Membrane Engineering

8/10/2019 Membrane Engineering

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PERSPECTIVESChinese Journal of Chemical Engineering, 19(6) 891903 (2011)

Stimuli-responsive Membranes: Smart Tools for Controllable

Mass-transfer and Separation Processes*

CHU Liangyin ()**, XIE Rui ()and JU Xiaojie ()School of Chemical Engineering, Sichuan University, Chengdu 610065, China

Abstract As emerging artificial biomimetic membranes, smart or intelligent membranes that are able to respondto environmental stimuli are attracting ever-increasing interests from various fields. Their permeation properties in-cluding hydraulic permeability and diffusional permeability can be dramatically controlled or adjustedself-regulatively in response to small chemical and/or physical stimuli in their environments. Such environmentalstimuli-responsive smart membranes could find myriad applications in numerous fields ranging from controlled re-lease to separations. Here the trans-membrane mass-transfer and membrane separation is introduced as the begin-ning to initiate the requirement of smart membranes, and then bio-inspired design of environmental stimuli-responsivesmart membranes and four essential elements for smart membranes are introduced and discussed. Next, smartmembrane types and their applications as smart tools for controllable mass-transfer in controlled release and separa-tions are reviewed. The research topics in the near future are also suggested.Keywords smart membranes, responsive membranes, bio-inspired membranes, gating membranes, mass-transfer,

controlled release, separation

1 INTRODUCTION

Membrane technology is playing a more andmore important role in modern life and global sus-tainable development. Although the achievements inthe membrane fields have been very significant up tonow, commercialized membranes are still single-function membranes. For example, membrane separa-tion is only achieved by either size difference, or dif-fusivity difference, or electrostatic charge difference,except for some charged ultrafiltration and nanofiltra-

tion processes being driven by both size and electro-static charge differences. The permeability of existingcommercial membranes cannot be self-regulativelyadjusted according to the change in environmentalconditions. That means the permeation performancesof membranes are not able to respond to environ-mental stimuli. However, the biomembranes in naturehave environmental stimuli-responsive channelsacross the membranes [1-3], that means the permeabil-ity of biomembranes has environmental stimuli-responsive characteristics.

Biomembranes provide original inspiration formembrane scientists and technologists to develop

mimetic functional membranes, which are highly at-tractive for achieving more advanced and comprehen-sive membrane systems, e.g., composite-functionmembranes with not only a selectivity factor but alsoan environmental stimuli-response factor and a gatefactor. Since the middle 1980s, membrane scientistsand technologists have devoted much to the develop-ment of bio-inspired environmental stimuli-responsivesmart membranes [4]. Because they have great poten-tial for applications as smart tools in myriad fields

from controlled release to separation, such environ-mental stimuli-responsive smart membranes are at-tracting ever-increasing attention from various fields.

In this paper, the bio-inspired design of environ-mental stimuli-responsive smart membranes and fouressential elements for smart membranes are introducedand discussed, smart membrane types and their appli-cations as smart tools for controllable mass-transfer incontrolled release and separations are reviewed, andthe research topics in the near future are also suggested.

2 BIO-INSPIRED DESIGN OF STIMULI-RESPONSIVE SMART MEMBRANES

2.1 Necessity of stimuli-responsive smart mem-branes

The trans-membrane mass-transfer and mem-brane separation processes are schematically illus-trated in Fig. 1: component M can selectively perme-ate across the membrane while component N can notpermeate across the membrane. The difference be-tween components M and N might be either size dif-ference, diffusivity difference, or electrostatic charge

difference. Thus, M and N can be separated by themembrane. In the membrane separation process, theflux of component M is dependent on the mass-transferof component M across the membrane:

M

AJ

R

= (1)

in which, JM if the flux of component M, is thedriving force for trans-membrane permeation,Ais theeffective membrane area for permeation, and Ris the

Received 2011-08-02, accepted 2011-10-08.* Supported by the National Basic Research Program of China (2009CB623407), and the National Natural Science Foundation

of China (20825622, 20806049, 20906064, 20990220, 21036002, 21076127, 21136006).** To whom correspondence should be addressed. E-mail: [email protected]


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Chin. J. Chem. Eng., Vol. 19, No. 6, December 2011892

membrane resistance for trans-membrane mass-transferof component M.

Usually, the driving force and the effective mem-brane area are fixed in a given case, and the mem-brane resistance of existing commercial membranes isunalterable if no membrane fouling occurs. Therefore,

the permeability of component M across the mem-brane is unchangeable. If environmental stimuli-responsive smart membranes are available, the mem-brane resistance for trans-membrane mass-transfer ofcomponent M can be self-regulatively adjusted by thechange in environmental conditions, due to the envi-ronment-responsive conformational change of mem-brane materials. As a result, the flux of component Macross the responsive smart membrane can be self-regulated responding to environmental stimuli. It hasbeen reported that for thermo-responsive smart mem-branes, the membrane resistance for trans-membranemass-transfer of permeate component could be re-

duced or reversibly increased significantly in a rangefrom several times to hundreds of times in response tothe environmental temperature change [5].

2.2 Stimuli-responsive gating function of biomem-branes

Nature gives us excellent examples of environ-mental stimuli-responsive smart membrane systems.Ion channels are pore-forming proteins that help es-tablish and control the small voltage gradient across

the cell membrane of all living cells, by allowing theflow of ions down their electrochemical gradient [1-3].In some ion channels of the cell membrane, passagethrough the pore is governed by a gate, which maybe opened or closed by chemical or electrical signals,

temperature or mechanical force, depending on thevariety of channels. For example, activated by a mem-brane voltage or a signaling molecule, a potassium ionchannel can switch from a closed state to an open stateand the process is reversible. Therefore potassium ionscan be selectively allowed to cross the membrane (Fig.2). Such an environmental stimuli-responsive gatingfunction of biomembranes provides an exciting modelfor membrane scientists and technologists to developartificial smart membranes with self-regulated mem-brane resistance.

2.3 Design of stimuli-responsive smart mem-

branes

Inspired by the stimuli-responsive ion channelsacross the cell membranes and according to the exist-ing smart materials, artificial environmental stim-uli-responsive smart membranes can be designed as (1)stimuli-responsive smart hydrogel membranes, (2)smart membranes with grafted stimuli-responsive sur-faces, and (3) smart membranes with porous sub-strates and stimuli-responsive gates.

Stimuli-responsive smart hydrogel membranesare those prepared with the whole membrane made ofstimuli-responsive smart hydrogels. The membraneresistance and the permeability of such membranescan be self-regulated by the stimuli-responsive con-formational change of smart hydrogels that constructthe whole membrane (Fig. 3). The resistance for solutediffusion and/or solvent permeation across the mem-brane changes with the conformational change of thesmart hydrogels. Such smart membranes are usuallyused for stimuli-responsive controlled release becausethe solute diffusion across the membrane can be easilycontrolled in response to environmental stimuli. Theadvantage of this type of hydrogel membranes is thatthe membrane preparation is relatively simple. On the

Figure 1 Schematic illustration of trans-membranemass-transfer and membrane separation

Figure 2 Stimuli-responsive ion channel gating model of the cell membrane (modified with permission from Ref. [3])


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other hand, the limitation of this type of smart mem-branes is that the response rate is relatively slow, be-cause the hydrogel is crosslinked and the responsespeed of crosslinked smart hydrogel is always muchslower than that of linear smart polymer. It has beenreported that, the larger the crosslinked hydrogel scaleis, the slower the response rate [6]. Therefore, in prac-

tical applications, this kind of smart membranes hadbetter be designed in small scale, such as microcap-sule membranes.

Smart membranes with grafted stimuli-responsivesurfaces are those prepared by grafting or coatingsmart materials onto the substrate membrane surfaceby certain chemical or physical methods. The surfacecharacteristics and/or the membrane resistance of suchmembranes can be adjusted by self-regulation accord-ing to the stimuli-responsive conformational changeof the grafted or coated smart materials on the mem-brane surfaces (Fig. 4). The substrate provides me-chanical strength and dimensional stability, while theconformational changes of the grafted functional

polymers result in the environment responsive char-acteristics. The grafted chains have freely mobile endsso that the prepared membranes respond faster to theenvironmental stimuli in compared with hydrogelswith crosslinked network structures. The permeabilityand/or the surface wettability of these membranes canbe controlled or adjusted by the grafted polymers ac-cording to the external chemical and/or physical envi-ronment. Such membranes can be used for both con-trolled release and separation by utilizing the stim-uli-responsive conformational change of the func-tional surface layer.

Smart membranes with porous substrates and

stimuli-responsive gates are those prepared by graftingor coating smart materials onto the porous membrane

substrate by certain chemical or physical methods.Various grafting techniques, including chemical graft-ing, plasma-induced grafting, and radiation-inducedgrafting and so on, can be employed to prepare stimuli-responsive membranes by grafting different functionalpolymers either onto the external membrane surface orboth the external surface and the inside surface of pores.

The porous substrate provides mechanical strengthand dimensional stability, and the conformationalchanges of the grafted functional polymers result inthe environment responsive characteristics. The mem-brane pore size or the membrane resistance of suchmembranes can be adjusted by self-regulation by thestimuli-responsive volume phase transition behaviorof the grafted or coated smart material gates in themembrane pores (Fig. 5). The grafted or coated smartmaterials in the membrane pores can act as smartvalves that respond to environmental stimuli. The mi-cro-architecture and response mechanism of this typeof smart membranes are the most similar to the stim-uli-responsive ion channel gating model of the cell

membrane shown in Fig. 2. Because the grafted chainshave freely mobile ends so that the grafted gatingmembranes respond fast to the environmental stimuli,and the length and density of the grafted chains can becontrolled to adjust the pore switching characteristics,this type of smart membranes may find broader andmore flexible applications than the above two types.

3 FOUR ESSENTIAL ELEMENTS FOR SMARTMEMBRANES

(1) Responsivity of smart membranes respondingto environmental stimuli is the first key factor for de-signing and developing smart membranes (Fig. 6). The

Figure 3 Stimuli-responsive smart hydrogel membrane

Figure 4 Stimuli-responsive smart membrane with grafted responsive surface


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indexes of responsivity of smart membranes include

both thermodynamic and dynamic ones, i.e., the responsedegree and the response speed. Usually, large responsedegree and rapid response speed are desired, althoughthe detailed requirements are case-dependent.

(2) Stability of the smart membrane processes isthe second key factor, which stands for a stable per-formance of smart membranes. During the operationprocesses, the smart membranes should maintain theirmaterial conformations as well as their membraneresistances when the environmental information isfixed. That is, the smart materials governing the re-sponsivity of smart membranes should be robustenough during the membrane operation.

(3) Reversibility of the response of smart mem-branes to the environmental stimuli is also an essentialelement for smart membranes to achieve self-regulativeadjustment of membrane resistance. For example, forthe smart membrane with porous substrate and respon-sive gates (Fig. 5), the gates in the membrane poresshould still retain their properties intact even thoughthey have undergone repeated environmental changes.Such reversibility enables the smart membranes to beused repeatedly.

(4) Reproducibility of smart membrane materialsand processes is another key factor, which is especiallyimportant for the practical applications of smart mem-branes. With the precondition of above-mentioned re-

sponsivity, stability and reversibility, the reproducibil-ity of smart membranes is usually dependent on themicro-morphology control of the smart membranematerials. For wide-spread or large-scale applicationof smart membranes, such reproducibility is definitelyessential.

Figure 6 Four essential elements for effective smartmembranes

At present stage, the first key factor, responsivity

of smart membranes, is still a challenging topic in thedesign and fabrication of smart membranes. Exceptthe response degree and the response speed of smartmembranes are usually case-dependent, responsivityof smart membranes responding to new stimuli is de-sired whenever new environmental information ap-pears. Besides, the reproducibility is also still a mainchallenging topic for the wide-spread or large-scaleapplication of smart membranes.

4 SMART MEMBRANE TYPES CLASSIFIEDBY STIMULI-RESPONSIVE PROPERTY

Environmental stimuli-responsive smart materi-als or intelligent materials are the kind of marvelousmaterials that have the capability to sense their envi-ronment signals, process these data and respond ac-cordingly. They have one or more properties that canbe significantly changed in a controlled fashion byexternal stimuli, such as temperature (T), pH, andsubstance concentration (C). Such smart materialsmake it possible to design and fabricate artificialbiomimetic smart membranes. As illustrated in Fig. 7,if the smart materials have dramatic volume change orconformational change responding to environmental T,pH, C, or other stimuli, they can be used to fabricate

smart gating membranes with positively or negativelyresponsive model according to their conformationalchange property.

4.1 Thermo-responsive smart membranes

4.1.1 Types and fabrication of thermo-responsivesmart membranes

Because there are many cases in which environ-mental temperature fluctuations occur naturally, andthe environmental temperature stimuli can be easilydesigned and artificially controlled, much attentionhas been focused on thermo-responsive membranes.

Poly(N-isopropylacrylamide) (PNIPAM) is apopular thermo-responsive polymer. It shows a distinct

Figure 5 Stimuli-responsive smart membrane with porous substrate and responsive gates


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and reversible phase transition at the lower critical

solution temperature (LCST) around 32 C [7]. Whenthe environmental temperature is lower than the LCST,the PNIPAM can bind plenty of water molecules on itsamide groups through hydrogen-bonding interaction,and thus it is in a swollen and hydrophilic state; how-ever, when the temperature is higher than the LCST,the PNIPAM is dehydrated because of the cleavage ofthe hydrogen-bonding, and thus it is in a shrunken andhydrophobic state. That is, the conformation change ofthe PNIPAM can result in volume phase transition ofPNIPAM hydrogels from a swollen and hydrophilicstate at temperatures below the LCST, to a shrunkenand hydrophobic state at temperatures above the LCST.

When PNIPAM-based polymers are used to fab-ricate thermo-responsive gates in porous membrane, apositively responsive model [Fig. 7 (a)] can beachieved for thermo-responsive gating membranes.When the grafting yield is in the proper range, thegrafted PNIPAM chains on the pore surface are in aswollen state at temperatures below the LCST, so thepores in the membrane are closed by the PNIPAMgates. In contrast, the grafted PNIPAM chains on thepore surface are in a shrunken state at temperaturesabove the LCST, and therefore the pores in the mem-brane are in an open state. As a result, from thethermo-responsive closed/open switching of thegates in the membrane pores, the hydraulic permeabil-

ity (pressure-driven convective flow of solvents) orthe diffusional permeability (concentration-drivenmolecular diffusion of solutes) across the membranescan be controlled by self-regulation by the environ-mental temperature [7-15].

If the responsive gates of the smart membranesare constructed from thermo-responsive interpenetrat-ing polymer networks (IPNs) of poly(acrylamide)(PAAM) and poly(acrylic acid) (PAAC), thermo-responsive gating membranes featured with negativelythermo-responsive gating characteristics [Fig. 7 (b)],i.e., the membrane pores opening is induced by adecrease rather than an increase in temperature, can be

achieved [16]. PAAM and PAAC form polycomplexesin solution through hydrogen bonding [17]. By coop-

erative zipping interactions between the molecules

that result from hydrogen bonding, it has been foundthat the PAAM/PAAC-based IPN hydrogels are fea-tured with a thermo-responsive volume phase transi-tion characteristic that is the reverse of that of PNI-PAM, i.e., the hydrogel swelling is induced by an in-crease rather than a decrease in temperature [17, 18].When the environmental temperature is lower than theupper critical solution temperature (UCST) of thePAAM/PAAC-based IPN gel, PAAC forms intermo-lecular hydrogen bonds with PAAM, and the IPN hy-drogels retain a shrinking state by the interaction be-tween two polymer chains or so-called chain-chainzipper effect. On the other hand, when the environ-

mental temperature is higher than the UCST of theIPN gel, PAAC dissociates intermolecular hydrogenbonds with PAAM and the IPN hydrogels retain aswelling state by the relaxation of the two polymerchains. Therefore, the membrane gates shrink at tem-peratures below the UCST, due to the PAAM/PAACcomplex formation by hydrogen bonding, and swell attemperatures above the UCST, due to PAAM/PAACcomplex dissociation by the breakage of hydrogenbonds. As a result, the membrane pores change froman open situation to a closed situation when thetemperature increases from one that is below theUCST to another that is above the UCST [16].

4.1.2 Phenomenological models for describingthermo-responsive solute diffusion coefficient of PNI-PAM-grafted porous membranes

For the above-mentioned PNIPAM-grafted po-rous membranes including both thermo-responsive flatmembranes and core-shell microcapsule membraneswith a porous membrane substrate and grafted PNI-PAM gates, the following phenomenological modelsare verified to be effective for describing thermo-responsive solute diffusion coefficient of PNIPAM-grafted porous membranes [5]. Owing to a phase tran-sition of the grafted PNIPAM gates in the pores of themembranes, the physical condition of the PNIPAM-

grafted membranes at temperatures above the LCST isdifferent from that below the LCST. Therefore, different

(a) Positively responsive model (b) Negatively responsive model

Figure 7 Positively and negatively responsive models of smart gating membranes


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models need to be developed respectively for thesetwo temperature ranges.

Above the LCST, the PNIPAM gates in themembrane pores are in the hydrophobic and shrunkenstate; the solute can move through the membrane only

if it finds a pore with a diameter greater than its di-ameter. The diffusion coefficient of the solute is de-pendent on the sieving behavior of the membrane.With some simplification and deduction, the diffusioncoefficient of the solute across the membrane abovethe LCST is given by [5]

2

s Bm m

g s

exp 3.14166

r k TD k

d r

=

(2)

in which Dm is the diffusion coefficient of soluteacross the membrane, rs is the Stokes-Einstein radiusof solute molecule, dg is the mean value of the porediameters of the grafted membranes, kB is Boltz-manns constant, Tis the absolute temperature, is theviscosity of solvent, and kmis an obstruction constantreflecting both the porosity and the pore tortuosity fora given membrane substrate (ungrafted) that can becalculated by

( )2 s ms om

o B

6exp 3.1416

r Drk

d k T

=

(3)

where do is the mean value of the pore diameters ofthe ungrafted membrane substrate, and (Dm)o is thediffusion coefficient of solute across the ungraftedmembrane substrate. That is, above the LCST, the

diffusion coefficient of a solute with radius, rs, acrossthe membrane can be predicted by knowing the char-acteristics of the membrane substrate before graftingand the pore size distribution of the PNIPAM-graftedmembrane.

Below the LCST, the PNIPAM gates are in thehydrophilic and swollen state, i.e., the gates are in thehydrogel state. The solute is able to pass through ahydrogel like a diffusion process. The solute transportwithin the hydrogels occurs primarily in the wa-ter-filled regions in the space delineated by the poly-mer chains [19]. The diffusion coefficient of the solutecan be described using the equation derived from hy-drodynamic theory [19, 20]:

( )0.75g o s m oexpD k r k D= (4)where Dg is the diffusion coefficient in the hydrogel,Do is the diffusion coefficient at infinite dilution cal-culated following the Stokes-Einstein equation, kcis aconstant for a given polymer-solvent system, and isthe volume fraction of the polymer in the gel that canbe calculated by [5]

2

g

o

1d

d

=

(5)

That is, below the LCST, the diffusion coefficient of a

solute across the PNIPAM-grafted membrane can bepredicted by detecting the pore-filling ratio of the

membrane at temperatures above the LCST.

4.2 pH-Responsive smart membranes

pH is an important environmental parameter forbiomedical applications, because the pH change oc-curs at many specific or pathological body sites, suchas the stomach, intestine, endosome, lysosome, bloodvessels, vagina and tumor extracellular sites. For ex-ample, there is an obvious change in pH along thegastrointestinal tract from the stomach (pH = 1-3) tothe intestine (pH= 5-8). Moreover, there are alsomore subtle changes within different tissues. Certaintumors, as well as inflamed or wound tissue, exhibit apH different from 7.4 as it is in circulation. For exam-ple, chronic wounds have been reported to have pHvalues between 7.4 and 5.4, and tumor tissue is alsoreported to be acidic extracellularly [21]. Besides, pH

variation is also very common in chemical reactionsand environmental changes. Therefore, pH-responsivesmart membranes have attracted considerable interestfrom various fields.

All pH-responsive materials with pH-responsiveswelling or shrinking properties contain either acidicor basic groups, which can respond to changes in en-vironmental pH by gaining or losing protons [21]. Forexample, the pH-responsive volume phase transitioncharacteristics of poly(methacrylic acid) (PMAA) andpoly(N,N-dimethylaminoethyl methacrylate) (PDM)hydrogels have been verified to be opposite [22].PMAA hydrogels are featured with a positively

pH-responsive volume phase transition characteristic,i.e., the hydrogel swelling is induced by an increase inthe environmental pH; on the contrary, PDM hy-drogels show a negatively pH-responsive volumephase transition characteristic, i.e., the hydrogelswelling is induced by a decrease in the environmentalpH. When the environmental pH is higher than thecorresponding value of the effective dissociation con-stant (pKa), the PDM hydrogel shrinks, but the PMAAhydrogel swells. On the other hand, when the ambientpH is decreased to be lower than the correspondingvalue of pKa, the PMAA hydrogel shrinks, but thePDM hydrogel swells. Therefore, PMAA can be usedto achieve negatively pH-responsive model for smart

gating membranes [Fig. 7 (b)] [22], while PDM can beused to achieve a positively pH-responsive model [Fig.7 (a)].

4.3 Glucose-responsive smart membranes

Glucose-responsive membranes and systems areconsidered to be very important candidates for devel-oping glucose-responsive self-regulated insulin releasesystems for therapy of diabetes, which is a majorcause of death in industrialized countries and is stilllacking better ways to administrate insulin delivery.

For glucose-responsive self-regulated insulin releasesystems, stability and responsivity of the system are


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very important and essential, because only a stablesystem can ensure safety during therapy and only afast response can ensure exact self-regulated insulin-release during changes in glucose concentration. Tomeet both stability and responsivity, glucose-responsive

gating membranes with porous substrates and linear-grafted functional polymeric gates are competent. Theporous membrane substrates can provide mechanicalstrength and dimensional stability. As the lineargrafted polymeric chains have freely mobile ends,which are different from the typical crosslinked net-work structure of the hydrogels that gives rise to rela-tively immobile chain ends, the responsiveness ofsuch smart membranes to the environmental stimulicould therefore be faster than that of their correspond-ing homogeneous analogs, owing to the more rapidconformational changes of the functional polymers.

By chemically immobilizing glucose oxidase(GOD) onto pH-responsive polymers, the polymeric

system could exhibit a glucose-responsive property.The immobilized GOD acts as the glucose sensor andcatalyst, because it is sensitive to glucose and couldcatalyze the glucose conversion to gluconic acid. Dueto the appearance of gluconic acid, the local pH valuedecreases in the microenvironment as a result. There-fore, the GOD-immobilized pH-responsive polymercould respond to environmental glucose concentrationvariation. For example, if the GOD is chemically im-mobilized onto PAAC chains, at neutral pH in the ab-sence of glucose, the carboxyl groups of the PAACchains are dissociated and negatively charged. There-fore, the repulsion between negative charges makes

the PAAC chains extended. However, when the glu-cose concentration increases, GOD catalyzes the oxi-dation of glucose into gluconic acid, thereby loweringthe local pH in the microenvironment, protonating thecarboxylate groups of the PAAC chains. Therefore,the chains shrink due to the reduced electrostatic re-pulsion between the PAAC chains. With graftedPAAC gates and covalently bound GOD fabricated inthe membrane pores, glucose-responsive gating mem-branes can be achieved [23-26].

4.4 Molecular-recognizable smart membranes

Molecular-recognizable smart materials can bedesigned with PNIPAM as actuator and crown ether orcyclodextrin as molecular recognizing receptor [27-33].By using such molecular-recognizable smart materials,molecular-recognition gating membranes can beachieved [34-43], which are usually fabricated by sus-pending molecular-recognizable host molecules ontothe freely mobile ends of grafted PNIPAM polymersin the membrane pores. The molecular-recognizablemolecules acting as sensors can recognize specialguest molecules, while the linear grafted thermo-responsive PNIPAM polymers acting as actuators cantransform their conformation after the sensors recog-

nize the guest molecules. As a result, the cooperationbetween the sensors and the actuators achieves the

switching function of molecular-recognizable gatingmembranes. If the host/guest complexation results in anegative shift of the LCST [28, 30], the molecular-recognizable smart materials could show an isother-mal shrinkage at a certain temperature, with which

positively responsive model can be achieved for smartgating membranes [Fig. 7 (a)]. That is, the membranepores can switch from closed to open state byrecognizing the presence of specific molecules in theenvironment. In contrast, if the host/guest complexa-tion results in a positive shift of the LCST [27, 28], themolecular-recognizable smart materials could show anisothermal swelling at a certain temperature, withwhich negatively responsive model can be achievedfor smart gating membranes [Fig. 7 (b)]. That is, themembrane pores can switch from open to closedstate inversely by recognizing specific molecules be-ing present in the environment. The above-mentionedtwo gating models of the smart membranes are desir-

able or applicable in different cases.

5 SMART TOOLS FOR CONTROLLABLERELEASE AND SEPARATION

5.1 Smart tools for controllable release

By applying the same principle from flat mem-branes to microcapsule membranes, environmentalstimuli-responsive smart microcapsules can be designedwith porous membranes and responsive gates (Fig. 8).Such microcapsules are highly valuable for achievingstimuli-responsive and self-regulated controlled re-lease and drug delivery.

Figure 8 Smart microcapsule with porous membrane andsmart gates for stimuli-responsive controlled release

The target of a controlled drug delivery system isfor an improved drug treatment (outcome) throughrate- and time-programmed and site-specific drug de-livery [44]. Environmental stimuli-responsive controlled-release systems are desired specifically for this pur-pose. These environmental stimuli-responsive releasesystems can release specified chemicals or drugs at aparticular site where an environmental condition, suchas temperature, pH or other information, is differentfrom that at other sites. In developing environmentalstimuli-responsive controlled-release systems, espe-cially pulsated release systems with an on-off switch-

ing response, one of the important parameters is toreduce the response time of the release rate to stimuli.


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As the release rate from microcapsules is generallycontrolled by the rate of diffusion of solute moleculesacross the thin microcapsule membrane, an increase inthe release rate in response to stimuli may be expectedwhen compared to gels and microspheres. Therefore,microcapsules with a thin membrane are suitable forstimuli-responsive controlled-release systems [4, 8, 26, 35].

5.2 Smart tools for controllable separation

With stimuli-responsive self-regulation of mem-brane resistance, smart membranes are good tools fornot only controllable adjustment of both diffusionalpermeability (Fig. 8) and hydraulic permeability [Fig.9 (a)], but also controllable size separation [Fig. 9 (b)],affinity separation (Fig. 10), chiral separation (Fig. 11),and so on.

5.2.1 Smart membranes for size separationIf the smart membranes are designed with proper

grafting or coating yield of smart materials, they canbe applied to achieve controllable separation by sizeeffect. As is the case in Fig. 9 (b), when the smart ma-terials are in the shrunken state and the membranepores are in the open state, both smaller and largermolecules/particles can permeate across the mem-brane. With environmental stimuli appear, the smartmaterials turn to swollen state and the membranepores switch to closed state, as a result only smallermolecules/particles can permeate across the membranebut the larger ones can not any more. With similarprinciple, diverse separation models by size effect canbe designed with smart membranes.

5.2.2 Smart membranes for affinity separationAffinity membranes are membranes that can

identify and separate specific molecules. In the fieldsof separation and purification of protein, enzyme,chiral substance, hydrophobic solutes and so on, affin-ity membranes have been widely studied. As men-tioned above, PNIPAM shows a distinct and reversiblephase transition at the LCST around 32 C. When theenvironmental temperature is lower than the LCST,the PNIPAM can bind plenty of water molecules on its

amide groups through hydrogen-bonding interaction,and thus it is in a swollen and hydrophilic state; how-ever, when the temperature is higher than the LCST,the PNIPAM is dehydrated because of the cleavage ofthe hydrogen-bonding, and thus it is in a shrunken andhydrophobic state. Furthermore, it has been reportedthat the phase transition of PNIPAM responding totemperature change could affect the association con-stant between -cyclodextrin (-CD) and guest mole-cules in a PNIPAM-modified -CD system. Such dra-matic phase transition characteristics make PNIPAMextremely attractive for developing thermo-responsivesmart membranes for affinity separation.

Because the surfaces of PNIPAM-grafted mem-

branes can change from a hydrophilic to hydrophobicstate when the environmental temperature increasesacross the LCST of PNIPAM and vice versa, thermo-responsive affinity membranes with PNIPAM func-tional surface layers can be used for hydrophobic ad-sorption and separation of hydrophobic solutes [45, 46].Fig. 10 shows the schematic illustration of thermo-responsive adsorption/desorption of bovine serumalbumin (BSA) molecules with PNIPAM-graftedmembranes by using their thermo-responsive hydro-phobic/hydrophilic property [46]. The affinity separa-tion is operated in a model of adsorption at a tem-perature above the LCSTdesorption at a tempera-

ture below the LCST.Because the binding constants of -CDs with

(a) Adjustment of hydraulic permeability

(b) Separation by size effect

Figure 9 Schematic illustration of controllable permeability adjustment and size separation with stimuli-responsive membranes


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association constant between -CD and guest mole-cules in a PNIPAM-modified -CD system. When thetemperature is above the LCST, the association con-stant of -CD toward guest molecules is much smallerthan that at a temperature below the LCST, due to the

steric hindrance caused by the shrunken and hydro-phobic PNIPAM chains. Therefore, by using such acooperation function between PNIPAM and -CD, aneffective membrane process can be achieved for chiralresolution with the smart membrane [50].

In the membrane shown in Fig. 11, -CD mole-cules act as host molecules or chiral selectors andPNIPAM chains act as micro-environmental adjustersfor the association constant of -CD molecules towardguest molecules. The chiral resolution of enantiomersthrough the membrane is operated at a temperaturebelow the LCST. Under this condition, the graftedPNIPAM chains are in a swollen and hydrophilic stateand the association constant of -CD toward recog-

nized molecules is large; as a result, one of the twoenantiomers is captured by -CD molecules due tochiral recognition during the permeation of racemates,while the other is permeated. When the complexationbetween -CD and captured molecules in the mem-brane reaches equilibrium, a wash process is carriedout to remove the uncaptured or free molecules. Then,the operating temperature is increased to be higherthan the LCST and the grafted PNIPAM chains turninto a shrunken and hydrophobic state. At the sametime, the association constant between -CD and cap-tured molecules decreases significantly. As a result,decomplexation of captured enantiomers from -CD

molecules occurs, and thus the enantiomers are sepa-rated and the membrane is regenerated. Compared withother affinity membrane processes, this smart mem-brane process, especially the decomplexation process,is environmentally friendly and can be easily operated.

5.3 Demonstrations for commercial and engi-neering applications

Because the smart membrane is still a newcomerin the membrane family, widespread applications ofsmart membranes on a large scale have not beenachieved yet up till now. However, there have been a

lot of demonstrations for commercial and engineeringapplications of smart membranes. Several examplesare listed as follows.

5.3.1 Initiation-cessation control of enzyme reactionusing pH-responsive capsule membranes

Kokufuta et al. [51, 52]proposed a kind of polye-lectrolyte-coated pH-reponsive microcapsule mem-branes and used for initiation/cessation (or on/off)control of enzyme reactions. Stable microcapsules(mean diameter of 8-10 m) with a semipermeablepolystyrene (PSt) membrane was prepared by depos-iting the polymer around emulsified aqueous droplets,

and polyelectrolyte adsorption was performed by stir-ring the microcapsules in appropriate buffers contain-

ing the desired polyelectrolyte at room temperature.Using the original enzyme-loaded PSt microcapsuleswithout the adsorbed polymer layer, enzymic hydroly-sis occurred both at pH 5.5 and pH 4.5, resulting inthe formation of both glucose and fructose. In contrast,

when the microcapsules with the pH-responsive mem-branes were employed at pH 4.5, the action of the en-trapped enzyme was almost completely suppressed(the concentration of the two sugars produced was lessthan 0.1 gml

1), but the reaction could be initiated

by adjusting the pH of the outer medium to 5.5. Suchon/off control could be repeated reversibly throughouta single run of measurements. Repeated measurementsover a period of eight days also gave excellent repro-ducible results without damage to the microcapsules.

5.3.2 Modulation of protein release from pH-responsivecapsule membranes

Okhamafe et al. [53]reported how a pH-sensitive

polymer, hydroxypropyl methylcellulose acetate suc-cinate (HPMCAS), can be employed to control therelease of protein from chitosan-alginate microcapsulemembranes generated using an electrostatic dropletgenerator. In particular, the in vitro release behavior ofalbumin from chitosan-HPMCAS-alginate microcap-sule membranes was examined under pH conditionsthat simulate the stomach and intestinal fluids in bothman and fish. The results showed that the unmodifiedchitosan-alginate microcapsules are unsuitable for oraldelivery of therapeutic/bioactive proteins due to itspoor protein retention capacity (20% and 6% after 4and 24 h, respectively) at the lower end of the gastricpH range. However, it has been demonstrated that bysuitably modifying the microcapsules with HPMCAS,protein retention capacity can be improved to nearly60% and 70% after 4 and 24 h, respectively.

5.3.3 Potential site-specific and controlled drug de-livery to the colonic region

Rodriguez et al. [54]proposed a multiparticulatesystem for colonic drug delivery based on a drug con-taining hydrophobic cores microencapsulated with apH-dependent polymeric membrane, to avoid drugdelivery in the upper gastrointestinal tract (GIT) andtarget drugs to the terminal ileum and colonic region.The system consists of a hydrophobic core [cellulose

acetate butyrate (CAB) microspheres] encapsulatedinto pH-sensitive (EudragitS) microcapsules. A con-trolled release of drugs from the CAB polymer matrix,once the enteric polymer had dissolved, was attemptedusing this double microencapsulation procedure. Thiswas achieved for budesonide (BDS), a very hydro-phobic drug, whose release was adequately controlledat pH values above 7. In this way, colonic diseasessuch as Crohns disease or ulcerative colitis could betreated locally, opening a new therapeutic use for thisdrug in inflammatory diseases.

5.3.4 Control of pH during denitrification usingpH-responsive capsule membranes

Vanukuru et al. [55] reported that acidic phos-phate granules encapsulated within a pH-responsive


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membrane were used to demonstrate pH control dur-ing denitrification. Numerous physico-chemical andbiological reactions of interest in the environmentalfield, such as the neutralization of industrial wastestreams, precipitation of metals, microbially-mediated

degradation, and disinfection with chlorine, are de-pendent on pH. The efficiency of these processes de-pends on the control of pH within an optimum range.pH control can easily be accomplished using auto-matic pH control dispensers. The basic operation ofthese devices involves dispensing measured amountsof an acid or a base to maintain the pH within a de-sired operating range. However, these devices may bedifficult to be used in relatively inaccessible locations,such as during in situbioremediation of contaminatedgroundwater. Control of pH in groundwater during insitu bioremediation is important because microbialactivity can result in pH changes. For example, de-pending on the intrinsic buffering capacity of the soil

and groundwater, denitrification activity can cause thepH of groundwater to rise beyond optimum ranges. Apromising means for controlling pH in inaccessiblelocations is through the use of encapsulated buffers[55]. Batch experiments were performed with an etha-nol-fed denitrifying culture to evaluate the effective-ness of the microcapsule membranes in controlling thepH of a suspended-growth system. The rise in pH forthe experiments without microcapsule membranes wasmore substantial than that with microcapsule mem-branes. The pH was controlled to within a narrowerrange closer to neutral when 1000 mg of microcap-sules was added to the batch system than when 100

mg was added.Up to now, it seems that smart membranes incapsule forms are easier to be designed and applied inpractical applications than those smart membraneswith flat or hollow-fiber architectures. The reason isthat the mass production of capsules with smart mem-branes is relatively simpler and easier to be achievedand controlled. However, it is still difficult to achievemass production of the flat or hollow-fiber smartmembranes with good reproducibility at the presentstage. To promote the commercial and engineeringapplications of smart membranes with flat or hol-low-fiber architectures, it is urgent to develop newtechniques to achieve the mass production of the smart

membranes, which is still challenging.

6 SOME CONCLUDING REMARKS

Membrane technologies are highly promising asstrong supporting technologies for the global sustain-able development [56]. Artificial smart membranes areconsidered as one of the most important and promis-ing topics in the field of membrane science and tech-nology in the 21st century, although they are still intheir initial development stage now. Worldwide, con-siderable effort is being deployed to develop smart

membrane materials and systems. The technologicalbenefits of smart membranes have begun to be identi-

fied and demonstrators are under construction for awide range of applications from controlled drug de-livery, to chemical separation, to water treatment, tobioseparation, to chemical sensors, to chemical valves,to tissue engineering, etc.

In the field of smart membranes, the followingtwo topics will be the main focus of research in thenear future. One is the development of novel and effi-cient smart membrane materials and the other is theenhancement of smart membrane processes. For thefirst topic, the process-oriented design and fabricationof efficient smart membrane materials, the conceptdesign of smart membrane materials and systems withnovel functions, the micro/nano-structure-controllablefabrication of smart membrane materials and the sta-bility and mass production of smart membrane mate-rials and systems are some foreseeably importantthemes. For the second topic, the improvement in theresponse rate of smart membranes, the improvement

in the sensitivity of smart membranes and the devel-opment of multi-stimuli-responsive complex smartmembrane processes are some important themes thatshould be involved. Besides, the quantitatively de-scription and modeling of the smart membrane proc-esses in controlled release and separations, which arevery important for the design and operation of smartmembranes, are still somewhat lacking at the presentstage and should be emphasized in the near future.

To innovate, learn from nature! This is defi-nitely the right way for scientists and technologists inthe field of smart membranes to develop novel smartmembrane materials and to improve smart membrane

processes. Nature is demonstrating numerous originalmodels for achieving efficient artificial biomimeticsmart membrane materials and systems. With moreand more smart membranes being developed and bet-ter and better performances being achieved, it is defi-nitely to be expected that smart membranes will beapplied more and more widely. The authors believethat smart membranes might be applied in some casesin the future that we cannot even imagine today.

REFERENCES

1 Dutzler, R., Campbell, E.B., MacKinnon, R., Gating the selectivity

filter in ClC chloride channels, Science, 300, 108-

112 (2003).

2 Jiang, Y., Lee, A., Chen, J., Cadene, M., Chait, B.T., MacKinnon, R.,

The open pore conformation of potassium channels, Nature, 417,

523-526 (2002).

3 The Nature Reviews Drug Discovery Ion Channel Questionnaire

Participants, The state of ion channel research in 2004,Nature Rev.

Drug Discov., 3, 239-278 (2004).

4 Chu, L.Y., Smart Membrane Materials and Systems, Springer-Verlag,

Berlin (2011).

5 Chu, L.Y., Niitsuma, T., Yamaguchi, T., Nakao, S., Thermo-responsive

transport through porous membranes with grafted PNIPAM gates,

AIChE J., 49, 896-909 (2003).

6 Tanaka, T., Fillmore, D.J., Kinetics of swelling of gels, J. Chem.

Phys., 70, 1214-1218 (1979).

7 Schild, H.G., Poly(N-isopropylacrylamide): Experiment, theory and


12/13


application,Prog.Polym. Sci., 17, 163-249 (1992).

8 Chu, L.Y., Park, S.H., Yamaguchi, T., Nakao, S., Preparation of

thermo-responsive core-shell microcapsules with a porous mem-

brane and poly(N-isopropylacrylamide) gates, J. Membr. Sci., 192,

27-39 (2001).

9

Chu, L.Y., Zhu, J.H., Chen, W.M., Niitsuma, T., Yamaguchi, T., Nakao,S., Effect of graft yield on the thermo-responsive permeability through

porous membranes with plasma-grafted poly(N-isopropylacrylamide)

gates, Chin.J. Chem.Eng., 11, 269-275 (2003).

10 Li, Y., Chu, L.Y., Zhu, J.H., Wang, H.D., Xia, S.L., Chen, W.M.,

Thermo-responsive gating characteristics of poly(N-isopropylacrylamide)-

grafted porous polyvinylidene fluoride membranes,Ind.Eng. Chem.

Res., 43, 2643-2649 (2004).

11 Xie, R., Chu, L.Y., Chen, W.M., Xiao, W., Wang, H.D., Qu, J.B.,

Characterization of microstructure of poly(N-isopropylacrylamide)-

grafted polycarbonate track-etched membranes prepared by plasma-

graft pore-filling polymerization, J. Membr. Sci., 258, 157-166

(2005).

12 Yang, M., Chu, L.Y., Li, Y., Zhao, X.J., Song, H., Chen, W.M.,

Thermo-responsive gating characteristics of poly(N-isopropylacrylamide)-

grafted membranes, Chem.Eng. Technol., 29, 631-636 (2006).

13 Xie, R., Li, Y., Chu, L.Y., Preparation of thermo-responsive gating

membranes with controllable response temperature,J.Membr. Sci.,

289, 76-85 (2007).

14 Li, P.F., Xie, R., Jiang, J.C., Meng, T., Yang, M., Ju, X.J., Yang, L.,

Chu, L.Y., Thermo-responsive gating membranes with controllable

length and density of poly(N-isopropylacrylamide) chains grafted by

ATRP method,J.Membr. Sci., 337, 310-317 (2009).

15 Chen, Y.C., Xie, R., Yang, M., Li, P.F., Zhu, X.L., Chu, L.Y., Gating

characteristics of thermo-responsive membranes with grafted linear

and crosslinked poly(N-isopropylacrylamide) gates, Chem. Eng.

Technol., 32, 622-631 (2009).

16

Chu, L.Y., Li, Y., Zhu, J.H., Chen, W.M., Negatively thermorespon-sive membranes with functional gates driven by zipper-type hydro-

gen-bonding interactions, Angew. Chem. Int. Ed., 44, 2124-2127

(2005).

17 Ilmain, F., Tanaka, T., Kokufuta, E., Volume transition in a gel

driven by hydrogen bonding,Nature, 349, 400-401 (1991).

18 Xiao, X.C., Chu, L.Y., Chen, W.M., Wang, S., Li, Y., Positively

thermo-sensitive monodisperse core-shell microspheres,Adv.Funct.

Mater., 13, 847-852 (2003).

19 Amsden, B., Solute diffusion within hydrogels. Mechanisms and

models,Macromolecules, 31, 8382-8395 (1998).

20 Cukier, R.I., Diffusion of brownian spheres in semidilute polymer

solutions,Macromolecules, 17, 252-255 (1984).

21 Ju, X.J., Xie, R., Yang, L., Chu, L.Y., Biodegradable intelligent

materials in response to chemical stimuli for biomedical applica-

tions,Expert Opin. Therap.Pat., 19, 683-696 (2009).

22 Qu, J.B., Chu, L.Y., Yang, M., Xie, R., Hu, L., Chen, W.M., A

pH-responsive gating membrane system with pumping effects for

improved controlled-release, Adv. Funct. Mater., 16, 1865-1872

(2006).

23 Ito, Y., Casolaro, M., Kono, K., Imanishi, Y., An insulin-releasing

system that is responsive to glucose, J. Control. Release, 10,

195-203 (1989).

24 Cartier, S., Horbett, T., Ratner, B.D., Glucose-sensitive membrane

coated porous filters for control of hydraulic permeability and insu-

lin delivery from a pressurized reservoir, J. Membr. Sci., 106,

17-24 (1995).

25

Chu, L.Y., Li, Y., Zhu, J.H., Wang, H.D., Liang, Y.J., Control ofpore size and permeability of a glucose-responsive gating membrane

for insulin delivery,J. Control.Release, 97, 43-53 (2004).

26 Chu, L.Y., Liang, Y.J., Chen, W.M., Ju, X.J., Wang, H.D., Prepara-

tion of glucose-sensitive microcapsules with a porous membrane and

functional gates, Colloids Surf.B Biointerf., 37, 9-14 (2004).

27 Irie, M., Yoshifumi, Y., Tanaka, T., Stimuli-responsive polymers:

chemical induced reversible phase separation of an aqueous solutionof poly(N-isopropylacrylamide) with pendent crown ether groups,

Polymer, 34, 4531-4535 (1993).

28 Yang, M., Chu, L.Y., Xie, R., Wang, C., Molecular-recognition in-

duced phase-transition of two thermo-responsive polymers with

pendent beta-cyclodextrin groups, Macromol. Chem. Phys., 209,

204-211 (2008).

29 Ju, X.J., Chu, L.Y., Liu, L., Mi, P., Lee, Y.M., A novel thermo-

responsive hydrogel with ion-recognition property through su-

pramolecular host-guest complexation, J. Phys. Chem. B, 112,

1112-1118 (2008).

30 Mi, P., Chu, L.Y., Ju, X.J., Niu, C.H., A smart polymer with

ion-induced negative shift of the lower critical solution temperature

for phase-transition,Macromol.RapidCommun., 29, 27-32 (2008).

31

Ju, X.J., Liu, L., Xie, R., Niu, C.H., Chu, L.Y., Dual

thermo-responsive and ion-recognizable monodisperse micro-

spheres,Polymer, 50, 922-929 (2009).

32 Ju, X.J., Zhang, S.B., Zhou, M.Y., Xie, R., Yang, L., Chu, L.Y.,

Novel heavy-metal adsorption material: ion-recognition

P(NIPAM-co-BCAm) hydrogels for removal of lead(II) ions, J.

Hazard.Mater., 167, 114-118 (2009).

33 Pi, S.W., Ju, X.J., Wu, H.G., Xie, R., Chu, L.Y., Smart responsive

microcapsules capable of recognizing heavy metal ions, J. Colloid

Interf. Sci., 349, 512-518 (2010).

34 Yamaguchi, T., Ito, T., Sato, T., Shinbo, T., Nakao, S., Development

of a fast response molecular recognition ion gating membrane, J.

Am. Chem. Soc., 121, 4078-4079 (1999).

35

Chu, L.Y., Yamaguchi, T., Nakao, S., A molecular recognitionmicrocapsule for environmental stimuli-responsive con-

trolled-release,Adv.Mater., 14, 386-389 (2002).

36 Ito, T., Hioki, T., Yamaguchi, T., Shinbo, T., Nakao, S., Kimura, S.,

Development of a molecular recognition ion gating membrane and

estimation of its pore size control,J.Am. Chem. Soc., 124, 7840-7846

(2002).

37 Ito, T., Sato, Y., Yamaguchi, T., Nakao, S., Response mechanism of

a molecular recognition ion gating membrane Macromolecules, 37,

3407-3414 (2004).

38 Ito, T., Yamaguchi, T., Osmotic pressure control in response to a

specific ion signal at physiological temperature using a molecular

recognition ion gating membrane,J.Am. Chem. Soc., 126, 6202-6203

(2004).

39

Ito, T., Yamaguchi, T., Controlled release of model drugs through a

molecular recognition ion gating membrane in response to a specific

ion signal,Langmuir, 22, 3945-3949 (2006).

40 Ito, T., Yamaguchi, T., Nonlinear self-excited oscillation of a syn-

thetic ion-channel-inspired membrane, Angew. Chem. Int. Ed., 45,

5630-5633 (2006).

41 Okajima, S., Sakai, Y., Yamaguchi, T., Development of a regener-

able cell culture system that senses and releases dead cells, Lang-

muir, 21, 4043-4049 (2005).

42 Okajima, S., Yamaguchi, T., Sakai, Y., Nakao, S., Regulation of cell

adhesion using a signal-responsive membrane substrate, Biotechnol.

Bioeng., 91, 237-243 (2005).

43 Yang, M., Xie, R., Wang, J.Y., Ju, X.J., Yang, L., Chu, L.Y., Gating

characteristics of thermo-responsive and molecular-recognizablemembranes based on poly(N-isopropylacrylamide) and -cyclodextrin,


13/13


J.Membr. Sci., 355, 142-150 (2010).

44 Breimer, D.D., Future challenges for drug delivery, J. Control.

Release, 62, 3-6 (1999).

45 Choi, Y.J., Yamaguchi, T., Nakao, S., A novel separation system

using porous thermosensitive membranes,Ind.Eng. Chem.Res., 39,

2491-

2495 (2000).46 Meng, T., Xie, R., Chen, Y.C., Cheng, C.J., Li, P.F., Ju, X.J., Chu,

L.Y., A thermo-responsive affinity membrane with nano-structured

pores and grafted poly(N-isopropylacrylamide) surface layer for hy-

drophobic adsorption,J.Membr. Sci., 349, 258-267 (2010).

47 Yanagioka, M., Kurita, H., Yamaguchi, T., Nakao, S., Development

of a molecular recognition polymer system controlled by thermosen-

sitive polymer chains,Ind.Eng. Chem.Res., 42, 380-385 (2003).

48 Xie, R., Zhang, S.B., Wang, H.D., Yang, M., Li, P.F., Zhu, X.L., Chu,

L.Y., Temperature-dependent molecular-recognizable membranes

based on poly(N-isopropylacrylamide) and -cyclodextrin, J.

Membr. Sci., 326, 618-626 (2009).

49 Xie, R., Chu, L.Y., Deng, J.G., Membranes and membrane proc-

esses for chiral resolution, Chem. Soc.Rev., 37, 1243-1263 (2008).

50

Yang, M., Chu, L.Y., Wang, H.D., Xie, R., Song, H., Niu, C.H., A

novel thermo-responsive membrane for chiral resolution, Adv.

Funct.Mater., 18, 652-663 (2008).

51 Kokufuta, E., Shimizu, N., Nakamura, I., Preparation of polyelec-

trolyte-coated pH-sensitive poly(styrene) microcapsules and their

application to initiation-cessation control of an enzyme reaction,

Biotechnol.Bioengin., 32, 289-294 (1988).

52

Kokufuta, E., Polyelectrolyte-coated microcapsules and their po-tential applications to biotechnology, Bioseparation, 7, 241-252

(1999).

53 Okhamafe, A.O., Amsden, B., Chu, W., Goosen, M.F.A., Modula-

tion of protein release from chitosan-alginate microcapsules using

the pH-sensitive polymer hydroxypropyl methylcellulose acetate

succinate,J.Microencaps., 13, 497-508 (1996).

54 Rodriguez, M., Vila-Jato, J.L., Torres, D., Design of a new multi-

particulate system for potential site-specific and controlled drug de-

livery to the colonic region,J. Control.Release, 55, 67-77 (1998).

55 Vanukuru, B., Flora, J.R.V., Petrou, M.F., Aelion, C.M., Control of

pH during denitrification using an encapsulated phosphate buffer,

WaterRes., 32, 2735-2745 (1998).

56 Koros, W.J., Evolving beyond the thermal age of separation proc-

esses: Membranes can lead the way, AIChE J., 50, 2326-2334

(2004).

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