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 label-free 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.

Hydrodynamic Assisted Multiparametric Particle Spectrometry

“…The TMR and the readout system also allow tracking the reflected light power (optical signal) by the device 25 . Hence, when a particle passes under the illuminated region by the laser spot it produces a dip in this optical signal due to the scattered light, which can be used to obtain additional information about the particle.…”

“…1.b). This interferometric system also allows tracking the reflected light power by the fused silica resonator to obtain information about the optical properties of the flowing analytes by analyzing in real-time the scattered light 24,25 . Moreover, the device is pressurized by means of a nitrogen pressure pump (Fluigent INC, MFCS-EZ-07000001), which allows flow control by setting a pressure difference.…”

“…Hence, when a particle passes under the illuminated region by the laser spot it produces a dip in this optical signal due to the scattered light, which can be used to obtain additional information about the particle. This dip in the optical signal consists of a double peak whose local maximum corresponds to the particle positioned in the center of the spot while its local minima correspond to the scattered light at the particle border: entering and leaving the illuminated spot area 25 . Hence, given the particle velocity obtained by fitting the mechanical signal, the particle diameter can be calculated by measuring the time-difference between the two local minima in the optical signal (Fig.…”

“…Among the SMR devices, transparent microcapillary resonators (TMR) not only combine a nanomechanical resonator with a microfluidic channel but also allow the optical probing of the flowing particles. These devices have been demonstrated in previous works as an interesting alternative to cantilever-type SMRs for mass sensing [18][19][20][21][22][23] , introducing a new source of information about the particle based on its optical characterization 24,25 . This double mechanooptical particle detection technique has been proved in recent work as a highly reliable technique for particle discerning, even in cases of particles of similar masses.…”

Theoretical modeling of tunable vibrations of three-dimensional serpentine structures for simultaneous measurement of adherent cell mass and modulus

“…[15][16][17][18] Vibration-based methods in cell mechanics is of growing interest because of their rapid and non-invasive ability to monitor cellular processes in real time. [1][2][3][4][5][6]9,[19][20][21][22] For example, a micrometer-scale cantilever actuated by a beam of laser light enables the continuous (millisecond time resolution) measurement of cell mass with high resolution (picogram) from the shift of its resonant frequency. 3 However, these and other related vibrational Cell mass and modulus are important indicators of cell behavior during growth, proliferation, differentiation, and interactions with external stimuli such as drugs and viruses.…”