Electrochemical sensing of blood proteins for mild traumatic brain injury (mTBI) diagnostics and prognostics: towards a point-of-care application

Traumatic Brain Injury (TBI) being one of the principal causes of death and acquired disability in the world imposes a large burden on the global economy. Mild TBI (mTBI) is particularly challenging to assess due to the frequent lack of well-pronounced post-injury symptoms. However, if left untreated mTBI (especially when repetitive) can lead to serious long-term implications such as cognitive and neuropathological disorders. Computer tomography and magnetic resonance imaging commonly used for TBI diagnostics require well-trained personnel, are costly, difficult to adapt for on-site measurements and are not always reliable in identifying small brain lesions. Thus, there is an increasing demand for sensitive point-of-care (POC) testing tools in order to aid mTBI diagnostics and prediction of long-term effects. Biomarker quantification in body fluids is a promising basis for POC measurements, even though establishing a clinically relevant mTBI biomarker panel remains a challenge. Actually, a minimally invasive, rapid and reliable multianalyte detection device would allow the efficient determination of injury biomarker release kinetics and thus support the preclinical evaluation and clinical validation of a proposed biomarker panel for future decentralized in vitro diagnostics. In this respect electrochemical biosensors have recently attracted great attention and the present article provides a critical study on the electrochemical protocols suggested in the literature for detection of mTBI-relevant protein biomarkers. The authors give an overview of the analytical approaches for transduction element functionalization, review recent technological advances and highlight the key challenges remaining in view of an eventual integration of the proposed concepts into POC diagnostic solutions.