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. 2023 Jan 18;20(198):20220406. doi: 10.1098/rsif.2022.0406

Table 2.

General description of the most important measurement technologies for Alzheimer's disease biofluid-based biomarkers [34]. The table includes technologies that may be useful for both blood- and CSF-based biomarkers but some of the biomarkers are present at very low concentrations in blood, which may require ultrasensitive assays (more sensitive than ELISA).

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 labelled with an enzyme that produces a measurable signal (fluorescence or colour) 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 pico-molar range.
immunoassay with electrochemiluminescence detection (ECL) A variant of ELISA but instead of an enzyme, the detection antibody is labelled 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-labelled 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 (sub-femtomolar analytical sensitivity).