AbstractA sandwich-type electrochemical cytosensor is described for quantitative determination of CD44-overexpressing HeLa cells. Hyaluronic acid (HA) acts as a targeting molecule that was in-situ incorporated into the sensor based on the use of an indium tin oxide (ITO) electrode modified with multi-walled carbon nanotubes (MWCNTs). The 3D-MWCNT structure is shown to strongly improve the electronic properties and surface chemical reactivities. The HA-modified sensor exhibits a highly sensitive response to HeLa cells. A sandwiched hybridization protocol was then established using BIO [an N-butyl-4-(6′-aminohexyl)amino-1,8-naphthalimide probe modified with HA] as the tracing labels of the fluorescent probes for targeting CD44-positive tumor cells. The signal amplification was thereby maximized and measured by chronocoulometry. The binding of CD44-positive HeLa cells to the HA modified sensing layer causes a decrease in chronocoulometric response. The signal decreases linearly in the 2.1 × 102 to 2.1 × 107 HeLa cells·mL−1 concentration range with a detection limit of 70 cells·mL−1. Such a sandwich-type assay may be tailored as a sensitive candidate for detecting low levels of tumor cells. Graphical abstractSchematic of a sandwich cytosensor based on hyaluronic acid-grafted 3D-MWCNT as biosensing interface and BIO as fluorescent probe. This biosensor possessed excellent electrochemical activity, high sensitivity and selectivity, providing a dynamical tracking and detecting platform for CD44-positive tumor cells.

中文翻译：

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透明质酸接枝的三维 MWCNT 阵列作为生物传感界面，用于 CD44 过表达癌细胞的计时库仑检测和荧光成像

摘要描述了一种夹心型电化学细胞传感器，用于定量测定过表达 CD44 的 HeLa 细胞。透明质酸 (HA) 作为靶向分子，基于使用多壁碳纳米管 (MWCNT) 修饰的氧化铟锡 (ITO) 电极原位整合到传感器中。3D-MWCNT 结构显示出极大地改善了电子特性和表面化学反应性。HA 修饰的传感器对 HeLa 细胞表现出高度敏感的响应。然后使用BIO [用HA修饰的N-丁基-4-(6'-氨基己基)氨基-1,8-萘二甲酰亚胺探针]作为靶向CD44阳性肿瘤细胞的荧光探针的示踪标记建立夹心杂交方案. 从而使信号放大最大化并通过计时库仑法测量。CD44 阳性 HeLa 细胞与 HA 修饰的传感层的结合导致计时库仑响应降低。信号在 2.1 × 102 至 2.1 × 107 HeLa 细胞·mL-1 浓度范围内线性下降，检测限为 70 个细胞·mL-1。这种夹心型测定可以被定制为检测低水平肿瘤细胞的敏感候选物。图形摘要基于透明质酸接枝的 3D-MWCNT 作为生物传感界面和 BIO 作为荧光探针的夹心细胞传感器的示意图。该生物传感器具有优异的电化学活性、高灵敏度和选择性，为CD44阳性肿瘤细胞提供了动态跟踪和检测平台。1 × 107 HeLa 细胞·mL-1 浓度范围，检测限为70 个细胞·mL-1。这种夹心型测定可以被定制为检测低水平肿瘤细胞的敏感候选物。图形摘要基于透明质酸接枝的 3D-MWCNT 作为生物传感界面和 BIO 作为荧光探针的夹心细胞传感器的示意图。该生物传感器具有优异的电化学活性、高灵敏度和选择性，为CD44阳性肿瘤细胞提供了动态跟踪和检测平台。1 × 107 HeLa 细胞·mL-1 浓度范围，检测限为70 个细胞·mL-1。这种夹心型测定可以被定制为检测低水平肿瘤细胞的敏感候选物。图形摘要基于透明质酸接枝的 3D-MWCNT 作为生物传感界面和 BIO 作为荧光探针的夹心细胞传感器的示意图。该生物传感器具有优异的电化学活性、高灵敏度和选择性，为CD44阳性肿瘤细胞提供了动态跟踪和检测平台。