Scalable, Membrane‐Based Microfluidic Passive Cross‐Flow Platform for Monodispersed, Water‐in‐Water Microdroplet Production

Abstract

diagnostics, [6] biomolecule evolution, [7] and food-grade quality control. [8] These applications use monodispersed picoliteror nanoliter-volume droplets, resulting in cost-effective and time-efficient procedures. [9] Classical microdroplet formation methods to form such microdroplets use oil and water as immiscible liquids. Oil, however, is a non-biocompatible medium that must be removed subsequent to droplet formation because the oil phase negatively impacts on encapsulated biological species, such as cells, in the water droplet phase. Thus, an additional step, typically a time-and labor-intensive oilremoval treatment, would be required. [10] Alternatively, aqueous two-phase systems (ATPSs) have recently made a high-impact appearance in the droplet formation field because of its biocompatibility. The applicability of ATPS as a medium for cells and biomolecules has been widely proven, allowing for it to be a reasonable option for biological applications and, furthermore, the elimination of post-processing washing. [11] ATPSs have been applied to partitioning and purification of proteins, [12] enzymes, [13,14] drug residues in food and water, [15,16] etc., as well as cell patterning [17] and fractionation. [18] There are many unique ATPS compositions available for implementation including, but not limited to, polymer-salt [19,20] and alcohol-salt. [21,22] The mixture of polyethylene glycol (PEG) and dextran (DEX) is a well-documented polymerpolymer composition that has been often-used for droplet formation. [23] The main challenge in the ATPS droplet formation is overcoming the ultra-low interfacial tension (< 1 mJ m −2 ) [24] of the two aqueous-phases making hydrodynamic thread break-up difficult and restricted to jetting droplet regimes. [25] For successful droplet break-up, active methods use external forces to overcome the viscous forces that stretch the interface between the aqueous continuous and dispersed phases. Active approaches thus require external components for flow perturbation, such as, piezo-electric disc actuation, [26,27] mechanical vibration, [28,29] inlet pressure pulsation, [30] and pneumatic valve control. [31] Recent passive approaches in flow focusing microfluidic platforms simplify the droplet formation mechanism by eliminating external component requirements. Passive methods canThe generation of water-in-water droplets has recently received great attention for its applicability in biological applications over traditional oil-water droplet systems because of their high biocompatibility. An aqueous twophase system (ATPS), aqueous mixture of polyethylene glycol (PEG) and dextran (DEX), has an ultra-low interfacial tension which makes monodispersed droplet formation challenging. Recent passive methods in microfluidics with flow-focusing configurations overcome this challenge, but they suffer either from polydispersity, narrow droplet size range, or low throughput. Successful droplet formation in such passive methods occurs in jetting flow regimes with low continuous phase flowrates, Q c < ...

Encapsulation of Caenorhabditis elegans in Water-in-Water Microdroplets to Study the Worm Viability: Alternative Avenue to Manipulate Microdroplet Environment

“…In a microneedle 3D flow-focusing device, the droplet generation was observed for capillary number between 0.8 and 4.5 . In a membrane cross-flow configuration, the droplets were generated for capillary number ranging between 0.04 and 0.19 . In a typical coflow setup, the dripping and jetting regimes were observed for Ca between O (10 –3 ) and O(1) and between O­(10 –3 ) and O(10), respectively …”

“…24 In a membrane cross-flow configuration, the droplets were generated for capillary number ranging between 0.04 and 0.19. 25 In a typical coflow setup, the dripping and jetting regimes were observed for Ca between O (10 −3 ) and O(1) and between O(10 −3 ) and O(10), respectively. 12 Droplet Size.…”

“…Considering the challenges involved in microfluidic fabrication, customization, and worm health, a passive method, which exploits the channel geometry and hydrodynamic forces to generate droplets, is highly desirable. The passive droplet generation has been achieved in microfluidics using flow-focusing, 23 microneedle-3D flowfocusing, 24 and membrane cross-flow 25 induced by either gravity-driven hydrostatics, high-precision pressure or syringe pump systems. Among the passive methods, the gravity-driven hydrostatics for flow control is more cost-effective, but the liquid level height for uniform hydrostatic pressure is difficult to maintain, which limits scale-up applications.…”

“…Among the passive methods, the gravity-driven hydrostatics for flow control is more cost-effective, but the liquid level height for uniform hydrostatic pressure is difficult to maintain, which limits scale-up applications. 25 The membrane cross-flow configuration enables successful monodispersed microdroplet generation by using a syringe pump. However, this cross-flow setup is inapplicable to encapsulate large biological organisms, such C. elegans.…”

“…The passive droplet generation has been achieved in microfluidics using flow-focusing, microneedle-3D flow-focusing, and membrane cross-flow induced by either gravity-driven hydrostatics, high-precision pressure or syringe pump systems. Among the passive methods, the gravity-driven hydrostatics for flow control is more cost-effective, but the liquid level height for uniform hydrostatic pressure is difficult to maintain, which limits scale-up applications . The membrane cross-flow configuration enables successful monodispersed microdroplet generation by using a syringe pump.…”