Microfluidic fabrication of responsive hierarchical microscale particles from macroscale materials and nanoscale particles

Accepted Manuscript Title: Microfluidic Fabrication of Responsive Hierarchical Microscale Particles from Macroscale Materials and Nanoscale Particles Author: Juan Wang Jan C.T. Eijkel Mingliang Jin Shuting Xie Dong Yuan Guofu Zhou Albert van den Berg Lingling Shui PII: DOI: Reference:

S0925-4005(17)30283-6 http://dx.doi.org/doi:10.1016/j.snb.2017.02.056 SNB 21787

To appear in:

Sensors and Actuators B

Received date: Revised date: Accepted date:

22-11-2016 25-1-2017 10-2-2017

Please cite this article as: J. Wang, J.C.T. Eijkel, M. Jin, S. Xie, D. Yuan, G. Zhou, A. van den Berg, L. Shui, Microfluidic Fabrication of Responsive Hierarchical Microscale Particles from Macroscale Materials and Nanoscale Particles, Sensors and Actuators B: Chemical (2017), http://dx.doi.org/10.1016/j.snb.2017.02.056 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Microfluidic Fabrication of Responsive Hierarchical Microscale Particles from Macroscale Materials and

ip t

Nanoscale Particles Juan Wang1,2, Jan C. T. Eijkel2,3, Mingliang Jin1,2, Shuting Xie1,2, Dong Yuan1,2,

1

cr

Guofu Zhou1,2, Albert van den Berg2,3 and Lingling Shui1,2*

Institute of Electronic Paper Displays, South China Academy of Advanced

Mega Center, Guangzhou 510006, China

Joint International Research Laboratory of Optical Information of the Chinese

an

2

us

Optoelectronics, South China Normal University, Guangzhou Higher Educational

Ministry of Education, South China Normal University, Guangzhou Higher

3

M

Educational Mega Center, Guangzhou 510006, China

BIOS/Lab-on-a-Chip Group, MESA+ Institute for Nanotechnology & MIRA Institute for Biomedical Technology and Technical Medicine, University of

Correspondence: [email protected]; Tel.: +86-20-39314813

Ac ce p

*

te

d

Twente, Enschede 7500AE, the Netherlands

Academic Editor: name

Received: date; Accepted: date; Published: date Abstract: Stimuli-responsive microparticles have been widely applied in sensors, actuators, chemical and biomedical analysis, and optoelectronic devices. Microfluidic technology has been demonstrated as a powerful top-down tool to create hierarchical microparticles with exquisite control over size, uniformity, morphology, structure and chemical composition. With the exploration of materials, various stimuli-responsive materials have been obtained, responding to magnetic, thermal, electrical, light and chemical stimuli. Self-assembly of nanoparticles is a quick bottom-up approach for the generation of functional materials with collective optical, electrical and magnetic properties. By combining macroscale materials and nanoscale particles using microfluidic technology, smart microparticles can be fabricated, possessing the responsive properties from the composing materials, the high surface-to-volume ratio and enhanced field effect from self-assembled nanostructures, and the advantages from microfluidics for controlling composition and structure of monodisperse microparticles. Therefore, better controlled physical and chemical properties and more sensitive and efficient performance can be achieved. In this

1 Page 1 of 34

review, we summarize the current status of the stimuli-responsive microparticles fabricated by microfluidic technology using polymers and nanoparticles, focusing on the microfluidic platforms, selection of responsive materials, and the achieved functions and applications.

Keywords:

Microfluidics;

Hierarchical

microparticle;

Stimuli-responsive;

Ac ce p

te

d

M

an

us

cr

ip t

Nanoparticle, Self-assembly

2 Page 2 of 34

1. Introduction Microscale hierarchical particles fabricated from macroscale polymer materials and nanoscale particles retain the native properties of both polymers and

ip t

nanoparticles, and possess the advantage of being hierarchical composition in the

range of macro-, micro- and nanometers. These smart microparticles with

cr

various compositions and structures, which respond to externally applied stimuli

or environmental variation, have received intensive attention for their broad

us

applications in the chemical, biomedical, photonic and electronic areas[1-13]. Responsive polymer materials are sometimes called “intelligent” materials

an

including polymers or liquid crystals which can quickly respond to specific external environmental variation or stimuli, accompanied with a remarkable

M

change in physical properties like color, structure, wettability, solubility or volume. Polymers, before and after polymerization, exist as pre-polymer solution and gel-like block materials, respectively. Therefore, they can be manipulated by

d

fluidic technologies before polymerization, and easily be combined with solid

te

devices after polymerization. According to the response mechanisms to external stimuli, these materials can be categorized in magnetically, thermally, electrically,

Ac ce p

light and chemically responsive groups. Table 1 summarizes various representative stimuli-responsive materials, responsive mechanisms, and their corresponding applications. The responsive behavior of these materials is mainly due to the molecular changes or internal interaction forces that are induced by external stimuli. Therefore, chemical design and synthesis is here the main road to obtain these functional materials. Self-assembly of colloidal nanoparticles has long and often been employed as a bottom-up fabrication method to construct ordered nanostructures. Self-assembly of colloidal particles opens novel avenues for the generation of functional materials with collective optical, electrical and magnetic properties[14, 15]. The nanoparticle materials, which can be organic, inorganic or organic-inorganic hybrids, are engineered by chemical or mechanical 3 Page 3 of 34

methodologies, and are regarded as reliable functional materials. They are applied in diverse fields from chemical engineering and mechanical engineering to bioengineering. Table 2 summarizes various representative nanoparticles which are responsive to external stimuli. Some nanoparticles by themselves

ip t

possess stimuli-responsive properties to external actuation. They can also be encapsulated and self-assembled in polymer solution and polymerized into stable

cr

and flexible block substrate with well-ordered nanoarrays functioning as

responsive photonic crystal materials[16]. Integration of nanoparticles in

us

responsive polymers amplifies their sensitivity, selectivity and responsiveness by increasing surface-to-volume ratio or creating functional nanostructures[6, 17].

an

The combination of responsive polymer materials with nanoparticles to construct responsive photonic crystals has been reviewed in references[18-20].

M

Table 1. Representative stimuli-responsive molecules/groups of polymers and their applications.

Responsive molecules/groups

Thermal

N-alkylacrylamides, eg. PNIPAM[21-23]; vinyl ether, eg. poly(vinylether)[24]; alkylene oxide, eg. poly(ethylene oxide)[25]

Electrical

-OH, -NH2, -CONH, -CONH2, -COOH, -HSO3, eg. poly(acrylic acid-co-acetoacetoxy ethyl methacrylate) (P(AA-co-AAEM)), Pluronic F127; conductive polymer, eg. poly(acetylene)s (PPV), poly(thiophene)s (PT), poly(p-phenylene sulfide) (PPS), poly(pyrrole)s (PPY), polyanilines (PANI), poly(acetylene)s (PAC); bismethacrylate-co-methacrylic acid sodium salt [30-32]; charged color pigments[16]

drug release[33, 34]; actuator[31]; sensing[32]

Light

azobenzene[35, 36]; spiropyran[37, 38]; triphenylmethane[39]; cholesteric liquid crystal[40]

microvalves[41, 42]; drug-release[43, 44]; optical switch[45]; reflection display[46]

carboxylic[47-49] eg. poly(acrylic acid) (PAA), poly(methacrylic acid) (PMMA), poly(methacrylic acid-g-ethylene glycol) (P(MAA-g-EG); amino groups[50-52] eg. chitosan, poly(ethylene imine) (PEI), poly(N,N-dimethyl aminoethyl methacrylate) (PDMAEMA); sulfonic acid[53]

drug delivery and release[54-56]; sensor[57, 58]; optical device[59]; photolithography[60]

Ac ce p

te

d

Stimuli

Chemical

pH

ionic strength redox

Applications textiles[24]; detection[26, 27]; anti-fouling[28], water harvesting[29]

poly(n-(morpholino)ethylmethacrylate)-b-poly (4-(2-sulfoethyl)-1-(4-vinylbenzyl)pyridinium betaine) (PMEMA-b-PSVBP)[61] poly(ferrocenylsilane)s[62]; poly(lactic/glycolic) acid[63]

4 Page 4 of 34

Stimuli

Responsive molecules/groups

solvent

Applications

poly(methyl methacrylate) (PMMA)[64]; polystyrene (PS)[65]

Table 2. Representative stimuli-responsive nanoparticles and their applications.

Thermal

Applications

iron(III) oxide nanoparticles (Fe3O4 NPs)[66]; cobalt ferrite (CoFe2O4 NPs)[67]; nickel ferrite[68] PNIPAM nanogels[6]; silver nanoparticles (Ag NPs)[72]; TiO2 nanoparticles[73]

therapy, imaging[67, 69]; sensor[70]; molecular detection[71]

Light

gold nanoparticles (AuNPs)[79]; Fe3O4 nanoparticles[80]; inorganic nanoparticles (eg. CuS NPs)[81]

Chemical

polystyrene (PS) nanoparticles[1], poly(methacrylic acid) (PMAA) nanoparticles[83]; cyclosporine A nanoparticles[84]; metal nanoparticles[85]

an

M

sensor[72]; photonic crystals[73] actuator[75]; drug release[33]; displays[74, 77]; energy storage[78]

us

Electrical

TiO2 nanoparticles[74, 75]; carbon black[76]; conductive nanoparticles (eg. polypyrrole)[33]

ip t

Magnetic

Responsive nanoparticles

cr

Stimuli

Cancer nanomedicine[79]; antibacterial activity[82] display[1]; drug delivery[83, 84]; sensing[85]

d

To tune functionality, physical methods play an important role besides chemical modification of the molecular structures. For instance, a block of material in normal phase show definitely different behavior

te

compared to the same material engineered to micro- and nano-scale or with nano-featured surfaces. Key factors like responsiveness and sensitivity can be physically improved by increasing the specific

Ac ce p

surface-to-volume ratio or by fabrication in specific structures[86, 87]. Structuring materials in the micro- and nanometer scale can be realized by various methods, such as template-assisted assembly[88], layer-by-layer assembly[89, 90], spraying[91], solvent evaporation[92] or microfluidics[59, 93]. Among them, microfluidic technology is becoming a powerful top-down tool to fabricate microcapsules due to its capability of engineering materials in the fluidic phase at the micro- to nanoscale. Microfluidics has recently emerged as a popular platform to construct microcapsules with various chemical compositions, diverse structures, monodisperse sizes and multiple functions. Microdroplets (microcapsules in liquid phase) with sizes in the range of 0.1-100 μm could be obtained by combination of various microchannel geometries (step-flow[94], flow focusing[95], co-flow[96], T-junction[97] and head-on[98] structures), fluidic flow rates and flow-rate ratios[99]. The microdroplet composition and structure (oil-in-water (O/W)[100], water-in-oil (W/O)[101, 102], oil-in-water-in-oil (O/W/O)[103], water-in-oil-in-water (W/O/W)[104], and complex emulsions[105] can be engineered by careful device design and material selection[1]. The generated microdroplets in microfluidic devices can then be either on-line or off-line polymerized by UV-irradiation[106], heating[7], chemical reaction[107] or solvent evaporation[108], yielding monodisperse micro- and nanoparticles/capsules in solid phase. Thus, homogeneous sphere, core-shell, Janus and complex microparticles could be obtained. They were subsequently applied in

5 Page 5 of 34

sensors[93, 109, 110], actuators[87, 111, 112], microvalves[113, 114], biological probes[115, 116], bioassays[117-119], bio-separation[3, 120], drug delivery[13, 121-123], controlled release[13, 44], water treatment[11, 124, 125], electronic displays[16] and optical devices[93, 106, 126, 127] with various responsiveness to magnetic[118], electrical[16], optical[126], thermal[128] and chemical[121] stimuli, or the combination of two or three[11-13].

ip t

When these three factors of microfluidic technology, macroscale polymer

materials and nanoparticles are judiciously combined, hierarchical structures

cr

composed of different materials can be obtained, as e.g. shown in Figure 1. Nanoparticles can be dispersed in fluidic pre-polymer solution as a dispersion

us

which can then be encapsulated as droplets dispersed in a continuous phase in a microfluidic device. The microdroplets can be further treated one by one

an

in-channel, or collected outside the channel. The nanoparticles in the pre-polymer solution can be anchored and trapped/organized and frozen on/in the polymer

M

microparticles by polymerization. Via this combination, the macroscale materials are divided into microscale particles with a nanoscale structure. Each microparticle is composed of responsive nanoparticles/polymers; and therefore

d

can respond to external stimuli. At the same time it possesses the properties of

te

large specific surface area, monodispersity, controllable size, and high stability as well as sensitive and rapid response.

Ac ce p

In this review, we focus on recent development of smart microparticles

fabricated using facile microfluidic technology by combining polymers (responsive or non-responsive) with nanoparticles (non-responsive or responsive) in single unit. The sections are categorized by the response mechanisms of materials to different stimuli, focusing on the microfluidic devices, the materials selection, the improved functionality and the application areas.

6 Page 6 of 34

ip t cr us an M te

polymers and nanoparticles.

d

Figure 1. Schematic drawing of the microfluidic fabrication of smart hierarchical microparticles with

Ac ce p

2. Magnetically Responsive Microparticles So far, magnetically responsive microparticles have been mainly fabricated by encapsulating magnetic-responsive nanoparticles into polymer materials. Alternatively, polymer molecules have been modified with magnetic-responsive nanoparticles, such as ferrite nanoparticles, metallic nanoparticles or metallic nanoparticles with shells. The stimuli induced responsive behavior is from the nanoparticles. Because of the high surface area, low cytotoxicity, magnetization saturation and modifiable surface, magnetic nanoparticles have been broadly investigated and applied in magnetic resonance imaging[129-131], drug delivery[132, 133], separation[134], sensing[135, 136] and cell tracking[137]. When magnetic nanoparticles are encapsulated in a polymer network, diverse structural variation can be obtained by controlling the strength and direction of the applied magnetic field, due to the tunable distance of the superparamagnetic particles. Colloidal photonic crystal (CPC) microparticles with a magnetically responsive structural color from assembled nanoparticles have been created using a triphase microfluidic technique[1]. The highly uniform emulsion droplets were fabricated by encapsulating a dispersion of magnetic nanoparticles in the photocurable resin trimethylolpropane ethoxylate triacrylate (EO3-TMPTA) in one flow stream and a dispersion of polystyrene (PS) nanoparticles as the other flow stream in a microfluidic flow-focusing

7 Page 7 of 34

device. The as-prepared droplets as templates were then in-situ polymerized by UV irradiation, as shown in Figure 2 (AI). Various structural colors have been obtained due to the lattice of close-packed PS nanoparticles in one hemisphere of the CPC by varying the nanoparticle size. A dipole moment and “OFF” & “ON” switchable behavior could be achieved by introducing the CPC microparticles in a substrate with arrays of well-ordered holes (Figure 2 (AII)). Each CPC microparticle could respond to

ip t

the applied magnetic field and act as a discrete pixel unit in a multipixel array. Thus, an information display was realized by using a magnetic needle. Moreover, monodisperse bi-compartmental microparticles with distinct hemisphere regions displaying magnetism and fluorescence have also been

cr

achieved via a facile microfluidic approach and solvent-evaporation with magnetic nanoparticles

occupied one hemisphere and quantum dots (QDs) in the other[138]. As a result, a magnetic-responsive fluorescent switch was achieved. A Janus-bead panel allowed free writing when an external magnetic

us

field was applied. It is therefore possible to construct flexible bead displays using this magnetically responsive technology.

Moreover, Lee et al. have created free-floating color-barcoded magnetic microparticles using a

an

PDMS microfluidic device[2], as shown in Figure 2 (BI). The color-barcoded microparticles were made of magnetic ink (M-Ink) acted as a code region and photocurable hydrogel as a probe region. By controlling the strength of the applied magnetic field, diverse structural colors of M-Ink were obtained

M

due to the tunable distance of the superparamagnetic inter-particles (Figure 2 (BII). Various shapes of color barcoded microparticles have been engineered by using an ultraviolet mask pattern assisted by a computer-controlled spatial light manipulation. Using this platform, a multiplex DNA detection assay

d

with encoding and decoding process was demonstrated. Color-barcoded magnetic microparticles with increased encoding capacity and multi-axis manipulation capacity are excellent candidates for

te

applications in bioassays, drug delivery, separation and clinical diagnostics. Kim and colleagues have fabricated monodisperse magnetically responsive microparticles with

Ac ce p

complex surfaces of self-assembled colloidal particles using a microfluidic device, and applied for biological sensing[3]. The magnetically responsive microparticles are composed of silica nanoparticles

and iron oxide (Į-Fe2O3) nanoparticles. Via a coaxial microfluidic glass capillary device, monodisperse droplets of a photocurable suspension were created, and then polymerized by UV-irradiation (Figure 2

(CI)). The rotational frequency of the particles in a rotating magnetic field as well as the surface roughness

and

size of the

Janus microparticles could be precisely

controlled.

These

magnetic-responsive Janus microparticles demonstrated a rotation and translation motion under

magnetic field. Separation of a mixture of three differently coded magnetic microparticles could be obtained by guiding them into target positions (Figure 2 (CII)). Moreover, the silica arrays on the

magnetically responsive microparticle surfaces could be decorated with chemical or biological groups, broadening their applications as biological probes, high-throughput immunoassays, microfluidic pumps and mixers. Yuet and colleagues have obtained monodisperse and multifunctional Janus hydrogel particles with superparamagnetic properties[139]. A microfluidic platform enabled manufacturing microdroplets encapsulating nanoparticles controlled by field-induced self-assembly. Control of the spatial distribution of biochemical payloads and complex construction was achieved. The orientation of Janus

8 Page 8 of 34

particles could be locally and precisely controlled by an externally applied magnetic field. As a result these particles could be employed in sorting, microrheological probes, magnetic imaging, tissue engineering, and novel metamaterials. Through a bottom-up assembly approach, magnetically responsive Janus particles with complex structures were obtained by modulating the particle concentration and composition as well as the type of the magnetic field. These magnetic-responsive

ip t

Janus microcapsules modified with functional groups or molecules could be potentially applied in drug delivery or cell mimicry systems[140]. By coding different chemistries per particle, multifunctional

superparamagnetic Janus particles with optical enhancement capabilities have also been fabricated,

cr

which could be potentially useful for novel sensing to achieve miniaturization of dot blot analysis[141].

Carbon-based nanomaterials have received significant momentum due to their

us

unique structure and properties (e.g. high mechanical strength, good stability, electrical, thermal and optical properties). Hierarchical nano-/micro-structures constructed using carbon-based nanomaterials combined with functional (e.g. magnetic, thermal or

an

fluorescent) particles would provide with multi-functional responsibility, being applied in biomedicine, environment and electronic devices[142-144]. Cheng Wang's group have proposed a facile microfluidic strategy to fabricate magnetic porous multi-walled carbon nanotube beads (MCNTs) with

M

flexible and controllable manipulation for organic contaminants adsorption[4]. The dispersed phase consisted of acidified MCNTs, polystyrene microspheres and Fe3O4 nanoparticles suspending in deionized water, while the dimethyl silicone oil was used as the continuous phase. Through a modified

d

microfluidic device, the MCNT/polystyrene/Fe3O4 droplets were generated at the junction of the T-shaped channel and then treated by thermal solidification and repeatedly washed with n-hexane. The

te

magnetic porous MCNTBs were obtained after calcination under a nitrogen atmosphere. The proposed MCNTs possess hierarchical pores which were beneficial for enhancing their adsorbing capacity and

Ac ce p

efficiency. These 3D magnetic-responsive hierarchical porous structure showed superhydrophobicity

and stable recyclability which could not only improve adsorption efficiency of organic solvents, but also benefit to oriented movement and recycling of the adsorbents. Dong Liang et al. has shown the high electrochemical sensitivity and selectivity by the integration of porous graphene-nTiO2 composite in microfluidic devices[143].

9 Page 9 of 34

(II)

(I)

A

cr

ip t

Methylsilicone oil PS solution

X

us

(I)

Hred

(II)

Time

X/

X/

an

X

Magnetic field intensity

Hblue> Hgreen > Hred dblue< dgreen < dred

M

Sequential ultraviolet pattern

Hblue Hgreen

(I)

Į-Fe2O3 Water nanoparticle Magnet

Figure 2.

(II)

C

Silica particle

Ac ce p

Photocurable droplets

te

DMD dynamic mask

d

Hred

Ultraviolet

B

UV Net magnet moment

(A) Janus microparticles fabricated using a triphase microfluidic device: (I) illustration of the

microparticles with various shapes prepared by tuning the interfacial tension among triple phases; (II) demonstration of the photonic patterns driven by applied magnetic field. Reproduced with permission from Ref. 1. Copyright 2012 Wiley. (B) Creation of (M-Ink)-based color-barcoded magnetic microparticles using a microfluidic platform: (I) illustration of the fabrication principle; (II) demonstration of the color-barcoded microparticles. Adapted from Ref. 2 with permission from Nature publishing group. (C) Fabrication of magnetic Janus particles using microfluidic device: (I) schematic of the microfluidic fabrication process and principle; (II) demonstration of the differently coded magnetic microparticles used for mixture separation application. Modified

10 Page 10 of 34

with permission from Ref. 3. Copyright 2010 Wiley.

In summary, magnetically responsive microparticles are created by either encapsulating magnetic nanoparticles in a polymer network or linking them to polymer molecules. Their response is induced by an externally applied magnetic field of specific strength and direction to achieve movement of the nanoparticles or change the inter-particle distance. These microparticles hold great promise for flexible

ip t

displays[1], micro-actuators and sensors[139], controlled release systems[13] and immunoassays[129]. 3. Thermally Responsive Microcapsules

cr

Thermo-responsive polymers typically exhibit a critical temperature at which a phase transition occurs. This property is mainly attributed to the change of intra- and/or intermolecular interactions, leading to

us

the expansion or contraction of the polymer chains in a specific medium. Thermally responsive polymer materials are generally classified into three types: low critical solution temperature polymer (LCST)[145,

146],

upper

critical

solution

temperature

polymer

(UCST)[147,

148]

and

an

solvent-dependent polymer[149]. Because of the remarkable changes in their configurations (size, volume or structure) which can be triggered by a temperature variation, they have been widely studied and applied in various fields[150, 151].

Poly (N-isopropyl acrylamide) (PNIPAM) hydrogel is commonly taken as an example because of

M

its dramatic phase transition in water at the critical temperature of about 32 °C[22, 152]. When the temperature is >32 °C, PNIPAM hydrogel exists in a shrunken state due to dehydration. On the contrary, the hydrogel presents a swollen state at <32 °C. To increase responsiveness and sensitivity,

d

either the molecular structure can be modified, or the surface-to-volume ratio is increased by

te

encapsulating nanoparticles[87] or creating nanopores[86] in hydrogel microcapsules. Microfluidic technology is a useful tool for these modifications. Thermally responsive microcapsules with colloidal crystal shells have been engineered using a

Ac ce p

microfluidic device combining co-flow and flow-focusing geometries by Weitz et al[5], as shown in Figure 3 (A). The colloidal crystals were immobilized in the thermo-responsive polymer network to

form the microcapsule shell. The optical properties (such as Bragg wavelength) of the gel-immobilized colloidal crystal shell could be flexibly tuned by selection of stimuli-sensitive polymer materials and control of particle concentration. The diffraction color or Bragg diffraction wavelength of the microcapsules could be triggered by temperature variation. This thermally induced change of optical properties could be applied as labels and biological/chemical sensors. Thermally responsive nanogels have also been encapsulated into the polymers to create smart

microcapsules with novel and complex structures, which could enhance performance efficiency and broaden applications[6, 17, 106]. Yue et al. have demonstrated a novel and facile strategy to construct thermally triggered microcapsules with fast response by encapsulating nanogels with a hierarchical phase-transition mechanism[17]. These thermo-sensitive microcapsules exhibited remarkably high response speed compared to normal homogenous thermo-responsive microspheres, according to the hierarchical phase-transition at different volume phase transition temperature (VPTT) of the embedded nanogels and the microsphere matrixes. Yuandu Hu and colleagues have taken a simple and robust microfluidic approach to fabricate monodisperse thermally responsive soft photonic crystal (PC)

11 Page 11 of 34

microcapsules[6], which is shown in Figure 3 (B). A co-flow microfluidic device was used to construct the W/O/W microdroplets. Monodisperse photonic crystal microcapsules were synthesized by UV polymerizing the W/O/W microdroplet shell of ethoxylated trimethylolpropane triacrylate (ETPTA) photocurable resin. The inner phase of the microcapsules consisted of thermally responsive PNIPAM crystalline nanogels which organized to form well-ordered photonic crystal structures through

ip t

evaporation-triggered crystallization. The intensity of the reflection spectra of the crystalline nanogel arrays in the core could be modulated reversibly by changing the shell thickness or the temperature. A

temperature change could induce internal structure variations, leading to changes in color and optical

cr

properties of these thermo-sensitive PC microcapsules. For example, when the temperature increased

from 20 °C to 35 °C, the color of the green PC microcapsules gradually changed from bright green to light green, and then to milky-white. Correspondingly, the reflection peak was broadened. Vice versa,

us

the opposite response was observed during cooling-down process. The thermally responsive behavior of these PC microcapsule is mainly attributed to the thermally-induced change of the nanogel size and the ordering of crystalline arrays. In further developments, microfluidic technology can be used to

an

engineer the PC microcapsule size and shell thickness, and thereby to tune the optical properties of the photonic band gaps and structural colors. Such composite microcapsules with highly efficient thermally

M

responsive properties open a door to drug delivery applications, and smart actuators and sensors.

d

(I)

(III)

(III)

Nanogel particles

ETPTA resin

B

PVA/Glycerol/H2O

Heating

Cooling

Intensity (a.u.)

(II)

Ac ce p

te

(II)

A

Intensity (a.u.)

(I)

Figure 3. (A) Microfluidic fabrication of thermally responsive microcapsules with hydrogel-immobilized PS colloidal crystal shell: (I) schematic of the fabrication process; (II) microscope images showing the changes of the microcapsules with PNIPAM-immobilized colloidal crystal shell induced by thermal stimuli; (III) reflection spectra of the microcapsule at different temperature. Reproduced with permission from Ref. 5. Copyright 2010 Wiley. (B) Thermally responsive photonic crystalline microcapsules fabricated using a co-flow microfluidic device: (I) schematic of the fabrication process; (II) illustration of the changes of the microcapsule with PNIPAM crystalline nanogels as inner core induced by thermal stimuli; (III) demonstration of the thermally reversible behavior of the PC microcapsules. Reproduced with permission from Ref. 6. Copyright 2012 American Chemical Society.

The thermally responsive microcapsules can be fabricated by microfluidic technology using different combinations of responsive polymer with non-responsive nanoparticles, non-responsive polymers with responsive nanoparticles or responsive polymer with responsive nanoparticles, while using templates of either single microcapsules or complex microcapsules with shell structures. The microcapsules show a reversible, quick and stable response to environmental temperature change or

12 Page 12 of 34

local heating-cooling manipulation. Each microcapsule acts as a single sensing unit or display pixel, which has shown excellent performance in practical applications, such as microactuators[86, 153], drug delivery and release systems[154], displays[6], sensors[125] and so on. 4. Electrically Responsive Microparticles

ip t

Electrically responsive materials are based on the use of polymers with electrical sensitivity such as ionic polymers[155, 156] and liquid crystals[157], or polymers containing electric-field responsive particles like carbon black[158], titanium oxide[74] and charged polystyrene particles[159]. Electric

cr

field as an external stimulus has particular merits, such as the wide availability of equipment, the precise controllability of the applied field by current or voltage control, including alternating current (AC) fields with controllable waveform shapes and frequency.

us

Typically, a pre-polymer dispersion containing electric-field responsive nanoparticles is employed as the microfluidic dispersed phase to produce electrical-responsive microparticles. Nisisako et al. demonstrated the engineering of uniform electrically responsive Janus microbeads using a microfluidic

an

device and thermal polymerization[7], as shown in Figure 4 (AI). These Janus beads had distinct composition and anisotropic properties. The bi-compartments were composed of carbon black (black color) in one hemisphere and titanium oxide (white color) in the other hemisphere. The location of the

M

carbon black and titanium oxide in two hemispheres caused an asymmetric charge distribution, as shown in Figure 4 (AII), leading to a different behavior to electrical stimulus. When an electric field was applied, each bi-colored microsphere could flip and display either a black or white color. Thus

d

complex information could be displayed by processing an electrical signal program. More colorful electrically responsive Janus microparticles have also been engineered by Kim et al. via a microfluidic

te

approach with colloidal particles self-assembled in polymer-based materials[16]. In one hemisphere colloidal nanoparticles were closely packed into a photonic crystalline structure and showed structural

Ac ce p

color. In the other hemisphere, carbon black nanoparticles with charges were encapsulated, enabling an electrically driven multi-color switch. Owing to the mechanical flexibility and wide range of electrical conductivity, electrically

conductive biocompatible materials have been investigated for various fields in terms of drug release system[160] and electronic devices[8]. Jin-Heong Yim et al. has reported the fabrication of functional monodisperse microparticles from Fe3O4-poly(3,4-ethylenedioxythiophene) (PEDOT)/polystyrene

sulfonate (PSS)-agarose hybrid materials using a microfluidic device[8]. The fabrication process was described in Figure 4 (BI). And Figure 4 (BII) confirmed the electric conduction of the hybrid PEDOT/PSS microparticles by turning on a light-emitting diode. Thus, it would be suitable for applications in biomedical and eco-friendly electronic systems because of their magnetic sensitivity and electric conductivity.

13 Page 13 of 34

Janus droplets

A

Aqueous phase

B

(I)

Monomer (black) Monomer (white)

135e Aqueous phase

:PEDOT/PSS :Hydrogel :Fe3O4 :Water :PVA

us

cr

(II)

ip t

(I)

an

(II)

M

Figure 4. (A) Microfluidic fabrication of electrically responsive bicolored Janus microcapsules: (I) schematic of the fabrication procedure; (II) optical images of an information display driven by electrical actuation of the

d

fabricated microcapsules. Reproduced with permission from Ref. 7. Copyright 2010 Wiley. (B) Hybrid PEDOT/PSS microparticle prepared using a flow-focusing microfluidic device: (I) illustration of the preparation

te

principle; (b) demonstration of the electrical property of the fabricated microparticles. Reproduced with

Ac ce p

permission from Ref. 8. Copyright 2016 Elsevier.

In summary, there exist two main groups of electrically responsive microparticles. One group is

composed of electrically responsive nanoparticles encapsulated in microcapsules, in which the nanoparticles can move up and down, the other group is Janus micropartciles that rotate to display different faces driven by applied electric field. With their response to precisely controllable electrical stimuli, these electrically responsive Janus beads can be applied in reflective displays, sensors and optical switches[7, 161].

5. Light Responsive Microcapsules

Light responsive materials have received considerable attention for diverse applications in liquid crystal devices[162, 163], optical switches[164] and drug delivery systems[165, 166], on the basis of their quick change in structure and color in response to light irradiation. Light irradiation has the advantages of remote controllability, intensity variation and wavelength tunability. Light-sensitive groups including azobenzene, triphenylmethane and spiropyran are commonly copolymerized with host polymers to achieve photo-responsiveness[167]. Light-responsive cholesteric liquid crystals have also

14 Page 14 of 34

been used to fabricate light-sensitive microspheres using microfluidic technology[126, 168]. Furthermore, nanomaterials like gold nanorods and Fe3O4 nanoparticles have been widely employed in light-responsive microcapsules for on-demand remote control of target release[169, 170]. Combining the advantages of microfluidic technology and light-responsive materials, numerous highly uniform microcapsules with light-triggered properties have been synthesized. Light-responsive microcapsules

ip t

can find applications in sensing[171], biological imaging[168], drug delivery[9, 12] and so on. Lee and co-workers have demonstrated a light-sensitive microcapsule fabrication process to

encapsulate gold nanorods in microgels and triggered-release of active ingredients[9]. The highly

cr

uniform core-shell double emulsions and the corresponding hydrogel microcapsules were synthesized using a glass capillary microfluidic device, as shown in Figure 5 (AI). Gold nanorods embedded in the

hydrogel network enabled the remote heating of the microcapsules by light irradiation[169], thus

us

providing the light-response of the hydrogel microcapsule shell (Figure 5 (AII)). The reversible diameter change of these photothermal hydrogels will tune the shell permeability and cause triggered-release of active ingredients, demonstrating potential applications in drug delivery, cosmetics

NIPAM

PDMS Oil

(II)

TEMED

M

PDMS Oil

Diameter [ȝm]

A

an

and food/nutrients[172].

(I)

IR (810 nm)

Time [s] 0s

40 s

80 s

120 s

160 s

200 s

240 s

280 s

0s

20 s

40 s

60 s

80 s

100 s

120 s

140 s

320 s

te

d

Cooling

Ac ce p

Figure 5. (A) Microfluidic fabrication of light-responsive hydrogel capsules: (I) demonstration of the fabrication procedure and obtained microcapsules; (II) exploration of the light responsiveness of the fabricated microcapsules. Reproduced with permission from Ref. 9. Copyright 2013 Royal Society of Chemistry.

6. Chemically responsive Particles

A chemical response of microparticles is mainly elicited by redox reactions or solvent absorption. The

redox response thereby is due to the effects of electron transfer; and the solvent responsive is due to the network swelling of polymers in different solvents. Both types of chemical stimuli can trigger a rapid

and remarkable response in microcapsules. pH-responsive microcapsules have been a focus of research because they can be applied for biomedical application in drug delivery[56, 173]. Microcapsules that released their agents under acidic conditions were synthesized by using a shell component such as the cationic triblock copolymer of poly(n-butyl methacrylate - (2-dimethylaminoethyl) - methacrylate - methyl methacrylate)[174]. These microcapsules were very stable, and only dissolved and released the encapsulated contents under acidic conditions due to the highly charged polymer chains[175]. On the other hand, an alkali-triggered microcapsule shell has been demonstrated, which can be dissolved at a constant rate at basic condition,

15 Page 15 of 34

releasing the encapsulated active ingredients[176]. Liu et al. have presented a microfluidic approach to produce core-shell chitosan microcapsules for pH-responsive burst release of hydrophobic drugs[107]. Furthermore, combination of acid-triggered and basic-triggered polymers provides a straightforward approach of designing sequential release of active ingredients at different pH values. Mixtures of the pH-responsive and pH-unresponsive polymers at different mass fractions were used as the middle oil

ip t

phase to prepare hybrid microcapsules using a microfluidic device[176]. Dual pH-responsive core-shell microcapsules have also been studied[177], for which the release rate could be precisely controlled according to the different composition of the hybrid shell. Chen et al. have reported

cr

multi-compartmental Janus microparticles composed of PNIPAM-based copolymer with dual stimuli

of pH- and thermo- responsive groups fabricated by a single emulsification step in a microfluidic device[10], as shown in Figure 6 (AI). Because of the disintegration of the polymer network which has

us

a dual pH- and thermally responsive nature, these Janus microparticles possess the property of a triggered release of the colloidal contents in water at increased pH value when the temperature < LCST (Figure 6(AII)). As a result, these Janus microparticles with a dual-stimulus property could achieve

an

efficient and controllable drug encapsulation and release.

Chemically responsive microcapsules/microparticles can exhibit distinct changes in their properties in response to a variation of pH and/or ionic strength. Chen et al. have demonstrated a

M

triphase microfluidics-assisted self-assembly method to create Janus CPC microparticles with various and changeable structural colors[1]. The changeable structural color of the Janus CPC microparticles was due to the different swelling degree of the polystyrene nanoparticles when the CPC microparticles

d

were treated with an aqueous solution of acrylic acid at different concentration. These Janus CPC microparticles showed a reversible color transition when the acrylic acid concentration was either

te

decreased (by dilution with water) or increased (by evaporation). This solvent-induced swelling causes an increase of the lattice constant and thereby the size of the microparticles. These CPC microparticles

Ac ce p

could be applied as chemical sensors.

A

(a)

Magnetic force Gravity force

(I)

Aqueous phase

(II)

Amphiphilic

Water-Soluble OH-

T
H+

Drying 60 Υ

0 min

1 min

5 min

25 min

0s

6s

27 s

30 s

Branched polymers

Fe3O4 magnetic nanoparticles

Hydrophobic T>LCST

0s 36 s

6s 45 s

56 s

27 s 75 s

PMMA microparticles

56 s

Figure 6. (A) pH-responsive microparticles engineered by a microfluidic device: (I) illustration of the triple-component Janus microparticles preparation process; (II) demonstration of the Janus microparticles responsibility to pH and temperature stimuli. Reproduced with permission from Ref. 10. Copyright 2013 American Chemical Society.

16 Page 16 of 34

The use of a microfluidic platform can contribute to the manufacturing of these microcapsules/microparticles by allowing precise design of the composition of the chemically responsive microparticles, their size, shell thickness and permeability. Thereby, their response to chemical reactions, solvents, variations in ionic strength or pH could be precisely controlled for chemical/biochemical sensing[1] and controlled drug release[178].

ip t

7. Multiple-responsive Microparticles

Design and development of multiple-responsive microparticles are increasingly attractive and desirable

cr

for scientific research and technological applications. Multi-stimuli responsive microparticles are

us

expected to incorporate two or more responsive components in one unit in order to either amplify one function or achieve multiple functions at the same time. Typical examples demonstrate how the multi-stimuli microparticles are designed, fabricated and achieved functions.

an

Su Chen and co-workers have reported a triphase microfluidic approach for the construction of Janus supraparticles with temperature-magnetism-optics triple sensitivity successfully, which can be

M

applied in various fields (environment monitor, bioassays, displays, optoelectronic devices and anticounterfeit)[11]. Supraparticles with dual optical performance of structure color (due to assembly of

d

the PS nanoparticles) and fluorescence (owing to the CdS quantum dots) were constructed assisted by the

te

easy-to-perform microfluidic approach, which can exhibit diverse colors when exposed to different wavelengths. To accomplish proposed multifunctional supraparticles, the as-prepared solution of

Ac ce p

Cd2+/PS hybrid latex, NIPAM photocurable monomer, crosslinker, surfactant, photoinitiator and a mixture of ethoxylated trimethylolpropane triacrylate (TMPTA) monomer, Fe3O4 nanoparticles were introduced into the corresponding microchannel to form into uniform biphasic droplets continuously, as described in Figure 7 (AI). Multiple components encapsulated in the same microparticle allowed color varying due to the temperature stimulus and freely rotation resulted from the magnetism response. The proposed triple-responsive supraparticles exhibited remarkable color variation under different stimuli (Figure 7 (AII)), and therefore, would be promising for applications in optoelectronic devices and bioassays. Figure 7 (AIII) demonstrated the fabricated Janus supraparticles applied as multiple-response displays. Multi-stimuli-responsive hydrogel microfibers by incorporating photothermal magnetite nanoparticles (MNPs) in the temperature-responsive PNIPAM hydrogel microfibers have been prepared by Jinhwan Yoon and colleges utilizing capillary-based microfluidic devices[12]. The discontinuous

17 Page 17 of 34

(droplet) solution was composed of Na-alginate, monomers, crosslinkers, the photo-initiator and magnetite (Fe3O4) nanoparticles (MNPs), while the calcium chloride solution was used as the continuous phase. The microfiber-shaped crosslinked Ca-alginate hydrogels were formed due to the rapid ionic bridge formation at the interfacial layer of the mixed solution and the continuous flow. PNIPAM

ip t

hydrogel microfibers containing MNPs were obtained under in-situ UV-irradiation (Figure 7 (BI)). The incorporated MNPs in the thermo-sensitive hydrogel microfibers absorbed the visible light and

cr

converted the photo-energy into thermal-energy which heated the hydrogel network and triggered local

us

volume changes confined in the light irradiation region, as shown in Figure 7 (BII). Additionally, the prepared hydrogel microfibers were sensitive to external magnetic stimuli because of the MNPs in the hydrogel matrix. Therefore, prepared multi-responsive hydrogel microfibers could be potentially applied

an

in tissue engineering, drug delivery and switching systems.

LiangYin Chu's group applied novel multi-stimuli-responsive microcapsules as smart drug delivery

M

system with "site-specific targeting" and adjustable controlled-release[13]. These microcapsules were constructed by embedding magnetic nanoparticles and temperature-sensitive nanoparticles as

d

"microvalves" into pH-sensitive microcapsule membrane. Figure 7 (C) illustrates the detailed fabrication procedure and the controlled-release mechanism of the multi-stimuli-responsive microcapsule. The

te

middle fluid was the chitosan aqueous solution containing magnetic-responsive nanoparticles and

Ac ce p

temperature-responsive nanoparticles, while the oil phase containing crosslinker glutaraldehyde (GA) was used as the inner fluid and outer fluid, respectively. Highly monodisperse oil-in-water-in-oil

(O/W/O) emulsions were obtained in the co-flow capillary microfluidic device, yielding multiple-stimuli-responsive microcapsules after polymerization. The targeting aggregation at specific pathological sites and effectively adjustable controlled-release could be achieved according to the patients' individual differences (related to body temperature and pH value), which is of critical

significance for more rational drug administration. As a result, this strategy provides with new technology to prepare this kind of "intelligent" controlled release systems.

18 Page 18 of 34

A

copolymerization

Macromonomer

(I)

Cd2+

PS-PMAA

(III)

S2-

Cd2+/PS-PMAA

CdS/PS-PMAA

NIPAm

Nanocrystalline reactor

ip t

Triphase microfluidic device

(II)

Inlet A

O-R Optical response

Inlet B

(I)

an

us

B

T-R Temperature response

cr

M-R Magnetism response

CaCl2

(II)

light

500 ȝm

dark

Ca-alginate

M

Photopolymerization

te

Ac ce p

C

Ca-alginate/PNIPAm gel

d

PNIPAm gel

500 ȝm

pH-responsive chitosan microcapsule membrane

Temperature-responsive sub-microsphere

+

Magnetic nanoparticle Encapsulated drug

Figure 7. (A) Construction of multi-stimuli-responsive supraparticles using a flow-focusing microfluidic device: (I) schematic of the microparticle generation procedure; (II) description of the applications of Janus supraparticles (JSs) as switches and sensors; (III) I-pad prepared from multifunctional JSs at different external stimuli. Reproduced with permission from Ref. 11. Copyright 2015 American Chemical Society. (B) Fabrication of multi-stimuli-responsive microfibers through a microfluidic device: (I) schematic of the microfluidic device

and mechanism of fabricating hydrogel microfibers; (II) optical images of photothermal responsibility of the microfibers. Reproduced with permission from Ref. 12. Copyright 2015 Royal Society of Chemistry. (C) Illustration of fabrication principle and controlled-release mechanism of the multi-stimuli-sensitive microcapsules. Adapted from Ref. 13 with permission from Wiley 2014.

19 Page 19 of 34

8. Summary and Outlook There has been a strong demand for smart/responsive materials with unique properties that can be tuned by external stimuli. In this review, we summarize the recent development in creating responsive microparticles with hierarchical structures obtained by combining macroscale polymer solutions and nanoscale particles. Microfluidic technology is a promising tool to fabricate the hierarchical structures

ip t

at the microscale with well-controlled composition and structure due to the precise control over fluidics and interfaces. By maximally exploiting these advantages, nanoparticles can be encapsulated into single, double or multiple emulsion droplets made of pre-polymer solutions with various shapes,

cr

structures and compartments, yielding various microparticles. Responsiveness can be endowed to the microparticles by introducing functional groups either to the polymer molecules or to the nanoparticles.

us

These microparticles can respond to external stimulus of magnetic, thermal, electrical, optical or chemical nature, which can be applied in sensors and actuators, information displays, drug release, and chemical/biomedical analysis. The responsiveness to stimuli stems either from the polymers or the

an

nanoparticles, which are contained in hierarchical structures optimized for the intended function. Different types of “intelligent” microparticles including homogenous, core-shell and Janus structures have been successfully constructed. A color change of the CPC structure in the microparticles, due to

M

Brag diffraction, can be employed to create a sensing unit or a display pixel. Core-shell microcapsules composed of a stimulus-triggered shell and/or encapsulated stimulus-sensitive nanogels can be used for drug release. It is to be expected that enhanced multi-stimuli-triggered microparticles with multi-compartmental and complex structures will also be fabricated using these strategies. Though

d

complex microparticles are not always necessary for real applications, adding complexity is one of the

te

effective strategies to improve critical functions for specific applications. Microfluidic technology derives its strength from the nature of the composing elements of the

Ac ce p

smart materials. The polymer materials, before polymerization, are in the fluidic phase which is highly suitable to be manipulated using a microfluidic platform; after polymerization, they are in the gel or solid phase which is preferential for encapsulating nanoparticles and for application in real devices. The nanoparticles are in the nanoscale domain, which is easy to be dispersed in a solvent to form a colloidal dispersion and to be entrapped in the polymer network after combination with the polymer material. Microfluidic technology thus provides a highly flexible tool for combining the fluidic polymer materials and the solid nanoparticles. As shown above, by the judicious combination of polymers and nanoparticles, properties can be finely tuned to broaden application areas with high flexibility and controllability. With the developments in both materials and microfluidic technology, intelligent particles with better performance are expected to be engineered using this strategy, exploring more applications in devices and industry. Acknowledgments: We appreciate the financial support from National Natural Science Foundation of China (61574065, 21575043, 51405166), National Key R&D Program of China (2016YFB0401502), Science and Technology Planning Project of Guangdong Province (2016B090906004), Guangdong Engineering

20 Page 20 of 34

Technology Center of Optofluidics Materials and Devices (2015B090903079), program for Changjiang Scholars and Innovative Research Team in University (IRT13064), and the International Cooperation Base of Infrared Reflection Liquid Crystal Polymers and Device (2015B050501010). Conflicts of Interest:

ip t

The authors declare no conflict of interest.

References

Ac ce p

te

d

M

an

us

cr

[1] Z. Yu, C. F. Wang, L. Ling, L. Chen, S. Chen, Triphase microfluidic directed self assembly: anisotropic colloidal photonic crystal supraparticles and multicolor patterns made easy, Angew. Chem. Int. Ed., 51(2012) 2375-2378. [2] H. Lee, J. Kim, H. Kim, J. Kim, S. Kwon, Colour-barcoded magnetic microparticles for multiplexed bioassays, Nat. Mater., 9(2010) 745-749. [3] S. H. Kim, J. Y. Sim, J. M. Lim, S. M. Yang, Magnetoresponsive microparticles with nanoscopic surface structures for remote controlled locomotion, Angew. Chem., 122(2010) 3874-3878. [4] X. Cao, L. Zang, Z. Bu, L. Sun, D. Guo, C. Wang, Microfluidic fabrication of magnetic porous multi-walled carbon nanotube beads for oils and organic solvents adsorption, J. Mater. Chem. A, 4(2016) 10479-10485. [5] T. Kanai, D. Lee, H. C. Shum, R. K. Shah, D. A. Weitz, Gel immobilized colloidal crystal shell with enhanced thermal sensitivity at photonic wavelengths, Adv. Mater., 22(2010) 4998-5002. [6] Y. Hu, J. Wang, H. Wang, Q. Wang, J. Zhu, Y. Yang, Microfluidic fabrication and thermoreversible response of core/shell photonic crystalline microspheres based on deformable nanogels, Langmuir, 28(2012) 17186-17192. [7] T. Nisisako, T. Torii, T. Takahashi, Y. Takizawa, Synthesis of monodisperse bicolored janus particles with electrical anisotropy using a microfluidic co flow system, Adv. Mater., 18(2006) 1152-1156. [8] S. W. Lee, J. S. Choi, K. Y. Cho, J. H. Yim, Facile fabrication of uniform-sized, magnetic, and electroconductive hybrid microspheres using a microfluidic droplet generator, Eur. Polym. J., 80(2016) 40-47. [9] H. Lee, Microfluidic fabrication of photo-responsive hydrogel capsules, Chem. Commun., 49(2013) 1865-1867. [10] Y. Chen, G. Nurumbetov, R. Chen, N. Ballard, S. A. Bon, Multicompartmental Janus microbeads from branched polymers by single-emulsion droplet microfluidics, Langmuir, 29(2013) 12657-12662. [11] H. Wang, S. Yang, S. N. Yin, L. Chen, S. Chen, Janus suprabead displays derived from the modified photonic crystals toward temperature magnetism and optics multiple responses, ACS Appl. Mater. Interfaces, 7(2015) 8827-8833. [12] D. Lim, E. Lee, H. Kim, S. Park, S. Baek, J. Yoon, Multi stimuli-responsive hydrogel microfibers containing magnetite nanoparticles prepared using microcapillary devices, Soft Matter, 11(2015) 1606-1613. 21

Page 21 of 34

Ac ce p

te

d

M

an

us

cr

ip t

[13] J. Wei, X. J. Ju, X. Y. Zou, R. Xie, W. Wang, Y. M. Liu, et al., Multi stimuli responsive microcapsules for adjustable controlled release, ACS Funct. Mater., 24(2014) 3312-3323. [14] Z. Nie, A. Petukhova, E. Kumacheva, Properties and emerging applications of self-assembled structures made from inorganic nanoparticles, Nat. Nanotechnol., 5(2010) 15-25. [15] G. Yang, L. Hu, T. D. Keiper, P. Xiong, D. T. Hallinan Jr, Gold nanoparticle monolayers with tunable optical and electrical properties, Langmuir, 32(2016) 4022-4033. [16] S. H. Kim, S. J. Jeon, W. C. Jeong, H. S. Park, S. M. Yang, Optofluidic synthesis of electroresponsive photonic janus balls with isotropic structural colors, Adv. Mater., 20(2008) 4129-4134. [17] L. L. Yue, R. Xie, J. Wei, X. J. Ju, W. Wang, L. Y. Chu, Nano-gel containing thermo-responsive microspheres with fast response rate owing to hierarchical phase-transition mechanism, J. Colloid Interface Sci., 377(2012) 137-144. [18] J. Ge, Y. Yin, Responsive photonic crystals, Angew. Chem. Int. Ed., 50(2011) 1492-1522. [19] J. Ge, Y. Yin, Magnetically responsive colloidal photonic crystals, J. Mater. Chem., 18(2008) 5041-5045. [20] J. D. Debord, L. A. Lyon, Thermoresponsive photonic crystals, J. Phys. Chem. B, 104(2000) 6327-6331. [21] Y. Liu, L. Meng, X. Lu, L. Zhang, Y. He, Thermo and pH sensitive fluorescent polymer sensor for metal cations in aqueous solution, Polym. Adv. Technol., 19(2008) 137-143. [22] C. J. Cheng, L. Y. Chu, P. W. Ren, J. Zhang, L. Hu, Preparation of monodisperse thermo-sensitive poly(N-isopropylacrylamide) hollow microcapsules, J. Colloid Interface Sci., 313(2007) 383-388. [23] M. Heskins, J. E. Guillet, Solution properties of poly(N-isopropylacrylamide), J. Macromol. Sci. Chem., 2(1968) 1441-1455. [24] D. Crespy, R. M. Rossi, Temperature responsive polymers with LCST in the physiological range and their applications in textiles, Polym. Int., 56(2007) 1461-1468. [25] J. Hu, C. Li, S. Liu, Hg2+-reactive double hydrophilic block copolymer assemblies as novel multifunctional fluorescent probes with improved performance, Langmuir, 26(2009) 724-729. [26] X. Wan, H. Liu, S. Yao, T. Liu, Y. Yao, A stimuli responsive nanogel based sensitive and selective fluorescent sensor for Cr3+ with thermo induced tunable detection sensitivity, Macromol. Rapid Commun., 35(2014) 323-329. [27] M. Balcioglu, B. Z. Buyukbekar, M. S. Yavuz, M. V. Yigit, Smart polymer functionalized graphene nano-devices for thermo-switch controlled biodetection, ACS Biomater. Sci. Eng., 33(2014) 47-48. [28] A. Baji, M. Abtahi, S. Ramakrishna, Bio-inspired electrospun micro/nanofibers with special wettability, J. Nanosci. Nanotechnol., 14(2014) 4781-4798. 22

Page 22 of 34

Ac ce p

te

d

M

an

us

cr

ip t

[29] H. Yang, H. Zhu, M. M. Hendrix, N. J. Lousberg, G. de With, A. Esteves, et al., Temperature triggered collection and release of water from fogs by a sponge like cotton fabric, Adv. Mater., 25(2013) 1150-1154. [30] M. Doi, M. Matsumoto, Y. Hirose, Deformation of ionic polymer gels by electric fields, Macromolecules, 25(1992) 5504-5511. [31] X. Jin, H. Kang, Y. Huang, H. Liu, Y. Hu, Synthesis and properties of electrically sensitive poly(acrylic acid co acetoacetoxy ethyl methacrylate) gels, J. Appl. Polym. Sci., 110(2008) 3690-3696. [32] K. Adesanya, E. Vanderleyden, A. Embrechts, P. Glazer, E. Mendes, P. Dubruel, Properties of electrically responsive hydrogels as a potential dynamic tool for biomedical applications, J. Appl. Polym. Sci., 131(2014) 205-212. [33] J. Ge, E. Neofytou, T. J. Cahill III, R. E. Beygui, R. N. Zare, Drug release from electric-field-responsive nanoparticles, ACS Nano, 6(2011) 227-233. [34] S. Y. Kim, Y. M. Lee, Drug release behavior of electrical responsive poly(vinyl alcohol)/poly(acrylic acid) IPN hydrogels under an electric stimulus, J. Appl. Polym. Sci., 74(1999) 1752-1761. [35] F. D. Jochum, L. Zur Borg, P. J. Roth, P. Theato, Thermo- and light-responsive polymers containing photoswitchable azobenzene end groups, Macromolecules, 42(2009) 7854-7862. [36] A. A. Beharry, G. A. Woolley, Azobenzene photoswitches for biomolecules, Chem. Soc. Rev., 40(2011) 4422-4437. [37] M. Rini, A. K. Holm, E. T. Nibbering, H. Fidder, Ultrafast UV-mid-IR investigation of the ring opening reaction of a photochromic spiropyran, J. Am. Chem. Soc., 125(2003) 3028-3034. [38] T. Hirakura, Y. Nomura, Y. Aoyama, K. Akiyoshi, Photoresponsive nanogels formed by the self-assembly of spiropyrane-bearing pullulan that act as artificial molecular chaperones, Biomacromolecules, 5(2004) 1804-1809. [39] P. Han, S. Li, C. Wang, H. Xu, Z. Wang, X. Zhang, et al., UV-responsive polymeric superamphiphile based on a complex of malachite green derivative and a double hydrophilic block copolymer, Langmuir, 27(2011) 14108-14111. [40] Y. Li, M. Wang, T. J. White, T. J. Bunning, Q. Li, Azoarenes with opposite chiral configurations: light driven reversible handedness inversion in self organized helical superstructures, Angew. Chem. Int. Ed., 52(2013) 8925-8929. [41] M. Chen, H. Huang, Y. Zhu, Z. Liu, X. Xing, F. Cheng, et al., Photodeformable CLCP material: study on photo-activated microvalve applications, Appl. Phys. A, 102(2011) 667-672. [42] M. Chen, X. Xing, Z. Liu, Y. Zhu, H. Liu, Y. Yu, et al., Photodeformable polymer material: towards light-driven micropump applications, Appl. Phys. A, 100(2010) 39-43. [43] B. Yan, J. C. Boyer, D. Habault, N. R. Branda, Y. Zhao, Near infrared light triggered release of biomacromolecules from hydrogels loaded with upconversion nanoparticles, J. Am. Chem. Soc., 134(2012) 16558-16561.

23 Page 23 of 34

Ac ce p

te

d

M

an

us

cr

ip t

[44] K. C. Hribar, M. H. Lee, D. Lee, J. A. Burdick, Enhanced release of small molecules from near-infrared light responsive polymer-nanorod composites, ACS Nano, 5(2011) 2948-2956. [45] Y. Huang, W. Liang, J. K. Poon, Y. Xu, R. K. Lee, A. Yariv, Spiro-oxazine photochromic fiber optical switch, Appl. Phys. Lett., 88(2006) 181102. [46] T. H. Lin, Y. Li, C. T. Wang, H. C. Jau, C. W. Chen, C. C. Li, et al., Red, green and blue reflections enabled in an optically tunable self organized 3D cubic nanostructured thin film, Adv. Mater., 25(2013) 5050-5054. [47] W. Zhao, B. Fang, N. Li, S. Nie, Q. Wei, C. Zhao, Fabrication of pH responsive molecularly imprinted polyethersulfone particles for bisphenol A uptake, J. Appl. Polym. Sci., 113(2009) 916-921. [48] M. Nuopponen, H. Tenhu, Gold nanoparticles protected with pH and temperature-sensitive diblock copolymers, Langmuir, 23(2007) 5352-5357. [49] J. Zhang, N. A. Peppas, Synthesis and characterization of pH- and temperature-sensitive poly(methacrylic acid)/poly(N-isopropylacrylamide) interpenetrating polymeric networks, Macromolecules, 33(2000) 102-107. [50] M. Abdelaal, E. Abdel Razik, E. Abdel Bary, I. El Sherbiny, Chitosan based interpolymeric pH responsive hydrogels for in vitro drug release, J. Appl. Polym. Sci., 103(2007) 2864-2874. [51] Z. Sideratou, D. Tsiourvas, C. Paleos, Quaternized poly(propylene imine) dendrimers as novel pH-sensitive controlled-release systems, Langmuir, 16(2000) 1766-1769. [52] F. Liu, M. W. Urban, Dual temperature and pH responsiveness of poly(2-(N, N-dimethylamino) ethyl methacrylate-co-N-butyl acrylate) colloidal dispersions and their films, Macromolecules, 41(2008) 6531-6539. [53] H. Wang, B. Tan, J. Wang, Z. Li, S. Zhang, Anion-based pH responsive ionic liquids: design, synthesis, and reversible self-assembling structural changes in aqueous solution, Langmuir, 30(2014) 3971-3978. [54] E. Song, W. Han, C. Li, D. Cheng, L. Li, L. Liu, et al., Hyaluronic acid-decorated graphene oxide nanohybrids as nanocarriers for targeted and pH-responsive anticancer drug delivery, ACS Appl. Mater. Interfaces, 6(2014) 11882-11890. [55] S. Lee, K. Saito, H. R. Lee, M. J. Lee, Y. Shibasaki, Y. Oishi, et al., Hyperbranched double hydrophilic block copolymer micelles of poly(ethylene oxide) and polyglycerol for pH-responsive drug delivery, Biomacromolecules, 13(2012) 1190-1196. [56] B. Mu, P. Liu, X. Li, P. Du, Y. Dong, Y. Wang, Fabrication of flocculation-resistant pH/ionic strength/temperature multiresponsive hollow microspheres and their controlled release, Mol. Pharm., 9(2011) 91-101. [57] W. Leng, S. Zhou, B. You, L. Wu, Formation of sulfonated aromatic ketone chromophores within styrene-acrylic acid copolymers and their pH-responsive color change, Langmuir, 26(2010) 17836-17839. [58] J. K. Chen, B. J. Bai, PH-switchable optical properties of the one-dimensional periodic grating of tethered poly(2-dimethylaminoethyl methacrylate) brushes on a silicon surface, J. Phys. Chem. C, 115(2011) 21341-21350. 24

Page 24 of 34

Ac ce p

te

d

M

an

us

cr

ip t

[59] J. Wang, Y. Hu, R. Deng, R. Liang, W. Li, S. Liu, et al., Multiresponsive hydrogel photonic crystal microparticles with inverse-opal structure, Langmuir, 29(2013) 8825-8834. [60] J. D. Cushen, I. Otsuka, C. M. Bates, S. Halila, S. Fort, C. Rochas, et al., Oligosaccharide/silicon-containing block copolymers with 5 nm features for lithographic applications, ACS Nano, 6(2012) 3424-3433. [61] D. Wang, T. Wu, X. Wan, X. Wang, S. Liu, Purely salt-responsive micelle formation and inversion based on a novel schizophrenic sulfobetaine block copolymer: structure and kinetics of micellization, Langmuir, 23(2007) 11866-11874. [62] G. R. Whittell, M. D. Hager, U. S. Schubert, I. Manners, Functional soft materials from metallopolymers and metallosupramolecular polymers, Nat. Mater., 10(2011) 176-188. [63] S. Cohen, T. Yoshioka, M. Lucarelli, L. H. Hwang, R. Langer, Controlled delivery systems for proteins based on poly(lactic/glycolic acid) microspheres, Pharm. Res., 8(1991) 713-720. [64] J. K. Chen, C. Y. Hsieh, C. F. Huang, P. M. Li, Characterization of patterned poly(methyl methacrylate) brushes under various structures upon solvent immersion, J. Colloid Interface Sci., 338(2009) 428-434. [65] J. Draper, I. Luzinov, S. Minko, I. Tokarev, M. Stamm, Mixed polymer brushes by sequential polymer addition: anchoring layer effect, Langmuir, 20(2004) 4064-4075. [66] C. Velez, I. Torres-Díaz, L. Maldonado-Camargo, C. Rinaldi, D. P. Arnold, Magnetic assembly and cross-linking of nanoparticles for releasable magnetic microstructures, ACS Nano, 9(2015) 10165-10172. [67] D. Yoo, J. H. Lee, T. H. Shin, J. Cheon, Theranostic magnetic nanoparticles, Acc. Chem. Res., 44(2011) 863-874. [68] F. Hong, C. Yan, Y. Si, J. He, J. Yu, B. Ding, Nickel ferrite nanoparticles anchored onto silica nanofibers for designing magnetic and flexible nanofibrous membranes, ACS Appl. Mater. Interfaces, 7(2015) 20200-20207. [69] J. Li, B. Arnal, C. W. Wei, J. Shang, T. M. Nguyen, M. O’Donnell, et al., Magneto-optical nanoparticles for cyclic magnetomotive photoacoustic imaging, ACS Nano, 9(2015) 1964-1976. [70] P. Chen, H. Jia, J. Zhang, J. Han, X. Liu, J. Qiu, Magnetic tuning of optical hysteresis behavior in lanthanide-doped nanoparticles, J. Phys. Chem. C, 119(2015) 5583-5588. [71] C. Min, H. Shao, M. Liong, T. J. Yoon, R. Weissleder, H. Lee, Mechanism of magnetic relaxation switching sensing, ACS Nano, 6(2012) 6821-6828. [72] B. Li, D. M. Smilgies, A. D. Price, D. L. Huber, P. G. Clem, H. Fan, Poly(N-isopropylacrylamide) surfactant-functionalized responsive silver nanoparticles and superlattices, ACS Nano, 8(2014) 4799-4804. [73] I. Pavlichenko, A. T. Exner, M. Guehl, P. Lugli, G. Scarpa, B. V. Lotsch, Humidity-enhanced thermally tunable TiO2/SiO2 bragg stacks, J. Phys. Chem. C, 116(2011) 298-305. 25

Page 25 of 34

Ac ce p

te

d

M

an

us

cr

ip t

[74] M. Werts, M. Badila, C. Brochon, A. Hebraud, G. Hadziioannou, Titanium dioxide- polymer core-shell particles dispersions as electronic inks for electrophoretic displays, Chem. Mater., 20(2008) 1292-1298. [75] M. Zrínyi, J. Fehér, G. Filipcsei, Novel gel actuator containing TiO2 particles operated under static electric field, Macromolecules, 33(2000) 5751-5753. [76] P. C. Ma, M. Y. Liu, H. Zhang, S. Q. Wang, R. Wang, K. Wang, et al., Enhanced electrical conductivity of nanocomposites containing hybrid fillers of carbon nanotubes and carbon black, ACS Appl. Mater. Interfaces, 1(2009) 1090-1096. [77] D. G. Yu, J. H. An, J. Y. Bae, S D. Ahn, S. Y. Kang, K. S. Suh, Negatively charged ultrafine black particles of p(MMA-co-EGDMA) by dispersion polymerization for electrophoretic displays, Macromolecules, 38(2005) 7485-7491. [78] C. Yang, P. Liu, T. Wang, Well-defined core-shell carbon black/polypyrrole nanocomposites for electrochemical energy storage, ACS Appl. Mater. Interfaces, 3(2011) 1109-1114. [79] S. Fazal, A. Jayasree, S. Sasidharan, M. Koyakutty, S. V. Nair, D. Menon, Green synthesis of anisotropic gold nanoparticles for photothermal therapy of cancer, ACS Appl. Mater. Interfaces, 6(2014) 8080-8089. [80] X. Zhang, X. Xu, T. Li, M. Lin, X. Lin, H. Zhang, et al., Composite photothermal platform of polypyrrole-enveloped Fe3O4 nanoparticle self-assembled superstructures, ACS Appl. Mater. Interfaces, 6(2014) 14552-14561. [81] L. Guo, D. D. Yan, D. Yang, Y. Li, X. Wang, O. Zalewski, et al., Combinatorial photothermal and immuno cancer therapy using chitosan-coated hollow copper sulfide nanoparticles, ACS Nano, 8(2014) 5670-5681. [82] C. J. Jeong, S. M. Sharker, I. In, S. Y. Park, Iron oxide@PEDOT-based recyclable photothermal nanoparticles with poly(vinylpyrrolidone) sulfobetaines for rapid and effective antibacterial activity, ACS Appl. Mater. Interfaces, 7(2015) 9469-9478. [83] W. Gao, J. M. Chan, O. C. Farokhzad, pH-responsive nanoparticles for drug delivery, Mol. Pharm., 7(2010) 1913-1920. [84] J. Dai, T. Nagai, X. Wang, T. Zhang, M. Meng, Q. Zhang, pH-sensitive nanoparticles for improving the oral bioavailability of cyclosporine a, Int. J. Pharm., 280(2004) 229-240. [85] J. E. Lee, K. Chung, Y. H. Jang, Y. J. Jang, S. T. Kochuveedu, D. Li, et al., Bimetallic multifunctional core@shell plasmonic nanoparticles for localized surface plasmon resonance based sensing and electrocatalysis, Anal. Chem., 84(2012) 6494-6500. [86] C. L. Mou, X. J. Ju, L. Zhang, R. Xie, W. Wang, N. N. Deng, et al., Monodisperse and fast-responsive poly(N-isopropylacrylamide) microgels with open-celled porous structure, Langmuir, 30(2014) 1455-1464. [87] B. M. Budhlall, M. Marquez, O. D. Velev, Microwave, photo- and thermally responsive PNIPAM-gold nanoparticle microgels, Langmuir, 24(2008) 11959-11966. 26

Page 26 of 34

Ac ce p

te

d

M

an

us

cr

ip t

[88] M. Lisunova, N. Holland, O. Shchepelina, V. V. Tsukruk, Template-assisted assembly of the functionalized cubic and spherical microparticles, Langmuir, 28(2012) 13345-13353. [89] J. Shi, C. Du, J. Shi, Y. Wang, S. Cao, Hollow multilayer microcapsules for pH /thermally responsive drug delivery using aliphatic poly(urethane amine) as smart component, Macromol. Biosci., 13(2013) 494-502. [90] B. G. De Geest, A. G. Skirtach, T. R. De Beer, G. B. Sukhorukov, L. Bracke, W. R. Baeyens, et al., Stimuli responsive multilayered hybrid nanoparticle/polyelectrolyte capsules, Macromol. Rapid Commun., 28(2007) 88-95. [91] A. M. Costa, M. Alatorre-Meda, N. M. Oliveira, J. F. Mano, Biocompatible polymeric microparticles produced by a simple biomimetic approach, Langmuir, 30(2014) 4535-4539. [92] W. L. Lee, E. Widjaja, S. C. J. Loo, One step fabrication of triple layered polymeric microparticles with layer localization of drugs as a novel drug delivery system, Small, 6(2010) 1003-1011. [93] S. S. Lee, B. Kim, S. K. Kim, J. C. Won, Y. H. Kim, S. H. Kim, Robust microfluidic encapsulation of cholesteric liquid crystals toward photonic ink capsules, Adv. Mater., 27(2014) 627-633. [94] L. Shui, A. van den Berg, J. C. Eijkel, Scalable attoliter monodisperse droplet formation using multiphase nano-microfluidics, Mcirofluid. nanofluid., 11(2011) 87-92. [95] T. Schneider, H. Zhao, J. K. Jackson, G. H. Chapman, J. Dykes, U. O. Häfeli, Use of hydrodynamic flow focusing for the generation of biodegradable camptothecin loaded polymer microspheres, J. Pharm. Sci., 97(2008) 4943-4954. [96] B. Yang, Y. Lu, G. Luo, Controllable preparation of polyacrylamide hydrogel microspheres in a coaxial microfluidic device, Ind. Eng. Chem. Res., 51(2012) 9016-9022. [97] S. Okushima, T. Nisisako, T. Torii, T. Higuchi, Controlled production of monodisperse double emulsions by two-step droplet breakup in microfluidic devices, Langmuir, 20(2004) 9905-9908. [98] L. Shui, F. Mugele, A. van den Berg, J. C. Eijkel, Geometry-controlled droplet generation in head-on microfluidic devices, Appl. Phys. Lett., 93(2008) 153113. [99] P. Garstecki, I. Gitlin, W. DiLuzio, G.M. Whitesides, E. Kumacheva, H.A. Stone, Formation of monodisperse bubbles in a microfluidic flow-focusing device, Appl. Phys. Lett., 85(2004) 2649-2651. [100] Q. Xu, M. Hashimoto, T. T. Dang, T. Hoare, D. S. Kohane, G. M. Whitesides, et al., Preparation of monodisperse biodegradable polymer microparticles using a microfluidic flow focusing device for controlled drug delivery, Small, 5(2009) 1575-1581. [101] H. Hwang, S. H. Kim, S. M. Yang, Microfluidic fabrication of SERS-active microspheres for molecular detection, Lab Chip, 11(2010) 87-92. 27

Page 27 of 34

Ac ce p

te

d

M

an

us

cr

ip t

[102] W. C. Jeong, J. M. Lim, J. H. Choi, J. H. Kim, Y. J. Lee, S. H. Kim, et al., Controlled generation of submicron emulsion droplets via highly stable tip-streaming mode in microfluidic devices, Lab Chip, 12(2012) 1446-1453. [103] N. N. Deng, Z. J. Meng, R. Xie, X. J. Ju, C. L. Mou, W. Wang, et al., Simple and cheap microfluidic devices for the preparation of monodisperse emulsions, Lab Chip, 11(2011) 3963-3969. [104] Z. Liu, L. Liu, X. J. Ju, R. Xie, B. Zhang, L. Y. Chu, K+-recognition capsules with squirting release mechanisms, Chem. Commun., 47(2011) 12283-12285. [105] L. Y. Chu, A. S. Utada, R. K. Shah, J. W. Kim, D. A. Weitz, Controllable monodisperse multiple emulsions, Angew. Chem. Int. Ed., 46(2007) 8970-8974. [106] Y. Hu, J. Wang, C. Li, Q. Wang, H. Wang, J. Zhu, et al., Janus photonic crystal microspheres: centrifugation-assisted generation and reversible optical property, Langmuir, 29(2013) 15529-15534. [107] L. Liu, J. P. Yang, X. J. Ju, R. Xie, Y. M. Liu, W. Wang, et al., Monodisperse core-shell chitosan microcapsules for pH-responsive burst release of hydrophobic drugs, Soft Matter, 7(2011) 4821-4827. [108] S. W. Kim, K. H. Hwangbo, J. H. Lee, K. Y. Cho, Microfluidic fabrication of microparticles with multiple structures from a biodegradable polymer blend, RSC Adv., 4(2014) 46536-46540. [109] H. G. Lee, S. Munir, S. Y. Park, Cholesteric liquid crystal droplets for biosensors, ACS Appl. Mater. Interfaces, 8(2016) 26407-26417. [110] J. Kim, M. Khan, S. Y. Park, Glucose sensor using liquid-crystal droplets made by microfluidics, ACS Appl. Mater. Interfaces, 5(2013) 13135-13139. [111] C. Ohm, N. Kapernaum, D. Nonnenmacher, F. Giesselmann, C. Serra, R. Zentel, Microfluidic synthesis of highly shape-anisotropic particles from liquid crystalline elastomers with defined director field configurations, J. Am. Chem. Soc., 133(2011) 5305-5311. [112] E. K. Fleischmann, H. L. Liang, N. Kapernaum, F. Giesselmann, J. Lagerwall, R. Zentel, One-piece micropumps from liquid crystalline core-shell particles, Nat. Commun., 3(2012) 1178. [113] E. Lee, H. Lee, S. I. Yoo, J. Yoon, Photothermally triggered fast responding hydrogels incorporating a hydrophobic moiety for light-controlled microvalves, ACS Appl. Mater. Interfaces, 6(2014) 16949-16955. [114] C. Ohm, C. Serra, R. Zentel, A continuous flow synthesis of micrometer sized actuators from liquid crystalline elastomers, Adv. Mater., 21(2009) 4859-4862. [115] D. KunáHwang, Microfluidic-based synthesis of non-spherical magnetic hydrogel microparticles, Lab Chip, 8(2008) 1640-1647. [116] M. Khan, S. Y. Park, General liquid-crystal droplets produced by microfluidics for urea detection, Sens. Actuators, B, 202(2014) 516-522. [117] S. Lone, J. I. Ahn, M. R. Kim, H. M. Lee, S. H. Kim, T. P. Lodge, et al., Photoresponsive phase separation of a poly(NIPAAm-co-SPO-co-fluorophore) random copolymer in w/o droplet, Langmuir, 30(2014) 9577-9583.

28 Page 28 of 34

Ac ce p

te

d

M

an

us

cr

ip t

[118] L. Shang, F. Shangguan, Y. Cheng, J. Lu, Z. Xie, Y. Zhao, et al., Microfluidic generation of magnetoresponsive janus photonic crystal particles, Nanoscale, 5(2013) 9553-9557. [119] J. H. Jang, S. Y. Park, pH-responsive cholesteric liquid crystal double emulsion droplets prepared by microfluidics, Sens. Actuators, B, 241(2017) 636-643. [120] Z. Shen, Y. Zhu, L. Wu, B. You, J. Zi, Fabrication of robust crystal balls from the electrospray of soft polymer spheres/silica dispersion, Langmuir, 26(2009) 6604-6609. [121] D. Liu, H. Zhang, B. Herranz Blanco, E. Mäkilä, V. P. Lehto, J. Salonen, et al., Microfluidic assembly of monodisperse multistage pH responsive polymer/porous silicon composites for precisely controlled multi drug delivery, Small, 10(2014) 2029-2038. [122] Z. Yu, Y. Zheng, R. M. Parker, Y. Lan, Y. Wu, R. J. Coulston, et al., Microfluidic droplet-facilitated hierarchical assembly for dual cargo loading and synergistic delivery, ACS Appl. Mater. Interfaces, 8(2016) 8811-8820. [123] R. C. Luo, S. Ranjan, Y. Zhang, C. H. Chen, Near-infrared photothermal activation of microgels incorporating polypyrrole nanotransducers through droplet microfluidics, Chem. Commun., 49(2013) 7887-7889. [124] M. T. Rahman, Z. Barikbin, A. Z. M. Badruddoza, P. S. Doyle, S. A. Khan, Monodisperse polymeric ionic liquid microgel beads with multiple chemically switchable functionalities, Langmuir, 29(2013) 9535-9543. [125] S. W. Pi, X. J. Ju, H. G. Wu, R. Xie, L. Y. Chu, Smart responsive microcapsules capable of recognizing heavy metal ions, J. Colloid Interface Sci., 349(2010) 512-518. [126] J. Fan, Y. Li, H. K. Bisoyi, R. S. Zola, D. K. Yang, T. J. Bunning, et al., Light directing omnidirectional circularly polarized reflection from liquid crystal droplets, Angew. Chem., 127(2015) 2188-2192. [127] S. J. Aȕhoff, S. Sukas, T. Yamaguchi, C. A. Hommersom, S. Le Gac, N. Katsonis, Superstructures of chiral nematic microspheres as all-optical switchable distributors of light, Sci. Rep., 5(2015)14183. [128] R. K. Shah, J. W. Kim, J. J. Agresti, D. A. Weitz, L. Y. Chu, Fabrication of monodisperse thermosensitive microgels and gel capsules in microfluidic devices, Soft Matter, 4(2008) 2303-2309. [129] E. Taboada, R. Solanas, E. Rodríguez, R. Weissleder, A. Roig, Supercritical fluid assisted one pot synthesis of biocompatible core (Ȗ Fe2O3)/shell (SiO2) nanoparticles as high relaxivity T2 contrast agents for magnetic resonance imaging, ACS Funct. Mater., 19(2009) 2319-2324. [130] D. Wang, X. Duan, J. Zhang, A. Yao, L. Zhou, W. Huang, Fabrication of superparamagnetic hydroxyapatite with highly ordered three-dimensional pores, J. Mater. Sci., 44(2009) 4020-4025. [131] X. Shi, S. H. Wang, S. D. Swanson, S. Ge, Z. Cao, M. E. Van Antwerp, et al., Dendrimer functionalized shell crosslinked iron oxide nanoparticles for in vivo magnetic resonance imaging of tumors, Adv. Mater., 20(2008) 1671-1678. 29

Page 29 of 34

[132] S. S. Banerjee, D. H. Chen, A multifunctional magnetic nanocarrier bearing fluorescent dye for targeted drug delivery by enhanced two-photon triggered release, Nanotechnology, 20(2009) 185103. [133] J. Dobson, Magnetic nanoparticles for drug delivery, Drug Dev. Res., 67(2006) 55-60. [134] A. Afkhami, R. Norooz-Asl, Removal, preconcentration and determination of Mo (VI) from water

ip t

and wastewater samples using maghemite nanoparticles, Colloid Surf. A-Physicochem. Eng. Asp., 346(2009) 52-57.

Ac ce p

te

d

M

an

us

cr

[135] Y. G. Li, H. S. Gao, W. L. Li, J. M. Xing, H. Z. Liu, In situ magnetic separation and immobilization of dibenzothiophene-desulfurizing bacteria, Bioresour. Technol., 100(2009) 5092-5096. [136] S. A. Corr, Y. P. Rakovich, Y. K. Gun’ko, Multifunctional magnetic-fluorescent nanocomposites for biomedical applications, Nanoscale Res. Lett., 3(2008) 87. [137] K. Vuu, J. Xie, M. A. McDonald, M. Bernardo, F. Hunter, Y. Zhang, et al., Gadolinium-rhodamine nanoparticles for cell labeling and tracking via magnetic resonance and optical imaging, Bioconjugate Chem., 16(2005) 995-999. [138] S. N. Yin, C. F. Wang, Z. Y. Yu, J. Wang, S. S. Liu, S. Chen, Versatile bifunctional magnetic fluorescent responsive Janus supraballs towards the flexible bead display, Adv. Mater., 23(2011) 2915-2919. [139] K. P. Yuet, D. K. Hwang, R. Haghgooie, P. S. Doyle, Multifunctional superparamagnetic Janus particles, Langmuir, 26(2009) 4281-4287. [140] S. Mitragotri, J. Lahann, Physical approaches to biomaterial design, Nat. Mater., 8(2009) 15-23. [141] S. F. Wright, J. B. Morton, Detection of vesicular-arbuscular mycorrhizal fungus colonization of roots by using a dot-immunoblot assay, Appl. Environ. Microb., 55(1989) 761-763. [142] C. Cha, S. R. Shin, N. Annabi, M. R. Dokmeci, A. Khademhosseini, Carbon-based nanomaterials: multifunctional materials for biomedical engineering, ACS Nano, 7(2013) 2891-2897. [143] A. Ma, K. Mondal, Y. Y. Jiao, S. Oren, Z. Xu, A. Sharma, L. Dong, Microfluidic immuo-bioship for detection of breast cancer biomarkers using hierarchical composite of porous graphene and titanium dioxide nanofibers, ACS Appl. Mater. Interfaces, 8(2016) 20570-20582. [144] S. C. Smith, D. F. Rodrigues, Carbon-based nanomaterials for removal of chemical and biological contaminants from water: A review of mechanisms and applications, Carbon, 91(2015) 122-143. [145] A. Miasnikova, A. Laschewsky, Influencing the phase transition temperature of poly(methoxy diethylene glycol acrylate) by molar mass, end groups, and polymer architecture, J. Polym. Sci. Part A: Polym. Chem., 50(2012) 3313-3323. [146] C. T. Lai, R. H. Chien, S. W. Kuo, J. L. Hong, Tetraphenylthiophene-functionalized poly(N-isopropylacrylamide): probing LCST with aggregation-induced emission, Macromolecules, 44(2011) 6546-6556. 30

Page 30 of 34

Ac ce p

te

d

M

an

us

cr

ip t

[147] T. Ueki, Y. Nakamura, A. Yamaguchi, K. Niitsuma, T. P. Lodge, M. Watanabe, UCST phase transition of azobenzene-containing random copolymer in an ionic liquid, Macromolecules, 44(2011) 6908-6914. [148] S. Glatzel, A. Laschewsky, J. F. Lutz, Well-defined uncharged polymers with a sharp UCST in water and in physiological milieu, Macromolecules, 44(2010) 413-415. [149] Y. Su, M. Dan, X. Xiao, X. Wang, W. Zhang, A new thermo responsive block copolymer with tunable upper critical solution temperature and lower critical solution temperature in the alcohol/water mixture, J. Polym. Sci. Part A: Polym. Chem., 51(2013) 4399-4412. [150] C. Weber, R. Hoogenboom, U. S. Schubert, Temperature responsive bio-compatible polymers based on poly(ethylene oxide) and poly(2-oxazoline)s, Prog. Polym. Sci., 37(2012) 686-714. [151] L. Gu, Y. Gao, Y. Qin, X. Chen, X. Wang, F. Wang, Biodegradable poly(carbonate ether)s with thermoresponsive feature at body temperature, J. Polym. Sci. Part A: Polym. Chem., 51(2013) 282-289. [152] J. W. Kim, A. S. Utada, A. Fernández Nieves, Z. Hu, D. A. Weitz, Fabrication of monodisperse gel shells and functional microgels in microfluidic devices, Angew. Chem., 119(2007) 1851-1854. [153] L. Y. Chu, J. W. Kim, R. K. Shah, D. A. Weitz, Monodisperse thermoresponsive microgels with tunable volume phase transition kinetics, ACS Funct. Mater., 17(2007) 3499-3504. [154] S. Seiffert, J. Thiele, A. R. Abate, D. A. Weitz, Smart microgel capsules from macromolecular precursors, J. Am. Chem. Soc., 132(2010) 6606-6609. [155] Y. Zhao, W. Liu, X. Yang, H. Xu, The studies on the stimuli response of poly(N, N dimethylamino ethyl methacrylate/acrylic acid co acrylamide) complex hydrogel under DC electric field, J. Appl. Polym. Sci., 110(2008) 2234-2242. [156] J. Kie Shim, S. Ryong Oh, S. Bong Lee, K. M. Cho, Preparation of hydrogels composed of poly(vinyl alcohol) and polyethyleneimine and their electrical response, J. Appl. Polym. Sci., 107(2008) 2136-2141. [157] Y. Xia, R. Verduzco, R. H. Grubbs, J. A. Kornfield, Well-defined liquid crystal gels from telechelic polymers, J. Am. Chem. Soc., 130(2008) 1735-1740. [158] X. Li, Y. T. Yang, L. J. Wu, Y. C. Li, M. Y. Ye, Z. Q. Chang, et al., Fabrication of electro-and color-responsive CB/PTFE Janus beads in a simple microfluidic device, Mater. Lett., 142(2015) 258-261. [159] T. S. Shim, S. H. Kim, J. Y. Sim, J. M. Lim, S. M. Yang, Dynamic modulation of photonic bandgaps in crystalline colloidal arrays under electric field, Adv. Mater., 22(2010) 4494-4498. [160] A. Alam, Q. Meng, G. Shi, S. Arabi, J. Ma, N. Zhao, et al., Electrically conductive, mechanically robust, pH-sensitive graphene/polymer composite hydrogels, Composites Science and Technology, 127(2016) 119-126.

31 Page 31 of 34

Ac ce p

te

d

M

an

us

cr

ip t

[161] C. Am Kim, M. J. Joung, S. D. Ahn, G. H. Kim, S. Y. Kang, I. K. You, et al., Microcapsules as an electronic ink to fabricate color electrophoretic displays, Synth. Met., 151(2005) 181-185. [162] D. Voloschenko, O. Lavrentovich, Light-induced director-controlled microassembly of dye molecules from a liquid crystal matrix, J. Appl. Phys., 86(1999) 4843-4846. [163] S. Prathap Chandran, F. Mondiot, O. Mondain-Monval, J. Loudet, Photonic control of surface anchoring on solid colloids dispersed in liquid crystals, Langmuir, 27(2011) 15185-15198. [164] K. Tamada, H. Akiyama, T. X. Wei, S. A. Kim, Photoisomerization reaction of unsymmetrical azobenzene disulfide self-assembled monolayers: modification of azobenzene dyes to improve thermal endurance for photoreaction, Langmuir, 19(2003) 2306-2312. [165] K. I. Ishii, T. Hamada, M. Hatakeyama, R. Sugimoto, T. Nagasaki, M. Takagi, Reversible control of exo and endo budding transitions in a photosensitive lipid membrane, ChemBioChem, 10(2009) 251-256. [166] K. A. Riske, T. P. Sudbrack, N. L. Archilha, A. F. Uchoa, A. P. Schroder, C. M. Marques, et al., Giant vesicles under oxidative stress induced by a membrane-anchored photosensitizer, Biophys.J., 97(2009) 1362-1370. [167] H. K. Bisoyi, Q. Li, Light-directing chiral liquid crystal nanostructures: from 1D to 3D, Acc. Chem. Res., 47(2014) 3184-3195. [168] L. Chen, Y. Li, J. Fan, H. K. Bisoyi, D. A. Weitz, Q. Li, Photoresponsive monodisperse cholesteric liquid crystalline microshells for tunable omnidirectional lasing enabled by a visible light driven chiral molecular switch, Adv. Opt. Mater., 2(2014) 845-848. [169] M. Das, N. Sanson, D. Fava, E. Kumacheva, Microgels loaded with gold nanorods: photothermally triggered volume transitions under physiological conditions, Langmuir, 23(2007) 196-201. [170] C. H. Zhu, Y. Lu, J. F. Chen, S. H. Yu, Photothermal poly(N isopropylacrylamide)/Fe3O4 nanocomposite hydrogel as a movable position heating source under remote control, Small, 10(2014) 2796-2800. [171] S. Lone, S. H. Kim, S. W. Nam, S. Park, I. W. Cheong, Microfluidic preparation of dual stimuli-responsive microparticles and light-directed clustering, Langmuir, 26(2010) 17975-17980. [172] W. C. Jeong, S. H. Kim, S. M. Yang, Photothermal control of membrane permeability of microcapsules for on-demand release, ACS Appl. Mater. Interfaces, 6(2014) 826-832. [173] P. Gupta, K. Vermani, S. Garg, Hydrogels: from controlled release to pH-responsive drug delivery, Drug discovery today, 7(2002) 569-579. [174] J. Eisele, G. Haynes, T. Rosamilia, Characterisation and toxicological behaviour of basic methacrylate copolymer for gras evaluation, Regul. Toxicol. Pharm., 61(2011) 32-43.

32 Page 32 of 34

us

cr

ip t

[175] H. Liu, P. Wang, X. Zhang, F. Shen, C.G. Gogos, Effects of extrusion process parameters on the dissolution behavior of indomethacin in eudragit® E PO solid dispersions, Int. J. Pharm., 383(2010) 161-169. [176] A. Abbaspourrad, S.S. Datta, D. A. Weitz, Controlling release from pH-responsive microcapsules, Langmuir, 29(2013) 12697-12702. [177] C. H. Yang, C. Y. Wang, A. M. Grumezescu, A. H. J. Wang, C. J. Hsiao, Z. Y. Chen, et al., Core shell structure microcapsules with dual pH responsive drug release function, Electrophoresis, 35(2014) 2673-2680. [178] A. den Berg, G. áJulius Vancso, Redox-responsive organometallic microgel particles prepared from poly(ferrocenylsilane)s generated using microfluidics, Chem. Commun., 50(2014) 3058-3060.

an

Author biographies

Prof. Lingling Shui received her PhD in Electrical Engineering from Twente University (2009), the Netherlands, and her MS and BS degrees in Colloid and Interface Chemistry from Shandong University, China (2003

M

and 2000). Now she is a professor at South China Academy of Advanced Optoelectronics of South China Normal University, China, where she

Lingling Shui

works on microfluidic fundamentals and applications including droplet

d

microfluidics, optofluidics and e-paper displays.

Ac ce p

te

Juan Wang obtained her Masters degree in Materials Physics and Chemistry from South China Normal University in 2016. She is currently a PhD candidate in Professor Shui's group at South China Academy of Advanced Optoelectronics of South China Normal University. Her research interests are microfluidics, self-assembly and responsive materials.



Juan Wang

Jan C. T. Eijkel is a full professor of micro- and nanofluidics in the BIOS/Lab-on-a-Chip group at the MESA+ Institute for Nanotechnology, University of Twente. He obtained his PhD from University of Twente in 1995. The focus of his research is on the investigation of physicochemical

Jan C. T. Eijkel phenomena in micro- and nanofluidic systems, and their applications.

Mingliang Jin

Dr. Mingliang Jin received his PhD in Electrical Engineering from Twente University in the Netherlands (2010). Now, he is a seniorresearcher at the South China Academy of Advanced Optoelectronics of South China Normal University, China. His research areas are surface-enhanced Raman Spectroscopy (SERS), microfluidics, optoelectronic devices and equipment 33 Page 33 of 34

design and manufacture.

ip t

Dr. Dong Yuan is a lecturer at South China Academy of Advanced Optoelectronics of South China Normal University. She got her PhD degree from South China University of Technology in 2013, majored in Mechanical Manufacturing and Automation. Her research interest are optoelectronic device design, liquid crystal and electronic paper displays.

an

 Dong Yuan

us

cr

Shuting Xie

Shuting Xie received her MS degree in school of chemistry and chemical engineering from Shandong University, China (2015). Since then, she has worked at South China Academy of Advanced Optoelectronics of South China Normal University, China. Her research interests droplet microfluidics, digital microfluidics and droplet PCR.

Prof. Guofu Zhou received his BS in Metal Materials from Chongqing

M

University in China in 1986, MS in Materials Science from Institute of Metal Research of Chinese Academy of Science in 1989, and PhD degrees in Materials Science from Institute of Metal Research in China in 1991 and in Physics from University of Amsterdam in the Netherlands in 1994. He is now the dean of the South China Academy of Advanced

d

Guofu Zhou

te

Optoelectronics of South China Normal University. His research interests are advanced technologies of electronic paper displays and functional

Ac ce p

materials.

Albert van den Berg is a full professor of University of Twente, member of Royal Dutch Academy of Science. He received his BS, MS and PhD from University of Twente in 1981, 1983 and 1988, respectively, with the

background of Applied Physics and Applied Science and Technology. He

Albert van den Berg

is a pioneer and active member in microfluidics and lab-on-a-chip research areas. His research interests include fundamentals and applications of microfluidics in sensors, actuators, biology and electronic devices.

34 Page 34 of 34