Multiplexed Protein Diagnostics for Complex Infection-Associated Conditions: Advancing Proof-of-Concept Biosensors toward Clinical Deployment

Infection-associated health conditions are often diagnostically overlooked, largely due to non-specific overlapping symptoms, and the limited availability of multiplexed assays. Their diagnosis is further exacerbated by differences in underlying patient-to-patient physiology, which results in considerable heterogeneity in disease presentation and diagnostic levels of candidate biomarkers. Multiplexed protein detection offers one approach to addressing confounding patient heterogeneities, providing a functional snapshot of current disease states. Commercial assays compatible with such disease profiling are often time-consuming and require trained operators, restricting their utility in rapid clinical decision making. Recently, miniaturized, multiplexed protein diagnostics have emerged in hopes of addressing these limitations but have largely been restricted to proof-of-concept demonstrations. The path towards deployable technologies is often not fully appreciated during fundamental method development, which can lead to downstream problems in translation and adoption. This review emphasizes the role of multiplexed protein-based diagnostics as exploratory and translational research tools for infection-associated health conditions. • Diagnostic requirements for infection-associated diseases are detailed. • Commercial multiplexed platforms for infectious disease profiling are surveyed. • Emerging multiplexed technologies for infection-associated conditions are explored. • Inter-patient differences complicate diagnosis of infection-associated conditions. • Key translational barriers for proof-of-concept platforms are evaluated.