title: A high-throughput nanoimmunoassay chip applied to large-scale vaccine adjuvant screening.
abstract: Large-scale experimentation is becoming instrumental in enabling new discoveries in systems biology and personalized medicine. We developed a multiplexed high-throughput nanoimmunoassay chip capable of quantifying four biomarkers in 384 5 nL samples, for a total of 1536 assays. Our platform, compared to conventional methods, reduces volume and reagent cost by ~1000-fold. We applied our platform in the context of systems vaccinology, to assess the synergistic production of inflammatory cytokines from dendritic cells (DCs) stimulated with 10 different adjuvants that target members of the Toll-like receptor (TLR) family. We quantified these adjuvants both alone and in all pairwise combinations, for a total of 435 conditions, revealing numerous synergistic pairs. We evaluated two synergistic interactions, MPLA + Gardiquimod and MPLA + CpG-B, in a mouse model, where we measured the same inflammatory cytokines in bronchoalveolar lavage and in blood serum at 4 different time points using our chip, and observed similar synergistic effects in vivo, demonstrating the potential of our microfluidic platform to predict agonistic immunogenicity. More generally, a high-throughput, matrix-insensitive, low sample volume technology can play an important role in the discovery of novel therapeutics and research areas requiring large-scale biomarker quantitation.
authors: Institute of Bioengineering, School of Engineering, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors: Jose L
authors: JL
authors: Garcia-Cordero
authors: Chiara
authors: C
authors: Nembrini
authors: Armando
authors: A
authors: Stano
authors: Jeffrey A
authors: JA
authors: Hubbell
authors: Sebastian J
authors: SJ
authors: Maerkl
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D004353:Drug Evaluation, Preclinical / Q000295:instrumentation*; D004867:Equipment Design; D019544:Equipment Failure Analysis; D017022:Flow Injection Analysis / Q000295:instrumentation; D007118:Immunoassay / Q000295:instrumentation*; D051379:Mice; D008810:Mice, Inbred C57BL; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation; D036103:Nanotechnology / Q000295:instrumentation*; D046888:Tissue Array Analysis / Q000295:instrumentation*; D051193:Toll-Like Receptors / Q000037:antagonists & inhibitors; D014612:Vaccines / Q000008:administration & dosage*
chemical_list: D000276:Adjuvants, Immunologic; D016207:Cytokines; D051193:Toll-Like Receptors; D014612:Vaccines