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Development of Nanodosimetry for Biomedical Applications

Development of Nanodosimetry for Biomedical Applications. Project Goals and Current Status. Project Participants. Loma Linda University (LLU) (Rad. Medicine). Reinhard Schulte Vladimir Bashkirov George Coutrakon Pete Koss. Weizmann Institute of Science (WIS) (Rad. Detection Physics Lab.).

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Development of Nanodosimetry for Biomedical Applications

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  1. Development of Nanodosimetry for Biomedical Applications Project Goals and Current Status RWS

  2. Project Participants Loma Linda University (LLU) (Rad. Medicine) Reinhard Schulte Vladimir Bashkirov George Coutrakon Pete Koss Weizmann Institute of Science (WIS) (Rad. Detection Physics Lab.) Amos Breskin Guy Garty Rachel Chechik Itzhak Orion Sergei Shchemelinin University of California at San Diego (UCSD) (Radiobiology) John F. Ward Jamie Milligan Joe Aguilera University of California Santa Cruz (UCSD) (Santa Cruz Institute of Particle Physics) Abe Seiden Patrick Spradlin Hartmut Sadrozinski Brian Keeney Wilko Kroeger RWS

  3. What is Nanodosimetry? A new experimental technique that measures energy deposition by ionizing radiation in wall-less low-pressure gas volumes equivalent to tissue-equivalent volumes of nanometer size RWS

  4. Radiation Damage to the DNA Ionization event (formation of water radicals) Light damage- reparable Primary particle track delta rays e- Water radicals attack the DNA OH• Clustered damage- irreparable The mean diffusion distance of OH radicals before they react is only 2-3 nm RWS

  5. What do we want to know? To better understand DNA damage we want to know how many ionization events occurred and where did they occur. Problem: How can we measure the formation of ions with nanometer precision? Using conventional techniques - impossible We can only measure ion formation with millimer resolution If we had millimeter DNA - no problem. Solution: We measure ionization patterns in low-pressure gas RWS

  6. Project Goals • Establishment of a nanodosimetric gas model to simulate ionizations in DNA and associated water • Plasmid-based DNA model to measure DNA damage • Develop models to correlate nanodosimetric spectra with DNA damage RWS

  7. Project Schedule YEAR 4 3D tracking system YEAR 3 ND characterization YEAR 2 ND fabrication (2 versions) YEAR 1 Ion counting nanodosimetry (proof of principle) Plasmid assays 2001 2000 1999 1998 SV mapping ND improvements 2 D particle tracking ND spectra MC simulation RWS

  8. x z y ion counter vacuum E2 (strong) d electron ion E1 (pulsed) primary charged particle low pressure gas primary particle detector Single-Charge Counting Dosimetry low pressure gas E3 (weak) electron Gas based electron multiplier RWS

  9. Current Status of the Ion Counting ND • Principle proven (1998) • Two prototype of NDs have been built: • LLUMC ND adapted to the proton synchrotron beam line • WIS ND adapted to the Pelletron beam line • 2-D particle selection implemented • Data Acquisition System • first version successfully implemented • new version under development RWS

  10. Prototype Nanodosimeter RWS

  11. Sensitive Volume Mapping The sensitive volume of the ND is defined by the relative ion collection efficiency map RWS

  12. 0 -5 millivolts -20 0 1 2 3 microseconds ND Ion Cluster Spectra Event with 6 ions A primary particle event is followed by an ion trail registered by the ion counter (electron multiplier) For low-LET irradiation, most events are empty RWS

  13. ND Ion Cluster Spectra Ion cluster spectra depend on particle type and energy as well as position of the primary particle track The average cluster size increases with increasing LET RWS

  14. Radiobiological Model • Plasmid (pHAZE) • Irradiation of thin film of plasmid DNA in aqueous solution • Three structural forms: • superhelical (no damage) • open circle (single strand break) • linear (double strand break) • Separation by agarose gel electrophoresis • Fluorescent staining and dedicated imaging system RWS

  15. Correlation between Nanodosimetry and Radiobiology RWS

  16. ND Data Acquisition(non-position sensitive) In the prototype ND all primary particles can contribute to the ion cluster size spectra The position of the primary particles is undefined RWS

  17. ND Data Acquisition(particle-position sensitive) In this (newer) version the primary beam is “imaged” by a MWPC Only particles that pass a narrow collimator in front of the rear scintillator/PMT are selected for analysis RWS

  18. The Goal: 3-D Position- and Energy-Sensitive Particle Tracking System interface board primary particle Y X RWS

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