| Summary: | Traumatic brain injury (TBI) is a serious health concern and a leading cause of death in all age groups, especially adults. Although the processes of prevention, lifestyle modification, accident safety, and therapeutic management of TBI are constantly evolving, the development of accurate and trustworthy procedures for diagnosing brain damage, such as detecting specific biomarkers is still in its infancy. Early detection of TBI biomarkers, especially blood biomarkers, can improve treatment approaches and significantly reduce diagnostic costs. Different routine analytical methods, including ELISA and PCR techniques, have been used to detect TBI biomarkers. These procedures are generally complex, expensive, time-consuming, and require trained personnel. In contrast, biosensing techniques have been developed precisely through addressing the aforementioned weaknesses along with offering an accessible, affordable, rapid, highly sensitive, and specific approach. This comprehensive review presents the six main TBI biomarkers (S100β, NSE, GFAP, UCHL-1, MBP, and TAU). It also focuses on the design mechanism of biosensing pathways of TBI biomarkers and nanotechnology integration methods, including the nanoparticles and nanostructures application in surface modification and improving the performance of the sensing procedures. Furthermore, through this study, the TBI-specific biosensors platform from the viewpoint of the transducer types and analysis output are evaluated. Finally, the current challenges and future perspectives regarding the development of biosensors for the early diagnosis of TBI are discussed.
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