Photoresponsive and Magnetoresponsive Graphene Oxide

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Photoresponsive and Magnetoresponsive Graphene Oxide Microcapsules Fabricated by Droplet Microfluidics Gilad Kaufman, Karla A. Montejo, Arthur Michaut, Pawel W. Majewski, and Chinedum O. Osuji ACS Appl. Mater. Interfaces, Just Accepted Manuscript • DOI: 10.1021/acsami.7b14448 • Publication Date (Web): 27 Nov 2017 Downloaded from http://pubs.acs.org on November 28, 2017

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ACS Applied Materials & Interfaces

Photoresponsive

and

Magnetoresponsive

Graphene

Oxide

Microcapsules

Fabricated by Droplet Microfluidics

Gilad Kaufman†#, Karla A. Montejo†‡#, Arthur Michaut§, Paweł W. Majewski§§, and Chinedum O. Osuji†* † Department of Chemical and Environmental Engineering, Yale University, New Haven CT 06511 § Department of Genetics, Harvard Medical School, Boston, MA, 02115 ‡ Department of Biomedical Engineering, Florida International University, Miami FL 33174 §§ Department of Chemistry, University of Warsaw, Warsaw, Poland #These authors contributed equally. KEYWORDS: photoresponsive microcapsules; magnetoresponsive; microcapsules; graphene oxide; microfluidics

Corresponding author: [email protected]

1 Environment ACS Paragon Plus


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ABSTRACT

Fluid compartmentalization by micro-encapsulation is important in scenarios where protection or controlled release of encapsulated species, or isolation of chemical transformations are central concerns. Realizing responsive encapsulation systems by incorporating functional nanomaterials is of particular interest. We report here on the development of graphene oxide microcapsules enabled by a single-step microfluidic process. Interfacial reaction of epoxide-bearing graphene oxide sheets and an amine-functionalized macromolecular silicone fluid creates a chemically crosslinked film with micron-scale thickness at the surface of water-in-oil droplets generated by microfluidic devices. The resulting microcapsules are monodisperse, mechanically resilient, and shape-tunable constructs. Ferrite nanoparticles are incorporated via the aqueous phase and enable microcapsule positioning by a magnetic field. We exploit the photothermal response of graphene oxide to realize microcapsules with photoresponsive release characteristics and show that the microcapsule permeability is significantly enhanced by near-IR illumination. The dual magnetic and photo-responsive characteristics, combined with the use of a single-step process employing biocompatible fluids represent highly compelling aspects for practical applications.

KEYWORDS: Microcapsules; photoresponsive; graphene oxide; triggered release


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INTRODUCTION

The successful mechanical exfoliation of single sheet graphene and observation of its remarkable electron mobility1 led to a concerted effort to explore and exploit the properties of graphene, along with a continually expanding array of other 2D materials.2 The generally poor solution processability of pristine graphene is circumvented by using graphene oxide (GO) as a precursor. GO, the single-layer form of graphitic oxide, can be readily suspended and processed in aqueous media. Subsequent chemical reduction yields a material that recovers some of the properties of pristine graphene monolayers. While GO is valued as a graphene precursor, its intrinsic properties make it a useful nanomaterial in its own right. GO is attractive as a chemically tunable optical material3, as a carbocatalyst for oxidative couplings4, and as an antimicrobial5-7 and antioxidant8-9 nanomaterial. These properties have spurred development of GO for a broad spectrum of applications, ranging from energy science to sensing and biomedical devices. 10

GO incorporation into microcapsule shells is of considerable interest, driven by the potential to leverage the near-IR (NIR) GO photothermal response for photo-stimulated release in biomedical applications,11-12 mirroring the use of nanoparticles of GO13-15 and reduced-GO16 use in photothermal therapy. Further, one can envision using GO-based shells to protect microcapsule contents from oxidative degradation, or as catalytic membranes separating products/reactants into interior/exterior fluids. Recent efforts have realized GO microcapsules by layer-by-layer (LbL) assembly on sacrificial particles11, fluids

in

double

emulsion

droplets20,

by

17-19

, by polymerizing GO-containing

interfacial


assembly

using

amphiphilic


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macromolecules21, and by crosslinking GO-based Pickering emulsions generated by high speed mixing.22

Here we pursue a novel route that circumvents several limitations associated with prior efforts while developing new capabilities. Specifically, we demonstrate fabrication of microcapsules in a single step by crosslinking GO using an amine-containing silicone fluid at the interface of single and double emulsion droplets generated in microfluidic devices. This approach avoids the time consuming sequential adsorption and washing steps associated with the LbL method. The capsules are near-monodisperse, and the fabrication employs biocompatible fluids while avoiding the use of accelerants or photoinitiators to facilitate crosslinking. The capsules are mechanically robust and exhibit accelerated release behavior on NIR illumination. Magnetic nanoparticle incorporation into the microcapsule shell provides magnetic field-based position control, and the formation of magnetically anisotropic, dumbbell-shaped microcapsules. To the best of our knowledge, this work represents the first realization of GO microcapsules with dual magnetoresponsive and photoresponsive characteristics generated using a single-step microfluidic process.

EXPERIMENTAL SECTION

Materials GO was obtained from Graphene Supermarket. An AFM image showing the characteristic 0.5 µm dimensions of the GO sheets is shown in Supporting Information. DC 200 silicone oil, and fluorescein

isothiocyanate

(FITC)

were

purchased

from


Sigma

Aldrich.

KF-860

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(amodimethicone) was kindly supplied by Shin-Etsu. All materials were used as received. MilliQ water (18.2 MΩ cm) was used for the preparation of aqueous solutions. Nickel-zinc ferrite magnetic nanoparticles were synthesized following previously reported hydrothermal synthesis protocol.23 Nanoferrites used in the experiment were negatively charged colloidal particles with mean diameter of 15 nm as determined by Scherrer analysis of powder x-ray diffraction reflexes’ broadening.

GO fluorescent labeling 0.5 wt.%. GO solution was added to 40 µM FITC (fluorescein isothiocyanate) and stirred overnight at room temperature in the dark. The solution was purified by repeated centrifugation (8,000 RPM, 10 min) and decanting cycles, followed by 48 hours of dialysis against deionized water.

NIR triggered release A 50 mW NIR laser providing 808 nm light was used to illuminate a collection of capsules in silicone oil suspended on a concave microscope slide for durations as needed. Additional details regarding experimental methods are provided in the Supporting Information.



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Figure 1. (A) Chemical structures of GO and the reactive silicone diamine, KF 860. (B) Schematic illustration of microcapsule shell formed by crosslinking between GO (hexagonal mesh) and KF 860 (linear strands). (C) Left, top: Schematic illustration of T-junction microfluidic device used to prepare microcapsules. The aqueous GO phase forms droplets (shown in blue) in the KF 860 oil. Left, bottom: The photograph shows stable 365±6 µm GO capsules in a collection vessel. Right: Microcapsule size as a function of the inner/outer phase flow rate ratio. (D-G) Optical microscope images taken during different time points during progressive drying of the capsules exposed to air on a microscope coverslip. (D) before drying; (E) 3 minutes; (F) 13 minutes, showing wrinkles on the surface of the capsules; (G) 38 minutes, with buckling of the capsules evident. Scale bar is 200 µm. (H) Confocal microscopy image of microcapsules prepared using fluorescently tagged GO showing core shell structure with ~ 8 µm thick shell. Scale bar is 100 µm (I) Top-down SEM image of a fully dried microcapsule. The high mechanical strength of the capsule is evident by its ability to keep its structure after drying. Scale bar is 60 µm. (J) Cross-sectional SEM of a microcapsule with ~ 7 µm thick shell. The GO sheets appear to be aligned parallel to the interface. Scale bar is 3 µm.

RESULTS AND DISCUSSION

Microcapsules are prepared using water-in-oil (W/O) emulsion droplets as templates as schematically illustrated in Fig. 1. The droplets consist of aqueous GO suspensions while the outer phase consists of amodimethicone (KF 860), a diamino-modified polymeric silicone,


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diluted in silicone oil. AFM imaging shows that the GO are roughly 0.5 µm in size and that they exist as discrete nanosheets (Supporting Information, Fig. S2) The chemical structures of GO and KF 860 are shown in Fig. 1A and a schematic of the shell structure is shown in Fig. 1B. We utilize a simple microfluidic T-junction tubing device to generate uniform drops between 275 and 440 µm diameter by varying the ratio of inner to outer flow rates, Fig. 1C.

The formation of a solid-like shell is evidenced by shrinkage-induced wrinkling due to osmotic water loss in collected microcapsules, Fig. 1 D-G, and by direct imaging of the shell by confocal microscopy and SEM, Fig. 1 H-J. The confocal image was obtained in oil-suspended microcapsules using fluorescently labeled GO, and clearly shows strong GO localization in the droplet periphery. Confocal images were analyzed by Gaussian fitting of the fluorescence intensity profile across the shell. The shell thicknesses determined from SEM of dried microcapsules, and by analysis of confocal images of oil-suspended microcapsules are similar, roughly 7 µm, and 8 µm respectively. The similarity in thickness for wet and dry preparations indicates that the shell is not strongly swollen by either water or oil. Close examination of the SEM images suggests that the shells are mainly composed of graphene oxide sheets that conform tangentially to the curved droplet interface.

It is important to note that neither GO nor KF 860 alone stabilizes the emulsion droplets against coalescence, which indicates clearly that shell formation and droplet stabilization are due to interactions between GO and KF 860. The fact that no coalescence is observed during microcapsule fabrication indicates the KF 860/GO association is rapid, but manageably so, as there is no clogging of the device. The abundance of complementary functional groups on GO24



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(carboxylic acid, hydroxyl, and ether oxygens of epoxide rings) suggests that simple physical association with the amine-containing KF 860 polymer may be responsible for the shell formation. Interfacial assembly driven by such physical interactions has been used to generate microcapsules in prior work.25-27 Here however, there is also the potential for chemically crosslinking GO by epoxide ring-opening with the primary amine groups of KF 860. The reaction of epoxides on GO by nucleophilic ring-opening with amines under ambient conditions is well documented24, 28-30 and the formation of a chemically crosslinked microcapsule shell is confirmed by the insolubility of the shell when challenged by organic solvents (Supporting Information, Fig. S3).

Figure 2. (A) Schematic of generation of W/O/W double emulsion in a glass capillary microfluidic device. (B) Schematic of diffusion of water molecules from the inner GO drop through the middle silicone fluid and into the surrounding exterior water phase. (C) Snapshots from a movie showing W/O/W in the collection capillary. (D) Stable W/O/W with GO inner


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aqueous drop stabilized by GO/KF 860 interfacial shell. (E) Shrinkage of the inner GO phase occurs due to water loss, or drying, as a result of osmotic-pressure mismatch between the inner and outer aqueous media of the double emulsion. The formation of a viscoelastic shell is evident from the wrinkles on the surfaces of the inner drops after water loss. Scale bar is 200 µm. Microcapsules were also generated using a double emulsion template, to produce a water-in-oilin-water (W/O/W) system, as schematically shown in Fig. 2A,B. Monodisperse double emulsions were formed on chip (Fig. 2C) and collected off chip (Fig. 2D). Shell formation at the inner water-oil interface is evidenced by the wrinkling that occurs due to osmotic loss of water through the middle fluid (Fig. 2E). Adjusting the osmotic pressure of the GO suspension using up to 60 mM NaCl reduced the water loss, but did not completely prevent deswelling. The use of appreciably larger NaCl concentrations (beyond 60 mM) was not feasible as it led to aggregation of the GO. Dewetting of the GO microcapsule from the silicone middle fluid occurred on a timescale of 5-10 minutes and resulted in GO microcapsules dispersed in the exterior water phase (Supporting Information, Fig. S4). The ability to collect the GO capsules in water is noteworthy as fabrication of such water-dispersed capsules is potentially useful for addressing encapsulation and controlled release applications (e.g. in some biomedical or consumer product applications) in aqueous, rather than organic, media.

We explored the role of GO and KF 860 concentration on microcapsule stability and morphology. With a fixed concentration of 2.5 wt.% KF 860, the produced microcapsules were stable against coalescence for GO concentrations between 0.1 and 5 wt. % (Supporting Information, Fig. S5). Microcapsules prepared using 0.1 and 0.5 wt% GO differ in size by less than 1%, but increasing the concentration of GO to 2.5 wt.% results in ~ 9% increase in the capsule size, which we attribute to the increased viscosity of the GO suspensions in this higher concentration regime31 and the resultant change in droplet breakup dynamics. At 5 wt.% GO



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microcapsules are non-spherical and have an opaque surface. The opacity of the shell is consistent with GO aggregation, while the non-spherical morphology likely originates from irreversible deformations during handling. The inability to relax the mechanical deformation suggests that the GO sheets are interfacially jammed in this concentration regime. The microcapsule stability was more sensitive to the KF 860 concentration, with partial or arrested coalescence observed at higher and lower concentrations, for a fixed GO concentration of 0.5 wt.% (Supporting Information, Fig. S5). The arrested coalescence indicates that the density or cohesive strength of the shell is initially insufficient to resist interfacial tension, but that the strength increases with coalescence, or with time (during which coalescence may occur), eventually becoming sufficient to inhibit further coalescence. We speculate that the observed effects at lower KF 860 concentrations are due to an underlying concentration dependence of the association and crosslinking kinetics, with longer timescales for shell formation permitting some coalescence. Conversely at higher concentrations it is possible the droplet surface is excessively populated by the polymer which delays interfacial access for sufficient GO to form a mechanically robust membrane.

We examined the microcapsule shell mechanics using micropipette aspiration. The results of a representative experiment are shown in Fig. 3. We first apply a small negative pressure (1 kPa) to capture the microcapsule, Fig. 3A. This is followed by a quasi-static increase of the aspiration pressure while measuring the length of the capsule drawn into the micropipette, the so-called tongue, Fig. 3B. As the aspiration pressure is increased the length of the tongue grows monotonically, but water simultaneously leaks from the capsule as evident from the difference in contrast observed along the length of the pipette, Fig. 3B. Around 2 kPa, the tongue is observed


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to increase in length without further increase of aspiration pressure, Fig. 3C. Eventually, the capsule loses its fluid completely and collapses into a crumpled mass at the mouth of the pipette, Fig. 3D. Quantitative measurements of the tongue length during the aspiration process are shown in Fig. 3E. Remarkably, the shell integrity is not lost and collapsed capsules can be reinflated to a spherical shape by reversing the aspiration pressure, Fig. 3F.

Figure 3. Micropipette aspiration of GO microcapsules (A) Microcapsules captured at the tip of the capillary by applying negative pressure of 1 kPa (B) The pressure is increased to 1.5 kPa and a tongue is formed. At the same time water leaks from the capsule core as evident from the contrast difference between the capillary mouth and downstream of the capillary. (C) Further increase of the pressure to 2 kPa results in increase in tongue length at constant pressure. (D) The increased in tongue length and decrease of drop’s volume eventually results in buckling of the capsule. Scale bar is 40 µm. (E) Measurement of tongue length and pressure during the aspiration process. (F) Inflation of a buckled capsule by applying positive pressure. Scale bar is 80 µm.

A video of the aspiration and reinflation of the capsule is available in Supporting Information. The creep observed at constant aspiration pressure due to the permeability of the capsule shell 11 Environment ACS Paragon Plus


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precludes quantitative analysis of the force-deformation data. Nonetheless, from the reinflation characteristics it is apparent that the capsules are highly resilient mechanically, as expected for a material consisting of high modulus nanosheets crosslinked by a low glass transition temperature polymer, such as the KF 860 fluid used here.

GO exhibits a strong NIR photothermal response. This response makes GO an attractive material for fabricating optically triggered microcapsules in which NIR absorption induced heating leads to a change in capsule shell permeability.11 We compared the release of a model permeant dye, methyl orange, in the presence and absence of NIR illumination. Results are shown in Fig. 4. Without NIR illumination the capsules shrink by 25% over the course of roughly 30 mins due to osmotic water loss into the surrounding fluid. There was comparatively little loss of dye from the capsule core as judged by the change in relative color intensity of the exterior to interior fluids. By comparison, under NIR illumination, the microcapsules shrink by roughly 90% over the same time period, and display a marked change in the relative color intensity of the exterior and interior fluids. Time evolution data show that the capsules have gradual, rather than burst, release characteristics (Supporting Information, Fig. S6). It is clear that NIR illumination led to significant acceleration of both water loss and dye release from the capsule. These results show that NIR is effective in inducing permeability changes of the capsule shell.


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Figure 4. Release of methyl orange from microcapsules as a function of time. Top panel: without laser irradiation the capsules shrink by 25% and the majority of the dye remains encapsulated. Bottom panel: under NIR irradiation an accelerated release of methyl orange is observed with a 90% decrease in capsule size. A far larger amount of dye is released as evident from the strong orange background color. Scale bar is 200 µm.

The functionalization of microcapsules by magnetic nanoparticles is of interest as such nanoparticles provide the potential for both position control for targeted delivery32, and heating by magnetic hyperthermia which can be used to control release33-34 or to provide a therapeutic function35. We incorporated magnetic nanoparticles into our microcapsule shells by adding NiZn ferrite nanoparticles to our aqueous GO fluid. The presence of the ferrite nanoparticles resulted in a pronounced change in the stability of the GO microcapsules, with a combination of nonspherical and spherical capsules resulting, and signs of arrested coalescence as observed earlier for non-optimum KF 860 concentrations. Indeed, examination of the capsules over time allowed us to observe arrested coalescence events. Many such events led to the formation of dumbbell, or peanut-shaped capsules. A representative example is shown in Figs. 5A-5C. The destabilization of the microcapsules by the ferrite nanoparticles was concentration dependent, with coalescence and non-spherical structures only produced above a critical concentration of about 0.01 wt.%



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nanoparticles, Fig 5D. SEM images of ferrite-modified microcapsules show evidence of dense accumulation of the nanoparticles on GO nanosheets (Supporting Information, Fig. S7). This suggests that GO adsorbs the nanoparticles, and the resulting obstruction of reactive sites for epoxide-amine coupling is the basis for the observed changes in microcapsule stability.

The presence of ferrite nanoparticles enabled the microcapsules to be positioned readily using an external magnetic field, as demonstrated with a permanent magnet in Fig. 5E. The combination of the dumbbell shape and the presence of ferrite nanoparticles in the capsule interior enabled the formation of Janus structures as shown in Fig. 5F. Magnetic field application results in magnetization and aggregation of the ferrite nanoparticles in one lobe of the dumbbell microcapsule. Notably, due to the field-induced magnetization, the nanoparticle aggregate is unable to relax and remains trapped in that lobe of the capsule, even on removal of the field.


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Figure 5. (A) Representative bright field microscope image of non-spherical capsules prepared when the concentration of ferrite magnetic nanoparticles is above 0.01 wt.% (B)-(C) Capsules (identified by the white ellipsoid) undergo arrested coalescence and form a stable dumbbell shape. (D) Stable spherical capsules with diameter of 371 ± 3.3 µm prepared using 0.009 wt%. ferrite nanoparticles. Scale bar is 210 µm. (E) Left: Before field application the capsules are located at the bottom of the containing vial due to the density mismatch between water and the surrounding silicone fluid. Middle, Right: The capsules move towards a magnet (Nd bar magnet, surface field ~ 1 T) held a few mm from the vial and move readily up the vial wall in response to the changes in the magnet position. (F) Left: Dumbbell shaped microcapsules before field application. Middle: Application of an in-plane magnetic field magnetizes the nanoparticles and causes them to aggregate in one lobe of the dumbbell structure. Right: The magnetized, aggregated nanoparticles remain localized in the lobe after field removal. Scale bar is 200 µm.

CONCLUSION

In summary, we have demonstrated that interfacial reaction between GO and a diamino-modified silicone oil can be exploited in a single-step microfluidic process to generate monodisperse, stable, and mechanically robust microcapsules with micron-scale shell thicknesses. Various anisotropic capsule shapes can be produced by leveraging arrested coalescence events that are



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controlled by the relative concentrations of the shell forming species. The microcapsule shells appear to be composed of GO sheets that are loosely arranged tangentially to the capsule surface. The photothermal nature of GO enables a strong photosensitive release behavior, while the incorporation of magnetic nanoparticles was accommodated readily to produce capsules which can be positioned magnetically. Overall, the engineering of a dual responsive nature in microcapsules that can be readily fabricated in a single-step microfluidic process represents a promising development with potential applications in controlled release in biomedicine and consumer product formulation, and in catalysis. Further studies are warranted, including to assess the capsule shell integrity and colloidal stability of capsule suspensions as functions of ionic strength and pH, and other potential application-relevant parameters.


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ASSOCIATED CONTENT Supporting Information. Additional experimental details, microscope images of microcapsules, AFM of graphene oxide, photographs of capsule suspensions, and a movie of capsule deflation and reinflation. Supporting Information is available free of charge on the ACS publications website. AUTHOR INFORMATION Corresponding Author *[email protected] Author Contributions G.K. and K.M. contributed equally to this manuscript. The manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript. ACKNOWLEDGMENTS We gratefully acknowledge support from the Raymond and Beverly Sackler Institute for Biological, Physical and Engineering Sciences. Facilities use was supported by NSF (DMR1119826) and the Yale Institute for Nano and Quantum Engineering (YINQE) C.O. acknowledges additional NSF support (DMR-1410568).



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Photoresponsive and Magnetoresponsive Graphene Oxide

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