Aptamer-Functionalized Carbon Nanotube Field-Effect Transistor Biosensors for Alzheimer’s Disease Serum Biomarker Detection

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 Aβ₄₂ and Aβ₄₀ 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% (Aβ₄₀) and 800% (Aβ₄₂). The aptamer-functionalized CNT FET biosensor exhibits a large dynamic range (>10⁴), 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.