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Label-free identification of non-activated lymphocytes using three-dimensional refractive index tomography and machine learning

Jonghee Yoon, YoungJu Jo, Min-hyeok Kim, Kyoohyun Kim, SangYun Lee, Suk-Jo Kang, YongKeun Park
doi: https://doi.org/10.1101/107805
Jonghee Yoon
1Department of Physics, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, South Korea
2KAIST Institute Health Science and Technology, Daejeon 34141, South Korea
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YoungJu Jo
1Department of Physics, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, South Korea
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Min-hyeok Kim
3Department of Biological Sciences, KAIST, Daejeon 34141, South Korea
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Kyoohyun Kim
1Department of Physics, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, South Korea
2KAIST Institute Health Science and Technology, Daejeon 34141, South Korea
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SangYun Lee
1Department of Physics, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, South Korea
2KAIST Institute Health Science and Technology, Daejeon 34141, South Korea
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Suk-Jo Kang
3Department of Biological Sciences, KAIST, Daejeon 34141, South Korea
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YongKeun Park
1Department of Physics, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, South Korea
2KAIST Institute Health Science and Technology, Daejeon 34141, South Korea
4Tomocube, Inc., Daejeon 34051, South Korea
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Abstract

Identification of lymphocyte cell types is crucial for understanding their pathophysiologic roles in human diseases. Current methods for discriminating lymphocyte cell types primarily relies on labelling techniques with magnetic beads or fluorescence agents, which take time and have costs for sample preparation and may also have a potential risk of altering cellular functions. Here, we present label-free identification of non-activated lymphocyte subtypes using refractive index tomography. From the measurements of three-dimensional refractive index maps of individual lymphocytes, the morphological and biochemical properties of the lymphocytes are quantitatively retrieved. Machine learning methods establish an optimized classification model using the retrieved quantitative characteristics of the lymphocytes to identify lymphocyte subtypes at the individual cell level. We show that our approach enables label-free identification of three lymphocyte cell types (B, CD4+ T, and CD8+ T lymphocytes) with high specificity and sensitivity. The present method will be a versatile tool for investigating the pathophysiological roles of lymphocytes in various diseases including cancers, autoimmune diseases, and virus infections.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted February 11, 2017.
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Label-free identification of non-activated lymphocytes using three-dimensional refractive index tomography and machine learning
Jonghee Yoon, YoungJu Jo, Min-hyeok Kim, Kyoohyun Kim, SangYun Lee, Suk-Jo Kang, YongKeun Park
bioRxiv 107805; doi: https://doi.org/10.1101/107805
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Label-free identification of non-activated lymphocytes using three-dimensional refractive index tomography and machine learning
Jonghee Yoon, YoungJu Jo, Min-hyeok Kim, Kyoohyun Kim, SangYun Lee, Suk-Jo Kang, YongKeun Park
bioRxiv 107805; doi: https://doi.org/10.1101/107805

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