Light-field flow cytometry for high-resolution, volumetric and multiparametric 3D single-cell analysis

Abstract Imaging flow cytometry (IFC) combines flow cytometry and fluorescence microscopy to enable high-throughput, multiparametric single-cell analysis with rich spatial details. However, current IFC techniques remain limited in their ability to reveal subcellular information with a high 3D resolu...

Full description

Bibliographic Details
Main Authors: Xuanwen Hua, Keyi Han, Biagio Mandracchia, Afsane Radmand, Wenhao Liu, Hyejin Kim, Zhou Yuan, Samuel M. Ehrlich, Kaitao Li, Corey Zheng, Jeonghwan Son, Aaron D. Silva Trenkle, Gabriel A. Kwong, Cheng Zhu, James E. Dahlman, Shu Jia
Format: Article
Language:English
Published: Nature Portfolio 2024-03-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-024-46250-7
_version_ 1797274087476690944
author Xuanwen Hua
Keyi Han
Biagio Mandracchia
Afsane Radmand
Wenhao Liu
Hyejin Kim
Zhou Yuan
Samuel M. Ehrlich
Kaitao Li
Corey Zheng
Jeonghwan Son
Aaron D. Silva Trenkle
Gabriel A. Kwong
Cheng Zhu
James E. Dahlman
Shu Jia
author_facet Xuanwen Hua
Keyi Han
Biagio Mandracchia
Afsane Radmand
Wenhao Liu
Hyejin Kim
Zhou Yuan
Samuel M. Ehrlich
Kaitao Li
Corey Zheng
Jeonghwan Son
Aaron D. Silva Trenkle
Gabriel A. Kwong
Cheng Zhu
James E. Dahlman
Shu Jia
author_sort Xuanwen Hua
collection DOAJ
description Abstract Imaging flow cytometry (IFC) combines flow cytometry and fluorescence microscopy to enable high-throughput, multiparametric single-cell analysis with rich spatial details. However, current IFC techniques remain limited in their ability to reveal subcellular information with a high 3D resolution, throughput, sensitivity, and instrumental simplicity. In this study, we introduce a light-field flow cytometer (LFC), an IFC system capable of high-content, single-shot, and multi-color acquisition of up to 5,750 cells per second with a near-diffraction-limited resolution of 400-600 nm in all three dimensions. The LFC system integrates optical, microfluidic, and computational strategies to facilitate the volumetric visualization of various 3D subcellular characteristics through convenient access to commonly used epi-fluorescence platforms. We demonstrate the effectiveness of LFC in assaying, analyzing, and enumerating intricate subcellular morphology, function, and heterogeneity using various phantoms and biological specimens. The advancement offered by the LFC system presents a promising methodological pathway for broad cell biological and translational discoveries, with the potential for widespread adoption in biomedical research.
first_indexed 2024-03-07T14:53:21Z
format Article
id doaj.art-4523c0533efd47cd8f5f386a1b3e847a
institution Directory Open Access Journal
issn 2041-1723
language English
last_indexed 2024-03-07T14:53:21Z
publishDate 2024-03-01
publisher Nature Portfolio
record_format Article
series Nature Communications
spelling doaj.art-4523c0533efd47cd8f5f386a1b3e847a2024-03-05T19:32:50ZengNature PortfolioNature Communications2041-17232024-03-0115111210.1038/s41467-024-46250-7Light-field flow cytometry for high-resolution, volumetric and multiparametric 3D single-cell analysisXuanwen Hua0Keyi Han1Biagio Mandracchia2Afsane Radmand3Wenhao Liu4Hyejin Kim5Zhou Yuan6Samuel M. Ehrlich7Kaitao Li8Corey Zheng9Jeonghwan Son10Aaron D. Silva Trenkle11Gabriel A. Kwong12Cheng Zhu13James E. Dahlman14Shu Jia15Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory UniversityWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory UniversityWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory UniversityParker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of TechnologyWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory UniversityWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory UniversityParker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of TechnologyParker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of TechnologyWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory UniversityWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory UniversityWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory UniversityWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory UniversityWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory UniversityWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory UniversityWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory UniversityWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory UniversityAbstract Imaging flow cytometry (IFC) combines flow cytometry and fluorescence microscopy to enable high-throughput, multiparametric single-cell analysis with rich spatial details. However, current IFC techniques remain limited in their ability to reveal subcellular information with a high 3D resolution, throughput, sensitivity, and instrumental simplicity. In this study, we introduce a light-field flow cytometer (LFC), an IFC system capable of high-content, single-shot, and multi-color acquisition of up to 5,750 cells per second with a near-diffraction-limited resolution of 400-600 nm in all three dimensions. The LFC system integrates optical, microfluidic, and computational strategies to facilitate the volumetric visualization of various 3D subcellular characteristics through convenient access to commonly used epi-fluorescence platforms. We demonstrate the effectiveness of LFC in assaying, analyzing, and enumerating intricate subcellular morphology, function, and heterogeneity using various phantoms and biological specimens. The advancement offered by the LFC system presents a promising methodological pathway for broad cell biological and translational discoveries, with the potential for widespread adoption in biomedical research.https://doi.org/10.1038/s41467-024-46250-7
spellingShingle Xuanwen Hua
Keyi Han
Biagio Mandracchia
Afsane Radmand
Wenhao Liu
Hyejin Kim
Zhou Yuan
Samuel M. Ehrlich
Kaitao Li
Corey Zheng
Jeonghwan Son
Aaron D. Silva Trenkle
Gabriel A. Kwong
Cheng Zhu
James E. Dahlman
Shu Jia
Light-field flow cytometry for high-resolution, volumetric and multiparametric 3D single-cell analysis
Nature Communications
title Light-field flow cytometry for high-resolution, volumetric and multiparametric 3D single-cell analysis
title_full Light-field flow cytometry for high-resolution, volumetric and multiparametric 3D single-cell analysis
title_fullStr Light-field flow cytometry for high-resolution, volumetric and multiparametric 3D single-cell analysis
title_full_unstemmed Light-field flow cytometry for high-resolution, volumetric and multiparametric 3D single-cell analysis
title_short Light-field flow cytometry for high-resolution, volumetric and multiparametric 3D single-cell analysis
title_sort light field flow cytometry for high resolution volumetric and multiparametric 3d single cell analysis
url https://doi.org/10.1038/s41467-024-46250-7
work_keys_str_mv AT xuanwenhua lightfieldflowcytometryforhighresolutionvolumetricandmultiparametric3dsinglecellanalysis
AT keyihan lightfieldflowcytometryforhighresolutionvolumetricandmultiparametric3dsinglecellanalysis
AT biagiomandracchia lightfieldflowcytometryforhighresolutionvolumetricandmultiparametric3dsinglecellanalysis
AT afsaneradmand lightfieldflowcytometryforhighresolutionvolumetricandmultiparametric3dsinglecellanalysis
AT wenhaoliu lightfieldflowcytometryforhighresolutionvolumetricandmultiparametric3dsinglecellanalysis
AT hyejinkim lightfieldflowcytometryforhighresolutionvolumetricandmultiparametric3dsinglecellanalysis
AT zhouyuan lightfieldflowcytometryforhighresolutionvolumetricandmultiparametric3dsinglecellanalysis
AT samuelmehrlich lightfieldflowcytometryforhighresolutionvolumetricandmultiparametric3dsinglecellanalysis
AT kaitaoli lightfieldflowcytometryforhighresolutionvolumetricandmultiparametric3dsinglecellanalysis
AT coreyzheng lightfieldflowcytometryforhighresolutionvolumetricandmultiparametric3dsinglecellanalysis
AT jeonghwanson lightfieldflowcytometryforhighresolutionvolumetricandmultiparametric3dsinglecellanalysis
AT aarondsilvatrenkle lightfieldflowcytometryforhighresolutionvolumetricandmultiparametric3dsinglecellanalysis
AT gabrielakwong lightfieldflowcytometryforhighresolutionvolumetricandmultiparametric3dsinglecellanalysis
AT chengzhu lightfieldflowcytometryforhighresolutionvolumetricandmultiparametric3dsinglecellanalysis
AT jamesedahlman lightfieldflowcytometryforhighresolutionvolumetricandmultiparametric3dsinglecellanalysis
AT shujia lightfieldflowcytometryforhighresolutionvolumetricandmultiparametric3dsinglecellanalysis