Abstract
Three-dimensional (3D) particle focusing in microfluidics is a fundamental capability with a wide range of applications, such as on-chip flow cytometry, where high-throughput analysis at the single-cell level is performed. Currently, 3D focusing is achieved mainly in devices with complex layouts, additional sheath fluids, and complex pumping systems. In this work, we present a compact microfluidic device capable of 3D particle focusing at high flow rates and with a small footprint, without the requirement of external fields or lateral sheath flows, but using only a single-inlet, single-outlet microfluidic sequence of straight channels and tightly curving vertical loops. This device exploits inertial fluidic effects that occur in a laminar regime at sufficiently high flow rates, manipulating the particle positions by the combination of inertial lift forces and Dean drag forces. The device is fabricated by femtosecond laser irradiation followed by chemical etching, which is a simple two-step process enabling the creation of 3D microfluidic networks in fused silica glass substrates. The use of tightly curving three-dimensional microfluidic loops produces strong Dean drag forces along the whole loop but also induces an asymmetric Dean flow decay in the subsequent straight channel, thus producing rapid cross-sectional mixing flows that assist with 3D particle focusing. The use of out-of-plane loops favors a compact parallelization of multiple focusing channels, allowing one to process large amounts of samples. In addition, the low fluidic resistance of the channel network is compatible with vacuum driven flows. The resulting device is quite interesting for high-throughput on-chip flow cytometry.
Highlights
On-chip flow cytometers promise several advantages in terms of cost reduction, portability, and increased device performance with respect to standard bench-top approaches
Inertial microfluidics has been successfully proposed to effectively manipulate particle positions in microfluidic channels13–15, by exploiting the channel geometry and the flow rate. This approach is extremely promising for flow cytometry applications, since it presents the great advantage of performing flow focusing within a single-inlet single-outlet microfluidic device without the need for external fields and at high throughput
An advantageous approach to reduce the number of equilibrium points and to speed up the particle repositioning is the introduction of curvature in the channel, which gives rise to a net secondary flow, known as Dean flow, that is orthogonal to the main flow direction
Summary
On-chip flow cytometers promise several advantages in terms of cost reduction, portability, and increased device performance with respect to standard bench-top approaches. Inertial microfluidics has been successfully proposed to effectively manipulate particle positions in microfluidic channels, by exploiting the channel geometry and the flow rate This approach is extremely promising for flow cytometry applications, since it presents the great advantage of performing flow focusing within a single-inlet single-outlet microfluidic device without the need for external fields (that complicate the setups) and at high throughput. For this geometrical layout the Dean flow effect is not constant in the device and is smaller given the large radius of curvature, long channels are typically required (in the order of few tens of centimeters17,15) Another planar approach uses asymmetric curving channels, made by a sequence of opposite curves alternating between tight and loose bending. We demonstrate compact channel parallelization with low fluidic resistance, yielding high throughput sample analysis, and making this device a valuable solution for sample focusing in on-chip flow cytometry
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