2026-10-14T13:12:50Z https://api.figshare.com/v2/oai

oai:figshare.com:article/34027224 2026-09-29T18:10:41Z category_4 category_146 category_7 category_21 category_106 category_46 category_133 portal_63 item_type_6 month_year_09_2026

An Internal-Standard-Integrated Digital SERS Immunoassay for Accurate and Precise Trace-Level Cytokine Quantification in Plasma Yiwen Zhang (512835) Fahimeh Farokhinejad (11653576) Jacob J. Crouse (6188990) Mirim Shin (20923118) Anjali K. Henders (10486568) Leanne M. Wallace (25138509) Richard J. Lobb (5181893) Fiach Antaw (2050555) Naomi R. Wray (6650309) Ian B. Hickie (6904997) Alain Wuethrich (1615159) Matt Trau (472531) Biochemistry Space Science Medicine Biotechnology Science Policy Immunology Plant Biology maintaining multiplex capability enhanced raman scattering clinically relevant context aberrant immune activation orthogonal recombinant protein defined quantification limits broader clinical adoption level cytokine quantification protein measurements precise quantification clinical studies level inflammation level detection level cytokines replicate coefficient related variability potential utility platform incorporating measurements support longitudinal biomarkers improved accuracy human plasma enabled surface concept application complex samples analytical robustness Accurate and precise quantification of trace-level cytokines in complex biological matrices remains challenging, limiting their use as longitudinal biomarkers in clinical studies. Here, we present a nanotechnology-enabled surface-enhanced Raman scattering (SERS) platform incorporating an internal standard (IS) for digital, attomolar-level multiplex cytokine quantification. This platform enables precise digital trace-level detection of IL-1β, IL-6, IL-12, and TNF-α. Using an orthogonal recombinant protein IS to correct assay- and SERS-related variability, this platform addresses key barriers to reliable trace-protein measurements and broader clinical adoption. Incorporation of the IS reduced the inter-replicate coefficient of variation from ∼40–60% to 2–3%, and improved accuracy to ∼95–105%, enabling robust cytokine quantification in human plasma. Compared with a widely used clinical electrochemiluminescence (ECL) assay, our internal-standard-integrated chip enables accurate and precise quantification while maintaining multiplex capability, consistently detecting cytokine levels near or below ECL-defined quantification limits. As a proof-of-concept application, we evaluated the platform using plasma samples from individuals with MDD, a clinically relevant context in which aberrant immune activation and low-level inflammation have been implicated. These measurements support the analytical robustness of the internal-standard-integrated digital SERS immunoassay and its potential utility for future longitudinal cytokine monitoring studies in complex samples. 2026-09-29T00:00:00Z Text Journal contribution 10.1021/acs.analchem.6c03298.s001 https://figshare.com/articles/journal_contribution/An_Internal-Standard-Integrated_Digital_SERS_Immunoassay_for_Accurate_and_Precise_Trace-Level_Cytokine_Quantification_in_Plasma/34027224 CC BY-NC 4.0