Effects of Flow‐Induced Microfluidic Chip Wall Deformation on Imaging Flow Cytometry

Abstract

Imaging flow cytometry is a powerful tool by virtue of its capability for high‐throughput cell analysis. The advent of high‐speed optical imaging methods on a microfluidic platform has significantly improved cell throughput and brought many degrees of freedom to instrumentation and applications over the last decade, but it also poses a predicament on microfluidic chips. Specifically, as the throughput increases, the flow speed also increases (currently reaching 10 m/s): consequently, the increased hydrodynamic pressure on the microfluidic chip deforms the wall of the microchannel and produces detrimental effects lead to defocused and blur image. Here, we present a comprehensive study of the effects of flow‐induced microfluidic chip wall deformation on imaging flow cytometry. We fabricated three types of microfluidic chips with the same geometry and different degrees of stiffness made of polydimethylsiloxane (PDMS) and glass to investigate material influence on image quality. First, we found the maximum deformation of a PDMS microchannel was >60 μm at a pressure of 0.6 MPa, while no appreciable deformation was identified in a glass microchannel at the same pressure. Second, we found the deviation of lag time that indicating velocity difference of migrating microbeads due to the deformation of the microchannel was 29.3 ms in a PDMS microchannel and 14.9 ms in a glass microchannel. Third, the glass microchannel focused cells into a slightly narrower stream in the X‐Y plane and a significantly narrower stream in the Z‐axis direction (focusing percentages were increased 30%, 32%, and 5.7% in the glass channel at flow velocities of 0.5, 1.5, and 3 m/s, respectively), and the glass microchannel showed stabler equilibrium positions of focused cells regardless of flow velocity. Finally, we achieved the world's fastest imaging flow cytometry by combining a glass microfluidic device with an optofluidic time‐stretch microscopy imaging technique at a flow velocity of 25 m/s. © 2019 International Society for Advancement of Cytometry

Dual-frequency impedance assays for intracellular components in microalgal cells

“…Although Raman flow cytometry (RFC) is known as a high-throughput and non-invasive method for mapping the distribution of distinct molecular groups in live cells, [15][16][17] it requires huge optical equipment, a complicated setup, and strict experimental conditions, such as three-dimensional (3D) cell focusing techniques for reproducible detection signals, 18 relatively low flow rates for high-quality imaging 15 and optical transmission of channel materials for light detection. [19][20][21] As an alternative, impedance cytometry has the potential to characterize intracellular components of single cells in a label-free manner. Xu et al theoretically demonstrated that impedance cytometry can characterize the components within the cellular membrane at high frequencies (typically >1 MHz) based on a single shell model, 22 as a highfrequency electric field can cross the membrane.…”

Fabrication of Perforated PDMS Microchannel by Successive Laser Pyrolysis

“…As a consequence of this research, we easily made a perforated PDMS microchannel which is difficult to fabricate with the mold replica method, especially in the case of thin PDMS layer. Based on the high mechanical strength and optical stability of the G-P-G configuration, we expect that the application we made be utilized in digital PCR applications and optical microfluidic systems such as biochips equipped with a high-speed camera [ 38 , 39 ] or laser-assisted reactive chamber usages.…”

A simple and reversible glass–glass bonding method to construct a microfluidic device and its application for cell recovery

“…Based on these glass properties and fundamental technologies, many unique applications such as detection by Raman microscopy, 12 thermal lens microscopy, 13 organic synthesis, 14,15 gas analysis, 16,17 cell patterning and analysis, 18,19 electrophoretic separations, 20 nanostructurebased molecule separations 21,22 and cell analysis by ultra-fast flow imaging 23 have been developed. These applications are difficult to realize with polymer-based microfluidic devices because polymers show lower performance of light transmission, chemical stability against organic solvents, retaining gas in microchannels, have lower values of Young's modulus which is a fundamental factor in cell scaffolding, and are less suitable for precise fabrication at microscale than glass does.…”