Single α-particle irradiation permits real-time visualization of RNF8 accumulation at DNA damaged sites

At a Glance

Metadata	Details
Publication Date	2017-01-31
Journal	Scientific Reports
Authors	Giovanna Muggiolu, M. Pomorski, Gérard Claverie, Guillaume Berthet, Christine Mer-Calfati
Institutions	Centre National de la Recherche Scientifique, Laboratoire de Physique des deux infinis Bordeaux
Citations	10
Analysis	Full AI Review Included

6CCVD Technical Documentation & Analysis: Ultra-Thin Boron-Doped Diamond for Single-Particle Radiobiology

Executive Summary

The reported research successfully demonstrates the use of ultra-thin Boron-doped Nano-Crystalline Diamond (BNCD) membranes as high-efficiency single $\alpha$-particle detectors, enabling real-time radiobiological studies. This methodology confirms the crucial role of high-purity, structurally controlled Chemical Vapor Deposition (CVD) diamond components in advancing particle physics and cellular dosimetry.

Core Material Achievement: Development of a 400 nm thick BNCD membrane optimized for minimal beam perturbation and maximal secondary electron (SE) detection yield.
Performance: Achieved 100% detection efficiency for 3 MeV $\alpha$-particles, separating the detector signal unambiguously from background noise.
Beam Control: The membrane functions as an active vacuum window, maintaining a tightly focused beam spot size (Full Width at Half Maximum (FWHM) $\sim 2$ $\mu\text{m}$) crucial for precise single-cell irradiation.
Application Success: Enabled the first-ever visualization and time-lapse tracking of RNF8 accumulation (a key DNA repair protein) at sites of DNA damage induced by single $\alpha$-particle traversals.
Methodology: BNCD films were synthesized using Microwave Assisted Chemical Vapor Deposition (MWCVD) onto $\text{Si}{3}\text{N}{4}$ windows, leveraging highly controlled gas and doping recipes.
Value Proposition: This application validates 6CCVD’s expertise in delivering custom, ultra-thin Boron-Doped Diamond (BDD) materials for high-precision dosimetry, microbeam steering, and sensitive particle detection.

Technical Specifications

The following hard data points were extracted, primarily related to the fabrication and performance of the BNCD detector membrane used in the single $\alpha$-particle microbeam system.

Parameter	Value	Unit	Context
Detector Material	BNCD (Boron-doped NCD)	N/A	Secondary electron emitter / Vacuum Window
BNCD Thickness (Estimated)	400	nm	Synthesized thickness, minimized for energy loss
SCD/PCD Thickness Capability (6CCVD)	$0.1 - 500$	$\mu\text{m}$	Full range available for comparable applications
Incident Particle Energy ($\text{He}^{+}$)	3	MeV	Single $\alpha$-particles used for cell irradiation
Mean Energy Loss through BNCD	$\sim 200$	keV	Minimal energy drop verified by silicon detector
SE Detection Efficiency	100	%	Achieved by Channeltron detection
Beam Spot Size (FWHM)	$\sim 2$	$\mu\text{m}$	Confirmed via CR39 track detectors
Beam Energy Loss Homogeneity	30	keV	Maximum variation across a $400 \times 400$ $\mu\text{m}$ scan area
MWCVD Microwave Power	1.2	kW	BNCD growth parameter
MWCVD Growth Pressure	40	mbar	BNCD growth parameter

Key Methodologies

The study relies on highly precise MWCVD growth of Boron-doped diamond (BDD) films and sophisticated microbeam integration.

Substrate Seeding: Commercially available $\text{Si}{3}\text{N}{4}$ vacuum windows (150 nm thick, $1 \text{ mm}^2$ open area) were electrostatically grafted with 5 nm diamond nanoparticles (ADAMAS nano).
MWCVD Growth: BNCD film was deposited using Microwave Assisted Chemical Vapor Deposition (MWCVD).
Doping and Gas Recipe: Trimethylborane (TMB) gas was used as the source for boron atoms, along with 33 sccm Methane ($\text{CH}{4}$) and 100 sccm Hydrogen ($\text{H}{2}$).
Growth Duration: The growth process lasted 6 hours, resulting in the desired $\sim 400$ nm BNCD film thickness, employed as-grown.
Detector Testing (Vacuum): The BNCD membrane was positioned in the beam path under vacuum. Secondary electrons (SE) were collected by a Channeltron Electron Multiplier (CEM).
Energy Transmission Measurement: $\alpha$-particles transmitted through the BNCD were simultaneously detected by a $100$ $\mu\text{m}$ thick silicon detector to measure transmitted energy and confirm 100% detection efficiency.
Air Extraction: The BNCD served as the vacuum window, allowing the 3 MeV $\alpha$-particle beam to be extracted into the air for subsequent irradiation of biological samples 60 $\mu\text{m}$ away.
Cellular Assay: HTB96 U2OS cells stably expressing the GFP-tagged RNF8 protein were irradiated with single $\alpha$-particles in precise patterns, followed by online fluorescence time-lapse imaging to track RNF8 foci formation over 30 minutes.

6CCVD Solutions & Capabilities

The development of high-performance BNCD membranes is a demanding application requiring expert control over crystal quality, thickness uniformity, and doping profile. 6CCVD is uniquely positioned to supply the materials required to replicate, scale, and extend this critical radiobiological research.

Applicable Materials

To replicate and advance the microbeam detector described, 6CCVD recommends:

Boron-Doped Nano-Crystalline Diamond (BDD-NCD): Required for high secondary electron yield detection applications. 6CCVD provides BDD with tailored doping concentrations for optimal conductivity and signal generation.
Optical Grade SCD or PCD Wafers: Required for large-area substrates (e.g., for mounting the final membrane structure or for use as windows in high-purity optical systems). 6CCVD offers PCD plates up to 125 mm diameter.

Customization Potential and Manufacturing Excellence

Paper Requirement	6CCVD Standard Capability	Sales Value Proposition
Ultra-Thin Film Synthesis (400 nm)	SCD and PCD available down to $0.1$ $\mu\text{m}$ (100 nm).	6CCVD can deliver thinner, highly uniform films, potentially reducing energy loss further (key for lower energy particles) or scaling membrane size.
Custom Wafer Dimensions	Plates/wafers available up to 125 mm.	Allows researchers to transition from small lab-scale $\text{Si}{3}\text{N}{4}$ frames to larger, rugged MPCVD diamond wafers for industrial or high-throughput systems.
Surface Finish (Ra < 1nm)	Polishing services achieving Ra < 1 nm (SCD) and Ra < 5 nm (PCD).	Critical for minimizing angular scattering of the $\alpha$-particles and ensuring homogenous secondary electron emission across the detector surface.
Detector Integration	Internal Metalization Services (Au, Pt, Pd, Ti, W, Cu).	6CCVD can integrate custom electrode patterns directly onto the BNCD surface, streamlining the fabrication of functional SE detectors and minimizing interface resistance.
Custom Substrate Integration	Substrates available up to 10 mm thick.	While the paper used $\text{Si}{3}\text{N}{4}$ windows, 6CCVD can assist in engineering robust, larger-area support structures compatible with microbeam end-stations.

Engineering Support

6CCVD’s in-house PhD team provides specialized engineering consultation to ensure optimal material selection and integration for advanced radiobiology and particle detection projects. We offer support in:

Doping Optimization: Tailoring Boron concentration for specific secondary electron yield or charge collection requirements.
Structural Control: Engineering NCD films for optimal mechanical stability and conductivity in ultra-thin, free-standing membrane applications.
Microbeam System Design: Assisting with material choices that guarantee negligible beam scattering and high radiation hardness, essential for long-term use in focused $\alpha$-particle irradiation experiments.

For custom specifications or material consultation, visit 6ccvd.com or contact our engineering team directly.

Tech Support

Original Source

DOI: https://doi.org/10.1038/srep41764