Focus small to find big – the microbeam story

Abstract

Purpose: Even though the first ultraviolet microbeam was described by S. Tschachotin back in 1912, the development of sophisticated micro-irradiation facilities only began to flourish in the late 1980s. In this article, we highlight significant microbeam experiments, describe the latest microbeam irradiator configurations and critical discoveries made by using the microbeam apparatus.

Materials and methods: Modern radiological microbeams facilities are capable of producing a beam size of a few micrometers, or even tens of nanometers in size, and can deposit radiation with high precision within a cellular target. In the past three decades, a variety of microbeams has been developed to deliver a range of radiations including charged particles, X-rays, and electrons. Despite the original intention for their development to measure the effects of a single radiation track, the ability to target radiation with microbeams at sub-cellular targets has been extensively used to investigate radiation-induced biological responses within cells.

Results: Studies conducted using microbeams to target specific cells in a tissue have elucidated bystander responses, and further studies have shown reactive oxygen species (ROS) and reactive nitrogen species (RNS) play critical roles in the process. The radiation-induced abscopal effect, which has a profound impact on cancer radiotherapy, further reaffirmed the importance of bystander effects. Finally, by targeting sub-cellular compartments with a microbeam, we have reported cytoplasmic-specific biological responses. Despite the common dogma that nuclear DNA is the primary target for radiation-induced cell death and carcinogenesis, studies conducted using microbeam suggested that targeted cytoplasmic irradiation induces mitochondrial dysfunction, cellular stress, and genomic instability. A more recent development in microbeam technology includes application of mouse models to visualize in vivo DNA double-strand breaks.

Conclusions: Microbeams are making important contributions towards our understanding of radiation responses in cells and tissue models.

Keywords:

• Radiation
• microbeam irradiator
• bystander effect
• cytoplasmic irradiation
• abscopal effect

Acknowledgments

The authors thank Dr. Sherry Yan and Mr. Yen-Ruh Wuu for helpful discussion and editorial assistance.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Notes on contributors

Dr. Jinhua Wu received her B.S. degree in biomedical engineering from Huazong University of Science and Technology in China and her Ph.D. degree in Biochemistry and Molecular Biology from Virginia Commonwealth University. She is currently a senior postdoctoral research scientist in Professor Tom Hei’s laboratory at the Center for Radiological Research of Columbia University.

Dr. Tom K. Hei is the associate director of Center for Radiological Research, Columbia University and vice-chairman of Department of Radiation Oncology. His research program focuses on environmental carcinogenesis, specifically mechanisms of chemical and radiation carcinogenesis/mutagenesis at the cellular and molecular levels.

Additional information

Funding

NIH5P01-CA49062-235R01-ES12888-09EB-002033

National Institute of Biomedical Imaging and Bioengineering10.13039/100000070This research was supported by the NIH grants 5P01-CA49062-23 and 5R01ES012888-07. The Radiological Research Accelerator Facilities is an NIH sponsored Resource Center through grant 5P41EB002033-22 (National Institute of Biomedical Imaging and Bioengineering).