poly(vinylidene fluoride) blend via VIPS for biofouling mitigation

Journal of Membrane Science 550 (2018) 377–388

Contents lists available at ScienceDirect

Journal of Membrane Science journal homepage: www.elsevier.com/locate/memsci

Zwitterionic bi-continuous membranes from a phosphobetaine copolymer/ poly(vinylidene fluoride) blend via VIPS for biofouling mitigation ⁎

Antoine Venaulta, , Chen-Hua Hsua, Kazuhiko Ishiharab, Yung Changa, a b

T

⁎

R&D Center for Membrane Technology and Department of Chemical Engineering, Chung Yuan Christian University, Chung-Li 32023, Taiwan Department of Bioengineering, The University of Tokyo, Tokyo, Japan

A R T I C L E I N F O

A B S T R A C T

Keywords: Antifouling membrane Zwitterionic PVDF membrane Bi-continuous structure VIPS process PMBU

The use of zwitterionic copolymers for the design of fouling resistant membranes by in-situ modification remains unexplored because these copolymers face solubility issues when blended with common hydrophobic membrane materials such as poly(vinylidene fluoride) (PVDF). Here, we overcame this issue using a copolymer of 2-methacryloyloxyethyl phosphorylcholine and methacryloyloxyethyl butylurethane groups, named PMBU. The resulting membranes formed by vapor-induced phase separation exhibited a highly porous (porosity of 75%) and strong (modulus of elasticity E > 80 MPa) bi-continuous structure, while the virgin PVDF membrane still contained nodules, resulting in weaker membrane (E = 67 MPa). ATR FT-IR in local and mapping modes evidenced a strong signal ascribed to the presence of ester groups of PMBU at 1730 cm−1, fairly well distributed at the surface of the membranes. It led to a significant improvement of their hydrophilic properties with a hydration capacity reaching 280 mg/cm3. Consequently, the modified membranes showed excellent antifouling properties when contacted with bacterial solutions (Escherichia coli) and totally inhibited biofouling by whole blood. Furthermore, a flux recovery ratio of 42% was measured with the best membrane after 4 water/humic acid filtration cycles, while it was 17% in the same conditions with a commercial hydrophilic PVDF membrane. Hence this work demonstrates that fouling-resistant zwitterionic bi-continuous PVDF-based membranes can be prepared by in-situ modification.

1. Introduction Over the past decade, most designs of antifouling membranes by insitu modification (also simply referred to as blending) reported in literature were similar in at least two aspects: the nature of the process and the nature of the surface-modifier. The process extensively used to prepare polymeric membranes is the wet-immersion process, also called non-solvent induced phase separation or liquid-induced phase separation (LIPS) process. Thus, numerous reports have been published on the design of antifouling membranes by LIPS over the past decade [1–8], even if the preparation of antifouling membranes by in-situ modification is not as popular as coating and grafting processes. The rationale for the use of the LIPS, rather than the more controllable vapor-induced phase separation (VIPS) process, is the ease of implementation: only a DI water bath is necessary for inducing phase separation of the polymeric system, which is entirely achieved, in most cases, in less than one minute. However, due to fast phase separation rates, the LIPS process is much less controllable than the VIPS process, using similar formulation components. For instance, with

⁎

water as a non-solvent, poly(vinylidene fluoride) (PVDF) based membranes prepared by LIPS will present a classic macrovoid structure. On the other hand, using water vapors as the non-solvent, the morphology of PVDF membranes prepared by VIPS can be more finely tuned and bicontinuous, as well as nodular membranes with various domain sizes are reported [9]. More parameters are controllable in VIPS than in LIPS (not considering the formulation parameters, i.e. the nature of the polymer, solvent, non-solvent nor their concentration). Combined to the existence of a gas/liquid resistance at the non-solvent/polymeric solution interface which slows down the mass transfers, VIPS is an ideal process for achieving a fine control of membrane morphology, and study the formation of novel membranes. Regarding now the nature of the surface-modifier, they are, in most cases, PEG-based [8,10–16]. This observation arises from a good compatibility of the hydrophobic polymers and the PEG-based copolymers in common solvents such as N-methylpyrrolidone or dimethylformamide. It is much harder to solubilize zwitterionic copolymers together with a hydrophobic polymer, because zwitterionic heads interact more strongly with water and solvents miscible with water, then decreasing

Corresponding authors. E-mail addresses: [email protected] (A. Venault), [email protected] (Y. Chang).

https://doi.org/10.1016/j.memsci.2017.12.075 Received 22 September 2017; Received in revised form 23 December 2017; Accepted 27 December 2017 Available online 29 December 2017 0376-7388/ © 2018 Elsevier B.V. All rights reserved.

Journal of Membrane Science 550 (2018) 377–388

A. Venault et al.

their solvency power and preventing the solubilization of the hydrophobic polymer. A method to address this concern is to first graft zwitterionic moieties to the polymeric material forming the membrane, and then mix the obtained copolymer with the initial polymer [17]. Because the hydrophobic block of the copolymer and the initial polymer have the same nature, the solubilization process is facilitated. However, the grafting process is not easy and mostly, this approach questions the versatility of the copolymer. The group of Prof. Ishihara has long been investigating the introduction of 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer and derivatives as antifouling coatings [18–20]. This material mimics the biological cell membranes, and thus is highly biocompatible and hemocompatible [21,22]. Given their excellent biocompatibility, some major successful applications of MPC-derivatives are the improvement of the hemocompatibility of heart stents, heart valves, and of medical tubing. MPC and MPC copolymers are now readily polymerized, even at an industrial scale. Also, a wide range of polymeric architectures is available and can be fairly well-controlled. Moreover, it was very recently shown that the coating of PVDF commercial membranes with MPC led to almost no irreversible flux loss during the deadend filtration of proteins solutions [23]. However, MPC has mostly been employed as a surface-modification agent, and never, to our knowledge for in-situ modification by VIPS process of PVDF-based membranes. Provided the use of an appropriate copolymer of MPC compatible with PVDF (material design), one could take advantage of the excellent antibiofouling properties of MPC, and in the same time, of the well-controlled VIPS process to form a new generation of antifouling PVDFbased membranes with controlled structure. By incorporating a methacryloyloxyethyl butylurethane groups, the resulting copolymer, that we will term PMBU in this manuscript, is compatible with PVDF in N-methylpyrrolidone solvent. In other words, a homogeneous solution is obtained, which can be used as a casting solution. This observation was the starting point of the present study. Provided (i) all the advantages of MPC-based copolymers to reduce biofouling and (ii) the worldwide usage of PVDF as a matrix polymer for UF and MF membranes, and considering that the preparation of lowbiofouling zwitterionic membranes by in-situ modification in a controlled fashion (controlled structure) remains unsuccessful, we decided to tackle this challenge by applying the vapor-induced phase separation process to a series of PVDF/PMBU/NMP casting solutions. A major objective was to create a bi-continuous fouling-resistant membrane, which can be achieved by VIPS process providing a fine tuning of both initial formulation conditions and process parameters. Bi-continuous structures are highly desired as the entanglement of polymer chains offers high mechanical stability while maintaining high permeability, but the structure, highly porous, is prone to physical entrapment of colloids and biofoulants. This physical phenomenon, combined to the hydrophobic chemical nature of PVDF, explains why bi-continuous PVDF membranes are readily fouled. Thus, the preparation of bi-continuous zwitterionic PVDF membranes could be useful to a number of applications in which high permeability, longevity and fouling-resistance are required (wastewater treatment, blood-contactors, etc…).

Fig. 1. The structure of poly(2-methacryloyloxyethyl phosphorylcholine-co-methacryloyloxyethyl butylurethane), PMBU, used in blend with PVDF to form the zwitterionic membranes.

was bought from Sigma-Aldrich. Bovine serum albumin and primary monoclonal antibody used in fibrinogen adsorption tests from a platelet-poor-plasma solution were purchased from Sigma-Aldrich and US Biological, respectively. 2.2. Methods 2.2.1. Solution preparation The casting solutions were prepared by solubilizing first PVDF in NMP at 35 °C. The PVDF content was fixed to 20 wt% for all membranes while the solvent content varied as indicated in Table 1. The temperature was set to minimize crystallization-driven membrane formation. Indeed, a low temperature of dissolution leads to a high nuclei density in the casting solution which growth is hindered because of large viscous forces [25], leading to earlier gelation and thus, noncrystallization gelling process during membrane formation. Once the polymer solubilized, the PMBU copolymer was added at various concentrations: 1 wt% for PMBU1 membrane to 5 wt% for PMBU5 membrane. No copolymer was added to the solutions used to prepare the virgin membranes (PMBU0). Viscosity measurements of the solution containing PVDF only in NMP and of that containing PVDF and 5 wt% PMBU in NMP were performed to confirm the expected increase of viscosity with the addition of copolymer. These measurements were carried out at 25 °C using a BROOKFIELD R/S rheometer, equipped with a C50-1 module and operated at 100 s−1 constant share rate. In order to check that PMBU copolymer was miscible with PVDF polymer, other than visually (obtaining of apparently homogeneous and transparent solutions), we conducted dynamic light scattering measurements on PMBU0 and PMBU5 solutions, with a DelsaTM Nano S particle analyzer (Beckman Coulter), setting the diffraction angle to 165° and controlling the temperature to 25 °C. For these measurements, a sample of the casting solutions was diluted 10 times in a Y-shape cuvette. The results of this basic, yet essential test, are presented in Fig. 2 and encouraged us to continue this work and prepare membranes, as it was verified that the particle size in the PMBU5 solution remained very low (peak at 4.5 nm) and close to that measured in PMBU0 solution (peak at 1.3 nm), indicating a good compatibility of the polymer and the copolymer in NMP solvent. Additionally, a narrow distribution was obtained in both cases. Hence, we could proceed and prepare zwitterionic PVDF membranes by in-situ modification.

2. Materials and methods 2.1. Materials

Table 1 Formulation and characterization of casting solutions.

PVDF (Mw: 150,000–180,000 g/mol) was purchased from Kynar®, and thoroughly washed with methanol and DI-water to remove all remaining impurities. Poly(2-methacryloyloxyethyl phosphorylcholineco-methacryloyloxyethyl butylurethane) (PMBU) synthesis and characterization have been reported elsewhere [24]. Its structure is reminded in Fig. 1. In this study, PMBU copolymer had a molecular weight of 40,000 g/mol. NMP solvent was bought from Tedia, and used as is without further purification. DI-water was produced by a water purification system (Millipore®). Phosphate buffered saline (pH 7.4) 378

Membrane ID

PVDF (wt%)

Copolymer (wt%)

NMP (wt%)

Viscosity (Pa s)

PMBU0 PMBU1 PMBU2 PMBU3 PMBU4 PMBU5

20 20 20 20 20 20

0 1 2 3 4 5

80 79 78 77 76 75

2421 ± 1 / / / / 5225 ± 1

Journal of Membrane Science 550 (2018) 377–388

A. Venault et al.

Jasco FT/IR 6700 instrument associated to a Jasco IRT-5200 microscope equipped with an automatic sample stage (Jasco IPS-5000) and a MCT-MD detector cooled with liquid nitrogen. Before the tests, the samples were freeze dried, then cut and fixed on a glass slide using double-sided adhesive. The spectral resolution used was 4 cm−1, and 32 scans were acquired on each measurement point. Mapping was performed at 1730 cm−1 (C=O stretching) with a ×16 cassegrain objective lens. All measurements were made using a gold mirror as the background, and the external reflection was used as the acquisition mode. The obtained spectra were not further processed, and the intensities in the different maps are shown with respect to the peak height of the specified peaks. 2.2.4. Membrane fouling characterization The hydration properties of virgin PVDF (PMBU0) and modified (PMBU1 to PMBU5) membranes were assessed by determining their water contact angle (WCA) and their hydration capacity. As for the surface hydrophilicity, an automatic contact angle meter (Kyowa Interface Science Co.) was used. A 4 µL-water droplet was deposited successively at 7 positions on the membrane sample previously fixed to a glass slide using double sided adhesive tape. After 5 s, a photograph of the membrane surface was taken, and the WCA automatically determined. For each condition of membrane preparation, 3 independent membrane samples were considered, such that a total of 21 measurements were averaged to obtain each WCA reported in this study. Regarding the hydration capacity of the membranes, samples of 1.3-cmdiameter were immersed in DI water for 24 h. Afterwards, the superficial water was gently wiped out. The hydration capacity was taken as the difference per unit volume between the wet weight of the membrane (measured after immersion) and its dry weight (measured before immersion). 5 independent measurements were performed for each condition, and the average taken as the final hydration capacity of the membrane considered. The adsorption tests using proteins, bacteria and cells described in the following paragraphs were all carried out after pre-wetting the membranes overnight in ethanol. The adsorption of human fibrinogen from a platelet-poor-plasma (PPP) solution on the virgin and modified membranes was studied by performing an Enzyme-Linked ImmunoSorbent Assay (ELISA) test. In this test, PPP was obtained after centrifuging 250 mL of whole blood at 3000 rpm, for about 10 min. 5 independent samples from the different membranes tested (virgin PMBU0, PMBU1 and PMBU5), having a 1 cm-diameter, and the sulfobetaine methacrylate hydrogel controls were positioned in individual well of a multiwell, and then soaked in PBS for 1 h at 37 °C. Thereafter, PBS was removed and replaced by 1 mL of PPP. Incubation of the samples with PPP solution was performed for 2 h at 37 °C. At the end of the incubation period, the membranes and controls (SBMA hydrogel and tissue culture polystyrene plate) were washed three times using PBS, and then incubated at 37 °C with a solution of bovine serum albumin (BSA), for 1 h. Afterwards, all samples were thoroughly washed (at least 3 times with PBS). 1 mL of a solution containing primary monoclonal antibody specifically reacting with fibrinogen was added to each well, and the reaction performed for 0.5 h at 37 °C. After another PBS triple washing, samples were blocked at 37 °C with a solution of BSA, for 1 h, followed by a supplementary PBS triple washing, their incubation for 0.5 h at 37 °C with 1 mL of a solution of 1 mg mL−1 horseradish peroxidase-conjugated secondary monoclonal antibody, and a final PBS washing step (at least 5 times). The last part of the ELISA test was performed in a clean multiwell into which samples were transferred and incubated for 5 min at 37 °C with 0.5 mL of a solution containing a mixture of 3,3′,5,5′-tetramethylbenzidine chromogen, Tween 20 and hydrogen peroxide (both at a content of 0.05 wt%). Then, 0.5 mL of sulfuric acid was added to each well, in order to stop the enzymatic reaction, and the absorbance of the incubation solution measured at 450 nm, with a PowerWave XS UV–Vis spectrophotometer (Biotech).

Fig. 2. Dynamic light scattering characterization of PMBU0 (PVDF/NMP) and PMBU5 (PVDF/PMBU/NMP) solutions.

2.2.2. Membrane preparation The casting solution, substrate and casting knife were placed in a VIPS chamber and parameters (relative humidity (RH), temperature) set 1.5 h prior casting, in order to reach thermodynamic equilibrium inside the chamber. Then, the solution at play was cast on a glass substrate, at an initial thickness of 300 µm, and exposed to the water vapors for 20 min. Afterwards, the glass substrate was taken out of the chamber and immersed in a DI-water bath for 24 h, to remove solvent traces. Newly formed membranes were then dried on paper at ambient temperature for 24 h (metal plates were positioned at each membrane extremity to avoid potential shrinkage), and the final membranes were stored at 4 °C until use.

2.2.3. Membrane physicochemical characterization The structure of the membranes was characterized by scanning electron microscopy (SEM). Membranes samples were positioned and maintained on a SEM holder using double-sided adhesive tape. Then, the membranes were sputter coated with gold for 150 s. Afterwards, the holder was positioned inside the SEM chamber, the accelerating voltage set to 10 keV, and images of the surfaces and cross-sections collected. The pore size was determined by using a PMI capillary flow porometer (CFP-1500-AXEL) using the same instrument and method reported by Kao et al. [26]. The porosity was assessed according to the method reported in Gu et al.’s study that consists in measuring the weight of the membrane samples before and after immersion in ethanol [27]. For these porosity assessments, we also hypothesized that the addition of PMBU copolymer, did not significantly affected the mass density of the system. Additionally, tapping-mode AFM characterization was performed in liquid state using a JPK Instruments AG multimode NanoWizard equipped with an AFM Zeiss Loop enabling to maintain the temperature constant. A commercial Si cantilever (TESP tip, model NSC14/AIBS, L: 125 µm ± 5, W: 35 µm ± 3, h: 2 µm ± 0.5, resonance frequency: 110–220 kHz, force constant: 1.85–12.5 N/m) was used and images processed with the JPK Image Processing software associated to the instrument. The mechanical properties of the membranes were determined in tension using a DMA 7e apparatus (Perkin-Elmer). After loading the membranes (8 cm × 0.5 cm) in the instrument clamps, the tensile force was progressively increased at a rate of 250 mN/min. The relationship between tensile stress and tensile strain, from which essential mechanical properties were determined, was continuously recorded for each membrane. Triplicate analysis was performed for each membrane sample, using independent samples (samples from 3 different membranes for each condition). ATR-FTIR and mapping ATR-FT-IR analyses were conducted using a 379

Journal of Membrane Science 550 (2018) 377–388

A. Venault et al.

Fig. 3. SEM images of the virgin (PMBU0) and the modified PVDF membranes (PMBU1–PMBU5). The top images are surface characterizations while the bottom images are cross-section images.

membranes in terms of their antifouling properties, can quickly be compared. The membrane used were either an as-prepared membrane or a commercial hydrophilic PVDF membrane purchased from Millipore and having an average pore size of 0.1 µm. Membranes, which diameter was 2.5 cm, were immersed in ethanol for 30 min, and then positioned in a stainless steel module, connected to a water tank. The pressure was first set to 1.5 atm to allow membrane compaction, then decreased to 1 atm after 0.5 h. DI water permeability was recorded to obtain Jw,0. Then, the water tank was replaced by a tank containing a solution of humic acid at pH 11.7 (which concentration was adjusted to 2 ppm and prepared similarly as in the study of Shao et al. [29]), and the permeability of the humic acid solution was monitored. Afterwards, the membranes underwent a washing procedure that consisted in flushing 1.5 L of DI water on the samples, followed by a backwashing with DI water for 30 min, to remove loosely adhering biofoulants. Three similar DI water/humic acid cycle were conducted, followed by similar cleaning procedure, and the entire operation was ended by a last water filtration run (Jw,4). From this filtration tests, it was possible to determine essential ratios related to the flux recovery (FRR), the reversible flux decline (DRr), the irreversible flux decline (DRir) and the total flux decline (DRt), defined as follows:

Bacterial attachment tests using Escherichia coli modified with a Green Fluorescent Protein were carried out for either 3 or 24 h. Before attachment tests, bacterial species were cultured, according to a procedure earlier reported [28]. Once the final cell concentration in the culture medium reached 107 cells/mL, obtained after a 12-h-incubation, 1 mL of bacterial solution was poured onto 1-cm-diameter disk membranes, previously PBS washed and disposed in a 24 multiwell plate. The multiwell plate was disposed in an incubator which temperature was fixed to 37 °C, for either 3 h or 24 h. In the 24 h case, the bacterial solution was removed and changed by a fresh one every 6 h, to ensure that the membranes would be in contact with healthy bacteria over the whole incubation period. After the incubation, the membranes were washed with PBS 3 times, to remove loosely adhering bacteria. Then, the samples were observed with a confocal laser scanning microscope (Nikon CLSM A1R). The observations were performed at λex = 488 nm/λem = 520 nm. As there was no driving force for cell penetration within the bulk, bacteria were more likely found at the surface (z = 0) of the membranes than trapped inside it, but the images presented correspond to the superposition of x-y planes over the entire membrane thickness (125 µm ± 11 µm). For each condition of membrane preparation, 3 independent tests were performed, and 3 different images taken for each sample, in order to quantify bacterial attachment from the confocal analysis. Image analysis was done using the open source ImageJ® software. Whole blood incubation tests were performed, using fresh blood obtained from healthy volunteers in the Taipei Blood Center (Beitou District, Taipei, Taiwan). Membranes (diameter: 1 cm) were washed with PBS and placed in individual wells of a 24 multiwell plate. Then, 200 µL of whole blood was poured in each well. Membranes were incubated at 37 °C with the blood for 2 h. Afterwards, the samples were cleaned with PBS, to remove loosely adhering cells. This washing procedure was followed by a 24-h-fixing/dying step at 4 °C, performed adding 0.8 mL of a glutaraldehyde solution (2.5% v/v, in PBS solvent) to the wells containing the membrane samples. Finally, the samples were observed by confocal microscope using a similar instrument and settings as those utilized for the characterization of bacterial attachment. In addition, to ensure reproducibility of the data, 3 independent tests were performed for each membrane preparation condition, and 3 observations made. Thus, in total, 9 images were analyzed for each membrane using ImageJ® software. Filtration cycles of DI water and humic acid in dead-end mode were carried out according to the following procedure. We worked at constant pressure and in dead-end mode, the worst situation for a membrane, as fouling can rapidly occur resulting from both a fast drag flow toward the membrane and the membrane's physicochemical properties. In this respect, only an antifouling membrane can retain for a significant amount of time its initial permeability in these conditions (dead-end, constant pressure), and the performances of several

FRR (%) =

Jw,4 × 100 Jw,0

(1)

DRr (%) =

Jw,4 − JHA,4 × 100 Jw,0

(2)

DRir (%) =

Jw,0 − Jw,4 × 100 Jw,0

(3)

JHA,4 ⎤ DRt (%) = ⎡1− × 100 ⎢ Jw,0 ⎥ ⎦ ⎣

(4)

3. Results and discussion 3.1. Morphological characterization and surface chemistry of membranes The structure of membranes was observed by SEM and AFM and the related images are presented in Figs. 3 and 4, respectively. The results indicate that virgin PVDF membranes present small nodules with a fibrillary network connecting them. These small nodules (< 500 nm in size) indicate that crystallization still occurred and thus, that the chosen initial temperature was not low enough to totally inhibit the growth of nuclei. However, the addition of PMBU copolymer, tended to further reduce the size and occurrence of the nodules, eventually leading to bicontinuous modified PVDF membrane. This morphological change is similar to that previously observed with PS-b-PEGMA/PVDF membranes [30], and is attributed to the increase of total polymer content in 380

Journal of Membrane Science 550 (2018) 377–388

A. Venault et al.

Fig. 4. 10 µm × 10 µm AFM images of the virgin (PMBU0) and the modified PVDF membranes (PMBU1, PMBU3 and PMBU5).

the casting solution, which then logically arises in an increasing of solution viscosity. In a more viscous environment, nuclei growth and nodule growth is hindered. As a result, membrane formation is driven by a non-crystallization gelling process [9]; in other words, bi-continuous membranes are formed, which are highly desired for their combination of large porosity (Table 2) and good mechanical properties (improved strength at break and modulus of elasticity, compared to virgin nodular membrane) arising from important chain entanglement and connectivity between the polymer domains. Additionally, the RMS roughness coefficients indicated in Fig. 4 decrease with the copolymer content (from 631.4 nm for PMBU0 to 59.6 for PMBU5), consistently with the transition from nodular structure (large polymer rich domains corresponding to the nodules) to bicontinuous structure (thinner and more entangled polymer domains).

Table 2 Physical properties of membranes. Membrane ID

Porosity (%)

Mean pore size (µm)

Tensile stress at break (MPa)

Tensile strain at break (%)

Young's Modulus (MPa)

PMBU0 PMBU1 PMBU2 PMBU3 PMBU4 PMBU5

72.0 ± 1.9 66.0 ± 1.9 75.5 ± 0.4 74.7 ± 0.1 75.6 ± 0.3 76.3 ± 0.3

0.1081 0.1094 0.1261 0.1069 0.0876 0.1558

0.86 ± 0.08 1.43 ± 0.27 / 1.50 ± 0.34 / 1.66 ± 0.06

4.9 ± 0.7 4.4 ± 1.1 / 3.4 ± 0.2 / 3.4 ± 0.3

57 ± 3 102 ± 4 / 84 ± 1 / 85 ± 1

Fig. 5. ATR FT-IR characterization of the membranes. (a) Characteristic spectra obtained by local analysis; (b) Color-coded maps of surfaces at 1730 cm−1 (right hand side) obtained from the surface analysis of membrane samples (top left corner); the surfaces were divided into squares of 50 µm × 50 µm as displayed on the microscope view (bottom left corner).

381

Journal of Membrane Science 550 (2018) 377–388

A. Venault et al.

was evaluated by measuring the water contact angle and the hydration capacity after immersion for 24 h in DI water. These tests are a first indication regarding the ability of the copolymer to provide a hydrated protective layer to the membranes. The results presented in Fig. 7, do evidence a significant decreasing of water contact angle from 137.3° ± 0.1° for PMBU0 membrane (virgin PVDF) to 113.7° ± 2.1° for PMBU5 membrane. One may argue that the membranes remained hydrophobic, which was indeed the case. This behavior is attributed to the physical contribution of the structure to the wetting behavior: the membranes are highly porous, which promotes the entrapment of air, and thus, contributes to the high value of WCA measured. But in addition to the high porosity, the structure of the membranes (porosity, pore shape and size, surface roughness), which arises from the two polymers (PVDF and MPC) organization, is not favorable to membrane wetting, hence explaining the hydrophobic character of all membranes. The addition of PMBU5 (chemical effect) alone did not permit to further reduce the WCA to lower values. As a result, one could also question the actual fouling resistance of the membranes. Although a clear answer will only be provided later in this manuscript after presenting the bacterial attachment, cell adhesion and filtration results, we observed in the past with other systems, but similar formulation conditions (concentrations of polymer/copolymer) and VIPS process conditions, a maximum decreasing of WCA on VIPS membranes of about 10° [30]. Yet fouling resistance of these membranes was significantly improved, because the membranes could still trap a significant amount of water in the pores after an incubation time with the hydrophilic medium long enough, as measured from the hydration capacity expressed in amount of water trapped per unit volume of membrane after a 24-h-incubation period. This is also seen here: the hydration capacity increased from about 75 (PMBU0) up to 280 mg/cm3 at the plateau. Considering the value of the hydration capacity and that of the membrane porosity, a part of the membrane pores does no trap water. Although it was not studied here, surface segregation of the copolymer probably occurred during membrane formation, as reported earlier in works on membrane formation by in-situ modification [33]. So, the membranes are asymmetric from a chemistry point of view. The copolymer diffuses toward the non-solvent/polymeric system interface during membrane formation. This phenomenon results in a higher MPC concentration near the top surface, the one that will be the most exposed to biofoulants during the different adsorption/filtration tests. Therefore, the top region of the membrane is likely to be highly hydrated, which enables to protect the membrane from biofouling, while the other regions are likely to be less hydrated as they contain less copolymer. Overall, the MPC concentration gradient should not sacrifice the resistance to biofouling, as what matters first is that the region in contact with biofoulants contains a MPC density high enough to prevent the adsorption of the biofoulants and their penetration in the membrane. So, this result and our past experience on antifouling VIPS membranes encouraged us to evaluate the feasibility of PMBU copolymer to be used to mitigate biofouling of PVDF membranes.

The surface chemistry of the membranes was investigated by local ATR FT-IR measurements, as well as by performing a mapping analysis at 1730 cm−1, wavenumber at which is observed the stretching band of O-C=O [30–32] possessed by both MPC and MEBU forming PMBU. These IR tests aimed at characterizing the surface chemistry of the membrane, and to ensure that the modification had been effective. This is a very common test performed whenever novel membranes are fabricated, and it is often referred to as a “surface characterization” test. However, one should note that the penetration depth of the infrared beam can vary (roughly between 0.5 and 2 µm). As the final membranes thickness was 125 ± 11 µm, about 2% of the bulk was actually exposed to the beam, and not just the surface. The related results are presented in Fig. 5a. The local ATR FT-IR analysis indicates that besides for PMBU0, the virgin PVDF membrane and PMBU1, formed from a casting solution containing 1 wt% copolymer only, the stretching band of the ester groups are well detected on all membranes spectra. In addition, this peak remains well detected even after a prolonged immersion in an aqueous medium (4 weeks), which indicates that the copolymer is tightly entangled in between the PVDF chains, that is, strong hydrophobic-hydrophobic interactions were established, ensuring stability of the system (Fig. S1 of the Supplementary information section). Then, a mapping analysis was performed at 1730 cm−1, and related color-coded maps are displayed in Fig. 5b. Dominating dark blue areas indicate the absence of copolymer. A change of color to green signifies that some copolymer could be detected, while the orange/red color is associated to a large amount of copolymer at the surface of the membranes. Different colors indicate heterogeneous distribution of the chemical group detected. Our analysis reveals that the map corresponding to PMBU0 is logically dark blue, the copolymer is slightly detected on PMBU1 but most areas remained blue. Light blue and green are the dominating color of the color-coded map of PMBU3 while orange is that of PMBU5. In addition, the surface of PMBU 5 membrane is quite homogeneous (one dominating color), further suggesting that many copolymer chains were packed at the surface of this membrane. In conclusion, this analysis reveal that the copolymer is not only present at the surface of the modified membranes (Fig. 5a) but also that its concentration increases with the initial content of copolymer in the casting solution as well as that it is fairly well distributed at the surface of the membranes (Fig. 5b). The FT-IR analysis was also useful to confirm the change of dominating membrane formation mechanism, crystallization gelling vs. non-crystallization gelling, through the analysis of the characteristic peaks of the α-polymorphs and that of the β-polymorphs found at 763 cm−1 and 840 cm−1, respectively. A dominating crystallizationgelling process arises in the formation of nodular-type structures, associated to dominating β-polymorphs, while a non-crystallization gelling mechanism leads to bi-continuous structures, associated to the occurrence of more numerous α-polymorphs [9]. Hence, the integration of the corresponding α-polymorphs and β-polymorphs peaks on the IR spectra provides useful information related to membrane formation mechanisms. The related results presented in Fig. 6 clearly prove that the amount of α-polymorphs is much higher from a 2 wt% initial copolymer content (that is, from PMBU2 membrane), with a relative fraction of α-polymorphs close to 0.5, while it is about 0.1 only for both PMBU0 and PMBU1 membranes, hence supporting the results of Fig. 3 regarding the change of membrane morphology, and the obtaining of a bi-continuous structure. This is also worth noting that there was no gradual increase of the fraction of α-polymorph, as the plateau was reached immediately from PMBU2 membrane. This observation suggests that there is a casting solution viscosity threshold associated to this system, below which nodules can grow during membrane formation and above which they cannot.

3.3. The effect of PMBU on the resistance to fibrinogen protein from platelet-poor-plasma The capability of zwitterionic polymers to protect membranes or model interfaces from the fouling by proteins has been well documented, when the modification at play was a surface modification process (coating, grafting, etc.) [34–37]. But given the scarceness of reports on membranes in-situ modified with a zwitterionic polymer, it was worth performing protein adsorption tests. Because PMBU is a block copolymer containing MPC, popular in the design of biocompatible interfaces, it was decided to directly test fibrinogen from plateletpoor-plasma rather than classic model proteins such as bovine serum albumin, lysozyme, or even isolated fibrinogen. Indeed, PPP is a much more complex medium than PBS, usually employed to solubilize the single proteins, as it not only contains elevated levels of fibrinogen but

3.2. The effect of PMBU on the hydration properties of membranes The effect of PMBU on the membrane hydration, surface and bulk, 382

Journal of Membrane Science 550 (2018) 377–388

A. Venault et al.

Fig. 6. The fraction of alpha polymorphs at the surface of the different membranes, obtained from the analysis of the peaks on the FT-IR spectra at 763 cm−1 (α-polymorph) and 840 cm−1 (β-polymorph). Examples of IR spectra with the bands of interest and associated structures are provided for PMBU0 (left side) and PMBU3 (right side).

biofoulants. The results of this investigation are gathered in Fig. 8. It is first seen that the virgin membrane (PMBU0) adsorbs much more protein than the tissue culture polystyrene plate, commonly used as a positive control (100% adsorption). This can be rationalized as follows: (1) polystyrene material is less hydrophobic than PVDF (chemical effect) and (2) the TCPS surface is smooth while the PVDF membranes are rough (physical effect). A rougher and more hydrophobic matrix will then adsorb more protein than a smoother and less hydrophobic surface. Thus, it is quite difficult to draw accurate comparisons with TCPS, and it makes more sense to compare membranes together. It is seen that PMBU1 membrane enabled to drastically reduce the extent of FN adsorption, compared with the virgin membrane, as the relative adsorptions were 350 ± 62% and 117 ± 19%, for PMBU0 and PMBU1, respectively. Using PMBU5, the relative adsorption went down to 66%. This important improvement of the fouling resistance tends to prove that PMBU can be efficiently used to modify in-situ PVDF membranes, and that, despite a rough and porous physical structure promoting the adhesion of biofoulants, the zwitterionic heads dispersed in the bulk of the membrane bind water tightly enough to efficiently protect the membranes from irreversible adsorption of proteins. It is difficult at this point to accurately compare this result with those of other groups, because zwitterionic membranes were prepared differently (often by coating or grafting) and fibrinogen from PPP untested. However, we presented a few years ago a series of fouling resistant bi-continuous PVDF membranes prepared by VIPS. Among the differences, a PEGbased copolymer was used and fibrinogen adsorption from single protein solution tested [30]. Compared to the virgin membrane, the protein adsorption was decreased by more than 80%. Hence, PMBU5 not only compares with the PEGylated membrane earlier presented, but actually outperforms it as FN was not adsorbed from PPP in the work on PEGsystems. A possible explanation is related to the complex nature of plasma, suspected to mediate PEG degradation. This is in line with previous works establishing a correlation between the relative hydrophobic character of PEG derivatives and their immunogenicity, compared with zwitterionic molecules, more hydrophilic [38,39]. In other words, zwitterionic molecules are more stable in biological fluids from human body. In conclusion, PMBU seems suitable to provide rough and hydrophobic membranes with fouling resistance properties in complex protein medium.

Fig. 7. Hydration properties of the membranes. The effect of PMBU on the surface hydration is seen from the WCA measurements while that on the bulk hydration is seen from the hydration capacity tests.

3.4. The effect of PMBU on the resistance to bacterial attachment

Fig. 8. The effect of PMBU on resistance of the membranes to the adsorption of fibrinogen from a platelet-poor-plasma solution. The positive control (100% adsorption) is TCPS; SBMA hydrogel relative adsorption is also reported.

Membranes biofouling by bacteria is a common phenomenon in water treatment related applications of membranes [40,41]. So, we tested the bacterial resistance of the PMBU/PVDF membranes after incubation with Escherichia coli suspensions for 3 h (Fig. 9a) and 24 h (Fig. 9b). The later incubation time was chosen to detect the possible formation of biofilm, the next stage of biofouling by bacteria after their

also globulin or albumin proteins, along with remaining platelets (although at low level). All these constituents can severely foul hydrophobic surfaces, or mediate the interactions of the surface with other 383

Journal of Membrane Science 550 (2018) 377–388

A. Venault et al.

Fig. 9. Confocal analysis of E. coli with GFP (green fluorescent protein) attachment onto/within the PVDF and modified PVDF membranes after (a) 3 h and (b) 24 h. Quantitative analysis was assessed using commercial ImageJ® software.

it is grafted from biofouling by proteins and larger biofoulants. A similar mechanism holds for in-situ modified membranes, provided a copolymer content high enough in the matrix. Water is tightly retained at the surface and within the matrix (particularly nearby the top-surface as surface segregation is likely to have happened during membrane formation). Here, it seems that a 2–3 wt% copolymer content is enough to protect the membrane from the adsorption of large biofoulants such as bacteria. It has to be noted again that the as-prepared membranes are all extremely porous and rough, as they were prepared by VIPS process. Such a structure promotes fouling by physical entrapment of bacteria while oppositely, it would not occur on dense smooth membranes. What is more, E. coli bacteria are well-known for their deformability which gives them the ability to squeeze through pores smaller than their actual size [42]. This important consideration further highlights the excellent antifouling property of PMBU.

irreversible attachment. Biofilm can be seen from a confocal analysis, and is characterized by large fluorescent areas, arising from bacterial agglomerates. Both confocal analysis and the related quantification of bacterial attachment show that even from a low PMBU concentration, there is an important reduction of bacterial attachment after a 3 h-incubation. From PMBU2, the membrane almost resisted entirely to biofouling by bacteria. Furthermore, after a 24 h-incubation period, if biofilm started to be formed on the virgin PVDF membrane, bacterial attachment was reduced by more than 90% using PMBU1, while all PMBU4 and PMBU5 membranes exhibited excellent resistance to E. coli. Therefore, these results demonstrate the excellent antifouling properties of PMBU even when incorporated in PVDF VIPS membranes. As reminded in the introductory section of this manuscript, zwitterionic materials are known for their excellent antifouling properties because they provide a tight hydration layer protecting the material onto which 384

Journal of Membrane Science 550 (2018) 377–388

A. Venault et al.

3.5. The effect of PMBU on whole blood attachment Whole blood is a highly foulant medium as both (1) very sticky proteins such as fibrinogen and (2) blood cells among which very sensitive platelets and erythrocytes can lead to irreversible fouling of the membranes employed in blood-contacting filtration devices. Fibrinogen is known for its role on coagulation pathways [43–45], hence mediating cells-membrane interactions, while blood cells adhesion onto non hemocompatible materials can readily occur, via hydrophobic-hydrophobic interactions. In addition, membranes for bloodcontacting devices are often highly porous, such as those used in blood oxygenators. For the same reason as that above-mentioned, physical entrapment of cells can easily occur in these systems. As blood cells are sensitive to environmental changes, platelet activation or red blood cell hemolysis, for instance, can occur once physically entrapped. Therefore, it is absolutely necessary to limit biofouling due to physical entrapment, by creating a protective hydration layer. So, resistance of a porous membrane to whole blood would reflect its antifouling character. For this reason, the PVDF and PVDF/PMBU membranes were incubated with whole blood. The results of whole blood attachment tests are displayed in Fig. 10. As expected, the virgin PVDF membrane is clearly not hemocompatible due to its hydrophobic porous nature. Not only hydrophobic interactions between the cell and the membrane, or the blood proteins and the membrane further mediating cell adhesion, occurred, but also physical

Fig. 10. Analysis of whole blood attachment conducted from an analysis of confocal images obtained after incubation of the membranes for 2 h with whole blood.

Fig. 11. Comparisons of the performances of PMBU5 with a commercial hydrophilic PVDF membrane during water/humic acid filtration cycles. (a) Permeate flux; (b) Dimensionless permeate flux; (c) Flux analysis items including the flux recovery ratio (FRR), the total flux decline ratio (DRt), the reversible flux decline ratio (DRr) and the irreversible flux decline ratio (DRir).

385

Journal of Membrane Science 550 (2018) 377–388

A. Venault et al.

entrapment of the cells within the membrane pores, hence explaining the high cell density detected by confocal microscopy, approaching 6000 cells/mm2. PMBU1 membrane, however, enabled to reduce the cell adhesion by a little more than 30%. If the nonfouling character of PMBU copolymer is seen when comparing PMBU0 and PMBU1 samples, it is clear that there was not enough copolymer at the surface of PMBU1 membrane to efficiently mitigate biofouling by whole blood. This has to be correlated with the observation of Fig. 5, that highlighted low copolymer content at the surface of the membrane. Even though PMBU1 fairly well resisted biofouling by bacteria (Fig. 9), its antifouling ability remained limited when contacted in a highly foulant medium. On the other hand, PMBU2 membrane reduced biofouling by 83%, value which fell down to 99% for PMBU4 and PMBU5 membranes. Therefore, the hemocompatible nature of PMBU copolymer, once incorporated in PVDF membrane, is maintained, making the resulting PVDF/PMBU membrane excellent candidates for utilization in blood contacting devices, for instance. More importantly, this test supported the antibiofouling properties of the as-prepared membranes when contacted with complex biological medium.

cycles. Another noticeable recent result is that reported by Ekambaram and Doraisamy, who prepared membranes by in-situ modification from the PVDF/carboxymethyl chitosan blend [51]. They reported a FRR of at least 82.75%, after 2 water/humic acid cycles, comparable to our result, and the authors claimed that the excellent fouling resistance of the membranes was imparted to the addition of carboxymethyl chitosan. These different results and comparisons with published work lead us to conclude that the in-situ modification of PVDF VIPS membranes with MPC copolymer is a credible strategy to readily develop porous membranes able to resist biofouling caused by various complex media. However, the drop in water permeability observed at the end of the 4 cycles may indicate that a long-term drag flow eventually destabilizes the entanglement of PMBU in the PVDF matrix, which could not be detected from the results of long term immersion tests (Fig. S1). Therefore, efforts should be oriented toward the reinforcement of these interactions to better stabilize and extend the antifouling performances of the membranes, by further tuning the composition of the hydrophobic blocks in the MPC copolymer.

3.6. Performances of modified membranes in filtration

4. Conclusions

The ultimate purpose of designing a membrane is to use it for the filtration of medium which are often complex (surface water, blood, etc…), that is, with a high fouling power. Studies on the design of antifouling membranes commonly report on filtration cycles using BSA and water [46–48]. However, because previous sections tended to highlight the excellent fouling resistance of PMBU5 membrane despite its incubation with complex medium such as whole blood, or despite long term incubation with bacterial solutions, we decided to carry out humic acid/water filtration tests. Humic acids are produced by the biodegradation of organic matter which leads to the formation of a complex mixture of acids which can readily foul membranes [49]. Test were carried out using our best membrane, PMBU5, and a commercial hydrophilic PVDF membrane. We report in Fig. 11 the permeate flux measured over time during the humic acid/water filtration cycles and their corresponding dimensionless plots, which permit to better apprehend the extent of fouling of the membranes. The initial DI water permeability of the commercial hydrophilic PVDF membrane is slightly lower than that of PMBU5 (1087 L/m2 h vs. 1143 L/m2 h) In both cases, the replacement of water by humic acid leads to a drastic reduction of the permeate flux, measured to be about 317 L/m2 h for the commercial PVDF membrane and 179 L/m2 h for PMBU5 membrane, which highlights the high fouling power of HA. However, after the washing procedure, only the permeability of PMBU5 membrane was maintained to a high level. Hence, after 2 water/HA cycles and, the water permeability of PMBU5 was still 870 L/m2 h. After 4 cycles, an overall flux recovery ratio of about 42%, while it was only 17% in the case of the hydrophilic commercial PVDF membrane. This suggests that fouling by HA was better mitigated in the case of PMBU5 (DRr: 33% and DRir: 58%) than in the case of the hydrophilic commercial PVDF membrane (DRr:3% and DRir: 83%) as clearly seen in Fig. 11c. Although necessary, accurate comparisons with already published works is difficult because of the absence, to our knowledge, of zwitterionic PVDF membranes prepared by in-situ modification. Therefore, we could only compare the results of the filtration tests with those obtained with different systems. Chiag et al. designed antifouling PEGbased membranes by surface coating [50]. Although the nature of the antifouling copolymer (PEG vs. zwitterionic) and the membrane modification process (surface coating vs. in-situ modification) were different, the initial membrane permeability of our system was in the same range as that measured with their system (1200 L/m2 h), and two water/humic acid filtration cycles were run. They reported a FRR of about 66% as the final water permeability of their best coated membrane was 800 L/m2 h, which highlights the superior antifouling of the membrane presented in this work as our FRR was about 80% after 2

This study has presented the unique combination of PVDF and a copolymer of 2-methacryloyloxyethyl phosphorylcholine and methacryloyloxyethyl butylurethane, referred to as PMBU, to form biofoulingresistant membranes by vapor-induced phase separation. We proved that it was possible to form zwitterionic-based PVDF membranes by insitu modification with a controllable structure. The major conclusions of this work are as follows:

• While the structure of the virgin PVDF membranes was mostly • • • •

•

nodular, increasing the viscosity of the casting solution by adding PMBU copolymer enabled to switch to the formation of bi-continuous structures, as evidenced by SEM images and the analysis of polymorphs in the final PVDF membranes; A local and mapping analysis of the surface by FT-IR proved that the membranes were efficiently modified with PMBU (presence of a strong signal due to the carboxylate groups) and in a relatively controlled fashion (homogeneous distribution); The hydration properties of the modified membranes were greatly improved, compared with those of the virgin PVDF membrane. In particular, the hydration capacity rose from 75 (virgin membrane, PMBU0) up to 280 mg/cm3 (PMBU5); Biofouling by bacteria after 3 h or 24 h was almost entirely mitigated, thus evidencing the membrane resistance to biofilm formation; The membranes prepared from casting solution containing 4 and 5 wt% PMBU resisted remarkably the adhesion of cells from whole blood, with a reduction of 99% of attachment, compared to virgin membrane. In addition, adsorption of fibrinogen from a PPP solution was decreased by 82% on PMBU5, compared with PMBU0 (virgin membrane). In terms of total flux recovery ratio after 4 water/HA filtration cycles, the results demonstrated that PMBU5 membrane outperformed a commercial hydrophilic PVDF membrane, as the FRR at the end of the procedure was found to be 42% for PMBU5 while it was only 17% for the commercial membrane.

Bi-continuous structures are highly desired in UF/MF applications of membranes. Combined to their excellent antifouling properties, the as-prepared PVDF/PMBU membranes hold promise for numerous applications of porous PVDF membranes, in particular blood-contacting devices for which there is an absolute need for blood-inert property. To finish and although the PMBU membranes were shown to be extremely efficient to prevent biofouling by versatile biofoulants, there is a need to investigate in details the effect of surface segregation on the 386

Journal of Membrane Science 550 (2018) 377–388

A. Venault et al.

wettability of the membranes and on biofouling. Considering more precisely the high porosity of the membranes, the hydration capacities reported for the PMBU membranes were low. Hydration must have occurred where the copolymer was highly segregated, likely nearby the top surface. This implied that some sites of the membranes, probably the deeper layers, were not wetted. Therefore, a question arises related to whether or not perfect nonfouling membranes could be obtained if more regions of the membranes were wetted.

hydrophilic surface of terry pile-like structure, J. Membr. Sci. 493 (2015) 243–251. [17] J.-H. Li, M.-Z. Li, J. Miao, J.-B. Wang, X.-Z. Shao, Q.-Q. Zhang, Improved surface property of PVDF membrane with amphiphilic zwitterionic copolymer as membrane additive, Appl. Surf. Sci. 258 (2012) 6398–6405. [18] K. Ishihara, T. Shinozuka, Y. Hanazaki, Y. Iwasaki, N. Nakabayashi, Improvement of blood compatibility on cellulose hemodialysis membrane: iv. Phospholipid polymer bonded to the membrane surface, J. Biomater. Sci. Polym. Ed. 10 (1999) 271–282. [19] K. Ishihara, Y. Iwasaki, S. Ebihara, Y. Shindo, N. Nakabayashi, Photoinduced graft polymerization of 2-methacryloyloxyethyl phosphorylcholine on polyethylene membrane surface for obtaining blood cell adhesion resistance, Colloids Surf. B 18 (2000) 325–335. [20] N. Morimoto, Y. Iwasaki, N. Nakabayashi, K. Ishihara, Physical properties and blood compatibility of surface modified segmented polyurethane by semi-interpenetrating polymer networks with a phospholipid polymer, Biomaterials 23 (2002) 4881–4887. [21] Y. Iwasaki, N. Nakabayashi, K. Ishihara, Preservation of platelet function on 2methacryloyloxyethyl phosphorylcholine graft polymer compared to various watersoluble graft polymers, J. Biomed. Mater. Res. 57 (2001) 74–79. [22] Y. Iwasaki, A. Yamasaki, K. Ishihara, Platelet compatible blood filtration fabrics using a phosphorylcholine polymer having high surface mobility, Biomaterials 24 (2003) 3599–3604. [23] P. Bengani-Lutz, E. Converse, P. Cebe, A. Asatekin, Self-assembling zwitterionic copolymers as membrane selective layers with excellent fouling resistance: effect of zwitterion chemistry, ACS Appl. Mater. Interfaces 9 (2017) 20859–20872. [24] K. Ishihara, H. Hanyuda, N. Nakabayashi, Synthesis of phospholipid polymers having a urethane bond in the side chain as coating material on segmented polyurethane and their platelet adhesion-resistant properties, Biomaterials 16 (1995) 873–879. [25] D.J. Lin, K. Beltsios, T.H. Young, Y.S. Jeng, L.P. Cheng, Strong effect of precursor preparation on the morphology of semicrystalline phase inversion poly(vinylidene fluoride) membranes, J. Membr. Sci. 274 (2006) 64–72. [26] S.T. Kao, M.Y. Teng, C.L. Li, C.Y. Kuo, C.Y. Hsieh, H.A. Tsai, D.M. Wang, K.R. Lee, J.Y. Lai, Fabricating PC/PAN composite membranes by vapor-induced phase separation, Desalination 233 (2008) 96–103. [27] M. Gu, J. Zhang, X. Wang, H. Tao, L. Ge, Formation of poly(vinylidene fluoride) (PVDF) membranes via thermally induced phase separation, Desalination 192 (2006) 160–167. [28] S.-W. Hsiao, A. Venault, H.-S. Yang, Y. Chang, Bacterial resistance of self-assembled surfaces using PPOm-b-PSBMAn zwitterionic copolymer – concomitant effects of surface topography and surface chemistry on attachment of live bacteria, Colloids Surf. B 118 (2014) 254–260. [29] J. Shao, L. Zhao, X. Chen, Y. He, Humic acid rejection and flux decline with negatively charged membranes of different spacer arm lengths and charge groups, J. Membr. Sci. 435 (2013) 38–45. [30] A. Venault, J.R. Wu, Y. Chang, P. Aimar, Fabricating hemocompatible bi-continuous PEGylated PVDF membranes via vapor-induced phase inversion, J. Membr. Sci. 470 (2014) 18–29. [31] L.-P. Zhu, Y.-Y. Xu, H.-B. Dong, Z. Yi, B.-K. Zhu, Amphiphilic PPESK-graft-P (PEGMA) copolymer for surface modification of PPESK membranes, Mater. Chem. Phys. 115 (2009) 223–228. [32] J. Jin, W. Jiang, Q. Shi, J. Zhao, J. Yin, P. Stagnaro, Fabrication of PP-g-PEGMA-gheparin and its hemocompatibility: from protein adsorption to anticoagulant tendency, Appl. Surf. Sci. 258 (2012) 5841–5849. [33] J.F. Hester, P. Banerjee, A.M. Mayes, Preparation of protein-resistant surfaces on poly(vinylidene fluoride) membranes via surface segregation, Macromolecules 32 (1999) 1643–1650. [34] C. Gao, G. Li, H. Xue, W. Yang, F. Zhang, S. Jiang, Functionalizable and ultra-low fouling zwitterionic surfaces via adhesive mussel mimetic linkages, Biomaterials 31 (2010) 1486–1492. [35] J. Zhao, Q. Shi, S. Luan, L. Song, H. Yang, H. Shi, J. Jin, X. Li, J. Yin, P. Stagnaro, Improved biocompatibility and antifouling property of polypropylene non-woven fabric membrane by surface grafting zwitterionic polymer, J. Membr. Sci. 369 (2011) 5–12. [36] S. Guo, D. Jańczewski, X. Zhu, R. Quintana, T. He, K.G. Neoh, Surface charge control for zwitterionic polymer brushes: tailoring surface properties to antifouling applications, J. Colloid Interface Sci. 452 (2015) 43–53. [37] M.-Z. Li, J.-H. Li, X.-S. Shao, J. Miao, J.-B. Wang, Q.-Q. Zhang, X.-P. Xu, Grafting zwitterionic brush on the surface of PVDF membrane using physisorbed free radical grafting technique, J. Membr. Sci. 405–406 (2012) 141–148. [38] R.P. Garay, R. El-Gewely, J.K. Armstrong, G. Garratty, P. Richette, Antibodies against polyethylene glycol in healthy subjects and in patients treated with PEGconjugated agents, Expert. Opin. Drug Deliv. 9 (2012) 1319–1323. [39] P. Zhang, F. Sun, C. Tsao, S. Liu, P. Jain, A. Sinclair, H.-C. Hung, T. Bai, K. Wu, S. Jiang, Zwitterionic gel encapsulation promotes protein stability, enhances pharmacokinetics, and reduces immunogenicity, Proc. Natl. Acad. Sci. USA 112 (2015) 12046–12051. [40] F. Mang, H. Zhang, F. Yang, Y. Li, J. Xiao, X. Zhang, Effect of filamentous bacteria on membrane fouling in submerged membrane bioreactor, J. Membr. Sci. 272 (2006) 161–168. [41] N. Hilal, V. Kochkodan, L. Al-Khatib, T. Levadna, Surface modified polymeric membranes to reduce (bio)fouling: a microbiological study using E. coli, Desalination 167 (2004) 293–300. [42] N. Lebleu, C. Roques, P. Aimar, C. Causserand, Role of the cell-wall structure in the retention of bacteria by microfiltration membranes, J. Membr. Sci. 326 (2009) 178–185. [43] W.B. Tsai, J.M. Grunkemeier, T.A. Horbett, Human plasma fibrinogen adsorption

Supporting information Supplementary data associated with this article can be found in the online version. Acknowledgments The authors thank the Ministry of Science and Technology for funding this project through the Grant MOST 104-2221-E-033-066-MY3 and MOST 106-2632-E-033-001. Appendix A. Supplementary material Supplementary data associated with this article can be found in the online version at http://dx.doi.org/10.1016/j.memsci.2017.12.075. References [1] W. Zhao, Y. Su, C. Li, Q. Shi, X. Ning, Z. Jiang, Fabrication of antifouling polyethersulfone ultrafiltration membranes using Pluronic F127 as both surface modifier and pore-forming agent, J. Membr. Sci. 318 (2008) 405–412. [2] H. Susanto, N. Stahra, M. Ulbricht, High performance polyethersulfone microfiltration membranes having high flux and stable hydrophilic property, J. Membr. Sci. 342 (2009) 153–164. [3] A. Rahimpour, S.S. Madaeni, Improvement of performance and surface properties of nano-porous polyethersulfone (PES) membrane using hydrophilic monomers as additives in the casting solution, J. Membr. Sci. 360 (2010) 371–379. [4] F. Ran, S. Nie, W. Zhao, J. Li, B. Su, S. Sun, C. Zhao, Biocompatibility of modified polyethersulfone membranes by blending an amphiphilic triblock co-polymer of poly(vinyl pyrrolidone)–b-poly(methyl methacrylate)–b-poly(vinyl pyrrolidone), Acta Biomater. 7 (2011) 3370–3381. [5] M. Peyravi, A. Rahimpour, M. Jahanshahi, A. Javadi, A. Shockravi, Tailoring the surface properties of PES ultrafiltration membranes to reduce the fouling resistance using synthesized hydrophilic copolymer, Microporous Mesoporous Mater. 160 (2012) 114–125. [6] J. Zhang, Q. Wang, Z. Wang, C. Zhu, Z. Wu, Modification of poly(vinylidene fluoride)/polyethersulfone blend membrane with polyvinyl alcohol for improving antifouling ability, J. Membr. Sci. 466 (2014) 293–301. [7] D. Liu, D. Li, D. Du, X. Zhao, A. Qin, X. Li, C. He, Antifouling PVDF membrane with hydrophilic surface of terry pile-like structure, J. Membr. Sci. 493 (2015) 243–251. [8] W. Ma, S. Rajabzadeh, A.R. Shaikh, Y. Kakihana, Y. Sun, H. Matsuyama, Effect of type of poly(ethylene glycol) (PEG) based amphiphilic copolymer on antifouling properties of copolymer/poly(vinylidene fluoride) (PVDF) blend membranes, J. Membr. Sci. 514 (2016) 429–439. [9] C.L. Li, D.M. Wang, A. Deratani, D. Quemener, D. Bouyer, J.Y. Lai, Insight into the preparation of poly(vinylidene fluoride) membranes by vapor-induced phase separation, J. Membr. Sci. 361 (2010) 154–166. [10] L.-P. Zhu, L. Xu, B.-K. Zhu, Y.-X. Feng, Y.-Y. Xu, Preparation and characterization of improved fouling-resistant PPESK ultrafiltration membranes with amphiphilic PPESK-graft-PEG copolymers as additives, J. Membr. Sci. 294 (2007) 196–206. [11] Y.-H. Zhao, Y.-L. Qian, B.-K. Zhu, Y.-Y. Xu, Modification of porous poly(vinylidene fluoride) membrane using amphiphilic polymers with different structures in phase inversion process, J. Membr. Sci. 310 (2008) 567–576. [12] Z. Yi, L.-P. Zhu, Y.-Y. Xu, X.-L. Li, J.-Z. Yu, B.-K. Zhu, F127-based multi-block copolymer additives with poly(N,N-dimethylamino-2-ethyl methacrylate) end chains: the hydrophilicity and stimuli-responsive behavior investigation in polyethersulfone membranes modification, J. Membr. Sci. 364 (2010) 34–42. [13] C.H. Loh, R. Wang, Effects of additives and coagulant temperature on fabrication of high performance PVDF/Pluronic F127 blend hollow fiber membranes via nonsolvent induced phase separation, Chin. J. Chem. Eng. 20 (2012) 71–79. [14] B. Liu, C. Chen, T. Li, J. Crittenden, Y. Chen, High performance ultrafiltration membrane composed of PVDF blended with its derivative copolymer PVDF-gPEGMA, J. Membr. Sci. 445 (2013) 66–75. [15] A. Venault, Y.-H. Liu, J.-R. Wu, H.-S. Yang, Y. Chang, J.-Y. Lai, P. Aimar, Low biofouling membranes prepared by liquid-induced phase separation of the PVDF/ polystyrene-b-poly(ethylene glycol) methacrylate blend, J. Membr. Sci. 450 (2014) 340–350. [16] D. Liu, D. Li, D. Du, X. Zhao, A. Qin, X. Li, C. He, Antifouling PVDF membrane with

387

Journal of Membrane Science 550 (2018) 377–388

A. Venault et al.

non-solvent-induced phase separation, J. Appl. Polym. Sci. 111 (2009) 1653–1658. [48] S. Rajabzadeh, D. Ogawa, Y. Ohmukai, Y. Zhou, T. Ishigami, H. Matsuyama, Preparation of a PVDF hollow fiber blend membrane via thermally induced phase separation (TIPS) method using new synthesized zwitterionic copolymer, Desalin. Water Treat. 54 (2015) 2911–2919. [49] W. Yuan, A.L. Zydney, Humic acid fouling during ultrafiltration, Environ. Sci. Technol. 34 (2000) 5043–5050. [50] Y.-C. Chiag, Y. Chang, W.-Y. Chen, R.-C. Ruaan, Biofouling resistance of ultrafiltration membranes controlled by surface self-assembled coating with PEGylated copolymers, Langmuir 28 (2012) 1399–1407. [51] K. Ekambaram, M. Doraisamy, Fouling resistant PVDF/carboxymethyl chitosan composite nanofiltration membranes for humic acid removal, Carbohydr. Polym. 173 (2017) 431–440.

and platelet adhesion to polystyrene, J. Biomed. Mater. Res. 44 (1999) 130–139. [44] W.H. Kuo, M.J. Wang, H.W. Chien, T.-C. Wei, C. Lee, W.B. Tsai, Surface modification with poly(sulfobetaine methacrylate-co-acrylic acid) to reduce fibrinogen adsorption, platelet adhesion, and plasma coagulation, Biomacromolecules 12 (2011) 4348–4356. [45] L.E. Corum, C.D. Eichinger, T.W. Hsiao, V. Hlady, Using microcontact printing of fibrinogen to control surface-induced platelet adhesion and activation, Langmuir 27 (2011) 8316–8322. [46] M. Zator, M. Ferrando, F. López, C. Güell, Membrane fouling characterization by confocal microscopy during filtration of BSA/dextran mixtures, J. Membr. Sci. 301 (2007) 57–66. [47] N. Arahman, T. Maruyama, T. Sotani, H. Matsuyama, Fouling reduction of a poly (ether sulfone) hollow-fiber membrane with a hydrophilic surfactant prepared via

388