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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. 

Photonic crystals are used to amplify the fluorescence emission and collection efficiency from quantum dots and plasmonic fluor nanoparticles to enable miRNA and proteins to be detected from plasma with single molecule precision, with simple 1-step assays. 

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. 

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. 

We present advanced biosensing methods with photonics crystal enhanced fluorescence emission from Quantum Dots, Plasmonic Fluorophores, and DNA Nano-grippers for nucleic acid, protein, and pathogen detection 

DNA-origami based nano-grippers, integrated with aptamer-based nanoswitches, generate fluorescent signals when detecting SARS-CoV-2. The integration of Photonic Crystal Enhanced Fluorescence Microscope enables a 104-fold enhancement compared to a single fluorophore reporter on glass substrate, providing a promising tool for ultrasensitive detection and rapid diagnostics. 

Plasmonic and photonic technologies have attracted strong interest in the past few decades toward several interdisciplinary applications stemming from unique light-matter interactions fostered by materials at the nanoscale. The versatility of plasmonic and photonic sensors for ultrasensitive, rapid, analyte sensing without extensive sample pre-treatment steps or sophisticated optics have resulted in their strong foothold in the broad arena of biosensing. Fluorescence-based bioanalytical techniques are widely used in liquid-biopsy diagnostics applications, but require many labeled target molecules to combine their emission output to achieve a practically useful signal-to-noise ratio. Approaches capable of amplifying fluorescence signals can provide signal-to-noise sufficient for digitally counting single emitters for ultrasensitive assays that are detected with simple and inexpensive instruments. [1]. Plasmonic and nano-photonics can function in synergy to amplify fluorescence signals. By concentrating optical energy well below the diffraction limit, plasmonic nanoantenna provide spatial control over excitation light, but their quality factor (Q) is modulated by radiative and dissipative losses. Photonic crystals (PC) as dielectric microcavities have a diffraction-limited optical mode volume despite being able to generate a high Q-factor. Here, we demonstrate a plasmonic-photonic hybrid system to produce a much stronger fluorescent enhancement for digital resolution biosensing. With an optimized dielectric spacer layer, around 200 Alexa-647 fluorophores have been coated over heterometallic Ag@Au core-shell plasmonic nanostructures with minimized Ohmic losses and quenching effects [2]. The target-specific molecule capture events enabled this plasmonic fluor to attach to the PC surface, forming a Plasmonic-Photonic hybrid mode. With much stronger local field enhancement, far-field directional emission, large Purcell enhancement, and high quantum efficiency, we report a two-orders signal enhancement from PC-enhanced plasmonic-fluor (104-fold brighter than a single fluorophore). This improved signal-to-noise ratio enabled us to perform single molecule imaging even with a 10x (NA=0.2) objective lens while offering 3 orders of magnitude boost in the limit of detection of Interleukine-6 (common biomarker for cancer, inflammation, sepsis, and autoimmune disease) compared with standard immunoassays in human plasma 

The ability to self-test for HIV is vital to preventing transmission, particularly when used in concert with HIV biomedical prevention modalities, such as pre-exposure prophylaxis (PrEP). In this paper, we review recent developments in HIV self-testing and self-sampling methods, and the potential future impact of novel materials and methods that emerged through efforts to develop more effective point-of-care (POC) SARS-CoV-2 diagnostics. We address the gaps in existing HIV self-testing technologies, where improvements in test sensitivity, sample-to-answer time, simplicity, and cost are needed to enhance diagnostic accuracy and widespread accessibility. We discuss potential paths toward the next generation of HIV self-testing through sample collection materials, biosensing assay techniques, and miniaturized instrumentation. We discuss the implications for other applications, such as self-monitoring of HIV viral load and other infectious diseases.