NANOGNOSTICS · Quantum Dot-Based Highly Sensitive Immunoassays for Multiplexed Diagnostics of Alzheimer's Disease

6.1 million people currently live with a form of dementia in the European Union with an addition of 1.4 million new cases every year. Combination of psychological testing, brain-imaging and exclusion of other neurological disorders makes the diagnosis of Alzheimer’s disease complicated and time consuming (taking up to 20 months). A rapid, sensitive and specific immunoassay for protein markers inside blood would largely improve early diagnosis and lead to a better treatment of dementia. Homogeneous assays based on FRET from one dye labeled specific antibody (AB1) to another (AB2) within an “AB1-biomarker-AB2” immune complex are an ideal basis to meet these diagnostic requirements. As the detection of several protein markers is obligatory for a highly sensitive and specific diagnosis an optical multiplexing approach with dyes of different colors is a smart solution. Semiconductor quantum dots (QDs) are the ideal candidates due to their size-dependent absorption and emission wavelengths. Moreover, they possess unique photophysical properties that overcome conventional fluorescence dyes. In combination with lanthanide complexes (LCs), that display long luminescence lifetimes and well separated emission bands, QDs render a powerful multiplexing tool for highly sensitive diagnostics even for large immune complexes. FRET applications using QDs are to date restricted to academic research and a profound understanding of QD-based FRET is not available. For a comprehensive analysis the use of LCs is mandatory, because they are the only known donors for efficient FRET to QD acceptors. NANOGNOSTICS strives for a profound understanding of QD-based FRET, the synthetic creation of highly efficient QD immune sensors for detection of several Alzheimer-specific protein markers and the development of a modular high-throughput-screening immuno analyzer for the integration of QD-based multiplexing immunoassays into early diagnosis for improved patient outcome in dementia therapy.