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One-step modification of nano-polyaniline/glucose oxidase on double-side printed flexible electrode for continuous glucose monitoring: Characterization, cytotoxicity evaluation and in vivo experiment.
Biosensors and Bioelectronics ( IF 12.6 ) Pub Date : 2020-06-29 , DOI: 10.1016/j.bios.2020.112408
Yu Cai 1 , Bo Liang 1 , Shidie Chen 1 , Qin Zhu 1 , Tingting Tu 1 , Ke Wu 2 , Qingpeng Cao 1 , Lu Fang 3 , Xiao Liang 2 , Xuesong Ye 1
Affiliation  

The single-step modification of the nanostructured polyaniline (PANI)/glucose oxidase (GOD) enzyme on double-sided, screen-printed, flexible electrodes doped with Prussian blue (PB), has been achieved and successfully applied in continuous glucose monitoring in vivo, and its biocompatibility has been evaluated systematically. The proposed fabrication procedure is simple, low cost, and suitable for large-scale production. PB doped with carbon ink catalyzes the reduction of hydrogen peroxide (H2O2) in low-voltage conditions, which could help eliminate interferences. And the PANI/GOD nanostructure makes the GOD enzyme more stable for long-term, in vivo monitoring. More importantly, a polyurethane (PU) layer is deposited on the electrode's surface as a diffusion limiting membrane that enhanced the linear range and biocompatibility. In tests in vitro, the proposed biosensor achieved a linear range of 0–12 mM and a good sensitivity of 16.66 μA·mM−1·cm−2(correlation coefficient R2 = 0.9962) with an excellent specificity to glucose. The biosensor exhibits long-term stability, with a maximum lifespan of 14 days when stored in phosphate buffer solution at 4 °C, and achieves a sensitivity of 120%. The biocompatibilities of the electrode materials have also been systematically evaluated in cytotoxicity and cell adhesion tests to ensure the safety of implantation. In experiments in vivo, the biosensor can successfully monitor the glucose level fluctuation of rats after 24 h following implantation. Overall, the biosensor fabricated with the double-side, screen-printing process, satisfies the glucose monitoring range in vivo and eliminates various types of interference, thus establishing a new, large-scale production procedure for flexible in vivo biosensors.



中文翻译:

双面印刷柔性电极上的纳米聚苯胺/葡萄糖氧化酶的一步修饰,用于连续葡萄糖监测:表征,细胞毒性评估和体内实验。

在掺杂有普鲁士蓝(PB)的双面丝网印刷柔性电极上,纳米结构聚苯胺(PANI)/葡萄糖氧化酶(GOD)酶的单步修饰已实现,并成功应用于体内连续葡萄糖监测,其生物相容性已得到系统评价。所提出的制造过程简单,成本低并且适合大规模生产。掺碳墨的PB催化过氧化氢(H 2 O 2)在低压条件下,这有助于消除干扰。PANI / GOD纳米结构使GOD酶更稳定,可进行长期体内监测。更重要的是,聚氨酯(PU)层作为扩散限制膜沉积在电极表面,增强了线性范围和生物相容性。在体外测试中,拟议的生物传感器的线性范围为0–12 mM,灵敏度为16.66μA·mM -1 ·cm -2(相关系数R 2 = 0.9962)对葡萄糖具有优异的特异性。该生物传感器具有长期稳定性,当将其存储在4°C的磷酸盐缓冲溶液中时,最长使用寿命为14天,灵敏度达到120%。电极材料的生物相容性也已在细胞毒性和细胞粘附试验中得到系统评估,以确保植入的安全性。在体内实验中,生物传感器可以成功监测植入后24小时大鼠的葡萄糖水平波动。总体而言,采用双面丝网印刷工艺制造的生物传感器满足了体内葡萄糖监测范围并消除了各种类型的干扰,从而为柔性体内生物传感器建立了新的大规模生产程序。

更新日期:2020-07-05
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