Aqueous Two-Phase System (ATPS)-Based Polymersomes for Particle Isolation and Separation

Abstract

Aqueous two-phase systems (ATPSs) have been widely used in the separation, purification, and enrichment of biomolecules for their excellent biocompatibility. While ultracentrifugation and microfluidic devices have been combined with ATPS to facilitate the separation of biomolecules and achieve high recovery yields, they often lack the ability to effectively isolate and separate biomolecules in low concentrations. In this work, we present a strategy that leverages the preferential partitioning of biomolecules in ATPS droplets to efficiently separate model extracellular vesicle (EV) particles. We demonstrate that the additional oil phase between the inner ATPS droplets and the aqueous continuous phase in triple emulsion droplets resolves the size controllability and instability issues of ATPS droplets, enabling the production of highly monodisperse ATPS-based polymersomes with enhanced stability for effective isolation of ATPS droplets from the surrounding environment. Furthermore, we achieve separation of model EV particles in a single dextran (DEX)-rich droplet by the massive production of ATPS-based polymersomes and osmotic-pressure-induced rupture of the selected polymersome in a hypertonic solution composed of poly­(ethylene glycol) (PEG).

Improving Isolation of Extracellular Vesicles by Utilizing Nanomaterials

“…This device can facilitate continuous EV isolation with 83.4% recovery efficiency without complex external equipment [87]. Seo et al further improved ATPS by introducing an additional oil phase between the inner ATPS droplets and achieved separation of EV particles in a single DEX-rich droplet [88].…”

Liquid-Liquid Nanogenerator basing on Aqueous-Aqueous Interface

“…The aqueous two-phase system (ATPS) is widely used for the separation, purification and enrichment of biomolecules 44,46,59,60 . Making full use of the morphology control ability of this system can lead to the development of brand-new electronic devices, so the biocompatibility analysis has important value for its future use in implantable device 61 .…”

Self-Encapsulation of Biomacromolecule Drugs in Porous Microscaffolds with Aqueous Two-Phase Systems

“…Next, the question turned into how to encapsulate the protein and close the pores. To close the pores, heating to glass transition temperature (Tg) or above can trigger a "self-Pharmaceutics 2021, 13, 426 2 of 13 healing" process based on the mobility of the polymer chains. The mechanism includes polymer-chain inter-diffusion driven by minimization of the energetically unfavorable interfacial area and/or transfer of potential energy stored in the defect [7].…”

“…Herein, we describe a loading strategy with an aqueous two-phase system (ATPS), greatly increasing the loading amount and avoiding any factor to denature the proteins. ATPS is available in several combinations such as two polymers, one polymer, and one salt or two salts, which are low cost and high efficiency and have been used for decades in biotechnology applications as non-denaturating and initial separation media [10][11][12][13][14]. One of the most well-known ATPS forming combinations is poly(ethylene glycol) (PEG) and salt (such as phosphate, sulfate, and citrate), since the salt will capture a large amount of the water present.…”