Three-Dimensional Holographic Refractive-Index Measurement of Continuously Flowing Cells in a Microfluidic Channel

The refractive index of biological specimens is a source of intrinsic contrast that can be explored without any concerns of photobleaching or harmful effects caused by extra contrast agents. In addition, the refractive index contains rich information related to the metabolism of cells at the cellula...

Full description

Bibliographic Details
Main Authors: Sung, Yongjin, Lue, Niyom, Hamza, Bashar, Martel, Joseph, Irimia, Daniel, Choi, Wonshik, Yaqoob, Zahid, Dasari, Ramachandra Rao, So, Peter T. C.
Other Authors: Lincoln Laboratory
Format: Article
Language:en_US
Published: American Physical Society 2015
Online Access:http://hdl.handle.net/1721.1/97724
https://orcid.org/0000-0003-4698-6488
_version_ 1826196241742036992
author Sung, Yongjin
Lue, Niyom
Hamza, Bashar
Martel, Joseph
Irimia, Daniel
Choi, Wonshik
Yaqoob, Zahid
Dasari, Ramachandra Rao
So, Peter T. C.
author2 Lincoln Laboratory
author_facet Lincoln Laboratory
Sung, Yongjin
Lue, Niyom
Hamza, Bashar
Martel, Joseph
Irimia, Daniel
Choi, Wonshik
Yaqoob, Zahid
Dasari, Ramachandra Rao
So, Peter T. C.
author_sort Sung, Yongjin
collection MIT
description The refractive index of biological specimens is a source of intrinsic contrast that can be explored without any concerns of photobleaching or harmful effects caused by extra contrast agents. In addition, the refractive index contains rich information related to the metabolism of cells at the cellular and subcellular levels. Here, we report a no-moving-parts approach that provides three-dimensional refractive-index maps of biological samples continuously flowing in a microfluidic channel. Specifically, we use line illumination and off-axis digital holography to record the angular spectra of light scattered from flowing samples at high speed. Applying the scalar diffraction theory, we obtain accurate refractive-index maps of the samples from the measured spectra. Using this method, we demonstrate label-free three-dimensional imaging of live RKO human colon cancer cells and RPMI8226 multiple myeloma cells, and obtain the volume, dry mass, and density of these cells from the measured three-dimensional refractive-index maps. Our results show that the reported method, alone or in combination with the existing flow cytometry techniques, shows promise as a quantitative tool for stain-free characterization of a large number of cells.
first_indexed 2024-09-23T10:23:45Z
format Article
id mit-1721.1/97724
institution Massachusetts Institute of Technology
language en_US
last_indexed 2024-09-23T10:23:45Z
publishDate 2015
publisher American Physical Society
record_format dspace
spelling mit-1721.1/977242022-09-30T20:48:56Z Three-Dimensional Holographic Refractive-Index Measurement of Continuously Flowing Cells in a Microfluidic Channel Sung, Yongjin Lue, Niyom Hamza, Bashar Martel, Joseph Irimia, Daniel Choi, Wonshik Yaqoob, Zahid Dasari, Ramachandra Rao So, Peter T. C. Lincoln Laboratory Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Chemistry Massachusetts Institute of Technology. Department of Mechanical Engineering Massachusetts Institute of Technology. Laser Biomedical Research Center Sung, Yongjin Lue, Niyom Dasari, Ramachandra Rao Yaqoob, Zahid So, Peter T. C. The refractive index of biological specimens is a source of intrinsic contrast that can be explored without any concerns of photobleaching or harmful effects caused by extra contrast agents. In addition, the refractive index contains rich information related to the metabolism of cells at the cellular and subcellular levels. Here, we report a no-moving-parts approach that provides three-dimensional refractive-index maps of biological samples continuously flowing in a microfluidic channel. Specifically, we use line illumination and off-axis digital holography to record the angular spectra of light scattered from flowing samples at high speed. Applying the scalar diffraction theory, we obtain accurate refractive-index maps of the samples from the measured spectra. Using this method, we demonstrate label-free three-dimensional imaging of live RKO human colon cancer cells and RPMI8226 multiple myeloma cells, and obtain the volume, dry mass, and density of these cells from the measured three-dimensional refractive-index maps. Our results show that the reported method, alone or in combination with the existing flow cytometry techniques, shows promise as a quantitative tool for stain-free characterization of a large number of cells. National Institutes of Health (U.S.) (9P41EB015871-26A1) National Institutes of Health (U.S.) (P41 EB002503) Hamamatsu Corporation 2015-07-13T14:49:00Z 2015-07-13T14:49:00Z 2014-02 2013-12 Article http://purl.org/eprint/type/JournalArticle 2331-7019 http://hdl.handle.net/1721.1/97724 Sung, Yongjin, Niyom Lue, Bashar Hamza, Joseph Martel, Daniel Irimia, Ramachandra R. Dasari, Wonshik Choi, Zahid Yaqoob, and Peter So. “Three-Dimensional Holographic Refractive-Index Measurement of Continuously Flowing Cells in a Microfluidic Channel.” Physical Review Applied 1, no. 1 (February 2014). https://orcid.org/0000-0003-4698-6488 en_US http://dx.doi.org/10.1103/PhysRevApplied.1.014002 Physical Review Applied Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf American Physical Society PMC
spellingShingle Sung, Yongjin
Lue, Niyom
Hamza, Bashar
Martel, Joseph
Irimia, Daniel
Choi, Wonshik
Yaqoob, Zahid
Dasari, Ramachandra Rao
So, Peter T. C.
Three-Dimensional Holographic Refractive-Index Measurement of Continuously Flowing Cells in a Microfluidic Channel
title Three-Dimensional Holographic Refractive-Index Measurement of Continuously Flowing Cells in a Microfluidic Channel
title_full Three-Dimensional Holographic Refractive-Index Measurement of Continuously Flowing Cells in a Microfluidic Channel
title_fullStr Three-Dimensional Holographic Refractive-Index Measurement of Continuously Flowing Cells in a Microfluidic Channel
title_full_unstemmed Three-Dimensional Holographic Refractive-Index Measurement of Continuously Flowing Cells in a Microfluidic Channel
title_short Three-Dimensional Holographic Refractive-Index Measurement of Continuously Flowing Cells in a Microfluidic Channel
title_sort three dimensional holographic refractive index measurement of continuously flowing cells in a microfluidic channel
url http://hdl.handle.net/1721.1/97724
https://orcid.org/0000-0003-4698-6488
work_keys_str_mv AT sungyongjin threedimensionalholographicrefractiveindexmeasurementofcontinuouslyflowingcellsinamicrofluidicchannel
AT lueniyom threedimensionalholographicrefractiveindexmeasurementofcontinuouslyflowingcellsinamicrofluidicchannel
AT hamzabashar threedimensionalholographicrefractiveindexmeasurementofcontinuouslyflowingcellsinamicrofluidicchannel
AT marteljoseph threedimensionalholographicrefractiveindexmeasurementofcontinuouslyflowingcellsinamicrofluidicchannel
AT irimiadaniel threedimensionalholographicrefractiveindexmeasurementofcontinuouslyflowingcellsinamicrofluidicchannel
AT choiwonshik threedimensionalholographicrefractiveindexmeasurementofcontinuouslyflowingcellsinamicrofluidicchannel
AT yaqoobzahid threedimensionalholographicrefractiveindexmeasurementofcontinuouslyflowingcellsinamicrofluidicchannel
AT dasariramachandrarao threedimensionalholographicrefractiveindexmeasurementofcontinuouslyflowingcellsinamicrofluidicchannel
AT sopetertc threedimensionalholographicrefractiveindexmeasurementofcontinuouslyflowingcellsinamicrofluidicchannel