1932

Abstract

Phase separation is a common occurrence in nature. Synthetic and natural polymers, salts, ionic liquids, surfactants, and biomacromolecules phase separate in water, resulting in an aqueous two-phase system (ATPS). This review discusses the properties, handling, and uses of ATPSs. These systems have been used for protein, nucleic acid, virus, and cell purification and have in recent years found new uses for small organics, polysaccharides, extracellular vesicles, and biopharmaceuticals. Analytical biochemistry applications such as quantifying protein–protein binding, probing for conformational changes, or monitoring enzyme activity have been performed with ATPSs. Not only are ATPSs biocompatible, they also retain their properties at the microscale, enabling miniaturization experiments such as droplet microfluidics, bacterial quorum sensing, multiplexed and point-of-care immunoassays, and cell patterning. ATPSs include coacervates and may find wider interest in the context of intracellular phase separation and origin of life. Recent advances in fundamental understanding and in commercial application are also considered.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-anchem-091520-101759
2021-07-27
2024-05-01
Loading full text...

Full text loading...

/deliver/fulltext/anchem/14/1/annurev-anchem-091520-101759.html?itemId=/content/journals/10.1146/annurev-anchem-091520-101759&mimeType=html&fmt=ahah

Literature Cited

  1. 1. 
    Albertsson P-Å 1985. History of aqueous polymer two-phase partition. Partitioning in Aqueous Two-Phase Systems: Theory, Methods, Uses, and Application to Biotechnology H Walter, DE Brooks, D Fisher 1–10 Orlando, FL: Academic
    [Google Scholar]
  2. 2. 
    Albertsson P-Å 1958. Partition of proteins in liquid polymer–polymer two-phase systems. Nature 182:709–11
    [Google Scholar]
  3. 3. 
    Albertsson P-Å 1986. Partition of Cell Particles and Macromolecules New York: Wiley
  4. 4. 
    Lif T, Frick G, Albertsson P-Å. 1961. Fractionation of nucleic acids in aqueous polymer two-phase systems. J. Mol. Biol. 3:727–40
    [Google Scholar]
  5. 5. 
    Baird GD, Albertsson P-Å, von Hofsten B 1961. Separation of bacteria by counter-current distribution. Nature 192:236–39
    [Google Scholar]
  6. 6. 
    Albertsson P-Å, Baird GD. 1962. Counter-current distribution of cells. Exp. Cell Res. 28:296–322
    [Google Scholar]
  7. 7. 
    Beijerinck MW. 1896. Über eine Eigentümlichkeit der löslichen Stärke. Zentralbl. Bakteriol. 2:697–99
    [Google Scholar]
  8. 8. 
    Dobry A, Boyer-Kawenoki F. 1947. Phase separation in polymer solution. J. Polym. Sci. 2:90–100
    [Google Scholar]
  9. 9. 
    Bungenberg de Jong HG, Kruyt HR 1929. Coacervation (partial miscibility in colloid systems). Proc. K. Ned. Akad. Wet. 32:849–56
    [Google Scholar]
  10. 10. 
    Zaslavsky BY, Bagirov TO, Borovskaya AA, Gulaeva ND, Miheeva LH et al. 1989. Structure of water as a key factor of phase separation in aqueous mixtures of two nonionic polymers. Polymer 30:2104–11
    [Google Scholar]
  11. 11. 
    Rogers BA, Rembert KB, Poyton MF, Okur HI, Kale AR et al. 2019. A stepwise mechanism for aqueous two-phase system formation in concentrated antibody solutions. PNAS 116:15784–91
    [Google Scholar]
  12. 12. 
    Zaslavsky BY. 1995. Aqueous Two-Phase Partitioning: Physical Chemistry and Bioanalytical Applications New York: M. Dekker
  13. 13. 
    Tavana H, Mosadegh B, Takayama S. 2010. Polymeric aqueous biphasic systems for non-contact cell printing on cells: engineering heterocellular embryonic stem cell niches. Adv. Mater. 22:2628–31
    [Google Scholar]
  14. 14. 
    Kojima T, Takayama S. 2013. Microscale determination of aqueous two phase system binodals by droplet dehydration in oil. Anal. Chem. 85:5213–18
    [Google Scholar]
  15. 15. 
    Kojima T, Lin CC, Takayama S, Fan SK. 2018. Determination of aqueous two-phase system binodals and tie-lines by electrowetting-on-dielectric droplet manipulation. ChemBioChem 20:270–75
    [Google Scholar]
  16. 16. 
    Shim J, Cristobal G, Link DR, Thorsen T, Jia Y et al. 2007. Control and measurement of the phase behavior of aqueous solutions using microfluidics. J. Am. Chem. Soc. 129:8825–35
    [Google Scholar]
  17. 17. 
    Atefi E, Fyffe D, Kaylan KB, Tavana H. 2016. Characterization of aqueous two-phase systems from volume and density measurements. J. Chem. Eng. Data 61:1531–39
    [Google Scholar]
  18. 18. 
    Liu Y, Lipowsky R, Dimova R. 2012. Concentration dependence of the interfacial tension for aqueous two-phase polymer solutions of dextran and polyethylene glycol. Langmuir 28:3831–39
    [Google Scholar]
  19. 19. 
    Ruthven M, Ko KR, Agarwal R, Frampton JP. 2017. Microscopic evaluation of aqueous two-phase system emulsion characteristics enables rapid determination of critical polymer concentrations for solution micropatterning. Analyst 142:1938–45
    [Google Scholar]
  20. 20. 
    Dewey DC, Strulson CA, Cacace DN, Bevilacqua PC, Keating CD. 2014. Bioreactor droplets from liposome-stabilized all-aqueous emulsions. Nat. Commun. 5:4670
    [Google Scholar]
  21. 21. 
    Song Y, Shimanovich U, Michaels TCT, Ma Q, Li J et al. 2016. Fabrication of fibrillosomes from droplets stabilized by protein nanofibrils at all-aqueous interfaces. Nat. Commun. 7:12934
    [Google Scholar]
  22. 22. 
    Song Y, Chan YK, Ma Q, Liu Z, Shum HC. 2015. All-aqueous electrosprayed emulsion for templated fabrication of cytocompatible microcapsules. ACS Appl. Mater. Interfaces 7:13925–33
    [Google Scholar]
  23. 23. 
    Lai D, Frampton JP, Sriram H, Takayama S. 2011. Rounded multi-level microchannels with orifices made in one exposure enable aqueous two-phase system droplet microfluidics. Lab Chip 11:3551–54
    [Google Scholar]
  24. 24. 
    Shum HC, Varnell J, Weitz DA. 2012. Microfluidic fabrication of water-in-water (w/w) jets and emulsions. Biomicrofluidics 6:012808
    [Google Scholar]
  25. 25. 
    Moon B-U, Jones SG, Hwang DK, Tsai SSH. 2015. Microfluidic generation of aqueous two-phase system (ATPS) droplets by controlled pulsating inlet pressures. Lab Chip 15:2437–44
    [Google Scholar]
  26. 26. 
    Moon B-U, Abbasi N, Jones SG, Hwang DK, Tsai SSH. 2016. Water-in-water droplets by passive microfluidic flow focusing. Anal. Chem. 88:3982–89
    [Google Scholar]
  27. 27. 
    Moon B-U, Hwang DK, Tsai SSH. 2016. Shrinking, growing, and bursting: microfluidic equilibrium control of water-in-water droplets. Lab Chip 16:2601–8
    [Google Scholar]
  28. 28. 
    Jeyhani M, Gnyawali V, Abbasi N, Hwang DK, Tsai SSH. 2019. Microneedle-assisted microfluidic flow focusing for versatile and high throughput water-in-water droplet generation. J. Colloid Interface Sci. 553:382–89
    [Google Scholar]
  29. 29. 
    Zhou C, Zhu P, Tian Y, Tang X, Shi R, Wang L. 2017. Microfluidic generation of aqueous two-phase-system (ATPS) droplets by oil-droplet choppers. Lab Chip 17:3310–17
    [Google Scholar]
  30. 30. 
    vanSwaay D, Dora Tang T-Y, Mann S, deMello A 2015. Microfluidic formation of membrane-free aqueous coacervate droplets in water. Angew. Chem. Int. Ed. 54:8398–401
    [Google Scholar]
  31. 31. 
    Song Y, Shum HC. 2012. Monodisperse w/w/w double emulsion induced by phase separation. Langmuir 28:12054–59
    [Google Scholar]
  32. 32. 
    Cui C, Zeng C, Wang C, Zhang L. 2017. Complex emulsions by extracting water from homogeneous solutions comprised of aqueous three-phase systems. Langmuir 33:12670–80
    [Google Scholar]
  33. 33. 
    Gutowski KE, Broker GA, Willauer HD, Huddleston JG, Swatloski RP et al. 2003. Controlling the aqueous miscibility of ionic liquids: aqueous biphasic systems of water-miscible ionic liquids and water-structuring salts for recycle, metathesis, and separations. J. Am. Chem. Soc. 125:6632–33
    [Google Scholar]
  34. 34. 
    Rogers RD, Willauer HD, ST Griffin, Huddleston JG. 1998. Partitioning of small organic molecules in aqueous biphasic systems. J. Chromatogr. B Biomed. Sci. Appl. 711:255–63
    [Google Scholar]
  35. 35. 
    Willauer HD, Huddleston JG, ST Griffin, Rogers RD. 1999. Partitioning of aromatic molecules in aqueous biphasic systems. Sep. Sci. Technol. 34:1069–90
    [Google Scholar]
  36. 36. 
    Ferreira AM, Coutinho JAP, Fernandes AM, Freire MG. 2014. Complete removal of textile dyes from aqueous media using ionic-liquid-based aqueous two-phase systems. Sep. Purif. Technol. 128:58–66
    [Google Scholar]
  37. 37. 
    Mageste AB, de Lemos LR, Ferreira GMD, da Silva MCH, da Silva LHM et al. 2009. Aqueous two-phase systems: an efficient, environmentally safe and economically viable method for purification of natural dye carmine. J. Chromatogr. A 1216:7623–29
    [Google Scholar]
  38. 38. 
    Nouri M, Shahriari S, Pazuki G. 2019. Increase of vanillin partitioning using aqueous two phase system with promising nanoparticles. Sci. Rep. 9:19665
    [Google Scholar]
  39. 39. 
    Abolghasembeyk T, Shahriari S, Salehifar M. 2017. Extraction of stevioside using aqueous two-phase systems formed by choline chloride and K3PO4. Food Bioprod. Process. 102:107–15
    [Google Scholar]
  40. 40. 
    Khripin CY, Fagan JA, Zheng M. 2013. Spontaneous partition of carbon nanotubes in polymer-modified aqueous phases. J. Am. Chem. Soc. 135:6822–25
    [Google Scholar]
  41. 41. 
    Fagan JA, Khripin CY, Silvera Batista CA, Simpson JR, Hároz EH et al. 2014. Isolation of specific small-diameter single-wall carbon nanotube species via aqueous two-phase extraction. Adv. Mater. 26:2800–4
    [Google Scholar]
  42. 42. 
    Rogers RD, Bond AH, Bauer CB. 1993. Metal ion separations in polyethylene glycol-based aqueous biphasic systems. Sep. Sci. Technol. 28:1091–126
    [Google Scholar]
  43. 43. 
    Bora MM, Borthakur S, Rao PC, Dutta NN. 2005. Aqueous two-phase partitioning of cephalosporin antibiotics: effect of solute chemical nature. Sep. Purif. Technol. 45:153–56
    [Google Scholar]
  44. 44. 
    Lee C-K, Sandler SI. 1990. Vancomycin partitioning in aqueous two-phase systems: effects of pH, salts, and an affinity ligand. Biotechnol. Bioeng. 35:408–16
    [Google Scholar]
  45. 45. 
    Mokhtarani B, Karimzadeh R, Amini MH, Manesh SD. 2008. Partitioning of ciprofloxacin in aqueous two-phase system of poly(ethylene glycol) and sodium sulphate. Biochem. Eng. J. 38:241–47
    [Google Scholar]
  46. 46. 
    Yang X, Zhang S, Yu W, Liu Z, Lei L et al. 2014. Ionic liquid-anionic surfactant based aqueous two-phase extraction for determination of antibiotics in honey by high-performance liquid chromatography. Talanta 124:1–6
    [Google Scholar]
  47. 47. 
    Gao S, Jin H, You J, Ding Y, Zhang N et al. 2011. Ionic liquid-based homogeneous liquid–liquid microextraction for the determination of antibiotics in milk by high-performance liquid chromatography. J. Chromatogr. A 1218:7254–63
    [Google Scholar]
  48. 48. 
    Shao M, Li N, Shi J, Jiang C, Lei L et al. 2013. Ionic liquid-based ultrasound-assisted aqueous two-phase extraction of the pyrethroid insecticides in tea drinks. Anal. Methods 5:2529–35
    [Google Scholar]
  49. 49. 
    Song G, Du Q. 2010. Isolation of a polysaccharide with anticancer activity from Auricularia polytricha using high-speed countercurrent chromatography with an aqueous two-phase system. J. Chromatogr. A 1217:5930–34
    [Google Scholar]
  50. 50. 
    Wang Y, Hu X, Han J, Ni L, Tang X et al. 2016. Integrated method of thermosensitive triblock copolymer–salt aqueous two phase extraction and dialysis membrane separation for purification of Lycium barbarum polysaccharide. Food Chem. 194:257–64
    [Google Scholar]
  51. 51. 
    Chandrakant P, Bisaria VS. 1998. Simultaneous bioconversion of cellulose and hemicellulose to ethanol. Crit. Rev. Biotechnol. 18:295–331
    [Google Scholar]
  52. 52. 
    Tjerneld F, Persson I, Albertsson P-Å, Hahn-Hägerdal B. 1985. Enzymatic hydrolysis of cellulose in aqueous two-phase systems. II. Semicontinuous conversion of a model substrate, Solka Floc BW 200. Biotechnol. Bioeng. 27:1044–50
    [Google Scholar]
  53. 53. 
    Hahn-Hägerdal B, Mattiasson B, Albertsson P-Å. 1981. Extractive bioconversion in aqueous two-phase systems. A model study on the conversion of cellulose to ethanol. Biotechnol. Lett. 3:53–58
    [Google Scholar]
  54. 54. 
    Taguchi F, Yamada K, Hasegawa K, Taki-Saito T, Hara K. 1996. Continuous hydrogen production by Clostridium sp. strain no. 2 from cellulose hydrolysate in an aqueous two-phase system. J. Ferment. Bioeng. 82:80–83
    [Google Scholar]
  55. 55. 
    Salabat A, Abnosi MH, Motahari A. 2008. Investigation of amino acid partitioning in aqueous two-phase systems containing polyethylene glycol and inorganic salts. J. Chem. Eng. Data 53:2018–21
    [Google Scholar]
  56. 56. 
    Shang QK, Li W, Jia Q, Li DQ. 2004. Partitioning behavior of amino acids in aqueous two-phase systems containing polyethylene glycol and phosphate buffer. Fluid Phase Equilibr 219:195–203
    [Google Scholar]
  57. 57. 
    Alves JGLF, Chumpitaz LDA, da Silva LHM, Franco TT, Meirelles AJA. 2000. Partitioning of whey proteins, bovine serum albumin and porcine insulin in aqueous two-phase systems. J. Chromatogr. B Biomed. Sci. Appl. 743:235–39
    [Google Scholar]
  58. 58. 
    Hart RA, Lester PM, Reifsnyder DH, Ogez JR, Builder SE. 1994. Large scale, in situ isolation of periplasmic IGF–I from E. coli. Nat. Biotechnol. 12:1113–17
    [Google Scholar]
  59. 59. 
    Pires MJ, Aires-Barros MR, Cabral JMS 1996. Liquid-liquid extraction of proteins with reversed micelles. Biotechnol. Prog. 12:290–301
    [Google Scholar]
  60. 60. 
    Cunha T, Aires-Barros R. 2002. Large-scale extraction of proteins. Mol. Biotechnol. 20:29–40
    [Google Scholar]
  61. 61. 
    Chames P, Van Regenmortel M, Weiss E, Baty D. 2009. Therapeutic antibodies: successes, limitations and hopes for the future. Br. J. Pharmacol. 157:220–33
    [Google Scholar]
  62. 62. 
    Grilo AL, Mantalaris A. 2019. The increasingly human and profitable monoclonal antibody market. Trends Biotechnol 37:9–16
    [Google Scholar]
  63. 63. 
    Azevedo AM, Gomes AG, Rosa PAJ, Ferreira IF, Pisco AMMO, Aires-Barros MR. 2009. Partitioning of human antibodies in polyethylene glycol–sodium citrate aqueous two-phase systems. Sep. Purif. Technol. 65:14–21
    [Google Scholar]
  64. 64. 
    Silva DFC, Azevedo AM, Fernandes P, Chu V, Conde JP, Aires-Barros MR. 2012. Design of a microfluidic platform for monoclonal antibody extraction using an aqueous two-phase system. J. Chromatogr. A 1249:1–7
    [Google Scholar]
  65. 65. 
    Gagnon P. 2012. Technology trends in antibody purification. J. Chromatogr. A 1221:57–70
    [Google Scholar]
  66. 66. 
    Lundberg S, Backman L. 1994. Protein-protein and protein-ligand interactions. Methods Enzymol. 228:241–54
    [Google Scholar]
  67. 67. 
    Patton JS, Albertsson P-Å, Erlanson C, Borgström B. 1978. Binding of porcine pancreatic lipase and colipase in the absence of substrate studied by two-phase partition and affinity chromatography. J. Biol. Chem. 253:4195–202
    [Google Scholar]
  68. 68. 
    Middaugh CR, Lawson EQ. 1980. Analysis of protein association by partitioning in aqueous two-phase polymer systems: applications to the tetramer-dimer dissociation of hemoglobin. Anal. Biochem. 105:364–68
    [Google Scholar]
  69. 69. 
    Zaslavsky A, Gulyaeva N, Chait A, Zaslavsky B. 2001. A new method for analysis of components in a mixture without preseparation: evaluation of the concentration ratio and protein–protein interaction. Anal. Biochem. 296:262–69
    [Google Scholar]
  70. 70. 
    Lundberg S, Lehto VP, Backman L. 1992. Characterization of calcium binding to spectrins. Biochemistry 31:5665–71
    [Google Scholar]
  71. 71. 
    Gray CW, Chamberlin MJ. 1971. Measurement of ligand-protein binding interactions in a biphasic aqueous polymer system. Anal. Biochem. 41:83–104
    [Google Scholar]
  72. 72. 
    Hansen JC, Gorski J. 1986. Conformational transitions of the estrogen receptor monomer. Effects of estrogens, antiestrogen, and temperature. J. Biol. Chem. 261:13990–96
    [Google Scholar]
  73. 73. 
    Fritsch M, Leary CM, Furlow JD, Ahrens H, Schuh TJ et al. 1992. A ligand-induced conformational change in the estrogen receptor is localized in the steroid binding domain. Biochemistry 31:5303–11
    [Google Scholar]
  74. 74. 
    Raymond FD, Moss DW, Fisher D. 1993. Phase partitioning detects differences between phospholipase-released forms of alkaline phosphatase—a GPI-linked protein. Biochim. Biophys. Acta Gen. Subj. 1156:117–22
    [Google Scholar]
  75. 75. 
    Zaslavsky A, Madeira P, Breydo L, Uversky VN, Chait A, Zaslavsky B. 2013. High throughput characterization of structural differences between closely related proteins in solution. Biochim. Biophys. Acta Proteins Proteom. 1834:583–92
    [Google Scholar]
  76. 76. 
    Berggren K, Wolf A, Asenjo JA, Andrews BA, Tjerneld F. 2002. The surface exposed amino acid residues of monomeric proteins determine the partitioning in aqueous two-phase systems. Biochim. Biophys. Acta Protein Struct. Mol. Enzymol. 1596:253–68
    [Google Scholar]
  77. 77. 
    Köhler K, Veide A, Enfors S-O. 1991. Partitioning of β-galactosidase fusion proteins in PEG/potassium phosphate aqueous two-phase systems. Enzyme Microb. Technol. 13:204–9
    [Google Scholar]
  78. 78. 
    Ferreira L, Fan X, Mikheeva LM, Madeira PP, Kurgan L et al. 2014. Structural features important for differences in protein partitioning in aqueous dextran–polyethylene glycol two-phase systems of different ionic compositions. Biochim. Biophys. Acta Proteins Proteom. 1844:694–704
    [Google Scholar]
  79. 79. 
    Breydo L, Mikheeva LM, Madeira PP, Zaslavsky BY, Uversky VN. 2013. Solvent interaction analysis of intrinsically disordered proteins in aqueous two-phase systems. Mol. BioSyst. 9:3068–79
    [Google Scholar]
  80. 80. 
    Albertsson P-Å, Sasakawa S, Walter H. 1970. Cross partition and isoelectric points of proteins. Nature 228:1329–30
    [Google Scholar]
  81. 81. 
    Walter H, Forciniti D. 1994. Cross-partitioning: determination of isoelectric point by partitioning. Methods Enzymol. 228:223–33
    [Google Scholar]
  82. 82. 
    Ericson I. 1974. Determination of the isoelectric point of rat liver mitochondria by cross-partition. Biochim. Biophys. Acta Biomembr. 356:100–7
    [Google Scholar]
  83. 83. 
    Kuznetsova I, Turoverov K, Uversky V. 2014. What macromolecular crowding can do to a protein. Int. J. Mol. Sci. 15:23090–140
    [Google Scholar]
  84. 84. 
    Lai D, Frampton JP, Tsuei M, Kao A, Takayama S. 2014. Label-free direct visual analysis of hydrolytic enzyme activity using aqueous two-phase system droplet phase transitions. Anal. Chem. 86:4052–57
    [Google Scholar]
  85. 85. 
    Kojima T, Takayama S. 2018. Membraneless compartmentalization facilitates enzymatic cascade reactions and reduces substrate inhibition. ACS Appl. Mater. Interfaces 10:32782–91
    [Google Scholar]
  86. 86. 
    Pavlovic M, Plucinski A, Zhang J, Antonietti M, Zeininger L, Schmidt BVKJ. 2020. Cascade kinetics in an enzyme-loaded aqueous two-phase system. Langmuir 36:1401–8
    [Google Scholar]
  87. 87. 
    Zhang Y, Cremer PS. 2010. Chemistry of Hofmeister anions and osmolytes. Annu. Rev. Phys. Chem. 61:63–83
    [Google Scholar]
  88. 88. 
    Wiendahl M, Oelmeier SA, Dismer F, Hubbuch J. 2012. High-throughput screening-based selection and scale-up of aqueous two-phase systems for pDNA purification. J. Sep. Sci. 35:3197–207
    [Google Scholar]
  89. 89. 
    Frerix A, Geilenkirchen P, Müller M, Kula M-R, Hubbuch J. 2007. Separation of genomic DNA, RNA, and open circular plasmid DNA from supercoiled plasmid DNA by combining denaturation, selective renaturation and aqueous two-phase extraction. Biotechnol. Bioeng. 96:57–66
    [Google Scholar]
  90. 90. 
    Ribeiro SC, Monteiro GA, Cabral JMS, Prazeres DMF. 2002. Isolation of plasmid DNA from cell lysates by aqueous two-phase systems. Biotechnol. Bioeng. 78:376–84
    [Google Scholar]
  91. 91. 
    Mashayekhi F, Meyer AS, Shiigi SA, Nguyen V, Kamei DT. 2009. Concentration of mammalian genomic DNA using two-phase aqueous micellar systems. Biotechnol. Bioeng. 102:1613–23
    [Google Scholar]
  92. 92. 
    Hahn T, Hardt S. 2011. Concentration and size separation of DNA samples at liquid–liquid interfaces. Anal. Chem. 83:5476–79
    [Google Scholar]
  93. 93. 
    Hardt S, Hartmann J, Zhao S, Bandopadhyay A. 2020. Electric-field-induced pattern formation in layers of DNA molecules at the interface between two immiscible liquids. Phys. Rev. Lett. 124:064501
    [Google Scholar]
  94. 94. 
    Matos T, Johansson H-O, Queiroz JA, Bulow L. 2014. Isolation of PCR DNA fragments using aqueous two-phase systems. Sep. Purif. Technol. 122:144–48
    [Google Scholar]
  95. 95. 
    Cheung SF, Yee MF, Le NK, Wu BM, Kamei DT. 2018. A one-pot, isothermal DNA sample preparation and amplification platform utilizing aqueous two-phase systems. Anal. Bioanal. Chem. 410:5255–63
    [Google Scholar]
  96. 96. 
    Jia TZ, Hentrich C, Szostak JW. 2014. Rapid RNA exchange in aqueous two-phase system and coacervate droplets. Orig. Life Evol. Biosph. 44:1–12
    [Google Scholar]
  97. 97. 
    Strulson CA, Molden RC, Keating CD, Bevilacqua PC. 2012. RNA catalysis through compartmentalization. Nat. Chem. 4:941–46
    [Google Scholar]
  98. 98. 
    Raposo G, Stoorvogel W. 2013. Extracellular vesicles: exosomes, microvesicles, and friends. J. Cell Biol. 200:373–83
    [Google Scholar]
  99. 99. 
    Shin H, Han C, Labuz JM, Kim J, Kim J et al. 2015. High-yield isolation of extracellular vesicles using aqueous two-phase system. Sci. Rep. 5:13103
    [Google Scholar]
  100. 100. 
    Park YH, Shin HW, Jung AR, Kwon OS, Choi Y-J et al. 2016. Prostate-specific extracellular vesicles as a novel biomarker in human prostate cancer. Sci. Rep. 6:30386
    [Google Scholar]
  101. 101. 
    Shin H, Park YH, Kim Y-G, Lee JY, Park J. 2018. Aqueous two-phase system to isolate extracellular vesicles from urine for prostate cancer diagnosis. PLOS ONE 13:e0194818
    [Google Scholar]
  102. 102. 
    Senior J, Delgado C, Fisher D, Tilcock C, Gregoriadis G. 1991. Influence of surface hydrophilicity of liposomes on their interaction with plasma protein and clearance from the circulation: studies with poly(ethylene glycol)-coated vesicles. Biochim. Biophys. Acta Biomembr. 1062:77–82
    [Google Scholar]
  103. 103. 
    Zhang X, Zong W, Bi H, Zhao K, Fuhs T et al. 2018. Hierarchical drug release of pH-sensitive liposomes encapsulating aqueous two phase system. Eur. J. Pharm. Biopharm. 127:177–82
    [Google Scholar]
  104. 104. 
    Beijerinck MW. 1898. Über ein Contagium vivum fluidum als Ursache der Fleckenkrankheit der Tabaksblätter. Verh. K. Akad. Wet. Amst. 6:3–21
    [Google Scholar]
  105. 105. 
    Hammar L. 2000. Concentration and purification of viruses. Aqueous Two-Phase Systems: Methods and Protocols R Hatti-Kaul 143–58 Totowa, NJ: Humana Press
    [Google Scholar]
  106. 106. 
    Yamamoto KR, Alberts BM, Benzinger R, Lawhorne L, Treiber G. 1970. Rapid bacteriophage sedimentation in the presence of polyethylene glycol and its application to large-scale virus purification. Virology 40:734–44
    [Google Scholar]
  107. 107. 
    Walter H, Edgell MH, Hutchison CA. 1970. Separation of bacteriophage ΦX174 mutants by countercurrent distribution in a two-polymer aqueous phase system. Biochim. Biophys. Acta Nucl. Acids Protein Synth. 204:248–51
    [Google Scholar]
  108. 108. 
    Philipson L, Killander J, Albertsson P-Å. 1966. Interaction between poliovirus and immunoglobulins: I. Detection of virus antibodies by partition in aqueous polymer phase systems. Virology 28:22–34
    [Google Scholar]
  109. 109. 
    Philipson L. 1966. Interaction between poliovirus and immunoglobulins: II. Basic aspects of virus-antibody interaction. Virology 28:35–46
    [Google Scholar]
  110. 110. 
    Yaguchi T, Dwidar M, Byun CK, Leung B, Lee S et al. 2012. Aqueous two-phase system-derived biofilms for bacterial interaction studies. Biomacromolecules 13:2655–61
    [Google Scholar]
  111. 111. 
    Dwidar M, Leung BM, Yaguchi T, Takayama S, Mitchell RJ. 2013. Patterning bacterial communities on epithelial cells. PLOS ONE 8:e67165
    [Google Scholar]
  112. 112. 
    Byun CK, Hwang H, Choi WS, Yaguchi T, Park J et al. 2013. Productive chemical interaction between a bacterial microcolony couple is enhanced by periodic relocation. J. Am. Chem. Soc. 135:2242–47
    [Google Scholar]
  113. 113. 
    Stocks SJ, Brooks DE. 1988. Development of a general ligand for immunoaffinity partitioning in two phase aqueous polymer systems. Anal. Biochem. 173:86–92
    [Google Scholar]
  114. 114. 
    Walter H, Webber TJ, Michalski JP, McCombs CC, Moncla BJ et al. 1979. Subfractionation of human peripheral blood lymphocytes on the basis of their surface properties by partitioning in two-polymer aqueous phase systems. J. Immunol. 123:1687–95
    [Google Scholar]
  115. 115. 
    Walter H, Krob EJ, Brooks DE. 1976. Membrane surface properties other than charge involved in cell separation by partition in polymer, aqueous two-phase systems. Biochemistry 15:2959–64
    [Google Scholar]
  116. 116. 
    Kumar AA, Patton MR, Hennek JW, Lee SYR, D'Alesio-Spina G et al. 2014. Density-based separation in multiphase systems provides a simple method to identify sickle cell disease. PNAS 111:14864–69
    [Google Scholar]
  117. 117. 
    Yamada M, Kasim V, Nakashima M, Edahiro Ji, Seki M. 2004. Continuous cell partitioning using an aqueous two-phase flow system in microfluidic devices. Biotechnol. Bioeng. 88:489–94
    [Google Scholar]
  118. 118. 
    SooHoo JR, Walker GM. 2009. Microfluidic aqueous two phase system for leukocyte concentration from whole blood. Biomed. Microdevices 11:323–29
    [Google Scholar]
  119. 119. 
    Mastiani M, Firoozi N, Petrozzi N, Seo S, Kim M. 2019. Polymer-salt aqueous two-phase system (ATPS) micro-droplets for cell encapsulation. Sci. Rep. 9:15561
    [Google Scholar]
  120. 120. 
    Frampton JP, White JB, Simon AB, Tsuei M, Paczesny S, Takayama S. 2014. Aqueous two-phase system patterning of detection antibody solutions for cross-reaction-free multiplex ELISA. Sci. Rep. 4:4878
    [Google Scholar]
  121. 121. 
    Eiden L, Yamanishi C, Takayama S, Dishinger JF. 2016. Aqueous two-phase system rehydration of antibody–polymer microarrays enables convenient compartmentalized multiplex immunoassays. Anal. Chem. 88:11328–34
    [Google Scholar]
  122. 122. 
    Tongdee M, Yamanishi C, Maeda M, Kojima T, Dishinger J et al. 2020. One-incubation one-hour multiplex ELISA enabled by aqueous two-phase systems. Analyst 145:3517–27
    [Google Scholar]
  123. 123. 
    Simon AB, Frampton JP, Huang N-T, Kurabayashi K, Paczesny S, Takayama S. 2014. Aqueous two-phase systems enable multiplexing of homogeneous immunoassays. Technology 2:176–84
    [Google Scholar]
  124. 124. 
    Jue E, Yamanishi CD, Chiu RYT, Wu BM, Kamei DT. 2014. Using an aqueous two-phase polymer-salt system to rapidly concentrate viruses for improving the detection limit of the lateral-flow immunoassay. Biotechnol. Bioeng. 111:2499–507
    [Google Scholar]
  125. 125. 
    Mashayekhi F, Le AM, Nafisi PM, Wu BM, Kamei DT. 2012. Enhancing the lateral-flow immunoassay for detection of proteins using an aqueous two-phase micellar system. Anal. Bioanal. Chem. 404:2057–66
    [Google Scholar]
  126. 126. 
    Chiu RYT, Thach AV, Wu CM, Wu BM, Kamei DT. 2015. An aqueous two-phase system for the concentration and extraction of proteins from the interface for detection using the lateral-flow immunoassay. PLOS ONE 10:e0142654
    [Google Scholar]
  127. 127. 
    Chiu RYT, Jue E, Yip AT, Berg AR, Wang SJ et al. 2014. Simultaneous concentration and detection of biomarkers on paper. Lab Chip 14:3021–28
    [Google Scholar]
  128. 128. 
    Roddie C, O'Reilly M, Pinto JDA, Vispute K, Lowdell M 2019. Manufacturing chimeric antigen receptor T cells: issues and challenges. Cytotherapy 21:327–40
    [Google Scholar]
  129. 129. 
    Tavana H, Jovic A, Mosadegh B, Lee QY, Liu X et al. 2009. Nanolitre liquid patterning in aqueous environments for spatially defined reagent delivery to mammalian cells. Nat. Mater. 8:736–41
    [Google Scholar]
  130. 130. 
    Hui SW, Stoicheva N, Zhao YL. 1996. High-efficiency loading, transfection, and fusion of cells by electroporation in two-phase polymer systems. Biophys. J. 71:1123–30
    [Google Scholar]
  131. 131. 
    Fan Z, Chen D, Deng CX 2013. Improving ultrasound gene transfection efficiency by controlling ultrasound excitation of microbubbles. J. Control. Release 170:401–13
    [Google Scholar]
  132. 132. 
    Frampton JP, Tsuei M, White JB, Abraham AT, Takayama S. 2015. Aqueous two-phase system-mediated antibody micropatterning enables multiplexed immunostaining of cell monolayers and tissues. Biotechnol. J. 10:121–25
    [Google Scholar]
  133. 133. 
    Kojima T, Takayama S. 2013. Patchy surfaces stabilize dextran–polyethylene glycol aqueous two-phase system liquid patterns. Langmuir 29:5508–14
    [Google Scholar]
  134. 134. 
    Joshi R, Fuller B, Mosadegh B, Tavana H. 2018. Stem cell colony interspacing effect on differentiation to neural cells. J. Tissue Eng. Regen. Med. 12:2041–54
    [Google Scholar]
  135. 135. 
    Frampton JP, Leung BM, Bingham EL, Lesher-Perez SC, Wang JD et al. 2015. Rapid self-assembly of macroscale tissue constructs at biphasic aqueous interfaces. Adv. Funct. Mater. 25:1694–99
    [Google Scholar]
  136. 136. 
    Frampton JP, Lai D, Sriram H, Takayama S. 2011. Precisely targeted delivery of cells and biomolecules within microchannels using aqueous two-phase systems. Biomed. Microdevices 13:1043–51
    [Google Scholar]
  137. 137. 
    Fang Y, Frampton JP, Raghavan S, Sabahi-Kaviani R, Luker G et al. 2012. Rapid generation of multiplexed cell cocultures using acoustic droplet ejection followed by aqueous two-phase exclusion patterning. Tissue Eng. C Methods 18:647–57
    [Google Scholar]
  138. 138. 
    Tavana H, Kaylan K, Bersano-Begey T, Luker KE, Luker GD, Takayama S. 2011. Rehydration of polymeric, aqueous, biphasic system facilitates high throughput cell exclusion patterning for cell migration studies. Adv. Funct. Mater. 21:2920–26
    [Google Scholar]
  139. 139. 
    Han C, Takayama S, Park J. 2015. Formation and manipulation of cell spheroids using a density adjusted PEG/DEX aqueous two phase system. Sci. Rep. 5:11891
    [Google Scholar]
  140. 140. 
    Moraes C, Simon AB, Putnam AJ, Takayama S. 2013. Aqueous two-phase printing of cell-containing contractile collagen microgels. Biomaterials 34:9623–31
    [Google Scholar]
  141. 141. 
    Singh S, Tavana H. 2018. Collagen partition in polymeric aqueous two-phase systems for tissue engineering. Front. Chem. 6:379
    [Google Scholar]
  142. 142. 
    Yamanishi C, Parigoris E, Takayama S. 2020. Kinetic analysis of label-free microscale collagen gel contraction using machine learning-aided image analysis. Front. Bioeng. Biotechnol. https://doi.org/10.3389/fbioe.2020.582602
    [Crossref] [Google Scholar]
  143. 143. 
    Oparin AI. 1953. The Origin of Life New York: Dover
  144. 144. 
    Long MS, Jones CD, Helfrich MR, Mangeney-Slavin LK, Keating CD 2005. Dynamic microcompartmentation in synthetic cells. PNAS 102:5920–25
    [Google Scholar]
  145. 145. 
    Long MS, Cans A-S, Keating CD. 2008. Budding and asymmetric protein microcompartmentation in giant vesicles containing two aqueous phases. J. Am. Chem. Soc. 130:756–62
    [Google Scholar]
  146. 146. 
    Koga S, Williams DS, Perriman AW, Mann S. 2011. Peptide–nucleotide microdroplets as a step towards a membrane-free protocell model. Nat. Chem. 3:720–24
    [Google Scholar]
  147. 147. 
    Drobot B, Iglesias-Artola JM, Le Vay K, Mayr V, Kar M et al. 2018. Compartmentalised RNA catalysis in membrane-free coacervate protocells. Nat. Commun. 9:3643
    [Google Scholar]
  148. 148. 
    Tang T-YD, van Swaay D, de Mello A, Ross Anderson JL, Mann S 2015. In vitro gene expression within membrane-free coacervate protocells. Chem. Commun. 51:11429–32
    [Google Scholar]
  149. 149. 
    Torre P, Keating CD, Mansy SS. 2014. Multiphase water-in-oil emulsion droplets for cell-free transcription–translation. Langmuir 30:5695–99
    [Google Scholar]
  150. 150. 
    Nott TJ, Craggs TD, Baldwin AJ. 2016. Membraneless organelles can melt nucleic acid duplexes and act as biomolecular filters. Nat. Chem. 8:569–75
    [Google Scholar]
/content/journals/10.1146/annurev-anchem-091520-101759
Loading
/content/journals/10.1146/annurev-anchem-091520-101759
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error