Concordance Between Capillary Dried Plasma Spot and Venous Plasma Biomarkers in Traumatic Brain Injury: An Analytical Feasibility Pilot Study
- 1Gryphon Bio, 611 Gateway Blvd, Suite 120 Unit 253, South San Francisco, CA 94080, USA; Owl Therapeutics, 255 Main St Ste 200, Cambridge, MA 02142, USA
Abstract
BackgroundTraumatic brain injury (TBI) increases long-term risk for cognitive decline and neurodegeneration, motivating objective blood biomarkers that can be measured repeatedly over time. However, reliance on venipuncture limits longitudinal monitoring, particularly outside clinic settings.
ObjectiveWe conducted a pilot feasibility study comparing fingerstick capillary blood collected as dried plasma spots (DPS) with matched venous EDTA plasma for quantification of glial fibrillary acidic protein (GFAP) and neurofilament light (NfL).
MethodsPaired samples were collected prospectively across matched time points spanning hours to decades post-injury and assayed using high-sensitivity immunoassays.
ResultsAbsolute protein recovery from DPS was lower and more variable than venous plasma, but paired GFAP and NfL measurements remained well-correlated. We further evaluated the GFAP/NfL ratio as an internal, sample-based normalization strategy and observed improved concordance between capillary DPS and venous plasma compared with either analyte alone.
ConclusionsThese pilot findings support the analytical feasibility of capillary DPS sampling for GFAP and NfL measurement in TBI and identify the GFAP/NfL ratio as an exploratory internal-normalization approach. Formal analytical and clinical validation -- including outcome linkage and prospective evaluation -- will be required before capillary DPS can be considered for clinical monitoring applications.
HighlightsO_LIFirst high-frequency (twice-daily for 14 days) paired capillary-DPS / venous-plasma GFAP and NfL trajectories in acute TBI (Cohort #1, n = 4). C_LIO_LIStrong within-subject capillary-venous correlations for GFAP ({rho} up to 0.647) and NfL ({rho} up to 0.902); the GFAP / NfL ratio reaches {rho} = 0.797-0.977. C_LIO_LICross-sectional capillary-DPS biomarkers separate acute, subacute, and chronic TBI populations across a multi-site cohort (Cohort #2). C_LIO_LIConcurrent work by Bouthors et al. (CCLM 2026) supports prioritizing GFAP and NfL over UCH-L1 for capillary panels because UCH-L1 is intra-erythrocytic and hemolysis-sensitive. C_LIO_LICapillary DPS sampling establishes analytical feasibility for paired capillary-venous GFAP and NfL measurement; formal validation of context-of-use, unsupervised collection, and outcome linkage is required before clinical deployment. C_LI
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BibTeX
@misc{jackson2026concordance,
title = {{Concordance Between Capillary Dried Plasma Spot and Venous Plasma Biomarkers in Traumatic Brain Injury: An Analytical Feasibility Pilot Study}},
author = {D. Jackson and K. Tehas and K. Radeker and A. DeLizza and C. Popper and E. Peskind and A. Puccio and R. C. Gardner and J. B. Williamson and A. B. Waters and L. H. Merck and G. Manley and K. K. Wang and W. E. Haskins},
howpublished = {medRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.16.26361861},
url = {https://www.medrxiv.org/content/10.64898/2026.09.16.26361861v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Concordance Between Capillary Dried Plasma Spot and Venous Plasma Biomarkers in Traumatic Brain Injury: An Analytical Feasibility Pilot Study
AU - D. Jackson
AU - K. Tehas
AU - K. Radeker
AU - A. DeLizza
AU - C. Popper
AU - E. Peskind
AU - A. Puccio
AU - R. C. Gardner
AU - J. B. Williamson
AU - A. B. Waters
AU - L. H. Merck
AU - G. Manley
AU - K. K. Wang
AU - W. E. Haskins
PY - 2026
DA - 2026/09/16
PB - medRxiv
DO - 10.64898/2026.09.16.26361861
UR - https://www.medrxiv.org/content/10.64898/2026.09.16.26361861v1
AB - BackgroundTraumatic brain injury (TBI) increases long-term risk for cognitive decline and neurodegeneration, motivating objective blood biomarkers that can be measured repeatedly over time. However, reliance on venipuncture limits longitudinal monitoring, particularly outside clinic settings. ObjectiveWe conducted a pilot feasibility study comparing fingerstick capillary blood collected as dried plasma spots (DPS) with matched venous EDTA plasma for quantification of glial fibrillary acidic protein (GFAP) and neurofilament light (NfL). MethodsPaired samples were collected prospectively across matched time points spanning hours to decades post-injury and assayed using high-sensitivity immunoassays. ResultsAbsolute protein recovery from DPS was lower and more variable than venous plasma, but paired GFAP and NfL measurements remained well-correlated. We further evaluated the GFAP/NfL ratio as an internal, sample-based normalization strategy and observed improved concordance between capillary DPS and venous plasma compared with either analyte alone. ConclusionsThese pilot findings support the analytical feasibility of capillary DPS sampling for GFAP and NfL measurement in TBI and identify the GFAP/NfL ratio as an exploratory internal-normalization approach. Formal analytical and clinical validation -- including outcome linkage and prospective evaluation -- will be required before capillary DPS can be considered for clinical monitoring applications. HighlightsO_LIFirst high-frequency (twice-daily for 14 days) paired capillary-DPS / venous-plasma GFAP and NfL trajectories in acute TBI (Cohort #1, n = 4). C_LIO_LIStrong within-subject capillary-venous correlations for GFAP ({rho} up to 0.647) and NfL ({rho} up to 0.902); the GFAP / NfL ratio reaches {rho} = 0.797-0.977. C_LIO_LICross-sectional capillary-DPS biomarkers separate acute, subacute, and chronic TBI populations across a multi-site cohort (Cohort #2). C_LIO_LIConcurrent work by Bouthors et al. (CCLM 2026) supports prioritizing GFAP and NfL over UCH-L1 for capillary panels because UCH-L1 is intra-erythrocytic and hemolysis-sensitive. C_LIO_LICapillary DPS sampling establishes analytical feasibility for paired capillary-venous GFAP and NfL measurement; formal validation of context-of-use, unsupervised collection, and outcome linkage is required before clinical deployment. C_LI
ER -