Imaging cells and nanoparticles using modulated optically computed phase microscopy

Abstract Nanoparticles (NPs) have been successfully used as drug delivery systems. To develop and optimize NP-based drug delivery systems, it is essential to understand the dynamics of cell-NP interactions. Quantitative phase imaging techniques enable label-free imaging and have the potential to rev...

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Main Authors: Xuan Liu, Rupak Bhakta, Emily Kryvorutsky, Yuanwei Zhang
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-025-86377-1
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author Xuan Liu
Rupak Bhakta
Emily Kryvorutsky
Yuanwei Zhang
author_facet Xuan Liu
Rupak Bhakta
Emily Kryvorutsky
Yuanwei Zhang
author_sort Xuan Liu
collection DOAJ
description Abstract Nanoparticles (NPs) have been successfully used as drug delivery systems. To develop and optimize NP-based drug delivery systems, it is essential to understand the dynamics of cell-NP interactions. Quantitative phase imaging techniques enable label-free imaging and have the potential to reveal how cells interact with NPs. To measure the subtle motion at cellular and subcellular scales, it requires a high phase sensitivity and a high spatial resolution. However, phase imaging techniques are limited by an intrinsic tradeoff between sensitivity and resolution. To overcome the tradeoff, we develop a technology termed as modulated optically computed phase microscopy (M-OCPM) based on low coherence interferometry and optical computation. The key innovation of M-OCPM is to utilize optical computation that performs Fourier transform of the interferometric spectra, imposes temporal modulation on the interference signal, and circumvents the sensitivity-resolution tradeoff. We evaluated the performance of M-OCPM using various samples, and demonstrated its label-free imaging capability, high sensitivity (nanometer scale displacement sensitivity) and high resolution (~ 250 nm). Particularly, we imaged NPs along with cultured cells and showed different signal characteristics for NPs that were adhered to the cells or in the cell culture medium. Our results clearly demonstrated the feasibility of M-OCPM in studying cell-NP interactions.
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spelling doaj-art-6c3a8c0cdba34e6082d43c4c89e164322025-01-26T12:33:30ZengNature PortfolioScientific Reports2045-23222025-01-0115111210.1038/s41598-025-86377-1Imaging cells and nanoparticles using modulated optically computed phase microscopyXuan Liu0Rupak Bhakta1Emily Kryvorutsky2Yuanwei Zhang3Department of Electrical and Computer Engineering, New Jersey Institute of TechnologyDepartment of Electrical and Computer Engineering, New Jersey Institute of TechnologyDepartment of Chemistry & Environmental Science, Jordan Hu College of Science and Liberal Arts, New Jersey Institute of TechnologyDepartment of Chemistry & Environmental Science, Jordan Hu College of Science and Liberal Arts, New Jersey Institute of TechnologyAbstract Nanoparticles (NPs) have been successfully used as drug delivery systems. To develop and optimize NP-based drug delivery systems, it is essential to understand the dynamics of cell-NP interactions. Quantitative phase imaging techniques enable label-free imaging and have the potential to reveal how cells interact with NPs. To measure the subtle motion at cellular and subcellular scales, it requires a high phase sensitivity and a high spatial resolution. However, phase imaging techniques are limited by an intrinsic tradeoff between sensitivity and resolution. To overcome the tradeoff, we develop a technology termed as modulated optically computed phase microscopy (M-OCPM) based on low coherence interferometry and optical computation. The key innovation of M-OCPM is to utilize optical computation that performs Fourier transform of the interferometric spectra, imposes temporal modulation on the interference signal, and circumvents the sensitivity-resolution tradeoff. We evaluated the performance of M-OCPM using various samples, and demonstrated its label-free imaging capability, high sensitivity (nanometer scale displacement sensitivity) and high resolution (~ 250 nm). Particularly, we imaged NPs along with cultured cells and showed different signal characteristics for NPs that were adhered to the cells or in the cell culture medium. Our results clearly demonstrated the feasibility of M-OCPM in studying cell-NP interactions.https://doi.org/10.1038/s41598-025-86377-1
spellingShingle Xuan Liu
Rupak Bhakta
Emily Kryvorutsky
Yuanwei Zhang
Imaging cells and nanoparticles using modulated optically computed phase microscopy
Scientific Reports
title Imaging cells and nanoparticles using modulated optically computed phase microscopy
title_full Imaging cells and nanoparticles using modulated optically computed phase microscopy
title_fullStr Imaging cells and nanoparticles using modulated optically computed phase microscopy
title_full_unstemmed Imaging cells and nanoparticles using modulated optically computed phase microscopy
title_short Imaging cells and nanoparticles using modulated optically computed phase microscopy
title_sort imaging cells and nanoparticles using modulated optically computed phase microscopy
url https://doi.org/10.1038/s41598-025-86377-1
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AT emilykryvorutsky imagingcellsandnanoparticlesusingmodulatedopticallycomputedphasemicroscopy
AT yuanweizhang imagingcellsandnanoparticlesusingmodulatedopticallycomputedphasemicroscopy