We describe progress towards developing a low-cost, simple, and compact imaging system for Digital Bead Assays (DBA) for use in Point-of-Care (POC) diagnostic systems. DBA — such as digital ELISA using single molecule arrays (Simoa) — have emerged as a key advance for the sensitive detection of proteins down to attomolar concentrations, i.e., single-digit numbers of proteins in a droplet of blood or another clinical sample. These assays have enabled unique clinical research and diagnostic measurements, e.g., the measurement in blood of protein biomarkers of neurological conditions, enabling “blood tests for the brain” that can detect Alzheimer’s disease 16 years before dementia symptoms arise. For DBA to have its maximum impact on society, it must be available in low-cost, compact equipment that can be used by anyone around the world. For this goal to become a reality, low-cost and simple imaging systems are needed. In this paper, we will describe a concept for a low-cost, simple, and compact DBA imager. We will describe evaluation of low-cost optics — such as cell-phone optics — and cameras, and how image analysis methods can be used to generate useful data from the lower resolution images provided by these systems.
William McGuigan, David Fournier, Gary Watson, Les Walling, Bill Gigante, David Duffy, David Rissin, Cheuk Kan, Raymond Meyer, Tomasz Piech, Matthew Fishburn
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.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
INSTITUTIONAL Select your institution to access the SPIE Digital Library.
PERSONAL Sign in with your SPIE account to access your personal subscriptions or to use specific features such as save to my library, sign up for alerts, save searches, etc.