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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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project participants
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

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what is nanodosimetry
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

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slide4

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

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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

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project goals
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

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project schedule
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

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slide8

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

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current status of the ion counting nd
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

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sensitive volume mapping
Sensitive Volume Mapping

The sensitive volume of the ND is defined by the relative ion collection efficiency map

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nd ion cluster spectra

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

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nd ion cluster spectra1
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

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radiobiological model
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

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nd data acquisition non position sensitive
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

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nd data acquisition particle position sensitive
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

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the goal 3 d position and energy sensitive particle tracking system
The Goal: 3-D Position- and Energy-Sensitive Particle Tracking System

interface board

primary particle

Y

X

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