Simoa and MSD platforms show analytical discordance but comparable diagnostic performance for GFAP, NF-L, and T-tau in adolescent concussion

Blood-based biomarkers like glial fibrillary acidic protein (GFAP), neurofilament light (NF-L), and total tau (T-tau) have shown promise for objective diagnosis of concussion and mTBI. However, differences in analytical platforms used to measure concentrations of these biomarkers like Single Molecule Array (Simoa) and Meso Scale Discovery (MSD), may impact their clinical utility. This study aimed to both qualify and quantify differences between platforms while also evaluate both inter- and intra-platform agreement using a novel statistical approach in a youth population. Plasma samples from 108 adolescent athletes (53 pre-injury controls, 55 post-concussion) in the SHRed Concussions cohort were analyzed using Simoa and MSD platforms. Platform variation was assessed using CVs, correlations, and mixed models for intraclass correlation coefficients. Diagnostic performance in classifying concussion was assessed and compared across platforms. Concentrations differed substantially (3-8 fold) with negligible correlations (ρ < 0.14). Intra-assay CVs were similar (7-10%), but Simoa showed higher CVs in concussed samples (p < 0.05 across biomarkers). Between-platform absolute agreement was poor (ICCs: GFAP 0.44, NF-L 0.14, T-tau 0.07), while within-platform consistency was excellent (0.880-0.999 for Simoa; 0.728-0.986 for MSD). Despite analytical discordance, both platforms yield similar diagnostic accuracy for adolescent concussion classification. Future development of platform-specific ranges is warranted.