Miniaturized biosensor platforms for early detection of neurodegenerative diseases and their potential for clinical translation

Abstract

Neurodegenerative disorders (NDs), such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and prion diseases, are defined by the gradual deterioration of neurons that frequently occurs prior to the onset of clinically observable symptoms. The early diagnosis of these conditions relies on analytical systems that are capable in detecting disease-related biomarkers at low concentrations within complex biological fluids. This analysis extensively evaluates miniaturized biosensor systems aimed at disease-specific biomarkers, such as amyloid-β and tau for Alzheimer’s disease, α-synuclein (α-syn) and DJ-1 for Parkinson’s disease, and prion protein isoforms for prion disorders. Electrochemical, optical, surface plasmon resonance, field-effect transistor, surface-enhanced Raman spectroscopy, microfluidic lab-on-a-chip, portable, and wearable systems are assessed concerning their biorecognition methodologies, signal-transduction processes, linear ranges, detection thresholds, selectivity, sample matrices, and suitability for point-of-care applications. Recent research indicates that nanostructured sensing interfaces and microfluidic integration can improve analytical sensitivity, minimize sample needs, and facilitate biomarker identification in blood, plasma, cerebrospinal fluid, saliva, and other therapeutically pertinent matrices. However, remarkably low detection thresholds alone do not establish clinical significance. Biofouling, matrix influences, intricate production, prolonged stability, insufficient clinical validation, and the absence of standardized multicenter research persist in limiting clinical application. This review evaluates the development of biosensors for the diagnosis of neurodegenerative diseases towards miniaturized and portable systems based on current studies. It also comprehensively addresses the key limitations in the clinical validation, standardization, scalable production, and commercialization processes.