Aptamer-based biosensing methods, despite achieving advancements in the detection of tumor-associated proteins, are only effective for a limited number of specific proteins and thus have restricted clinical value. This is mainly attributed to the requirement of prior knowledge and precise modulation of the aptamer structure, or the special spatial distribution of multiple binding sites in the target protein molecule. To address this limitation, we here report a new electrochemical method for aptamer-based biosensing of tumor-associated proteins. This method utilizes a universal signal transduction module (i.e., electrochemistry-empowered nano-labeling) that depends on the electrochemical protein bioconjugation at natural tyrosine residues and incorporates electroactive quantum dots to produce considerable signals. Consequently, this method neither relies on the particular structure or design of the aptamer nor necessitates the presence of distinct binding sites in protein molecules, affording excellent broad-spectrum applicability for protein detection. Validation with mucin 1, carcinoembryonic antigen, and alpha-fetoprotein has evidenced this method’s good sensitivity with a detection limit of 0.41 pg/mL, as well as its practicality in clinical samples and versatility in detecting different proteins. Moreover, this method can be readily accommodated to detect specific tumor cells, exhibiting excellent scalability. As such, this method holds great potential to be a user-friendly and widely applicable tool for detecting tumor-associated proteins and may offer new insights into the use of aptamers in biosensing applications.

中文翻译：

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电化学驱动的纳米标记，用于基于适配体的肿瘤相关蛋白的多功能生物传感


基于适配子的生物传感方法尽管在肿瘤相关蛋白的检测方面取得了进步，但仅对有限数量的特定蛋白质有效，因此临床价值有限。这主要归因于对适配体结构的先验知识和精确调节的要求，或者说靶蛋白分子中多个结合位点的特殊空间分布。为了解决这一限制，我们在这里报告了一种新的电化学方法，用于基于适配体的肿瘤相关蛋白生物传感。该方法利用通用信号转导模块（即电化学赋能的纳米标记），该模块依赖于天然酪氨酸残基处的电化学蛋白质生物共轭，并结合电活性量子点以产生相当大的信号。因此，该方法既不依赖于适配体的特定结构或设计，也不需要在蛋白质分子中存在不同的结合位点，为蛋白质检测提供了极好的广谱适用性。用粘蛋白 1、癌胚抗原和甲胎蛋白进行的验证证明了该方法具有良好的灵敏度，检测限为 0.41 pg/mL，以及它在临床样品中的实用性和检测不同蛋白质的多功能性。此外，该方法可以很容易地用于检测特定的肿瘤细胞，表现出优异的可扩展性。因此，该方法具有巨大的潜力，可以成为检测肿瘤相关蛋白的用户友好且广泛适用的工具，并可能为适配体在生物传感应用中的使用提供新的见解。