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A High Throughput, Multiplexed and Targeted Proteomic CSF Assay to Quantify Neurodegenerative Biomarkers and Apolipoprotein E Isoforms Status
Published on: October 20, 2016
Multiplexed EDL-FET biosensor with tannic acid stabilization for simultaneous p-Tau217 and Aβ42/Aβ40 detection in
Shang-Chi Chien1, I-Yin Chang2, Yong-Chuan Chen3
1Institute of Intelligent Bioelectrical Engineering, National Yang Ming Chiao Tung University, Hsinchu, 300, Taiwan; Department of Electronics and Electrical Engineering, National Yang Ming Chiao Tung University, Hsinchu, 300, Taiwan.
Abstract:
Alzheimer's disease (AD) is a leading cause of disability in aging societies, underscoring the need for practical blood-based biomarker assays. Stroke patients face an elevated risk of AD-related cognitive impairment, yet reliable, scalable tools for early biomarker assessment in this population remain lacking. Current platforms are limited by low throughput, instability, and demanding sample preparation that restricts point-of-care translation. This study addresses the need for a multiplexed, clinically practical biosensor capable of simultaneously measuring AD-relevant biomarkers in both plasma and whole blood. An eight-channel electric double-layer field-effect transistor (EDL-FET) platform was developed to simultaneously measure phosphorylated tau (p-tau217) and the Aβ42/Aβ40 ratio in plasma and whole blood. Standardized surface modification with tannic acid (TA)-assisted antibody immobilization enabled stable chip performance under wet storage for at least 10 days. Clinically, 54 plasma and 32 whole-blood samples from stroke patients were stratified into cognitively impaired (MMSE ≤24) and unimpaired (MMSE >24) groups. p-tau217 significantly differentiated cognitive status in both matrices, with the strongest performance in plasma. Combining p-tau217 with Aβ42/Aβ40 in plasma yielded a receiver operating characteristic (ROC) area under the curve (AUC) of 0.938. Plasma p-tau217, alone or in combination, demonstrated higher sensitivity for detecting cognitive impairment, while whole-blood measurements offered practicality, with preserved sample integrity and minimal pre-analytical requirements. This work presents the first multiplexed EDL-FET platform for simultaneous AD biomarker profiling in stroke patients using both plasma and whole blood. The integration of p-tau217 and Aβ42/Aβ40 on a stable, multi-channel chip demonstrates a novel route toward point-of-care AD risk stratification in high-risk populations, pending validation in larger, multi-center cohorts.
