Detection of human disease conditions by single-cell morpho-rheological phenotyping of blood

  1. Nicole Toepfner
  2. Christoph Herold
  3. Oliver Otto
  4. Philipp Rosendahl
  5. Angela Jacobi
  6. Martin Kräter
  7. Julia Stächele
  8. Leonard Menschner
  9. Maik Herbig
  10. Laura Ciuffreda
  11. Lisa Ranford-Cartwright
  12. Michal Grzybek
  13. Ünal Coskun
  14. Elisabeth Reithuber
  15. Genevieve Garriss
  16. Peter Mellroth
  17. Birgitta Henriques Normark
  18. Nicola Tregay
  19. Meinolf Suttorp
  20. Martin Bornhäuser
  21. Edwin R Chilvers
  22. Reinhard Berner
  23. Jochen Guck  Is a corresponding author
  1. Technische Universität Dresden, Germany
  2. University Clinic Carl Gustav Carus, Technische Universität Dresden, Germany
  3. University of Glasgow, United Kingdom
  4. Karolinska Institutet, Sweden
  5. University of Cambridge, United Kingdom

Abstract

Blood is arguably the most important bodily fluid and its analysis provides crucial health status information. A first routine measure to narrow down diagnosis in clinical practice is the differential blood count, determining the frequency of all major blood cells. What is lacking to advance initial blood diagnostics is an unbiased and quick functional assessment of blood that can narrow down the diagnosis and generate specific hypotheses. To address this need, we introduce the continuous, cell-by-cell morpho-rheological (MORE) analysis of diluted whole blood, without labeling, enrichment or separation, at rates of 1,000 cells/sec. In a drop of blood we can identify all major blood cells and characterize their pathological changes in several disease conditions in vitro and in patient samples. This approach takes previous results of mechanical studies on specifically isolated blood cells to the level of application directly in blood and adds a functional dimension to conventional blood analysis.

Data availability

The following data sets were generated

Article and author information

Author details

  1. Nicole Toepfner

    Center of Molecular and Cellular Bioengineering, Technische Universität Dresden, Dresden, Germany
    Competing interests
    No competing interests declared.
  2. Christoph Herold

    Center of Molecular and Cellular Bioengineering, Technische Universität Dresden, Dresden, Germany
    Competing interests
    Christoph Herold, Owns shares of, and is full-time employed at, Zellmechanik Dresden GmbH, a company selling devices based on real-time deformability cytometry. The author has no other financial interests to declare. Zellmechanik Dresden GmbH did not have any role in the conception and planning of this study, or its preparation for publication.
  3. Oliver Otto

    Center of Molecular and Cellular Bioengineering, Technische Universität Dresden, Dresden, Germany
    Competing interests
    Oliver Otto, Owns shares of, and is part-time employed at, Zellmechanik Dresden GmbH, a company selling devices based on real-time deformability cytometry. The author has no other financial interests to declare. Zellmechanik Dresden GmbH did not have any role in the conception and planning of this study, or its preparation for publication.
  4. Philipp Rosendahl

    Center of Molecular and Cellular Bioengineering, Technische Universität Dresden, Dresden, Germany
    Competing interests
    Philipp Rosendahl, Owns shares of, and is part-time employed at, Zellmechanik Dresden GmbH, a company selling devices based on real-time deformability cytometry. The author has no other financial interests to declare. Zellmechanik Dresden GmbH did not have any role in the conception and planning of this study, or its preparation for publication.
  5. Angela Jacobi

    Center of Molecular and Cellular Bioengineering, Technische Universität Dresden, Dresden, Germany
    Competing interests
    No competing interests declared.
  6. Martin Kräter

    Department of Hematology and Oncology, University Clinic Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7122-7331
  7. Julia Stächele

    Department of Pediatrics, University Clinic Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
    Competing interests
    No competing interests declared.
  8. Leonard Menschner

    Department of Pediatrics, University Clinic Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
    Competing interests
    No competing interests declared.
  9. Maik Herbig

    Center of Molecular and Cellular Bioengineering, Technische Universität Dresden, Dresden, Germany
    Competing interests
    No competing interests declared.
  10. Laura Ciuffreda

    Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom
    Competing interests
    No competing interests declared.
  11. Lisa Ranford-Cartwright

    Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom
    Competing interests
    No competing interests declared.
  12. Michal Grzybek

    Paul Langerhans Institute, University Clinic Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
    Competing interests
    No competing interests declared.
  13. Ünal Coskun

    Paul Langerhans Institute, University Clinic Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4375-3144
  14. Elisabeth Reithuber

    Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden
    Competing interests
    No competing interests declared.
  15. Genevieve Garriss

    Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5361-0975
  16. Peter Mellroth

    Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden
    Competing interests
    No competing interests declared.
  17. Birgitta Henriques Normark

    Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden
    Competing interests
    No competing interests declared.
  18. Nicola Tregay

    Department of Medicine, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    No competing interests declared.
  19. Meinolf Suttorp

    Department of Pediatrics, University Clinic Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
    Competing interests
    No competing interests declared.
  20. Martin Bornhäuser

    Department of Hematology and Oncology, University Clinic Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
    Competing interests
    No competing interests declared.
  21. Edwin R Chilvers

    Department of Medicine, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4230-9677
  22. Reinhard Berner

    Department of Pediatrics, University Clinic Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
    Competing interests
    No competing interests declared.
  23. Jochen Guck

    Center of Molecular and Cellular Bioengineering, Technische Universität Dresden, Dresden, Germany
    For correspondence
    jochen.guck@tu-dresden.de
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1453-6119

Funding

Alexander von Humboldt-Stiftung (Alexander von Humboldt Professorship)

  • Jochen Guck

National Institute for Health Research (Cambridge Biomedical Research Centre)

  • Edwin R Chilvers

GlaxoSmithKline (noncommercial grant)

  • Edwin R Chilvers

Seventh Framework Programme (ERC Starting Grant #282060)

  • Jochen Guck

Deutsche Forschungsgemeinschaft (TRR83 and SFB655)

  • Ünal Coskun
  • Martin Bornhäuser

Seventh Framework Programme (ITN)

  • Lisa Ranford-Cartwright
  • Birgitta Henriques Normark
  • Jochen Guck

Bundesministerium für Bildung und Forschung (German Center for Diabetes Research (DZD e.V.))

  • Ünal Coskun

Sächsisches Staatsministerium für Wissenschaft und Kunst (TG70 AZ 4-7531.60/29/45)

  • Oliver Otto
  • Jochen Guck

Tour der Hoffnung (noncommercial grant)

  • Julia Stächele

Sonnenstrahl e.V. Dresden (noncommercial grant)

  • Meinolf Suttorp

Center for Regenerative Therapies Dresden (Seed grant FZ 111)

  • Jochen Guck

Technische Universität Dresden (Support the Best Program)

  • Reinhard Berner
  • Jochen Guck

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: The work involved measurements of human blood samples. All studies complied with the Declaration of Helsinki and involved written informed consent from all participants or their legal guardians. Ethics for experiments with human blood were approved by the ethics committee of the Technische Universität Dresden (EK89032013, EK458102015), and for human blood and LPS inhalation in healthy volunteers by the East of England, Cambridge Central ethics committee (Study No. 06/Q0108/281 and ClinicalTrialReference NCT02551614).

Reviewing Editor

  1. Patricia Bassereau, Institut Curie, France

Publication history

  1. Received: June 1, 2017
  2. Accepted: January 3, 2018
  3. Accepted Manuscript published: January 13, 2018 (version 1)
  4. Version of Record published: January 30, 2018 (version 2)

Copyright

© 2018, Toepfner et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Nicole Toepfner
  2. Christoph Herold
  3. Oliver Otto
  4. Philipp Rosendahl
  5. Angela Jacobi
  6. Martin Kräter
  7. Julia Stächele
  8. Leonard Menschner
  9. Maik Herbig
  10. Laura Ciuffreda
  11. Lisa Ranford-Cartwright
  12. Michal Grzybek
  13. Ünal Coskun
  14. Elisabeth Reithuber
  15. Genevieve Garriss
  16. Peter Mellroth
  17. Birgitta Henriques Normark
  18. Nicola Tregay
  19. Meinolf Suttorp
  20. Martin Bornhäuser
  21. Edwin R Chilvers
  22. Reinhard Berner
  23. Jochen Guck
(2018)
Detection of human disease conditions by single-cell morpho-rheological phenotyping of blood
eLife 7:e29213.
https://doi.org/10.7554/eLife.29213
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