# Matrix Optical Biosensor for Determining YKL-40/CHI3L1—A Biomarker Potentially Associated with Alzheimer’s Disease

## TL;DR

A new biosensor was developed to detect YKL-40, a potential biomarker for Alzheimer’s disease, with high sensitivity and accuracy in blood plasma.

## Contribution

A novel SPRi-based biosensor for YKL-40 detection with low detection limits and validation in complex biological samples.

## Key findings

- The biosensor has a detection limit of 2 pg/mL and quantification limit of 7 pg/mL.
- It showed high precision and accuracy with standard deviations and coefficients of variation within acceptable ranges.
- The biosensor successfully differentiated YKL-40 levels in Alzheimer’s patients versus control groups.

## Abstract

YKL-40 is a glycoprotein that may be present at elevated levels in many cancers and neurodegenerative diseases. It has been investigated in numerous studies as a potential biomarker for several conditions, including Alzheimer’s Disease (AD). In this study, a biosensor with Surface Plasmon Resonance imaging (SPRi) detection, sensitive to YKL-40, was constructed for the detection of this analyte in the blood plasma of AD patients. Extensive validation of the biosensor was performed. This included the determination of analytical parameters such as the biosensor’s response characteristics, detection and quantification limits, precision, accuracy, repeatability, selectivity, stability, and performance in natural samples. Validation parameters were primarily tested using standard solutions, while natural samples were employed to evaluate repeatability, stability, and assay accuracy in three groups of samples from different patients. A YKL-40-specific antibody was used as the receptor layer, immobilized on a gold plate using the EDC/NHS protocol on thiol 11-MUA. The biosensor exhibited a wide operating range (1–200 ng/mL), a low detection limit (LOD) of 2 pg/mL, and a quantification limit (LOQ) of 7 pg/mL. High precision and accuracy were confirmed by the calculated standard deviations (SD) and coefficients of variation (CV), which ranged from 0.0009 to 7.02 ng/mL and from 0.12% to 9.24%, respectively. The sensor also demonstrated good repeatability (CV = 4.995%) and was capable of detecting the analyte of interest in complex biological matrices. Its applicability was confirmed in a study using plasma from AD patients and two selected control groups: plasma from smokers and patients with prostatitis. This allowed the assessment of YKL-40 levels across different groups. The results were consistent with literature values, and statistical analysis confirmed the significance of concentration differences between groups. Furthermore, ROC curve analysis confirmed the diagnostic usefulness of the constructed YKL-40 test in the context of Alzheimer’s disease.