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Applied Sciences
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Applications of Digital Holography in Biomedical Engineering
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Applications of Digital Holography in Biomedical Engineering

A special issue of Applied Sciences (ISSN 2076-3417). This special issue belongs to the section "Applied Biosciences and Bioengineering".

Deadline for manuscript submissions: closed (31 May 2020) | Viewed by 27135

Special Issue Editors

Prof. Dr. Anette Gjörloff Wingren

E-Mail Website
Guest Editor
Department of Biomedical Science, Faculty of Health and Society, Malmö University, 205 06 Malmö, Sweden
Interests: tumor biology; immunology; imaging; digital holographic cytometry; nanotechnology
Special Issues, Collections and Topics in MDPI journals
Dr. Zahra El-Schich

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Guest Editor
Department of Biomedical Sciences, Faculty of Health and Society, Malmö University, Malmö, Sweden
Interests: tumor biology; microscopy; imaging; digital holographic cytometry; nanotechnology
Dr. Kersti Alm

E-Mail Website
Guest Editor
Phase Holographic Imaging, 223 63 Lund, Sweden
Interests: tumor biology; imaging; digital holographic cytometry
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We cordially invite you to submit a paper for this Special Issue dedicated to digital holographic microscopy and applications in the field of biomedical engineering. The scope of this Special Issue is methods of quantitative phase imaging (QPI) and different technical implementations thereof, and their applications on biological material, such as normal and diseased cells, tissues, and bacteria. The main core relates to the biomedical imaging of different types of diseased cells and tissues; morphological analysis of living and dead cells; cell-cycle analysis; motility and migration of cells; clinical imaging of cells, tissues, or bacteria; and more. Automated QPI, in combination with machine-learning, will further be a part of this Issue. We hope that you find the content of this call relevant for your research, and will consider the publication of your work within this Special Issue.

Prof. Dr. Anette Gjörloff Wingren
Dr. Zahra El-Schich
Dr. Kersti Alm
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Applied Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2400 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Bioengineering
  • biomedicine
  • cancer
  • cytometry
  • digital holography
  • imaging
  • microscopy
  • quantitative phase imaging

Published Papers (7 papers)

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Research

9 pages, 1918 KiB  
Communication
Discrimination between Breast Cancer Cells and White Blood Cells by Non-Invasive Measurements: Implications for a Novel In Vitro-Based Circulating Tumor Cell Model Using Digital Holographic Cytometry
by Zahra El-Schich, Birgit Janicke, Kersti Alm, Nishtman Dizeyi, Jenny L. Persson and Anette Gjörloff Wingren
Appl. Sci. 2020, 10(14), 4854; https://doi.org/10.3390/app10144854 - 15 Jul 2020
Cited by 6 | Viewed by 3150
Abstract
Breast cancer is the second most common cancer worldwide. Metastasis is the main reason for death in breast cancer, and today, there is a lack of methods to detect and isolate circulating tumor cells (CTCs), mainly due to their heterogeneity and rarity. There [...] Read more.
Breast cancer is the second most common cancer worldwide. Metastasis is the main reason for death in breast cancer, and today, there is a lack of methods to detect and isolate circulating tumor cells (CTCs), mainly due to their heterogeneity and rarity. There are some systems that are designed to detect rare epithelial cancer cells in whole blood based on the most common marker used today, the epithelial cell adhesion molecule (EpCAM). It has been shown that aggressive breast cancer metastases are of non-epithelial origin and are therefore not always detected using EpCAM as a marker. In the present study, we used an in vitro-based circulating tumor cell model comprising a collection of six breast cancer cell lines and white blood cell lines. We used digital holographic cytometry (DHC) to characterize and distinguish between the different cell types by area, volume and thickness. Here, we present significant differences in cell size-related parameters observed when comparing white blood cells and breast cancer cells by using DHC. In conclusion, DHC can be a powerful diagnostic tool for the characterization of CTCs in the blood. Full article
(This article belongs to the Special Issue Applications of Digital Holography in Biomedical Engineering)
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14 pages, 5073 KiB  
Article
Salinomycin Treatment Specifically Inhibits Cell Proliferation of Cancer Stem Cells Revealed by Longitudinal Single Cell Tracking in Combination with Fluorescence Microscopy
by Sofia Kamlund, Birgit Janicke, Kersti Alm and Stina Oredsson
Appl. Sci. 2020, 10(14), 4732; https://doi.org/10.3390/app10144732 - 9 Jul 2020
Cited by 6 | Viewed by 4709
Abstract
A cell line derived from a tumor is a heterogeneous mixture of phenotypically different cells. Such cancer cell lines are used extensively in the search for new anticancer drugs and for investigating their mechanisms of action. Most studies today are population-based, implying that [...] Read more.
A cell line derived from a tumor is a heterogeneous mixture of phenotypically different cells. Such cancer cell lines are used extensively in the search for new anticancer drugs and for investigating their mechanisms of action. Most studies today are population-based, implying that small subpopulations of cells, reacting differently to the potential drug go undetected. This is a problem specifically related to the most aggressive single cancer cells in a tumor as they appear to be insensitive to the drugs used today. These cells are not detected in population-based studies when developing new anticancer drugs. Thus, to get a deeper understanding of how all individual cancer cells react to chemotherapeutic drugs, longitudinal tracking of individual cells is needed. Here we have used digital holography for long time imaging and longitudinal tracking of individual JIMT-1 breast cancer cells. To gain further knowledge about the tracked cells, we combined digital holography with fluorescence microscopy. We grouped the JIMT-1 cells into different subpopulations based on expression of CD24 and E-cadherin and analyzed cell proliferation and cell migration for 72 h. We investigated how the cancer stem cell (CSC) targeting drug salinomycin affected the different subpopulations. By uniquely combining digital holography with fluorescence microscopy we show that salinomycin specifically targeted the CD24− subpopulation, i.e., the CSCs, by inhibiting cell proliferation, which was evident already after 24 h of drug treatment. We further found that after salinomycin treatment, the surviving cells were more epithelial-like due to the selection of the CD24+ cells. Full article
(This article belongs to the Special Issue Applications of Digital Holography in Biomedical Engineering)
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11 pages, 2759 KiB  
Article
Quantifying the Rate, Degree, and Heterogeneity of Morphological Change during an Epithelial to Mesenchymal Transition Using Digital Holographic Cytometry
by Sofia Kamlund, Birgit Janicke, Kersti Alm, Robert L. Judson-Torres and Stina Oredsson
Appl. Sci. 2020, 10(14), 4726; https://doi.org/10.3390/app10144726 - 9 Jul 2020
Cited by 4 | Viewed by 2741
Abstract
Cells in complex organisms can transition between epithelial and mesenchymal phenotypes during both normal and malignant physiological events. These two phenotypes are not binary, but rather describe a spectrum of cell states along an axis. Mammalian cells can undergo dynamic and heterogenous bidirectional [...] Read more.
Cells in complex organisms can transition between epithelial and mesenchymal phenotypes during both normal and malignant physiological events. These two phenotypes are not binary, but rather describe a spectrum of cell states along an axis. Mammalian cells can undergo dynamic and heterogenous bidirectional interconversions along the epithelial–mesenchymal phenotypic (EMP) spectrum, and such transitions are marked by morphological change. Here, we exploit digital holographic cytometry (DHC) to develop a tractable method for monitoring the degree, kinetics, and heterogeneity of epithelial and mesenchymal phenotypes in adherent mammalian cell populations. First, we demonstrate that the epithelial and mesenchymal states of the same cell line present distinct DHC-derived morphological features. Second, we identify quantitative changes in these features that occur hours after induction of the epithelial to mesenchymal transition (EMT). We apply this approach to achieve label-free tracking of the degree and the rate of EMP transitions. We conclude that DHC is an efficient method to investigate morphological changes during transitions between epithelial and mesenchymal states. Full article
(This article belongs to the Special Issue Applications of Digital Holography in Biomedical Engineering)
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Figure 1

8 pages, 1651 KiB  
Article
Subpopulations of Organoid-Forming Cells Have Different Motility
by David Gomez Jimenez, Sofia Carreira Santos, Lennart Greiff, Kersti Alm and Malin Lindstedt
Appl. Sci. 2020, 10(13), 4673; https://doi.org/10.3390/app10134673 - 7 Jul 2020
Cited by 1 | Viewed by 3666
Abstract
Cancer stem cells from oropharyngeal squamous cell carcinoma (OPSCC) have the ability to self-renew and differentiate into heterogeneous three-dimensional structures carrying features of tumor cells. Here, we describe a simple and label-free method for generating tumor organoids, and imaging them using live digital [...] Read more.
Cancer stem cells from oropharyngeal squamous cell carcinoma (OPSCC) have the ability to self-renew and differentiate into heterogeneous three-dimensional structures carrying features of tumor cells. Here, we describe a simple and label-free method for generating tumor organoids, and imaging them using live digital holographic microscopy (DHM) on the basis of the phase shift caused by light passing through the cells. We show early events of cell aggregation during tumor-organoid formation, and display their heterogeneity in terms of optical parameters up to an optical volume of 105 µm3. Lastly, by sorting OPSCC epithelial cells, we demonstrate that CD44+ cells displayed greater motility and tumor-forming capacity than those of CD44− cells. These results were in line with previous reports highlighting increased invasive and tumorigenic potential in tumor cells expressing high levels of CD44. Our method provides insight into the formation of tumor organoids, and could be used to assess stemness-associated biomarkers and drug screenings on the basis of tumor organoids. Full article
(This article belongs to the Special Issue Applications of Digital Holography in Biomedical Engineering)
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13 pages, 4413 KiB  
Article
Label-Free Classification of Apoptosis, Ferroptosis and Necroptosis Using Digital Holographic Cytometry
by Kendra L. Barker, Kenneth M. Boucher and Robert L. Judson-Torres
Appl. Sci. 2020, 10(13), 4439; https://doi.org/10.3390/app10134439 - 27 Jun 2020
Cited by 8 | Viewed by 4258
Abstract
Apoptosis, ferroptosis and necroptosis are three distinct forms of programmed cell death. Each of these pathways can be exploited to terminate cancer cells. One promising therapeutic strategy is to activate alternative programmed cell death pathways subsequent to cancer cells evolving mechanisms to evade [...] Read more.
Apoptosis, ferroptosis and necroptosis are three distinct forms of programmed cell death. Each of these pathways can be exploited to terminate cancer cells. One promising therapeutic strategy is to activate alternative programmed cell death pathways subsequent to cancer cells evolving mechanisms to evade apoptosis. However, the interplay between distinct programmed cell death pathways and cancer progression is complex and can paradoxically promote the disease. There is a need for high-throughput assays for real-time classification of programmed cell death, both to further investigate these important biologic processes and to assess the case-by-case efficacy of targeting each pathway in patient-derived tumor cells. Here, we sought to develop a label-free, live-imaging-based assay for classifying forms of programmed cell death with single cell resolution. We used digital holographic cytometry (DHC) to monitor human melanoma cells undergoing apoptosis, ferroptosis, and necroptosis. We developed and validated models that used DHC-derived features to classify each form of cell death with 91–93% accuracy in the test sets. We conclude that high-accuracy, high-throughput, label-free classification of apoptosis, ferroptosis and necroptosis can be achieved with DHC. Full article
(This article belongs to the Special Issue Applications of Digital Holography in Biomedical Engineering)
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13 pages, 1979 KiB  
Article
Quantitative Phase Dynamics of Cancer Cell Populations Affected by Blue Light
by Marek Feith, Tomáš Vičar, Jaromír Gumulec, Martina Raudenská, Anette Gjörloff Wingren, Michal Masařík and Jan Balvan
Appl. Sci. 2020, 10(7), 2597; https://doi.org/10.3390/app10072597 - 9 Apr 2020
Cited by 6 | Viewed by 4268
Abstract
Increased exposition to blue light may induce many changes in cell behavior and significantly affect the critical characteristics of cells. Here we show that multimodal holographic microscopy (MHM) within advanced image analysis is capable of correctly distinguishing between changes in cell motility, cell [...] Read more.
Increased exposition to blue light may induce many changes in cell behavior and significantly affect the critical characteristics of cells. Here we show that multimodal holographic microscopy (MHM) within advanced image analysis is capable of correctly distinguishing between changes in cell motility, cell dry mass, cell density, and cell death induced by blue light. We focused on the effect of blue light with a wavelength of 485 nm on morphological and dynamical parameters of four cell lines, malignant PC-3, A2780, G361 cell lines, and the benign PNT1A cell line. We used MHM with blue light doses 24 mJ/cm2, 208 mJ/cm2 and two kinds of expositions (500 and 1000 ms) to acquire real-time quantitative phase information about cellular parameters. It has been shown that specific doses of the blue light significantly influence cell motility, cell dry mass and cell density. These changes were often specific for the malignant status of tested cells. Blue light dose 208 mJ/cm2 × 1000 ms affected malignant cell motility but did not change the motility of benign cell line PNT1A. This light dose also significantly decreased proliferation activity in all tested cell lines but was not so deleterious for benign cell line PNT1A as for malignant cells. Light dose 208 mJ/cm2 × 1000 ms oppositely affected cell mass in A2780 and PC-3 cells and induced different types of cell death in A2780 and G361 cell lines. Cells obtained the least damage on lower doses of light with shorter time of exposition. Full article
(This article belongs to the Special Issue Applications of Digital Holography in Biomedical Engineering)
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10 pages, 1620 KiB  
Article
Evaluation of the Impact of Imprinted Polymer Particles on Morphology and Motility of Breast Cancer Cells by Using Digital Holographic Cytometry
by Megha Patel, Marek Feith, Birgit Janicke, Kersti Alm and Zahra El-Schich
Appl. Sci. 2020, 10(3), 750; https://doi.org/10.3390/app10030750 - 21 Jan 2020
Cited by 16 | Viewed by 3277
Abstract
Breast cancer is the second most common cancer type worldwide and breast cancer metastasis accounts for the majority of breast cancer-related deaths. Tumour cells produce increased levels of sialic acid (SA) that terminates the monosaccharide on glycan chains of the glycosylated proteins. SA [...] Read more.
Breast cancer is the second most common cancer type worldwide and breast cancer metastasis accounts for the majority of breast cancer-related deaths. Tumour cells produce increased levels of sialic acid (SA) that terminates the monosaccharide on glycan chains of the glycosylated proteins. SA can contribute to cellular recognition, cancer invasiveness and increase the metastatic potential of cancer cells. SA-templated molecularly imprinted polymers (MIPs) have been proposed as promising reporters for specific targeting of cancer cells when deployed in nanoparticle format. The sialic acid-molecularly imprinted polymers (SA-MIPs), which use SA for the generation of binding sites through which the nanoparticles can target and stain breast cancer cells, opens new strategies for efficient diagnostic tools. This study aims at monitoring the effects of SA-MIPs on morphology and motility of the epithelial type MCF-7 and the highly metastatic MDAMB231 breast cancer cell lines, using digital holographic cytometry (DHC). DHC is a label-free technique that is used in cell morphology studies of e.g., cell volume, area and thickness as well as in motility studies. Here, we show that MCF-7 cells move slower than MDAMB231 cells. We also show that SA-MIPs have an effect on cell morphology, motility and viability of both cell lines. In conclusion, by using DH microscopy, we could detect SA-MIPs impact on different breast cancer cells regarding morphology and motility. Full article
(This article belongs to the Special Issue Applications of Digital Holography in Biomedical Engineering)
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