Department of Chemical Engineering, Kwangwoon University, 20 Kwangwoon-Ro, Nowon-Gu, Seoul 01897, Republic of Korea.
School of Integrative Engineering Chung-Ang University, Heukseok-dong, Dongjak-gu, Seoul 06910, Republic of Korea.
ACS Sens. 2023 Aug 25;8(8):3174-3186. doi: 10.1021/acssensors.3c00879. Epub 2023 Aug 16.
Cancer progresses silently to the terminal stage of the impossible operable condition. There are many limitations in the treatment options of cancer, but diagnosis in an early stage can improve survival rates and low recurrence. Exosomes are the biomolecules released from cancer cells and are promising candidates for clinical diagnosis. Among them, the cluster of differentiation 9 (CD9) protein is an important exosomal biomarker that can be used for exosome determination. Therefore, here, a CD9 aptamer was first synthesized and applied to an extended-gate field-effect transistor (EGFET)-type biosensor containing a disposable sensing membrane to suggest the possibility of detecting exosomes in a clinical environment. Systematically evaluating ligands using the exponential enrichment (SELEX) technique was performed to select nucleic acid sequences that can specifically target the CD9 protein. Exosomes were detected according to the electrical signal changes on a membrane, which is an extended gate using an Au microelectrode. The fabricated biosensor showed a limit of detection (LOD) of 10.64 pM for CD9 proteins, and the detection range was determined from 10 pM to 1 μM in the buffer. In the case of the clinical test, the LOD and detection ranges of exosomes in human serum samples were 6.41 × 10 exosomes/mL and 1 × 10 to 1 × 10 exosomes/mL, respectively, showing highly reliable results with low error rates. These findings suggest that the proposed aptasensor can be a powerful tool for a simple and early diagnosis of exosomes.
癌症进展到无法手术的终末期是无声的。癌症的治疗选择有很多局限性，但早期诊断可以提高生存率和降低复发率。外泌体是癌细胞释放的生物分子，是临床诊断的有前途的候选物。其中，分化群 9（CD9）蛋白是一种重要的外泌体生物标志物，可用于外泌体的测定。因此，在这里，首先合成了一种 CD9 适体，并将其应用于包含一次性传感膜的扩展门场效应晶体管（EGFET）型生物传感器中，以提示在临床环境中检测外泌体的可能性。使用指数富集（SELEX）技术系统地评估配体，以选择可以特异性靶向 CD9 蛋白的核酸序列。根据膜上的电信号变化检测外泌体，该膜是使用 Au 微电极的扩展门。所制造的生物传感器对 CD9 蛋白的检测限（LOD）为 10.64 pM，在缓冲液中的检测范围从 10 pM 到 1 μM 确定。在临床测试中，人血清样本中外泌体的 LOD 和检测范围分别为 6.41×10 个外泌体/mL 和 1×10 到 1×10 个外泌体/mL，显示出具有低错误率的高度可靠结果。这些发现表明，所提出的适体传感器可以成为一种简单且早期诊断外泌体的有力工具。
