Mechano-Optical Analysis of Single Cells with Transparent Microcapillary Resonators

Abstract

The study of biophysical properties of single cells is becoming increasingly relevant in cell biology and pathology. The measurement and tracking of magnitudes such as cell stiffness, morphology, and mass or refractive index have brought otherwise inaccessible knowledge about cell physiology, as well as innovative methods for high-throughput labelfree cell classification. In this work, we present hollow resonator devices based on suspended glass microcapillaries for the simultaneous measurement of single-cell buoyant mass and reflectivity with a throughput of 300 cells/minute. In the experimental methodology presented here, both magnitudes are extracted from the devices' response to a single probe, a focused laser beam that enables simultaneous readout of changes in resonance frequency and reflected optical power of the devices as cells flow within them. Through its application to MCF-7 human breast adenocarcinoma cells and MCF-10A nontumorigenic cells, we demonstrate that this mechano-optical technique can successfully discriminate pathological from healthy cells of the same tissue type. ; This work was supported by the European Union's Horizon 2020 research and innovation program under European Research Council Grant 681275-LIQUIDMASS-ERC-CoG2015 and by the Spanish Science, Innovation and Universities Ministry through project CELLTANGLE reference RTI2018- 099369-B-I00, project MOMPs reference TEC2017-89765-R and Ramon y Cajal grant RYC-2017-21640 to P.M.K.; by the ́ Comunidad de Madrid (iLUNG B2017/BMD-3884) with support from EU (FEDER, FSE). E.G.-S. received funding from Fundacion General CSIC (Programa ComFuturo), as ́ well as Marie-Sklodowska Curie Actions (H2020-MSCA-IF2015) under NOMBIS project (703354).The service from the Micro and Nanofabrication Laboratory (MiNa) and X-SEM Laboratory, is funded by MCIU (CSIC13-4E-1794) and EU (FEDER, FSE). We have received support for part of the publication fee by CSIC open access publication support initiative through URICI. ; Peer reviewed