一种新型分离传感膜的制备及其血糖的动态监测

doi:10.11949/0438-1157.20221096

摘要/Abstract

摘要：

血糖是临床手术中非常重要的生理指标之一，其不仅能灵敏反映术中患者的肾脏功能情况，还直接影响了术后愈合及生理康复。然而，现有的临床检测设备，如血糖仪、生化分析仪等，仅能间歇性反馈检测结果，难以实现术中病患血糖的动态监测。针对以上难题，提出将膜分离技术与生物传感技术相结合，构建可同步实现全血动态分离与血糖在线监测的分离传感膜。通过层层自组装法将普鲁士蓝(PB)纳米颗粒和金(Au)纳米颗粒原位共生长在钇稳定的氧化锆(YSZ)陶瓷中空纤维膜上，探究了不同组装层数的PB/Au对分离传感膜的表面亲疏水性的影响，评估最佳制膜条件下的血浆分离效果与血糖电化学检测性能。结果表明，当PB/Au组装层数为60层时所得分离传感膜具有最佳的亲水性，且能完全截留住全血中的红细胞、白细胞及血小板。该分离传感膜对葡萄糖的检测灵敏度为0.876 μA/(mmol/L)，检测范围达到1~15 mmol/L，并能同步实现真实人血样本的动态分离与检测过程。

关键词: 膜, 传感, 血液, 葡萄糖, 纳米材料

Abstract:

Blood glucose is one of the most important physiological indicators. In clinical surgery, blood glucose can sensitively reflect the kidney function of patients to affect the postoperative healing and physiological. However, the existing clinical testing equipment, such as blood glucose meters, biochemical analyzers, etc., can only provide intermittent feedback of test results, and it is difficult to achieve dynamic monitoring of patients’ blood sugar during surgery. As they can only collect intermittent feedback of detection results rely on discrete index points. In view of the above problems, this work proposed the combination of membrane separation technology and biosensing technology to construct a separation-sensing membrane which can synchronously realize dynamic separation of whole blood and online monitoring of blood glucose. Prussian blue (PB) nanoparticles and gold (Au) nanoparticles were grown in situ and synchronously on zirconia ceramic hollow fiber membrane (YSZ) via layer-by-layer self-assembly method. The effect of PB/Au on the hydrophilicity and hydrophobicity of the sensing membrane was investigated, and the plasma separation effect and blood glucose electrochemical detection performance were evaluated under the optimal membrane preparation conditions. The results showed that the best condition was 60 layers which can completely reject all the red blood cells, white blood cells and platelets in the whole blood. The separation-sensing membrane showed a sensitivity of 0.876 μA/(mmol/L), a liner range of 1—15 mmol/L to blood glucose and realized dynamic separation and detection in real human blood samples.

Key words: membrane, sensing, blood, glucose, nanomaterials

中图分类号:

TP 212.3

张静, 刘涛, 张伟, 储震宇, 金万勤. 一种新型分离传感膜的制备及其血糖的动态监测[J]. 化工学报, 2023, 74(1): 459-468.

Jing ZHANG, Tao LIU, Wei ZHANG, Zhenyu CHU, Wanqin JIN. Preparation of a novel separation-sensing membrane and its dynamic monitoring of blood glucose[J]. CIESC Journal, 2023, 74(1): 459-468.

图/表 15

图1 分离传感膜的分离原理示意图（a）及传感原理示意图（b）

Fig.1 Schematic illustration of separation principle (a) and sensing principle (b) of separation-sensing membrane

图2 PB/Au/YSZ分离传感膜的制备流程示意图及实物图

Fig.2 Schematic diagram of the preparation process and photograph of PB/Au/YSZ separation-sensing membrane

图3 实验测试装置图(a) PBS体系测试装置图；(b) 真实血样体系装置图

Fig.3 Schematic diagram of detection devices(a) based on PBS system; (b) based on real blood sample

图4 YSZ支撑体以及PB/Au/YSZ分离传感膜的XRD谱图

Fig.4 XRD patterns of YSZ support and PB/Au/YSZ separation-sensing membrane

图5 (a) YSZ支撑体以及PB/Au/YSZ分离传感膜的FT-IR谱图；(b) PB/Au/YSZ分离传感膜的XPS全谱图；(c), (d) Fe 2p 和Au 4f 的XPS精细谱

Fig.5 (a) FT-IR spectra of YSZ support and PB/Au/YSZ separation-sensing membrane; (b) XPS full spectra of PB/Au/YSZ separation-sensing membrane; (c), (d) XPS spectra of Fe 2p and Au 4f

图6 分离传感膜在外表面(a)、孔道内(b)、内表面(c)的SEM图

Fig.6 SEM images of outer surface (a)， pore (b)， and inner surface (c) of separation-sensing membrane

图7 Fe, C, O, N, Au元素在分离传感膜的孔道内及内表面的分布情况

Fig.7 The element distributions of Fe, C, O, N, Au in pore and inner surface of separation-sensing membrane

图8 不同自组装层数的分离传感膜接触角测试结果

Fig.8 The contact angles of separation-sensing membranes with different numbers of self-assembled layers

图9 PB/Au/YSZ膜第1次和第100次CV扫描结果

Fig.9 CV result of the 1st and 100th of PB/Au/YSZ membrane

图10 PB/YSZ和PB/Au/YSZ膜的EIS测试

Fig.10 EIS test of curves of PB/YSZ and PB/Au/YSZ membrane

图11 (a) PB/Au/YSZ分离传感膜对不同浓度葡萄糖的DPV响应曲线；(b) DPV峰强度变化量与葡萄糖浓度的线性拟合曲线

Fig.11 (a) DPV curves of PB/Au/YSZ separation-sensing membrane toward various glucose concentrations; (b) the calibration curve of DPV peak current change and glucose concentration

图12 分离传感膜加入干扰物质及葡萄糖的信号响应结果

Fig.12 The signals responses of separation-sensing membrane after adding various interferents and glucose

图13 分离传感膜和医用仪器对真实血样测试的比对结果

Fig.13 The detection results of separation-sensing membrane and biochemical analyzer in real blood samples

图14 分离传感膜的电流变化及血浆通量随时间的变化

Fig.14 The real-time current response and plasma flux of separation-sensing membrane

表1 YSZ空白膜及PB/Au/YSZ膜分离效果测试

Table 1 Separation effect test of YSZ blank membrane and PB/Au/YSZ membrane

项目	序号	红细胞	血小板
YSZ	1	1×10⁹/L	28×10⁹/L
	2	0	12×10⁹/L
	3	0	8×10⁹/L
PB/Au/YSZ	4	0	0
	5	0	0
	6	0	0

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