Specificity

For most protein assays, specificity means one thing:
binding affinity

The SomaScan® Assay accomplishes specificity in two ways:
binding affinity and dissociation rate

Binding Affinity

SOMAmer® reagents are aptamers, synthetic ssDNA sequences, that have been developed to bind specific protein targets through a selected evolution process called SELEX (Systematic Evolution of Ligands by EXponential enrichment).

Unlike many affinity strategies, SOMAmer reagents are trained on conformational epitopes for exquisite shape complementarity. Further, extensive surface area contact between a SOMAmer reagent and its epitope is accomplished via protein-like functional groups that are added at the 5-position of deoxyuridine of each SOMAmer reagent.

X=ray crystal structure of a SOMAmer reagent bound to PDGF-BB
Figure 2. X-ray crystal structure of a SOMAmer reagent bound to PDGF-BB. Modifications to the bases are shown in purple, and the DNA backbone and unmodified bases are in teal.
Graph showing typical dissociation for a SOMAmer reagent (in this case targeting C3)

Dissociation Rate

The word SOMAmer stands for Slow Off-rate Modified Aptamer. As the name suggests, the SOMAmer reagents not only bind certain conformational epitopes specifically, but they also remain bound to their protein target for a significant length of time (typical half-lives of 30 minutes or more).

The slow off-rate is accomplished in part by the fact that SOMAmer:epitope interfaces are considerably more hydrophobic than conventional aptamer:protein interfaces. Additionally, because the SOMAmer reagents are composed of DNA, SomaScan technology utilizes polyanionic competitors to selectively reduce non-specific interactions (which have much shorter half lifes).