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Abstract Digital‐resolution biosensing based on resonant reflection from photonic crystals (PC) has demonstrated significant potential for detection of proteomic and genomic biomarkers in serology, infectious disease diagnostics, and cancer diagnostics. An important intrinsic characteristic of resonant metamaterial surfaces is that enhanced electromagnetic fields are not uniformly distributed, resulting in spatially variable light‐matter interactions with nanoparticle tags that signal the presence of biomarker molecules. In this work, the spatial uniformity of resonantly enhanced, surface‐confined electromagnetic fields of a 1D PC is compared with a 2D PC with fourfold symmetry. When illuminated with unpolarized light, the simultaneously excited electromagnetic fields of transverse electric and transverse magnetic modes of the 2D PC present equally strong but complementary spatial distribution, leading to a >100% increased average near‐field intensity accompanied with a >50% compressed standard deviation compared to the 1D PC. Utilizing Photonic Resonator Absorption Microscopy (PRAM) to experimentally measure the absorption uniformity of ≈80 nm gold nanoparticles distributed upon the PC surface, a >100% improvement of the signal uniformity is observed when using the 2D PC. Overall, improvement in AuNP detection contrast, uniformity, and point spread function is demonstrated by PRAM performed upon a 2D PC surface. 

Abstract Assays utilizing fluorophores are common throughout life science research and diagnostics, although detection limits are generally limited by weak emission intensity, thus requiring many labeled target molecules to combine their output to achieve higher signal‐to‐noise. We describe how the synergistic coupling of plasmonic and photonic modes can significantly boost the emission from fluorophores. By optimally matching the resonant modes of a plasmonic fluor (PF) nanoparticle and a photonic crystal (PC) with the absorption and emission spectrum of the fluorescent dye, a 52‐fold improvement in signal intensity is observed, enabling individual PFs to be observed and digitally counted, where one PF tag represents one detected target molecule. The amplification can be attributed to the strong near‐field enhancement due to the cavity‐induced activation of the PF, PC band structure‐mediated improvement in collection efficiency, and increased rate of spontaneous emission. The applicability of the method by dose‐response characterization of a sandwich immunoassay for human interleukin‐6, a biomarker used to assist diagnosis of cancer, inflammation, sepsis, and autoimmune disease is demonstrated. A limit of detection of 10 fg mL⁻¹and 100 fg mL⁻¹in buffer and human plasma respectively, is achieved, representing a capability nearly three orders of magnitude lower than standard immunoassays.