  DNA and protein microarrays are a high-throughput technology that allow the
simultaneous quantification of tens of thousands of different biomolecular
species. The mediocre sensitivity and dynamic range of traditional fluorescence
microarrays compared to other techniques have been the technology's Achilles'
Heel, and prevented their adoption for many biomedical and clinical diagnostic
applications. Previous work to enhance the sensitivity of microarray readout to
the single-molecule ('digital') regime have either required signal amplifying
chemistry or sacrificed throughput, nixing the platform's primary advantages.
Here, we report the development of a digital microarray which extends both the
sensitivity and dynamic range of microarrays by about three orders of
magnitude. This technique uses functionalized gold nanorods as single-molecule
labels and an interferometric scanner which can rapidly enumerate individual
nanorods by imaging them with a 10x objective lens. This approach does not
require any chemical enhancement such as silver deposition, and scans arrays
with a throughput similar to commercial fluorescence devices. By combining
single-nanoparticle enumeration and ensemble measurements of spots when the
particles are very dense, this system achieves a dynamic range of about one
million directly from a single scan.
