Until about a hundred years ago, clinical diagnosis relied mostly on medical history and physical examination. However, there are many diseases that exhibit similar symptoms, making it difficult to achieve direct diagnosis based on clinical presentation. Doctors have always sought complementary validation, and rudimentary clinical tests date back thousands of years, when the color and odor of urine was utilized in diagnostics. In modern medicine, in vitro tests are a cornerstone of clinical practice, with the sensitivity of standard immunoassays measuring protein biomarkers at picomolar concentrations.1 However, while this level of sensitivity is sufficient for the diagnosis of infectious diseases when clear symptoms are present, it falls short—perhaps by a factor of many thousands—for the detection of proteins that are important in cancer,2 neurological disorders,3 and the early stages of infection.4 Devastating epidemics have exposed the limitations of current technologies, and emphasized the importance of continuing innovation and refinement of in vitro diagnostics, especially at an affordable cost.
