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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. 

DNA has shown great biocompatibility, programmable mechanical properties, and precise structural addressability at the nanometer scale, rendering it a material for constructing versatile nanorobots for biomedical applications. Here, we present the design principle, synthesis, and characterization of a DNA nanorobotic hand, called DNA NanoGripper, that contains a palm and four bendable fingers as inspired by naturally evolved human hands, bird claws, and bacteriophages. Each NanoGripper finger consists of three phalanges connected by three rotatable joints that are bendable in response to the binding of other entities. NanoGripper functions are enabled and driven by the interactions between moieties attached to the fingers and their binding partners. We demonstrate that the NanoGripper can be engineered to effectively interact with and capture nanometer-scale objects, including gold nanoparticles, gold NanoUrchins, and SARS-CoV-2 virions. With multiple DNA aptamer nanoswitches programmed to generate a fluorescent signal that is enhanced on a photonic crystal platform, the NanoGripper functions as a highly sensitive biosensor that selectively detects intact SARS-CoV-2 virions in human saliva with a limit of detection of ~100 copies per milliliter, providing a sensitivity equal to that of reverse transcription quantitative polymerase chain reaction (RT-qPCR). Quantified by flow cytometry assays, we demonstrated that the NanoGripper-aptamer complex can effectively block viral entry into the host cells, suggesting its potential for inhibiting virus infections. The design, synthesis, and characterization of a sophisticated nanomachine that can be tailored for specific applications highlight a promising pathway toward feasible and efficient solutions to the detection and potential inhibition of virus infections. 

DNA has shown great biocompatibility, programmable mechanical properties, and precise structural addressabil- ity at the nanometer scale, rendering it a material for constructing versatile nanorobots for biomedical applica- tions. Here, we present the design principle, synthesis, and characterization of a DNA nanorobotic hand, called DNA NanoGripper, that contains a palm and four bendable fingers as inspired by naturally evolved human hands, bird claws, and bacteriophages. Each NanoGripper finger consists of three phalanges connected by three rotat- able joints that are bendable in response to the binding of other entities. NanoGripper functions are enabled and driven by the interactions between moieties attached to the fingers and their binding partners. We demonstrate that the NanoGripper can be engineered to effectively interact with and capture nanometer-scale objects, includ- ing gold nanoparticles, gold NanoUrchins, and SARS-CoV-2 virions. With multiple DNA aptamer nanoswitches programmed to generate a fluorescent signal that is enhanced on a photonic crystal platform, the NanoGripper functions as a highly sensitive biosensor that selectively detects intact SARS-CoV-2 virions in human saliva with a limit of detection of ~100 copies per milliliter, providing a sensitivity equal to that of reverse transcription quanti- tative polymerase chain reaction (RT-qPCR). Quantified by flow cytometry assays, we demonstrated that the NanoGripper-aptamer complex can effectively block viral entry into the host cells, suggesting its potential for in- hibiting virus infections. The design, synthesis, and characterization of a sophisticated nanomachine that can be tailored for specific applications highlight a promising pathway toward feasible and efficient solutions to the de- tection and potential inhibition of virus infections. 

The requirements of augmented signal contrast provided by nanoparticle tags in biosensor microscopy-based point-of-care technologies for cancer and infectious disease diagnostics can be addressed through metallo-dielectric nanoarchitectures that enhance optical scattering and absorption to provide digital resolution detection of single tags with simple instrumentation. Photonic Resonator Interferometric Scattering Microscopy (PRISM) enables label-free visualization of nanometer-scale analytes such as extracellular vesicles and virions, and its applicability can be extended to biomolecular analyte counting through nanoparticle tags. Here, we present template-free, linker-less cryosoret nano-assemblies fabricated via adiabatic cooling (−196 °C) as plasmonic nano-antennas that provide high scattering contrast in PRISM. Plasmonic Ag and Au nanomaterials and their cryosorets are evaluated through imaging experiments and simulations based on the finite element method to understand the photo-plasmonic coupling effect at the surface of a photonic crystal (PC) interface. The Ag and Au cryosorets provide at most 8.29-fold and 6.77-fold higher signal contrast compared to their singlet counterpart. Through the simulations, the averaged field magnitude enhancements of 2.77-fold and 3.68-fold are observed for Ag and Au cryosorets when interfacing with PCs compared to bare glass substrates. The hybrid coupling between the localized Mie and delocalized Bragg plasmons of cryosorets and the underlying PC's guided mode resonance provides insights for developing nano-assembly-based nano-tags for biosensing applications. 

Diagnostic assays utilizing fluorescent reporters in the context of low abundance biomarkers for cancer and infectious disease can reach lower limits of detection through efficient collection of emitted photons into an optical sensor. In this work, we present the rational design, fabrication, and application of one-dimensional photonic crystal (PC) grating interfaces to accomplish a cost-effective prism-free, metal-free, and objective-free platform for augmentation of fluorescence emission collection efficiency. Guided mode resonance (GMR) of the PC is engineered to match the laser excitation (532 nm) and emission maximum (580 nm) of the radiating dipoles to arrive at optimized conditions. The photo-plasmonic hybrid nano-engineering using silver nanoparticles presented >110-fold steering fluorescence enhancement enabling placement of the sample between the excitation source and detector that are in a straight line. From the experimental and simulation inferences, we propose a radiating GMR model by scrutinizing the polarized emission properties of the hybrid substrate, in accordance with the radiating plasmon model. The augmented fluorescence intensity realized here with a simple detection instrument provides sub-nanomolar sensitivity to provide a path toward point-of-care scenarios.