Graphene oxide (GO) laminar membranes for concentrating pharmaceuticals and food additives in organic solvents

Accepted Manuscript Graphene oxide (GO) laminar membranes for concentrating pharmaceuticals and food additives in organic solvents Bofan Li, Yue Cui, Susilo Japip, Zhiwei Thong, Tai-Shung Chung PII:

S0008-6223(18)30047-2

DOI:

10.1016/j.carbon.2018.01.040

Reference:

CARBON 12781

To appear in:

Carbon

Received Date: 26 October 2017 Revised Date:

8 January 2018

Accepted Date: 9 January 2018

Please cite this article as: B. Li, Y. Cui, S. Japip, Z. Thong, T.-S. Chung, Graphene oxide (GO) laminar membranes for concentrating pharmaceuticals and food additives in organic solvents, Carbon (2018), doi: 10.1016/j.carbon.2018.01.040. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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~70nm

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100 nm

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Graphene Oxide (GO) Laminar Membranes for Concentrating

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Pharmaceuticals and Food Additives in Organic Solvents

Department of Chemical & Biomolecular Engineering

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Bofan Li1, Yue Cui1, Susilo Japip1, Zhiwei Thong1, Tai-Shung Chung*,1,

National University of Singapore, 4 Engineering Drive 4

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Singapore 117585

*Corresponding author

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Tel: +65-65166645; fax: +65-67791936; Email: [email protected]

*Corresponding author. Tel: +65-65166645; fax: +65-67791936; Email: [email protected]

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Abstract An ultrathin Graphene oxide (GO) laminar composite membrane has been fabricated in-house via pressure-assisted filtration. It has a relatively high pure water permeability of 7.70 LMH/bar

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with a molecular weight cut-off (MWCO) of 1243 Da. When being treated with various solvents, the membrane exhibits good stability in both polar and nonpolar solvents. The GO laminar composite membrane has relatively high pure solvent fluxes of 24.89 Lm-2h-1, 7.95 Lm-2h-1 and

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12.08 Lm-2h-1 for ethanol, isopropanol and hexane, respectively. Its rejections to orange II sodium salt, safranin O, solvent blue 35, rhodamine B and remazol brilliant blue are 56.60%,

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86.52%, 4.39%, 66.95% and 97.11%, respectively. Experimental results suggest that the Donnan exclusion is less effective in OSN than in aqueous systems, while the size exclusion and solutemembrane affinity are the dominant factors in determining separation performance. Some active pharmaceutical ingredients (APIs) and food additives, e.g. tetracycline, rifampicin,

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roxithromycin, spiramycin, vitamin B12 and lecithin, are used to demonstrate the separation capability of the newly developed membrane in real-life applications. It can effectively retain those compounds with rejections of 65.80%, 82.67%, 84.27%, 92.21%, 95.34% and 98.44%,

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respectively. Several 7-day tests of vitamin B12 in isopropanol also confirm the membrane integrity and separation performance for continuous OSN uses.

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Keywords: graphene oxide; organic solvent nanofiltration; pharmaceuticals; food additives; dyes

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1. Introduction Organic solvent nanofiltration (OSN), also known as solvent resistant nanofiltration (SRNF), is an emerging separation technology for the recovery of organic solvents and re-concentration of

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solutes. It is a membrane-based process to separate solutes ranging from 200 - 1000 Da in a variety of organic solvents [1-6]. OSN has received much attention in recent years as it can substitute the traditional separation processes, such as distillation and evaporation, in

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pharmaceutical, food and petrochemical industries to recover valuable solvents and minimize energy consumption, processing costs and CO2 emission. Since most active pharmaceutical

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ingredients (APIs) and food additives are light or heat sensitive, athermal separation processes are preferred. OSN is therefore superior to the conventional thermal processes for the concentration and crystallization of APIs and food additives. Despite of many advantages, a number of challenges must be overcome before OSN being widely used in various industries.

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One major challenge is to develop membranes with both high separation performance and stability in organic solvents. Up to now, only a limited number of OSN membranes have been developed and reported, and there are few commercially available OSN membranes on the

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market [1-5]. Hence, exploring the capabilities of various materials and membranes is imperative

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for the development of OSN.

In order to confine the pore size to the nanofiltration range, OSN membranes comprising an ultra-thin dense selective layer on top of porous substrates are preferred [1-8]. Coating is one of the most common and effective methods to form the selective layer. Among different coating materials, GO is well-known for its easy assembly as well as good chemical and mechanical stabilities. The two dimensional stacking structure and tunable spacing enable its function as a 3

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separation layer. Its applicability has also been widely evaluated in gas separation, water purification and pervaporation processes [9-12]. To achieve a high flux and avoid mechanical weakness, GO is usually deposited onto a porous substrate to form an ultra-thin selective layer

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[10, 12-15]. The choice of substrate materials is limited to a small number of candidates because organic solvents tend to swell or even dissolve the polymeric substrates. The most common ones are polybenzimidazole (PBI) [16-19] and polyimides including P84, Matrimid®, Torlon® and

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Ultem®, due to their ability to be crosslinked easily with enhanced resistance to harsh solvents [1-5, 7, 8, 20, 21]. Thus, in this study, Matrimid® is adopted as the substrate material to provide

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the mechanical strength for the thin GO laminate. Currently, there are several methods to deposit GO on porous substrates; namely, pressure-assisted filtration [12, 22, 23], drop-coating [24, 25], layer-by-layer (LbL) [10, 13, 26]and evaporation [27]. However, different assembling methods can result in distinctive packing structures and performance of GO layers [28]. Among them,

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operation.

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pressure-assisted filtration is the most studied and commonly used method due to its ease of

In this work, the GO laminate is assembled by pressure-assisted filtration on the top surface of a

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crosslinked Matrimid® substrate to demonstrate its capability in OSN applications. The membrane substrate is a lab-fabricated Matrimid® membrane crosslinked with 1,6hexanediamine (HDA) to improve its chemical stability [7, 29]. GO dispersions are centrifuged and diluted before filtration to minimize the defects of the resultant GO selective layer. The asfabricated membrane is tested in several organic solvents, such as ethanol, isopropanol (IPA) and hexane. The membrane demonstrates good stability, high solvent fluxes and > 90% rejection towards several organic solutes, such as dyes, APIs and food additives, (i.e., remazol brilliant 4

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blue, roxithromycin, vitamin B12 and L- -lecithin). Thus, this study may provide new insights

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for designing and fabrication of new generation OSN membranes.

2. Experimental Methods 2.1 Materials

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The membrane substrate was fabricated in-house using a commercially available polyimide polymer, Matrimid® 5218 (Vantico Inc.). The solvent, N-methyl-2-pyrrolidinone (NMP, >

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99.5%), was purchased from Merck and the pore former, polyethylene glycol 400 (PEG 400, MW = 400 g·mol-1), was purchased from Acros (USA). 1,6-Hexanediamine (HDA, 98%, Sigma Aldrich) and dopamine hydrochloride (99.8%, TCI) were used for crosslinking and modification of the substrate. A 0.5 wt% GO aqueous solution was purchased from Angstron Materials.

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Ethylenediamine (EDA, 99.5 wt%, Sigma-Aldrich) was utilized to crosslink the GO nanosheets. Diethylene glycol, sucrose, and polyethylene glycols with different molecular weights, purchased from Sigma-Aldrich, were employed to determine the pore size distribution of the

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membrane. Ethanol, isopropanol (IPA) and hexane were purchased from VWR Inc. for OSN performance tests. Various dyes, including orange II sodium salt (85%, MW= 350.32 g·mol-1),

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safranin O (85%, MW= 350.84 g·mol-1), solvent blue 35 (85%, MW= 350.46 g·mol-1), rhodamine B (95%, MW= 479.02 g·mol-1) and remazol brilliant blue (50%, MW= 626.54 g·mol1

), were procured from Sigma-Aldrich for dye rejection tests. Five APIs, i.e., tetracycline (≥ 98%,

MW= 444.43 g·mol-1), rifampicin (≥ 97%, MW= 822.94 g·mol-1), roxithromycin (≥ 90%, MW= 837.05 g·mol-1), spiramycin (mixture of spiramycin I, II and III) and vitamin B12 (≥ 98%, MW= 1355.37g·mol-1), and one food additive, L- -Phosphatidylcholin (L- -lecithin, mixture of

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phosphatidylcholine and phosphatides), were obtained from Sigma-Aldrich for application tests.

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The deionized (DI) water was produced using a Milli-Q ultrapure water system (Millipore, USA).

2.2 Fabrication and Crosslinking Modification of Matrimid® Membrane Substrates

Matrimid® flat-sheet substrates were fabricated via a non-solvent induced phase inversion

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method [30-32]. Before preparing the dope, Matrimid® was first vacuum dried at 70 °C for 24 hours to remove any adsorbed moisture. The dried polymer was then dissolved in a mixture of

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NMP and PEG400 with a weight ratio of 18/66/16. The mixture was stirred at 60 °C for one day and the resultant homogeneous solution was degassed overnight before usage. Subsequently, the membrane substrate was cast on a glass plate with a casting knife, followed by immersing it in deionized (DI) water to remove the residual NMP and PEG400. The as-cast substrate was soaked

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in DI water for at least 1 day before further use. To crosslink the substrate, it was cut into a proper size and immersed into a 5 wt% HDA/IPA solution for 24 hours. Afterwards, the membrane substrate was rinsed with DI water to wash away unreacted HDA and stored in fresh

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DI water prior to further modifications.

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2.3 Preparation of GO Laminar Composite Membranes Prior to GO deposition, the crosslinked substrate was modified with dopamine to increase its affinity with GO nanosheets. Dopamine was selected in view of its good adhesion property and simple deposition method. It might facilitate the deposition of GO flakes, so that the GO laminates could not be easily delaminated from the substrate. First, 0.2 g dopamine hydrochloride was dissolved in a 0.01 M Tris buffer of 100 mL at pH 8.5. The resulting solution 6

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was then deposited onto the top surface of the substrate at room temperature for 1 hour. After

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this, the substrate was rinsed with DI water to remove the residues.

For the preparation of GO laminar composite membranes, a 0.5 wt% GO aqueous solution was diluted and centrifuged at 10,000 rpm for 30 min. The centrifugation was used to remove big GO

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aggregates and facilitate the formation of a uniform GO selective layer [11]. The effects of centrifugation on the formation of GO laminar composite membranes and their performance are

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briefly provided in Figures S1 and S2. As a result, the lateral dimension of GO after centrifugation is around 1 µm. The GO nanosheets have a monolayer or double layer structure, as measured by AFM (Fig. S1).Subsequently, 1 wt% EDA was dissolved in a certain amount of the GO solution to crosslink the GO framework, thereby increased the mechanical strength of

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GO layer and prevented the swelling of GO laminates in the wet state as described elsewhere [12, 33-35]. The GO/EDA solution was then filtered through the dopamine-coated substrate in a dead-end filtration cell at 1 bar by means of pressure-assisted filtration based on our experiments

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using different coating methods. The resultant GO membrane has an area of about 9.62 cm2 when filtrating a GO solution with a loading of 20 mg/m2. Then the composite membranes were

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cured at 50 °C for 5 min in an oven to evaporate the residual water and EDA in the framework and to further stabilize the structure. The fabricated GO laminar composite membranes were preserved in DI water for later use. Fig. 1 illustrates the stepwise diagram to fabricate the GO laminar composite membranes.

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2.5 Characterizations

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Both top surface and cross-section morphologies of the membranes were observed using field emission scanning electron microscopy (FESEM, JEOL JSM-6700F). To prepare the samples,

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membranes were freeze-dried, fractured in liquid nitrogen and then coated with a layer of platinum using a JEOL JFC-1300 platinum coater. The variations of bulk chemistry of both pristine and HDA crosslinked substrates were examined using Fourier Transform Infrared Spectroscopy (FTIR, Bruker FTIR spectrometers, VERTEX 70/70v) in an attenuated total reflectance (ATR) mode, while the surface chemistry was analyzed using X-ray photoelectron spectroscopy (XPS) on a Kratos AXIS UltraDLD spectrometer (Kratos Analytical Ltd.) equipped with a monochromatized Al Kα X-ray source (1486.71 eV, 5 mA, 15 kV). In addition, the 8

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thicknesses of GO nanosheets were measured by atomic force microscopy (AFM, Bruker

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Dimension ICON) under the tapping mode.

The variation of microstructure as a function of membrane depth was studied by Doppler broadening energy spectroscopy (DBES) using position annihilation spectroscopy (PAS) coupled 22

Na was utilized as the

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with a variable mono-energy slow positron beam in our laboratory.

source of positrons and 30 distinct spectra were collected with each spectrum consisting of one

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million counts. The detailed procedures were given in the referenced literature [36, 37]. In this study, the depth profiles of the membranes were characterized by the S- and R-parameters of DBES. In general, the S-parameter refers to the free volume changes of the membrane as a function of positron penetration depth, while the R-parameter signifies the evolution of voids or

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large pores (nm-µm) along the membrane depth profile. The latter often indicates the changes in pore size and pore size distribution of a membrane greater than the interstitial space among polymer chains. The mean depth (Z) is calculated using the following equation with the incident

.

(1)

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=

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positron energy (E+) and average membrane density (ρ):

2.6 Pure Water Permeability (PWP) and Pore Size Distribution The pure water permeability (PWP, LMH/bar) of the membrane was determined using dead-end filtration cells with an applied trans-membrane pressure, ∆P (bar), of 15 bar at room temperature. The PWP was calculated using the following equation:

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PWP =

Q A∆ P

(2)

where Q (L/h) is the water flux at the permeate side and A (m2) is the effective filtration area of

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the membrane. The membranes were stabilized for 5 hours before taking any measurements. At least three membrane samples were measured for each condition to ensure the reproducibility

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and the average results were reported.

The mean effective pore size and pore size distribution of each membrane were determined using

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the solute rejection method as reported previously [38]. Various solutions containing PEGs and sugars with concentrations of 200 ppm were used as the feed solutions. Depending on the pore size distributions of the membranes, different sizes of organic solutes could be used. PEGs with larger Stoke diameters, were employed in determining the pore size distributions of the pristine and crosslinked Matrimid® membrane substrates, whereas smaller organic solutes were used for

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the GO laminar composite membranes. Table S1 summarizes the molecular weights (MW) and Stoke diameters (ds) of the smaller organic solutes. The Stoke diameters of the PEG solutes were

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calculated by the following equations [39-41]:

(3)

ds = 20.88×10−12 × M 0.587, (MW ≥ 100,000)

(4)

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ds = 33.46×10−12 × M 0.557, (MW ≤ 35,000)

Trans-membrane pressures of 5 bar and 15 bar were employed during the tests for (1) the pristine and crosslinked substrates and (2) GO laminar composite membranes, respectively, with prestabilization of 5 hours before taking any measurement. A total organic carbon analyzer (TOC ASI-5000A, Shimadzu, Japan) was used to determine the solute concentrations in both feed and

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permeate. The effective rejection coefficient, R (%), for each organic solute was obtained from Eq. 5:

 Cp  R = 1 −  ×100%  C  f  

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(5)

where Cf and Cp are the solute concentrations of the feed and permeate, respectively.

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Subsequently, a straight line was plotted by linear regression of the solute rejection, R, against the Stoke diameter on a log-normal probability paper. The molecular weight cut-off (MWCO),

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mean effective pore diameter (µ p) and the geometric standard deviation (σp) of a membrane were determined from this straight line. The MWCO is defined as the molecular weight of the solute where the rejection is 90% while µ p is the size of the solute where R=50%. σp is the ratio of solute sizes where R=84.13% and 50%. Afterwards, the pore size distribution of the membrane

dR(d p ) dd p

=

1 d p ln σ p

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was evaluated using Eq. 6:

 (ln d p − ln µ p )2  exp−  2 2(ln σ p ) 2π  

(6)

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where dp is the pore diameter.

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2.7 OSN Performance of GO Laminar Composite Membranes Since the as-prepared GO laminar composite membrane was originally preserved in DI water, solvent exchange before testing it in organic solvents was required to preserve the membrane microstructure. The membrane was immersed in the testing organic solvent/water mixtures with an increasing concentration gradient step by step and finally the membrane was preserved in the testing organic solvent before tests. This procedure was to minimize the effects of solvent11

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induced swelling on substrates and avoid the structural disruption of the GO framework. However, if hexane was the solvent, the cured membrane was directly immersed into it because

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the swelling effect of hexane on the membrane is relatively insignificant.

The OSN performance of the GO laminar composite membranes was determined using dead-end

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filtration cells with a trans-membrane pressure, ∆P, of 15 bar at room temperature. The pure solvent flux was calculated using Eq. (7)

=

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(7)

where Q (L/h) is the solvent flux at the permeate side and A (m2) is the effective filtration area of the membrane. The membranes were stabilized for 5 hours before taking measurements.

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The rejections to dyes and APIs were determined using feed solutions containing 50 ppm dyes or APIs under a trans-membrane pressure of 15 bar with pre-stabilization of 5 hours. The concentrations of both feed and permeate solutions were measured using a UV-Vis

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spectrophotometer (Pharo 300, Merck) according to the Beer-Lambert law. The rejections were

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then calculated using Eq. (5). More than three membrane samples were measured for each condition and the average results were reported. In addition, three 168-hour stability tests were also conducted after the 5-hour stabilization to ensure the reproducibility. Samples were collected every 12 hours during the tests, while the feed solution was refilled and its concentration was adjusted every 24 hours.

3. Results and Discussion 12

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3.1 Membrane Fabrication and Characterizations 3.1.1 Crosslinking of Membrane Substrates The successful crosslinking reaction between Matrimid® and HDA is confirmed by FTIR, as

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shown in Fig. 2. The absence of imide peaks at 1778 cm-1 (C=O stretching) and 1719 cm-1 (C=O stretching), the reduction of 1369 cm-1 (C-N stretching) as well as the presence of amide peaks at 1642 cm-1 (C=O stretching) and 1538 cm-1 (C-N stretching) suggest the change of the imide ring

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to the amide group during the crosslinking. This reaction is also confirmed by the doubling N/C

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ratio of the HDA crosslinked substrate as compared to the pristine one (Table S2).

3.1.2 Membrane Morphologies Fig. 3 displays the morphologies of the pristine, HDA crosslinked substrates and GO laminar composite membranes. The morphologies of the membrane substrates remain unchanged after the HDA crosslinking modification. Both substrates consist of relative dense top layers with a 13

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thickness of ~200nm and highly porous cross-sections. This type of structures generally makes the membrane substrates highly permeable with reasonable rejections. After the GO deposition, the as-prepared GO laminar composite membrane possesses an ultrathin selective layer of ~70

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nm on top of the substrate. Typical wrinkled and folded morphologies are observed due to the irregular stacking of GO nanosheets [42]. In addition, a slight increase in the ratio of O/C atomic

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contain many oxygen containing functional groups.

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concentration measured by XPS in Table S2 confirms the presence of GO flakes because they

3.1.3 PWP and Pore Size Distributions The PWP values and pore size distributions of the pristine, HDA crosslinked substrates and GO laminar composite membranes are shown in Fig. 4. Both the pristine and HDA crosslinked substrates have PWP values and pore sizes in the range of ultrafiltration. Interestingly, the PWP and MWCO values of the substrates become even higher after the crosslinking modification 14

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possibly due to: (1) the swelling effects induced by HDA and IPA and (2) the change of polarity of the membrane [20, 29]. However, since PEGs are adopted, which have weak interactions with the membrane, to determine the pore size distribution, the rejection to PEGs may not be

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significantly affected by the polarity of the membrane. Thus, the change in MWCO may mainly be attributed to the first reason. After the formation of the GO laminar selective layer, the pore size has a drastic reduction while its distribution becomes much sharper. As a result, the GO

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laminar composite membrane has a MWCO of 1243 Da and a PWP of 7.70 LMH/bar. However, this MWCO is determined using linear PEG molecules as solutes in aqueous systems by

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assuming no interactions between the membrane and solutes as well as treating the PEG solutes as spheres [35-37]. Thus, this MWCO is only an indication of membrane performance for its

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usage in aqueous nanofiltration.

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3.1.4 Membrane Microstructures Characterized by PAS

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To study the depth profile of microstructure and understand the evolution of pore size, the

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pristine and HDA crosslinked substrates as well as the GO laminar composite membrane are characterized by PAS. Two parameters, S and R, are evaluated. The S parameter is an indicator of free volume intensity where a larger S-parameter represents a higher free volume. Similarly, the R parameter represents the pore size distribution along the depth, and a larger R-parameter indicates a higher intensity of voids in the range of nm-µm.

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As shown in Fig. 5a, the S-parameter of the pristine substrate remains low along the depth. This can be attributed to the quenching effect of the polyimide membrane that traps positrons (e+) and induces severe chemical quenching to positronium formation [43]. However, the S-parameter

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alters after the HDA crosslinking modification; namely, its slope increases and its value becomes larger, as illustrated in the insert of Fig. 5a. These may be attributed to (1) the chemical change of polymeric backbone introduced by the HDA crosslinking reaction and (2) the effects of HDA-

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and IPA-induced chain swelling on free volume. As HDA converts the imide rings of Matrimid® to amide groups during the reaction, the quenching effect is significantly inhibited. This

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hypothesis is supported by FTIR and XPS data. In addition, consistent with the increases in PWP and MWCO after the HDA crosslinking modification (Fig. 4), the higher S parameter confirms a

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looser structure after the crosslinking due to the chain swelling induced by HDA and IPA.

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In contrast, the S profiles of the HDA crosslinked substrate and the GO laminar composite

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membrane exhibit a similar trend. The initial sharp increase is attributed to the scattering and back diffusion of positoniums near the membrane surface [36, 37]. Subsequently, a plateau is reached which represents the selective layer. Then the S-parameter attains a higher value at the

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bulk membrane substrate. A comparison of S-parameter values between the selective layers of the HDA crosslinked substrate and the GO laminar composite membrane indicates that the latter

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has a much lower S value than the former, suggesting that the GO laminar selective layer is much denser than the HDA crosslinked one.

The R-parameters of all membranes display a similar concave trend where it first decreases to the lowest level before a drastic increase, as depicted in Fig. 5b. The initial decrease and subsequent increase of the R-parameter are attributed to the dense and thin selective layer of the asymmetric membranes. Hence, the width of the valley in R-parameter can be used to interpret 18

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the thickness of the selective layer. The pristine and the HDA crosslinked substrates have very similar R profiles except the latter has a slightly large R value and a thicker selective layer because of the HDA- and IPA-induced swelling effects. In contrast, the GO laminar composite

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membrane has a different valley of R-parameter. Its selective-layer thickness becomes wider with a much lower R value as compared to the pristine and HDA modified substrates. This suggests that the selective layer becomes thicker with fewer or smaller voids as GO is assembled.

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In summary, the assembly of an ultrathin GO layer on top of the HDA crosslinked substrate results in the selective layer to be much dense and thick, thus the pore size distribution of the GO

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laminar composite membrane becomes narrow.

3.2 Pure Solvent Fluxes

In order to evaluate the OSN performance of GO laminar composite membranes in both polar

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and nonpolar organic solvents, ethanol, IPA and hexane are chosen as benchmark solvents. Table 1 tabulates the physicochemical properties of these solvents such as viscosity, kinetic diameter and solubility parameter [44-46], while Fig. 6 summarizes their pure solvent fluxes. Generally, a

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solvent with a small kinetic diameter, low viscosity and high affinity towards the selective layer, which is reflected from the closeness of their solubility parameters, is able to pass through the

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membrane with relative ease at a high flux [44, 45]. Among the three solvents, ethanol gives the highest flux of 24.89 L m-2 h-1 due to its low viscosity, small kinetic diameter and the highest affinity to GO (i.e., |

!"#

%$−

'( |

= 1.1) [47]. In comparison, IPA has a higher viscosity,

which is almost double the viscosity of ethanol, larger kinetic diameter and relatively lower affinity to GO (i.e., |

*+

−

'( |

= 1.9). As a result, the IPA flux is 7.95 L m-2 h-1, which is 68%

lower than that of ethanol. As hexane has the lowest viscosity and the smallest kinetic diameter

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among these three solvents, it can still pass through the membrane with a relatively high flux of ! -"#

−

'( |

= 10.5).

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12.08 L m-2 h-1 despite its poor affinity to GO (i.e., |

The pure IPA flux as a function of trans-membrane pressure is further investigated. As shown in

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Fig. 6b, the pure IPA flux increases logarithmically. Theoretically, the pure solvent flux is proportional to the trans-membrane pressure. However, real membranes are usually compacted at high pressures which may result in the attenuated flux. A similar behavior has also been reported in aqueous systems [48].

3.3 OSN Separation Performance

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Table 2 summarizes the molecular weights, structures and solubility parameters of the selected dyes to evaluate the OSN performance of GO laminar composite membranes [49, 50]. Each of them is dissolved in IPA with a concentration of 50 ppm as the feed solution. Since separation

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performance is normally a function of (1) solute molecular weight, (2) its size and (3) affinity with the membrane as well as (4) the affinity between the solvent and membrane, one can fix the affinity between the solvent and membrane by using the same solvent, i.e., IPA, and the same

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GO laminar composite membrane, and determining the effects of solute’s molecular weight, size and affinity toward the membrane on OSN performance. Herein, the selected dyes are classified

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into 2 groups: one consists of dyes with roughly the same molecular weight, while the other

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comprises dyes with similar affinity based on their similarity in solubility parameter.

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3.3.1 Dyes with Similar Molecular Weights Fig. 7a shows the separation performance of GO laminar composite membranes towards a group of dyes with roughly the same molecular weight of 350 Da. They are solvent blue 35, safranin O

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and orange II sodium salt with charge characteristics of neutral, positive and negative, respectively. Among them, safranin O shows the highest rejection of 86.52%, followed by orange II sodium salt (56.60%) and the lowest one is solvent blue 35 with a rejection of only

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4.39%. Apparently, the Donnan exclusion in organic solvents is not so significant because of the order of rejection is totally different from what in aqueous systems. Hypothetically, if the dyes

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were fully disassociated in organic solvents, the membrane rejection towards those dyes would be in the order of orange II sodium salt (negative) > solvent blue 35 (neutral) > safranin O (positive) because the functional groups on GO surface would also be ionized and make the membrane negatively charged [12, 13, 26]. Conversely, the membrane shows nearly zero

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rejection towards the neutral dye of solvent blue 35, a high rejection towards the positively charged dye of safranin O and an average rejection towards the negatively charged dye of orange II sodium salt. This surprising phenomenon is probably due to the fact that IPA has a lower

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dielectric constant than water [2, 51-53]. As a result, these dyes are not fully disassociated in IPA and the Donnan exclusion becomes less effective, while the size exclusion and solute-membrane

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affinity turn out to be the dominant factors in determining OSN performance.

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Despite the three selected dyes have a similar molecular weight, they have different molecular sizes and structures. Hence, their molecular sizes and affinities towards the membrane also affect the separation performance. In the case of safranin O, though its solubility parameter is the −

'( 0

= 0.2), it possesses a relatively large molecular size and

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nearest to GO (i.e., 0

1"23"#4# (

sterically-hindered bulky structure, making it difficult to pass through the transport channels in

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the GO layer. Thus, the membrane has a relatively high rejection to safranin O. Interestingly, the rejection to solvent blue 35 is much lower than that to safranin O because the former has a

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linearly conjugated ring structure and the freely-rotating aliphatic groups. Consequently, the former has a lower steric hindrance than the latter to pass through the porous channels across the GO selective layer. A similar phenomenon has also been reported in previous studies [50, 54]. As for orange II sodium salt, it has the smallest molecular size but it can still be rejected by the membrane with a reasonable rejection of 56.60% possibly because it has a lower affinity to the membrane compared to the rest two dyes, as0

$3"#6 **

−

'( 0

= 3.8.

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It is also important to note that despite the membrane has an MWCO of 1243 Da determined in aqueous systems, it can still retain smaller molecules at relatively high rejections in organic solvents. This phenomenon may be ascribed to the different behaviors of the membrane in

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different solvents. It has also been reported that the MWCO determined in one solvent may not be the same with that in another solvent [53, 55, 56]. In addition, the MWCO obtained in this study uses PEG molecules, which are generally linear and may easily pass through the transport

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chanels of GO. Conversely, dye molecules are usually bulkier, increasing their steric hindrance and resistance to permeate across the selective layer. Furthermore, there are several assumptions

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in the mathematical model for determinating the MWCO, which may contribute to the inaccuracies in the final result. Neverthless, the use of PEG to determine an MWCO of a membrane is still valuable as it provides the preliminary membrane performance.

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3.3.2 Dyes with Similar Solubility Parameters

Three dyes of similar solubility parameters are selected to study the effects of molecular weight and size on OSN separation performance, they are orange II sodium salt (350.32 Da), rhodamine

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B (479.02 Da) and remazol brilliant blue (626.54 Da). As illustrated in Fig. 7b, the membrane rejections towards those dyes increase with molecular weight and size. Starting from the smallest

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dye, orange II sodium salt, the rejection of GO laminar composite membranes towards it is 56.60%. By increasing the molecular weight and size to rhodamine B, the rejection increases to 66.95%. If a larger dye, remazol brilliant blue, is utilized, the rejection can even reach 97.11%. This result suggests that the coupling of both molecular weight and size significantly affects OSN separation performance due to the enlarged 3-dimensional molecular size and the increased molecular weight. Therefore, with solutes having similar affinity towards the membrane, the

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OSN separation performance strongly depends on the coupling of their molecular weights and 3-

3.4 Applications to Concentrate APIs and a Food Additive

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dimensional sizes.

Since one of important OSN applications is to recycle the mother liquor and concentrate pharmaceuticals and food additives with less energy consumption. To demonstrate the

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applicability, the newly developed GO laminar composite membranes are tested by using IPA solutions containing various APIs and a hexane solution containing a food additive. Four

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commonly used antibiotics, tetracycline, rifampicin, roxithromycin and spiramycin together with one vitamin, vitamin B12, are selected. Another food additive extracted from soybeans, L- -

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lecithin, is also used to be separated from hexane. Fig. 8 illustrates their molecular structures.

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IPA is used as the solvent in this study because there is a trend to shift the commonly used organic solvents in the pharmaceutical industry from hazardous organic solvents to “greener”

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solvents, such as ethanol, IPA and n-butanol [57-59]. The selected APIs are dissolved in IPA with a concentration of 50 ppm as feed solutions. Fig 9 shows the testing results at a transmembrane pressure of 15 bar. The OSN separation performance of the GO laminar composite

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membrane towards tetracycline is reasonable with a rejection of 65.80%. The rejections towards rifampicin and spiramycin can reach around 82-85%, which are promising for concentrating the

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mother liquor in their production processes to minimize energy-cost. Moreover, roxithromycin and Vitamin B12 can be mostly rejected with rejections of 92.21% and 95.34%, respectively. Fig.

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S3 documents their UV-vis spectra and color changes from the feeds to the permeates.

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To mimic the industrial production process, L-

-lecithin is dissolved in hexane with a

concentration of 2 g/L and filtered through the GO laminar composite membrane at a transmembrane pressure of 15 bar. The collected permeate is clear as displayed in Fig. S3. The

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membrane can reject 98.44% of L- -lecithin in the feed solution. This result elucidates the potential of utilizing the as-prepared GO laminar composite membrane to effectively concentrate L- -lecithin mother liquor and to cut down the cost on energy input for evaporating the solvents.

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various industries involving organic solvents.

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Clearly, the newly developed GO laminar composite membranes can be potentially applied in

3.5 7-Day Stability Tests

To evaluate the long-term stability of GO laminar composite membranes, three 7-day stability tests are conducted with a feed solution of vitamin B12 in IPA and ethanol at 50 ppm as well as

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lecithin in hexane at 2 g/L under 15 bar. Fig. 10 shows the evolution of flux and rejection with vitamin B12 in IPA as a function of time. The results of the other two stability tests are shown in the supporting information (Fig. S4 and Fig. S5). Initially, the flux and rejection are 7.05 L m-2hand 96.18 %, respectively, which are relatively high. The flux and rejection fluctuate in a very

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1

narrow range in the following days, indicating that an equilibrium is being established. During

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the 7-day tests, the membrane exhibits a good rejection with a reasonable flux in IPA, ethanol and hexane, suggesting its integrity is maintained. These results confirm good stability of the GO laminar composite membrane in IPA, ethanol and hexane under a high pressure of 15 bar for a reasonable duration and assure its potential for industrial applications.

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3.6 Benchmark

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Table 3 compares the separation performance of the newly developed GO laminar composite membranes with other reported OSN membranes for the separation of solute/IPA mixtures. The

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newly developed GO laminar membranes have higher rejections with satisfactory permeances compared to other polymeric membranes reported in literatures.

Pure IPA

Molecule Rejection

Membrane

permeance

Solute

weight (g

Ref. (%)

(Lm-2h-1bar-1)

mol-1)

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0.48

PEG600

600

~ 66

[46]

MPF-50

0.72

Rose bengal

1017

98.1

[60]

StarmemTM 122

1.13

Rose bengal

1017

99.9

[60]

PPSf hollow fiber

0.02

Rose bengal

1017

98.6

[61]

PDMS/PI

0.2

Rose bengal

1017

100

[62]

polypyrrole/PAN-H

0.79

Rose bengal

1017

99.2

[63]

PBI

0.15

Rose bengal

1017

82

[18]

626

97.11

0.53

This

Roxithromycin

837

92.21

Vitamine B12

1355

95.34

work

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4. Conclusions

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brilliant blue

GO/PI

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Remazol

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Puramem®

In this work, an ultrathin layer of GO framework is formed on HDA crosslinked Matrimid® membrane substrates and utilized for OSN applications. The PWP value of the GO laminar

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composite membrane is 7.70 LMH/bar with a MWCO of 1243 Da. The membrane functions well in both polar and nonpolar solvents as demonstrated using ethanol, IPA and hexane as

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benchmark solvents. To illustrate the transport mechanism, several dyes with similar molecular weight or solubility parameter are separated from IPA. The results show that the Donnan exclusion becomes less effective in OSN compared to that in aqueous systems, while the size exclusion and solute-membrane affinity turn out to be the dominant factors in determining the separation performance. Solutes with a large size and bulky structure or low affinity to the membrane tend to achieve higher rejections. In addition, satisfactory results have been

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demonstrated by using the GO laminar composite membrane to concentrate a variety of API and food additive solutions. The newly developed membrane also exhibit structural integrity and OSN performance in IPA for at least 168 hours (one week) at 15 bar. Therefore, the novel GO

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laminar composite membrane is promising in concentrating and purifying of organic solvents in pharmaceutical, food and petrochemical industries.

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Acknowledgement

The authors would like to acknowledge the National Research Foundation, Prime Minister's

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Office, Singapore for funding this research under its Competitive Research Program for the project entitled, “Development of solvent resistant nanofiltration membranes for sustainable pharmaceutical and petrochemical manufacture”; (CRP Award no. NRF-CRP14-2014-01 (NUS grant number: R-279-000-466-281)). The authors are also grateful to Mr. Yuqi Gao and Dr. Yu

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Zhang for their valuable suggestions and assistance in this work.

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