The Current State of Traumatic Brain Injury Biomarker Measurement Methods

Abstract

Traumatic brain injury (TBI) is associated with high rates of morbidity and mortality partially due to the limited tools available for diagnosis and classification. Measuring panels of protein biomarkers released into the bloodstream after injury has been proposed to diagnose TBI, inform treatment decisions, and monitor the progression of the injury. Being able to measure these protein biomarkers at the point-of-care would enable assessment of TBIs from the point-of-injury to the patient's hospital bedside. In this review, we provide a detailed discussion of devices reported in the academic literature and available on the market that have been designed to measure TBI protein biomarkers in various biofluids and contexts. We also assess the challenges associated with TBI biomarker measurement devices and suggest future research directions to encourage translation of these devices to clinical use.

Keywords: biomarkers; electrochemical detection; immunosensors; microfluidics; optical detection; traumatic brain injury.

Figure 1

The µDrop system from Khetani et al. designed to perform differential pulse voltammetry to quantify C-tau and NF-L. Reprinted with permission from [36]. Elsevier 2021.

Figure 2

An organic field effect transistor (OFET) with an extended solution gate from Song et al. designed to measure GFAP. Reprinted with permission from [49]. John Wiley and Sons, 2017.

Figure 3

The variable height device from Krausz et al. designed to passively multiplex bead-based QLISAs (quantum dot-linked immunosorbent assays) for GFAP, IL-6, and IL-8 [46].

Figure 4

A SERS-based microfluidic device capable of a sample-in, results-out workflow from Rickard et al. Reprinted with permission from [48]. Springer Nature, 2020.

Figure 5

An ultra-high-frequency surface-acoustic-wave chip from Agostini et al. with the ability to multiplex up to four biomarkers. The red scale bar is 1 cm long. Reprinted with permission from [42]. Elsevier, 2021.

Figure 6

A traumatic brain injury biomarker measurement device can only be developed with constant feedback between clinicians and engineers. The clinical parameters inform the device parameters and vice versa until the optimal device is realized.