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All-aqueous emulsions as miniaturized chemicalreactors in the food and bioprocess technologyAshkan Madadlou1, Vittorio Saggiomo2, Karin Schroen3,4 andVincenzo Fogliano1
Available online at www.sciencedirect.com
ScienceDirect
All-aqueous emulsions are conventionally formed at bulk
scale by mild shaking of aqueous two-phase systems. They
can be used to carry out reactions both in droplets
(compartmentalized) and on droplet surfaces in conditions
free of synthetic surfactants and organic solvents. The use of
all-aqueous emulsions for extractive bioconversion is a
routine application; however, these emulsions hold many
more promises. A renowned, rapidly evolving application is
bio-microgel synthesis through biopolymer crosslinking within
the emulsion internal phase. When polyelectrolyte
crosslinking is achieved at the interface rather than in
droplets, microcapsules can be formed, and when in situ
colloidal particle generation at the droplet surface is obtained,
colloidosomes are produced. The use of microfluidics to
control the formation of all-aqueous emulsions offers many
advantages in reactions monitoring and partitioning of
reactants.
Addresses1 Food Quality and Design Group, Department of Agrotechnology and
Food Sciences, Wageningen University and Research, Wageningen, P.
O. Box 17, 6700 AA Wageningen, The Netherlands
2 Laboratory of BioNanoTechnology, Wageningen University and
Research, P.O. Box 8038, 6700 EK Wageningen, The Netherlands3 Food Process Engineering Group, Department of Agrotechnology and
Food Sciences, Wageningen University and Research, Bornse
Weilanden 9, 6708 WG Wageningen, The Netherlands4Membrane Processes for Food, University of Twente, Drienerlolaan 5,
7522 NB Enschede, The Netherlands
Corresponding author: Fogliano, Vincenzo (vincenzo.fogliano@wur.nl)
Current Opinion in Food Science 2020, 33:165–172
This review comes from a themed issue on Food physics and
materials science
Edited by Maria Teresa Pedrosa Silva Clerici
For a complete overview see the Issue and the Editorial
Available online 5th July 2020
https://doi.org/10.1016/j.cofs.2020.06.005
2214-7993/ã 2020 The Authors. Published by Elsevier Ltd. This is an
open access article under the CC BY license (http://creativecommons.
org/licenses/by/4.0/).
Conventional emulsion microreactorsMiniaturized chemical reactors provide inimitable advan-
tages over running reactions at large scales, including
reduced use of chemicals and solvents, increased safety,
enhanced reaction rates, and the ability to screen and vary
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reaction conditions pretty much at will [1]. Various sorts of
microreactors such as liquid marbles and liquid biphasic
systems (LBSs, liquid-liquid systems) have been devel-
oped and exploited. Oil-water LBSs can be effectively
miniaturized by standard emulsification (bulk scale), and
within fluidic microchannels which allows unprecedented
control over droplet size. Running reactions in oil-water
LBS microreactors enables combining immiscible part-
ners of a reaction at the oil-water interface [2,3]. Alterna-
tively, the interface might serve as the purging site for
removal of specific compounds produced in either of the
emulsion phases into the opposite phase. For example,
oil-in-water emulsion droplets stabilized by lipase-loaded
mesoporous carbon nanospheres functioned as a micro-
reactor with reactants in the oil phase for enzymatic
transesterification of phytosterols and concurrent removal
of the produced H2O across the oil-water interface into
the aqueous phase [4]. Likewise, the aqueous phase of
water-in-oil emulsions can be used as compartmentalized
microreactors, for instance, for synthesis of protein [5],
peptide [6], and starch [7] microgel particles by enzy-
matic, chemical and thermal crosslinking. Although in
limited cases, for example, during hydrolysis of vegetable
oils, surface active products can be formed, synthetic
surfactants are very commonly required to decrease the
interfacial tension at the oil-water interface, and thus
facilitate emulsification. However, these surfactants cause
high carbon footprints during their production, and are
detrimental to human health and the environment. To
mitigate this, W/O Pickering emulsions that are free of
surfactants [2] have been used; however Pickering particles
are not necessarily intrinsically safe, and they may be
cumbersome to prepare. Besides, tedious purification steps
that involve the use of organic solvents that subsequently
have to be fully removed are needed. Moreover, oil oxida-
tion of may occur during production, potentially jeopardiz-
ing quality and safety of the final product.
All-aqueous emulsions: a green alternativeAll-aqueous emulsions are genuine alternatives to water-oil
emulsions and can be used for chemical reactions without
the need of synthetic surfactants and organic phase. These
emulsions are aqueous two-phase systems (ATPSs) and
comprise two immiscible aqueous solutions. The interfa-
cial tension between the immiscible aqueous phases is
several orders of magnitude lower than at typical oil-water
interfaces [8]. This allows formation of microdroplets by
mild mechanical forces, that is, shaking/stirring at bulk
Current Opinion in Food Science 2020, 33:165–172
166 Food physics and materials science
scale and perturbation of water-water (W-W) jets in micro-
fluidic channels, yielding all-aqueous emulsions [9�]. The
thickness of the W-W interface typically exceeds the
effective length of the constituent polymers and the ultra-
low interfacial tension basically takesaway thedriving force
for low molecular weight surfactants to adsorb at the inter-
face. Comparable to the oil-water interface, particles can
accumulate at the W-W interface, which hinders spinodal
decomposition and macroscopic phase separation of all-
aqueous emulsions [10].
Components that can form all-aqueous emulsions are
pairs of i) noncharged polymers for example, polyethyl-
ene glycol (PEG)-dextran (Dex), ii) a noncharged poly-
mer (e.g. PEG) with a salt (e.g. K2HPO4) or with a
charged polymer (e.g. chitosan), or iii) two co-charged
polymers [11]. Dex is listed generally recognized as safe
(GRAS) and PEG is a biocompatible polymer approved
for human oral applications [12]. Within the food sector
good quality ATPS were obtained using whey proteins
which were hydrophobized through a food-grade acetyla-
tion procedure and heat treatment [13], resulting in
immiscibility of the negatively charged proteins with
Na-alginate [14]. Based on interfacial rheology assess-
ments, it was found that the most hydrophobic particles
accumulated at the W-W interface [15], and other parti-
cles remained in the protein phase.
Partitioning in all-aqueous emulsionsAll-aqueous emulsions segregate guest molecules (such as
DNA, proteins andenzymes) through partitioning between
the two aqueous phases, as well as at the interface. Efficient
partitioning of reactants between the two (inner and exte-
rior) phases of emulsions is a prerequisite for accomplishing
chemical reactions either in the inner phase or at the W-W
interface. Partitioning in the inner phase enables running
compartmentalized reactions, whereas partitioning at the
interface allows to carry out on-droplet reactions. Within
Table 1
Examples of the bio-compounds segregated using ATPSs
ATPS pair Segregated compound
UCON‒KH2PO4 Laccase
PEG‒Na2SO4 Laccase
PEG‒Na3PO4 Recombinant chymosin
PEG‒K3PO4 Gallic acid, Epicatechin, Chlorogenic
PEG113-b-PNIPAM149‒Salt Bromelain
PEG‒Dex Immunoglobulin monomers
Immunoglobulin aggregates
Ethanol‒K2HPO4 Vanillin
Ascorbic acid
Kp: Partition coefficient.
RE: Recovery extent (%).
UCON 50-HB-5100: A random copolymer of ethylene oxide and propylene
PEG113-b-PNIPAM149: Block copolymer of PEG (mean degree of polymeriz
LCST 28.6�C.
Current Opinion in Food Science 2020, 33:165–172
the most common pair, that is, PEG-Dex, PEG forms the
less polar phase [11] and it can be removed by gel perme-
ation chromatography [16] once the reaction is accom-
plished. The utilization of thermo-separating polymers
such as UCON (a copolymer of ethylene oxide and pro-
pyleneoxide) facilitatespolymer recoverybyheatingabove
its lower critical solution temperature (LCST) [17]. Com-
parably, certain food-grade polymers, for example, hydro-
xypropyl cellulose have an LCST of 43ᵒC at 0 M NaCl [18].
A plethora of enzyme and other biomolecules have been
segregated/compartmentalized using ATPSs. In Table 1,
examples of ATPSs with the segregated compounds are
provided. Recovery of proteolytic enzymes from micro-
bial fermentations into the PEG-rich phases of PEG/
phosphate and PEG/Citrate is also known [19]. The
protease partitioning efficacy is dependent on PEG
molecular weight, pH, and NaCl concentration [20].
PEG retains a higher enzymatic activity of the recovered
recombinant chymosin, compared to other affinity phases
for example, poly(ethylene glycol)-block-poly-(propyl-
ene glycol)-block-poly-(ethylene glycol) [21].
Compartmentalized reactionsExtractive bioconversion using all-aqueous emulsion
reactors
All-aqueous emulsions are widely used for extractive
bioconversion. To this end, a pair of phase-forming poly-
mers (without being stabilized by Pickering particles) are
mildly stirred typically for hours to days, and consecu-
tively separated [22]. Extractive bioconversion relies on
preferential partitioning of the biocatalyst (microbial
cells, enzymes) and its substrate in one of the aqueous
phases (usually droplets) and recovery of the bioconver-
sion product(s) into the other phase. Product partitioning
away from the biocatalyst can for example, lift product
inhibition, and drive the reaction to higher conversion
rates, as well as prevent cell toxicity [11,23��].
Host phase Kp; RE Ref.
KH2PO4 >3 [17]
Na2SO4 �100% [51]
PEG 4�6 [21]
acid PEG 1.01�4.6,
>75%
[52]
PEG113-b-PNIPAM149 �95% [53]
Either PEG or Dex ‒[16]Interface �100%
Ethanol �96%[54]K2HPO4 92‒2%
oxide.
ation: 113, Mn = 5.0 KDa) and poly (N-isopropylacrylamide) (PNIPAM);
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All-aqueous emulsion microreactors Madadlou et al. 167
Product partitioning into the recovering phase can be
improved by adding-specific ligands coupled to a phase-
forming polymer and engineering of the product, for
example via tagging the recombinant proteins [22]. Fer-
mentative production of pullulan in PEG-salt and PEG-
Dex ATPSs and recovery of pullulan into the PEG phase
[24] is a recent illustrative example of what all-aqueous
emulsions can deliver to extractive bioconversion.
In the food sector, ATPSs have been used for the post-
hydrolysis fractionation of food proteins. Recovery of
bioactive peptides having inhibitory effects on angioten-
sin-converting enzyme from tryptic hydrolysates of casein
was a pioneering case study; the peptides had a substan-
tially greater affinity (yield � 99%) towards the polymer-
rich phase of PEG/potassium phosphate ATPSs [25]. As a
recent instance, recovery of antioxidant peptides from
hydrolysates of whey proteins was achieved using ATPSs
of poly(ethylene glycol-ran-propylene glycol) monobutyl
ether/phosphate [26] and 1-propanol/NaH2PO4 [27].
We expect that ATPS emulsions can be additionally
exploited for the in situ generation of bioactive peptides
from food proteins and concurrent fractionation of the
peptides within either of the aqueous phases. This appli-
cation would rely on preferential partitioning of food
proteins and proteolytic enzymes within the inner com-
partment and extraction of the released peptides into the
exterior phase. Since the phase behavior can be tuned
Figure 1
PEG-CaCl2bath
PEG inlet
Outlet
Glass slide PDMS
DEX-alginateinlet Intermed
Schematic illustration of the setup used for formation of pollen-like alginate
inside the outlet tubing, and flow into a bath of PEG and CaCl2 for 30 s. Th
droplets proceed over time. Scale bar indicates 50 mm [29�].
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extensively, we expect that several possibilities for indus-
trial use of food-grade all-aqueous emulsions for proteol-
ysis reactions are within reach.
Fabrication of microgels using all-aqueous emulsions
The utilization of all-aqueous emulsions for bioparticle
(microgel) synthesis via solidification of the inner phase
is appealing from the perspectives of consumer and
environmental concerns. Synthesis of hydrogel micro-
particles through crosslinking of methacrylated dextran
(mDex) in mDex-in-PEG or dimethacrylated PEG
(m2PEG) in m2PEG-in-Dex (or m2PEG-in-magnesium
sulfate) emulsions were pioneering instances. Similarly,
gelatin microparticles were made by emulsification of a
gelatin solution in an aqueous solution of poly(vinylpyr-
rolidone) or dextran at high temperature [28] and subse-
quent cooling to ambient conditions. In addition to
solidification of the polymer which constitutes the inter-
nal phase, all-aqueous emulsions have been used as
scaffolds for bioparticle synthesis via crosslinking of a
guest ingredient in the dispersed phase. Recently, algi-
nate which mainly partitioned into the inner phase of
Dex-in-PEG emulsions was crosslinked with CaCl2 to
yield pollen-like microparticles (i.e. non-spherical vehi-
cles with protruding spikes). For this, a flow-focusing
microfluidic device (Figure 1) was employed to make
alginate-Dex droplets (50�80 mm) in the PEG phase,
followed by polymerization in a bath containing PEG
and CaCl2. In the bath, a sudden change in concentration
DEX-alginate
PEG
PEG-CaCl2
iate PEGA polymerized DEX particle, 40minutes after reaching the bath
Current Opinion in Food Science
microparticles. The alginate-containing Dex droplets are generated
e polymerization and growth of spikes across the DEX–alginate
Current Opinion in Food Science 2020, 33:165–172
168 Food physics and materials science
across the Dex-PEG interface occurs, resulting in for-
mation of alginate spikes across the droplet surface, of
which the length could be tuned by the PEG concen-
tration [29�].
Comparable to ionic microgelation, which takes place
between oppositely charged ions and biopolymers, elec-
trostatic attraction between two oppositely charged bio-
polymers can be exploited for synthesis of microgel
particles. Bicomponent protein microparticles consisting
of hemoglobin (positively charged) and bovine serum
albumin (BSA, negatively charged) or immunoglobulin
G (negatively charged) were prepared in the droplet
phase of Dex-in-PEG emulsions at pH 7.0 (Figure 2a).
Before emulsification, the anionic and cationic proteins
were placed in the Dex and PEG phases, respectively.
Once the emulsion droplets were fabricated via a glass
capillary-based microfluidic electrospray strategy, BSA
remained in the Dex phase (partitioning coefficient
was 0.96 in Dex and 0.04 in PEG), whereas, hemoglobin
migrated from the PEG phase into the Dex phase (parti-
tioning coefficient in Dex was 0.7). Gradual changes took
place with the Dex droplets becoming darker because of
the electrostatic attractive, as well as hydrophobic inter-
actions between the proteins [30]. Comparable methods
can be used for preparation of bicomponent food protein,
and protein-polysaccharide (positively charged proteins
and negatively charged polysaccharides) composite
microgels. Moreover, bio-microgels consisting of a
charged bioactive cargo of interest can be encapsulated.
The PEG phase needs to be removed for harvesting the
bioparticles.
Interfacial reactions using all-aqueousemulsionsCapsule formation
Besides microgel formation, electrostatic attraction
between charged species can be used for solidification
of the interface, resulting in formation of microcapsules (i.
e. the internal phase remains liquid). The first report [31�]included the self-assembly of oppositely charged poly-
electrolytes, namely poly(allylamine hydrochloride)
(PAH) and poly(sodium-4-styrenesulfonate) (PSS) at
the W-W interface of all-aqueous PEG-Dex emulsions
(Figure 2b). Formation of microcapsules (i.e. on-droplet
self-assembly) rather than microgels (i.e. in-droplet
self-assembly) requires several customizations. A key
point is prevention of free diffusion of polyelectrolytes
across the interface [31�]. As the interfacial tension in
ATPSs is very low, polyelectrolytes are not adsorbed to
the interface, but rather tend to migrate across the inter-
face due to concentration differences between the phases.
It is crucial to tune the relative fluxes of polyelectrolytes
so that they meet at the interface. Moreover, the concen-
tration of polymers in each aqueous phase has to be close
to the equilibrium condition in the ternary phase diagram
of the corresponding ATPS, so that, intermixing of the
Current Opinion in Food Science 2020, 33:165–172
polymers is weak when the two solutions come into
contact [32]. In order to tailor polyelectrolyte diffusion,
they were added to the aqueous phase with poorer
affinity. The polyanion PSS with much higher affinity
for Dex (partitioning coefficient 0.69) was added to the
PEG phase and the polycation PAH with almost no
preference between the phases (partitioning coefficient
in Dex: 0.51) was added into the Dex phase. Once the
Dex phase was electrosprayed into the PEG phase, PSS
strongly migrated from the continuous PEG phase
inwards to the droplet phase (Dex), while PAH weakly
migrated outwards. The opposite transfer of PSS and
PAH caused complexation at the W-W interface, thus
forming microcapsules [31�].
Recently, BSA-loaded or catalase-loaded colloidosomes
were fabricated by in situ generation of colloidal particles
at all-aqueous interfaces. Colloidosomes are microcap-
sules with shells consisting of colloidal particles. The
dispersed phase, which consisted of Dex containing
Na-alginate and urease (also BSA or catalase) was peri-
odically injected into a continuous phase of PEG using a
glass capillary microfluidic device (Figure 2c). Upon
existing the microfluidic device, the emulsion droplets
were directed into a bath containing PEG, CaCl2 and
urea: CaCl2 and urea could freely diffuse across the
interface and enter into the Dex phase, while, urease
tended to stay in the Dex phase. The diffusion of Ca2+
crosslinked the alginate at the droplet surface, and urease
concurrently formed ammonium carbonate from urea that
in the presence of Ca2+ ions generated CaCO3 particles.
The CaCO3 particles nucleated and grew into a solid shell
on the microgels (Figure 2c). The encapsulation effi-
ciency was high (>85%) [33].
Reactions at the droplet interface
The W-W interface can be exploited as a liquid-staying
reaction site for reactants partitioned in the discrete
phases of all-aqueous emulsions. To illustrate this, an
enzyme-assisted oxidation reaction was investigated in
macroscopically phase-separated solutions of PEG and
sodium citrate (Figure 3). The citrate-rich phase con-
tained the enzymes glucose oxidase (28:1 concentration
excess compared to the PEG-rich phase) and horseradish
peroxidase (1.6:1), as well as high concentrations of glu-
cose (1.9:1) and peroxide (1.65:1). The hydrophobic
substrate, amplex red and the reaction product, resorufin
strongly partitioned into the PEG-rich phase. First, resor-
ufin formation (pink color) was observed in the citrate-
rich phase, and after 10 min also at the interface.
The reaction product continuously partitioned into the
PEG-rich phase, so that after 3 hour the PEG-rich phase
was uniformly pink [23��]. Fabrication of fibrillosomes
through growing amyloid fibrils from hen egg lysozyme
as monomer at all-aqueous interfaces seeded with pre-
formed lysozyme fibrils also holds a merit [34].
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All-aqueous emulsion microreactors Madadlou et al. 169
Figure 2
(a)
(b) (c)
a
b c d
Droplet phase
Droplet template
Continuous phase
Polycations Polyanions
PEG, urea
PEG
PEGinlet
Dex, Na-algand ureaseinlet
Dex, Na-algand urease
Urease-mediatedbiomineralization
Colloidosome formed fromgelation and biomineralization
Dex PEG Na-alg Urease Urea Ca-algCa2+ CaCO3
CaCl2
“Drainage”5mg/ml 10mg/ml 15mg/ml 20mg/ml
Concentrations of PSS & FITC-PAH
Microcapsule
Droplet Phase Continuous Phase Hb (+) BSA (-)
Assembly
AffinityPartitioning
Dual -Component ProteinMicroparticles
Current Opinion in Food Science
(a) Schematic illustration of the formation of bicomponent (dual component) protein particles in all-aqueous emulsion (a); Optical microscope
images of hemoglobin–bovine serum albumin microparticles taken at the (b) beginning and (c) end of the fabrication process; Cryo-scanning
electron microscopy image of the microparticles (d). Scale bar: 100 mm [30].
(b) Scheme of the self-assembly of polyelectrolytes at the W-W interface and confocal microscopy images of the microcapsules, scale bar: 50 mm
[31�].(c) Optical images of the microfluidic device (a), the taper showing droplet movement when the pump was turn on (b), and off (c), and Dex
droplets containing Na-alginate moving in the outer tube (d). The bottom scheme illustrates the fabrication mechanism of Ca-alginate microgels
through urease-mediated biomineralization (CaCO3 generation) at the Dex-alginate phase interface [33].
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170 Food physics and materials science
Figure 3
PEG-rich phase
PEG-rich phase
Citrate-rich phase
Citrate-rich phase
Citrate-rich phase
1.5 5 10 30 60 90 180Minutes
resorufin
D-glucono-1,5-lactoneD-(+)-glucose
glucoseoxidase
horseradishperoxidase
Amplex Red
Current Opinion in Food Science
Progress of the reaction between amplex red and hydrogen peroxide in the presence of horseradish peroxidase at the W-W interface between a
citrate-rich aqueous phase and a PEG-rich aqueous phase [23��].
Microfluidics for all-aqueous emulsionsMicrofluidic emulsification enables fabrication of highly
monodisperse all-aqueous emulsions. Because of the
inherently laminar flow conditions in the small channels,
the droplet formation is highly repeatable and can be
precisely controlled at low energy input [35,36�]. Appli-
cation of microfluidics for generation of all-aqueous emul-
sions is rapidly developing. Because of the very low
interfacial tension of all aqueous emulsions, the droplet
formation mechanism is rather different from those pre-
sented for other two-phase systems. For example, for oil
in water emulsions, inflow of the water phase at the point
of droplet formation is essential for droplet formation to
take place, and this occurs through the ‘gutters’ that form
at the edges/corners of the rectangular channel [37–39].
For ATPSs, destabilization takes place through shear
forces, which leads to destabilization of the neck which
can perfectly take place in round channels. Development
of non-planar microfluidic channels is ongoing and should
be taken in consideration for future all-aqueous emulsion
production [40].
Recently, a microfluidics platform to make double and
triple all-aqueous emulsions based on hybridization of a
Current Opinion in Food Science 2020, 33:165–172
conventional microfluidic flow-focusing geometry with a
coaxial microneedle and a glass capillary embedded in
flow-focusing junctions was presented for making Dex-in-
PEG-in-Dex emulsions [41]. Fabrication of such micro-
fluidic devices, however, is sometimes cumbersome and
not easily available for scientists without a background in
microfabrication. Recent developments in microfluidic
fabrication have brought this out of the clean room, using
3D printers, laser cutters and sacrificial mold to create
microchannels [42–45]. One example is the Embedded
Scaffold RemovinG Open Technology (ESCARGOT), a
simple and versatile 3D printing method which allows to
make multilayered and intricate micrometric channels in
a single block of polydimethylsiloxane (PDMS) [46]. This
can be combined with various components such as heat-
ing units, color sensors and even a solenoidal micro-coil
allowing NMR-spectroscopy in flow [46] for example, for
the quantification of reactions in flow [47].
Due to the small amounts of reactants, analytical detec-
tion and reaction monitoring (on single droplet level) are
usually challenging. Still, some options are available that
use optical detection (mostly fluorescence), electrochem-
ical signals, but also Mass Spectrometry and NMR [48�].
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All-aqueous emulsion microreactors Madadlou et al. 171
As analytical devices are improving in sensitivity and
specificity year after year, the detection of small-scale
reactions will improve along with the analytical devices.
In-line ultrasound-enhanced Raman spectroscopy for sus-
pensions [49] and in-line nuclear magnetic resonance
(NMR) embedded into flow reactors [50] are instances
of the analytical techniques which can be used for moni-
toring reactions in microfluidic cells.
Concluding remarksAll-aqueous emulsions are a promising tool for running
bioconversion reactions, synthesis of bio-microgels and
bio-microcapsules. The main advantages of using all-
aqueous emulsions as microreaction vessels include
avoiding the utilization of synthetic surfactants, and
organic solvents. Moreover, the emulsion fabrication is
readily achieved on large scale without need to high-
pressure and high-speed homogenizers.
Although the application of all-aqueous emulsions for
microgel synthesis is already advanced, performing reac-
tions at the W-W interfaces is still in its infancy. The W-W
interfacial reactions are promising for making food-grade
core-liquid microcapsules, as well as to produce com-
pounds that leave the interface and partition into either
of the aqueous phases.
Conflict of interest statementNothing declared.
CRediT authorship contribution statementAshkan Madadlou: Conceptualization, Writing - original
draft. Vittorio Saggiomo: Writing - original draft. KarinSchroen: Writing - review & editing. Vincenzo Fogliano:Writing - review & editing.
References and recommended readingPapers of particular interest, published within the period of review,have been highlighted as:
� of special interest�� of outstanding interest
1. Xin Z, Skrydstrup T: Liquid marbles: a promising and versatileplatform for miniaturized chemical reactions. Angew Chem - IntEd 2019, 58:11952-11954.
2. Pera-Titus M, Leclercq L, Clacens J-M, De Campo F, Nardello-Rataj V: Pickering interfacial catalysis for biphasic systems:from emulsion design to green reactions. Angew Chem Int Ed2015, 54:2006-2021.
3. Piradashvili K, Alexandrino EM, Wurm FR, Landfester K:Reactions and polymerizations at the liquid–liquid interface.Chem Rev 2016, 116:2141-2169.
4. Dong Z, Liu Z, Shi J, Tang H, Xiang X, Huang F, Zheng M: Carbonnanoparticle-stabilized pickering emulsion as a sustainableand high-performance interfacial catalysis platform forenzymatic esterification/transesterification. ACS SustainChem Eng 2019, 7:7619-7629.
5. Madadlou A, Jaberipour S, Eskandari MH: Nanoparticulation ofenzymatically cross-linked whey proteins to encapsulatecaffeine via microemulsification/heat gelation procedure. LWT- Food Sci Technol 2014, 57:725-730.
www.sciencedirect.com
6. Nourbakhsh H, Madadlou A, Emam-Djomeh Z, Wang Y-C,Gunasekaran S: One-pot nanoparticulation of potentiallybioactive peptides and gallic acid encapsulation. Food Chem2016, 210:317-324.
7. Yu D, Xiao S, Tong C, Chen L, Liu X: Dialdehyde starchnanoparticles: preparation and application in drug carrier.Chin Sci Bull 2007, 52:2913-2918.
8. Zou Y, Song J, You X, Yao J, Xie S, Jin M, Wang X, Yan Z, Zhou G,Shui L: Interfacial complexation induced controllablefabrication of stable polyelectrolyte microcapsules using all-aqueous droplet microfluidics for enzyme release. ACS ApplMater Interfaces 2019, 11:21227-21238.
9.�
Dewey DC, Strulson CA, Cacace DN, Bevilacqua PC, Keating CD:Bioreactor droplets from liposome-stabilized all-aqueousemulsions. Nat Commun 2014:5
A strategic review on particle-stabilized and segregatively phase sepa-rated biopolymer mixtures.
10. Dickinson E: Particle-based stabilization of water-in-wateremulsions containing mixed biopolymers. Trends Food SciTechnol 2019, 83:31-40.
11. Iqbal M, Tao Y, Xie S, Zhu Y, Chen D, Wang X, Huang L, Peng D,Sattar A, Shabbir MAB et al.: Aqueous two-phase system(ATPS): an overview and advances in its applications. BiolProced Online 2016, 18:18.
12. Cheng T-L, Chuang K-H, Chen B-M, Roffler SR: Analyticalmeasurement of PEGylated molecules. Bioconjug Chem 2012,23:881-899.
13. Madadlou A, Floury J, Dupont D: Structural assessment andcatalytic oxidation activity of hydrophobized whey proteins. JAgric Food Chem 2018, 66:12025-12033.
14. Madadlou A, Saint-Jalmes A, Guyomarc’h F, Floury J, Dupont D:Development of an aqueous two-phase emulsion usinghydrophobized whey proteins and erythritol. FoodHydrocolloids 2019, 93:351-360.
15. Madadlou A, Famelart M-H, Pezennec S, Rousseau F, Floury J,Dupont D: Interfacial and (emulsion) gel rheology ofhydrophobised whey proteins. Int Dairy J 2020, 100:104556.
16. Shibata C, Iwashita K, Shiraki K: Selective separation method ofaggregates from IgG solution by aqueous two-phase system.Protein Exp Purif 2019, 161:57-62.
17. Silverio SC, Rodrıguez O, Tavares APM, Teixeira JA, Macedo EA:Laccase recovery with aqueous two-phase systems: Enzymepartitioning and stability. J Mol Catal B Enzym 2013, 87:37-43.
18. Weißenborn E, Braunschweig B: Hydroxypropyl cellulose as agreen polymer for thermo-responsive aqueous foams. SoftMatter 2019, 15:2876-2883.
19. Brandelli A, Sala L, Kalil SJ: Microbial enzymes forbioconversion of poultry waste into added-value products.Food Res Int 2015, 73:3-12.
20. Lahore HMF, Miranda MV, Fraile ER, Bonino MJB de J,Cascone O: Partition behaviour and purification of a Mucorbacilliformis acid protease in aqueous two-phase systems.Process Biochem 1995, 30:615-621.
21. Reh G, Spelzini D, Tubio G, Pico G, Farruggia B: Partition featuresand renaturation enhancement of chymosin in aqueous two-phase systems. J Chromatogr B 2007, 860:98-105.
22. Andersson E, Hahn-Hagerdal B: Bioconversions in aqueoustwo-phase systems. Enzyme Microb Technol 1990, 12:242-254.
23.��
Aumiller WM, Davis BW, Hashemian N, Maranas C, Armaou A,Keating CD: Coupled enzyme reactions performed inheterogeneous reaction media: experiments and modeling forglucose oxidase and horseradish peroxidase in a PEG/citrateaqueous two-phase system. J Phys Chem B 2014, 118:2506-2517
A pioneering and unique report on accomploishing enzymatic/chemicalreactions at the water-water interface that stays liquid.
24. Badhwar P, Kumar P, Dubey KK: Extractive fermentation forprocess integration and amplified pullulan production by A.pullulans in aqueous two phase systems. Sci Rep 2019, 9:32.
Current Opinion in Food Science 2020, 33:165–172
172 Food physics and materials science
25. de Souza EC, Dos Reis Coimbra JS, de Oliveira EB, Bonomo RCF:Recovery of casein-derived peptides with in vitro inhibitoryactivity of angiotensin converting enzyme (ACE) usingaqueous two-phase systems. J Chromatogr B 2014, 973:84-88.
26. Jiang B, Zhang X, Yuan Y, Qu Y, Feng Z: Separation ofantioxidant peptides from pepsin hydrolysate of whey proteinisolate by ATPS of EOPO co-polymer (UCON)/phosphate. SciRep 2017, 7:13320.
27. Jiang B, Na J, Wang L, Li D, Liu C, Feng Z: Separation andenrichment of antioxidant peptides from whey protein isolatehydrolysate by aqueous two-phase extraction and aqueoustwo-phase flotation. Foods 2019, 8:34.
28. Franssen O, Hennink WE: A novel preparation method forpolymeric microparticles without the use of organic solvents.Int J Pharm 1998, 168:1-7.
29.�
Abbasi N, Navi M, Nunes JK, Tsai SSH: Controlled generation ofspiky microparticles by ionic cross-linking within an aqueoustwo-phase system. Soft Matter 2019, 15:3301-3306
A unique and facile chemical synthesis approach, for controlled genera-tion of pollen-like microparticles, based on ionic cross-linking of alginateand calcium chloride (CaCl2), within an all-biocompatible ATPS of DEXand PEG is developed.
30. Deng Y, Ma Q, Yuan H, Lum GC, Shum HC: Development of dual-component protein microparticles in all-aqueous systems forbiomedical applications. J Mater Chem B 2019, 7:3059-3065.
31.�
Ma Q, Song Y, Kim JW, Choi HS, Shum HC: Affinity partitioning-induced self-assembly in aqueous two-phase systems:templating for polyelectrolyte microcapsules. ACS Macro Lett2016, 5:666-670
The affinity partitioning of polyelectrolytes in ATPS to induce their self-assembly into polyelectrolyte microcapsules is introduced.
32. Hann SD, Niepa THR, Stebe KJ, Lee D: One-step generation ofcell-encapsulating compartments via polyelectrolytecomplexation in an aqueous two phase system. ACS ApplMater Interfaces 2016, 8:25603-25611.
33. Qu F, Meng T, Dong Y, Sun H, Tang Q, Liu T, Wang Y: Aqueoustwo-phase droplet-templated colloidosomes composed ofself-formed particles via spatial confined biomineralization.ACS Appl Mater Interfaces 2019, 11:35613-35621.
34. Song Y, Shimanovich U, Michaels TCT, Ma Q, Li J, Knowles TPJ,Shum HC: Fabrication of fibrillosomes from droplets stabilizedby protein nanofibrils at all-aqueous interfaces. Nat Commun2016, 7:12934.
35. Muijlwijk K, Berton-Carabin C, Schroen K: Cross-flowmicrofluidic emulsification from a food perspective. TrendsFood Sci Technol 2016, 49:51-63.
36.�
Schroen K, Bliznyuk O, Muijlwijk K, Sahin S, Berton-Carabin CC:Microfluidic emulsification devices: from micrometer insightsto large-scale food emulsion production. Curr Opin Food Sci2015, 3:33-40
The paper addresses microfluidic techniques for emulsion preparation.Both scale-up of standard microfluidic devices, and characterisation ofemulsion formation and stability using purpose built microfluidics arediscussed.
37. ten Klooster S, Sahin S, Schroen K: Monodisperse dropletformation by spontaneous and interaction based mechanismsin partitioned EDGE microfluidic device. Sci Rep 2019, 9:7820.
38. van der Graaf S, Steegmans MLJ, van der Sman RGM,Schroen CGPH, Boom RM: Droplet formation in a T-shapedmicrochannel junction: a model system for membraneemulsification. Colloids Surf A Physicochem Eng Asp 2005,266:106-116.
Current Opinion in Food Science 2020, 33:165–172
39. Garstecki P, Fuerstman MJ, Stone HA, Whitesides GM: Formationof droplets and bubbles in a microfluidic T-junction—scalingand mechanism of break-up. Lab Chip 2006, 6:437.
40. Hwang Y, Candler RN: Non-planar PDMS microfluidic channelsand actuators: a review. Lab Chip 2017, 17:3948-3959.
41. Jeyhani M, Thevakumaran R, Abbasi N, Hwang DK, Tsai SSH:Microfluidic generation of all-aqueous double and tripleemulsions. Small 2020, 16:1906565.
42. Goh WH, Hashimoto M: Fabrication of 3D microfluidic channelsand in-channel features using 3D printed, water-solublesacrificial mold. Macromol Mater Eng 2018, 303:1700484.
43. Dahlberg T, Stangner T, Zhang H, Wiklund K, Lundberg P,Edman L: Andersson M: 3D printed water-soluble scaffolds forrapid production of PDMS micro-fluidic flow chambers. SciRep 2018, 8:3372.
44. Chen YY, Kingston BR, Chan WCW: Transcribing in vivo bloodvessel networks into in vitro perfusable microfluidic devices.Adv Mater Technol 2020, 5:2000103.
45. Walsh DI, Kong DS, Murthy SK, Carr PA: Enabling microfluidics:from clean rooms to makerspaces. Trends Biotechnol 2017,35:383-392.
46. Saggiomo V, Velders AH: Simple 3D printed scaffold-removalmethod for the fabrication of intricate microfluidic devices.Adv Sci 2015, 2:1500125.
47. Mompean M, Sanchez-Donoso RM, de la Hoz A, Saggiomo V,Velders AH, Gomez MV: Pushing nuclear magnetic resonancesensitivity limits with microfluidics and photo-chemicallyinduced dynamic nuclear polarization. Nat Commun 2018, 9:108.
48.�
Suea-Ngam A, Howes PD, Srisa-Art M, DeMello AJ: Dropletmicrofluidics: from proof-of-concept to real-world utility?Chem Commun 2019, 55:9895-9903
A recent review on droplet microfluidics, from fabrication to analysis andfuture applications.
49. Wieland K, Tauber S, Gasser C, Rettenbacher LA, Lux L, Radel S,Lendl B: In-line ultrasound-enhanced Raman spectroscopyallows for highly sensitive analysis with improved selectivity insuspensions. Anal Chem 2019, 91:14231-14238.
50. Giraudeau P, Felpin F-X: Flow reactors integrated with in-linemonitoring using benchtop NMR spectroscopy. React ChemEng 2018, 3:399-413.
51. Agrawal K, Verma P: Potential removal of hazardous wastesusing white laccase purified by ATPS–PEG–salt system: anoperational study. Environ Technol Innov 2020, 17:100556.
52. Simental-Martınez J, Montalvo-Hernandez B, Rito-Palomares M,Benavides J: Application of aqueous two-phase systems forthe recovery of bioactive low-molecular weight compounds.Sep Sci Technol 2014, 49:1872-1882.
53. Wang L, Li W, Liu Y, Zhi W, Han J, Wang Y, Ni L: Green separationof bromelain in food sample with high retention of enzymeactivity using recyclable aqueous two-phase systemcontaining a new synthesized thermo-responsive copolymerand salt. Food Chem 2019, 282:48-57.
54. Veloso AV, Silva BC, Bomfim SA, de Souza RL, Soares CMF,Lima AS: Selective and continuous recovery of ascorbic acidand vanillin from commercial diet pudding waste using anaqueous two-phase system. Food Bioprod Process 2020,119:268-276.
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