Universally applicable three-dimensional hydrodynamic microfluidic flow focusing

Abstract

We have demonstrated a microfluidic device that can not only achieve three-dimensional flow focusing but also confine particles to the center stream along the channel. The device has a sample channel of smaller height and two sheath flow channels of greater height, merged into the downstream main channel where 3D focusing effects occur. We have demonstrated that both beads and cells in our device display significantly lower CVs in velocity and position distributions as well as reduced probability of coincidental events than they do in conventional 2D-confined microfluidic channels. The improved particle confinement in the microfluidic channel is highly desirable for microfluidic flow cytometers and in fluorescence-activated cell sorting (FACS). We have also reported a novel method to measure the velocity of each individual particle in the microfluidic channel. The method is compatible with the flow cytometer setup and requires no sophisticated visualization equipment. The principles and methods of device design and characterization can be applicable to many types of microfluidic systems.

Brillouin flow cytometry for label-free mechanical phenotyping of the nucleus

“…The potential misalignment in the vertical direction may introduce an artificial broadening of the histogram distribution and thus reduce the sensitivity of the measurement. To address this issue, recently developed hydrodynamic focusing techniques, such as inertial microfluidics 44–49 , 3D symmetric focusing 50–51 and surface acoustic wave microfluidics 52 , could be used.…”

Microfluidic hydrodynamic focusing for synthesis of nanomaterials

“…In the basic HF process, a central solution with a lower flow rate flows within an outer sheath fluid with a higher flow rate, enabling the compression of the central flow [29,30]. This compression decreases mixing times significantly by reducing the required diffusion length [31,32].…”

“…Later, efforts were made to reduce the number of layers in order to decrease the required fabrication steps and cost. For example, by introducing a height variation in microfluidic channels using two-layer fabrication, focusing on the horizontal and vertical planes can be introduced sequentially to achieve 3D HF (Figure 4a and 4b) [30,57,58]. …”

Monolithic cell counter based on 3D hydrodynamic focusing in microfluidic channels

“…Also the 3D focusing can be achieved through centrifugal forces 6,7 exploiting simple and planar structures, but a crucial point in these cases is represented by the flow rates at which the devices are supposed to work, thus leading to less flexible devices. Finally, few examples of multi-level devices 8,9,10,11,12 proved to be quite efficient in the realization of 3D hydrodynamic focusing also tested as cytometers. Anyway these approaches generally leads to complicated fabrication processes and the devices require the assembly of external component for particle detection and counting.…”

“…Furthermore many of the device presented above use three or even more inlets to implement the 3D focusing, while few inlets, enhancing the simplicity of the operations, are to be preferred. In addition, they usually provide asymmetric focusing in the two directions, with the focused sample showing an elliptical cross-section 8 and in several cases flowing close to one edge of the microchannel and not in its center 13 . A different fabrication technique with important advantages with respect to the standard lithographic approaches is femtosecond laser micromachining (FLM) 14 followed by chemical etching.…”