(Invited) Cerebrospinal Fluid Leakage Detection with Carbon Nanotube-Based Field-Effect Transistors

Abstract

Cerebrospinal fluid (CSF) leakage is a life-threatening medical condition that could result in significant morbidity and mortality if left untreated. However, the gold-standard test for confirming CSF leakage by detecting beta2-transferrin (β2-Tf) proteins using gel electrophoresis and Western blot is labor intensive and requires 3–6 hours. Carbon nanotube-based field-effect transistors (NTFET) are promising candidates for point-of-care diagnostic devices, owing to the outstanding electronic and mechanical properties of carbon nanotubes. The use of enriched semiconducting (sc) single-walled carbon nanotubes (SWCNT) significantly improves the performance of NTFET devices and enables label-free protein detection. To demonstrate that sensitive and specific detection of β2-Tf in biological fluids can be achieved by using NTFET biosensor platform, we have developed a three-step strategy for β2-Tf detection using NTFET devices. The three-step strategy for β2-Tf detection includes two steps of affinity chromatography to isolate β2-Tf and a rapid β2-Tf sensing step utilizing a high-purity sc-SWCNT FET device. Three different sensing configurations for the sc-SWCNT FET sensor were investigated for obtaining the optimal β2-Tf sensing results. Compared to current methods for CSF leak diagnosis, such as electrophoresis and imaging methods, our three-step strategy can offer high quality CSF leak detection with a short turnaround time (around 1 hour), easy instrument access and simple operations, which could potentially benefit medical treatment of traumatic brain injury (TBI) patients and other people in need. The versatility of our sensing platform could also open opportunities for point-of-care applications for other disease-related protein detection, as we have recently demonstrated by rapid detection of SARS-CoV-2 antigens for COVID-19 testing.