A digital microarray using interferometric detection of plasmonic nanorod labels

TL;DR

This paper introduces a digital microarray technology that uses interferometric detection of plasmonic gold nanorods, significantly improving sensitivity and dynamic range without sacrificing throughput, enabling single-molecule detection in biomolecular assays.

Contribution

The authors develop a novel interferometric microarray platform utilizing gold nanorods as labels, achieving high sensitivity and wide dynamic range without chemical amplification.

Findings

Extends microarray sensitivity and dynamic range by about three orders of magnitude.

Achieves a dynamic range of approximately one million from a single scan.

Does not require chemical enhancement, maintaining high throughput.

Abstract

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.