Part One
`Synthesis
`
`Microgd Suspensions: Fundamentals and Applications
`Edited by Alberto Fernandez-Nieves,
`and David A. Weitz
`Hans M. Wyss, Johan Mattsson,
`© 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
`Copyright
`lSBN: 978-3-527-32158-2
`
`SNF Holding Company et al v BASF Corporation,
`
`Page 1 of 32
`IPR2015-00600
`
`EXHIBIT
`
`V29
`E 3984
`
`Q
`
`

`
`1 M
`
`icrogels and Their Synthesis:An introduction
`Robert Pelton and Todd Hoare
`
`Introduction
`
`their preparation, cleaning, and
`and overviews
`introduces microgels
`This chapter
`characterization. Some aspects of microgel derivatization and storage will also be
`summarized.
`
`Defining Microgels
`
`In a 1949 publication entitled "Microgel, a new macromolecule," Baker coined the
`latex particles [1]. The word
`term "microgel" to describe cross-linked
`polybutadiene
`"micro" referredto the size of the gel particles, which might now be termed "nano"
`since the diameters of his gels were less than 1000 nm. The "gel" part of Baker's
`microgel referred to the ability of the particles to swell
`in organic solvents. Baker's
`consisted of very high molecular weight polymer
`that microgels
`work emphasized
`each gel particle was an individual polymer molecule.
`In other words,
`networks.
`A revised definition of microgels
`followed by an introduction to the
`is now given,
`unique characteristics of microgels.
`a colloidal dispersion of gel particles.
`We define a microgel
`as
`definition are three criteria:
`1) Microgels fall within the particle size range of 10-1000 nm,
`particles [2].
`2) Microgels are dispersed in a solvent.
`3) Microgels are swollen by the solvent.
`Our definition encompasses a wide range of microgel materials. At one extreme
`the other extreme,
`latex particles
`in swelling
`solvent;
`are Baker's cross-linked
`at
`the above definition. However, with the possible
`many biological
`cells satisfy
`exception of Pollack's book [3],
`few links have been made between biological
`cells
`and microgels. Thus, the discussion of microgel preparationin this chapter will be
`
`Implicit
`
`in this
`
`typical of colloidal
`
`Microgel Suspensions: Fundamentals and Applications
`Hans M. Wyss, Johan Mattsson, and David A. Weitz
`Edited by Alberto Fernandez-Nieves,
`© 2011 WILEY-VCH verlag GmbH & Co. KGaA, Weinheim
`Copyright
`ISBN: 978-3-527-32158-2
`
`Page 3 of 32
`
`

`
`4
`
`1 Microgels and Their Synthesis:
`
`An Introduction
`
`based on polymers of both petrochemical and
`
`restricted to synthetic microgels
`biological origin.
`Both surfactant and polymeric micelles
`also fit the above three criteria. However,
`these species are not usually called microgels.
`In the case of surfactant micelles,
`individual micelles have a finite lifetime with rapidly exchanging surfactant mono-
`mers whereas microgels have a static composition. At the other extreme, aqueous
`block copolymer micelles
`based on long hydrophobic blocks
`be long-lived;
`can
`however, the hydrophobic cores
`tend not to swell very much with water. Thus, stable
`block copolymermicelles
`are more akin to latex than to microgels. These considera-
`tions lead to a fourth criterion for defining microgels.
`4) Microgels have stable structures. Either covalent or strong physical
`forces
`like any colloidal dispersion,
`stabilize the polymer network. On the other hand,
`in
`microgel particles
`(flocculate or coagulate)
`aggregate
`as described
`can
`Chapter 6.
`Finally, Baker suggests that each microgel particle is composed of one polymer
`molecule (1]. Although this is true for many microgels preparedby vinyl polymer-
`too restrictive. For example, we will
`this requirement is
`that
`ization, we propose
`describe microgels preparedby polyelectrolyte complex formation giving particles
`containing many polymer chains.
`can be problematic at
`Of course, attempts to define a class of materials
`the
`for example,
`a polystyrene-core (water-insoluble) poly(N-
`boundaries. Compare,
`isopropylacrylamide)(PNIPAM)-shell (water swellable) microgel with a polystyrene
`latex bearing a monolayer of surface PNIPAM. Are they both microgels? Where is
`and nanogels? Does a microgel have to be swollen?
`the boundarybetween microgels
`Some speak of the latex-to-microgeltransition [4]
`is this useful? We leave these
`for others.
`questions
`
`-
`
`~500
`
`The Generic Microgel: Structure and Characterization
`1.1.1.1
`it is useful to consider
`To facilitate our discussion of microgelpreparationstrategies,
`representationof the generic
`the generic microgel. Figure 1.1
`a schematic
`shows
`the data are based on a PNIPAM microgel [5]. The
`microgel at three distance scales -
`consists of a dispersion of uniform gel particles
`nm in diameter.
`suspension
`as distinct particles undergoing Brownian motion.
`Themicrogel particles are present
`To the naked eye, highly swollen microgel suspensions
`are nearly transparent,
`are milky white like a conventional latex
`whereas slightly swollen gel suspensions
`have a refractive index close to that of water.
`dispersion. Highly swollen particles
`little light compared to dispersions of unswollen
`Thus, swollen microgels scatter
`organic polymers, such as polystyrene.
`to aggregation (i.e., colloidally stable)
`In general, microgels are very resistant
`because the surfaces oftenbear electrical charges and dangling surface chains (hairs).
`High colloidal stability is further illustrated by the ability of freeze-dried [6] or
`in water. This
`precipitated(ultracentrifuged)microgels to spontaneously redisperse
`is unusual. For example, dried or coagulated polystyrene latex is virtually impossible
`tend to be more colloidally
`to redisperse completely in water.
`In general, microgels
`
`Page 4 of 32
`
`

`
`OO
`
`L7
`
`Introduction
`
`5
`
`e
`
`1000 nm
`
`10 nm
`
`1 nm
`
`Figure1.1
`The essential
`a colloidal dispersion.
`as
`
`features of
`
`a microgel: a water
`
`(solvent)
`
`swollen polymer network present
`
`stable in the swollen form where van der Waals attraction is diminished and surface
`hairs can sterically stabilize the microgel particles.
`and consist of a water swollen
`Individual microgel particles are usually spherical
`cross-linkedpolymer network. Figure 1.2 shows
`a transmission electron micrograph
`of the first PNIPAM microgel
`[7]. The dark
`are disks arising from the
`circles
`dehydration of an ordered layer of spheres.
`We will learn from the following sections and in other chapters
`that although gels
`is very difEcult to prepare
`with a uniform particle distribution are quite common, it
`microgels with a uniform distribution ofcross-links or bound charge throughout the
`volume of individual gel particles.
`
`Swollengel
`on TEM grid
`
`Dehyrate Gel
`on TEM grid
`- cross section
`
`Figure 1.2
`
`Transmission electron micrograph of
`
`the first PNIPAM microget
`
`Page 5 of 32
`
`

`
`6
`
`1 Microgels and Their Synthesis:
`
`An Introduction
`
`for microgels vary from 10 to 90 wt% depending upon the
`Typical water contents
`detailed chemistryofthe microgel dispersion. Microgel swelling is described in detail
`in Chapter 4. Many publications give swelling ratios that are derived from particle
`size measurementsunder two different solvency conditions. In contrast, relatively
`few papers give microgel molecular weight because it is surprisingly difficult to
`measure the average dry mass per microgel particle. A consequence of this difficulty
`is that many publications give neither the water content nor the number concen-
`tration of microgel dispersions. Microgel molecular weight can be measured
`by
`(1) the measurementof the size of the microgels under low swelling conditions and
`assuming a water content -for
`two watermolecules per NIPAM moiety [8];
`example,
`(2) packingthe microgels into colloidal crystals and estimating the degree of swelling
`from the wet and dry masses of the colloidal crystal
`(3) calculating the effective
`[5];
`particle volume fraction from viscosity measurements
`[9], which when coupled to
`the swollen diameter and dry solids
`content gives number concentration and
`molecular weight.
`Microgel number concentration can
`directly by single-particle
`be measured
`counting using flow cytometry [10] or manually with a hemocytometer.
`Indirect
`are usually based on measurement of the dry solids content and the
`methods
`microgel molecular weight.
`The schematic
`representationof the generic microgel in Figure 1.1
`the
`shows
`presence of short polymer chains extending from the gel surface. The presence of
`these chains was postulated in the first PNIPAM microgel publication in order to
`explain the exceptionally high colloidal
`stability in concentrated electrolyte. Surface
`chains would provide steric stabilization (7].
`In general,
`the surface topology of
`In most cases, we know neither
`has been poorly described in the literature.
`microgels
`the length distributions nor the density of surface chains. We are likely to know more
`the surface chains when (i) living radical
`techniques are used to grow surface
`about
`[11-13]; (ii) monomers such as vinyl acetic acid are used,
`chains on existing particles
`which act as chain transfer agents [14]; or (iii) macromonomersare used to decorate
`the microgel surface with polyethylene glycol chains [15]. An elegant example from
`Kawaguchi's group involved using living radical polymerization to grow PNIPAM
`hairs on a core particle [16].
`Thegeneric microgel in Figure 1.1 has negative charge groupscovalently bound to
`is difEcult to
`the polymer network. Virtually all microgels are electrically charged -it
`prepare a nonionic aqueous microgel. The main sources of the electrically charged
`initiators and/or ionic monomers copolymerized into
`groups are ionic free radical
`the polymer network.
`
`1.1.2
`Microgels Are Special
`
`The existence of hundreds of scientific publications, patents, and this book suggests
`that microgelsare important. Interest in microgels comes from their unique blend of
`properties combining useful aspects of conventionalmacrogels with useful proper-
`ties of colloidal dispersions.
`
`Page 6 of 32
`
`

`
`L1 Introduction
`
`7
`
`Microgels share a number of properties with macrogels. Most
`importantly, both
`and microgels swell with water (or solvent) to an extent controlled by the
`macrogels
`the polymer/water compatibility, and the presence of electrical
`cross-link density,
`charges. Microgel swelling properties are described in Chapter4. Perhaps one of the
`biggest driving forces for microgel research is that, like macrogels[17], microgels can
`be "intelligent" or "responsive," meaning their degree of swelling can be controlled
`by temperature, pH, magnetic fields,
`light, and specific solutes
`such as glucose
`[18-21]. Controllable swelling has been applied to demonstrate the uptake and
`release of solutes,
`including drugs [22], proteins, and surfactants [23, 24].
`The colloidal nature of microgels gives them significant advantages over macro-
`gels. These include, in decreasing order of importance, the following:
`
`3)
`
`1) Microgel suspensions
`free-flowing liquids unless highly concentrated.
`are
`Indeed, their flow properties depend upon the volume fraction of swollen
`particles and are approximately independent of cross-link density, whereas
`flow only at very low levels of cross-linking near the gel point.
`macrogels
`2) Microgels respondvery rapidly to environmental changes. The very high surface
`to volume ratios facilitate mass transport to and from the microgels.
`Exotic microgel morphologies can be used to fine-tune properties. For example,
`there is no macrogel equivalent of
`the wide range of core-shell particle
`architectures.
`4) Colloidal science techniques including electrophoresis, dynamic light scatter-
`ing, and small-anglelight scattering provide structural information not usually
`availablefor macrogels.
`into useful larger objects such as 2D assemblies
`5) Microgels can be assembled
`at
`the air-water [25, 26] and oil-water interfaces[27-29]. Examples of 3D structures
`are colloidal crystals giving environmentally sensitiveoptical properties [30, 31]
`[32-42].
`and layer-by-layer assemblies
`
`1.1.3
`The Microgel Landscape
`
`The microgel field is rapidly evolving with ever increasing complexity. However,
`some generalizationscan be made to help create perspective. There are two microgel
`worlds that are virtually exclusive - commercial microgels and academic microgels.
`The commercial gels have been used in large quantities since the 1960s. Two
`common classes of commercial gels are nonaqueousand alkali swellable microgels.
`Nonaqueousmicrogels are described in the paints and coatings patent literature [43].
`Alkali swellable microgels are based on cross-linked acrylic acid latexes that swell
`when the pH is raised. These are widely used in formulated products to control
`rheological properties [44-46].
`literature has exploded in the last decade and we can
`The academic microgel
`generalize to emphasize major trends. First, most scientific publications employ
`"homemade" instead of commercial microgels. Second, most of the publications
`involve aqueous microgels. Finally, most of the aqueous microgel studies describe
`
`Page 7 of 32
`
`

`
`8
`
`1 Microgels and Their Synthesis:
`
`An Introduction
`
`microgel particles on the basis of PNIPAM, which is readily polymerized into linear
`water-solublepolymers [47], microgels (7], or macrogels [48]. PNIPAM derivatives
`have received much attention because the microgels are very uniform and the
`swelling properties are temperature sensitive[7]. The organic chemistry of PNIPAM
`and the other major microgel platform polymers will be summarized in another
`section later on.
`
`1.2
`Microgel Synthesis
`
`1.2.1
`Introduction
`
`include controlling the particle size distribution, the
`The goals of microgel synthesis
`colloidal stability, and the distribution of specific
`functional groups such as cross-
`linker, chargedgroups, or reactivecenters for further chemical derivatization. There
`are three possible starting points for microgel preparation:
`
`1)
`
`2)
`
`3)
`
`From monomer. This is the most common approachand is described in the most
`detail here. Table 1.1 lists many of the vinyl monomers that have been used to
`preparemicrogels. Monofunctional monomers are nonionic, cationic, or anion-
`ic. Of the bifunctional cross-linking monomers N,N-methylenebisacrylamide
`(MBA) is
`the most widely used. Polyethylene glycol dimethacrylate is an
`attractive choice for acrylate-based microgels given that it offers the additional
`flexibilityof varying the length of the PEG chain between the cross-link points.
`The cross-linker solubility can influence microgel properties [49].
`From polymer. Aqueous polymer solutions can be emulsified in oil and chem-
`ically cross-linked.Another route to microgels based on existing polymers is the
`formation of colloidal polyelectrolyte complexes
`by mixing oppositely charged
`polymers in dilute solution.
`to mechanically grind a macrogel to form
`It
`From macrogels.
`is possible
`microgels. There are very few reports of this in the literature [50]. We tried
`grinding polyvinylamine (PVAm) macrogels
`irregularly
`and obtained large,
`shaped microgels [51].
`It is convenient to divide the diverse range of microgel preparation strategies
`based on the particle formation mechanism -
`into three classifications
`those
`formed by emulsgication, and those
`formed by homogeneous
`those
`nucleation,
`formed by complexation. Homogeneous nucleation refers to those preparations
`in which microgel particles are generated from initially homogeneous (or nearly
`so) solutions. Emulsification refers to those methods where aqueous droplets of
`in the second step,
`a "pregel" solution are formed in an oil or brine phase and,
`the
`droplets are polymerized and/or cross-linked into a microgel. Finally, microgels
`can be prepared by mixing two dilute, water-solublepolymers that form complexes
`in water.
`
`Page 8 of 32
`
`

`
`Table 1.1
`
`Vinyl monomers used to prepare microgels.
`
`Monofunctional nonionic
`
`1.2 Microgel Synthesis
`
`9
`
`NH2
`
`Acrylamide (AM)
`
`O
`
`MEthylacrylamide (126]
`
`MEthyl methacrylamide [49]
`
`N
`
`O
`
`MIsopropylacrylamide
`(NIPAM)
`[7]
`
`MVinylformamide
`(NVF) [51]
`
`KVinyl caprolactam [127]
`
`Vinylpyrrolidone [127]
`
`Anionic monofunctional
`
`HO'
`
`'OH
`
`4-Vinylphenylboronic
`acid [128]
`
`O
`
`HO
`Acrylic acid
`
`O
`
`O
`
`HO
`
`OH
`
`Maleic acid [118]
`Cationic monofunctional
`
`O
`
`HN
`
`OH
`
`OH
`
`Phenylboronicacid
`methacrylamide [129]
`
`O
`
`O
`
`HO
`
`Methacrylic acid
`
`HO
`Vinyl acetic acid [14]
`
`O=S=O
`OH
`
`[130]
`
`O
`
`HO
`
`Fumaric acid [118]
`
`NH2
`
`Allylamine [131]
`
`Diallyldimethyl ammonium chlo-
`ride (DADMAC) [132]
`
`[133]
`
`N
`
`N
`
`(Continued )
`
`Page 9 of 32
`
`

`
`10
`
`1 Microgels and Their Synthes¡s: An Introduction
`
`Table 1.1
`
`(Continued)
`
`N"
`
`O
`
`[134]
`
`2-(Dimethylamino)ethyl
`methacrylate (135]
`
`1-Vinylimidazole [136]
`
`N
`
`N
`
`O
`
`N
`
`N-3-Dimethylaminopropyl
`methacrylamide [137]
`Bifunctional nonionic cross-linker
`
`2-(Methacryloyloxy)
`ethyl
`ammonium chloride [74]
`
`trimethyl
`
`N
`
`N
`
`N
`
`N
`
`N
`
`1,3-Divinylimidazolid-2-one
`(BVU)
`[51]
`
`N,N'-
`Methylenebisacrylamide [7]
`
`N,N'-(1,2-Dihydroxyethy-
`lene) bisacrylamide [81]
`
`O
`
`O
`
`O
`
`1,4-Butanediol diacrylate
`
`[46]
`
`O
`
`O
`
`O
`
`1,3-Butanediol
`dimethacrylate [49]
`
`Tetraethylene glycol
`dimethacrylate [49]
`
`O
`
`NS,SN_
`
`O'O
`
`1,4-Butanediol
`dimethacrylate [49]
`
`N,N'-Bis(acryloyl)cystamine
`[91, 92]
`
`Polyethyleneglycol
`dimethacrylate [138]
`
`1.2.2
`Approach 1: Microgels Formed by Homogeneous Nucleation
`
`In homogeneous nucleation, a solution of soluble monomer, including some type
`of cross-linking agent,
`fed into the reactor and microgel particles form over the
`is
`course of polymerization. A key requirement for discrete microgel particle forma-
`insoluble under the polymerization
`tion is
`that
`the polymer formed must be
`conditions; monomers giving soluble polymers under the polymerization condi-
`
`Page 10 of 32
`
`

`
`L2 Microgel Synthesis
`
`11
`
`tions will form a macrogel. For example, PNIPAM microgels readily form when the
`monomer is polymerized in water at 70°C because PNIPAM is water insoluble at
`high temperature [47]. In contrast, acrylamide (see Table 1.1), a common monomer
`with a similar chemical structure to PNIPAM, gives a water-soluble polymer at all
`temperatures, so polyacrylamide microgels cannot be prepared by homogeneous
`polymerization in water. Polymerization of aqueous acrylamide solutions gives a
`macrogel.
`Microgel preparations involving homogeneousnucleation include the following
`types of polymerizations: emulsion polymerization (EP), surfactant-free emulsion
`polymerization (SEP), and microgel formation from dilute polymer solution. Each of
`these is described in the following sections.
`
`-
`
`Emulsion Polymerization and Surfactant-Free Emulsion Polymerization
`1.2.2.1
`Emulsion polymerization is the primary process for preparation of commercial latex
`dispersions involving monomers of limited water solubility. Typically,
`the reactor is
`chargedwith water, surfactant, monomer, and a water-solublefree radical initiator.
`The monomer is initially presentas a suspensionoflarge monomer drops, whereasat
`the end of the polymerization the polymer is present as surfactant-stabilized latex
`typically about 100 nm in diameter. The locus of polymerization is in the
`particles,
`the monomer droplets serve as a
`aqueous phase and the growing latex particles
`reservoir replenishing the dissolvedmonomer in the aqueous phase. The theoretical
`basis of emulsion polymerization has been investigated extensively -
`the major
`conclusions are well described in virtually every polymer textbook, and more details
`are given in specialized works such as Gilbert's [52].
`In the mid-1970s, there was much activity in the academic community around a
`variation of emulsion polymerization called surfactant-free emulsion polymeriza-
`tion [53]. For example, with this method monodisperse polystyrene latexes can be
`prepared simply with water, styrene monomer, and potassium persulfate initiator.
`~ 60 °C under nitrogen, the persulfate decomposes
`into sulfate
`Upon heating at
`radicals that initiate styrene polymerization. Sulfate groups terminating polystyrene
`chains end up at the water/polystyreneinterface,conferring electrostatic stabilization
`and preventing aggregation.
`The first PNIPAM microgel was preparedwith a variation of the polystyrene SEP
`recipe in which styrene was replacedwith NIPAM and a little MBA was included to
`prevent microgels from dissolving when the temperature was lowered at the end of
`the mechanism of PNIPAM microgel
`the polymerization [7]. Figure L3 shows
`generated in solution initiate the homogeneous poly-
`formation. Sulfate radicals
`merization of NIPAMand MBA. However,the insolubility ofthe PNIPAM network
`the growing polymer chain to phase
`under polymerization conditions causes
`forming precursor particlesthat are not colloidally stable. As the aggregated
`separate,
`the charged chain ends tend to concentrate at
`precursor particles coalesce,
`the
`particle/water interface.Therefore, as the aggregates grow,
`the surface charge density
`increases until a point is reached where the growing particle is colloidally stable with
`to similar sized or larger particles. These first formed stable particles are
`respect
`called primary particles. To achieve a monodisperseproduct, the primary particles
`
`Page 11 of 32
`
`

`
`72
`
`7 Microgels and Their Synthesis:
`
`An Introduction
`
`O
`O= -O +
`O
`
`¯l
`
`R
`
`n
`
`· eQ
`Precursor
`Particle
`
`8--
`Growing
`Oligiomer
`
`New
`Primary
`Particle
`
`Gro
`
`e
`
`emulsion polymerization.
`Initially, unstable
`formation by surfactant-free
`Figure I.3 Microgel
`the end of nucleation stage, all new
`precursor
`particles aggregate to form new primary particles. At
`are captured by existing stable particles,
`precursor
`particles
`
`low monomer conversion. In later stages of polymerization, all
`must be formed at
`newly formed precursor particles deposit onto existing stable microgels contributing
`to particle growth.
`is difScult to
`There are few variables in the above PNIPAM microgel SEP, thus it
`obtain a wide range of average microgel diameters. Using a surfactant,
`such as
`influences microgel particle nucleation and thus the
`sodium dodecyl sulfate (SDS)
`that microgel diameter decreases with SDS
`54]. Figure 1.4
`fmal
`size
`shows
`[5,
`
`800
`
`600
`
`400
`
`E
`
`e
`
`-
`
`.
`
`200-
`
`SDS stabilizes
`more, smaller
`primary particles
`
`Charge from
`initiator
`
`g
`
`0
`
`0
`
`(cid:127)(cid:127)'I'''
`
`0.4
`
`0.8
`SDS conc. (g/l)
`
`-
`
`1.2
`
`Adsorbed
`SDS
`
`1.6
`
`The influence of sodium dodecyl sulfate on the size ofthe resulting PNI PAM microgels.
`Figure1.4
`Data from Ref.
`[5].
`
`Page 12 of 32
`
`

`
`7.2 M¡crogel Synthes¡s
`
`13
`
`concentration by a factor of7. The role ofthe SDS is to stabilize the primary particles
`so that they are smaller than those preparedwithout SDS. The smaller the primary
`the higher the total number of primary particles that are initially formed,
`particles,
`resulting in smaller microgels for the same dose of monomer. Figure 1.4 illustrates
`the transition from SEP (i.e., no SDS)
`to EP (i.e., SDS above the critical micelle
`concentration). SDS addition also gave higher microgel yields and more uniform
`particles. Of course,
`it may be necessary
`to remove the surfactant after the prepa-
`ration, depending upon the application. Standard approaches
`to microgel cleaning
`are described in a later section.
`Herein we refer to the process shown in Figure 1.3 as surfactant-free emulsion
`polymerization because ofthe similarities with styrene SEP. However,there is some
`difficulty with this nomenclature. Emulsion polymerization applies
`to monomers
`with low water solubility, whereas
`virtually all vinyl monomers used to make
`microgels are water soluble (see Table 1.1). Therefore, many authors use the term
`"precipitation polymerization" to describe
`these microgel SEPs.
`involve batch EP or SEP in which all of the
`The majority of microgel recipes
`monomer and initiators are added at
`the beginning. However, even the simplest
`PNIPAM microgel has two comonomers (NIPAM and MBA) and many of the most
`interesting microgels have been prepared with three or more monomers. The
`presence of more than one monomer type introduces complexity in any free radical
`copolymerization arising from the differences in monomer reactivity. For example,
`we showed many years ago that MBA polymerizessubstantiallyfaster than NI PAM in
`the PNIPAM microgel SEP [55]. Thus, the cross-linker density is higher in the first
`formed polymer than in the last.
`In other words,
`the microgel periphery will be less
`cross-linked and more swollen than the microgel core.
`Recently, Hoare has employed kinetic modeling to predict the radial distribution
`of cross-links
`and carboxyl groups across a microgel particle [56]. The distributions
`are sensitive to the monomer chemistry and reactivity. For example, Figure 1.5
`the distributionof carboxyl groups across
`an individual gel for PNIPAM
`compares
`microgels prepared using methacrylic acid or vinyl acetic acid as
`the carboxylic
`than PNIPAM; thus,
`comonomer. Methacrylic acid polymerizes faster
`the carboxyl
`In contrast, vinyl acetic acid reacts
`groups are concentrated in the particle core.
`more slowly and primarily by chain transfer instead of free radical propagation,
`the end of hairs on the
`resulting in the concentration of carboxyl groups at
`a more detailed account of polymerization
`microgel surfaces. Chapter 2 gives
`kinetics and Chapter 5 describes microgel structural characterization by neutron
`scattering.
`In summary, most microgel recipes employ batch polymerizations and a few use
`semibatch strategies. Furthermore, there have been very few reaction engineering
`there have
`involving significant modeling of microgel formation. Finally,
`studies
`been some unusual variations of EP and SEP. Cao et al.
`reported microgel poly-
`merizations in supercritical carbondioxide [57]. Boyko et al. comparedwater and D20
`for the preparation of poly(N-vinylcaprolactam-co-N-vinylpyrrolidone)- heavy water
`a poor solvent for microgels.
`was
`
`Page 13 of 32
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`

`
`14
`
`7 Microgels and Their Synthesis:
`
`An Introduction
`
`VINYLACETIC ACID
`
`7000
`
`1000
`
`=
`
`2500
`
`METHACRYLIC ACID
`
`o
`1000 .re
`
`-¯ 2
`é o
`
`oÛ
`
`O
`
`O -
`
`1000
`
`o
`
`1
`
`.
`0.5
`0.5
`Relative Radius (r/r
`
`0
`
`1
`
`0.5
`0.5
`Relative Radius (r/r.)
`
`0
`
`Doo
`
`)
`
`1
`
`1
`
`E
`
`O
`
`DE
`
`5DO
`
`o
`
`1
`
`.
`,
`0.5
`0.5
`Relative Radius (r/r
`
`0
`
`)
`
`1
`
`0.5
`0.5
`Relative Radius (r/r.)
`
`0
`
`',
`
`1
`
`1
`
`Distribution ofcross-links and carboxyl groups for microgels prepared with vinyl acetic
`Figure1.5
`(VAA-NIPAM)and methacrylic acid
`(MAA-NIPAM}.The top curves were computed whereas
`acid
`the bottom figures
`are experimental
`[56L
`
`Nucleation of Microgels from Linear Polymers
`L2.2.2 Homogeneous
`There have been a few reports describing the conversionof linear polymer solutions
`to microgels [58-64]. In the case of PNI PAM, heating dilute linear polymer solutions
`above the VPTT gives slightly swollen, colloidally stable microgels [60]. To prevent
`to cross-link the gels. For
`microgels from dissolving on cooling,
`it
`is necessary
`example, Kuckling et al. used UV photocross-linking to stabilize phase-separated
`microgels [62].
`A related approach is to prepare diblock copolymers that micellize [65] and cross-
`link the core. For example. Charleux'sgroup reportedmicrogels preparedby adding a
`little cross-linker during the nitroxide-mediatedliving radical polymerization of poly
`(acrylic acid-b-diethylacrylamide)under conditions in which the diethylacrylamide
`so this method
`block phase separates [66]. Block copolymermicelles tend to be small,
`will give relatively small microgels.
`
`1.2.2.3 Core--Shell Microgels
`Core-shell latex particles preparedby emulsion polymerization have been available
`are first prepared by conventional emulsion poly-
`for decades. The core particles
`for the
`merization. In the second step,
`particles are used as seeds
`the first-stage
`shell polymerization. There are a number of challenges
`in the prep-
`second-stage
`including microgels. First, we must control nucleation
`aration ofcore-shell particles,
`in the first stage to generate uniform seeds, whereas in the second stage, nucleation
`
`Page 14 of 32
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`

`
`1.2 Microgel Synthesis
`
`15
`
`must be prevented. That is, for uniform core-shell particles, all new stage-2 polymer
`chains must deposit on existing particles, avoiding secondary nucleation of stage-2
`particles. Secondary nucleation of stage-2 polymer is a common problem easily
`identified with electron microscopy, which can reveal a population of small stage-2
`particles coexisting with larger core—shell latex. Another challenge involves rear-
`rangement ofcore-—shell particles into more complex morphologies. For example, it is
`frequently difficult to prepare core—shell particles in which the shell
`is more
`hydrophobic than the core. There is a strong thermodynamic driving force to
`minimize interfacial energies by producing raspberry, stuffed olive, and other
`complex shapes [67]. To achieve nonequilibrium structures, it is necessary to freeze
`structures by cross-linking or working below Tg.
`Core—shell microgels have been prepared since the earliest days of rnicrogel
`development. We prepared the first polystyrene-core, PNIPAM-shell microgels in a
`two-step procedure — first preparing a polystyrene surfactant-free latex and then
`grafting PNIPAM onto the particles [68]. The key point is that the PNIPAM
`polymerization must be carried out at room temperature where PNIPAM is soluble
`and will not nucleate new particles. The state of the art in core—shell microgels is
`exemplified by a series of papers from Lyon's group, who prepared PNIPAM-core
`plus PNIPAM-co-acrylate shell gels and the inverse gels [69]. There have been more
`than 50 scientific publications on core-shell microgels from 1988 to 2008, with most
`appearing after 2000. This activity reflects the promise of core—shell architectures in
`controlled swelling, uptake, release, and sensing applications. On the negative side,
`most papers assume core—shell morphology without proving it.
`
`1.2.3
`
`Approach 2: Microgels from Emulsification
`
`In this group ofmethods, an aqueous “pregel” solution is suspended in an oil or brine
`phase to give a water-in-oil emulsion — see Figure 1.6. The pregel can be either a
`monomer or a polymer solution. In the second gelation step, the emulsion droplets
`undergo a chemical reaction to gel each emulsion droplet. This type of polymeri-
`zation is often called “inverse emulsion polymerization” or “miniemulsion poly-
`merization” [70, 71]. A distinction between these two types ofpolymerizations is that
`miniemulsion recipes include a solute for the dispersed phase with ultralow
`solubility in the continuous phase to prevent Oswald ripening. For oil-in-water
`emulsions, the solute is a hydrophobic long-chain alkane, whereas for water-in—oil
`emulsions, salts provide this fimction.
`Two cases for the gelation step are illustrated in Figure 1.6. In the homogeneous
`case, essentially a solution polymerization or cross-linking reaction occurs through-
`out the drop. An example of this case is Landfester’s preparation of cross-linked
`100 nm polyacrylic acid microgels using cyclohexane as the continuous phase and
`50% water in the dispersed (monomer) phase [71].
`The second case illustrated in Figure 1.6 occurs when reaction ofthe pregel causes
`new particles to nucleate within the emulsion droplet. A good example of this is the
`work of Dowding, Vincent, and Williams, who reported the evolution of emulsion
`
`Page 15 of 32
`
`

`
`OO
`
`Homogeneous
`
`Nucleation
`Within Drop
`
`16
`
`7 Microgels and Their synthesis: An Introduction
`
`Oil
`
`Ge lation
`
`O
`
`Emulsion
`
`Figure 1.6
`
`Pregel emulsifÌcation followed
`
`by gelation to give microgels.
`
`droplet size for the inverse emulsion polymerization of PNIPAM [72]. They found
`the produced microgels were much smaller than the emulsion droplets,
`that
`suggesting more than one microgel particle formed per emulsion droplet.
`Finally, emulsion can be preparedby conventional oil-in-water techniques [73] or
`[74]. An interesting variation,
`using a particle-at-a-time microfluidic methods
`involves forcing a gelling polymer solution through a
`in a patent,
`described
`membrane or packed bed to generate a rnicrogel suspension [63].
`
`1.2.4
`Approach 3: Microgels by Polymer Complexation
`
`involves the mixing of dilute
`A completely different approach to microgel synthesis
`solutions of oppositely charged polyelectrolytes to form colloidally dispersed,
`poly-
`illustrated in Figure 1.7. The
`76]. The principle is
`electrolyte complexes
`[75,
`cooperativeelectrostatic attraction between oppositely charged chains
`gives stable
`polymer networks.
`it is critical that one of the components is in
`To achieve colloidally stable microgels,
`to give chargedmicrogels that are electrosterically stabilized. This is illustrated
`excess
`in a recent example from our laboratorywhere we determined the phase diagram for
`microgel formation when dilute, cationic polyvinylamine is mixed with anionic
`{CMC) [77]. The phase diagram, reproduced in Figure 1.8,
`carboxymethyl cellulose
`illustrates that stable microgels were obtainedwhen either polymer was in excess.
`In
`contrast, stoichiometric mixtures gave macroscopic precipitates. The swelling of
`PVAm-CMC rnicrogels is determined by the effective cross-link density, charge
`content, and poly