LhARA radiobiology; meeting: 23Jul26; 14:00 GMT

ZOOM: ​https://imperial-ac-uk.zoom.us/j/98220889714?pwd=SM90vOF7BKSXoU3mD9q7OwBQo4IVB3.1

Meeting Notes

Attended: KL, CD, JMcG, AG, JB, PP, AFr, AT, BS, CW, DA, GS, JuP, MD, MH, NK, RH, RA, RW

1. Long-term LhARA Biology Plan
   • KL: Presentation Slides
     • Radiobiology is a key component throughout the LhARA program
       • Aim for the program to be definitive
       • Must be multi-disciplinary. Have to do the radiobiology but in new ways
       • Multi-national: Need greater expertise
       • Multisource: laser-driven, electrons, X-rays, and gamma-rays for reference sources
       • Multi-messenger: Diverse cell lines, diverse markers (need to integrate automation)
       • Systematic: Same conditions at a variety of sources across borders
       • AI-enabled: Consistent sample handling and irradiation
         • Interpretation: AI as well to develop more on TOPAS and G4DNA
   • JMcG: Presentation Slides
     • Long-term vision of a facility that can support: FLASH, SFRT, Advanced Imaging and Beam Monitoring
     • PoPLaR Current Vision:
       • Improve setup and workflow protocols and instrumentation needed
       • Becomes a comparison against X-ray and cyclotron proton beams
       • Measuring: Clonogenics, Comet assays, Fixed IF (immunofluorescence) imaging
     • Live Cell Imaging:
       • Understand underlying mechanisms in real-time
       • Builds on Tony's SFRT work and FLASH comparisons
       • Biggest limitation on previous fixed IF SFRT work was only able to compare different cell samples at each time point.
         • Live cell imaging would help fix this.
   • General Discussion
     • Strong agreement that comparison between laser-driven and cyclotron is key.
     • Next vary the beam, looking at FLASH and SFRT
       • Agreement that this needs to focus on particular biological hypotheses
       • Need to understand mechanisms being discussed behind both and what the current hypotheses are
         • Review literature
           • Literature review: Mechanisms, challenges and opportunities for FLASH radiotherapy in cancer Marie-Catherine Vozenin  1   2 , Pierre Montay-Gruel  3   4 , Pelagia Tsoutsou  5   6 , Charles L Limoli  7 DOI: 10.1038/s41568-025-00878-9
         • Invite experts in: Jason et al, Yolanda et al, Dresden group, Maria Catherine at PSI
           • Also, input from Jason, Emma, Marie and Katya (Munich) about what they expect at each stage as the instrumentation and beamline gets better.
         • Identify which hypotheses LhARA is uniquely capable of testing
         • Josie to coordinate
     • Strong agreement that it is better to start now so when the beamline is ready the technique is ready to go
     • Warning that if we do not see differences at the cell level does not mean there is no difference at the tissue or for whole organisms
     • Strong agreement that dosimetry must be included from the outset

• General Discussion

2. Overview of Current SCAPA Plan
   • Solutions to the three main problems:
     • Move the scatterer further up the beamline (closer to the laser-target).
     • Use a real-time diagnostic
     • Investigate how long the cells survive and the cause of death
   • Additions:
     • Collect more biology results?
   • When?:
     • Robbie mentioned February
     • Need to be ready to latch onto any downtime of other experiments
   • More information: ​https://docs.google.com/document/d/1OTARVtxhLRu02S6CLdRDB2QlGvCqDfZ3aWBifjIFs_Q/edit?tab=t.0
   • Steps required: Below and at ​https://trello.com/invite/b/67587c515b0c69656ee78b48/ATTIe86f94b24e3e5884e4cb87e5ed3b89ab64321B83/poplar

3. Instrumentation Discussion
   • Options:
     • Sparse scintillating fibre arrays in the vacuum chamber
     • Scintillating fibre around the cell dish
     • Lanex around the cell dish
     • Integrated Current Transformers (ICTs)
     • Laser Diagnostics (Backscatter etc)
     • Replace the scatterer with a scintillating sheet
     • (RCF around the cell dish (if desperate))
   • Testing method:
     • Calibrate with RCF?
     • No calibration. Use lots of cell dishes and match the distribution of variation in diagnostic output to the "known" distribution of the shot-to-shot variation
   • LET Detector

4. BioPrep Discussion
   • Spatial Variation: Is a CV of 8% acceptable?
   • Cell Control Survival:
     • Need to test how long cells can remain vertical
     • Can reduce the time taken to conduct the irradiations (and therefore the time the cells are vertical for)
     • Monitor the temperature of the thermostat
   • Better instrumentation:
     • Inverted microscope
     • Multi-chamber haemocytometer
   • More results (as well as clonogenics):
     • Comet analyses
     • X-ray comparison on-site

5. Alternate Beamlines
   • ELI Rejected
     • Waiting for feedback

6. Discussion on Ion-Acoustic Plan
   • Current updates

7. DoNM
   • 06/08/26

8. AoB

Summary of actions required

In-Beam Diagnostics

• Unassigned: Acquire a glass sheet
• Unassigned: Get a new RCF batch and calibrate
• TP: Testing delaminating EBT3
• PH: Obtain transparent fibre or an alternative method for light transport
• PH: Obtain a lens for hollow fibre tests
• CD: Simulate energy deposited in transport fibres
• KL, CD, JMcG, PH: Design a system to make full scifi prototypes
• KL, CD, JMcG, PH: Make a full scifi prototype
• KL, CD, JMcG, PH: Discuss visit to Birmingham to test SciFi
• RW, CD: Study the correlation between laser diagnostics and mean dose
• Unassigned: Investigate how a phosphor sheet could be incorporated into the design of the cell dish
• CW: Investigate the feasibility of ICTs for our beamline
• MH: Investigate LET detector

Bio Next Steps

• EM, CD, JMcG: Write up technical summary of Phase 2
• EM: Write up a biology plan for a 2 PMQ setup
• Unassigned: Obtain an inverted microscope
• Unassigned: Obtain multi-chamber haemocytometers (Might be able to use Birmingham's)
• Unassigned: Obtain a thermostat for the incubator
• MB, JP, MB: Meet up to plan cell survival dry run and a bio plan for a 2 Quad setup
• EM: Run controls to examine how long the cells can survive vertically

Beamline Modelling

• CD: Examine energy spectra variation
• RW, CD: Source characterisation

Alternate Beamlines

• JMcG: Simulate BELLA
• JMcG: Simulate ELI

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