Malmö University

PHI and Malmö University have a long-standing collaboration, dating back to 2008. The collaboration has resulted in several peer reviewed publications and a doctoral thesis. In late 2016, the European Commission granted 2.1 million euro to GlycoImaging – a joint cancer research project to develop improved methods for clinically diagnosing cancer.

Current methods for diagnosing cancer primarily focus on the proteins associated with cancer. However, there is increasing evidence that carbohydrates play an important role in the development and progression of malignant cancer. Current methods use and rely on antibodies created by living organisms. These natural antibodies, however, are not sufficiently specific to accurately detect and image carbohydrates.

The GlycoImaging project is coordinated by Malmö University and commercialized by PHI. Additional partners are Bundesanstalt für Materialforschung und Prüfung (Germany’s federal technology research institute), Umeå, Copenhagen and Turku University.

Quantitative Phase Imaging for Label-Free Analysis of Cancer Cells – Focus on Digital Holographic Microscopy

Z. El-Schich, A Leida Mölder and A Gjörloff Wingren

Appl Sci (2018)

Review providing a current insight into QPI (quantitative phase imaging) applied to cancer research. The authors conclude that QPI is an ideal method for studying live cell dynamics by providing data from noninvasive monitoring over arbitrary time scales. The effect of drugs on migration, proliferation, and apoptosis of cancer cells are emerging fields suitable for QPI analysis. The authors also point out that need for QPI applications in clinical cancer diagnostics and treatments is emerging.

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Non-invasive, Label-free Cell Counting and Quantitative Analysis of Adherent Cells Using Digital Holography

A. MÖLDER, M. SEBESTA, M. GUSTAFSSON, L. GISSELSON, A. GJÖRLOFF WINGREN, K. ALM

Journal of Microscopy (2008)

Using a unique non-invasive label-free cell counting method comparable to conventional cell counting using a hemocytometer was produced. The major advantage of using HoloMonitor™ M2 is the opportunity to easily access information about cell number, size, optical thickness, and confluence in an automatic, non-invasive manner.

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Digital Holographic Microscopy — Innovative and Non-destructive Analysis of Living Cells

Z. El-Schich, A. Mölder, M. Sebesta, L. Gisselsson, K. Alm, A. Gjörloff Wingren

Microscopy: Science, Technology, Applications and Education (2010)

Digital holography is a novel technique that has been developed recently to study living cells. The technique is an innovative, non-destructive method with possibilities to study living cells over time. We are investigating cell number, growth, viability, and death of adherent cells using digital holography, which is a novel, label-free, imaging technique for biological applications. Digital holography is a method that gives us information about the refractive index of cells, which can change under different circumstances. The technique is cheap, fast, and simple to use. The unique measurable parameters are the cell number, cell area, thickness, and volume, which can be transformed to proliferation, migration, viability, and cell death. The digital holographic images produced can provide both quantitative and qualitative phase information from a single hologram. Future applications can include real-time cell monitoring of various parameters of cells of different diseases in response to clinically relevant compounds.

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Digital Holography and Cell Studies

K. Alm, H. Cirenajwis, L. Gisselsson, A. Gjörloff Wingren, B. Janicke, A. Mölder, S. Oredsson, J. Persson

Holography-Research and technologies (2011)

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Cells and Holograms — Holograms and Digital Holographic Microscopy as a Tool to Study the Morphology of Living Cells

K. Alm, Z. El-Schich, M. Falck Miniotis, A. Gjörloff Wingren, B. Janicke and S. Oredsson

Holography — Basic Principles and Contemporary Applications (2013)

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Digital Holographic Microscopy for Non-invasive Monitoring of Cell Cycle Arrest in L929 Cells

Maria Falck Miniotis, Anthonny Mukwaya and Anette Gjörloff Wingren

PLOS ONE (2014)

We show that average cell phase volume results from DHM readings are comparable to the flow cytometry findings. DHM thus provides a non-disruptive alternative to flow cytometry. The technique has the potential to develop into a fast and cost-efficient method for pre-clinical monitoring of cancer treatment efficacy.

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Interfacing Antibody-based Microarrays and Digital Holography Enables Label-free Detection for Loss of Cell Volume

Zahra El-Schich, Emmy Nilsson, Anna S Gerdtsson, Christer Wingren and Anette Gjörloff Wingren

Future science oa (2015)

The article provides proof of concept for using holographic microscopy combined with antibody-based microarray technology for detecting morphological changes in captured cells.

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Supervised Classification of Etoposide-treated in Vitro Adherent Cells Based on Noninvasive Imaging Morphology

Anna Leida Mölder, Johan Persson, Zahra El-Schich, Silvester Czanner, Anette Gjörloff-Wingren

Journal of Medical Imaging (2017)

The morphological changes observed occur before and at lower concentrations than a reduction in cell metabolic activity or viability. Three classifiers are compared and we report a best case sensitivity of 88% and specificity of 94% for classification of cells as treated/untreated.

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Holography: the Usefulness of Digital Holographic Microscopy for Clinical Diagnostics

Zahra El-Schich, Sofia Kamlund, Birgit Janicke, Kersti Alm and Anette Gjörloff Wingren

Holographic Materials and Optical Systems (2017)

Open access book chapter discussing the potential of holographic microscopy in clinical applications

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Quantitative Phase-contrast Imaging – a Potential Tool for Future Cancer Diagnostics

Anette Gjörloff-Wingren

Cytometry Part A (2017)

Prof. Gjörloff-Wingren has used holographic microscopy in cancer-related research for over a decade. Gjörloff-Wingren discusses the emerging field of quantitative phase imaging and the novel label-free capabilities that promise to improve and succeed in invasive laborious photochemical procedures.

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Moving into a New Dimension: Tracking Migrating Cells with Digital Holographic Cytometry in 3D

A. Görloff Wingren

Cytometry Part A (2018)

Commentary article discussing the fundamental role of cell movement studies in cancer research. Advantages of the HoloMonitor Cell Tracking and Wound Healing Applications over the transwell migration and invasion assays are highlighted, and includes the possibility to use the cells in experiments for other purposes after completing the imaging. In addition to single cell tracking, the HoloMonitor technology also benefits from the fact that morphology analysis can be performed of each cell. The author concludes that this indeed opens up for almost unlimited possibilities to perform cell morphology analysis using this methodology, since each image is very rich in cellular information.

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Digital Holographic Cytometry: Macrophage Uptake of Nanoprobes

Louise Sternbæk, Martha Wamaitha Kimani, Kornelia Gawlitza, Birgit Janicke, Kersti Alm, Anette, Gjörloff Wingren

Imaging & Microscopy (2019)

Various nanoprobes are designed to have drug-delivery or detection properties. However, as a foreign bodies in human blood circulation, nanoprobes can potentially induce inflamatory response and active macrophages. In this study, L. Sternbæk et al. have employed HoloMonitor M4 to study the effects of nanoprobes (molecularly imprinted polymers targeted to sialic acid) on macrophage cell line, RAW 264.7 by evaluating cell morphology (cell area, volume, and thickness) and cell count. Authors have shown that neither the HoloMonitor M4 nor nanoprobes affected the physiological functions of macrophages.

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Evaluation of the Impact of Imprinted Polymer Particles on Morphology and Motility of Breast Cancer Cells by Using Digital Holographic Cytometry

Megha Patel, Marek Feith,Birgit Janicke,Kersti Alm and Zahra El-Schich

Applied Sciences (2021)

In order to find a way to increase breast cancer patient prognosis, scientists need to understand cell behavior and metastasis. One of the possible tools in the efficient diagnosis is sialic acid-molecularly imprinted polymers (SA-MIPs). The aim of this paper was to study the effects of SA-MIPs on cell morphology and behavior. Using HoloMonitor M4 M. Patel with colleagues show SA-MIP can change cell motility (slower down MCF-7 cells and increase MDAMB231 cell speed), cell morphology for both cell lines.

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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

Zahra El-Schich, Birgit Janicke, Kersti Alm, Nishtman Dizeyi, Jenny L. Persson and Anette Gjörloff Wingren

Applied Sciences (2021)

Circulating Tumor Cells (CTC) are the main cause of cancer metastasis and regeneration. However, at the moment there is a lack of methods capable to detect and isolate CTC, as they are rare and heterogeneous. In this work, Z. El-Scich with colleagues have studied the morphological differences between white blood cell lines and human breast cancer cell lines. Authors have utilized HoloMonitor M4 and results show that there are significant differences in cell size-related parameters (cell area, cell volume, and cell thickness) between white blood cell lines and breast cancer cell lines, implying that HoloMonitor M4 and digital holographic cytometry can become a powerful diagnostic tool to characterize and detect CTCs in the blood.

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Novel Imaging Technology and Tools for Biomarker Detection in Cancer

Health and Society, Malmö University

Zahra El-Schich (2016)

To analyze morphological changes of dead cells, HoloMonitor was used. A digital holographic microscopy is an approach for label-free non-invasive 3D imaging of cultured cells. We have analyzed cell death of adherent cancer cells using HoloMonitor and developed it to analyze suspension cells by combining this technique with antibody-based microassays. HoloMonitor can be used for cell-death induced cell analysis of both adherent cells and suspension cells.

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