The Polymerization Of Biocompatible Zwitterionic Gel And Its Application Research In Implantable Glucose Sensors

In the development of implantable biosensors,the long-time stability in vivo maybe is the most challenging issue,especially when other requirements like sensitivity,linear range,accuracy etc.have been greatly improved over the past few decades.The sensitivities of those sensors have exceeded clinical needs for a long time.Sensors work under complicated physical conditions.Reasons like foreign body reaction(FBR)could directly cause the failures of enzyme biosensors in vivo.Nonspecific protein adsorption(biofouling),as one of the first steps of FBR during implantation,plays a key role.Althrough numerous materials have been developed to protect surfaces from nonspecific protein adsorption,few has been put onto implantable sensors.How those materials can be applied to sensors and their long term impact on implantable sensors remain unknow.In this work,Sulfobetaine methacrylate(SBMA),a typical zwitterionic monomor had been coated to biosensors by electro-polymerization,electrochemically induced atom transfer radical polymerization(eATRP).Both the features of polymer layers and the in vivo,in vitro impact of those coatings on biosensors had been studied.First,SBMA monomer had been polymerizated on the surface of matal electrods by typical electro-polymerization.The results showed that with presence of Zn2+,SBMA monomer was polymerized on the anode by cyclic voltammetry(CVA).The thickness was determined by CVA cycles.Best antifouling achieved by 2 cycles of CVA with a polymer layer thickness of 21 nm.The relative nonspecific protein adsorption was about 21.4%.Additional stability test showed that glucose sensor with this hydrogel coating prolonged the life of glucose sensor in full blood serum at 37℃.Second,eATRP was applied to polymerize SBMA(pSBMA)on gold electrodes.The relationship of applied voltage,polymerization time with polymer layer thickness and anti-biofouling performance was inspected.The performences of electrodes with SBMA coating in vitro and in vivo have been studied as well.Results revealed that SBMA was polymerized on Au electrodes surfaces.Polymerization speed was controlled by applid voltage.Protein absorption was reduced to 0.8%in Enzyme-linked immunosorbent assay(ELISA),which was a better result than most of the previous researches.Further in vitro and in vivo impedance-time scan showed that pSBMA coating reduced pre-stable period of those eletrodes to minutes.The total impedance decreased as well.pSBMA coatings effectively delayed sensitivity decay of electrodes.Animal experiments shows the same results.Third,a versatile fabrication method of preparing enzyme-based biosensors and a refined overall bromination were developed for the first time.eATRP was applied to polymerize the zwitterionic SBMA monomers on coarse enzyme-based electrode surfaces.ELISA results show that the hydrogel coating could reduce biofouling effectively while naked Au electrodes and Polyurethane(PU)coating absorb protein strongly.The treatment of overall bromination reduced defeats on polymer layers surfaces and the antifouling performences of pSBMA coating increased greatly.Electrodes with 3 hours of polymarition under the applid potencial of-0.4 V repelled over 99%nonspecific protein adsorption.In votro experiments,pSBMA coated sensor maintained 94%relative sensitivities after 15 days soaking in undeluted bovine serum in 37℃ and the overall sensitivity drift was 7%which was better than commercially available Dexcom G4 glucose sensors.Meanwhile,the PU-coated sensors lost 40%of the original sensitivities.