A Surface-Engineered Microfluidic Platform with Algorithmic Optimization for Plasma Biomarker Detection in
Yue Cheng1,2,3,4, Limoran Tang1,2,3,4, Yi Tan1,2,3,4
1Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China.
ACS Sensors
|November 24, 2025
Summary
A new microfluidic platform improves Alzheimer's disease (AD) blood biomarker detection by reducing errors and extending measurement range. This enhances early diagnosis and monitoring of neurodegenerative diseases.
Area of Science:
- Biomedical Engineering
- Neuroscience
- Analytical Chemistry
Background:
- Early Alzheimer's disease (AD) diagnosis relies on detecting low-abundance blood biomarkers.
- Conventional assays like enzyme-linked immunosorbent assay (ELISA) and even the sensitive Simoa platform face limitations in clinical utility due to nonspecific binding and limited dynamic range.
- Accurate quantification of biomarkers such as Aβ1-42 and pTau181 is crucial for effective disease management.
Purpose of the Study:
- To develop and validate a surface-engineered microfluidic platform for sensitive and accurate detection of Alzheimer's disease biomarkers in blood.
- To overcome the limitations of existing platforms, specifically addressing nonspecific binding and extending the dynamic range for improved clinical utility.
- To assess the diagnostic performance of the novel platform compared to established methods and evaluate its potential for clinical translation.
Main Methods:
- Development of a microfluidic platform with engineered beads to minimize nonspecific binding.
- Implementation of electrostatic bead-microwell pairing to enhance biomarker capture efficiency.
- Integration of an algorithmic calibration model to extend the dynamic range of biomarker quantification.
- Validation of the platform's performance using plasma samples from Alzheimer's disease patients and cognitively normal controls, with comparisons to Quanterix Simoa.
Main Results:
- The surface-engineered microfluidic platform demonstrated improved analytical sensitivity and quantification accuracy for plasma Aβ1-42 and pTau181.
- Statistical analysis confirmed a strong correlation between the microfluidic platform and the Quanterix Simoa, with superior diagnostic performance observed.
- The platform showed significant potential in differentiating individuals with AD from controls and enabling reliable longitudinal biomarker monitoring.
Conclusions:
- The developed surface-engineered microfluidic platform offers enhanced capabilities for sensitive and accurate detection of Alzheimer's disease biomarkers.
- This innovative platform addresses key limitations of current assays, paving the way for improved early diagnosis and monitoring of neurodegenerative diseases.
- The findings support the clinical translation potential of this microfluidic technology in the field of neurological diagnostics.


