Evaluation of a novel high-capacity dry plasma biosampling-lateral flow device for the testing of traumatic brain injury protein biomarkers

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Background and purpose Current blood-based diagnostic tests for traumatic brain injury (TBI), such as those measuring UCH-L1 and GFAP, require venous whole blood or plasma samples collection and cold-chain handling. No FDA-cleared TBI test currently supports capillary blood or dried sample formats. We propose incorporating a novel dried plasma collection device into future TBI diagnostic workflows. This format is compatible with fingerstick sampling, simplifies storage and transport, reduces biosampling burdens, and preserves key TBI biomarker detectability. Our study evaluates this device’s analytical performance, focusing on biomarker stability under various storage conditions and its compatibility with multiplex TBI biomarker assays. Methods Capillary blood (50–70 µL) or archived plasma was applied to a Dried Plasma Biosampling Lateral Flow (DPB-LF) device. The device separates plasma via a cell filter onto a nitrocellulose strip. After air-drying for 30 min, samples were stored with desiccants under various temperatures and durations. Later, dried plasma was rehydrated and analyzed using the Quanterix Neurology 4-Plex B assay, and biomarker levels were compared to matched wet plasma samples. Results With capillary blood from healthy controls, the DPB-LF device demonstrated consistent plasma separation. SDS-PAGE analysis showed similar protein profiles in dried versus wet plasma. As proof of principle, pooled plasma samples from TBI patients and healthy controls were applied to DPB-LF devices and stored at different temperatures (4 °C, room temperature, and 40 °C) and durations (1, 7, 14, and 21 days). Upon rehydration, dried TBI plasma samples consistently yield robust recovery of GFAP, UCH-L1, NfL, and Tau signals at 4 °C across all time points and at room temperature for up to 7 days. Extended storage durations and elevated temperatures (14–21 days at room temperature, or 7–21 days at 40 °C) led to partial reductions in biomarker signal recovery, as expected. Additionally, archived plasma samples from 16 geriatric TBI patients (GCS 13–15) were applied to the DPB-LF device. Upon rehydration, biomarker levels from the dried samples showed strong correlations with matched wet plasma, with R 2 ranging from 0.829 to 0.995 for GFAP, NfL, Tau, and UCH-L1. We further examined the DPB-LF device using plasma samples from a second independent cohort of 44 adult TBI subjects (GCS 3–15) collected on post-injury day 1. Dried plasma demonstrated robust prediction of cranial lesions on computed tomography, with AUC/ROC values of 0.756, 0.734, 0.738, and 0.703 for GFAP, NfL, Tau, and UCH-L1, respectively. All four biomarker levels measured in dried plasma also showed significant correlations with injury severity categories (GCS 3–8, 9–12, and 13–15) using nonparametric Kruskal-Wallis testing. Conclusion The DPB-LF device enables minimally invasive capillary blood collection and stable dried plasma storage, supporting multiplex TBI biomarker analysis. This technology shows promise for clinical and field use, with potential application in future TBI studies and diagnostic purposes.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.