机器学习辅助的印刷杂链蛋白质生物标志物的高通量识别和定量。
Machine Learning-Assisted High-Throughput Identification and Quantification of Protein Biomarkers with Printed Heterochains.
发表日期:2024 Jul 01
作者:
Xiangyu Pan, Zeying Zhang, Yang Yun, Xu Zhang, Yali Sun, Zixuan Zhang, Huadong Wang, Xu Yang, Zhiyu Tan, Yaqi Yang, Hongfei Xie, Bogdan Bogdanov, Georgii Zmaga, Pavel Senyushkin, Xuemei Wei, Yanlin Song, Meng Su
来源:
BIOSENSORS & BIOELECTRONICS
摘要:
先进的体外诊断技术对于疾病的早期检测、预后和进展监测非常重要。在这里,我们设计了一种基于多材料杂链的可调液体限制自组装的多重蛋白质生物传感策略,与标准 ELISA 试剂盒相比,该策略显示出更高的灵敏度、通量和准确性。通过控制材料组合和配体纳米粒子(NP)的数量,我们观察到聚合物半导体杂链中强大的近场增强以及强电磁共振。特别是,它们的光信号在很宽的范围内对半导体纳米粒子的配位数表现出线性响应。因此,通过功能化中心聚合物链上的抗体开发了可见纳米光子生物传感器,该传感器可以识别附着在半导体纳米颗粒上的目标蛋白质。这样就可以以超低检测限 (1 pg/mL) 一次性特异性检测健康人和胰腺癌患者的多种蛋白质生物标志物。此外,结合神经网络算法实现了缓冲液、尿液、血清等多种临床样本中蛋白表达水平的快速、高通量定量,平均准确度达到97.3%。这项工作表明,基于杂链的生物传感器是构建下一代诊断工具的典范候选者,并且适用于许多临床环境。
Advanced in vitro diagnosis technologies are highly desirable in early detection, prognosis, and progression monitoring of diseases. Here, we engineer a multiplex protein biosensing strategy based on the tunable liquid confinement self-assembly of multi-material heterochains, which show improved sensitivity, throughput, and accuracy compared to standard ELISA kits. By controlling the material combination and the number of ligand nanoparticles (NPs), we observe robust near-field enhancement as well as both strong electromagnetic resonance in polymer-semiconductor heterochains. In particular, their optical signals show a linear response to the coordination number of the semiconductor NPs in a wide range. Accordingly, a visible nanophotonic biosensor is developed by functionalizing antibodies on central polymer chains that can identify target proteins attached to semiconductor NPs. This allows for the specific detection of multiple protein biomarkers from healthy people and pancreatic cancer patients in one step with an ultralow detection limit (1 pg/mL). Furthermore, rapid and high-throughput quantification of protein expression levels in diverse clinical samples such as buffer, urine, and serum is achieved by combining a neural network algorithm, with an average accuracy of 97.3%. This work demonstrates that the heterochain-based biosensor is an exemplary candidate for constructing next-generation diagnostic tools and suitable for many clinical settings.