Holotomography: refractive index as an intrinsic imaging contrast for 3-D label-free live cell imaging

Kim, Doyeon; Lee, Sang-Yun; Oh, Juntaek; Yang, Su-A; Park, YongKeun

doi:10.1101/106328

Cited by 37 publications

(45 citation statements)

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“…3D RI tomograms of samples are measured at an individual cell level using optical diffraction tomography (ODT) (22)(23)(24)(25), which will provide quantitative morphological and biophysical information of the samples. 3D RI tomograms of samples are measured at an individual cell level using optical diffraction tomography (ODT) (22)(23)(24)(25), which will provide quantitative morphological and biophysical information of the samples.…”

Section: Introductionmentioning

confidence: 99%

“…Here, we report the investigation of early neurotoxic effects in vitro PD model using 3D QPI techniques. 3D RI tomograms of samples are measured at an individual cell level using optical diffraction tomography (ODT) (22)(23)(24)(25), which will provide quantitative morphological and biophysical information of the samples. We exploit the fact that RI is an intrinsic optical property of materials and linearly proportional to material concentration (26).…”

Section: Introductionmentioning

confidence: 99%

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Measurements of morphological and biophysical alterations in individual neuron cells associated with early neurotoxic effects in Parkinson's disease

Yang

Yoon

et al. 2017

Cytometry Pt A

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Parkinson's disease (PD) is a common neurodegenerative disease. However, therapeutic methods of PD are still limited due to complex pathophysiology in PD. Here, optical measurements of individual neurons from in vitro PD model using optical diffraction tomography (ODT) are presented. By measuring 3D refractive index distribution of neurons, morphological and biophysical alterations in in-vitro PD model are quantitatively investigated. It was found that neurons show apoptotic features in early PD progression. The present approach will open up new opportunities for quantitative investigation of the pathophysiology of various neurodegenerative diseases. © 2017 International Society for Advancement of Cytometry.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Measurements of morphological and biophysical alterations in individual neuron cells associated with early neurotoxic effects in Parkinson's disease

Yang

Yoon

et al. 2017

Cytometry Pt A

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“…Another interesting possibility is to improve SNR using template-matching techniques based on full spatial and temporal correlations in the 4D spike-induced deformation movie. These could include machine learning algorithms, along with spatial averaging over the ROI predicted by the 3D cell model from confocal microscopy or holographic tomography 9,46 .…”

Section: Discussionmentioning

confidence: 99%

How neurons move during action potentials

Ling

Boyle

Zuckerman

et al. 2019

Preprint

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Neurons undergo nanometer-scale deformations during action potentials, and the underlying mechanism has been actively debated for decades. Previous observations were limited to a single spot or the cell boundary, while movement across the entire neuron during the action potential remained unclear.We report full-field imaging of cellular deformations accompanying the action potential in mammalian neuron somas (-1.8nm~1.3nm) and neurites (-0.7nm~0.9nm), using fast quantitative phase imaging with a temporal resolution of 0.1ms and an optical pathlength sensitivity of <4pm per pixel. Spike-triggered average, synchronized to electrical recording, demonstrates that the time course of the optical phase changes matches the dynamics of the electrical signal, with the optical signal revealing the intracellular potential rather than its time derivative detected via extracellular electrodes. Using 3D cellular morphology extracted via confocal microscopy, we demonstrate that the voltage-dependent changes in the membrane tension induced by ionic repulsion can explain the magnitude, time course and spatial features of the phase imaging. Our full-field observations of the spike-induced deformations in mammalian neurons opens the door to non-invasive label-free imaging of neural signaling.

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“…tomogram of a sample which quantitatively provides morphological and biochemical information 13,14 . Previously, ODT has been widely used to study various biological samples including red blood cells [15][16][17][18][19][20][21][22] however, we were unable to identify lymphocyte cell types due to their indistinguishable cellular morphology and biochemical characteristics.…”

Section: Identification Of Lymphocyte Cell Types Is Crucial For Undermentioning

confidence: 99%

“…tomogram of a sample which quantitatively provides morphological and biochemical information 13,14 . Previously, ODT has been widely used to study various biological samples including red blood cells [15][16][17][18][19][20][21][22] , white blood cells (WBC) 23,24 , hepatocytes 25 , cancer cells 16,[26][27][28][29][30][31][32] , neurons 32,33 , bacteria 34,35 , phytoplankton 36 , and hair 37 .…”

mentioning

confidence: 99%

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

Yoon

Kim

et al. 2017

Preprint

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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.Lymphocytes consisting of various cell types including B, helper (CD4+) T, cytotoxic (CD8+) T, and regulatory T lymphocytes, and play crucial roles in the adaptive immune system 1 . Each lymphocyte cell type has different functions: B lymphocytes produce antibodies, and T lymphocytes recognize a specific antigen and execute effector functions. The lymphocyte population and function are tightly regulated to defend the host against harmful invaders or abnormal conditions 1,2 . Disturbances in lymphocyte function and regulation are related to various diseases including cancers 3-5 , autoimmune diseases 6,7 , and virus infections 8,9 .. CC-BY 4.0 International license not peer-reviewed) is the author/funder. It is made available under a The copyright holder for this preprint (which was . http://dx.doi.org/10.1101/107805 doi: bioRxiv preprint first posted online Feb. 11, 2017; To understand the roles of different types of lymphocytes, several methods based on labelling techniques have been developed to identify and discriminate lymphocyte cell types. Because different kinds of lymphocytes have very similar cellular morphology such as a large nucleus with small cytosolic regions and round shapes, conventional optical methods such as bright-field microscopy or phase contrast microscopy have limited ability in classifying lymphocyte cell types 10 .To overcome this, a specific surface membrane proteins, known as surface markers, are recognized and tagged with magnetic beads or fluorescence molecules via antigen-antibody binding. And then, specific types of lymphocytes are identified and separated by magnetic forces or fluorescence signals 11 . Targeting surface markers is a precise and efficient manner to determine the cell types; however, labelling methods have potential risks of altering cellular functions b...

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Holotomography: refractive index as an intrinsic imaging contrast for 3-D label-free live cell imaging

Cited by 37 publications

References 155 publications

Measurements of morphological and biophysical alterations in individual neuron cells associated with early neurotoxic effects in Parkinson's disease

Measurements of morphological and biophysical alterations in individual neuron cells associated with early neurotoxic effects in Parkinson's disease

How neurons move during action potentials

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

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