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Table 1 General description of the most important measurement technologies for Alzheimer’s disease biofluid-based biomarkers

From: Moving fluid biomarkers for Alzheimer’s disease from research tools to routine clinical diagnostics

Technology Explanation
Sandwich enzyme-linked immunosorbent assay (ELISA) The target analyte is captured between two antibodies (capture and detection). The capture antibody is immobilized onto a surface (often the plastic surface of a well, e.g., in a 96-well plate). The detection antibody is labeled with an enzyme that produces a measurable signal (fluorescence or color) by converting a substrate to a product. The lower limit of quantification of an ELISA depends on the antibodies and the target analyte but is often in the nano- to picomolar range.
Immunoassay with electrochemiluminescence detection (ECL) A variant of ELISA but instead of an enzyme, the detection antibody is labeled with a molecule that directly produces luminescence during an electrochemical reaction. This detection principle is often a little bit more sensitive than ELISA.
Single molecule array (Simoa) This is a classical sandwich ELISA, but the capture antibody is conjugated to magnetic beads instead of the bottom of a 96-well plate, and the sandwich complexes (bead, capture antibody, target analyte and enzyme-labeled detection antibody) are pulled down in microwells (one bead per well), where the detection reaction is allowed to occur. This compartmentalized detection reaction in a very small volume allows for the detection of the biomarker at the single molecule level. In biofluids, the Simoa assays can be 100 to 1000 times as sensitive as a regular ELISA (subfemtomolar analytical sensitivity).
Immunoprecipitation mass spectrometry (IP-MS) This technology has been particularly useful for the development of reliable plasma amyloid β tests. Antibodies against the target analyte are conjugated to beads, and the target analyte is isolated from the sample by immunoprecipitation, eluted, and then quantified by mass spectrometry, together with an isotope-labeled internal standard. The mass spectrometric detection makes the assay very specific for the target analyte.
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