Heroes or Villains? How Nontraditional Luminescent Materials Do and Do Not Enhance Bioanalysis and Imaging

Fluorescent dyes and fluorescent proteins (FPs) are the standard materials for fluorescence-based bioanalysis and imaging. They are popular to such an extent that the use of any other material remains nontraditional, particularly beyond the materials science and chemistry research communities. "Nontraditional" luminescent materials (NTLMs) thus include luminescent metal complexes and both organic and inorganic luminescent nanoparticles, the varieties of which now number in the double digits. Despite remarkable developments with NTLMs, the popularity of fluorescent dyes and FPs in bioanalysis and imaging has not waned. In this perspective, we address the reasons for the foregoing, including the different value propositions between NTLMs and dyes and FPs, and the remaining challenges and opportunities with luminescent nanoparticles. The different value propositions of NTLMs are illustrated with examples from our research, further highlighted with other examples from the literature, and include instances where NTLMs displace dyes and instances where dyes and NTLMs partner synergistically. For the effective development and translation of NTLMs for cross-disciplinary bioanalysis and imaging, it must be understood that NTLMs are powerful alternatives to dyes and FPs but are not one-for-one replacements. Substantial impact will come from addressing obstacles to the routine use of NTLMs, from using NTLMs to succeed where dyes and FPs struggle, and from demonstrating applications for NTLMs that are impractical, impossible, or unimagined with dyes and FPs.