Optical biosensors for diagnosing neurodegenerative diseases

Abstract

Neurodegenerative diseases involve the progressive loss of neurons in the brain and nervous system, leading to functional decline. Early detection is critical for improving outcomes and advancing therapies. Optical biosensors, some of which offer rapid, label-free, and ultra-sensitive detection, have been applied to early diagnosis and drug screening. This review examines the principles and performance of different optical biosensors used for diagnosing neurodegenerative diseases and discusses potential future advancements.

Keywords: Diagnostic markers; Imaging and sensing; Neurological disorders.

Fig. 1. Concepts underlying fluorescence-based biosensors.

a Schematic representation of ELISA, highlighting antibody-antigen interactions and fluorescent signal generation; b schematic of SIMOA, showing molecular detection using microwells and paramagnetic beads; c schematic of a CRISPR-based fluorescence biosensor, illustrating target recognition and fluorescent signal release through Cas enzyme activity; and d schematic of FRET, demonstrating energy transfer between donor and acceptor fluorophores during close-range protein binding.

Fig. 2. Working principles of SPR and localized surface plasmon resonance (LSPR) in biosensing.

a SPR uses surface plasmons excited at a metal-dielectric interface to detect refractive index changes from analyte binding. b LSPR relies on localized plasmons in metallic nanoparticles, with analyte binding causing shifts in the resonance peak.

Fig. 3. Concept of SERS in biosensing.

Metallic nanoparticles or nanostructured surfaces enhance the Raman scattering signal of biomolecules through localized surface plasmon resonance (LSPR). Incident light excites the plasmon resonance, generating a strong electromagnetic field near the surface, amplifying the signal from nearby molecules.

Fig. 4. Commonly used label-free WGM optical resonators for biosensing.

a Microring resonator. Microrings are compact, chip-integrated, and compatible with microfluidic systems, but have lower sensitivity than microspheres or microtoroids. b Microsphere resonator. Microspheres have ultra-high Q factors but are difficult to integrate on chip as they are not fabricated in a planar format and c Microtoroid resonators. Microtoroids have both ultra-high-Q factors and are fabricated on a chip, opening up the potential for a high-sensitivity multiplexed assay.

Fig. 5. Overview of how optical biosensors can be used for neurodegenerative disease diagnostics.

Samples may include human-derived fluids, murine models, or commercially available purified protein fragments, such as amyloid β 1-42. Optical biosensor platforms can detect, for example, target biomolecules through specific antibody binding, producing measurable optical signals. These signals are analyzed to generate response curves, providing quantitative data for biomarker detection and disease progression assessment.