Rani Dipti, Pachauri Vivek, Madaboosi Narayanan, Jolly Pawan, Vu Xuan-Thang, Estrela Pedro, Chu Virginia, Conde João Pedro, Ingebrandt Sven
Department of Informatics and Microsystem Technology, University of Applied Sciences Kaiserslautern, Amerikastrasse 1, 66482 Zweibrücken, Germany.
INESC Microsistemas e Nanotecnologias, Rua Alves Redol, 91000-029 Lisbon, Portugal.
ACS Omega. 2018 Aug 1;3(8):8471-8482. doi: 10.1021/acsomega.8b00990. eCollection 2018 Aug 31.
Highly sensitive electrical detection of biomarkers for the early stage screening of cancer is desired for future, ultrafast diagnostic platforms. In the case of prostate cancer (PCa), the prostate-specific antigen (PSA) is of prime interest and its detection in combination with other PCa-relevant biomarkers in a multiplex approach is advised. Toward this goal, we demonstrate the label-free, potentiometric detection of PSA with silicon nanowire ion-sensitive field-effect transistor (Si NW-ISFET) arrays. To realize the field-effect detection, we utilized the DNA aptamer-receptors specific for PSA, which were covalently and site-specifically immobilized on Si NW-ISFETs. The platform was used for quantitative detection of PSA and the change in threshold voltage of the Si NW-ISEFTs was correlated with the concentration of PSA. Concentration-dependent measurements were done in a wide range of 1 pg/mL to 1 μg/mL, which covers the clinical range of interest. To confirm the PSA-DNA aptamer binding on the Si NW surfaces, a sandwich-immunoassay based on chemiluminescence was implemented. The electrical approach using the Si NW-ISFET platform shows a lower limit of detection and a wide dynamic range of the assay. In future, our platform should be utilized to detect multiple biomarkers in one assay to obtain more reliable information about cancer-related diseases.
未来的超快速诊断平台需要对生物标志物进行高灵敏度的电学检测,以用于癌症的早期筛查。就前列腺癌(PCa)而言,前列腺特异性抗原(PSA)是主要关注对象,建议采用多重方法将其与其他与PCa相关的生物标志物结合进行检测。为了实现这一目标,我们展示了利用硅纳米线离子敏感场效应晶体管(Si NW-ISFET)阵列对PSA进行无标记电位检测。为了实现场效应检测,我们利用了对PSA具有特异性的DNA适配体受体,它们被共价且位点特异性地固定在Si NW-ISFET上。该平台用于PSA的定量检测,Si NW-ISEFT的阈值电压变化与PSA浓度相关。在1 pg/mL至1 μg/mL的宽范围内进行了浓度依赖性测量,该范围涵盖了临床关注范围。为了确认PSA-DNA适配体在Si NW表面的结合,实施了基于化学发光的夹心免疫测定。使用Si NW-ISFET平台的电学方法显示出较低的检测限和较宽的测定动态范围。未来,我们的平台应被用于在一次检测中检测多种生物标志物,以获得有关癌症相关疾病的更可靠信息。