Target particle encapsulation is crucial in droplet microfluidics for high-throughput applications like single-cell sequencing and drug screening. However, it faces limitations, with encapsulation rates of only 10% to 30% due to suspension density and the inherent functionality of the chip being restricted by the Poisson distribution. This leads to reagent waste and reduced effectiveness in applications requiring ultra-high multiplexing or extensive particle analysis, due to the massive empty droplets. Here we propose a droplet microfluidic system integrating surface acoustic wave (SAW) and sheath flow control. Suspensions of varying concentrations within the channel are initially pre-focused by sheath fluid, and then acoustically focused into a linear arrangement by SAW. Spacing between particles can be regulated by modulating the sheath fluid, ensuring sequential encapsulation of cells or beads in individual droplets. Thermal shock generated by the SAW, particle and droplet frequency, and particle encapsulation ratio are all elaborately evaluated. The results demonstrate that our system reaches an exciting single-bead packing efficiency of up to 78%, and achieves a packing rate of more than 60% for both high and low concentrations of solutions for polystyrene microspheres, magnetic beads and H22 cells, 6 times higher than the theoretical upper limit of the conventional method and 1.8 times higher than the Poisson distribution. More importantly, our system is designed to be free of structural and parametric constraints, which is quite important in future practical application. Thus, our on-chip particle focusing control method and droplet microfluidic system provide great potential in biological applications needing a high single-particle encapsulation ratio in limited partitions, such as ultra-high multiplex digital biomolecular detection, single-cell analysis, drug screening, and single exosome detection.
In this paper, we describe a robust sheath flow-based CE-MS interface with minimal interface dead volume based on an extended pattern. A 20 µm i.d. × 90 µm o.d. fused-silica capillary with a chemically-etched thin-wall tip (30 µm o.d.) was used as the separation capillary as well as electrospray emitter, and a 200 µm i.d. × 375 µm o.d. capillary with a tapered tip (40 µm o.d.) was used as the sheath flow capillary. An extendable sheath-flow interface mode was adopted by decreasing the thickness of separation capillary tip and extending the separation capillary tip out from the sheath flow capillary tip, and allowing the sheath flow to be transferred to the separation capillary tip along its outer surface, forming a surface sheath flow to mix with sample flow at the separation capillary tip. Such a strategy could significantly reduce the interface dead volume and thus improve the CE separation efficiency and detection sensitivity, as well as evidently enhance the working reliability of the CE-MS interface. We investigated various factors affecting the interface performance, including capillary extending distance, emitter diameters, sheath flow capillary shape , and sheath flow rate . Under the optimized conditions, a minimal interface dead volume of ca. 4 pL was obtained which is the smallest one compared with previously-reported sheath flow-based CE-MS interfaces. The feasibility and applicability of the present CE-MS interface were demonstrated in the separation of a peptide mixture with high separation efficiency of 2.07–3.38 µm plate heights and good repeatabilities (< 6.1% RSD, n = 5). We except such a simple and robust interface could provide a possible solution for the development of commercial CE-MS interfaces differing from the currently-used ones, and has the potentials to be applied in routine analytical laboratories for various studies such as proteomics, metabolomics, or single cell analysis.
We developed a new approach for particle separation by introducing viscosity difference of the sheath flows to form an asymmetric focusing of sample particle flow. This approach relies on the high-velocity gradient in the asymmetric focusing of the particle flow to generate a lift force, which plays a dominated role in the particle separation. The larger particles migrate away from the original streamline to the side of the higher relative velocity, while the smaller particles remain close to the streamline. Under high-viscosity (glycerol–water solution) and low-viscosity (PBS) sheath flows, a significant large stroke separation between the smaller (1.0 μm) and larger (9.9 μm) particles was achieved in a sample microfluidic device. We demonstrate that the flow rate and the viscosity difference of the sheath flows have an impact on the interval distance of the particle separation that affects the collected purity and on the focusing distribution of the smaller particles that affects the collected concentration. The interval distance of 293 μm (relative to the channel width: 0.281) and the focusing distribution of 112 μm (relative to the channel width: 0.107) were obtained in the 1042-μm-width separation area of the device. This separation method proposed in our work can potentially be applied to biological and medical applications due to the wide interval distance and the narrow focusing distribution of the particle separation, by easy manufacturing in a simple device.
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