Ali Md Azahar, Mondal Kunal, Singh Chandan, Malhotra Bansi Dhar, Sharma Ashutosh
Department of Chemical Engineering, Indian Institute of Technology, Kanpur, India.
Nanoscale. 2015 Apr 28;7(16):7234-45. doi: 10.1039/c5nr00194c.
We report the fabrication of an efficient, label-free, selective and highly reproducible immunosensor with unprecedented sensitivity (femto-molar) to detect a breast cancer biomarker for early diagnostics. Mesoporous zinc oxide nanofibers (ZnOnFs) are synthesized by electrospinning technique with a fiber diameter in the range of 50-150 nm. Fragments of ZnOnFs are electrophoretically deposited on an indium tin oxide glass substrate and conjugated via covalent or electrostatic interactions with a biomarker (anti-ErbB2; epidermal growth factor receptor 2). Oxygen plasma treatment of the carbon doped ZnOnFs generates functional groups (-COOH, -OH, etc.) that are effective for the conjugation of anti-ErbB2. ZnOnFs without plasma treatment that conjugate via electrostatic interactions were also tested for comparison. Label-free detection of the breast cancer biomarker by this point-of-care device is achieved by an electrochemical impedance technique that has high sensitivity (7.76 kΩ μM(-1)) and can detect 1 fM (4.34 × 10(-5) ng mL(-1)) concentration. The excellent impedimetric response of this immunosensor provides a fast detection (128 s) in a wide detection test range (1.0 fM-0.5 μM). The oxy-plasma treated ZnOnF immunoelectrode shows a higher association constant (404.8 kM(-1) s(-1)) indicating a higher affinity towards the ErbB2 antigen compared to the untreated ZnOnF immunoelectrode (165.6 kM(-1) s(-1)). This sensor is about an order of magnitude more sensitive than the best demonstrated in the literature based on different nanomaterials and about three orders of magnitude better than the ELISA standard for breast cancer biomarker detection. This proposed point-of-care cancer diagnostic offers several advantages, such as higher stability, rapid monitoring, simplicity, cost-effectiveness, etc., and should prove to be useful for the detection of other bio- and cancer markers.
我们报告了一种高效、无标记、选择性且高度可重复的免疫传感器的制备，该传感器对检测用于早期诊断的乳腺癌生物标志物具有前所未有的灵敏度（飞摩尔级）。通过静电纺丝技术合成了中孔氧化锌纳米纤维（ZnOnFs），其纤维直径在50 - 150纳米范围内。ZnOnFs片段通过电泳沉积在氧化铟锡玻璃基板上，并通过与生物标志物（抗ErbB2；表皮生长因子受体2）的共价或静电相互作用进行缀合。对碳掺杂的ZnOnFs进行氧等离子体处理会产生对抗ErbB2缀合有效的官能团（-COOH、-OH等）。还测试了通过静电相互作用进行缀合的未经等离子体处理的ZnOnFs以作比较。通过这种即时检测设备对乳腺癌生物标志物进行无标记检测是通过一种具有高灵敏度（7.76 kΩ μM⁻¹）且能检测1 fM（4.34×10⁻⁵ ng mL⁻¹）浓度的电化学阻抗技术实现的。这种免疫传感器出色的阻抗响应在宽检测范围（1.0 fM - 0.5 μM）内提供快速检测（128秒）。经氧等离子体处理的ZnOnF免疫电极显示出更高的缔合常数（404.8 kM⁻¹ s⁻¹），表明与未处理的ZnOnF免疫电极（165.6 kM⁻¹ s⁻¹）相比，对ErbB2抗原有更高的亲和力。该传感器的灵敏度比基于不同纳米材料在文献中所展示的最佳结果高约一个数量级，并且比用于乳腺癌生物标志物检测的ELISA标准要好约三个数量级。这种提议的即时检测癌症诊断方法具有几个优点，如更高的稳定性、快速监测、简单性、成本效益等，并且应该证明对检测其他生物和癌症标志物是有用的。
