Emerging Biotechnology Applications of Aqueous Two‐Phase Systems

Abstract

Liquid–liquid phase separation between aqueous solutions containing two incompatible polymers, a polymer and a salt, or a polymer and a surfactant, has been exploited for a wide variety of biotechnology applications throughout the years. While many applications for aqueous two‐phase systems fall within the realm of separation science, the ability to partition many different materials within these systems, coupled with recent advances in materials science and liquid handling, has allowed bioengineers to imagine new applications. This progress report provides an overview of the history and key properties of aqueous two‐phase systems to lend context to how these materials have progressed to modern applications such as cellular micropatterning and bioprinting, high‐throughput 3D tissue assembly, microscale biomolecular assay development, facilitation of cell separation and microcapsule production using microfluidic devices, and synthetic biology. Future directions and present limitations and design considerations of this adaptable and promising toolkit for biomolecule and cellular manipulation are further evaluated.

Advanced biomedical applications based on emerging 3D cell culturing platforms

“…Teixeira et al 109 and Pereira et al 110 compared and discussed novel ATPS-based pattern bioprinting techniques, emphasizing their potential for three major aspects of (i) cell analysis, (ii) cell assembly and cell co-culture, and (iii) bacterial co-culture system.…”

Complex emulsions for shape control based on mass transfer and phase separation

“…The interfacial tension between the PEGDA-rich phase (P-R) and the DEX-rich phase (D-R) is too small to be measured, and the range is between 0.0001 and 0.1 mN m À1 . 27,40 The interfacial tension (g P/C ) between the PEGDA with the continuous phase (C) decreases and the interfacial tension (g E/C ) between the ETPTA and the continuous phase increases while the PEGDA content increases. Besides, the interfacial tension (g D/C ) between the DEX aqueous solution and the continuous phase decreases with the increasing DEX content.…”

“…The aqueous two-phase system (ATPS) consists of two incompatible polymers. 27 When the concentration of a component exceeds a specific value, the solution will spontaneously form two phases. The ATPS can be used to prepare multiple emulsions, 28 microcapsules 29 or particles.…”

Precision cell delivery in biphasic polymer systems enhances growth of keratinocytes in culture and promotes their attachment on acellular dermal matrices

“…This approach uses an aqueous twophase systems (ATPSs) to confine the cells as they are seeded. ATPSs are composed of two incompatible polymers, or a polymer and a salt, that when dissolved together above threshold concentrations in an aqueous solvent, remain separated by a discrete interface (Albertsson, 1986;Teixeira et al, 2017). Recent work has demonstrated that cells and biomolecules can be confined within ATPSs to support the development of a variety of in vitro cell-based assays (Fang et al, 2012;Frampton, White, Abraham, & Takayama, 2013;Tavana et al, 2009;Tavana, Mosadegh, & Takayama, 2010).…”