Electric Field Induced Cutting of Hydrogel Microfibers with Precise

Subscriber access provided by The University of Texas at El Paso (UTEP)

Surfaces, Interfaces, and Applications

Electric Field Induced Cutting of Hydrogel Microfibers with Precise Length Control for Micromotors and Building Blocks Xiaokang Deng, Yukun Ren, Likai Hou, Weiyu Liu, Yankai Jia, and Hongyuan Jiang ACS Appl. Mater. Interfaces, Just Accepted Manuscript • DOI: 10.1021/acsami.8b12597 • Publication Date (Web): 26 Oct 2018 Downloaded from http://pubs.acs.org on October 31, 2018

Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.

is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.

Page 1 of 48 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Applied Materials & Interfaces

Electric Field Induced Cutting of Hydrogel Microfibers with Precise Length Control for Micromotors and Building Blocks Xiaokang Deng1, Yukun Ren1,2,*, Likai Hou1,*, Weiyu Liu3, Yankai Jia1, Hongyuan Jiang1,2,*

1State

Key Laboratory of Robotics and System and 2School of Mechatronics

Engineering, Harbin Institute of Technology, West Da-zhi Street 92, Harbin 150001, PR China

3School

of Electronics and Control Engineering, Chang’an University, Middle-Section of Nan’er Huan Road, Xi’an 710064, PR China

KEYWORDS ： microfiber-cutting, nonlinear electrokinetics, double-emulsion droplets, micromotors, building blocks, microfluidics, Maxwell-Wagner interfacial polarization

ACS Paragon Plus Environment

1

ACS Applied Materials & Interfaces 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 2 of 48

ABSTRACT：Microfiber modules with controllable lengths emerged as novel biomimetic platforms are significant for many engineering tissue applications. However, accurately controlling the length of microfibers on the scale of millimeter or even micrometer still remains challenging. Here, a novel and scalable strategy to generate microfiber modules with precisely tunable lengths ranging from 100 to 3500 μm via an alternating current (AC) electric field is presented. To control the microfiber length, double-emulsion droplets containing a chelating agent (sodium citrate) as spacing nodes are first uniformly embedded in the microfibers in a controllable spatial arrangement. This process is precisely tuned by adjusting the flow rates, thus tailoring the resulting multicompartmental microfiber structure. Next, an AC voltage signal is used to trigger the electric field induced cutting process, where the time-averaged electrical force acting on the induced bipolar charge from the Maxwell-Wagner structural polarization mechanism breaks the stress balance at the interfaces, rupturing the double-emulsion droplets, and resulting in the burst release of the encapsulated chelating agents into the hydrogel cavity. The outer


2

Page 3 of 48 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


hydrogel shell is quickly dissolved by a chemical reaction, cutting the long fiber into a series of microfiber units of given length. Further, adding magnetic nanoparticles endows magnetic functionality to these microfiber modules, which are allowed to serve as micromotors and building blocks. This electro-induced cutting method provides a facile strategy for the fabrication of microfibers with desired lengths, showing considerable promise for various chemical and biological applications.

Introduction Hydrogel-based microfibers are drawing increased attention from materials science and biomedical researchers owing to their extensive applications in optics,1,2 electronics,3 biomimetic materials4,5 and biomedical engineering.6,7 In particular, The biocompatible alginate hydrogel microfibers possess many fascinating properties such as excellent biodegradability, low cytotoxicity and nonimmunogenicity,8 making them promising for drug loading,9,10 wound healing,11,12 cell encapsulation,13,14 and biosensing.15 A critical requirement for hydrogel microfibers intended for various practical applications is precise control of their length. Monodisperse microfibers with customized lengths show excellent


3


Page 4 of 48

characteristics in many fields for various applications such as tissue engineering,16,17 water collection18,19, magnetic-driven motion20,21 and microreactor.22 For example, rodshaped neural units covered with hydrogel layer can be used to construct spatially complex three-dimensional (3D) neural networks in vitro.23 Rod-shaped hydrogel microcapsules have been used for high density cell culture to obtain desired morphologies of cell aggregates.24 The cavity-microfibers with prescribed lengths have been assembled into different 3D scaffolds for large-scale dehumidifying.19 Helical microstructured materials with controllable lengths can be used as micromotors by converting various energies into mechanical movements in liquid media, showing great potential for many applications.20 In addition, microfiber with uniform length can be used as experimental platforms to study the rheological feature of fiber suspensions.25 By virtue of its precise microflow manipulation, microfluidic approaches for microfiber fabrication enable continuous production of microfibers with excellent size and flexible morphology as well as good chemical complexity.26 Typically, during the microfluidic spinning process, a stable liquid jet that is enclosed by another sheath flow, undergoes either a physical or chemical transformation, thus producing solid microfibers. To date,


4

Page 5 of 48 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


hollow,27,28 porous,29,30 grooved,31,32 and composite33,34 fibers have all been successfully produced using microfluidics. Despite these heterogeneous structures, few works have focused on generating microfibers with tailored lengths ranging from the micro- to macroscale. In one report, an electronically controlled single layer membrane valve and a pulsed irradiation source was used to mechanically cut the microfibers to the required length.35 Another scheme has applied a buffer sheath flow with a pulsatile pressure to segment an alginate precursor jet, demonstrating the ability to generate microfibers with controllable length ranging from 200 to 1000 μm.36 Despite their effectiveness, both of these previous reports have adopted segmentation of the fiber precursor solution jet prior to gelation to generate microfiber segments of defined lengths. The morphology of the resultant microfibers is inferior due to the effect of the surface tension on the hydrogel precursor filaments. Electrical manipulation of micro-objects in microfluidic systems is a well-established technology and provides an excellent platform for myriad applications.37 In particular, an active area of research uses an electric field to manipulate droplets, in ways that include droplet splitting,38 coalescence39 and sorting.40 In the case of double-emulsion droplets,


5


Page 6 of 48

electric fields have recently been effectively introduced to trigger the fast release of encapsulated contents from the droplets by rupturing their oil shell.41 It is predicted that such a method is scalable to initiate a burst of double-emulsion droplets embedded in a microfiber, leading to the location-specific release of the encapsulated substance within droplet. If the substance released is a fiber lyase or chelating agent, the double-emulsion droplets can function as tipping points to cut the hydrogel microfiber into a series of elements of given length. This may provide a length control strategy for hydrogel microfibers. Instead of segmenting the jet templates, herein we present a novel microfluidic strategy to cut the hydrogel microfiber into discrete microfiber units of prescribed length by an AC electric field, as shown in Figure 1. (i) To control the fiber length, precisely-tailored multicompartmental alginate fibers with uniformly-entrapped water-in-oil-in-water (W/O/W) double-emulsion droplets are introduced by a two-stage microfluidic system. (ii) The

resultant

multicompartmental

microfibers

are

transferred

to

another

polydimethylsiloxane (PDMS) microfluidic device where an electric field is established across the suspending medium between the embedded acupuncture needle electrodes.


6

Page 7 of 48 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


At the appropriate field strength and frequency, the embedded W/O/W droplets burst to release the encapsulated chelating agents due to Maxwell-Wagner interfacial polarization, inducing the multicompartmental microfibers with varying internal droplet arrangements to be cut into discrete microfiber modules with variously defined lengths. (iii) Magnetic functionality is added to these microfiber modules to achieve precise manipulation including controlled motion of a predefined trajectory and 3D assembly. This work provides a simple and flexible strategy for tailoring the microfiber length on demand, offering numerous of useful properties for various biological applications. Results and discussion

Microfluidic fabrication of alginate microfibers incorporated with double-emulsion droplets Figure 1a illustrates schematically the two-stage capillary microfluidic device for fabricating the multicompartmental alginate hydrogel microfibers (details in the Experimental section). W/O/W droplets that function as spacing nodes are uniformly embedded in the microfiber, giving rise to equal-length fiber compartments. The stability of the W/O/W double-emulsion droplets in the hydrogel is demonstrated, as shown in Figure S1 in the Supporting Information (SI). The fabrication of multicompartmental


7


Page 8 of 48

microfibers is taken in two steps, including the generation of the droplets and the embedding of the droplets into the microfibers. In the first step, a flow-focusing geometry composed of a coaxially-aligned injection tube and a transition tube is used to emulsify the innermost phase (Wi) and the middle oil phase (Om) to generate the W/O/W doubleemulsion droplets. The transition tube facilitates the regular arrangement of the resultant W/O/W droplets along the middle water phase (Wm) flow direction. In the second fabrication step, a flow of Wm carrying a stable array of droplets is sheathed and gelled in situ by another outer phase (Wo), producing cross-linked hydrogel microfibers. Here, the

Wi fluid was 0.3 mol/L sodium citrate supplemented with 2.5 wt% pluronic, where the latter acted as a surfactant to stabilize the emulsions. The Wi solution then had Rhodamine B dye added for color identification. The Om fluid was PDMS oil mixed with silicon oil at a volume ratio of 3:7, while the Wm fluid comprised an aqueous solution of 0.8 wt% sodium alginate and 1 wt% poly(vinyl alcohol) (PVA) solution mixed with 0.02% (v/v) fluorescent polystyrene nanoparticles. The Wo fluid was an aqueous solution of 2.5 wt% calcium chloride (CaCl2) mixed with 80 wt% glycerol. With this design, W/O/W double-emulsion droplets are stably encapsulated into the hydrogel microfiber with a high degree of


8

Page 9 of 48 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


flexibility and controllability. Figure 1b and 1c show the microfibers in bulk and under a microscope, respectively. The W/O/W droplet-in-fiber structure with multiple layers is shown in Figure 1d. Because of the special configuration of the microfluidic device, some specific operation procedures must be followed to generate and/or control the droplet-in-fiber structure. First, the Wm and Wo flows were initially pumped into the device from the same direction, whereupon pure alginate microfibers were formed upon contact of the two phase fluids. While this fibering process reached a steady state, the Wi and Om flows were simultaneously introduced into the chip, and hydrodynamically focused by the Wm flow, breaking into monodisperse W/O/W double-emulsion droplets with the core-shell structure. Then, the resultant W/O/W droplets, which were spontaneously aligned in the transition tube, were successively encapsulated in the alginate hydrogel microfiber at the location where the Wm fluid was extruded from the transition tube and immediately gelled by the Ca2+ ions from the Wo fluid (Figure 2a and Video S1 in the SI). By this procedure, multicompartmental microfibers with diverse morphologies and configurations can be


9


Page 10 of 48

produced (Figure 2b). We found that a transition tube length less than 4 cm allowed the droplets to be equidistantly and stably embedded in the alginate microfibers. Owing to the excellent capability of microfluidics to control fluid at the microscale, the size and morphological features of the multicompartmental alginate hydrogel fibers can be quantitatively controlled by simply adjusting the flow rates. Figure S2 in the SI shows that the relative shell thickness of W/O/W double-emulsion droplets, which is the ratio of shell thickness to outer diameter of droplet, is inversely proportional to the flow rate ratio of the Wi to Om fluid, which is in good agreement with a previous study.42 Thus, in the entire experiment, we fixed this flow rate ratio of the Wi to Om at 4 to produce a constant relative oil shell thickness of approximately 0.072 in the W/O/W droplets embedded in the fiber. Here, we systematically studied the effects that the flow rate of each phase has on the morphologies of this type of multicompartmental microfiber. The effects of the Wi flow rate on the distance between the droplets and the sizes of the droplets and microfibers are shown in Figure 2c. It should be noted that, here, the flow rates of Wi and Om were adjusted simultaneously. For convenience, we mentioned the adjustment of inner flow rate only. Previous study has shown that the distance between the adjacent single-


10

Page 11 of 48 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


emulsion droplets embedded in microfiber was negatively correlated with the inner disperse phase flow rate.33 As for the encapsulation of double-emulsion droplets into microfiber in this study, the Wi and Om fluid can be seen as inner disperse phase in singleemulsion droplets generation system. Accordingly, this effect of the inner disperse phase flow rate on the single-emulsion droplet interval is also applicable to our work, which is also verified by our experiments, as displayed in Figure 2d. When the Wi flow rate increases from 25 to 200 μl/h, the distance between droplets decreases from 1621 to 301.9 μm and exhibits a good distribution (as shown by the graph in the inset of Figure 2d), where the flow rates of Wm and Wo are maintained at 4 and 20 ml/h respectively. The diameter of double-emulsion droplets can be predicted by using a mass balance assumptions:43 d 2  d1 (Q1  Q2 ) (Q1  Q2  Q3 )

(1)

where d2 is the diameter of the coaxial jet, which is directly proportional to the diameter of droplet, d1 is the diameter of the tip orifice of transition tube. Q1, Q2, Q3 are the flow rates of the Wi, Om and Wm, respectively. Equation 1 shows that d2 should decrease with


11


Page 12 of 48

decreasing the total flow rates of the Wi and Om, which is consistent with our experiment results, as shown in Figure 2e. The diameter of the embedded W/O/W droplets increases from 128.3 to 158.9 μm with varying Wi flow rate (red line in Figure 2e), while the microfiber diameter exhibits almost no effect (black line in Figure 2e). Because the diameter of microfiber is a function of the sample stream and total volume flow rates:44   Qsheath Rs  R 1     Qsample  Qsheath 

12 12

  

   

(2)

where Rs is the radius of the sample flow, R is the radius of the exit orifice of the transition tube, Qsample and Qsheath are the flow rates of Wm and Wo. Equation 2 shows that the diameter of hydrogel microfiber mainly depends on the flow rate ratio of Wm to Wo and is almost unaffected by the flow rates of Wi and Om. In addition, the effects of the Wm and

Wo flow rates on the size and morphology of multicompartmental microfibers are also studied. For example, the distance between droplets negatively correlates with the Wm flow rate and positively correlates with the Wo flow rate; while an opposite relationship is observed between the microfiber diameter and the Wm and Wo flow rates (details given in Figure S3 and S4 of the SI). In this study, the spacing of adjacent embedded droplets


12

Page 13 of 48 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


can be freely changed in the range of 60 μm to 3.5 mm. All of these results imply that the distance between the embedded droplets is directly proportional to the spinning rate of the microfibers and inversely proportional to the generation frequency of the doubleemulsion droplets. The diameters of the microfibers directly depend on the flow rate ratio of Wm to Wo, and the diameters of W/O/W droplets are negatively correlated with the flow rates of Wm and positively correlated with the net flow rate of Om and Wi, respectively.43,44 More robust microfibers can be produced by increasing the concentration of alginate in the precursor solution. It is predicted that such multi-component water/oil/hydrogel fibers can serve as important carriers for multi-encapsulation and multi-step release.

Electro-induced cutting of multicompartmental alginate hydrogel microfibers Based on the multicompartmental microfibers with the typical structure of W/O/W droplet-in-fiber, where the droplets will function as tipping points, we further demonstrate the feasibility of our concept of electric field induced multicompartmental microfiber cutting for the generation of microfiber modules with different lengths (Figure 1e and 1f). A PDMS microfluidic device, composed of a square frame-shaped PDMS slab with embedded acupuncture needle electrodes and a glass substrate, was used to controllably tailor the


13


Page 14 of 48

microfiber length (details in the Experimental section). The distance between the two electrodes embedded in the PDMS slab was about 400 μm. The suspending medium in the groove of the PDMS chip was a low-ionic-strength sodium chloride solution (conductivity of 0.03 S/m). And the core conductivity of the droplet was greater than 2 S/m, which was hundreds of times greater than the medium conductivity, so the inner core of droplet was ideally polarizable and always an equipotential body in a field gradient. An AC electric field was developed across the suspending medium between the electrodes by externally imposing an AC voltage signal on the acupuncture needles. The multicompartmental microfibers were manually placed between the two acupuncture needle electrodes with care, ensuring the long fiber body was effectively influenced by the alternating field. The microfiber-cutting process is divided into two sequential stages including the double-emulsion droplet rupture due to the action of interfacial polarization and the reaction-induced microfiber fracture, between which there exists almost no time interval, as displayed in Figure 3a and Video S2 of the SI. In a typical experiment, a square-wave AC voltage signal (32.5 V, 100 kHz) was applied through the electrode pair for fiber-


14

Page 15 of 48 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


cutting. Initially, owing to the action of the time-averaged electrical stresses on the oil membrane, the internal surface of the middle oil shell deformed and wrinkled,45 resulting in the rapid bursting of the double-emulsion droplet and the instant release of its inner aqueous solution. Meanwhile, the resultant flow shock induced the expansion of the surrounding hydrogel shell. Almost simultaneously, the chelating agent (sodium citrate) in the inner aqueous solution contacted with and dissolved the hydrogel shell, leading to a location-specific fracture of the microfiber, and ultimately achieving the controllable electro-induced cutting of microfibers, including pure and magnetic alginate microfibers, as shown in Figure 3b and 3c. It is noted that the electro-induced cutting phenomenon is not limited by whether the initial microfiber’s location is between the parallel electrodes. The microfibers located near the external of the electrodes can firstly be pushed into the inter-electrode gap region by the sizeable global-scale negative dielectrophoresis (DEP) force on account of its large volume, and then be cut off by the steady electric stress (see Video S3, SI). The tailored pure and magnetic microfibers of various lengths are shown in Figure 3d and S5 of the SI.


15


Page 16 of 48

The electro-induced cutting of microfibers is the result of physical disturbance and chemical reaction, wherein the sudden release of sodium citrate encapsulated in the double-emulsion droplet embedded in the microfibers is prerequisite and the foundation. A control experiment is conducted under the same experiment conditions as shown in Video S4 of the SI, where potassium chloride aqueous solution of an identical conductivity, rather than sodium citrate, is used as the inner phase. The results showed that after the burst of the encapsulated droplets the hydrogel swelled to some extent, but no rupture or break of the gel shell occurred, which indicates that the sodium citrate solution is essential for the fiber cutting process in our experiment. We ascribe the bursting of the double-emulsion droplet to a breakdown of stress balance between the disjointing pressure, the surface tension on a curved surface, and inhomogeneous electrical stress at the oil shell/suspending medium and oil shell/aqueous core interfaces. In this process, the nonlinear time-averaged electrical stress arises from a synchronous switching of the electric field direction and the induced surface charge polarity under harmonic actuations of multiple Fourier modes, as shown in Figure 4a and 4b. Moreover, the induced dipole moment phasor and time-averaged electrical stress distribution on the


16

Page 17 of 48 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


embedded droplets are numerically simulated using COMSOL MULTIPHYSICS (Version 5.3a), with the relevant calculation results presented in Figure 4c. In the absence of an AC signal, the multicompartmental microfibers remain fairly intact owing to the uniform Laplace pressure, and are suspended freely in the liquid medium. When an external square-wave electric field is applied, however, the inhomogeneous electrical stress induced by structural polarization cannot just be sufficiently compensated by a static pressure gradient across the sharp material interface. Thus, in response to the AC field, a viscous fluid flow occurs in the immediate vicinity of the phase boundary that attempts to balance with both the Maxwell force and surface tension. Because of the relatively large electrical Bond number of the oil phase that experiences the greatest transient voltage drop, the AC electrohydrodynamics results in the rapid bursting of the doubleemulsion droplet. Upon contact of the inner aqueous phase and the suspending medium, a sudden loss of surface tension at the resulting water/water interface generates an additional pressure gradient pushing the high conductivity inner aqueous solution within the droplet to quickly blast out into the suspending medium, and thereafter the ejection process of the inner aqueous droplet is further accelerated taking into account liquid DEP


17


Page 18 of 48

in an imposed conductivity gradient.46 It is noteworthy that, the magnitude of typical timeaveraged electric stress acting on droplet surface is on the order of 1 Pa under practical experimental condition of electrical field intensity E=81.25 V·mm-1, and oscillation frequency f=100 kHz (Figure 4c), as obtained directly from numerical simulation (See Figure S6 of the SI for detailed information about the physical model). Though not appreciable, it is sufficient to overcome the Laplace pressure to initiate a minor mechanical perturbation to the microsystem, leading to continuous electro-deformation of the thin oil membrane and then burst rupture of the double-emulsion droplets. In this way, the resulting driving force inflates the outer hydrogel shell and thins it. Simultaneously under the chemical action between the chelating agents and the hydrogel wall, the long microfibers are segmented into multiple sections of specific length. In addition, we find in the experiment that the oil shell thickness (δ) has an effect on the rupture of the double-emulsion droplets. the double-emulsion droplet with thin shell is easier to break up, whereas the droplet with thicker shell takes a longer time to be ruptured under the same AC electric field. We fix the frequency at 100KHz and investigate the influence of the oil shell thickness on the rupture time of droplet, as shown in Figure


18

Page 19 of 48 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


S7 of the SI. In this work, the double-emulsion droplets embedded in hydrogel microfiber are used for the encapsulation and burst release of sodium citrate instantaneously. To facilitate this process, we used the droplet with thinner shell (Wi/Om=4) in experiments without changing this parameter. Further on, the threshold fiber-cutting voltage U for various frequencies is also studied, as shown in Figure 4d. When the applied voltage is higher than the critical voltage (yellow region in Figure 4d), the microfibers can be cut, otherwise the electro-induced cutting process will not occur (bluish green region in Figure 4d). The critical voltage increases along with the increase of the applied field frequency. This is because when the field frequency grows and surpasses the reciprocal interfacial charge relaxation time, the displacement current dominates over the Ohm conduction, which reduces the Coulomb force acting on the induced free charge and finally leaves only the dielectric force to act on the polarized bound charge at the material interface in the high-frequency limit. On account of this dielectric dispersion process, a higher critical voltage is needed for the electrical stress to conquer the interfacial surface tension at higher field frequencies.

Manipulation of the fabricated alginate microfibers with prescribed length


19


Page 20 of 48

These tailored microfibers can be used as micromotors and building blocks for various manipulations. Characterized by their low cost and easy integration, the magnetic actuation of micromotors is one of the most promising fuel-free propulsion strategies.47 To impart our microfibers, which will serve as micromotors, with the characteristic of a magnetic field responsiveness, magnetic nanoparticles were dispersed in the precursor solution (sodium alginate solution). After these magnetic microfiber modules were synthesized by electro-induced cutting process, their locomotion response to an external magnetic field was investigated. Figure 5a, 5b and Video S5 of the SI illustrate the motion of the microfiber module in a liquid medium along a predefined Z-shaped trajectory. Under a two-dimensional (2D) counterclockwise rotating magnetic field, once the magnet rotates, the microfiber module directly below the magnet immediately begins to turn counterclockwise. A circular rotation trajectory is observed, as illustrated in Figure 5c, 5d and Video S5 of the SI. In this process, we find that the radius of the circular trajectory is negatively related to the rotational frequency of the magnet, as shown in Figure S8 of the SI. In particular, the movement of the microfiber can change from a circular rotation to a fixed-point rotation when the rotational frequency of the magnet reaches to a certain


20

Page 21 of 48 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


value, as illustrated in Figure 5e, 5f and Video S5 of the SI. In addition, using a multipledegrees-of-freedom manipulator, the magnetic-field-guided patterning and assembly of microfiber modules is accomplished, where these modules served as building blocks. Figure 5g illustrates the 2D patterning of the microfiber elements, demonstrating the initials of our university (i.e., “HIT”). A 3D microstructure is also created by stacking these microfiber elements layer by layer, as shown in Figure 5h. These processes indicate that these microfiber segments have sufficient strength and maneuverability to achieve various micro-operations. Because the microfiber elements presented herein are made of only alginate hydrogel and magnetic nanoparticles, they are highly biocompatible. Therefore, these microfiber modules are an ideal basis material for various biomedical applications. Conclusion In conclusion, we developed a novel and flexible microfluidic approach for the controllable fabrication of microfiber modules with customizable length via electroinduced cutting of multicompartmental microfibers possessing a W/O/W droplet-in-fiber structure. Microfibers with a regular arrangement of embedded double-emulsion droplets


21


Page 22 of 48

along the length of the fiber body were fabricated by sequentially combining the doubleemulsion droplet generation process and the hydrogel fiber fabrication process. Benefiting from the relative independence of the droplet generation and fiber spinning processes, the sizes of the microfibers and droplets and the droplet spacing could be easily controlled by adjusting the flow rates of the different phases. Based on this process, the formed hydrogel microfibers were uniformly segmented initially by the doubleemulsion droplets. Subsequently, an imposed AC electric field induces ponderomotive interfacial stresses that helped trigger a rapid rupture of the double-emulsion droplets to release the internal chelating agents, thus enabling the electro-induced cutting of the microfibers under the synergy of physical disturbance and chemical reaction. This process was demonstrated by cutting microfibers with different structures into microfiber segments of different lengths for various manipulations, including the controllable motion of a predefined trajectory and 3D assembly. The novelty of this approach lies in the controllable encapsulation of double-emulsion droplets in the microfibers and the flexible electro-induced cutting of the microfibers. In addition, the hierarchical structure of the multicompartmental microfibers allows the encapsulation of diverse materials as needed


22

Page 23 of 48 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


in the double-emulsion droplets. Thus, our approach can be easily scalable to cut various biodegradable hydrogel microfibers. These results suggest that our microfluidic strategy demonstrates great advantages for the flexible cutting of hydrogel microfibers into discrete, monodispersed microfiber modules of required length, ranging from a few hundreds of micrometers to several millimeters. Further, the resultant microfiber modules are highly-promising for targeted delivery and tissue engineering applications Experimental section

Materials: The sodium alginate(Na-Alg), calcium chloride, Sodium citrate, glycerol and ethylene oxide–propylene oxide–ethylene oxide triblock copolymer (Pluronic F108) were all obtained from Aladdin. Polyvinyl alcohol (PVA, 87–89% hydrolyzed, average Mw = 13 000–23 000), Rhodamine B and methylene blue were purchased from Sigma-Aldrich. EMG 408 ferrofluid was purchased from Ferrotec Corp and diluted by DI water. As the innermost phase (Wi), an aqueous solution of a mixture of 0.3 mol L−1 sodium citrate and 2.5 wt% Pluronic were used. PVA and Pluronic were used as surfactants to facilitate the stable formation of emulsion droplets. The middle water phase (Wm) was 0.8 wt% sodium alginate and 1 wt% PVA solution with 0.02% (v/v) fluorescent polystyrene nanoparticles.


23


Page 24 of 48

The middle oil phase (Om) was mixture of PDMS (Sylgard 184, Dow Corning) and silicone oil (50 cSt, PMX‐200, Dow Corning) with the volume ratio of 3:7. As the outer phase (Wo), an aqueous solution of 2.5 wt% calcium chloride mixed with 80 wt% glycerol was used. The addition of glycerol, used for matching the viscosity of the out phase and the middle water phase, made it easier to form a liquid jet. Solutions were all filtered before pumped into glass capillary microfluidics device.

Fabrication of the glass capillary microfluidics device: A glass capillary microfluidic device combining hydrodynamic flow-focusing and co-flowing configuration was designed for the preparation of multicompartmental alginate microfibers. The device consisted of five coaxially assembled glass capillaries with different sizes and shapes on glass slides, as illustrated in Figure 1a. Two cylindrical capillaries (ID 0.58 mm, OD 1.03 mm, World precision instruments, Inc., 1B100−6) and another circular capillary (ID 0.2 mm, OD 0.33 mm, World precision instruments, Inc., 1B100−6) were respectively used as injection tube, collection tube and transition tube. The tapered tips of the injection tube and collection tube were shaped by a micropipette puller (P-97, Sutter Instrument) and then adjusted by the microforge (MF-900, Narishige, Tritech Research, Inc.) to the designed


24

Page 25 of 48 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


sizes, with the inner diameter of 40 µm and 180 µm, respectively. The outer wall of the injection

tube

and

both

sides

of

the

collection

tube

were

treated

with

octadecyltrichlorosilane (OTS, Sigma-Aldrich) to be hydrophobic. Finally, three cylindrical capillaries were coaxially and oppositely fitted into two square glass tubes with an inner dimension of 1.05mm in proper sequence, then a transparent epoxy resin (Devcon 5 Minute Epoxy) was used to fixed and sealed all tubes when necessary.

Fabrication of the polydimethylsiloxane (PDMS) microfluidics device: The fabrication of PDMS chip used for length control of microfiber was based on standard soft lithographical method. The device was composed of a square frame-shaped PDMS slab (3×4×0.5 cm) with embedded acupuncture needle electrodes and a glass substrate. The distance between the two electrodes embedded in the PDMS slab was about 400 μm. The PDMS slab had a square groove for manipulation, generated from a polymethylmethacrylate (PMMA) mold. First, the PDMS (Dow Corning, Sylgard 184) mixture was poured onto the mold and cured at 80 C for 2 h. Next, the resultant PDMS slab was peeled off from mold and treated about 32s in an O2 plasma cleaner. Finally, the glass substrate and the


25


Page 26 of 48

plasma treated PDMS slab were bonded together and the parallel fixed acupuncture needle electrode pair was manually inserted into the PDMS slab to form a complete microfluidic device under an optical microscope.

Operation of the Microfluidic Device: Four glass syringes (Hamilton) containing Wi, Om, Wm and Wo were installed onto syringe pumps (Harvard Apparatus) and connected to corresponding inlets of the device. All phases were then injected into the glass device at a constant flow rate using the pumps to fabricate multicompartmental microfibers. The microfibers were collected in a vessel with 0.5% CaCl2 aqueous solution and then manually transferred to the PDMS chip for the fiber-cutting process. In this process, the AC signal energized on acupuncture needle electrodes was generated by a function generator (TGA 12104, TTi, UK), amplified by an amplifier (Model 2350, TEGAM, USA).


26

Page 27 of 48 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Figure 1. Microfluidic fabrication of alginate microfibers with tailored lengths via electroinduced cutting process. (a) Schematic diagram of the two stage capillary microfluidic device for fabricating multicompartmental alginate hydrogel microfibers; the detail views show the sequential steps of fluid emulsifying, droplets aligning and fibering. (b)


27


Page 28 of 48

Macroscopic and (c) microscopic optical images of double-emulsion droplets embedded in microfiber. (d) Diagram explains the typical structure of multicompartmental microfiber, including an aqueous core loaded with sodium citrate and a double-layer shell consisting of a middle oil shell and outer hydrogel shell. (e) Schematic of PDMS microfluidic device for electro-induced cutting of microfibers. (f) Schematic illustration showing the controllable electro-induced cutting of multicompartmental fibers into different lengths.


28

Page 29 of 48 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60



29


Page 30 of 48

Figure 2. Various morphologies of multicompartmental alginate fibers with incorporated double-emulsion droplets affected by flow rates. (a) Real-time microscope images showing the process of droplet generation and alginate microfiber fabrication. (b) Brightfield and corresponding fluorescent images of the resultant microfibers with different droplet alignments. (c) Bright-field and corresponding fluorescent images of the alginate microfiber with various droplets distributions under different flow rates of inner phase. (d) The relationship between inner flow rate and droplets spacing. The inset figure showing the spacing distribution of neighbored droplets under the flow rate of Wi at 75 μl/h. (e) The relationship between inner flow rate and the diameter of droplets (red line) and microfibers (black line)


30

Page 31 of 48 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Figure 3. The electro-induced cutting of multicompartmental microfiber to set the length of fiber. (a) Schematic illustration of the specific process of fiber-cutting. (b) Fluorescent image of the electro-induced cutting process of pure microfiber. (c) Bright-field image of the electro-induced cutting process of magnetic microfiber. (d) Bright-field and corresponding fluorescent images of the microfibers with different lengths after electroinduced cutting process.


31


Page 32 of 48

Figure 4. The electro-triggered abrupt burst of W/O/W double-emulsion droplets. (a, b) Schematic illustration of the induced charges and nonlinear electrical stress distribution on the W/O/W droplets in (a) the positive half cycle and (b) the negative half cycle of voltage. (c) A surface plot of the complex amplitude of induced charge phasor (unit: C/m2) and arrow plot of steady electrical stress component (unit: Pa) on the inner W/O/W droplets from numerical simulation. (d) Plot of the critical voltage for microfiber fracture as a function of the field frequency, above the critical voltage are the fracture region (yellow part) and the below this threshold are non-fracture region (bluish green part).


32

Page 33 of 48 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Figure 5. The magnetic alginate fiber modules serving as micromotors and building blocks for various manipulation. (a) Predefined trajectory and (b) composite fluorescence images of the translational movement. (c) Predefined trajectory and (d) composite fluorescence images of the circular movement. (e) Predefined trajectory and (f) composite fluorescence images of the fixed point rotational movement. (g) Fluorescent image of the patterned


33


Page 34 of 48

microfiber modules with shape of “HIT”. (h) Fluorescent image of the layer-by-layer architecture by stacking the microfiber modules.

ASSOCIATED CONTENT

Supporting Information. The experimental equipment; the stability of W/O/W double emulsion droplets embedded in the alginate hydrogel; the relationship between the flow rates of Wm and

Wo and the morphology of microfibers; The experimental detail of electric field induced cutting of hydrogel microfibers; The detailed description of the physical model; The fluorescent images of the magnetic microfibers with different length; The relationship between the relative shell thickness of W/O/W double-emulsion droplets and the flow rate ratio of the Wi to Om fluid; the influence of the oil shell thickness on the rupture time of droplet under a fixed frequency of 100KHz; Dependence of the radius of the circular trajectory on the rotational frequency of the applied magnetic field and Nomenclature. (PDF) Continuous spinning of multicompartmental microfiber with regularly embedded W/O/W


34

Page 35 of 48 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


double-emulsion droplets. (MP4) The electro-induced cutting process of multicompartmental microfiber with diverse droplet arrangements. (MP4) The electro-induced cutting process of multicompartmental microfibers inside or outside the electrodes. (MP4) The control experiment conducted under the same experiment conditions, where sodium citrate is replaced with potassium chloride aqueous solution of the same conductivity. (MP4) Various locomotion of microfiber modules responded to external magnetic field. (MP4)

AUTHOR INFORMATION

Corresponding Author *E-mail: [email protected];

*E-mail: [email protected];


35


Page 36 of 48

*E-mail: [email protected]

Author Contributions HY.J., YK.R. and LK.H. conceived the idea and designed the experiment; XK.D. and LK.H. carried out the experiments; XK.D. analyzed data; and XK.D., YK.R. LK.H. WY.L. YK.J. and HY.J. wrote the paper; WY.L. contributed to the theoretical analysis of the article.

Notes The authors declare no competing financial interest.

ACKNOWLEDGMENT This work was supported financially by the National Natural Science Foundation of China (Grant No. 11672095, NO. 11702035 and NO. 11702075), and the Foundation for Innovative Research Groups of the National Natural Science Foundation of China (Grant No. 51521003). The authors acknowledge Prof. Huijun Gao’s group (Harbin


36

Page 37 of 48 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Institute of Technology) for their assistance with the micropipette puller. The authors also acknowledge Xiangsong Feng for his suggestions to the paper writing.

REFERENCES (1) Zhang, Y.; Wang, C.-F.; Chen, L.; Chen, S.; Ryan, A. J. Microfluidic-SpinningDirected Microreactors Toward Generation of Multiple Nanocrystals Loaded Anisotropic Fluorescent Microfibers Adv. Func. Mater. 2015, 25, 7253− 7262.

(2) Yetisen, A. K.; Jiang, N.; Fallahi, A.; Montelongo, Y.; Ruiz-Esparza, G. U.; Tamayol, A.; Zhang, Y. S.; Mahmood, I.; Yang, S. A.; Kim, K. S.; Butt, H.; Khademhosseini, A.; Yun, S. H. Glucose-Sensitive Hydrogel Optical Fibers Functionalized with Phenylboronic Acid Adv. Mater. 2017, 29, 1606380.

(3) Wei, S.; Qu, G.; Luo, G.; Huang, Y.; Zhang, H.; Zhou, X.; Wang, L.; Liu, Z.; Kong, T. Scalable and Automated Fabrication of Conductive Tough-Hydrogel Microfibers with Ultrastretchability, 3D Printability, and Stress Sensitivity ACS Appl. Mater.

Interfaces 2018, 10, 11204− 11212.


37


Page 38 of 48

(4) Tian, Y.; Zhu, P.; Tang, X.; Zhou, C.; Wang, J.; Kong, T.; Xu, M.; Wang, L. LargeScale Water Collection of Bioinspired Cavity-Microfibers Nat. Commun. 2017, 8, 1080.

(5) Liu, Y.; Ge, D.; Cong, J.; Piao, H. G.; Huang, X.; Xu, Y.; Lu, G.; Pan, L.; Liu, M. Magnetically Powered Annelid-Worm-Like Microswimmers Small 2018, 14, e1704546.

(6) Jun, Y.; Kang, E.; Chae, S.; Lee, S. H. Microfluidic Spinning of Micro- and NanoScale Fibers for Tissue Engineering Lab Chip 2014, 14, 2145− 2160.

(7) Cheng, J.; Jun, Y.; Qin, J.; Lee, S. H. Electrospinning Versus Microfluidic Spinning of Functional Fibers for Biomedical Applications Biomaterials 2017, 114, 121− 143.

(8) Lee, K. Y.; Mooney, D. J., Alginate: Properties and Biomedical Applications Prog.

Polym. Sci. 2012, 37, 106− 126.

(9) Perez, R. A.; Kim, H. W. Core-Shell Designed Scaffolds for Drug Delivery and Tissue Engineering Acta Biomater. 2015, 21, 2− 19.


38

Page 39 of 48 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


(10) Um, E.; Nunes, J. K.; Pico, T.; Stone, H. A. Multicompartment Microfibers: Fabrication and Selective Dissolution of Composite Droplet-in-Fiber Structures J.

Mater. Chem. B 2014, 2, 7866− 7871.

(11) Ahn, S. Y.; Mun, C. H.; Lee, S. H. Microfluidic Spinning of Fibrous Alginate Carrier Having Highly Enhanced Drug Loading Capability and Delayed Release Profile

RSC Adv. 2015, 5, 15172− 15181.

(12) Masood, R.; Miraftab, M. Novel Materials for Moist Wound Management: AlginatePsyllium Hybrid Fibres J. Wound Care. 2014, 23, 153− 159.

(13) Onoe, H.; Okitsu, T.; Itou, A.; Kato-Negishi, M.; Gojo, R.; Kiriya, D.; Sato, K.; Miura, S.; Iwanaga, S.; Kuribayashi-Shigetomi, K.; Matsunaga, Y. T.; Shimoyama, Y.; Takeuchi, S. Metre-Long Cell-Laden Microfibres Exhibit Tissue Morphologies and Functions Nat. Mater. 2013, 12, 584− 590.


39


Page 40 of 48

(14) Cheng, Y.; Zheng, F.; Lu, J.; Shang, L.; Xie, Z.; Zhao, Y.; Chen, Y.; Gu, Z. Bioinspired Multicompartmental Microfibers from Microfluidics Adv. Mater. 2014,

26, 5184− 5190.

(15) Yu, Y.; Fu, F.; Shang, L.; Cheng, Y.; Gu, Z.; Zhao, Y. Bioinspired Helical Microfibers from Microfluidics Adv. Mater. 2017, 29, 1605765.

(16) Cheng, Y.; Yu, Y.; Fu, F.; Wang, J.; Shang, L.; Gu, Z.; Zhao, Y. Controlled Fabrication of Bioactive Microfibers for Creating Tissue Constructs Using Microfluidic Techniques ACS Appl. Mater. Interfaces 2016, 8, 1080− 1086.

(17) Sun, T.; Shi, Q.; Huang, Q.; Wang, H.; Xiong, X.; Hu, C.; Fukuda, T. Magnetic Alginate Microfibers as Scaffolding Elements for the Fabrication of MicrovascularLike Structures Acta Biomater. 2018, 66, 272− 281.

(18) He, X. H.; Wang, W.; Liu, Y. M.; Jiang, M. Y.; Wu, F.; Deng, K.; Liu, Z.; Ju, X. J.; Xie, R.; Chu, L. Y. Microfluidic Fabrication of Bio-Inspired Microfibers with


40

Page 41 of 48 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Controllable Magnetic Spindle-Knots for 3D Assembly and Water Collection ACS

Appl. Mater. Interfaces 2015, 7, 17471− 17481.

(19) Tian, Y.; Wang, J.; Wang, L. Microfluidic Fabrication of Bioinspired CavityMicrofibers for 3D Scaffolds ACS Appl. Mater. Interfaces 2018, 10, 29219− 29226.

(20) Yu, Y.; Shang, L.; Gao, W.; Zhao, Z.; Wang, H.; Zhao, Y. Microfluidic Lithography of Bioinspired Helical Micromotors Angew. Chem., Int. Ed. 2017, 129, 12295− 12299.

(21) Tang, M. J.; Wang, W.; Li, Z. L.; Liu, Z. M.; Guo, Z. Y.; Tian, H. Y.; Liu, Z.; Ju, X. J.; Xie, R.; Chu, L. Y. Controllable Microfluidic Fabrication of Magnetic Hybrid Microswimmers with Hollow Helical Structures Ind. Eng. Chem. Res. 2018, 57, 9430− 9438.

(22) Xu, L. L.; Wang, C. F.; Chen, S. Microarrays Formed by Microfluidic Spinning as Multidimensional Microreactors Angew. Chem., Int. Ed. 2014, 53, 3988− 3992.


41


Page 42 of 48

(23) Kato-Negishi, M.; Onoe, H.; Ito, A.; Takeuchi, S. Rod-Shaped Neural Units for Aligned 3D Neural Network Connection Adv. Healthcare Mater. 2017, 6, 1700143.

(24) Liu, Z.; Takeuchi, M.; Nakajima, M.; Hasegawa, Y.; Huang, Q.; Fukuda, T. ShapeControlled High Cell-Density Microcapsules by Electrodeposition Acta Biomater. 2016, 37, 93− 100.

(25) Perazzo, A.; Nunes, J. K.; Guido, S.; Stone, H. A. Flow-Induced Gelation of Microfiber Suspensions Proc. Natl. Acad. Sci. USA 2017, 114, E8557-E8564.

(26) Daniele, M. A.; Boyd, D. A.; Adams, A. A.; Ligler, F. S. Microfluidic Strategies for Design and Assembly of Microfibers and Nanofibers with Tissue Engineering and Regenerative Medicine Applications Adv. Healthcare Mater. 2015, 4, 11− 28.

(27) Xu, P.; Xie, R.; Liu, Y.; Luo, G.; Ding, M.; Liang, Q. Bioinspired Microfibers with Embedded Perfusable Helical Channels Adv. Mater. 2017, 29, 1701664.


42

Page 43 of 48 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


(28) Xie, R.; Xu, P.; Liu, Y.; Li, L.; Luo, G.; Ding, M.; Liang, Q. Necklace-Like Microfibers with Variable Knots and Perfusable Channels Fabricated by an Oil-Free Microfluidic Spinning Process Adv. Mater. 2018, 30, e1705082.

(29) Daniele, M. A.; North, S. H.; Naciri, J.; Howell, P. B.; Foulger, S. H.; Ligler, F. S.; Adams, A. A. Rapid and Continuous Hydrodynamically Controlled Fabrication of Biohybrid Microfibers Adv. Func. Mater. 2013, 23, 698− 704.

(30) Hou, L.; Jiang, H.; Lee, D. Bubble-Filled Silica Microfibers from Multiphasic Flows for Lightweight Composite Fabrication Chem. Eng. J. 2016, 288, 539− 545.

(31) Kang, E.; Choi, Y. Y.; Chae, S. K.; Moon, J. H.; Chang, J. Y.; Lee, S. H. Microfluidic Spinning of Flat Alginate Fibers with Grooves for Cell-Aligning Scaffolds Adv.

Mater. 2012, 24, 4271− 4277.

(32) Shi, X.; Ostrovidov, S.; Zhao, Y.; Liang, X.; Kasuya, M.; Kurihara, K.; Nakajima, K.; Bae, H.; Wu, H.; Khademhosseini, A. Microfluidic Spinning of Cell-Responsive Grooved Microfibers Adv. Func. Mater. 2015, 25, 2250− 2259.


43


Page 44 of 48

(33) Yu, Y.; Wen, H.; Ma, J.; Lykkemark, S.; Xu, H.; Qin, J. Flexible Fabrication of Biomimetic Bamboo-Like Hybrid Microfibers Adv. Mater. 2014, 26, 2494− 2499.

(34) Shang, L.; Fu, F.; Cheng, Y.; Yu, Y.; Wang, J.; Gu, Z.; Zhao, Y. Bioinspired Multifunctional Spindle-Knotted Microfibers from Microfluidics Small 2017, 13, 1600286.

(35) Nunes, J. K.; Sadlej, K.; Tam, J. I.; Stone, H. A. Control of the Length of Microfibers

Lab Chip 2012, 12, 2301− 2304.

(36) Martino, C.; Statzer, C.; Vigolo, D.; deMello, A. J. Controllable Generation and Encapsulation of Alginate Fibers Using Droplet-Based Microfluidics Lab Chip 2016,

16, 59− 64.

(37) Fan, S. K.; Huang, P. W.; Wang, T. T.; Peng, Y. H. Cross-Scale Electric Manipulations of Cells and Droplets by Frequency-Modulated Dielectrophoresis and Electrowetting Lab Chip 2008, 8, 1325− 1331.


44

Page 45 of 48 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


(38) Choi, K.; Ng, A. H.; Fobel, R.; Wheeler, A. R. Digital Microfluidics Annu. Rev. Anal.

Chem. 2012, 5, 413− 440.

(39) Jia, Y.; Ren, Y.; Hou, L.; Liu, W.; Deng, X.; Jiang, H. Sequential Coalescence Enabled Two-Step Microreactions in Triple-Core Double-Emulsion Droplets Triggered by an Electric Field Small 2017, 13, 1702188.

(40) Xi, H. D.; Zheng, H.; Guo, W.; Ganan-Calvo, A. M.; Ai, Y.; Tsao, C. W.; Zhou, J.; Li, W.; Huang, Y.; Nguyen, N. T.; Tan, S. H. Active Droplet Sorting in Microfluidics: A Review Lab Chip 2017, 17, 751− 771.

(41) Jia, Y.; Ren, Y.; Hou, L.; Liu, W.; Jiang, T.; Deng, X.; Tao, Y.; Jiang, H. Electrically Controlled Rapid Release of Actives Encapsulated in Double-Emulsion Droplets

Lab Chip 2018, 18, 1121− 1129.

(42) Hou, L.; Ren, Y.; Jia, Y.; Deng, X.; Tang, Z.; Tao, Y.; Jiang, H. A Simple Microfluidic Method for One-Step Encapsulation of Reagents with Varying


45


Page 46 of 48

Concentrations in Double Emulsion Drops for Nanoliter-Scale Reactions and Analyses Anal. Methods 2017, 9, 2511− 2516.

(43) Erb, R. M.; Obrist, D.; Chen, P. W.; Studer, J.; Studart, A. R. Predicting Sizes of Droplets Made by Microfluidic Flow-Induced Dripping Soft Matter 2011, 7, 8757− 8761.

(44) Jeong, W.; Kim, J.; Kim, S.; Lee, S.; Mensing, G.; Beebe, D. J. Hydrodynamic Microfabrication via ″On the Fly″ Photopolymerization of Microscale Fibers and Tubes Lab Chip 2004, 4, 576− 580.

(45) Melcher, J. R.; Taylor, G. I. Electrohydrodynamics: A Review of the Role of Interfacial Shear Stresses Annu. Rev. Fluid Mech. 1969, 1, 111− 146.

(46) García-Sánchez, P.; Ferney, M.; Ren, Y.; Ramos, A. Actuation of Co-Flowing Electrolytes in a Microfluidic System by Microelectrode Arrays Microfluid.

Nanofluidics 2012, 13, 441− 449.


46

Page 47 of 48 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


(47) Chalupniak, A.; Morales-Narvaez, E.; Merkoci, A. Micro and Nanomotors in Diagnostics Adv. Drug Delivery Rev. 2015, 95, 104− 116.


47


Page 48 of 48

Table of contents


48

Electric Field Induced Cutting of Hydrogel Microfibers with Precise

Recommend Documents