Hunan Institute of Advanced Sensing and Information Technology, Xiangtan University, Xiangtan 411105, Hunan, China.
Key Laboratory for the Physics and Chemistry of Nanodevices and Center for Carbon-based Electronics, School of Electronics, Peking University, Beijing 100871, China.
ACS Sens. 2022 Jul 22;7(7):2075-2083. doi: 10.1021/acssensors.2c00967. Epub 2022 Jul 11.
Blood-biomarker-based tests are highly important for the early clinical diagnosis of Alzheimer's disease (AD) and the treatment and care of AD patients, but the complex serum environment and extremely low abundance of AD blood protein biomarkers present challenges. Nanomaterials are promising for constructing highly sensitive transistor-based biosensors due to their small size. However, such biosensors are difficult to fabricate on a large scale and suffer from the lack of combined optimization of reproducibility and sensitivity in complex physiological fluids. In this work, field-effect transistor (FET) biosensors based on highly uniform semiconducting carbon nanotube (CNT) thin films are mass produced to achieve highly sensitive and selective detection of the AD core blood biomarkers of β-amyloid (Aβ). The combination of the mass-produced CNT FET sensors and oligonucleotide aptamers as efficient bioreceptors enables reliable and reproducible sub-femtomolar detection in full human serum for Aβ and Aβ peptides and has outperformed other methods reported to date. The adsorption of biological substrates to the sensor was significantly reduced by multiple blocking steps, resulting in selectivity ratios of up to 730% (Aβ) and 800% (Aβ). The aptamer-functionalized CNT FET biosensor exhibits a large dynamic range (>10), rapid response time (several minutes), and low variation (<10%) and can be delivered as a low-cost and rapid clinical detection technology for the early diagnosis and mass screening of AD. This platform will help bring complex laboratory-based and expensive diagnostic tools to the point of care.
基于血液生物标志物的检测对于阿尔茨海默病（AD）的早期临床诊断以及 AD 患者的治疗和护理非常重要，但复杂的血清环境和 AD 血液蛋白生物标志物的极低丰度带来了挑战。由于其尺寸小，纳米材料对于构建高度灵敏的基于晶体管的生物传感器具有很大的潜力。然而，由于缺乏在复杂生理流体中对重现性和灵敏度的综合优化，这种生物传感器难以大规模制造。在这项工作中，基于高度均匀的半导体碳纳米管（CNT）薄膜的场效应晶体管（FET）生物传感器被大规模生产，以实现对 AD 核心血液生物标志物β-淀粉样蛋白（Aβ）的高灵敏度和选择性检测。大量生产的 CNT FET 传感器与寡核苷酸适体的结合作为有效的生物受体，能够在全人血清中可靠且可重复地检测亚皮摩尔级别的 Aβ和 Aβ肽，其性能优于迄今为止报道的其他方法。通过多次阻断步骤，显著减少了生物底物在传感器上的吸附，从而使 Aβ的选择性比高达 730%（Aβ）和 800%（Aβ）。经适体功能化的 CNT FET 生物传感器具有大的动态范围（>10）、快速的响应时间（几分钟）和低变化（<10%），可以作为一种低成本、快速的临床检测技术，用于 AD 的早期诊断和大规模筛查。该平台将有助于将复杂的基于实验室的昂贵诊断工具推向护理点。
