Controlled Formation of All-Aqueous Janus Droplets by Liquid–Liquid Phase Separation of an Aqueous Three-Phase System

Abstract

Janus droplets have been demonstrated in a wide range of applications, ranging from drug delivery, to biomedical imaging, to bacterial detection. However, existing fabrication strategies often involve nonaqueous solvents, such as organic solvent or oil, which largely limits their use in fields that require a high degree of biocompatibility. Here, we present a method to achieve all-aqueous Janus droplets by liquid–liquid phase separation of an aqueous three-phase system (A3PS). An aqueous droplet containing two initially miscible polymers is first injected into an aqueous solution of another concentrated polymer, and then it spontaneously phase-separates into a Janus droplet due to the diffusive mass exchange between the drop and bulk phases during equilibration. To achieve continuous generation of the Janus droplets, the A3PS is further integrated with microfluidics and electrospray. The size and shape of the phase-separated Janus droplets can be easily controlled by tuning the operation parameters, such as the flow rate and/or the initial composition of the drop phases. Dumbbell-shaped and snowman-shaped Janus droplets with average sizes between 100 and 400 μm can be generated by both coflow microfluidics and electrospray. In particular, the phase-separated Janus droplets can simultaneously load two different liposomes into each compartment, which are promising carriers for combination drugs. The obtained Janus droplets are superior templates for biocompatible materials, which can serve as building blocks such as high-order droplet patterns for constructing advanced biomaterials.

Janus Droplet Formation via Thermally Induced Phase Separation: A Numerical Model with Diffusion and Convection

“…Bright: dextran (DEX); gray: poly(2-ethyl-2-oxazoline) (PEtOx), and gray matrix: polyethylene glycol (PEG). Reproduced with permission from ref ( 85 ) copyright ⓒ 2021, American Chemical Society.…”

“…In some experiments, − non-equal compositions of polymers A and B are adopted to synthesize different droplet morphologies, for example, vesicle, uneven Janus, and so forth. In Figure I, we perform simulations with unequal polymer compositions, namely, c 1 / c 2 = 3:7 and c 1 / c 2 = 7:3, for a precursor droplet with r 0 = 80 μm.…”

Complex Suspended Janus Droplets Constructed through Solvent Evaporation-Induced Phase Separation at the Air–Liquid Interface

“…Despite many researchers that have studied the droplet's phase separation phenomenon in noncontinuous surroundings, 47,48 there are few studies on the phase separation phenomenon and spreading behavior of suspended droplets at the air−liquid interface. 49,50 Herein, we reported a novel interfacial phase separation phenomenon with a mixture material system consisting of poly(ethylene glycol) diacrylate (PEGDA), ethanol, glycerol, and liquid paraffin, which occurred within a suspended droplet at the air−liquid interface due to the influences of three interfacial tensions. The suspended droplets at the air−droplet interface would be phase-separated into a patchy structure, which was a new phase-separation phenomenon.…”

“…Chao et al presented a facile approach to creating flower-like suspended microdroplets via a phase-separating aqueous film self-emulsification. Despite many researchers that have studied the droplet’s phase separation phenomenon in noncontinuous surroundings, , there are few studies on the phase separation phenomenon and spreading behavior of suspended droplets at the air–liquid interface. , …”

Liquid–Liquid Phase Separation: A Widespread and Versatile Way to Organize Aqueous Solutions

“…18 Also included are a simple calculation for phase diagrams in solutions of two solutes, 19 and a theory for the measurement of condensate materials properties by droplet deformation. 20 Experimental advances include an NMR method to acquire 1 H N spectra for IDPs despite rapid amide proton exchange, 21 a microfluidic approach for generating Janus droplets based on all all-aqueous three phase system, 22 and a transmission electron microscopy study of size-dependent LLPS in nanoscale, atmospheric aerosol-relevant droplets. 23 Time-and temperature-resolved USAXS (ultrasmall angle X-ray scattering) techniques are used to understand the relationship between the LLPS binodal and the glass transition.…”