MnO2 nanosheet decorated gold nano cluster-antibody conjugates as a FRET-based immunosensor for the selective visual detection of Caspase-3: A biomarker for traumatic brain injury

Traumatic brain injury (TBI) remains a pervasive and catastrophic condition, ranking as a leading cause of global mortality, morbidity and disability. Assessing TBI poses a significant challenge due to the lack of sensitive diagnostic tools. Clinicians currently resort to CT scans and MRI scans, which are not only expensive and insensitive but also inaccessible to rural areas, delaying timely diagnosis and treatment. To overcome this limitation, we have developed a novel biomarker-based detection method for assessing brain injuries, employing caspase-3 as the biomarker. For this a a fluorescence resonance energy transfer (FRET) based biosensor was developed using gold nano cluster-antibody conjugates decorated with MnO₂ nanosheets. Upon addition of caspase-3 antigen (ACa3), the sensor exhibited a significant fluorescent enhancement, achieving a limit of detection as low as 23 pg/mL. The study was further extended to detect ACa3 in human serum samples yielding a recovery percentage ranging from 93 to 98 %. To assess the clinical feasibility of the sensor and to enable visual detection, a paper-based test strip was also developed, which specifically detects ACa3 amidst other competing biomolecules and ions present in the body.