Publications by authors named "Lionel Guillou"

4 Publications

  • Page 1 of 1

Development and validation of a cellular host response test as an early diagnostic for sepsis.

PLoS One 2021 15;16(4):e0246980. Epub 2021 Apr 15.

Louisiana State University Health Sciences Center, Baton Rouge, Louisiana, United States of America.

Sepsis must be diagnosed quickly to avoid morbidity and mortality. However, the clinical manifestations of sepsis are highly variable and emergency department (ED) clinicians often must make rapid, impactful decisions before laboratory results are known. We previously developed a technique that allows the measurement of the biophysical properties of white blood cells as they are stretched through a microfluidic channel. In this study we describe and validate the resultant output as a model and score-the IntelliSep Index (ISI)-that aids in the diagnosis of sepsis in patients with suspected or confirmed infection from a single blood draw performed at the time of ED presentation. By applying this technique to a high acuity cohort with a 23.5% sepsis incidence (n = 307), we defined specific metrics-the aspect ratio and visco-elastic inertial response-that are more sensitive than cell size or cell count in predicting disease severity. The final model was trained and cross-validated on the high acuity cohort, and the performance and generalizability of the model was evaluated on a separate low acuity cohort with a 6.4% sepsis incidence (n = 94) and healthy donors (n = 72). For easier clinical interpretation, the ISI is divided into three interpretation bands of Green, Yellow, and Red that correspond to increasing disease severity. The ISI agreed with the diagnosis established by retrospective physician adjudication, and accurately identified subjects with severe illness as measured by SOFA, APACHE-II, hospital-free days, and intensive care unit admission. Measured using routinely collected blood samples, with a short run-time and no requirement for patient or laboratory information, the ISI is well suited to aid ED clinicians in rapidly diagnosing sepsis.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0246980PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049231PMC
April 2021

Mechanical Criterion for the Rupture of a Cell Membrane under Compression.

Biophys J 2016 Dec;111(12):2711-2721

Hydrodynamics Laboratory, CNRS UMR 7646, Department of Mechanics, École Polytechnique, Palaiseau, France. Electronic address:

We investigate the mechanical conditions leading to the rupture of the plasma membrane of an endothelial cell subjected to a local, compressive force. Membrane rupture is induced by tilted microindentation, a technique used to perform mechanical measurements on adherent cells. In this technique, the applied force can be deduced from the measured horizontal displacement of a microindenter's tip, as imaged with an inverted microscope and without the need for optical sensors to measure the microindenter's deflection. We show that plasma membrane rupture of endothelial cells occurs at a well-defined value of the applied compressive stress. As a point of reference, we use numerical simulations to estimate the magnitude of the compressive stresses exerted on endothelial cells during the deployment of a stent.
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http://dx.doi.org/10.1016/j.bpj.2016.11.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5192693PMC
December 2016

T-lymphocyte passive deformation is controlled by unfolding of membrane surface reservoirs.

Mol Biol Cell 2016 11 7;27(22):3574-3582. Epub 2016 Sep 7.

Laboratoire d'Hydrodynamique, Ecole Polytechnique, CNRS UMR 7646, 91128 Palaiseau, France

T-lymphocytes in the human body routinely undergo large deformations, both passively, when going through narrow capillaries, and actively, when transmigrating across endothelial cells or squeezing through tissue. We investigate physical factors that enable and limit such deformations and explore how passive and active deformations may differ. Employing micropipette aspiration to mimic squeezing through narrow capillaries, we find that T-lymphocytes maintain a constant volume while they increase their apparent membrane surface area upon aspiration. Human resting T-lymphocytes, T-lymphoblasts, and the leukemic Jurkat T-cells all exhibit membrane rupture above a critical membrane area expansion that is independent of either micropipette size or aspiration pressure. The unfolded membrane matches the excess membrane contained in microvilli and membrane folds, as determined using scanning electron microscopy. In contrast, during transendothelial migration, a form of active deformation, we find that the membrane surface exceeds by a factor of two the amount of membrane stored in microvilli and folds. These results suggest that internal membrane reservoirs need to be recruited, possibly through exocytosis, for large active deformations to occur.
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http://dx.doi.org/10.1091/mbc.E16-06-0414DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5221589PMC
November 2016

Measuring Cell Viscoelastic Properties Using a Microfluidic Extensional Flow Device.

Biophys J 2016 Nov;111(9):2039-2050

Department of Bioengineering, UC Berkeley, Berkeley, California; Department of Chemical and Biomolecular Engineering, UC Berkeley, Berkeley, California; The UC Berkeley-UCSF Graduate Program in Bioengineering, UC Berkeley, Berkeley, California. Electronic address:

The quantification of cellular mechanical properties is of tremendous interest in biology and medicine. Recent microfluidic technologies that infer cellular mechanical properties based on analysis of cellular deformations during microchannel traversal have dramatically improved throughput over traditional single-cell rheological tools, yet the extraction of material parameters from these measurements remains quite complex due to challenges such as confinement by channel walls and the domination of complex inertial forces. Here, we describe a simple microfluidic platform that uses hydrodynamic forces at low Reynolds number and low confinement to elongate single cells near the stagnation point of a planar extensional flow. In tandem, we present, to our knowledge, a novel analytical framework that enables determination of cellular viscoelastic properties (stiffness and fluidity) from these measurements. We validated our system and analysis by measuring the stiffness of cross-linked dextran microparticles, which yielded reasonable agreement with previously reported values and our micropipette aspiration measurements. We then measured viscoelastic properties of 3T3 fibroblasts and glioblastoma tumor initiating cells. Our system captures the expected changes in elastic modulus induced in 3T3 fibroblasts and tumor initiating cells in response to agents that soften (cytochalasin D) or stiffen (paraformaldehyde) the cytoskeleton. The simplicity of the device coupled with our analytical model allows straightforward measurement of the viscoelastic properties of cells and soft, spherical objects.
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http://dx.doi.org/10.1016/j.bpj.2016.09.034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5103028PMC
November 2016