The main objective is the development of highly multiplexed affinity proteomics tools for point of care diagnostics. Enabled by the world's largest resource of antibodies to human protein targets generated within the framework of the Human Protein Atlas program, the aim of this application is to develop new concepts in translational medical research to allow dramatic improvement in performance and accessibility of point of care tests in both high and low resource clinical settings in infectious diseases, autoimmune conditions and several cancers. To achieve the goal, developments will be made in 1) detection principles and sample preparation, 2) rapid and low cost protein microarrays assays and 3) novel amplification strategies. Strategies will be developed to for the first time enable highly multiplexed sandwich detection across the analytical range of the plasma proteome. Four different novel microarray formats amenable for point of care are presented that each will allow dramatically improved multiplexity and high performance. Different types of new multifunctional silica/gold nanoparticles exhibiting combinations of magnetic, fluorescent, electro-active, enzymatic and optical qualities that will allow deterministic actuation and multimodal detection options will be synthesized and applied for exquisite sensitivity and rapid detection. Following the technology development, developed assay systems will be implemented for full plasma proteome analysis and in the three clinical areas: infectious diseases, autoimmune conditions and cancers. Collaborations with clinical researchers in all the relevant fields have already been established. In theses clinical fields, a body of previous research efforts has shown that highly multiplexed plasma analysis may dramatically improve diagnostic accuracy, and it is here that the novel comprehensive point of care systems presented in this proposal may conceivably create the largest impact for patients and health care systems.