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Aqueous two-phase systems for biomolecule separation

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Book cover Bioseparation

Part of the book series: Advances in Biochemical Engineering/Biotechnology ((ABE,volume 47))

Abstract

Over the past-thirty years, aqueous polymer two-phase technology has evolved, both experimentally and theoretically, into a separation science with many useful applications in biomolecule purification and bioconversion. This paper summarizes the developments in the applications of aqueous two-phase systems to biotechnology. The main topics to be considered are the phase diagram and its characteristics, fundamentals of biomolecule partition, large-scale and multi-stage aqueous two-phase biomolecule purification, and extractive bioconversions. The first topic involves a discussion of the thermodynamics of aqueous polymer two-phase formation and how it is influenced by such factors as polymer molecular weight and concentration, temperature, and salt type and concentration. Next, the theoretical and experimental aspects of biomolecule partition in aqueous two-phase systems will be discussed in light of the factors which influence biomolecule partition: polymer concentration and molecular weight; temperature; salt type and concentration; the addition of charged, hydrophobic and affinity derivatives. Having reviewed the fundamentals of phase diagram formation and biomolecule partition, the next two topics are applications of aqueous two-phase technology. The first set of applications involve the large-scale extraction of proteins using one to three equilibrium stages and multi-stage purifications using countercurrent distribution, liquid-liquid partition chromatography and continuous countercurrent chromatography. The second application, and very promising area for future aqueous two-phase technology, is the extractive bioconversion which permits the simultaneous production and purification of a biomolecule.

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Abbreviations

A:

\(\begin{gathered}m_3 (\alpha _1 (\tfrac{1}{{m_1 }} - 1 + \chi _{03} - \chi _{13} + \chi _{01} ) \hfill \\+ \alpha _2 \phi (\tfrac{1}{{m_2 }} - 1 + \chi _{03} - \chi _{23} + \chi _{02} )) \hfill \\\end{gathered}\)

A1 :

\(m_1 (\alpha _1 (\tfrac{1}{{m_1 }} - 1 + 2\chi _{01} ) + \alpha _2 \phi (\tfrac{1}{{m_2 }} - 1 + \chi _{01} + \chi _{02} - \chi _{12} ))\)

A2 :

\(m_2 (\alpha _2 \phi (\tfrac{1}{{m_2 }} - 1 + 2\chi _{02} ) + \alpha _1 (\tfrac{1}{{m_1 }} - 1 + \chi _{02} + \chi _{01} - \chi _{12} ))\)

A* :

\(A + \frac{{z_b Fg}}{{RT}}\)

b:

m3(χ02α 22 φ2-φ01α 21 )

b* :

\(b + \frac{{z_b Fh}}{{RT}}\)

ci :

concentration of species i, % (w/w)

d:

density of a phase, g ml−1

F:

Faraday constant

g:

regression constant in Eq. (19)

h:

regression constant in Eq. (19)

Ka :

binding constant for protein-ligand complex

Ki :

w″i/w′i, partition coefficient for species i

KL :

partition coefficient of biomolecule in the presence of polymer bound ligand

KL,o :

partition coefficient of biomolecule in the absence of polymer bound ligand

K3,o :

partition coefficient of biomolecule when δψ=0 or zb=0

K+ :

partition coefficient of a cation

K− :

partition coefficient of an anion

k:

Boltzman's constant

L:

ligand concentration, %(w/w)

mi :

molar volume ratio of species i to that of water

M:

molarity, mol l−1

n:

number of independent binding sites on a protein

Ps :

C is /c Dexs , distribution coefficient

R:

gas law constant, (K-atm)/(mol-K)

T:

absolute temperature, K

V:

volume fraction of a phase, %(v/v)

W:

weight fraction of a phase, %(w/w)

wj :

weight fraction of species i, %(w/w)

Y3 :

biomolecule yield, %

z:

lattice coordinate number

zb :

charge of a biomolecule

z+ :

charge of a cation

z− :

charge of an anion

αi :

proportionality factor between volume and weight fraction for species i

Î’s :

regression constant in Eq. (8)

γ* :

constant in Eq. (16)

δGm :

Gibbs free energy of mixing, J mol−1

δHm :

enthalpy change on mixing, J mol−1

δSm :

entropy change on mixing, J mol-K−1

δwij :

energy change for the formation of a contact between species i and j, J

δψ:

electrostatic potential difference between the phases, Volts

δ* :

constant in Eq. (16)

ε* :

constant in Eq. (17)

Φ:

W″2−W′2/W″1−W′1

χij :

Flory-Huggins interaction parameter between species i and j

ψ:

electrostatic potential, Volts

″:

top phase

′:

bottom phase

DEX:

dextran-rich phase

i:

i-rich phase

1:

PEG in the PEG/dextran/water and PEG/potassium phosphate/water systems; dextran in the ficoll/dextran/water system

2:

dextran in the PEG/dextran/water system; potassium phosphate in the PEG/potassium phosphate/water system; ficoll in the ficoll/dextran/ water system

3:

biomolecule

i:

component i

s:

salt

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  1. Bioprocessing Institute, Department of Chemical Engineering, Lehigh University, 18015, Bethlehem, PA, USA

    A. D. Diamond & J. T. Hsu

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Diamond, A.D., Hsu, J.T. (1992). Aqueous two-phase systems for biomolecule separation. In: Tsao, G.T. (eds) Bioseparation. Advances in Biochemical Engineering/Biotechnology, vol 47. Springer, Berlin, Heidelberg. https://doi.org/10.1007/BFb0046198

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