Quanterix and Stratec Biomedical have developed an instrument that enables the automated measurement of multiple
proteins at concentration ~1000 times lower than existing immunoassays. The instrument is based on Quanterix’s
proprietary Single Molecule Array technology (Simoa™ ) that facilitates the detection and quantification of biomarkers
previously difficult to measure, thus opening up new applications in life science research and in-vitro diagnostics.
Simoa is based on trapping individual beads in arrays of femtoliter-sized wells that, when imaged with sufficient
resolution, allows for counting of single molecules associated with each bead. When used to capture and detect proteins,
this approach is known as digital ELISA (Enzyme-linked immunosorbent assay).
The platform developed is a merger of many science and engineering disciplines. This paper concentrates on the optical
technologies that have enabled the development of a fully-automated single molecule analyzer. At the core of the
system is a custom, wide field-of-view, fluorescence microscope that images arrays of microwells containing single
molecules bound to magnetic beads. A consumable disc containing 24 microstructure arrays was developed previously
in collaboration with Sony DADC. The system cadence requirements, array dimensions, and requirement to detect
single molecules presented significant optical challenges. Specifically, the wide field-of-view needed to image the entire
array resulted in the need for a custom objective lens. Additionally, cost considerations for the system required a custom
solution that leveraged the image processing capabilities. This paper will discuss the design considerations and
resultant optical architecture that has enabled the development of an automated digital ELISA platform.