Biosensor for deconvolution of individual cell fate in response to ion beam irradiation

Martin Niklas; Julian Schlegel; Hans Liew; Ferdinand Zimmermann; Katrin Rein; Dietrich W M Walsh; Oleh Dzyubachyk; Tim Holland-Letz; Shirin Rahmanian; Steffen Greilich; Armin Runz; Oliver Jäkel; Jürgen Debus; Amir Abdollahi

doi:10.1016/j.crmeth.2022.100169

Biosensor for deconvolution of individual cell fate in response to ion beam irradiation

Cell Rep Methods. 2022 Feb 17;2(2):100169. doi: 10.1016/j.crmeth.2022.100169. eCollection 2022 Feb 28.

Authors

Martin Niklas^{1

2}, Julian Schlegel^{1

2}, Hans Liew^{1

2}, Ferdinand Zimmermann^{1

2}, Katrin Rein^{1

2}, Dietrich W M Walsh^{1

2}, Oleh Dzyubachyk³, Tim Holland-Letz⁴, Shirin Rahmanian⁵, Steffen Greilich⁵, Armin Runz⁵, Oliver Jäkel^{2

5

6}, Jürgen Debus^{1

2

6}, Amir Abdollahi^{1

2

6}

Affiliations

¹ Division of Molecular and Translational Radiation Oncology and Clinical Cooperation Unit Translational Radiation Oncology, German Cancer Research Center (DKFZ) and Heidelberg University Hospital, 69120 Heidelberg, Germany.
² National Center for Tumor Diseases, German Cancer Consortium, Heidelberg Institute of Radiation Oncology and National Center for Radiation Oncology, 69120 Heidelberg, Germany.
³ Department of Radiology and Department of Cell and Chemical Biology, Leiden University Medical Center, 2333 ZC Leiden, the Netherlands.
⁴ Division of Biostatistics, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
⁵ Division of Medical Physics in Radiation Oncology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
⁶ Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg, Germany.

Abstract

Clonogenic survival assay constitutes the gold standard method for quantifying radiobiological effects. However, it neglects cellular radiation response variability and heterogeneous energy deposition by ion beams on the microscopic scale. We introduce "Cell-Fit-HD^4D" a biosensor that enables a deconvolution of individual cell fate in response to the microscopic energy deposition as visualized by optical microscopy. Cell-Fit-HD^4D enables single-cell dosimetry in clinically relevant complex radiation fields by correlating microscopic beam parameters with biological endpoints. Decrypting the ion beam's energy deposition and molecular effects at the single-cell level has the potential to improve our understanding of radiobiological dose concepts as well as radiobiological study approaches in general.

Keywords: Cell-Fit-HD; FNTD; biodosimetry; biosensor; clinical ion beam irradiation; double strand breaks; fluorescent nuclear track detector; ion beam cancer therapy; particle therapy; radiobiological effects.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Biosensing Techniques*
Heavy Ion Radiotherapy* / methods
Radiometry / methods

Grants and funding

P01 CA257904/CA/NCI NIH HHS/United States