Alzheimer's diagnosis beyond cerebrospinal fluid: Probe-Free Detection of Tau Proteins using MXene based redox systems and molecularly imprinted polymers

Ajith Mohan Arjun; Sudhaunsh Deshpande; Tom Dunlop; Beth Norman; Daniela Oliviera; Georgeta Vulpe; Felismina Moreira; Sanjiv Sharma

doi:10.1016/j.biosx.2024.100513

Alzheimer's diagnosis beyond cerebrospinal fluid: Probe-Free Detection of Tau Proteins using MXene based redox systems and molecularly imprinted polymers

Biosens Bioelectron X. 2024 Oct:20:100513. doi: 10.1016/j.biosx.2024.100513.

Authors

Ajith Mohan Arjun¹, Sudhaunsh Deshpande¹, Tom Dunlop², Beth Norman¹, Daniela Oliviera³, Georgeta Vulpe¹, Felismina Moreira³, Sanjiv Sharma¹

Affiliations

¹ Dept. of Biomedical Engineering, Faculty of Science and Engineering, Swansea University, UK.
² The Advanced Imaging of Materials (AIM) Facility, Faculty of Science and Engineering, Swansea University, UK.
³ CIETI - LabRISE-School of Engineering, Polytechnic of Porto, R. Dr. António Bernardino de Almeida, 431, 4249-015, Porto, Portugal.

Abstract

Phosphorylated Tau proteins are promising biomarkers for the diagnosis and prognosis of Alzheimer's disease. This study presents a novel voltametric sensor using a vanadium MXene polydopamine (V_xPDA) redox active composite and a Tau-441-specific polyaniline molecularly imprinted polymer (PANI MIP) for the sensitive detection of Tau-441 in interstitial fluid (ISF) and plasma. The V_xPDA/PANI MIP sensor demonstrates a broad detection range of 5 fg/mL to 5 ng/mL (122 aM/L to 122 pM/L) in ISF without the use of redox mediators, with a lower limit of detection (LOD) of 2.3 fg/mL (60 aM/L). Furthermore, a handheld device utilizing this technology successfully detects Tau-441 in artificial serum with high sensitivity (5 fg/mL to 150 fg/mL (122 aM/L to 366 aM/L)) and specificity within a clinically relevant range. The rapid detection time (∼32 min) and low cost (∼£20/device) of this sensor highlight its potential for minimally invasive, early AD diagnosis in clinical settings. This advancement aims to facilitate a transition away from invasive cerebrospinal fluid (CSF)-based diagnostic techniques for AD.