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Nanophotonic devices, which control light in subwavelength volumes and enhance light–matter interactions, have opened up exciting prospects for biosensing. Numerous nanophotonic biosensors have emerged to address the limitations of the current bioanalytical methods in terms of sensitivity, throughput, ease-of-use and miniaturization. In this Review, we provide an overview of the recent developments of label-free nanophotonic biosensors using evanescent-field-based sensing with plasmon resonances in metals and Mie resonances in dielectrics. We highlight the prospects of achieving an improved sensor performance and added functionalities by leveraging nanostructures and on-chip and optoelectronic integration, as well as microfluidics, biochemistry and data science toolkits. We also discuss open challenges in nanophotonic biosensing, such as reducing the overall cost and handling of complex biological samples, and provide an outlook for future opportunities to improve these technologies and thereby increase their impact in terms of improving health and safety.This Review discusses the progresses in label-free nanophotonic biosensors based on photonic or dielectric surfaces and metasurfaces and highlights the challenges and benefits of their applications in the fields of public health, well-being and biosafety.

Metasurfaces based on resonant subwavelength photonic structures enable novel ways of wavefront control and light focusing, underpinning a new generation of flat-optics devices1. Recently emerged all-dielectric asymmetric metasurfaces, composed of arrays of metaunits with broken in-plane inversion symmetry2–7, exhibit high-quality resonances originating from the intriguing physics of bound states in the continuum. Here, we combine dielectric metasurfaces and hyperspectral imaging to develop an ultrasensitive label-free analytical platform for biosensing. Our technique can acquire spatially resolved spectra from millions of image pixels and use smart data-processing tools to extract high-throughput digital sensing information at the unprecedented level of less than three molecules per μm2. We further show spectral data retrieval from a single image without using spectrometers, enabled by our unique sensor design, paving the way for portable diagnostic applications. This combination of nanophotonics and imaging optics extends the capabilities of dielectric metasurfaces to analyse biological entities and atomic-layer-thick two-dimensional materials over large areas.Spatially resolved spectra from millions of pixels and information extraction from three molecules per μm2 is now possible using dielectric metasurfaces.

Biosensors are indispensable tools for public, global, and personalized healthcare as they provide tests that can be used from early disease detection and treatment monitoring to preventing pandemics. We introduce single-wavelength imaging biosensors capable of reconstructing spectral shift information induced by biomarkers dynamically using an advanced data processing technique based on an optimal linear estimator. Our method achieves superior sensitivity without wavelength scanning or spectroscopy instruments. We engineered diatomic dielectric metasurfaces supporting bound states in the continuum that allows high-quality resonances with accessible near-fields by in-plane symmetry breaking. The large-area metasurface chips are configured as microarrays and integrated with microfluidics on an imaging platform for real-time detection of breast cancer extracellular vesicles encompassing exosomes. The optofluidic system has high sensing performance with nearly 70 1/RIU figure-of-merit enabling detection of on average 0.41 nanoparticle/µm 2 and real-time measurements of extracellular vesicles binding from down to 204 femtomolar solutions. Our biosensors provide the robustness of spectrometric approaches while substituting complex instrumentation with a single-wavelength light source and a complementary-metal-oxide-semiconductor camera, paving the way toward miniaturized devices for point-of-care diagnostics. The authors engineer a type of bound states in the continuum in diatomic dielectric metasurfaces, allowing for high-quality resonances with accessible enhanced fields. Metasurface microarrays are integrated with microfluidics on an imaging platform for real-time detection of biosamples, based on reconstructing spectral shift information.

Although mid-infrared (mid-IR) spectroscopy is a mainstay of molecular fingerprinting, its sensitivity is diminished somewhat when looking at small volumes of sample. Nanophotonics provides a platform to enhance the detection capability. Tittl et al. built a mid-IR nanophotonic sensor based on reflection from an all-dielectric metasurface array of specially designed scattering elements. The scattering elements could be tuned via geometry across a broad range of wavelengths in the mid-IR. The approach successfully detected and differentiated the absorption fingerprints of various molecules. The technique offers the prospect of on-chip molecular fingerprinting without the need for spectrometry, frequency scanning, or moving mechanical parts. Science , this issue p. 1105 A pixelated dielectric metasurface is used for the mid-infrared detection of molecular fingerprints. Metasurfaces provide opportunities for wavefront control, flat optics, and subwavelength light focusing. We developed an imaging-based nanophotonic method for detecting mid-infrared molecular fingerprints and implemented it for the chemical identification and compositional analysis of surface-bound analytes. Our technique features a two-dimensional pixelated dielectric metasurface with a range of ultrasharp resonances, each tuned to a discrete frequency; this enables molecular absorption signatures to be read out at multiple spectral points, and the resulting information is then translated into a barcode-like spatial absorption map for imaging. The signatures of biological, polymer, and pesticide molecules can be detected with high sensitivity, covering applications such as biosensing and environmental monitoring. Our chemically specific technique can resolve absorption fingerprints without the need for spectrometry, frequency scanning, or moving mechanical parts, thereby paving the way toward sensitive and versatile miniaturized mid-infrared spectroscopy devices.

Low-dimensional van der Waals (vdW) materials can harness tightly confined polaritonic waves to deliver unique advantages for nanophotonic biosensing. The reduced dimensionality of vdW materials, as in the case of two-dimensional graphene, can greatly enhance plasmonic field confinement, boosting sensitivity and efficiency compared to conventional nanophotonic devices that rely on surface plasmon resonance in metallic films. Furthermore, the reduction of dielectric screening in vdW materials enables electrostatic tunability of different polariton modes, including plasmons, excitons, and phonons. One-dimensional vdW materials, particularly single-walled carbon nanotubes, possess unique form factors with confined excitons to enable single-molecule detection as well as in vivo biosensing. We discuss basic sensing principles based on vdW materials, followed by technological challenges such as surface chemistry, integration, and toxicity. Finally, we highlight progress in harnessing vdW materials to demonstrate new sensing functionalities that are difficult to perform with conventional metal/dielectric sensors. This review presents an overview of scenarios where van der Waals (vdW) materials provide unique advantages for nanophotonic biosensing applications. The authors discuss basic sensing principles based on vdW materials, advantages of the reduced dimensionality as well as technological challenges.

Nanoplasmonic structures can tightly confine light onto a material’s surface to probe biomolecular interactions not easily accessed by other sensing techniques. New and exciting developments in nanofabrication processes, nano-optical trapping, graphene devices, mid-infrared spectroscopy, and metasurfaces will greatly empower the performance and functionalities of nanoplasmonic sensors.

Engineered optical metamaterials present a unique platform for biosensing applications owing to their ability to confine light to nanoscale regions and to their spectral selectivity. Infrared plasmonic metamaterials are especially attractive because their resonant response can be accurately tuned to that of the vibrational modes of the target biomolecules. Here we introduce an infrared plasmonic surface based on a Fano-resonant asymmetric metamaterial exhibiting sharp resonances caused by the interference between subradiant and superradiant plasmonic resonances. Owing to the metamaterial’s asymmetry, the frequency of the subradiant resonance can be precisely determined and matched to the molecule’s vibrational fingerprints. A multipixel array of Fano-resonant asymmetric metamaterials is used as a platform for multispectral biosensing of nanometre-scale monolayers of recognition proteins and their surface orientation, as well as for detecting chemical binding of target antibodies to recognition proteins. Plasmonic nanostructures are known to be an attractive platform for highly sensitive molecular sensors, although they often lack specificity. A plasmonic device with a sharp optical resonance tuned to biomolecules selectively captured on the surface of the device now offers a versatile yet highly specific platform for molecular sensing.

A multitude of biological processes are enabled by complex interactions between lipid membranes and proteins. To understand such dynamic processes, it is crucial to differentiate the constituent biomolecular species and track their individual time evolution without invasive labels. Here, we present a label-free mid-infrared biosensor capable of distinguishing multiple analytes in heterogeneous biological samples with high sensitivity. Our technology leverages a multi-resonant metasurface to simultaneously enhance the different vibrational fingerprints of multiple biomolecules. By providing up to 1000-fold near-field intensity enhancement over both amide and methylene bands, our sensor resolves the interactions of lipid membranes with different polypeptides in real time. Significantly, we demonstrate that our label-free chemically specific sensor can analyze peptide-induced neurotransmitter cargo release from synaptic vesicle mimics. Our sensor opens up exciting possibilities for gaining new insights into biological processes such as signaling or transport in basic research as well as provides a valuable toolkit for bioanalytical and pharmaceutical applications. Complex protein-lipid interactions are difficult to study in real-time without labels. Here, Rodrigo et al . introduce a multimodal plasmonic infrared biosensor to simultaneously distinguish multiple analytes with high sensitivity.

Spontaneous emission is not inherent to an emitter, but rather depends on its electromagnetic environment. In a microcavity, the spontaneous emission rate can be greatly enhanced compared with that in free space. This so-called Purcell effect can dramatically increase laser modulation speeds, although to date no time-domain measurements have demonstrated this. Here we show extremely fast photonic crystal nanocavity lasers with response times as short as a few picoseconds resulting from 75-fold spontaneous emission rate enhancement in the cavity. We demonstrate direct modulation speeds far exceeding 100 GHz (limited by the detector response time), already more than an order of magnitude above the fastest semiconductor lasers. Such ultrafast, efficient, and compact lasers show great promise for applications in high-speed communications, information processing, and on-chip optical interconnects.

Modern devices require the tuning of the size, shape and spatial arrangement of nano-objects and their assemblies with nanometre-scale precision, over large-area and sometimes soft substrates. Such stringent requirements are beyond the reach of conventional lithographic techniques or self-assembly approaches. Here, we show nanoscale control over the fluid instabilities of optical thin glass films for the fabrication of self-assembled all-dielectric optical metasurfaces. We show and model the tailoring of the position, shape and size of nano-objects with feature sizes below 100 nm and with interparticle distances down to 10 nm. This approach can generate optical nanostructures over rigid and soft substrates that are more than tens of centimetres in size, with optical performance and resolution on a par with advanced traditional lithography-based processes. To underline the potential of our approach, which reconciles high-performance optical metasurfaces and simple self-assembly fabrication approaches, we demonstrate experimentally and via numerical simulation sharp Fano resonances with a quality factor, Q, as high as ∼300 in the visible for all-dielectric nanostructures, to realize protein monolayer detection.Optical glasses can form high-quality dielectric metasurfaces by controlled dewetting and fluid instabilities.