Towards a Point-of-Care (POC) Diagnostic Platform for the Multiplex Electrochemiluminescent (ECL) Sensing of Mild Traumatic Brain Injury (mTBI) Biomarkers

Globally, 70 million people are annually affected by TBI. A significant proportion of all TBI cases are actually mild TBI (concussion, 70-85%), which is considerably more difficult to diagnose due to the absence of apparent symptoms. Current clinical practice of diagnosing mTBI largely resides on the patients' history, clinical aspects, and CT and MRI neuroimaging observations. The latter methods are costly, time-consuming, and not amenable for decentralized or accident site measurements. As an alternative (and/or complementary), mTBI diagnostics can be performed by detection of mTBI biomarkers from patients' blood. Herein, we proposed two strategies for the detection of three mTBI-relevant biomarkers (GFAP, h-FABP, and S100 beta), in standard solutions and in human serum samples by using an electrochemiluminescence (ECL) immunoassay on (i) a commercial ECL platform in 96-well plate format, and (ii) a POC-friendly platform with disposable screen-printed carbon electrodes (SPCE) and a portable ECL reader. We further demonstrated a proof-of-concept for integrating three individually developed mTBI assays (singleplex) into a three-plex (multiplex) assay on a single SPCE using a spatially resolved ECL approach. The presented methodology demonstrates feasibility and a first step towards the development of a rapid POC multiplex diagnostic system for the detection of a mTBI biomarker panel on a single SPCE.

Automated summary

Globally, 70 million people are affected by traumatic brain injury (TBI) annually. Diagnosis of mild TBI (mTBI) is challenging due to the absence of apparent symptoms. Current diagnostic methods rely on patient history, clinical aspects, and neuroimaging observations, which are costly and time-consuming. As an alternative, mTBI diagnostics can be done by detecting biomarkers in patients' blood. This study proposed two strategies for detecting mTBI biomarkers using electrochemiluminescence (ECL) immunoassay. Multiplex assays on a single disposable screen-printed carbon electrode (SPCE) were also developed. The methodology presented demonstrates the feasibility of a rapid point-of-care (POC) multiplex diagnostic system for mTBI biomarkers.