使用苯硼酸修饰的自组装单层金电极对细胞膜进行无创唾液酸检测,Journal of the American Chemical Society

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使用苯硼酸修饰的自组装单层金电极对细胞膜进行无创唾液酸检测
Journal of the American Chemical Society ( IF 14.4 ) Pub Date : 2009-09-02 , DOI: 10.1021/ja902964m
Akira Matsumoto ₁ , Naoko Sato ₁ , Kazunori Kataoka ₁ , Yuji Miyahara ₁

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细胞表面聚糖链上唾液酸 (SA) 含量的变化与许多正常和病理过程有关，包括发育、分化和肿瘤转移。SA 的过度表达与许多不同类型癌症的恶性和转移表型有关，而在糖尿病患者的红细胞中也发现 SA 表达降低。因此，方便地监测细胞表面 SA 的技术将与细胞学密切相关。然而，现有的量化 SA 的方法涉及多种酶促、染料标记和致死程序，这些程序既昂贵又耗时。在这里，我们使用苯基硼酸 (PBA) 化合物开发了一种电位 SA 检测，该化合物以自组装单层 (SAM) 的形式集成到场效应晶体管 (FET) 扩展金栅电极上。由于在其他聚糖链成分单糖中未分离的 PBA 和 SA 在 pH 7.4 之间选择性结合，我们发现 SA 的羧基阴离子可作为 PBA 修饰的 FET 的阈值电压 (V(T)) 的变化专门检测到。该技术被应用于分析兔红细胞上改变的 SA 表达作为糖尿病模型。对每个健康和患病模型的比较 SA 表达分析表明，只需将已知计数的细胞悬液放置在设备上，无需任何标记和酶促程序，即可简单地诊断疾病。这种技术还可以在术中和术后诊断期间为肿瘤恶性程度和转移潜力的组织学评估提供定量辅助手段。同样有利的是，这里描述的技术全部在CMOS（互补金属氧化物半导体）兼容格式内，因此有望通过先进的半导体处理技术实现小型化和集成化的高效和低成本制造。

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Noninvasive Sialic Acid Detection at Cell Membrane by Using Phenylboronic Acid Modified Self-Assembled Monolayer Gold Electrode

Alternations of sialic acid (SA) content on cell surface glycan chains have been implicated in numerous normal and pathological processes including developments, differentiations, and tumor metastasis. Overexpressions of SA have been implicated in the malignant and metastatic phenotypes for many different types of cancers, while decreased SA expression has also been identified in erythrocytes of diabetic mellitus. Techniques to conveniently monitor cell surface SA would therefore have great relevance to cytology. Preexisting methodologies to quantify SA, however, involve multiple enzymatic, dye-labeling, and lethal procedures, which are costly and time-consuming. Here we developed a potentiometric SA detection using a phenylboronic acid (PBA) compound integrated into the form of a self-assembled monolayer (SAM) onto a field effect transistor (FET) extended gold gate electrode. Due to selective binding between undisassociated PBA and SA at pH 7.4 among other glycan chain constituent monosaccharides, we found that carboxyl anions of SA were exclusively detectable as the change in threshold voltage (V(T)) of the PBA-modified FET. The technique was applied to analyses of altered SA expressions on rabbit erythrocyte as a model for diabetes. Comparative SA expression analyses for each healthy and diseased model revealed that the disease could be feasibly diagnosed simply by placing the known-count cell suspensions onto the device without any labeling and enzymatic procedures. Such a technique may also provide a quantitative adjunct to histological evaluation of tumor malignancy and metastatic potential during intra- and postoperative diagnoses. Also advantageously, a technique herein described is all within a CMOS (Complementary Metal Oxide Semiconductor) compatible format thus promising for highly efficient and low cost manufacturing with readiness of downsizing and integration by virtue of advanced semiconductor processing technologies.

更新日期：2009-09-02

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