@misc{9240691,
  abstract     = {{This dissertation investigates the reliability boundaries of optical photothermal infrared spectroscopy (O-PTIR) for semi-quantitative β-sheet analysis and its application to the detection of Parkinson’s disease (PD)-related skin biomarkers. The work is divided into two sub-projects.

Sub-project I used atomic force microscopy–infrared spectroscopy (AFM-IR) as a reference technique to systematically evaluate the conditions under which O-PTIR can provide reliable semi-quantitative analysis of β-sheet content. The experimental samples included Aβ amyloid fibrils with three morphologies (Thick, Thin, and Twist) and two single-chain recombinant amyloid proteins (SCRAP0 and SCRAP3). The results showed that the parallel β-sheet peak near 1630 cm−1 was the only component with consistent semi-quantitative reliability, with coefficient of variation (CV) values between 4% and 13%, whereas the CV values of the other structural components generally exceeded 30%. AFM-IR analysis further demonstrated that the β-sheet ratio was independent of fibril morphology, supporting the use of normalized peak area ratios as a robust structural parameter. When the structural homogeneity of the sample was sufficiently high (O-PTIR CV < 15%), the deviation between O-PTIR measurements and independently validated circular dichroism (CD) results was approximately 1.7%, demonstrating the semi-quantitative capability of O-PTIR under controlled conditions.

Sub-project II independently investigated ATR-FTIR spectral signatures of Parkinson’s disease-related changes in A53T transgenic mouse skin. Principal component analysis (PCA) combined with t-tests identified three PD-sensitive wavenumbers: 1647 cm−1 (amide I band, protein conformational changes), 2871 cm−1 (lipid C–H stretching), and 3356 cm−1 (skin hydration state). The clearest separation between WT and PD groups was observed in forelimb skin from 12-month-old mice. The 1647 cm−1 signal reflects a broad conformational shift in skin proteins rather than an isolated β-sheet fibril signal, indicating that the skin matrix introduces additional complexity not present in in vitro systems. Based on these target wavenumbers, commercially available quantum cascade laser (QCL) systems were systematically evaluated for potential wearable sensor integration.

Overall, this study established a reliability assessment framework for semi-quantitative O-PTIR analysis and provided both a methodological basis and target wavenumbers for the future development of photothermal infrared skin sensors for Parkinson’s disease detection.}},
  author       = {{Sun, Mingxue}},
  language     = {{eng}},
  note         = {{Student Paper}},
  title        = {{Non-Invasive Infrared Spectroscopic Detection of Parkinson's Disease Related Spectral Signatures}},
  year         = {{2026}},
}