Lin Tan

Star-shaped poly(2-methyl-2-oxazoline)-based films: rapid preparation and effects of polymer architecture on antifouling properties

Development of surfaces with antifouling properties is of great interest in biomedical applications. In this paper, the research was aimed at rapid preparation of poly(2-methyl-2-oxazoline)-based antifouling coating. We designed and synthesized a set of well-defined multiarm star copolymers hyperbranched poly(ethylenimine)-graft-poly(2-methyl-2-oxazoline) (PEI-g-PMOXA) with different PMOXA grafting ratios and chain lengths. The cytotoxicity of the polymer was tested and the PMOXA-based films were successfully deposited rapidly onto substrates via a simple one-step dopamine-assisted codeposition method. The effect of polymer architecture (linear PMOXA with different molecular weights, star PMOXA with different PMOXA grafting ratios and arm lengths) on deposited films with respect to their deposition kinetics, surface composition, wettability, morphology, cytotoxicity, and antifouling properties was investigated systematically. The antifouling properties of PMOXA-based films were found to be dependent on the surface PMOXA chain densities, which were controlled by the PMOXA grafting ratios and chain lengths. Moreover, the star PMOXA structures gave the surfaces with higher PMOXA chain densities and enhanced antifouling properties compared to the linear ones. Among the star copolymers, PEI-g(70)-PMOXA(5K)/polydopamine and PEI-g(70)-PMOXA(7K)/polydopamine deposited films showed the highest resistance to protein adsorption (96-99% relative to the bare gold surface) and cell attachment (97-99% relative to the bare glass surface), as well as complete inhibition against platelet adhesion. At last, the stability test results showed that the PMOXA-based film exhibited superior stability in long-term applications than the poly(ethylene glycol)-based film.

Preparation and characterizations of poly(2-methyl-2-oxazoline) based antifouling coating by thermally induced immobilization

Poly(2-methyl-2-oxazoline) (PMOXA) has been proved to be a kind of potential antifouling coating material. In this work, a series of comb copolymers, poly[(2-methyl-2-oxazoline)-random-glycidyl methacrylate] (PMOXA-r-GMA), with a variety of compositions were synthesized by free radical polymerization of the oligo(2-methyl-2-oxazoline) methacrylate macromonomer and glycidyl methacrylate, and then characterized and used to coat silicon/glass surfaces. A one-step coating procedure by a simple annealing protocol was used to yield covalent and cross-linked PMOXA-based antifouling coatings. The coatings were rigorously characterized in terms of the surface chemical composition, hydrophilicity, thickness and morphology using X-ray photoelectron spectroscopy (XPS), the water contact angle (WCA) test, ellipsometry and atomic force microscopy. The results demonstrated that the PMOXA-r-GMA brushes could successfully be bonded onto silicon/glass surfaces. Finally, the fouling resistance ability of the modified surface was evaluated by analyzing the adsorption of bovine serum albumin protein, bacterial cell attachment and platelet adhesion, which indicated that the modified silicon/glass surfaces had a superior resistance to protein, bacterial cell and platelet adsorption, and the performance of fouling resistance was enhanced with the content of PMOXA segments in the copolymers.

Antifouling property of monothiol-terminated bottle-brush poly(methylacrylic acid)-graft-poly(2-methyl-2-oxazoline) copolymer on gold surfaces

In this study, a series of well-controlled bottle-brush polymers, poly(methylacrylic acid)-g-poly(2-methyl-2-oxazoline) with monothiol-terminated group ((PMAA-g-PMOXA)-SH) were synthesized by using reversible addition-fragmentation chain transfer (RAFT) polymerization and cationic ring-opening polymerization (CROP). (PMAA-g-PMOXA)-SH were grafted to the surface of gold sensors in in situ aminolysis reactions. Cyclic voltammetry (CV), X-ray photoelectron spectroscopy (XPS), variable angle spectroscopic ellipsometry (VASE), water contact angle (CA), and atomic force microscopy (AFM) were used to characterize the copolymer modified gold sensor. The protein-resistant properties were investigated by surface plasmon resonance (SPR), and platelet adhesion was observed by scanning electron microscopy (SEM). Compared with the bare gold sensor, the (PMAA20-g-PMOXA12)-SH modified gold sensor can reduce the levels of fibrinogen (Fg), bovine serum albumin (BSA), and lysozyme (Lyz) adsorption by 96.5 ± 3.1%, 85.8 ± 5.7%, and 49.4 ± 1.6%, respectively. Meanwhile, the (PMAA20-g-PMOXA12)-SH modified gold sensor also possesses excellent resistance to platelet adhesion. All these data demonstrate that this simple method is feasible, and that a bottle-brush (PMAA-g-PMOXA)-SH modified gold sensor has potential applications in biosensors and biomedical areas.

Brush-like copolymer as a physically adsorbed coating for protein separation by capillary electrophoresis

A brush-like copolymer consisting of poly(ethylene glycol) methyl ether methacrylate and N,N-dimethylacrylamide (PEGMA-DMA) was synthesized and used as a novel static physically adsorbed coating for protein separation by capillary electrophoresis for the first time, in order to stabilize electroosmotic flow (EOF) and suppress adsorption of proteins onto the capillary wall. Very stable and low EOF was obtained in PEGMA-DMA-coated capillary at pH 2.2-7.8. The effects of molar ratio of PEGMA to DMA, copolymer molecular mass, and pH on the separation of basic proteins were discussed. A comparative study of bare capillary with PEGMA-DMA-coated capillary for protein separation was also performed. The basic proteins could be well separated in PEGMA-DMA-coated capillary over the investigated pH range of 2.8-6.8 with good repeatability and high separation efficiency because the copolymer coating combines good protein-resistant property of PEG side chains with excellent coating ability of PDMA-contained backbone. Finally, the coating was successfully applied to the fast separation of other protein samples, such as protein mixture and egg white, which reveals that it is a potential coating for further proteomics analysis.

Assembly of poly(dopamine)/poly(acrylamide) mixed coatings by a single-step surface modification strategy and its application to the separation of proteins using capillary electrophoresis.

In this work, a facile approach was developed to modify a fused-silica capillary inner surface based on poly(dopamine) and poly(acrylamide) mixed coatings for protein separation by capillary electrophoresis. The surface morphology, thickness, and chemical components of poly(dopamine)/poly(acrylamide) mixed coatings on glass slides and silicon wafers were studied by atom force microscopy, ellipsometry, and X-ray photoelectron spectroscopy, respectively. The hydrophilicity and stability of the mixed coatings on glass slides were investigated by static water contact angle measurements. A comparative study of electroosmotic flow showed that the poly(dopamine)/poly(acrylamide) mixed coatings could provide effective suppression of electroosmotic flow. Meanwhile, the fast and efficient separations of the mixture of four alkaline proteins, the mixture of acidic, basic, and neutral proteins and egg white proteins were obtained by capillary electrophoresis. Furthermore, the consecutive protein separation runs and low RSDs of migration time demonstrated that these poly(dopamine)/poly(acrylamide) mixed coatings were capable of minimizing protein adsorption during the protein separation by using capillary electrophoresis.

A high efficiency approach for a titanium surface antifouling modification: PEG-o-quinone linked with titanium via electron transfer process

We explored a novel approach for the modification of titanium surfaces to improve the biocompatibility and antifouling properties using PEG-catechol. As is well-known, PEG-catechol can easily self-assemble onto titanium surfaces. However, the higher grafting density by this approach is hard to obtain. In our paper, o-quinone (the oxide of catechol) as the adhesive segment was used for the first time to graft PEG brushes onto titanium surfaces using the electroreduction process. Variable angle spectroscopic ellipsometer showed that the ultrahigh-density PEG brush adlayer could be grafted to the titanium surface when the o-quinone segment performs electrochemical reduction on the titanium. We called the adlayers that grafted onto the titanium surfaces by this kind of approach, electro-assembly monolayers (e-AMs). This distinguishes it from the PEG-catechol self-assembly monolayers (SAMs). The XPS, AFM and WCA techniques were also used to characterize the coating grafted onto the titanium surfaces via the two different ways. A clear result is that the grafted density of e-AMs can be higher than that of SAMs, and the grafted density of the e-AMs can be easily modulated. In addition, the long-term stability of e-AMs against full blood serum, FITC marked BSA and platelet adsorption was better than that of the SAMs.

Surface modification by grafting of poly(SBMA-co-AEMA)-g-PDA coating and its application in CE.

In this paper, a novel copolymer consisting of sulfobetaine methacrylate (SBMA) and 2-aminoethyl methacrylate (AEMA) named as poly(SBMA-co-AEMA) was synthesized by conventional free-radical polymerization, the poly(SBMA-co-AEMA) zwitterionic copolymer was immobilized onto glass slides surface through polydopamine (PDA)-anchored coating and formed poly(SBMA-co-AEMA)-g-PDA coating. The defined copolymer was characterized by nuclear magnetic resonance hydrogen spectroscopy (1H NMR) and gel permeation chromatography. The surface morphology, thickness, and chemical component of poly(SBMA-co-AEMA)-g-PDA coating were studied by atom force microscope, ellipsometry, and X-ray photoelectron spectroscopy, respectively. The hydrophilicity and stability of these coatings were investigated by static water contact angles. And finally, the poly(SBMA-co-AEMA)-g-PDA coating was successfully applied into capillary inner surface for suppression electro-osmotic flow and protein separation by capillary electrophoresis.

Application of the copolymers containing sulfobetaine methacrylate in protein separation by capillary electrophoresis

This study describes the formation of highly efficient antiprotein adsorption random copolymer coating of poly(N,N-dimethylacrylamide-co-sulfobetaine methacrylate) (poly(DMA-co-SBMA)) on the fused-silica capillary inner wall. Firstly, the poly(DMA-co-SBMA)s with different feed ratio (SBMA/DMA) were synthesized via the reversible addition fragmentation chain transfer polymerization. And then, X-ray photoelectron spectroscopy (XPS) and water contact angle (CA) were used to investigate the composition and hydrophilicity of poly(DMA-co-SBMA) coating formed on the glass slide surfaces. CA measurements revealed that the poly(DMA-co-SBMA) coating became more hydrophilic with the increment of feed ratio (SBMA/DMA), and at the same time, the XPS results showed that the coating ability was also increased with the increment of feed ratio. Followed, the copolymer was applied to coat the fused-silica capillary inner wall, and the coated capillary was used to separate the mixture of proteins (lysozyme, cytochrome c, ribonuclease A, and α-chymotrypsinogen A) in a pH range from 3.0 to 5.0. Under the optimum conditions, an excellent separation of basic proteins with peak efficiencies ranging from 551,000 to 1509,000 N/m had been accomplished within 10 min. Furthermore, the effect of coating composition on protein separation was also investigated through the comparison of separation efficiency achieved by using bare, PSBMA- and poly(DMA-co-SBMA)-coated capillary, respectively.

Quality testing of human albumin by capillary electrophoresis using thermally cross-linked poly(vinyl pyrrolidone)-coated fused-silica capillary

To detect the quality of medicinal human albumin by capillary electrophoresis, we produced a fused-silica capillary coated with thermally cross-linked poly(vinyl pyrrolidone) to prohibit protein adsorption. This type of capillary was easily obtained by injecting an aqueous poly(vinyl pyrrolidone) solution into a fused-silica capillary and thermally annealing it at 200°C. Notably, stable and low electro-osmotic flow was obtained in the poly(vinyl pyrrolidone)-coated capillary at pH 2.20-9.00, and the separation of a mixture of four basic proteins indicated that the poly(vinyl pyrrolidone)-coated capillary exhibits excellent repeatability and separation efficiency; moreover, the separation of these four basic proteins could even be achieved at pH 7.00. The protein recovery percentage of human serum albumin in a single-protein solution and a mixed blood proteins solution was determined to be 97.03 and 95.40% in the poly(vinyl pyrrolidone)50-3 (representing the concentration of the capillary-injected poly(vinyl pyrrolidone) aqueous solution, 50 mg/mL, and thermal annealing time, 3 h) capillary, respectively. Based on these results, we used the poly(vinyl pyrrolidone)50-3-coated capillary to quantify the protein content of human albumin, and the results obtained from run to run, day to day and capillary to capillary demonstrated that the coated capillary could be used for quality testing commercially available human albumin.

Stable antifouling coatings by hydrogen-bonding interaction between poly(2-methyl-2-oxazoline)- block -poly(4-vinyl pyridine) and poly(acrylic acid)

Surface modified with so-called protein-repellent or antifouling polymers has become indispensable for the development of modern therapeutic and diagnostic medical devices. In this work, a series of novel well-defined poly(2-methyl-2-oxazoline)-block-poly(4-vinyl pyridine) (PMOXA-b-P4VP) diblock copolymers were synthesized by using copper-catalyzed azide-alkyne cycloaddition reaction of α-alkynyl-PMOXA and ω-N3-P4VP, in which α-alkynyl-PMOXA and ω-N3-P4VP were prepared by cationic ring opening polymerization and atom transfer radical polymerization, respectively. Stable coatings were formed when dropping PAA solution on the top of PMOXA-b-P4VP pre-coatings, due to hydrogen-bonding interaction between P4VP and poly(acrylic acid) (PAA). The long-term stability of these PMOXA-b-P4VP/PAA coatings showed that increasing PMOXA chain length can improve not only the hydrophilicity but also the stability of the coatings. This simple method can form stable coatings on either inorganic (such as, silicon wafer and coverslip) or organic material [such as, poly(methyl methacrylate) sheet] surface. At the same time, for the high-hydratability of PMOXA chains, these crosslinked coatings showed well protein-resistant and platelet/cell-repellent properties, and the antifouling properties and long-term availability were enhanced increasing PMOXA polymerization degree.