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Biological and Medical Applications of Materials and Interfaces

Biofouling-Resistant Porous Membranes with Precisely Adjustable Pore Diameter via 3D Polymer Grafting Hidenori Kuroki, Alexey Gruzd, Igor Tokarev, Taras Patsahan, Jaroslav M Ilnytskyi, Karsten Hinrichs, and Sergiy Minko ACS Appl. Mater. Interfaces, Just Accepted Manuscript • Publication Date (Web): 29 Apr 2019 Downloaded from http://pubs.acs.org on April 29, 2019

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ACS Applied Materials & Interfaces

Biofouling-Resistant Porous Membranes with Precisely Adjustable Pore Diameter via 3D Polymer Grafting Hidenori Kuroki,† ┴ Alexey Gruzd#, Igor Tokarev,† Taras Patsahan ,‡ Jaroslav Ilnytskyi,‡ Karsten Hinrichs,§ and Sergiy Minko†#,* †

Department of Chemistry and Biomolecular Science, Clarkson University, Potsdam, NY

13699-5810, USA ┴Laboratory

for Chemistry and Life Science, Tokyo Institute of Technology, R1-17, 4259

Nagatsuta, Midori-ku, Yokohama, Kanagawa 226-8503, Japan ‡

Department of Computer Simulations of Many-Particle Systems, Institute for Condensed

Matter Physics of the National Academy of Sciences of Ukraine, Lviv, 79011, Ukraine §

Leibniz-Institut für Analytische Wissenschaften – ISAS – e.V., 12489 Berlin, Germany

#

Nanostructured Materials Lab, University of Georgia, Athens, GA 30602, USA

KEYWORDS: responsive materials, porous membranes, polymer networks, thin films, polymer grafting, biocompatibility, particle dynamic simulations

ACS Paragon Plus Environment

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ABSTRACT: A facile route to biofouling-resistant porous thin-film membranes that can be finetuned for specific needs in diverse bioseparation, mass flow control, sensors, and drug delivery applications is reported. The proposed approach is based on combining two distinct macromolecular systems  a cross-linked poly(2-vinyl pyridine) network and a 3D-grafted PEO layer  in one robust porous material whose porosity can be adjusted within a wide range, covering the macroporous and mesoporous size regimes. Notably, this reconfigurable material maintains its anti-fouling properties throughout the entire range of pore-size configurations due to a dense surface carpet of PEO chains with self-healing properties that immobilized both onto the surface and inside the polymer network through what was termed 3D grafting. Experimental results are supplemented by computer simulations of a coarse-grained model of a porous membrane that shows qualitatively similar pore swelling behavior.

Introduction Responsive polymer membranes1-13 remain in the focus of the scientific community for over two decades due to a range of practically important properties of this class of materials, involving the ability to regulate and/or switch on-off a liquid flow and release of drugs, with a built-in feedback response mechanism relying on diverse environmental and (bio)chemical cues, to tune pore-size or molecular-weight cut-off values of colloidal and protein filtration membranes, and to function as (bio)sensing materials. The potential of such ‘smart’ membranes for advanced mass-transport regulating systems for biotechnological and biomedical applications was the driving force behind the intense research efforts. Despite the significant progress, the technology is not robust enough yet for broad commercialization. The possible reasons for this are briefly outlined below. The common route to designing ‘smart’ membranes is to use pre-fabricated polymeric and inorganic porous media, typically commercial filtration membranes, and to decorate their pore


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walls with stimuli-responsive polymer layers by surface grafting of polymeric chains in the form of a brush or by immobilizing cross-linked polymeric networks. These polymer layers undergo volumetric phase (swelling-shrinking) transitions triggered by certain environmental stimuli, including temperature sweeps,14-18 pH changes,19-22 exposure to light,23 and exposure to specific small molecules and ions24-27 and an external magnetic field,28 which ultimately lead to changes in the geometry (pore size and shape) of polymer-decorated pores and hence to changes in mass transport properties. An obvious shortcoming of this approach to the porosity regulation is that the surface properties of the pore walls depend on the physicochemical state of the polymer chains constituting the responsive layer. Thus, the stimuli-triggered swelling-shrinking transition of this layer may lead to dramatic shifts in the hydrophilic-hydrophobic balance and to changes in the density of surface charges (for polyelectrolyte-based responsive layers) inside the pores. Those changes may adversely impair the membrane performance, specifically, causing fouling of the membrane pores with proteins (due to hydrophobic or/and electrostatic interactions) in bioseparation applications. In protein filtration applications, membranes incorporating naturally hydrophilic polymers or special wetting agents are widely employed. A popular technique to minimize protein binding and, consequently, a pore clogging problem in non-biocompatible porous media is to decorate their surface with an anti-fouling carpet of polyethylene glycol (PEG) or polyethylene oxide (PEO) chains by various methods.29 However, when exposed to physiological conditions (e.g., bodily fluids) for extended times, the PEG or PEO-modified surfaces fail, undergoing oxidative degradation and hydrolytic dissociation of ester bonds that tether the polymer and hence uncovering the underlying non-biocompatible host substrate.30-33


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In this work, we propose a novel approach to robust responsive polymeric membranes that address the aforesaid challenges, enabling a precise control over the porous morphology of a membrane without compromising its antifouling properties. This work hinges at large on our previously published studies. Specifically, we have demonstrated a concept of thin-film porous membranes whose entire body consists of a chemically crosslinked stimuli-responsive polymer gel and whose pore size is comparable or exceeds the membrane thickness, being typically in a 100 to 200 nm range.34-37 Unlike the above-mentioned ‘smart’ membranes prepared by modification of porous host media with responsive polymers, our tunable membranes operate by swellingshrinking of its entire gel body, enabling dramatic, still well-controlled, reversible changes in the membrane porosity between the two distinct limiting states: an open state of highly permeable, hundred-nanometer-sized pores and a closed state of impermeable, completely contracted pores. In another study relevant to this work, we have demonstrated a concept of 3D polymer grafting to generate self-healing biofouling-resistant surfaces.33 To achieve the long-lasting biocompatibility, a substrate surface was first coated with a layer of chemically crosslinked polymeric gel and then functionalized with PEO chains grafted both to the surface and inside the polymer network, thus the term 3D grafting. Contrary to the conventional PEGylated surfaces, the loss of the surface-exposed PEO chains through degradation was replenished by the PEO chains stored inside the network that migrated to the damaged surface from the gel interior, thus considerably extending the lifetime of the material via the self-healing effect. The above two concepts were combined in the present study to yield a novel idea of a robust tunable membrane capable of maintaining biocompatibility in the entire range of the swellingtransition-induced pore-size configurations.


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Results and Discussion The membrane preparation, shown in Figure 1, is a simple and well reproducible procedure (see also Supporting Information (SI) for experimental details) which involves the following basic fabrication steps: the formation of a porous poly(2-vinyl pyridine) (P2VP, Mn = 152 kg/mol) thinfilm membrane via phase separation (Fig. 1a) followed by its crosslinking with diiodobutane via a quaternization reaction, and concluded by 3D grafting of reactive chloro-terminated PEO (Mn = 5.0 kg/mol) to form a biocompatible interface (Fig 1b). A number fraction of the pyridine groups quaternized with diiodobutane and hence involved in crosslinking of the P2VP network was estimated at 6.1  1.0% from FTIR analysis data. The crosslinking density of the P2VP gel was maintained the same for membranes and continuous (non-porous) films throughout the study.

Figure 1. Schematic illustration of controlled geometries and surface decoration of pores via 3Dgrafting in a stimuli-responsive polymeric thin membrane. (a) P2VP porous thin membrane, and (b) P2VP membrane with tuned pore-geometry and biocompatible PEO carpet due to 3D polymer grafting.


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During the grafting step, performed at 120 °C, two concurring competing processes took place: (1) PEO chains diffused into the crosslinked P2VP network and (2) PEO chains were grafted to pyridine rings of P2VP via a quaternization reaction with the halogen terminal groups of PEO. At a temperature above the glass transition temperature of P2VP (Tg ≈100 oC), PEO is miscible with P2VP and could be considered as a high molecular weight solvent for P2VP. Hence, the P2VP membrane was 3D-swollen in PEO in the X-Y plane and in Z-direction. Since the membrane was adhered to the solid substrate, the membrane swelling in the X-Y plain resulted in contraction of the pores. After grafting, the excess of PEO (non-grafted PEO) was extracted in chloroform. The remaining grafted PEO secured the swelling state of the membrane whereas the swelling degree depended on the grafted amount of PEO. The latter was adjusted by grafting time. The kinetics of 3D grafting of PEO was studied using model non-porous P2VP films on Si wafers using ellipsometry, with the results presented in Figure 2. The thickness of the P2VP films increased steadily with the grafting time until a plateau was reached in 70 h. In the plateau region the PEO-grafted film was more than three times thicker than the original 15 nm thick P2VP film. This result verifies diffusion of 5 kg/mol PEO chains into the crosslinked P2VP network whose mesh size was large enough for allowing the chain penetration. For comparison, PEO brushes grafted directly onto impermeable solid substrates yielded film thicknesses of less than 10 nm.38


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Figure 2. PEO-grafted P2VP films prepared by varying grafting times -: the increased film thickness (closed circle ) and the water contact angle (opened circle ) after grafting of PEO as a function of the grafting time. The 3D grafting of PEO for more than 20 h led to hydrophilic surfaces with water contact angles less than 40° (Figure 2). Those values are well below the contact angle value of the non-grafted P2VP film, found to be ca. 70±5°. The grafting of halogen-terminated PEO inside the 15 nm thick non-porous P2VP films was also examined by infrared ellipsometry (details of the characterization procedure can be found in Section S2 of SI).39 The infrared ellipsometric spectra of the P2VP film before and after the grafting are shown in Figure 3. The characteristic bands of the P2VP membrane26 attributed to the pyridine ring at about 1435/1473 and 1569/1591 cm−1 have similar amplitudes in the spectra of non-grafted and PEO-grafted P2VP films. On other hand, new well discernible bands assigned to PEO evolve after 20 h of grafting at about 965 cm−1, 1119 cm−1, 1243 cm−1, 1345 cm−1 and 1455 cm−1.40 An optical calculation using a layer model and an effective medium approximation for the


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3D-grafted surface yielded a 21 nm thick PEO film. This result corroborates well with our previous work where 3D grafting into continuous P2VP films was evaluated using null ellipsometry and Xray reflectivity.33

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Figure 3. Infrared ellipsometry analysis of non-grafted (dotted line) and PEO-grafted (solid line) P2VP films. The baselines are shifted for clarity. The concept of tuning of pores’ geometry via 3D-grafting was verified in the following experiment. The P2VP porous membranes were prepared according to the previously-reported procedure.34-35 The grafting amount of PEO within the P2VP matrix was adjusted by changing the grafting time, between 0 and 70 hours. The surface morphology of the resulting membranes was


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evaluated with atomic force microscopy (AFM). Figure 4 shows the topological AFM images of the non-grafted and 3D-grafted membranes. The images (Figure 4a-d) reveal gradual shrinking of the pore size with the grafting time. The average pore diameter (Figure 5a) decreases until a vast majority of pores end up in the completely closed state for the 70-h-grafting-time sample (Figure 4d). Thus the experiment demonstrates that the pore dimensions could be simply tuned by the grafting kinetics from ~ 300 nm (the average pore size of the non-modified membrane) to the zerosize state (70-h grafting). Figure 5c shows that the membrane thickness (acquired from the AFM scratch analysis) increases with the grafting time but the relative changes are not as dramatic as observed for the pore dimensions, consistently with our prior studies.41 The membrane becomes increasingly hydrophilic (Figure 5d) with the grafting time, reflecting an increase in the grafting amount and a decrease in the membrane’s porosity. The comparison of wetting experiments for the model P2VP films (Figure 2) and the membranes (Figure 5d) reveals the following. Upon grafting of PEO, the P2VP film became hydrophilic (water contact angle of 35±5o) after the 20 h grafting time as compared with the original (no PEO grafted) hydrophobic P2VP film with the contact angle of 70±5o. In contrast to the flat film, the porous P2VP membranes showed a progressive decline in the water contact angle from of 85o to of 52o as the grafting time increased. These changes resulted from the overlap of two effects: grafting of PEO and changes of the film topographical structure. A water droplet placed on the membrane surface is in the contact with the membrane material and the substrate through the open pores. Siwafer substrates (unless etched) are typically characterized by high water contact angles due to adsorbed impurities. For the porous membranes, such open pores could pin the contact line. The


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latter was manifested with increased contact angle values. With an increase of the grafted PEO amount, the porosity decreased and the contact angles on the membranes decreased accordingly.

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Figure 4. AFM topological images and cross-sectional profiles of the grafted membranes via 3Dgrafting of PEO. The cross-sectional profiles are obtained along the lines shown on the images.

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Figure 5. Characteristics of the 3D PEO-grafted membranes as a function of the grafting time: (a) the average pore diameter, (b) the pore density, (c) the membrane thickness, and (d) the water contact angle (CA). The characteristics in the panels (a) through (c) were acquired from the analysis of AFM images of the membranes in the dry state (solid symbols) and under PBS solutions (open symbols). Importantly, the membranes underwent additional swelling in aqueous solutions. The swelling became greater with an increase of grafted amount of PEO as concluded from AFM-measured thicknesses of the swollen membranes (Figure 5c and SI). This additional swelling caused further shrinking of the pores (Figure 5a). The estimation of the pore diameter for membranes with PEO


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grafting time greater than 20 h was hindered by the AFM tip size (about 20 nm). Hence, the choice of the grafting time and the initial pore size of the membranes should be made with consideration of the additional swelling in a specific medium of an application. In our previous study, we demonstrated that the initial state of the P2VP membrane can be precisely tuned to a desired pore size in a very broad range through changes in diiodobutane concentration or ambient humidity during the membrane preparation.35

Figure 6. 1.2×1.2 mm2 fluorescence microscopy images of 3D PEO-grafted P2VP membranes with different grafting times incubated in dye-labeled BSA solutions for 3 and 19 days.

The 3D grafting of PEO chains renders the material with antifouling properties. It was demonstrated in the experiment when P2VP membranes with different grafting amounts of P2VP were incubated in a buffered solution of fluorescent dye-labeled protein (bovine serum albumin, BSA) for different times (up to 19 days), and their performance as the antifouling surfaces was inferred by comparing fluorescence signals of individual samples. These samples were examined


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using AFM to quantify amounts of deposited BSA on the membrane surface. Figure 6 and 7 summarize the results of the adsorption study. The non-grafted membrane exhibited strong fluorescence after 3-day exposure to the protein solution (Figure 6). The fluorescence intensity continued to grow with longer adsorption times. The fluorescent intensities for the non-grafted membrane and membranes with 20, 40 and 72 h PEO grafting times after 3, 9 and 19 days of incubation in BSA solutions are shown in Figure 7a. The AFM data reveal a ca. 5 nm increase in the membrane thickness due to adsorption of roughly a monolayer of BSA for 3 days (Figure 7b). The 20 h grafting time was sufficient to drastically suppress BSA absorption onto the surface of the grafted samples. The greater incubation time in BSA PBS solutions corresponded to the greater adsorption of BSA on the non-grafted membrane, while for all the PEO-grafted membranes we observed a small decrease in thickness. The latter is attributed to the oxidative hydrolyses of PEO as discussed above. However, the 3D-grafted structure of the membrane indeed extended the antifouling properties of the membranes for at least 19 days of incubation period via the selfhealing mechanism.


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Figure 7. The fluorescence intensity (a) and the average thickness change (b) of the 3D PEOgrafted P2VP membranes incubated in dye-labeled BSA solutions for 3, 9 and 19 days plotted as a function of the grafting time. It is noteworthy that the fluorescent intensity was non-zero for 20, 40 and 72 h grafted membranes. However, this signal decreased with the grafted amount. We attribute this signal to BSA which diffused through the pores and adsorbed on the Si-wafer substrates. Unfortunately, the fluorescent signal data is just a qualitative proof for the transport of BSA across the pores. The data cannot be used for quantitative evaluation of porosity due to partial quenching of fluorescence of the BSA labels adsorbed on the Si-wafer substrate. It has to be noted that for this study we selected membranes with a non-zero pore-size polydispersity (see Section S4 and Figure S4-1a in SI). This provides an opportunity for a combinatorial method to examine the shrinking behavior of pores in surface-confined thin-film polymer networks undergoing volumetric swelling. Our results show that the pore shrinkage is diameter-dependent. Specifically, in the intermediate-grafting-time cases (see Figure 4b and c), the fate of the pores depended on their initial size (i.e. their size prior to grafting). The AFM images (Figure 4) show that the smallest pores tend to shrink to the zero-size state first, followed by increasingly larger pores as the grafting time rises. As a result, the effective density of the open pores decreases with the PEO grafting as shown in Figure 5b. The swelling behavior of porous polymer films was simulated using the method of dissipative particle dynamics (DPD).42 The coarse-grained model for a membrane developed in our work is similar to that in Refs.43-44 proposed for a simulation of polymer chains end-grafted to the surfaces in the presence of a two-component solvent. We applied the same approach to describe a membrane formed by the polymer chains with multiple randomly arranged circular pores. The


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detailed description of the model employed in the current study as well as technical details of our DPD simulations can be found in Section S5 of SI. Figure 8 presents snapshots of the membrane at different stages of swelling, capturing gradual evolution of the pore structure from fully open pores in the non-swollen membrane (Figure 8a) to completely closed pores at a certain degree of swelling (Figure 8d). It is important to point out that 3D grafted PEO can be considered as a good solvent for the P2VP membrane since it readily penetrates the network but, unlike the solvent, cannot be removed from the network, resulting in its irreversible swelling. From the simulation standpoint, PEO is not much different from other solvents or chemicals that swell the P2VP membrane, such as acidic water, cholesterol and pentadecyl phenol used in our previous publications.34-35, 41, 45


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Figure 8. Images of the membrane (top view) presented in a form of isosurfaces constructed using simulation trajectories of polymer beads at different stages of a swelling process and characterized by swelling degrees of: (a) 1 (non-swollen), (b) 1.13, (c) 1.26, and (d) 1.39. The images are complemented with the corresponding snapshots of cross-sectional profiles (side view) of a selected single pore that are obtained along the lines shown on the images. Yellow denotes polymer beads, blue denotes beads of a good solvent. Poor solvent is located out of the membrane and removed from snapshots for more clear presentation.


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In the model, each pore was generated by a circular region of the same diameter D which was free of grafted chains. However, in the simulations, due to entropy reasons, polymer chains bent around the initially circular region of each pore, yielding curved pore walls with a belly-shape profile and the effective pore size smaller than D. The effective pore sizes (see Section S5 and Figure S5-2 in SI) of the membrane undergoing swelling revealed a significant degree of polydispersity, which was attributed to interactions of adjacent pores. As follows from Figure 8, more isolated pores are found to shrink faster upon membrane swelling than those that are more closely spaced. A slower rate of closing for less separated pores is a result of sharing chains and, consequently, their shortage. This observation suggests that the pore monodispersity alone is not a sufficient requirement for uniform shrinking of pores, which is anticipated to benefit separation applications where a sharp pore-size cut-off is desired; a uniform and well-separated arrangement of pores is also crucial. One of the consequences of the pore-size polydispersity and random arrangement of the pores is the experimentally (Figure 4d) and theoretically (Figure 8d) observed situation where, while a vast majority of pores are closed in the swollen membrane, few pores remain sufficiently open, which could adversely affect the overall performance of a separation membrane. As already mentioned, the pore walls attain the characteristic belly-shaped profile clearly visible (see Figure 8) in the cross-sectional views of a single pore at different stages of swelling. It has to be noted that the complex geometry of pores in 3D grafted membranes cannot be exactly assessed with the AFM imaging, because the overhang portion of the pore bottom is not accessible to a pyramid-like AFM tip. The experimental and simulation data from Figures 4 and 8 were used to plot the average (or effective) pore size as a function of a swelling degree, with the result presented in Figure 9. The


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swelling degree was defined as a ratio of the volume of a swollen membrane to that of an original (non-swollen) membrane, and the average pore size was normalized to the size of the fully open (non-swollen) pore. Both plots exhibit an inverse linear relationship between the effective pores size and the swelling degree. Although such relationship is not necessarily obvious for shrinking round pores, the result demonstrates that the model correctly captures this process by demonstrating the same scaling law (Figure 9). However, when comparing how the membrane thickness changes with the swelling degree, a substantial disagreement arises between the experiment and simulations data (see Figure S5-3 in SI). In the simulations, polymer chains expand at nearly the same rate in both vertical and lateral (inside the pore) dimensions upon the membrane swelling. On the contrary, our experimental data show that on average the pores contract at a faster rate than the accompanying increase in the membrane thickness (compare Figures 5a and 5c). It is unclear what is the primary cause of such anisotropic swelling behavior. Intrinsic structural anisotropy related to the crosslinking density distribution and the tendency of the polymer network to form folds and creases upon swelling could be contributing factors.

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Experimental Preparation of porous membranes 2 w/v% P2VP (Mn = 152 kg/mol, Sigma-Aldrich) and 2 vol% diiodobutane (DIB, Sigma-Aldrich) were dissolved in a mixture of nitromethane and tetrahydrofuran (9:1volume ratio). The solution was heated at 60 °C for 2h or 80 °C for 1h. In this reaction condition, only one of two iodoalkyl groups in DIB reacted with pyridine rings of P2VP. The resulting solution was filtered and then spin-coated on the surface of Si-wafers at 3000 rpm at 60 RH% for the preparation of the porous membranes. For the preparation of the flat films, the solution was diluted to 1/4 with a mixture of nitromethane and tetrahydrofuran (9:1volume ratio), and then spin-coated at 3000 rpm at a low humidity (< 10 RH%). The obtained films and membranes were annealed at 100 °C in a vacuum for at least 1h to complete the cross-linking reaction of P2VP with residual functional groups of DIB. The grafting of PEO on the P2VP films and membranes was conducted as follows. A 2 w/v% solution of chloro-terminated PEO (Mn = 5.0 kg/mol, Polymer Sources) was spin-coated on the films and membranes at 3000 rpm. The grafting reaction was carried out by thermal annealing at 120°C in vacuum. After the grafting step, the films and membranes were rinsed with chloroform to remove unreacted PEO, and then dried with a nitrogen gas flow. Characterization of membranes The thicknesses of the prepared flat films and porous membranes were estimated by ellipsometric measurements and atomic force microscopy (Dimension 3100 Scanning Probe Microscope, Veeco Instruments) over scratched film areas. For the ellipsometric measurements, a multiskop nullellipsometer (Optrel) equipped with a He-Ne laser (λ = 633 nm) was used. For infrared (IR) ellipsometry measurements of non- and PEO-grafted P2VP films, a custom-build ellipsometric


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set-up attached to an FT-IR spectrometer (IFS 55, Bruker, Germany) was used. Spectra were taken with a resolution of 4 cm−1 at an incidence angle of 64.2° using a mercury cadmium telluride (MCT) detector cooled by liquid nitrogen in a with dry air purged set-up. See SI for further details. Biofouling-resistant properties were characterized with protein adsorption tests of albuminfluorescein isothiocyanate conjugate (BSA-FITC, Sigma-Aldrich). The prepared membranes were immersed into 0.5 g/L solution of BSA-FITC in phosphate buffer PBS) at pH 7.4 for 3-19 days. The membranes with adsorbed BSA were immediately rinsed with PBS, DI water, and dried with an argon flow. BSA adsorption was examined using fluorescence microscopy and AFM. Fluorescence intensity was estimated using Olympus BX51 optical microscope equipped with a FITC/EGFP filter (excitation 460 -500nm; emission >510nm, Chroma Technology). Fluorescent images were captured with a constant excitation intensity and an exposure time of 250 ms and processed using the CellSens Dimension software. After the adsorption assessment tests the membranes were washed with ethanol and purged with argon before returning them to BSA-FITC solution for longer incubations times. See SI for further details. Conclusions In conclusion, we demonstrated that wo distinct macromolecular systemscross-linked stimuliresponsive poly(2-vinyl pyridine) network and 3D-grafted PEO layercan be combined to produce antifouling thin-film membranes whose pore size can be adjusted within a broad range, from several hundred nanometers down to the dimensions defined by the mesh of the polymer network. The pore diameter was adjusted simply by variations in the grafting time of PEG at a temperature greater than the glass transition temperature of P2VP. At this temperature, the P2VP membrane swelled in PEG. Variable amounts of PEG were grafted both in bulk of the swollen membrane and on the membrane surface according to the grafting time and remained in the


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membrane after washing. The resulting 3D-grafted structure provided long lasting, at least 19 days, protein antifouling properties in agreement with the previously reported self-healing mechanism.33 The experimental study was complemented by computer modeling. Due to the intrinsic length scale of the problem, the modelling of the membrane swelling was performed on a mesoscopic level using dissipative particle dynamics simulations. While not representing a chemically detailed picture, the simulation data showed qualitatively accurate picture of changes in the membrane porosity upon gradual swelling. Further refinement of the model is possible and planned in the follow-up studies. We believe that the concept of reconfigurable membranes can be tailored to specific needs in diverse bioseparation, mass flow control and drug delivery applications. An example of a candidate material was demonstrated in our previous publication,41 where a membrane with a narrow pore-size distribution was prepared using a colloidal-particle template method. The evaluation of such materials for colloidal separation of is the subject of our ongoing effort and is out of scope of the present study.

ASSOCIATED CONTENT Supporting Information. The procedures for the preparation of the 3D grafted P2VP films and porous membranes. The experimental details of infrared ellipsometric analysis of the non-grafted and PEO-grafted P2VP films. The characterization of the swollen membranes in water. The experimental results of the studies of the antibiofouling properties of the membranes. The DPD simulation procedures and results for porous polymer membranes at different stages of swelling. This material is available free of charge via the Internet at http://pubs.acs.org.


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AUTHOR INFORMATION Corresponding Author *E-mail: [email protected] Notes The authors declare no competing financial interest. ACKNOWLEDGMENTS This work was supported by NSF awards DMR 1107786 and 1904365. H. Kuroki thanks Japan Society for the Promotion of Science (JSPS, Japan) for the support of his research fellowship. K. Hinrichs thanks I. Engler and Ö. Savas for technical support. Financial support by the Ministerium für Innovation, Wissenschaft und Forschung des Landes Nordrhein-Westfalen, the regierende Bürgermeister

von

Berlin

–

Senatskanzlei

Wissenschaft

und

Forschung,

and

the

Bundesministerium für Bildung und Forschung as well as the European Union through the EFRE program EFRE 1.8/13 is gratefully acknowledged. REFERENCES (1) Ulbricht, M. Advanced functional polymer membranes. Polymer 2006, 47 (7), 2217-2262. (2) Tokarev, I.; Minko, S. Stimuli-Responsive Porous Hydrogels at Interfaces for Molecular Filtration, Separation, Controlled Release, and Gating in Capsules and Membranes. Adv. Mater. 2010, 22 (31), 3446-3462. (3) Wandera, D.; Wickramasinghe, S. R.; Husson, S. M. Stimuli-responsive membranes. J. Membr. Sci. 2010, 357 (1–2), 6-35. (4) Kuroki, H.; Tokarev, I.; Minko, S. Responsive Surfaces for Life Science Applications. Annu. Rev. Mater. Res. 2012, 42 (1), 343-372. (5) Zhang, W. Y.; Zhao, Q.; Yuan, J. Y. Porous Polyelectrolytes: The Interplay of Charge and Pores for New Functionalities. Angew. Chem.-Int. Ed. 2018, 57 (23), 6754-6773.


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