Rapid Trapping and Label-free Optical Characterization of Single Nanoscale Extracellular Vesicles and Nanoparticles in Solution

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Abstract Achieving high-throughput, comprehensive analysis of single nanoparticles to determine their size, shape, and composition is essential for understanding particle heterogeneity with applications ranging from drug delivery to environmental monitoring. Existing techniques are hindered by low throughput, lengthy trapping times, irreversible particle adsorption, or limited characterization capabilities. Here, we introduce Interferometric Electrohydrodynamic Tweezers (IET), an integrated platform that combines rapid molecular trapping, interferometric scattering imaging, and Raman scattering to rapidly trap and characterize single nanoparticles in parallel within seconds in one integrated platform. The IET platform enables to perform both trapping and Raman analysis within seconds in contrast with laser trapping Raman spectroscopy that often require at least ten minutes per measurement, especially in low particle concentration media, where particle loading is slow. We demonstrate the platform's capabilities by trapping and characterizing the size and chemical composition of colloidal polymer beads and nanoscale extracellular vesicles (EVs), while trapped in solution. Our IET represents a powerful optofluidics platform for comprehensive characterization of nanoscale objects, opening new avenues in nanomedicine, environmental monitoring, and beyond.
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Rapid Trapping and Label-free Optical Characterization of Single Nanoscale Extracellular Vesicles and Nanoparticles in Solution | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Rapid Trapping and Label-free Optical Characterization of Single Nanoscale Extracellular Vesicles and Nanoparticles in Solution Justus Ndukaife, Ikjun Hong, Chuchuan Hong, Theodore Anyika, Guodong Zhu, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6279645/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 20 Mar, 2026 Read the published version in Light: Science & Applications → Version 1 posted 9 You are reading this latest preprint version Abstract Achieving high-throughput, comprehensive analysis of single nanoparticles to determine their size, shape, and composition is essential for understanding particle heterogeneity with applications ranging from drug delivery to environmental monitoring. Existing techniques are hindered by low throughput, lengthy trapping times, irreversible particle adsorption, or limited characterization capabilities. Here, we introduce Interferometric Electrohydrodynamic Tweezers (IET), an integrated platform that combines rapid molecular trapping, interferometric scattering imaging, and Raman scattering to rapidly trap and characterize single nanoparticles in parallel within seconds in one integrated platform. The IET platform enables to perform both trapping and Raman analysis within seconds in contrast with laser trapping Raman spectroscopy that often require at least ten minutes per measurement, especially in low particle concentration media, where particle loading is slow. We demonstrate the platform's capabilities by trapping and characterizing the size and chemical composition of colloidal polymer beads and nanoscale extracellular vesicles (EVs), while trapped in solution. Our IET represents a powerful optofluidics platform for comprehensive characterization of nanoscale objects, opening new avenues in nanomedicine, environmental monitoring, and beyond. Physical sciences/Optics and photonics/Optical techniques/Optical manipulation and tweezers Physical sciences/Optics and photonics/Optical techniques/Optical spectroscopy/Raman spectroscopy Physical sciences/Optics and photonics/Optical techniques/Imaging and sensing Full Text Additional Declarations There is no conflict of interest Supplementary Files RapidTrappingandLabelSI.pdf Rapid Trapping and Label-free Optical Characterization of Single Nanoscale Extracellular Vesicles and Nanoparticles in Solution Movie1.mov Rapid and parallel trapping of a 300 nm PS bead for the raw video. Movie2.mp4 Rapid and parallel trapping of a 300 nm PS bead after the background subtraction. Movie3.mp4 100nm, 200 nm, and 300 nm PS beads trapping and releasing after the background subtraction. Movie4.mp4 EVs trapping and release after the background subtraction. Movie5.mp4 EVs rotational motion after the background subtraction showing that our approach can detect irregular shaped particles that are non-spherical such as two EVs fused together. Movie6.mp4 Supermeres trapping and releasing after the background subtraction. Cite Share Download PDF Status: Published Journal Publication published 20 Mar, 2026 Read the published version in Light: Science & Applications → Version 1 posted Editorial decision: revise 25 Jun, 2025 Review # 2 received at journal 07 Jun, 2025 Reviewer # 2 agreed at journal 16 May, 2025 Review # 1 received at journal 15 Apr, 2025 Reviewer # 1 agreed at journal 04 Apr, 2025 Reviewers invited by journal 02 Apr, 2025 Submission checks completed at journal 25 Mar, 2025 Editor assigned by journal 21 Mar, 2025 First submitted to journal 21 Mar, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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