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...

Rapid, ultrasensitive, and selective quantification of circulating microRNA (miRNA) biomarkers in body fluids is increasingly deployed in early cancer diagnosis, prognosis, and therapy monitoring. While nanoparticle tags enable detection of nucleic acid or protein biomarkers with digital resolution and subfemtomolar detection limits without enzymatic amplification, the response time of these assays is typically dominated by diffusion-limited transport of the analytes or nanotags to the biosensor surface. Here, we present a magnetic activate capture and digital counting (mAC+DC) approach that utilizes magneto-plasmonic nanoparticles (MPNPs) to accelerate single-molecule sensing, demonstrated by miRNA detection via toehold-mediated strand displacement. Spiky Fe3O4@Au MPNPs with immobilized target-specific probes are “activated” by binding with miRNA targets, followed by magnetically driven transport through the bulk fluid toward nanoparticle capture probes on a photonic crystal (PC). By spectrally matching the localized surface plasmon resonance of the MPNPs to the PC-guided resonance, each captured MPNP locally quenches the PC reflection efficiency, thus enabling captured MPNPs to be individually visualized with high contrast for counting. We demonstrate quantification of the miR-375 cancer biomarker directly from unprocessed human serum with a 1 min response time, a detection limit of 61.9 aM, a broad dynamic range (100 aM to 10 pM), and a single-base mismatch selectivity. The approach is well-suited for minimally invasive biomarker quantification, enabling potential applications in point-of-care testing with short sample-to-answer time.

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.