Circulating exosomal microRNA (miR) represents a new class of blood-based biomarkers for cancer liquid biopsy. The detection of miR at a very low concentration and with single-base discrimination without the need for sophisticated equipment, large volumes, or elaborate sample processing is a challenge. To address this, we present an approach that is highly specific for a target miR sequence and has the ability to provide “digital” resolution of individual target molecules with high signal-to-noise ratio. Gold nanoparticle tags are prepared with thermodynamically optimized nucleic acid toehold probes that, when binding to a target miR sequence, displace a probe-protecting oligonucleotide and reveal a capture sequence that is used to selectively pull down the target-probe–nanoparticle complex to a photonic crystal (PC) biosensor surface. By matching the surface plasmon-resonant wavelength of the nanoparticle tag to the resonant wavelength of the PC nanostructure, the reflected light intensity from the PC is dramatically and locally quenched by the presence of each individual nanoparticle, enabling a form of biosensor microscopy that we call Photonic Resonator Absorption Microscopy (PRAM). Dynamic PRAM imaging of nanoparticle tag capture enables direct 100-aM limit of detection and single-base mismatch selectivity in a 2-h kinetic discrimination assay. The PRAM assay demonstrates that ultrasensitivity (<1 pM) and high selectivity can be achieved on a direct readout diagnostic.

Surface plasmon resonance (SPR) and localized SPR (LSPR) effects have been shown as the principles of some highlysensitive sensors in recent decades. Due to the advances in nano-fabrication technology, the plasmon nano-array sensors based on SPR and LSPR phenomena have been widely used in chemical and bioloical analysis. Sensing with surface-enhanced field and sensing for refractive index changes are able to identify the analytes quantitatively and qualitatively. With the newly developed ultrasensitive plasmonic biosensors, platforms with excellent performance have been built for various biomedical applications, including point-of-care diagnosis and personalized medicine. In addition, flexible integration of plasmonics nano-arrays and combining them with electrochemical sensing have significantly enlarged the application scenarios of the plasmonic nano-array sensors, as well as improved the sensing accuracy.

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Plasmonic nanoparticles (NPs) hold tremendous promise for catalyzing light-driven chemical reactions. The conventionally assumed detrimental absorption loss from plasmon damping can now be harvested to drive chemical transformations of the NP adsorbent, through the excitation and transfer of energetic "hot" carriers. The rate and selectivity of plasmonic photocatalysis are dependent on the characteristics of the incident light. By engineering the strength and wavelength of the light harvesting of a NP, it is possible to achieve more efficient and predictive photocatalysts.We report a plasmonic-photonic resonance hybridization strategy to substantially enhance hot electron generation at tunable, narrow-band wavelengths. By coupling the plasmon resonance of silver NPs to the guided mode resonance in a photonic crystal (PC) slab, the reaction rate of a hotelectron-driven reduction conversion is greatly accelerated. The mechanism is broadly compatible with NPs with manifold materials and shapes optimized for the targeted chemistry. The novel enhancement platform sheds light on rational design of high-performance plasmonic photocatalysts.

One of the frontiers in the field of biosensors is the ability to quantify specific target molecules with enough precision to count individual units in a test sample, and to...

We demonstrate a rapid and ultrasensitive assay for protein quantification through the nanoparticle–photonic crystal coupling embedded in microfluidic cartridges.

Interferometric scattering microscopy is increasingly employed in biomedical research owing to its extraordinary capability of detecting nano-objects individually through their intrinsic elastic scattering. To significantly improve the signal-to-noise ratio without increasing illumination intensity, we developed photonic resonator interferometric scattering microscopy (PRISM) in which a dielectric photonic crystal (PC) resonator is utilized as the sample substrate. The scattered light is amplified by the PC through resonant near-field enhancement, which then interferes with the <1% transmitted light to create a large intensity contrast. Importantly, the scattered photons assume the wavevectors delineated by PC’s photonic band structure, resulting in the ability to utilize a non-immersion objective without significant loss at illumination density as low as 25 W cm−2. An analytical model of the scattering process is discussed, followed by demonstration of virus and protein detection. The results showcase the promise of nanophotonic surfaces in the development of resonance-enhanced interferometric microscopies.

Several applications in health diagnostics, food, safety, and environmental monitoring require rapid, simple, selective, and quantitatively accurate viral load monitoring. Here, we introduce the first label-free biosensing method that rapidly detects and quantifies intact virus in human saliva with single-virion resolution. Using pseudotype SARS-CoV-2 as a representative target, we immobilize aptamers with the ability to differentiate active from inactive virions on a photonic crystal, where the virions are captured through affinity with the spike protein displayed on the outer surface. Once captured, the intrinsic scattering of the virions is amplified and detected through interferometric imaging. Our approach analyzes the motion trajectory of each captured virion, enabling highly selective recognition against nontarget virions, while providing a limit of detection of 1 × 10 3 copies/mL at room temperature. The approach offers an alternative to enzymatic amplification assays for point-of-collection diagnostics.