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A single-cell microbeam is a very narrow beam of radiation, of micrometer or submicrometer size, corresponding to cellular or sub-cellular dimensions. Together with appropriately integrated imaging techniques for individual cellular or sub-cellular targets, it allows rapid sequential irradiation of these targets, one by one, in individual cells.

Radiological Research Accelerator Facility

Contents

• Contact Information
• Grant Number
• Research Emphasis
• Current Research
• Resource Capabilities
• References

Contact Information

Columbia University Center for Radiological Research
630 West 168th Street
New York, NY 10032
http://www.raraf.org

Principal Investigator/Contact
David J. Brenner, Ph.D.
Phone: 212-305-9930
Fax: 212-305-3229
djb3@columbia.edu

Contact/Lab Manager
Steve Marino
Phone: 914-591-9244
Fax: 914-591-9405
sm14@columbia.edu

Grant Number

Grant No. EB002033

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Research Emphasis

The Columbia University Radiological Research Accelerator Facility (RARAF) is a dedicated facility for radiobiological research with available ionizing radiations such as protons, alpha particles, and neutrons. RARAF is well-established and highly user-friendly. The focus of RARAF is the development of high-throughput single-cell/single-particle microbeams, which can deliver defined amounts of ionizing radiation into individual cells with a spatial resolution of a few microns or better. The ability of a microbeam to put double strand break damage at any specific known location in a given cell has allowed new approaches to the study of damage signaling.

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Current Research

The biological interest in the single-cell/single-particle microbeam stems from its potential to deliver, with high throughput, well-defined radiation damage into cells or parts of cells—well defined in terms of space, time, and energy. The microbeam allows irradiation to localized spatial regions within cells, such as part of the nucleus, or the cytoplasm, or of immediate neighbor cells of a given cell. This enables us to address such questions as the effects of irradiation of neighboring cells (the so called "bystander effect", the effects of single tracks of radiation [the lowest possible radiation dose], and the relative sensitivities of different parts of the cell, such as nucleus vs. cytoplasm).

As examples of results obtained using the single-cell microbeam, it is now clear that:

• Information about damage to a given cell can be transmitted to nearby initially undamaged neighbor cells and can result in mutational or oncogenic damage in these "bystander" cells.
• Damage to the cytoplasm of a cell can have deleterious consequences in term of mutations induced in the nuclear DNA.

Current technology development focuses on four areas which our users have identified as ripe for enhancement (see the RARAF Web site):

1. Improvements in spatial precision, through state-of-the art electrostatic lenses
2. Enhancements in imaging capabilities, for example an on-line multi-photon imaging system is being integrated into the system to allow microbeam irradiation of 3-D tissues and time-lapse fluorescent imaging of early (scale of seconds to minutes) radiation events in individual live cells
3. Extension of the charged-particle microbeam to x-rays
4. Development of a simple stand-alone microbeam, based on a radioactive source rather than a particle accelerator, that can potentially be exported to other labs.

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Resource Capabilities

• A single-cell/single-particle microbeam beamline and endstation:
  • The microbeam facility delivers a predetermined number of charged particles (>1) in a given location through each of a number of cells growing on a dish.
  • The current maximum throughput is ~15,000 irradiated cells per hour, with a current precision of ± 2¼m
  • We have completed construction of an electrostatic lens focusing system that will improve the precision of the microbeam to about ± 0.4 ¼m. Installation is scheduled for 2005.
  • We are replacing our present 4.2 MV Van de Graaff accelerator with a new 5 MV linear accelerator (manufactured by High Voltage Engineering, Holland) later in 2005. During this scheduled upgrade we will have available a "stand-alone" microbeam based on a radioactive polonium isotopic source.
• Three fully-equipped, dedicated biology labs for use with our irradiation facilities.
• A "track segment" charged particle beamline.
• A monoenergetic fast neutron irradiation facility.

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References

1. Zhou H, Randers-Pehrson G, Waldren CA, Vannais D, Hall EJ, Hei TK. Induction of a bystander mutagenic effect of alpha particles in mammalian cells. Proc Natl Acad Sci USA 2000;97:2099-2104.
2. Randers-Pehrson G, Geard CR, Johnson G, Elliston CD, Brenner DJ. The Columbia University single-ion microbeam. Radiat. Res. 2001;156:210-214.
3. Zhou H, Suzuki M, Randers-Pehrson G, Vannais D, Chen G, Trosko JE, Waldren CA, Hei TK. Radiation risk to low fluences of alpha particles may be greater than we thought. Proc. Natl. Acad. Sci. U. S. A. 2001;98:14410-14415.
4. Mitchell SA, Randers-Pehrson G, Brenner DJ, Hall EJ. The bystander response in C3H 10T1/2 cells: the influence of cell-to-cell contact. Radiat. Res. 2004;161:397-401.
5. Ponnaiya B, Jenkins-Baker G, Brenner DJ, Hall EJ, Randers-Pehrson G, Geard CR. Biological responses in known bystander cells relative to known microbeam-irradiated cells. Radiat. Res. 2004;162:426-432.