A smartphone-based laser-scanning imaging device and evaluation of colloidal assemblies of quantum dots for fluorescent lateral flow assays.

Abstract

Smartphones are promising platforms for portable molecular diagnostic assays, particularly for non-urban communities and low-resource settings that lack laboratory facilities. Engineering of peripheral components around smartphones, and the adoption of advanced light-emitting materials like semiconductor quantum dots (QDs), have enabled sensitive fluorescence detection with smartphone cameras. Here, we investigated two complementary strategies for enhancing fluorescence signals and signal-to-background ratios with smartphone-based devices: adoption of "supra-QD" and "super-QD" colloidal assemblies of QDs, and a simple and robust implementation of laser-scanning illumination. The latter has been unexplored to date, with nearly all smartphone-based devices based on conventional epi-illumination for excitation of fluorescence. The laser scanning increased signal-to-background ratios (up to 8-fold) for imaging microwell chips with fluorescent solutions, was suitable for Förster resonance energy transfer (FRET)-based sensing in this format, and was far superior to epi-illumination for imaging lateral flow membranes (14-fold increase in signal-to-background ratio). Compared to individual QDs, the supra-QD and super-QD assemblies lowered detection limits by orders of magnitude, both in bulk solution and in lateral flow binding assays. The combined benefits of laser scanning and super-QDs is projected to provide nanogram per millilitre or better limits of detection in lateral flow immunochromatographic assays. As a head-to-head comparison that demonstrates and quantifies the potential gains from an atypical illumination approach and emerging ultra-bright materials, this work informs strategies toward realizing globally accessible point-of-care diagnostic technologies based on smartphones.