Abstract
Neurofilament light chain (NfL) is a cytoplasmic protein predominantly found in neurons. Its primary role is to provide structural support to myelinated axons during their growth and maintenance. When axons are damaged due to injury or neurodegenerative processes, NfL levels increase in various bodily fluids, including the extracellular matrix, cerebrospinal fluid (CSF), and blood. The clinical significance of NfL lies in its association with neurological conditions. High levels of NfL have been observed in several contexts: Medical Emergencies: In acute medical emergencies such as stroke and head injuries, elevated NfL levels are detected. This rapid response makes NfL a potential biomarker for assessing acute neuronal damage.Neurodegenerative Diseases: Chronic neurodegenerative conditions, including multiple sclerosis (MS) and Alzheimer's disease, are characterized by progressive neuronal loss. NfL levels are significantly elevated in these diseases, reflecting ongoing axonal damage.Monitoring Neurodegeneration: Utilizing NfL as a monitoring tool has gained attention. Its presence in easily accessible bodily fluids (such as blood) makes it valuable for creating point-of-care mechanisms. By tracking NfL levels over time, clinicians can assess disease progression, treatment response, and overall neuronal health. Current NfL monitoring techniques such as Fourth-Generation Immunoassays (SIMOA or Quanterix). These highly sensitive assays allow quantification of NfL even at low levels. They are particularly useful for measuring NfL in plasma and serum. However, they require specialized equipment and trained personnel, limiting their widespread adoption. Microfluidic Cartridge-Based Automated Immunoassay Platforms such as ELLA have also been employed. While these platforms offer automated NfL measurement more conveniently, they also require expensive equipment and proper sample transportation.In this proposal, we introduce a novel Point-of-Care (PoC) mechanism designed for the rapid detection of Neurofilament Light Chain (NfL) in blood plasma. Our approach aims to eliminate the need for sample transportation, reduce procedural delays, and improve turnaround time. We have developed an Electrochemical Impedance Spectroscopy (EIS) platform specifically tailored for quantifying NfL levels within the physiological range in plasma. By leveraging the chemical interactions between the NfL antibody and antigen, we detect changes in impedance at the electrode-electrolyte interface as a factor of the chemical interaction. To validate our platform, we conducted spike and recovery experiments. These experiments illustrate the platform's ability to detect NfL in plasma samples reliably. In summary, our proposed PoC mechanism represents a significant advancement in NfL monitoring for neurodegenerative diseases. By combining accessibility, precision, and rapidity, we aim to enhance patient care and disease management.
Published Version
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