strategy for molecular editing of available -kauranic natural scaffolds has been developed based on radical mediated C-C bond formation. Iodine atom transfer radical addition (ATRA) followed by rapid ionic elimination and radical azidoalkylation were investigated. Both reactions involve radical addition to the -methylenic double bond of the parent substrate. Easy transformations of the obtained adducts lead to extended diterpenes of broad structural diversity and artificial diterpene-alkaloid hybrids possessing lactam and pyrrolidine pharmacophores. The cytotoxicity of selected diterpenic derivatives was examined by in vitro testing on several tumor cell lines. The terpene-alkaloid hybrids containing -heterocycles with unprecedented spiro-junction have shown relevant cytotoxicity and promising selectivity indexes. These results represent a solid basis for following research on the synthesis of such derivatives based on available natural product templates.
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http://dx.doi.org/10.3390/molecules26154549DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8347134PMC
July 2021

In-flow electrochemical detection of chemicals in droplets with pyrolysed photoresist electrodes: application as a module for quantification of microsampled dopamine.

Lab Chip 2021 09 12;21(17):3328-3337. Epub 2021 Jul 12.

EPFL-STI-IMT-LMIS4, École Polytechnique Fédérale de Lausanne, Station 17, CH-1015 Lausanne, Switzerland.

The electrochemical quantification of analytes in droplets of PBS separated by a fluorinated phase was investigated. PDMS-fused silica chips with pyrolysed photoresist electrodes were prepared using a simple fabrication technique and used to analyze droplets in flow. Potentiostatic chronoamperometry provided current readouts consistent with mass transport and the concentration inside the droplets. This paper highlights measurements of dopamine in droplets in T-junction microfluidic chips at unprecedently low concentrations, with a limit of detection of 207 nM and a linear range of 0.21-20 μM, giving results similar to continuous flow electrochemistry and allowing the analysis in the striatal extracellular range (<1 μM). The system was applied to the quick and reliable on-line detection of dopamine concentration steps in droplets collected with a microsampling probe in vitro, demonstrating the usefulness of the electrochemical device as a quantification module for microsampled chemicals in droplets.
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http://dx.doi.org/10.1039/d1lc00116gDOI Listing
September 2021

A Giese reaction for electron-rich alkenes.

Chem Sci 2020 Dec 17;12(6):2225-2230. Epub 2020 Dec 17.

Department of Chemistry and Biochemistry, University of Bern Freiestrasse 3 CH-3012 Bern Switzerland

A general method for the hydroalkylation of electron-rich terminal and non-terminal alkenes such as enol esters, alkenyl sulfides, enol ethers, silyl enol ethers, enamides and enecarbamates has been developed. The reactions are carried out at room temperature under air initiation in the presence of triethylborane acting as a chain transfer reagent and 4--butylcatechol (TBC) as a source of hydrogen atom. The efficacy of the reaction is best explained by very favorable polar effects supporting the chain process and minimizing undesired polar reactions. The stereoselective hydroalkylation of chiral -(alk-1-en-1-yl)oxazolidin-2-ones takes place with good to excellent diastereocontrol.
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http://dx.doi.org/10.1039/d0sc06341jDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8179299PMC
December 2020

Stereoselective and Stereospecific Triflate-Mediated Intramolecular Schmidt Reaction: Ready Access to Alkaloid Skeletons*.

Angew Chem Int Ed Engl 2021 04 23;60(18):10179-10185. Epub 2021 Mar 23.

Department of Chemistry and Biochemistry, University of Bern, Freiestrasse 3, 3012, Bern, Switzerland.

The stereoselectivity and stereospecificity of the triflate-mediated intramolecular Schmidt reaction of substituted 3-(1-azidocyclohexyl)propanol derivatives leading to octahydro-1H-pyrrolo[1,2-a]azepine, the structural skeleton of several important families of alkaloids such as the Stemona alkaloids, has been examined. The reaction involves an initial intramolecular S 2 reaction between the azide moiety and the triflate affording an intermediate spirocyclic aminodiazonoium salt that undergoes the expected 1,2-shift/N -elimination followed by hydride-mediated iminium salt reduction. Remarkably, chiral alcohols are converted to the azabicyclic derivative with no or limited racemization. The initial asymmetric alcohol center controls the diastereoselectivity of the whole process, leading to the formation of one out of the four possible diastereoisomers of disubstituted octahydro-1H-pyrrolo[1,2-a]azepine. The origin of the stereoselectivity is rationalized based on theoretical calculations. The concise synthesis of (-)-(cis)-3-propylindolizidine and (-)-(cis)-3-butyllehmizidine, two alkaloids found in the venom of workers of the ant Myrmicaria melanogaster, is reported.
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http://dx.doi.org/10.1002/anie.202016892DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8251548PMC
April 2021

Oxygen-rich Environment Ameliorates Cell Therapy Outcomes of Cardiac Progenitor Cells for Myocardial Infarction.

Mater Sci Eng C Mater Biol Appl 2021 Feb 29;121:111836. Epub 2020 Dec 29.

Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran; Department of Developmental Biology, University of Science and Culture, Tehran, Iran. Electronic address:

To some extent, cell therapy for myocardial infarction (MI) has supported the idea of cardiac repair; however, further optimizations are inevitable. Combined approaches that comprise suitable cell sources and supporting molecules considerably improved its effect. Here, we devised a strategy of simultaneous transplantation of human cardiac progenitor cells (CPCs) and an optimized oxygen generating microparticles (MPs) embedded in fibrin hydrogel, which was injected into a left anterior descending artery (LAD) ligating-based rat model of acute myocardial infarction (AMI). Functional parameters of the heart, particularly left ventricular systolic function, markedly improved and reached pre-AMI levels. This functional restoration was well correlated with substantially lower fibrotic tissue formation and greater vascular density in the infarct area. Our novel approach promoted CPCs retention and differentiation into cardiovascular lineages. We propose this novel co-transplantation strategy for more efficient cell therapy of AMI which may function by providing an oxygen-rich microenvironment, and thus regulate cell survival and differentiation.
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http://dx.doi.org/10.1016/j.msec.2020.111836DOI Listing
February 2021

An integrated microfluidic device for stem cell differentiation based on cell-imprinted substrate designed for cartilage regeneration in a rabbit model.

Mater Sci Eng C Mater Biol Appl 2021 Feb 16;121:111794. Epub 2020 Dec 16.

National Cell Bank Department, Pasteur Institute of Iran, P.O. Box 13169-43551, Tehran, Iran. Electronic address:

Separating cells from the body and cultivating them in vitro will alter the function of cells. Therefore, for optimal cell culture in the laboratory, conditions similar to those of their natural growth should be provided. In previous studies, it has been shown that the use of cellular shape at the culture surface can regulate cellular function. In this work, the efficiency of the imprinting method increased by using microfluidic chip design and fabrication. In this method, first, a cell-imprinted substrate of chondrocytes was made using a microfluidic chip. Afterwards, stem cells were cultured on a cell-imprinted substrate using a second microfluidic chip aligned with the substrate. Therefore, stem cells were precisely placed on the chondrocyte patterns on the substrate and their fibroblast-like morphology was changed to chondrocyte's spherical morphology after 14-days culture in the chip without using any chemical growth factor. After chondrogenic differentiation and in vitro assessments (real-time PCR and immunocytotoxicity), differentiated stem cells were transferred on a collagen-hyaluronic acid scaffold and transplanted in articular cartilage defect of the rabbit. After 6 months, the post-transplantation analysis showed that the articular cartilage defect had been successfully regenerated in differentiated stem cell groups in comparison with the controls. In conclusion, this study showed the potency of the imprinting method for inducing chondrogenicity in stem cells, which can be used in clinical trials due to the safety of the procedure.
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http://dx.doi.org/10.1016/j.msec.2020.111794DOI Listing
February 2021

The relationship between trunk rotation and shot speed when performing ice hockey wrist shots.

J Sports Sci 2021 May 9;39(9):1001-1009. Epub 2020 Dec 9.

Department of Kinesiology and Physical Education, McGill Research Centre for Physical Activity and Health, McGill University, Montreal, Canada.

There has been minimal work examining kinematics of ice hockey wrist shots. The objective was to determine if puck and blade speed were related to trunk rotation during wrist shots in elite and recreational players. Elite (n = 10) and recreational (n = 10) ice hockey players completed wrist shots while skating and from a stationary position on real ice. A 14 camera motion capture system collected kinematic data for the trunk, pelvis, stick, and puck. Dependent variables included peak puck and blade speeds. Independent variables included peak trunk rotation angles, trunk rotation range of motion (ROM), and group (elite vs. recreational). Hierarchical linear models compared relationships between dependent and independent variables for both skating and stationary wrist shots. Greater peak trunk rotation away from the net was related (p < 0.05) to faster puck and blade speeds for skating and stationary wrist shots. This relationship was stronger in the recreational group for skating wrist shots (p < 0.01). Greater trunk rotation ROM was related (p = 0.01) to faster puck and blade speeds for the skating wrist shots only. Coaches should encourage players to increase trunk rotation away from the net during wrist shots, especially in recreational players.
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http://dx.doi.org/10.1080/02640414.2020.1853336DOI Listing
May 2021

Microfluidic-assisted bioprinting of tissues and organoids at high cell concentrations.

Biofabrication 2021 03 10;13(2). Epub 2021 Mar 10.

Institute of Microengineering, Swiss Federal Institute of Technology in Lausanne (EPFL), 1015 Lausanne, Switzerland.

Despite its simplicity, which makes it the most commonly used bioprinting method today, extrusion-based bioprinting suffers from its inability to reproduce the complex tissue architecture found in organs. Generally, this printing method allows for the dispensing of solutions of a predefined cell concentration through a rudimentary needle. Moreover, to avoid cell lysis in the dispensing needle, which is detrimental to the viability of the printed tissue, as well as cell loss in dead volumes of tubing, thereby increasing the cost of printing tissue, a common strategy has been to print with cell concentrations much lower in comparison to the concentrations found in living tissues. As a result, cell-to-cell distance is increased in the dispensed samples impairing communication through cytokines. Here, we present a microfluidic-based print head capable of modulating the printed cell concentration in real-time. This device allows bioprinting at high cell concentrations by concentrating and dispensing fibroblasts at concentrations up to 10 million cells∙mL. We also demonstrate that this device can be used to print bladder organoids. As the cell seeding concentration is of major importance for organogenesis in 3D culture, organoid printing allows the user to standardize the process of organoid formation and achieve more reliable and reproducible results.
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http://dx.doi.org/10.1088/1758-5090/abca80DOI Listing
March 2021

Neural priming of adipose-derived stem cells by cell-imprinted substrates.

Biofabrication 2021 04 2;13(3). Epub 2021 Apr 2.

Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland.

Cell-imprinting technology is a novel method for directing stem cell fate using substrates molded from target cells. Here, we fabricated and studied cell-imprinted substrates for neural priming in human adipose-derived stem cells in the absence of chemical cues. We molded polydimethylsiloxane silicone substrates on fixed differentiated neural progenitor cells (ReNcellVM). The ReNcellcell line consists of immortalized human neural progenitor cells that are capable to differentiate into neural cells. The fabricated cell-imprinted silicone substrates represent the geometrical micro- and nanotopology of the target cell morphology. During the molding procedure, no transfer of cellular proteins was detectable. In the first test with undifferentiated ReNcellVM cells, the cell-imprinted substrates could accelerate neural differentiation. With adipose-derived stem cells cultivated on the imprinted substrates, we observed modifications of cell morphology, shifting from spread to elongated shape. Both immunofluorescence and quantitative gene expression analysis showed upregulation of neural stem cell and early neuronal markers. Our study, for the first time, demonstrated the effectiveness of cell-imprinted substrates for neural priming of adipose-derived stem cells for regenerative medicine applications.
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http://dx.doi.org/10.1088/1758-5090/abc66fDOI Listing
April 2021

Positional dependence of particles and cells in microfluidic electrical impedance flow cytometry: origin, challenges and opportunities.

Lab Chip 2020 10 11;20(20):3665-3689. Epub 2020 Sep 11.

FEMTO-ST Institute, CNRS, Univ. Bourgogne Franche-Comté, AS2M Department, 24 rue Alain Savary, F-25000 Besançon, France.

Microfluidic electrical impedance flow cytometry is now a well-known and established method for single-cell analysis. Given the richness of the information provided by impedance measurements, this non-invasive and label-free approach can be used in a wide field of applications ranging from simple cell counting to disease diagnostics. One of its major limitations is the variation of the impedance signal with the position of the cell in the sensing area. Indeed, identical particles traveling along different trajectories do not result in the same data. The positional dependence can be considered as a challenge for the accuracy of microfluidic impedance cytometers. On the other hand, it has recently been regarded by several groups as an opportunity to estimate the position of particles in the microchannel and thus take a further step in the logic of integrating sensors in so-called "Lab-on-a-chip" devices. This review provides a comprehensive overview of the physical grounds of the positional dependence of impedance measurements. Then, both the developed strategies to reduce position influence in impedance-based assays and the recent reported technologies exploiting that dependence for the integration of position detection in microfluidic devices are reviewed.
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http://dx.doi.org/10.1039/d0lc00616eDOI Listing
October 2020

Differences in inter-segment coordination between high- and low-calibre ice hockey players during forward skating.

Sports Biomech 2020 Aug 30:1-16. Epub 2020 Aug 30.

Centre for Interdisciplinary Research in Rehabilitation, Lethbridge-Layton-Mackay Rehabilitation Centre, and the School of Physical and Occupational Therapy, McGill University, Montreal, Quebec, Canada.

The objective was to compare lower extremity inter-segment coordination between high-calibre and low-calibre ice hockey players during forward full stride skating. A 10-camera Vicon motion capture system collected kinematic data on male high-calibre (n = 8) and low-calibre (n = 8) participants. Continuous relative phase (CRP) was calculated for shank-/thigh, shank-s/thigh- and foot-/shank- segment pairs. Principal component analysis (PCA) was used to extract features of greatest variability of the CRP and hierarchical linear model investigated relationships between principal components and skill level. High-calibre players demonstrated more out-of-phase coordination (higher CRP) of shank-thigh- throughout glide/push-off (0.011) as well as a delay in the transition to more in-phase coordination during early recovery phase (0.014). For shank-/thigh- ( 0.013), high-calibre players had more out-of-phase coordination throughout the entire stride. High-calibre players were also associated with an earlier transition to more out-of-phase coordination of the foot-shank- during push-off (0.007) and a smaller difference in CRP between mid-glide/early recovery (0.016). Utilising more out-of-phase modes of coordination may allow players to more easily adjust to optimal modes of coordination throughout skating strides. Skating drills incorporating varying speed, directionality and external stimuli may encourage the development of more optimal coordination during skating.
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http://dx.doi.org/10.1080/14763141.2020.1797151DOI Listing
August 2020

A General Approach to Deboronative Radical Chain Reactions with Pinacol Alkylboronic Esters.

Angew Chem Int Ed Engl 2020 Aug 4;59(33):13859-13864. Epub 2020 Jun 4.

University of Bern, Department of Chemistry and Biochemistry, Freiestrasse 3, 3012, Bern, Switzerland.

The generation of carbon-centered radicals from air-sensitive organoboron compounds through nucleohomolytic substitution at boron is a general method to generate non-functionalized and functionalized radicals. Due to their reduced Lewis acidity, alkylboronic pinacol esters are not suitable substrates. We report their in situ conversion into alkylboronic catechol esters by boron-transesterification with a substoichiometric amount of catechol methyl borate combined with an array of radical chain processes. This simple one-pot radical-chain deboronative method enables the conversion of pinacol boronic esters into iodides, bromides, chlorides, and thioethers. The process is also suitable the formation of nitriles and allylated compounds through C-C bond formation using sulfonyl radical traps. The power of combining radical and classical boron chemistry is illustrated with a modular 5-membered ring formation using a combination of three-component coupling and protodeboronative cyclization.
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http://dx.doi.org/10.1002/anie.202004012DOI Listing
August 2020

Radical Reactions of Boron-Ate Complexes Promoting a 1,2-Metallate Rearrangement.

Chimia (Aarau) 2020 Feb;74(1):33-38

Department of Chemistry and Biochemistry, University of Bern, Freiestrasse 3, CH-3012 Bern;, Email:

Recently there has been an explosion of interest in the synthetic community for the addition of radicals into unsaturated organoboron-ate complexes. This review will give a concise outline for radical processes involving boron-ate complexes which trigger a subsequent anionotropic rearrangement.
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http://dx.doi.org/10.2533/chimia.2020.33DOI Listing
February 2020

Impedance-Based Single-Cell Pipetting.

SLAS Technol 2020 06 14;25(3):222-233. Epub 2020 Mar 14.

Laboratory of Microsystems 4, IMT, STI, Ecole Polytechnique Fédérale de Lausanne, Lausanne, VD, Switzerland.

Many biological methods are based on single-cell isolation. In single-cell line development, the gold standard involves the dilution of cells by means of a pipet. This process is time-consuming as it is repeated over several weeks to ensure clonality. Here, we report the modeling, designing, and testing of a disposable pipet tip integrating a cell sensor based on the Coulter principle. We investigate, test, and discuss the effects of design parameters on the sensor performances with an analytical model. We also describe a system that enables the dispensing of single cells using an instrumented pipet coupled with the sensing tip. Most importantly, this system allows the recording of an impedance trace to be used as proof of single-cell isolation. We assess the performances of the system with beads and cells. Finally, we show that the electrical detection has no effect on cell viability.
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http://dx.doi.org/10.1177/2472630320911636DOI Listing
June 2020

Traceable Impedance-Based Dispensing and Cloning of Living Single Cells.

SLAS Technol 2020 06 18;25(3):215-221. Epub 2020 Feb 18.

Laboratory of Stem Cell Dynamics, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.

Single-cell cloning is essential in stem cell biology, cancer research, and biotechnology. Regulatory agencies now require an indisputable proof of clonality that current technologies do not readily provide. Here, we report a one-step cloning method using an engineered pipet combined with an impedance-based sensing tip. This technology permits the efficient and traceable isolation of living cells, stem cells, and cancer stem cells that can be individually expanded in culture and transplanted.
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http://dx.doi.org/10.1177/2472630320905574DOI Listing
June 2020

Biotechnologies to tackle the challenge of neoantigen identification.

Curr Opin Biotechnol 2020 10 8;65:52-59. Epub 2020 Jan 8.

Department of oncology, Ludwig Institute for Cancer Research Lausanne, Lausanne University Hospital (CHUV), University of Lausanne (UNIL), CH-1005, Switzerland. Electronic address:

Among immune correlates of clinical responses, tumor-specific neoantigens took the spotlight as relevant targets for cancer immunotherapy. The implementation of pipelines for personalized cancer therapy remains challenging due to the privacy, that is patient-specificity, of neoantigens and the low-frequency of neoantigen-specific T cells in blood and tumor samples. To overcome these obstacles, recent developments in the field of biotechnology have allowed the multiplexed identification of neoepitope-specific T cells. This review addresses the pros and cons of conventional neoantigen screening methodologies and highlights the current as well as the prospective biotechnological opportunities in the field.
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http://dx.doi.org/10.1016/j.copbio.2019.12.014DOI Listing
October 2020

Effect of input voltage frequency on the distribution of electrical stresses on the cell surface based on single-cell dielectrophoresis analysis.

Sci Rep 2020 01 9;10(1):68. Epub 2020 Jan 9.

École Polytechnique Fédérale de Lausanne, STI IMT LMIS4, Station 17, CH-1015, Lausanne, Switzerland.

Electroporation is defined as cell membrane permeabilization under the application of electric fields. The mechanism of hydrophilic pore formation is not yet well understood. When cells are exposed to electric fields, electrical stresses act on their surfaces. These electrical stresses play a crucial role in cell membrane structural changes, which lead to cell permeabilization. These electrical stresses depend on the dielectric properties of the cell, buffer solution, and the applied electric field characteristics. In the current study, the effect of electric field frequency on the electrical stresses distribution on the cell surface and cell deformation is numerically and experimentally investigated. As previous studies were mostly focused on the effect of electric fields on a group of cells, the present study focused on the behavior of a single cell exposed to an electric field. To accomplish this, the effect of cells on electrostatic potential distribution and electric field must be considered. To do this, Fast immersed interface method (IIM) was used to discretize the governing quasi-electrostatic equations. Numerical results confirmed the accuracy of fast IIM in satisfying the internal electrical boundary conditions on the cell surface. Finally, experimental results showed the effect of applied electric field on cell deformation at different frequencies.
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http://dx.doi.org/10.1038/s41598-019-56952-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6952456PMC
January 2020

Microfluidic device performing on flow study of serial cell-cell interactions of two cell populations.

RSC Adv 2019 Dec 13;9(70):41066-41073. Epub 2019 Dec 13.

Laboratory of Microsystems LMIS4, Ecole Polytechnique Fédérale de Lausanne (EPFL) Lausanne Switzerland

In this study we present a novel microfluidic hydrodynamic trapping device to probe the cell-cell interaction between all cell samples of two distinct populations. We have exploited an hydrodynamic trapping method using microfluidics to immobilize a batch of cells from the first population at specific locations, then relied on hydrodynamic filtering principles, the flowing cells from the second cell population are placed in contact with the trapped ones, through a roll-over mechanism. The rolling cells interact with the serially trapped cells one after the other. The proposed microfluidic phenomenon was characterized with beads. We have shown the validity of our method by detecting the capacity of olfactory receptors to induce adhesion of cell doublets overexpressing these receptors. We report here the first controlled on-flow single cell resolution cell-cell interaction assay in a microfluidic device for future application in cell-cell interactions-based cell library screenings.
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http://dx.doi.org/10.1039/c9ra09504gDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9076435PMC
December 2019

Swiss Summer School 'Trends in Organic Synthesis' Villars-sur-Ollon, August 18-22, 2019.

Chimia (Aarau) 2019 Nov;73(11):950-951

Swiss Chemical Society Foundation, Laupenstrasse 7, CH-3001 Bern;, Email:

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http://dx.doi.org/10.2533/chimia.2019.950DOI Listing
November 2019

Two-Step Azidoalkenylation of Terminal Alkenes Using Iodomethyl Sulfones.

Molecules 2019 Nov 18;24(22). Epub 2019 Nov 18.

Department of Chemistry and Biochemistry, University of Bern, Freiestrasse 3, CH-3012 Bern, Switzerland.

The radical azidoalkylation of alkenes that was initially developed with α-iodoesters and α-iodoketones was extended to other activated iodomethyl derivatives. By using iodomethyl aryl sulfones, the preparation of γ-azidosulfones was easily achieved. Facile conversion of these azidosulfones to homoallylic azides using a Julia-Kocienski olefination reaction is reported, making the whole process equivalent to the azidoalkenylation of terminal alkenes.
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http://dx.doi.org/10.3390/molecules24224184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6891591PMC
November 2019
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