Meso Scale Discovery (MSD) is a technique to quantitate the presence of an analyte. The technique is quite similar to ELISA, with an exception to the detection technique. MSD assay uses electrochemiluminescence (ECL) for detection, whereas ELISA assays rely on a colorimetric reaction.
Meso Scale Discovery Electrochemiluminescence is a well-regarded technique for use with Ligand Binding Assays (LBA). This technique has a few advantages that set it apart from other popular techniques like ELISA validation. However, it remains very similar to the general methods through which ELISA operates.
Detection Using MSD
MSD involves the use of high binding carbon electrodes at the bottom of multi-array and multi-spot microplates. MSD assays use conjugated electrochemiluminescent labels for the detection of antibodies. Electricity from the carbon electrodes is applied to these SULFO-TAG labels that provide ultra-sensitive detection.
Light intensity from these labels is the key to identify and quantitate the presence of an analyte in the samples. MSD can work with a broad range of sample types, including blood, serum, and tissue. Amongst the applications of this technique is the ability to perform ADA immunogenicity testing, biomarkers, and PK/TK analysis.
A useful aspect of MSD and ECL is that it requires a very low sample volume. A sample volume as low as 10-25 µL is sufficient to carry out the analysis. This is very useful throughout the drug development process, but more so in early stages where sample availability is limited. In comparison, the conventional ELISA needs 50–100 μL of sample volume per analyte.
Dynamic Range and High Sensitivity
Amongst the most useful qualities of Meso Scale Discovery are its high dynamic range and high sensitivity. Its use of non-radioactive ECL labels enables this technique to have high sensitivity over a broad dynamic range.
For better detection and higher sensitivity, the system decouples electricity from the signal. This means only labels close to the electrode surface are detected, thus reducing the noise from the matrix.
For example, in a sandwich assay, the capture antibody is placed at the bottom of the well. The second antibody is bound to ruthenium (Ru) metal ion. As we know, the bottom of the well in MSD is an electrode. If the second antibody binds the antigen, the Ru-ion will produce luminescence, which can be captured and detected.
Other advantages it brings over ELISA include signal amplification, low background noise, and reduced matrix effects. This leads to the system being more efficient and capable. Although, as you see, there is an element of increased complexity as compared to ELISA.
Meso Scale Discovery Electrochemiluminescence allows multiplexing to detect multiple analytes in the sample matrix. The technique can be used for the detection of up to 10 analytes. Compared to ELISA, this means a single plate of MSD-ECL can accomplish what would otherwise require 10 ELISA plates.
Multiplexing offers general advantages, especially with the ability to test multiple analytes in one go. The plates available for MSD include single-spot, four-spot, seven-spot, and ten-spot. The “spot” in this terminology represents the multiplexing wells available for analysis. The plates are available in the conventional 96-well and 384-well configuration.
Pre-made kits are available. Depending on specific requirements, these can be pre-validated V-plex, customized multiplexing U-plex, ultra-sensitive assay S-plex, and non-multiplexed R-plex.