We present an inexpensive, generalizable approach for modifying visible wavelength fluorescence microplate readers to detect emission in the near-infrared (NIR) I (650–950 nm) and NIR II (1000-1350 nm) tissue imaging windows. These wavelength ranges are promising for high sensitivity fluorescence-based cell assays and biological imaging, but the inaccessibility of NIR microplate readers is limiting development of the requisite, biocompatible fluorescent probes. Our modifications enable rapid screening of NIR candidate probes, using short pulses of UV light to provide excitation of diverse systems including dye molecules, semiconductor quantum dots, and metal clusters. To confirm the utility of our approach for rapid discovery of new NIR probes, we examine the silver cluster synthesis products formed on 375 candidate DNA strands that were originally designed to produce green-emitting, DNA-stabilized silver clusters. The fast, sensitive system developed here discovered DNA strands that unexpectedly stabilize NIR-emitting silver clusters.