Accurate and comprehensive cardiac troponin I assay enabled by nanotechnology and proteomics

Abstract

This invention provides mass spectrometry (MS) compatible nanomaterials for the selective capture and enrichment of low abundance proteins as well as MS analysis of different proteoforms of proteins, particularly cardiac proteins and different proteoforms of cardiac troponin I (cTnI) arising from post-translational modifications and sequence variations. The surface of superparamagnetic nanoparticles is functionalized with probe molecules that specifically bind to the desired protein. In an embodiment, the nanoparticles are functionalized with probe molecules having high affinity and selectivity for cTnI within the human cardiac troponin complex. This allows for MS-analysis and characterization of cTnI proteoforms from human heart tissue lysates and human blood or serum samples, and provides an accurate assay for detection of cTnI with molecular details. Such assays are useful for accurate diagnosis of acute coronary syndrome and chronic diseases, including acute myocardial infarction and other cardiac injuries, as well as risk stratification and outcome assessment for patients.

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