Hortin, G. L., Carr, S. A. & Anderson, N. L. Introduction: Advances in protein analysis for the clinical laboratory. Clin. Chem. 56 , 149–151 (2010)..

Borrebaeck, C. A. K. Precision diagnostics: Moving towards protein biomarker signatures of clinical utility in cancer. Nat. Rev. Cancer 17 , 199–204 (2017)..

Hanash, S. & Taguchi, A. Application of proteomics to cancer early detection. Cancer J. 17 , 423–428 (2011)..

Van Poppel, H. et al. Serum PSA-based early detection of prostate cancer in Europe and globally: Past, present and future. Nat. Rev. Urol. 19 , 562–572 (2022)..

Rao, S. et al. Past, present, and future of serum tumor markers in management of ovarian cancer: A guide for the radiologist. RadioGraphics 41 , 1839–1856 (2021)..

Shao, H. L. et al. New technologies for analysis of extracellular vesicles. Chem. Rev. 118 , 1917–1950 (2018)..

Xu, R. et al. Extracellular vesicles in cancer—implications for future improvements in cancer care. Nat. Rev. Clin. Oncol. 15 , 617–638 (2018)..

Jo, A. et al. Inaugurating high‐throughput profiling of extracellular vesicles for earlier ovarian cancerdetection. Adv. Sci. 10 , 2301930 (2023)..

Park, J. et al. An integrated magneto-electrochemical device for the rapid profiling of tumour extracellular vesicles from blood plasma. Nat. Biomed. Eng. 5 , 678–689 (2021)..

Choi, B. D. et al. Intraventricular CARv3-TEAM-E T cells in recurrent glioblastoma. N. Engl. J. Med. 390 , 1290–1298 (2024)..

Alix-Panabières, C. & Pantel, K. Liquid biopsy: from discovery to clinical application. Cancer Discov. 11 , 858–873 (2021)..

Hayrapetyan, H. et al. Enzyme-linked immunosorbent assay: Types and applications. Methods Mol. Biol. 2612 , 1–17 (2023)..

Matson, R. S. ELISA-based biosensors. Methods Mol. Biol. 2612 , 225–238 (2023)..

Porstmann, T. & Kiessig, S. T. Enzyme immunoassay techniques an overview. J. Immunol. Methods 150 , 5–21 (1992)..

Sakamoto, S. et al. Enzyme-linked immunosorbent assay for the quantitative/qualitative analysis of plant secondary metabolites. J. Nat. Med. 72 , 32–42 (2018)..

Krauss, T. F. et al. Photonic and electrochemical biosensors for near-patient tests–a critical comparison. Optica 11 , 1408–1418 (2024)..

Altug, H. et al. Advances and applications of nanophotonic biosensors. Nat. Nanotechnol. 17 , 5–16 (2022)..

Suthar, J. et al. Recent developments in biosensing methods for extracellular vesicle protein characterization. WIREs Nanomed. Nanobiotechnol. 15 , e1839 (2023)..

Javaid, Z. et al. Reviewing advances i n nanophotonic biosensors. Front. Chem. 12 , 1449161 (2024)..

Shaked, N. T. et al. Label-free biomedical optical imaging. Nat. Photonics 17 , 1031–1041 (2023)..

Barth, I. et al. Phase noise matching in resonant metasurfaces for intrinsic sensing stability. Optica 11 , 354–361 (2024)..

Kenaan, A. et al. Guided mode resonance sensor for the parallel detection of multiple protein biomarkers in human urine with high sensitivity. Biosens. Bioelectron. 153 , 112047 (2020)..

Cetin, A. E. et al. Handheld high-throughput plasmonic biosensor using computational on-chip imaging. Light Sci. Appl. 3 , e122 (2014)..

Li, X. K. et al. Plasmonic nanohole array biosensor for label-free and real-time analysis of live cell secretion. Lab on a Chip 17 , 2208–2217 (2017)..

Jahani, Y. et al. Imaging-based spectrometer-less optofluidic biosensors based on dielectric metasurfaces for detecting extracellular vesicles. Nat. Commun. 12 , 3246 (2021)..

Conteduca, D., Quinn, S. D. & Krauss, T. F. Dielectric metasurface for high-precision detection of large unilamellar vesicles. J. Opt. 23 , 114002 (2021)..

Chin, L. K. et al. Plasmonic sensors for extracellular vesicle analysis: from scientific development to translational research. ACS Nano 14 , 14528–14548 (2020)..

De Leebeeck, A. et al. On-chip surface-based detection with nanohole arrays. Anal. Chem. 79 , 4094–4100 (2007)..

Brolo, A. G. et al. Surface plasmon sensor based on the enhanced light transmission through arrays of nanoholes in gold films. Langmuir 20 , 4813–4815 (2004)..

Cunningham, B. et al. Colorimetric resonant reflection as a direct biochemical assay technique. Sens. Actuators B: Chem. 81 , 316–328 (2002)..

Pitruzzello, G. & Krauss, T. F. Photonic crystal resonances for sensing and imaging. J. Opt. 20 , 073004 (2018)..

Drayton, A., Barth, I. & Krauss, T. F. Guided mode resonances and photonic crystals for biosensing and imaging. Semiconductors Semimet. 100 , 115–148 (2019)..

Huang, L. J. et al. Resonant leaky modes in all-dielectric metasystems: Fundamentals and applications. Phys. Rep. 1008 , 1–66 (2023)..

Prasad, A. et al. Nanohole array plasmonic biosensors: Emerging point-of-care applications. Biosens. Bioelectron. 130 , 185–203 (2019)..

Bosio, N. et al. Plasmonic versus all-dielectric nanoantennas for refractometric sensing: A direct comparison. ACS Photonics 6 , 1556–1564 (2019)..

Conteduca, D. et al. Beyond Q : the importance of the resonance amplitude for photonic sensors. ACS Photonics 9 , 1757–1763 (2022)..

Balderas-Valadez, R. F. & Pacholski, C. Plasmonic nanohole arrays on top of porous silicon sensors: a win–win situation. ACS Appl. Mater. Interfaces 13 , 36436–36444 (2021)..

Franco, A. et al. A label-free optical system with a nanohole arr ay biosensor for discriminating live single cancer cells from normal cells. Nanophotonics 11 , 315–328 (2022)..

White, I. M. & Fan, X. D. On the performance quantification of resonant refractive index sensors. Opt. Expr. 16 , 1020–1028 (2008)..

Bläsi, J. & Gerken, M. Multiplex optical biosensors based on multi-pinhole interferometry. Biomed. Opt. Expr. 12 , 4265–4275 (2021)..

Chiang, M. X., Tongpakpanang, J. & Kuo, W. K. Phase measurement of guided-mode resonance device using digital micromirror device gratings. Photonics 8 , 136 (2021)..

Barth, I. et al. Common-path interferometric label-free protein sensing with resonant dielectric nanostructures. Light Sci. Appl. 9 , 96 (2020)..

Barth, I. & Lee, H. Phase-driven progress in nanophotonic biosensing. Light Sci. Appl. 13 , 76 (2024)..

Conteduca, D. et al. Dielectric nanohole array metasurface for high-resolution near-field sensing and imaging. Nat. Commun. 12 , 3293 (2021)..

Triggs, G. J. et al. Chirped guided-mode resonance biosensor. Optica 4 , 229–234 (2017)..

Tittl, A. et al. Imaging-based molecular barcoding with pixelated dielectric metasurfaces. Science 360 , 1105–1109 (2018)..

Cetin, A. E. & Topkaya, S. N. Photonic crystal and plasmonic nanohole based label-free biodetection. Biosens. Bioelectron. 132 , 196–202 (2019)..

Yesilkoy, F. et al. Ultrasensitive hyperspectral imaging and biodetection enabled by dielectric metasurfaces. Nat. Photonics 13 , 390–396 (2019)..

Inan, H. et al. Photonic crystals: emerging biosensors and their promise for point-of-care applications. Chem. Soc. Rev. 46 , 366–388 (2017)..

Hsu, C. W. et al. Bound states in the continuum. Nat. Rev. Mater. 1 , 16048 (2016)..

Koshelev, K. et al. Asymmetric metasurfaces with high- Q resonances governed b y bound states in the continuum. Phys. Rev. Lett. 121 , 193903 (2018)..

Paddon, P. & Young, J. F. Two-dimensional vector-coupled-mode theory for textured planar waveguides. Phys. Rev. B 61 , 2090–2101 (2000)..

Ochiai, T. & Sakoda, K. Dispersion relation and optical transmittance of a hexagonal photonic crystal slab. Phys. Rev. B 63 , 125107 (2001)..

Fan, S. H. & Joannopoulos, J. D. Analysis of guided resonances in photonic crystal slabs. Phys. Rev. B 65 , 235112 (2002)..

Lee, J. et al. Observation and differentiation of unique high- Q optical resonances near zero wave vector in macroscopic photonic crystal slabs. Phys. Rev. Lett. 109 , 067401 (2012)..

Marinica, D. C., Borisov, A. G. & Shabanov, S. V. Bound states in the continuum in photonics. Phys. Rev. Lett. 100 , 183902 (2008)..

Romano, S. et al. Ultrasensitive surface refractive index imaging based on quasi-bound states in the continuum. ACS Nano 14 , 15417–15427 (2020)..

Block, I. D., Chan, L. L. & Cunningham, B. T. Photonic crystal optical biosensor incorporating structured low-index porous dielectric. Sens. Actuators B: Chem. 120 , 187–193 (2006)..

Hu, J. et al. Rapid genetic screening with high quality factor metasurfaces. Nat. Commun. 14 , 4486 (2023)..

Li, G. Y. & Liu, Y. H. Homogeneous and significant near-field enhancement in all-dielectric metasurfaces for sensing applications. Adv. Opt. Mater. 12 , 2470069 (2024)..

Yesilkoy, F. et al. Phase-sensitive plasmonic biosensor using a portable and large field-of-view interferometric microarray imager. Light Sci. Appl. 7 , 17152 (2018)..

Soler, M. et al. How nanophotonic label-free biosensors can contribute to rapid and massive diagnostics of respiratory virus infections: COVID-19 case. ACS Sens. 5 , 2663–2678 (2020)..

Zhu, Y. Z. et al. State of the art in integrated biosensors for organ-on-a-chip applications. Curr. Opin. Biomed. Eng. 19 , 100309 (2021)..

Taha, B. A. et al. Next-generation nanophotonic-enabled biosensors for intelligent diagnosis of SARS-CoV-2 variants. Sci. Total Environ. 880 , 163333 (2023)..

Cetin, A. E. et al. Plasmonic nanohole arrays on a robust hybrid substrate for highly sensitive label-free biosensing. ACS Photonics 2 , 1167–1174 (2015)..

Ferguson, S., Yang, K. S. & Weissleder, R. Single extracellular vesicle analysis for early cancer detection. Trends Mol. Med. 28 , 681–692 (2022)..

Bordanaba-Florit, G. et al. Using single-vesicle technologies to unravel the heterogeneity of extracellular vesicles. Nat. Protoc. 16 , 3163–3185 (2021)..

Zhai, C. H. et al. Correlation between membrane proteins and sizes of extracellular vesicles and particles: a potential signature for cancer diagnosis. J. Extracell. Vesicles 12 , 12391 (2023)..

Im, H. et al. Label-free detection and molecular profiling of exosomes with a nano-plasmonic sensor. Nat. Biotechnol. 32 , 490–495 (2014)..

Zhu, S. Y. et al. Highly sensitive detection of exosomes by 3D plasmonic photonic crystal biosensor. Nanoscale 10 , 19927–19936 (2018)..

Bakshi, S. et al. Bio-inspired polydopamine layer as a versatile functionalisation protocol for silicon-based photonic biosensors. Talanta 268 , 125300 (2024)..

Reiner, A. T. et al. Magnetic nanoparticle-enhanced surface plasmon resonance biosensor for extracellular vesicle analysis. Analyst 142 , 3913–3921 (2017)..

Fraser, K. et al. Characterization of single microvesicles in plasma from glioblastoma patients. Neuro-Oncol. 21 , 606–615 (2019)..

Lee, K. et al. Multiplexed profiling of single extracellular vesicles. ACS Nano 12 , 494–503 (2018)..

Inglis, H. C. et al. Techniques to improve detection and analysis of extracellular vesicles using flow cytometry. Cytom. Part A 87 , 1052–1063 (2015)..

Zhang, J. et al. Extracellular vesicles: techniques and biomedical applications related to single vesicle analysis. ACS Nano 17 , 17668–17698 (2023)..

Tatischeff, I. et al. Fast characterisation of cell-derived extracellular vesicles by nanoparticles tracking analysis, cryo-electron microscopy, and Raman tweezers microspectroscopy. J. Extracell. Vesicles 1 , 19179 (2012)..

Daaboul, G. G. et al. Digital detection of exosomes by interferometric imaging. Sci. Rep. 6 , 37246 (2016)..

Ortiz-Orruño, U. et al. Precise nanosizing with high dynamic range holography. Nano Lett. 21 , 317–322 (2021)..

Yang, Z. J. et al. Ultrasensitive single extracellular vesicle detection using high throughput droplet digital enzyme-linked immunosorbent assay. Nano Lett. 22 , 4315–4324 (2022)..

Liang, K. et al. Nanoplasmonic quantification of tumour-derived extracellular vesicles in plasma microsamples for diagnosis and treatment monitoring. Nat. Biomed. Eng. 1 , 0021 (2017)..

Stollmann, A. et al. M olecular fingerprinting of biological nanoparticles with a label-free optofluidic platform. Nat. Commun. 15 , 4109 (2024)..

Avci, O. et al. Interferometric reflectance imaging sensor (IRIS)—a platform technology for multiplexed diagnostics and digital detection. Sensors 15 , 17649–17665 (2015)..

Yang, Y. T. et al. Interferometric plasmonic imaging and detection of single exosomes. Proc. Natl. Acad. Sci. USA 115 , 10275–10280 (2018)..

Taylor, R. W. & Sandoghdar, V. Interferometric scattering microscopy: seeing single nanoparticles and molecules via Rayleigh scattering. Nano Lett. 19 , 4827–4835 (2019)..

Kashkanova, A. D. et al. Precision size and refractive index analysis of weakly scattering nanoparticles in polydispersions. Nat. Methods 19 , 586–593 (2022)..

Küppers, M. et al. Confocal interferometric scattering microscopy reveals 3D nanoscopic structure and dynamics in live cells. Nat. Commun. 14 , 1962 (2023)..

Liebel, M. et al. 3D tracking of extracellular ves icles by holographic fluorescence imaging. Sci. Adv. 6 , eabc2508 (2020)..

Ciaparrone, G. et al. Label-free cell classification in holographic flow cytometry through an unbiased learning strategy. Lab on a Chip 24 , 924–932 (2024)..

Yang, Y. T. et al. Multifunctional detection of extracellular vesicles with surface plasmon resonance microscopy. Anal. Chem. 92 , 4884–4890 (2020)..

Panagopoulou, M. S. et al. Phenotypic analysis of extracellular vesicles: a review on the applications of fluorescence. J. Extracell. Vesicles 9 , 1710020 (2020)..

Jeong, M. H. et al. Plasmon‐enhanced single extracellular vesicle analysis for cholangiocarcinoma diagnosis. Adv. Sci. 10 , 2205148 (2023)..

Romano, S. et al. Surface-enhanced Raman and fluorescence spectroscopy with an all-dielectric metasurface. J. Phys. Chem. C. 122 , 19738–19745 (2018)..

Valsecchi, C., Gomez Armas, L. E. & Weber de Menezes, J. Large area nanohole arrays for sensing fabricated by interference lithography. Sensors 19 , 2182 (2019)..

Oh, D. K. et al. Nanoimprint lithography for high-throughput fabrication of metasurfaces. Front. Optoelectron. 14 , 229–251 (2021)..

Seo, J. H. et al. Nanopatterning by laser interference lithography: applications to optical devices. J. Nanosci. Nanotechnol. 14 , 1521–1532 (2014)..

Harder, P. et al. Molecular conformation in oligo (ethylene glycol)-terminated self-assembled monolayers on gold and silver surfaces determines their ability to resist protein adsorption. J. Phys. Chem. B 102 , 426–436 (1998)..

Latour, R. A. Fundamental principles of the thermodynamics and kinetics of protein adsorption to material surfaces. Colloids Surf. B: Biointerfaces 191 , 110992 (2020)..

Nagasaki, Y. Construction of a densely poly(ethylene glycol)-chain-tethered surface and its performance. Polym. J. 43 , 949–958 (2011)..

Landeros, C. et al. Deep learning pipeline for automated cell profiling from cyclic imaging. Sci. Rep. 14 , 23600 (2024)..

Pachitariu, M. & Stringer, C. Cellpose 2.0: how to train your own model. Nat. Methods 19 , 1634–1641 (2022)..

Weissleder, R. & Lee, H. Automated molecular-image cytometry and analysis in modern oncology. Nat. Rev. Mater. 5 , 409–422 (2020)..

Van Valen, D. A. et al. Deep learning automates the quantitative analysis of individual cells in live-cell imaging experiments. PLoS Comput. Biol. 12 , e1005177 (2016)..

Blume, J. E. et al. Rapid, deep and precise profiling of the plasma proteome with multi-nanoparticle protein corona. Nat. Commun. 11 , 3662 (2020)..

Anderson, N. L. & Anderson, N. G. The human plasma proteome: history, character, and diagnostic prospects. Mol. Cell. Proteom. 1 , 845–867 (2002)..

Barth, I. Common-path interferometric sensing with resonant dielectric nanostructures. PhD thesis, University of York, York, 2021.

Guang, J. Y. et al. Visible light-illuminated gold nanohole arrays with tunable on-chip plasmonic sensing properties. Photonic Sens. 14 , 240311 (2024)..

Dastjerdi, H. M. et al. Optimized analysis for sensitive detection and analysis of single proteins via interferometric scattering microscopy. J. Phys. D Appl. Phys. 55 , 054002 (2022)..

Li, N. T. et al. Photonic resonator interferometric scattering microscopy. Nat. Commun. 12 , 1744 (2021)..

Wallucks, A. et al. Size photometry and fluorescence imaging of immobilized immersed extracellular vesicles. J. Extracell. Vesicles 13 , e12512 (2024)..

Iwanaga, M. All-dielectric metasurface fluorescence biosensors for high-sensitivity antibody/antigen detection. ACS Nano 14 , 17458–17467 (2020)..