Accelerator proton beam intensity regulation and control device and method and storage medium

Abstract

The embodiment of the invention provides an accelerator proton beam intensity regulation and control device and method and a storage medium, and belongs to the technical field of accelerator irradiation experiment equipment. The device comprises a diaphragm body which is used for carrying out current limiting and diffusion regulation and control on an accelerator proton beam; the cell culture plate is used for bearing a cell sample irradiated by the proton beam; the high-precision movement adjusting module is respectively connected with the diaphragm body and the cell culture plate, and is used for adjusting the relative spatial position of the diaphragm body and the cell culture plate, so that the diaphragm body is aligned with the proton beam axis of the accelerator; the clamp fixing mechanism is used for fixing the diaphragm body and the cell culture plate; and the dose monitoring device is used for monitoring the proton beam dose regulated and controlled by the diaphragm body. According to the scheme, controllable intensity adjustment, accurate alignment and uniform dose irradiation of the accelerator proton beam on the 96-hole cell culture plate are realized, and the stability and repeatability of a cell irradiation experiment are guaranteed.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of accelerator irradiation experiment equipment, in particular to an accelerator proton beam intensity regulating device, an accelerator proton beam intensity regulating method and a storage medium. BACKGROUND

[0002] As an accelerator device capable of generating high-energy and high-purity proton beam, it occupies a core position in cell radiation biology research. Through precise irradiation of cell samples by proton beam, the quantitative law of radiation dose-biological effect can be revealed, and key experimental data for dose optimization of clinical tumor proton radiotherapy and development of radiation damage protection strategies can be provided. In batch cell experiments, 96-well cell culture plates have become the mainstream experimental carrier due to their high standardization, and their standardized design can directly adapt to subsequent cell biological experiments such as CCK8, without the need for cell transplantation operations, which can avoid unnecessary cell death caused by mechanical damage and environmental changes during transplantation, reduce experimental errors, and is crucial for improving the reliability of experimental data.

[0003] However, the existing accelerator irradiation equipment has the following technical defects that are difficult to solve when adapting to 96-well plates: The initial particle flux of the accelerator is usually in the order of ≥109 particle / (cm 2 The appropriate range for cell irradiation experiments is 10³-10 5 particle / (cm² s), which differs by several orders of magnitude. The existing beam current limiting technology is mostly based on metal sheet shielding or ordinary straight-hole diaphragms, which have the technical limitations of not establishing a scientific quantitative control model or only relying on empirical values for rough adjustment, resulting in actual control errors of up to ±20% or more. At the same time, the existing diaphragm structure is single, which cannot effectively control the beam diffusion while limiting the beam intensity, causing a conflict between the limiting effect and the beam spot uniformity. In cell irradiation applications, this defect can easily lead to uncontrolled particle flux: too high flux can cause acute apoptosis of cells, and too low flux can lead to long experimental periods and non-specific cell inactivation, seriously affecting the reliability of experimental results.

[0004] Currently, the diaphragm materials are mostly selected from Fe, Al, Cu and other metals. When high-energy protons and metal atoms undergo nuclear reactions, a large number of secondary particles are generated, including neutrons (generated by proton-nuclear elastic scattering and inelastic scattering) and gamma rays (generated by nuclear excitation de-excitation). These secondary particles will cause additional radiation dose to the cell sample, resulting in that the biological effects measured in the experiment are not caused by the proton beam flow alone, which seriously interferes with the accurate establishment of the dose-effect relationship. In the prior art, some schemes attempt to reduce pollution by adding a shielding layer, but this will increase the volume and weight of the device, and cannot inhibit the generation of secondary particles from the source, so the pollution control effect is limited.

[0005] In summary, the prior art cannot simultaneously meet the core requirements of precise regulation, uniform distribution, low pollution and high-precision positioning. Although the 96-well plate itself has the advantage of cell transplantation, the defects of the existing adaptive equipment prevent it from fully exerting this advantage, so a special diaphragm device with optimized structure, adapted material and precise control is needed to break through the technical bottleneck of 96-well plate cell irradiation experiment. SUMMARY

[0006] The purpose of the embodiments of the present application is to provide an accelerator proton beam flow intensity regulation device, method and storage medium to at least solve the problems of difficulty in accurately regulating the intensity of the proton beam flow, unclear irradiation dose characterization and insufficient experimental adaptability in the existing cell irradiation experiment.

[0007] To achieve the above-mentioned purpose, the first aspect of the present application provides an accelerator proton beam flow intensity regulation device, which comprises: a diaphragm body for regulating the flow and diffusion of the accelerator proton beam flow; a cell culture plate for carrying cell samples subjected to proton beam flow irradiation; a high-precision moving adjustment module connected with the diaphragm body and the cell culture plate respectively, for adjusting the relative spatial position of the diaphragm body and the cell culture plate, so that the diaphragm body is aligned with the axis of the accelerator proton beam flow; a clamp fixing mechanism for fixing the diaphragm body and the cell culture plate; and a dose monitoring device for monitoring the dose of the proton beam flow regulated by the diaphragm body.

[0008] Optionally, the diaphragm body is arranged on the exit path of the accelerator proton beam flow and is arranged upstream of the cell culture plate along the propagation direction of the accelerator proton beam flow; a space segment for the propagation of the proton beam flow is formed between the diaphragm body and the cell culture plate, so that the proton beam flow is incident to the cell culture plate after passing through the diaphragm body.

[0009] Optionally, the space section between the diaphragm body and the cell culture plate is continuously arranged along the propagation direction of the accelerator proton beam, and no structural component for shielding or guiding the proton beam is arranged in the space section, so that the proton beam reaches the cell culture plate along the original propagation direction after leaving the diaphragm body.

[0010] Optionally, the high-precision movement adjustment module comprises a diaphragm movement device and a culture plate movement device; the diaphragm movement device is connected with the diaphragm body and is used to drive the position adjustment of the diaphragm body relative to the axis of the accelerator proton beam; the culture plate movement device is connected with the cell culture plate and is used to drive the position adjustment of the cell culture plate relative to the axis of the accelerator proton beam; the diaphragm movement device and the culture plate movement device are independently arranged to respectively complete the spatial positioning of the diaphragm body and the cell culture plate.

[0011] Optionally, the diaphragm movement device and the culture plate movement device respectively comprise a lifting mechanism for adjusting the vertical height and a guided movement mechanism for adjusting the horizontal direction position; the guided movement mechanism comprises a front-to-back guided mechanism arranged in the front-to-back direction and a left-to-right guided mechanism arranged in the left-to-right direction, so as to realize the independent adjustment of the diaphragm body and the cell culture plate in the vertical direction, the front-to-back direction and the left-to-right direction, and support the collinear arrangement of the diaphragm body, the cell culture plate and the axis of the accelerator proton beam.

[0012] Optionally, the clamp fixing mechanism comprises a diaphragm clamp and a culture plate clamp; the diaphragm clamp is fixedly connected with the high-precision movement adjustment module and is used to detachably fix the diaphragm body, so as to limit the attitude change of the diaphragm body during the adjustment of the high-precision movement adjustment module; the culture plate clamp is fixedly connected with the high-precision movement adjustment module and is used to detachably fix the cell culture plate, so as to limit the relative displacement of the cell culture plate during irradiation.

[0013] Optionally, the dose monitoring device is arranged on the irradiation path of the cell culture plate and is coaxially arranged with the diaphragm body and the cell culture plate along the propagation direction of the accelerator proton beam, and is used to obtain the dose information of the proton beam regulated by the diaphragm body.

[0014] Optionally, the dose monitoring device is configured to: based on the monitored dose of the proton beam at the setting position of the dose monitoring device, take the monitored dose of the proton beam as a characterization basis reflecting the dose level of the proton beam at the cell culture plate after being incident on the cell culture plate and being regulated by the diaphragm body, according to the arrangement relationship that the cell culture plate is collinear with the propagation direction of the accelerator proton beam.

[0015] The second aspect of the present application provides an accelerator proton beam intensity regulation method, which is realized based on the accelerator proton beam intensity regulation device described above, and the method comprises the following steps: obtaining a proton beam output by an accelerator, and making the proton beam enter a diaphragm body along a preset beam path; performing current limiting and diffusion regulation on the entering proton beam by the diaphragm body to form a regulated proton beam; under the action of a high-precision moving adjustment module, adjusting the relative spatial position of the diaphragm body and a cell culture plate, so that the diaphragm body is aligned with the axis of the accelerator proton beam, and the regulated proton beam is incident on the cell culture plate; in the process of the proton beam being incident on the cell culture plate, a dose monitoring device is used to monitor the dose of the proton beam regulated by the diaphragm body, and corresponding dose monitoring data is obtained.

[0016] In another aspect, the present application provides a computer-readable storage medium, which stores instructions that, when executed on a computer, cause the computer to perform the accelerator proton beam intensity regulation method described above.

[0017] Through the above technical solution, the accelerator proton beam intensity regulation device provided by the present application scheme realizes the coordinated regulation of the current limiting, diffusion and incident position of the proton beam by arranging the diaphragm body on the proton beam emission path of the accelerator, and cooperating with the high-precision moving adjustment module and the clamp fixing mechanism, so that the proton beam can be incident on the cell culture plate with a controlled intensity and a stable spatial position. Through the adjustment of the relative spatial position of the diaphragm body and the cell culture plate by the high-precision moving adjustment module, the alignment relationship between the diaphragm body and the axis of the proton beam is ensured, thereby improving the positioning consistency during irradiation. At the same time, the dose monitoring device monitors the dose of the proton beam regulated by the diaphragm body in real time, so that the irradiation dose at the cell culture plate has a clear characterization basis. The above-mentioned structure cooperates to help reduce the proton beam intensity regulation error and improve the stability of dose control and spatial alignment in cell irradiation experiments, and provides a reliable device basis for batch cell irradiation experiments.

[0018] Other features and advantages of the present application will be described in detail in the following detailed description. BRIEF DESCRIPTION OF DRAWINGS

[0019] The accompanying drawings are included to provide a further understanding of the present application and constitute a part of the specification, and are used together with the following detailed description to explain the present application, but do not constitute a limitation on the present application. In the drawings: Figure 1 is a device structure diagram of an accelerator proton beam intensity regulation device provided by an embodiment of the present application; Figure 2is a light barrier outer plate, a horn-shaped through hole and a 96-well cell culture plate Monte Carlo model space arrangement schematic diagram provided by an embodiment of the present application; Figure 3 is a 96-well cell culture plate special fixture structure schematic diagram provided by an embodiment of the present application; Figure 4 is a high-precision mobile adjustment module structure schematic diagram provided by an embodiment of the present application; Figure 5 is a light barrier special fixture structure schematic diagram provided by an embodiment of the present application; Figure 6 is a unit pixel point proton deposition quantity distribution cloud diagram provided by an embodiment of the present application; Figure 7 is a particle distribution uniformity statistical diagram under different light barrier outlet to hole plate distance conditions provided by an embodiment of the present application; Figure 8 is a light barrier design and experiment process schematic diagram based on Monte Carlo simulation and dose rate conversion provided by an embodiment of the present application; Figure 9 is a step flow chart of an accelerator proton beam flow intensity regulation method provided by an embodiment of the present application.

[0020] Legend of reference signs 11-accelerator proton beam emission pipeline; 12-ultra-clean workbench; 13-light barrier device system; 14-dose monitoring device; 15-96-well cell culture plate device system; 16-light barrier moving device; 17-culture plate moving device; 18-computer equipment; 19-proton beam simulation source; 131-light barrier outer plate; 132-horn-shaped through hole emission end; 133-horn-shaped through hole incidence end; 134-light barrier fixture base; 135-light barrier fixture stainless steel fastening screw; 136-light barrier fixture base fixed end; 141-left end semiconductor detector; 142-right end semiconductor detector; 151-96-well cell culture plate shell; 152-96-well cell culture plate cell culture hole; 153-culture plate fixture base; 154-culture plate fixture stainless steel fastening screw; 155-culture plate fixture base fixed end; 161-light barrier lifting mechanism; 162-light barrier front and rear guide mechanism; 163-light barrier left and right guide mechanism; 171-culture plate lifting mechanism; 172-culture plate front and rear guide mechanism; 173-culture plate left and right guide mechanism. DETAILED DESCRIPTION

[0021] The specific embodiments of the present application will be described in detail below with reference to the accompanying drawings. It should be understood that the specific embodiments described herein are merely intended to illustrate and explain the present application, and are not intended to limit the present application.

[0022] Figure 1 is a device structure diagram of an accelerator proton beam intensity regulating device provided by an embodiment of the present application. As shown in Figure 1 , the present application provides an accelerator proton beam intensity regulating device, which comprises: an aperture body for regulating the flow and diffusion of the accelerator proton beam; a cell culture plate for carrying cell samples subjected to proton beam irradiation; a high-precision moving adjustment module connected with the aperture body and the cell culture plate respectively, for adjusting the relative spatial position of the aperture body and the cell culture plate, so that the aperture body is aligned with the axis of the accelerator proton beam; a clamp fixing mechanism for fixing the aperture body and the cell culture plate; and a dose monitoring device for monitoring the dose of the proton beam regulated by the aperture body. For the convenience of understanding the correspondence between the technical features claimed in the present application and the drawings, part of the nouns are explained as follows.

[0023] The aperture body corresponds to the aperture outer plate 131 and the horn-shaped through-hole structure provided on the aperture outer plate in the Figure 2 , wherein the horn-shaped through-hole comprises an incident end 133 and an exit end 132, and the aperture outer plate 131 and the horn-shaped through-hole together constitute the overall structure of the aperture body for regulating the flow and diffusion of the accelerator proton beam.

[0024] The cell culture plate corresponds to the 96-well cell culture plate shell 151 and the plurality of cell culture holes 152 provided thereon in the , wherein the cell culture holes are used to carry cell samples subjected to proton beam irradiation.

[0025] Figure 3 The high-precision moving adjustment module corresponds to the moving mechanism for adjusting the spatial position of the aperture body and the 96-well cell culture plate in the , which comprises a mechanical cross-lifting platform 161 for the aperture body and the cell culture plate respectively, and ball screw guide rail sliding tables 162 and 163 for realizing the adjustment in the front-back direction and the left-right direction, and the above-mentioned structures together realize the precise positioning and adjustment of the aperture body and the cell culture plate in the vertical direction, the front-back direction and the left-right direction.

[0026] Figure 5 The clamp fixing mechanism corresponds to the clamp structure for detachably fixing the aperture body and the 96-well cell culture plate in the , which comprises an aperture clamp base 134, aperture clamp stainless steel fastening screws 135 and their fixed ends 136, and a culture plate clamp base, fastening screws and fixed end structure provided on the 96-well cell culture plate, which are used to limit the attitude change and relative displacement of the related components during the adjustment and irradiation process.

[0027] The dose monitoring device corresponds to the attached Figure 3 The semiconductor detector structure arranged near the cell culture plate and along the propagation direction of the accelerator proton beam includes a left semiconductor detector 141 and a right semiconductor detector 142, which are used for real-time monitoring of the dose of the proton beam regulated by the diaphragm body.

[0028] As Figure 1 , including a super-clean bench 12, a diaphragm device system, a 96-well cell culture plate device system 17, and a dose real-time detection device 14 and a high-precision mobile adjustment module; the high-precision mobile adjustment module includes a diaphragm moving device 16 and a 96-well cell culture plate moving device 17 for controlling the movement adjustment of the two; the dose real-time detection device 14 is a semiconductor detector, which is used to detect the fluence and energy data information of the proton beam generated by the accelerator proton beam source emission pipeline 11 after passing through the diaphragm device system 13; the dose real-time detection device 14 is connected to the computer equipment 18 by a signal line for real-time data transmission; the computer equipment 18 adjusts the position of the diaphragm or the hole plate in real time according to the built-in calculation module and the control program, or controls the accelerator control system to adjust the initial beam particle fluence Φ0.

[0029] In the embodiment of the present application, the diaphragm body is arranged on the accelerator proton beam emission path to regulate the flow and diffusion of the proton beam, so that the intensity of the proton beam entering the cell culture plate is in a controllable state. At the same time, the cell culture plate as a carrier of the cell sample forms a controlled irradiation relationship with the diaphragm body in space. The high-precision mobile adjustment module is connected with the diaphragm body and the cell culture plate respectively, and by adjusting the relative spatial position of the two, the diaphragm body is aligned with the axis of the accelerator proton beam, so as to ensure the spatial consistency of the proton beam during the process of entering the cell culture plate. The fixture fixing mechanism fixes the diaphragm body and the cell culture plate, which is used to limit the attitude change during the adjustment and irradiation process, and improves the stability of the whole device. During the irradiation process, the dose monitoring device 14 monitors the dose of the proton beam regulated by the diaphragm body, so that the irradiation dose at the cell culture plate has a clear monitoring basis. Through the cooperative arrangement of the above structure, the embodiment of the present application can realize the stable control of the intensity and incident position of the proton beam, and is suitable for the application scene with high requirements for beam regulation accuracy and repeatability in cell irradiation experiment.

[0030] Preferably, the diaphragm body is arranged on the emission path of the accelerator proton beam and arranged upstream of the cell culture plate along the propagation direction of the accelerator proton beam; the diaphragm body and the cell culture plate form a space segment for the propagation of the proton beam, so that the proton beam enters the cell culture plate after passing through the diaphragm body.

[0031] In the embodiment of the present application, the overall thickness of the diaphragm body is 4 mm, so that the proton beam has a clear and stable flow path when passing through the diaphragm body, which is beneficial to avoid unnecessary scattering effects caused by excessive thickness while ensuring mechanical strength. The through hole is arranged at the center position of the diaphragm body, so that the incident accelerator proton beam can pass through the diaphragm body along the predetermined axial direction, thereby reducing the influence of beam deviation on the subsequent irradiation process.

[0032] The through hole adopts a horn-shaped structure design, wherein the aperture of the incident end of the through hole is 0.5 mm, which is used to preliminarily limit the proton beam entering the diaphragm body, so that the number of proton beam particles entering the through hole is effectively constrained; the aperture of the exit end of the through hole is 6 mm, so that the proton beam after passing through the through hole obtains gradually expanding space conditions on the exit side, thereby avoiding sudden scattering of the beam at the exit end. Through the gradual change between the incident end aperture and the exit end aperture, the proton beam can realize continuous transition inside the through hole.

[0033] The inner wall of the through hole is arranged as a smooth conical structure, so that the probability of inelastic collision between the proton beam and the inner wall during the passing through process is reduced, which helps to reduce the irregular scattering phenomenon of protons inside the through hole. At the same time, the smooth conical inner wall structure is beneficial to the stable propagation of the beam along the axial direction of the through hole, so that the proton beam regulated by the diaphragm body has a relatively stable beam shape when entering the subsequent space section.

[0034] Through the cooperation of the above structural parameters, the diaphragm body not only limits the accelerator proton beam, but also considers the continuity of beam expansion, thereby providing stable and repeatable incident conditions for the subsequent proton beam incident to the cell culture plate.

[0035] In a specific embodiment, as Figure 2 , the spatial position relationship of the diaphragm outer plate 131, the horn-shaped through hole and the 96-well cell culture plate on the same beam propagation axis is sequentially constructed in the Monte Carlo model. The proton beam is incident from the right along the accelerator beam direction, first enters the diaphragm outer plate 131 and passes through the horn-shaped through hole arranged at the center thereof. Inside the through hole, the proton beam is subjected to geometric constraints and guiding effects of aperture change, and the particle trajectory gradually expands in space while keeping the overall propagation direction consistent. After the proton beam is emitted from the horn-shaped through hole, it enters the air propagation area, where the particles are further scattered to form a beam distribution with a certain lateral expansion range. The 96-well cell culture plate arranged downstream along the beam axis, and the hole array structure is arranged corresponding to the center area of the diaphragm through hole, so that the proton beam regulated by the diaphragm and scattered in the air can cover the cell sample area at the bottom of the hole plate. Through the construction of the Monte Carlo model, the influence of the diaphragm structure and the hole plate arrangement on the beam propagation path and spatial distribution can be intuitively displayed, which provides a basis for beam regulation effect analysis and irradiation uniformity evaluation.

[0036] In a specific embodiment, the diaphragm body material should be PMMA to reduce the generation of secondary particles and contamination of the experimental object. The diaphragm aperture satisfies the proton fluence reduction relationship general formula: (1) Where A in is the incident hole area, A out is the exit hole area, T(θ, E) is the transmittance of protons at incident angle θ and energy E, Φ in is the proton beam fluence before entering the diaphragm body, Φ out is the proton beam fluence obtained at the exit side of the diaphragm after current limiting and diffusion regulation by the diaphragm body; the distance from the diaphragm exit to the hole plate upper surface is 9 cm, and the distance from the titanium film to the hole bottom is 15 cm, so as to realize proton beam flow distribution homogenization, and the average variance of particle number distribution is less than 1.1.

[0037] Preferably, the space segment between the diaphragm body and the cell culture plate is continuously arranged along the propagation direction of the accelerator proton beam; no structural components for shielding or guiding the proton beam are arranged in the space segment, so that the proton beam reaches the cell culture plate along the original propagation direction after leaving the diaphragm body.

[0038] In the embodiment of the present application, the diaphragm body and the 96-hole cell culture plate are continuously arranged in the space region along the propagation direction of the accelerator proton beam. The space region corresponds to the air propagation segment of the proton beam after leaving the diaphragm body, and is used to provide a free propagation path for the proton beam without additional structure interference. As described in the foregoing embodiment, a predetermined distance is maintained between the diaphragm exit and the upper surface of the cell culture plate, and within the distance range, the proton beam scatters in the air and gradually expands, so as to be incident to the bottom of the cell culture plate to form a relatively uniform irradiation distribution.

[0039] In a specific embodiment, as Figure 3 , the 96-hole plate special fixture includes a base and a stainless steel fastening screw; the length of the periphery of the base is 100 mm, the width is 19 mm, and the height is 66 mm; wherein the length of the rear end of the base is 85.6 mm, and the width is 9 mm; the length of the front end of the base is 82.3 mm, and the width is 10 mm, which is perpendicularly and fixedly connected with the base; the left and right sides are fixed by M3x2 stainless steel fastening screws, and the clamping travel is 0-10 mm; the inside of the two sides of the fixture is made of silicone material with a Shore hardness of 50, a thickness of 2 mm, and a width of 9 mm, and the surface in contact with the hole plate is provided with anti-slip texture, and the horizontal error of the hole plate after installation is ≤0.03 mm.

[0040] No structural components are arranged in the space section for shielding or guiding the proton beam, so that the proton beam, after passing through the diaphragm body, only relies on its exit direction and natural scattering characteristics in the air to proceed along the original propagation direction, avoiding the introduction of additional scattering sources or deflection factors by secondary optics or mechanical structures. In this way, the proton beam maintains stable and repeatable propagation conditions before it is incident on the cell culture plate, which is beneficial to ensure the consistency of irradiation between different experimental batches.

[0041] In combination with the Monte Carlo simulation results and the actual irradiation experiments, it can be known that, under the above spatial arrangement conditions, the proton beam can achieve relatively uniform particle distribution within the scale of the well plate, and can meet the requirements of dose uniformity and stability for cell irradiation experiments without relying on additional guiding structures.

[0042] Preferably, the high-precision mobile adjustment module includes a diaphragm moving device 16 and a culture plate moving device 17; the diaphragm moving device 16 is connected with the diaphragm body and is used to drive the position adjustment of the diaphragm body relative to the axis of the accelerator proton beam; the culture plate moving device 17 is connected with the cell culture plate and is used to drive the position adjustment of the cell culture plate relative to the axis of the accelerator proton beam; the diaphragm moving device 16 and the culture plate moving device 17 are independently arranged to respectively complete the spatial positioning of the diaphragm body and the cell culture plate.

[0043] In the embodiment of the present application, the high-precision mobile adjustment module includes a diaphragm moving device 16 and a culture plate moving device 17, which are independently arranged to respectively complete the spatial positioning of the diaphragm body and the 96-well cell culture plate relative to the axis of the accelerator proton beam. The diaphragm moving device 16 and the culture plate moving device 17 are not abstract functional units, but are realized by specific mechanical structure combinations defined in the original specification.

[0044] Specifically, the high-precision mobile adjustment module as a whole is composed of two mechanical cross-lifting tables, four ball screw guide rail sliding tables, and two sets of customized clamps. One mechanical cross-lifting table, two ball screw guide rail sliding tables, and one set of customized clamps together constitute the diaphragm moving device 16; the other mechanical cross-lifting table, the other two ball screw guide rail sliding tables, and the other set of customized clamps together constitute the culture plate moving device 17. Through the above structure division, the diaphragm moving device 16 and the culture plate moving device 17 are independent of each other in structure and do not interfere with each other during adjustment.

[0045] In a specific embodiment, the ball screw linear guide rail sliding table has a length of 250mm±0.5mm and a width of ≤30mm; the ball screw lead is 4mm, and the repeat positioning accuracy is ≤±0.003mm; the maximum stroke of the front-to-back guide rail sliding table is 250mm, the minimum fitting distance is 30mm, and the maximum relative movement distance is 220mm; and the maximum stroke of the left-to-right guide rail sliding table is 150mm. The two sets of sliding tables are respectively installed on the corresponding cross-lifting tables.

[0046] In the culture plate moving device 17, a structure corresponding to the diaphragm moving device 16 is also provided with a set of mechanical cross-lifting tables and two ball screw linear guide rail sliding tables, which are used to respectively realize independent adjustment of the 96-well cell culture plate in the vertical direction, the front-to-back direction and the left-to-right direction. Through the structure, the position adjustment of the 96-well cell culture plate is independent of the position state of the diaphragm body, thereby realizing independent spatial positioning of the culture plate relative to the accelerator proton beam axis.

[0047] The two sets of customized clamp supports are respectively a diaphragm special clamp and a 96-well cell culture plate special clamp, which are prepared by an aluminum alloy anodic oxidation process and are used to detachably fix the diaphragm body and the 96-well cell culture plate on the corresponding diaphragm moving device 16 and culture plate moving device 17. Through the special clamp, it is ensured that the diaphragm body and the 96-well cell culture plate can maintain a stable posture and do not displace relative to each other during position adjustment and irradiation.

[0048] Through the above structure configuration, the diaphragm moving device 16 and the culture plate moving device 17 realize functional separation in the same high-precision moving adjustment module, so that the diaphragm body and the 96-well cell culture plate can respectively complete spatial positioning relative to the accelerator proton beam axis, thereby providing stable and repeatable geometric conditions for proton beam intensity regulation and cell irradiation experiments.

[0049] Preferably, the diaphragm moving device 16 and the culture plate moving device 17 respectively include a lifting mechanism for adjusting the vertical height and a guide moving mechanism for adjusting the horizontal direction position; the guide moving mechanism includes a front-to-back guide mechanism arranged in the front-to-back direction and a left-to-right guide mechanism arranged in the left-to-right direction, so as to realize independent adjustment of the diaphragm body and the cell culture plate in the vertical direction, the front-to-back direction and the left-to-right direction, and to support the collinear arrangement of the diaphragm body, the cell culture plate and the accelerator proton beam axis.

[0050] In the embodiment of the present application, the diaphragm moving device 16 and the culture plate moving device 17 respectively include a lifting mechanism for adjusting the vertical height and a guide moving mechanism for adjusting the horizontal direction position, so as to realize independent adjustment of the diaphragm body and the 96-well cell culture plate in multiple spatial directions.

[0051] The lifting mechanism for adjusting the vertical height is composed of a mechanical cross-lifting platform. Two mechanical cross-lifting platforms are arranged in the high-precision movement adjustment module, which are respectively arranged corresponding to the diaphragm movement device 16 and the culture plate movement device 17, and are used for independently adjusting the vertical height of the diaphragm body and the 96-well cell culture plate. The mechanical cross-lifting platform adopts a cross-lifting structure, the adjustment stroke is 70-130mm, the minimum movement unit is 0.05mm, the positioning accuracy is ≤±0.05mm, the bearing capacity is ≥5kg, the size of the platform surface is 100mm×150mm, and the flatness error of the platform surface is ≤0.05mm. Through the above structure, the positions of the diaphragm body and the 96-well cell culture plate in the vertical direction can be finely, stably and independently adjusted.

[0052] The guide movement mechanism for adjusting the horizontal direction position is composed of a ball screw guide rail sliding table. Four ball screw guide rail sliding tables are arranged in the high-precision movement adjustment module, which are divided into two groups, each group of guide rail sliding tables includes one front-back guide rail sliding table arranged in the front-back direction and one left-right guide rail sliding table arranged in the left-right direction. The two groups of guide rail sliding tables are respectively arranged corresponding to the diaphragm body and the 96-well cell culture plate one by one, which are used to realize the independent and accurate movement of the diaphragm body and the 96-well cell culture plate in the front-back direction and the left-right direction.

[0053] By combining the mechanical cross-lifting platform with the front-back guide rail sliding table and the left-right guide rail sliding table, the diaphragm body and the 96-well cell culture plate have independent adjustment capabilities in the vertical direction, the front-back direction and the left-right direction. In the actual adjustment process, the positions of the diaphragm body and the 96-well cell culture plate in the three orthogonal directions can be adjusted respectively, so as to support the alignment relationship between the diaphragm body, the cell culture plate and the accelerator proton beam axis, and ensure that the proton beam regulated by the diaphragm is stably incident to the cell culture plate along the predetermined propagation direction.

[0054] In a specific embodiment, as Figure 4The high-precision mobile adjustment module is integrally formed in a layered combination structure, and is used for realizing accurate positioning and independent adjustment of the diaphragm body and the cell culture plate in multiple directions. The lower part of the module is a cross-shaped lifting platform structure, and the lifting platform realizes stable lifting in the vertical direction through a cross-bearing mechanism, thereby providing a reliable height adjustment basis for the upper adjustment structure. A guiding mobile mechanism is arranged above the lifting platform in sequence, and the guiding mobile mechanism is formed by guide rail slides arranged in mutual orthogonality, and is used for realizing forward and backward and left and right mobile adjustment in the horizontal direction. Driving and adjusting components are arranged at both ends of the guide rail slide, the ball screw is driven to move through a knob or a matching driving structure, so that fine displacement of the slide along the guide rail direction is realized. An installation platform is arranged on the upper surface of the slide, and is used for fixing the diaphragm clamp or the cell culture plate clamp, so that the adjusted component can move synchronously with the slide. Through the combination of the lifting platform and the guide rail slide, the high-precision mobile adjustment module can realize independent adjustment in the vertical direction, the forward and backward direction and the left and right direction, and good structural rigidity and positioning stability can be maintained during the adjustment process. The structure is suitable for use in a proton beam experiment environment, and provides reliable mechanical support conditions for accurate alignment of the diaphragm and the cell culture plate.

[0055] Preferably, the clamp fixing mechanism includes a diaphragm clamp and a culture plate clamp; the diaphragm clamp is fixedly connected to the high-precision mobile adjustment module and is used for detachably fixing the diaphragm body, so as to limit the attitude change of the diaphragm body during the adjustment of the high-precision mobile adjustment module; and the culture plate clamp is fixedly connected to the high-precision mobile adjustment module and is used for detachably fixing the cell culture plate, so as to limit the relative displacement of the cell culture plate during irradiation.

[0056] In the embodiment of the present application, the clamp fixing mechanism includes a diaphragm clamp and a culture plate clamp, which are used for fixing and installing the diaphragm body and the 96-hole cell culture plate on the high-precision mobile adjustment module respectively. The clamp fixing mechanism is an important component of the high-precision mobile adjustment module, and is used for providing stable support for the diaphragm body and the cell culture plate during adjustment and irradiation.

[0057] Specifically, two sets of customized clamp supports are arranged in the high-precision mobile adjustment module, one set of which is a diaphragm special clamp, and the other set is a 96-hole cell culture plate special clamp. The diaphragm clamp is used for detachably fixing the diaphragm body, and the culture plate clamp is used for detachably fixing the 96-hole cell culture plate. Through the arrangement of the special clamp, the diaphragm body and the 96-hole cell culture plate can be respectively installed on the corresponding mobile adjustment mechanism, and can be quickly disassembled and replaced when needed.

[0058] The diaphragm clamp is fixedly connected to the high-precision moving adjustment module and moves synchronously with the adjustment action of the diaphragm moving device 16. During the position adjustment of the diaphragm body in the front-rear direction, the left-right direction and the vertical direction by the high-precision moving adjustment module, the diaphragm clamp stably supports the diaphragm body to limit the attitude change of the diaphragm body during the adjustment, so that the consistent installation attitude of the diaphragm body before and after the adjustment is ensured.

[0059] The culture plate clamp is fixedly connected to the high-precision moving adjustment module and is correspondingly arranged with the culture plate moving device 17, and is used for fixedly installing the 96-hole cell culture plate on the culture plate moving device 17. During the proton beam irradiation, the culture plate clamp stably clamps the 96-hole cell culture plate to limit the relative displacement of the cell culture plate during the irradiation, so that the fixed position state of the cell culture plate during the entire irradiation period is ensured.

[0060] Through the arrangement of the clamp fixing mechanism, the diaphragm body and the 96-hole cell culture plate can maintain a stable and controllable installation state during the adjustment and use of the high-precision moving adjustment module, thereby providing a reliable structural basis for the proton beam intensity control and cell irradiation experiment.

[0061] In a specific embodiment, as shown in Figure 5 , the diaphragm special clamp includes a positioning base and a stainless steel fastening screw, the positioning base has the same size as the 96-hole cell culture plate special clamp except that the front end has a length of 81.55 mm and a width of 10 mm; six M5x6 stainless steel fastening screws are arranged along the two sides of the positioning base at an interval of 15 mm, and a polytetrafluoroethylene gasket is arranged at the end of the screw to control the pressing force by a torque wrench to 5-8 N m, so as to ensure the stability of the diaphragm fixing and the convenience of disassembly.

[0062] In a specific positioning process, as shown in Figure 6 and Figure 7 , the distribution of the number of protons deposited in a unit pixel and the change rule thereof with the propagation distance are jointly verified to illustrate the influence of the high-precision positioning and distance control on the irradiation uniformity in the present application. During the positioning process, first, a laser level positioning instrument is used as an auxiliary alignment means to align the projection reference line with the accelerator beam center axis, and then the vertical height of the diaphragm body and the 96-hole cell culture plate is adjusted by the cross-shaped lifting platform to make the diaphragm center axis and the hole plate center axis keep collinear with the accelerator beam center axis in the horizontal direction. After the height alignment is completed, the relative position of the diaphragm body and the cell culture plate is fine-adjusted by the front-rear and left-right guide rail sliding tables to make the axis of the diaphragm horn-shaped through hole and the corresponding cell culture hole 152 of the 96-hole cell culture plate vertically collinear in space.

[0063] After the above collinear relationship is established, the distance from the diaphragm exit to the upper surface of the hole plate is accurately adjusted to 9 cm, and the distance from the titanium film to the bottom of the hole plate is adjusted to 15 cm, so that the proton beam can be fully scattered and expanded in the air after leaving the diaphragm. Figure 6 The cloud chart of the number of protons deposited per pixel in the local area of the hole plate under the above arrangement is given, and it can be seen that the particle distribution patterns in the regions corresponding to the cell culture holes are basically the same, and there is no obvious central overexposure or edge underexposure phenomenon. Figure 7 As shown in the statistical results, during the process of increasing the distance from the diaphragm exit to the hole plate from 5 cm to 9 cm, the average variance of the particle number distribution shows a continuous downward trend, and the average variance is less than 1.1 at the position of 9 cm, indicating that the particle deposition uniformity in the hole plate reaches an optimal state at this time. As can be seen, through the above positioning and distance adjustment mode, stable and uniform proton beam irradiation conditions can be provided for the 96-hole cell culture plate, and a reliable foundation is laid for subsequent cell radiation biology experiments.

[0064] Preferably, the dose monitoring device 14 is arranged on the irradiation path of the cell culture plate and located between the diaphragm body and the cell culture plate or coaxially arranged with the cell culture plate along the propagation direction of the accelerator proton beam, for acquiring the dose information of the proton beam regulated by the diaphragm body.

[0065] Further, the dose monitoring device 14 is configured to: based on the monitored dose of the proton beam at the setting position of the dose monitoring device 14, according to the arrangement relationship collinear with the cell culture plate along the propagation direction of the accelerator proton beam, taking the monitored dose of the proton beam as a characterization basis reflecting the dose level of the proton beam regulated by the diaphragm body and incident to the cell culture plate at the cell culture plate.

[0066] In the embodiment of the present application, the dose monitoring device 14 is arranged on the irradiation path of the cell culture plate and located between the diaphragm body and the cell culture plate. Specifically, the dose monitoring device 14 is arranged on the exit side of the diaphragm body and arranged along the propagation direction of the accelerator proton beam, so that the proton beam regulated by the diaphragm body for limiting current and diffusion is first passed through the position of the dose monitoring device 14 before being incident to the cell culture plate.

[0067] In one arrangement, the dose monitoring device 14 is coaxially arranged with the cell culture plate along the propagation direction of the accelerator proton beam, so that the dose monitoring device 14 is on the same beam propagation axis as the cell culture plate. Through this arrangement, the state of the proton beam monitored by the dose monitoring device 14 is consistent with the state of the proton beam finally incident to the cell culture plate in terms of propagation direction and spatial position relationship.

[0068] The dose monitoring device 14 is configured to acquire the dose information of the proton beam after the regulation by the diaphragm body. Since the dose monitoring device 14 is arranged between the diaphragm body and the cell culture plate along the propagation direction of the proton beam, the dose information monitored by the dose monitoring device 14 reflects the dose state of the beam after the regulation of flow control and diffusion, rather than the original dose of the accelerator beam.

[0069] Further, the dose monitoring device 14 is configured to, based on the dose of the proton beam monitored at the arrangement position of the dose monitoring device 14, take the monitored dose of the proton beam as a characterization basis of the dose level of the proton beam regulated by the diaphragm body and incident on the cell culture plate at the cell culture plate, in a collinear arrangement relationship along the propagation direction of the accelerator proton beam. By utilizing the continuous propagation characteristics of the proton beam on the same propagation axis, the dose information acquired at the dose monitoring device 14 can be used to evaluate the actual irradiation dose level received by the cell culture plate.

[0070] Through the above-mentioned arrangement and dose characterization of the dose monitoring device 14, the dose of the proton beam regulated by the diaphragm can be effectively monitored and evaluated without interfering with the normal arrangement of the cell culture plate during the cell irradiation experiment, thereby providing a reliable dose reference basis for the cell irradiation experiment.

[0071] In a specific embodiment, the accelerator proton beam intensity regulation device according to the present application is arranged as a whole in the clean bench 12 to complete the proton beam irradiation experiment of the cell sample in a controlled clean environment. The proton beam generated by the accelerator is introduced by the accelerator proton beam outlet pipe 11, the proton beam can be simulated and modeled by the proton beam simulation source 19, and enters the subsequent beam regulation and positioning structure along the preset beam direction.

[0072] The proton beam first enters the diaphragm device system 13. The diaphragm device system 13 includes a diaphragm outer plate 131 and a horn-shaped through-hole structure arranged inside the diaphragm outer plate 131, the horn-shaped through-hole sequentially forms a horn-shaped through-hole incident end 133 and a horn-shaped through-hole exit end 132 along the propagation direction of the proton beam. The proton beam enters the horn-shaped through-hole incident end 133, is geometrically constrained inside the through-hole, realizes the flow control and direction guiding effect of the beam particle fluence, and exits from the horn-shaped through-hole exit end 132, thereby forming the proton beam regulated by the diaphragm.

[0073] The diaphragm device system 13 is fixedly installed through a diaphragm clamp base 134. The diaphragm clamp base 134 is attached to a diaphragm outer plate 131, and is fixed to a diaphragm clamp base fixed end 136 through a diaphragm clamp stainless steel fastening screw 135, so as to detachably fix the diaphragm outer plate 131, so that the diaphragm device system 13 maintains a stable posture during position adjustment and irradiation, and is convenient for disassembly, replacement or maintenance of the diaphragm after the experiment is completed.

[0074] A 96-well cell culture plate device system 15 is arranged in a downstream direction of the diaphragm device system 13. The 96-well cell culture plate device system 15 comprises a 96-well cell culture plate shell 151 and a plurality of cell culture holes 152 arranged on the 96-well cell culture plate shell 151, each cell culture hole 152 being used to carry a cell sample to be irradiated. The 96-well cell culture plate device system 15 is fixedly installed through a culture plate clamp base 153, and the culture plate clamp base 153 is fixed to a culture plate clamp base fixed end 155 through a culture plate clamp stainless steel fastening screw 154, so as to detachably fix the 96-well cell culture plate shell 151, thereby effectively limiting the relative displacement of the 96-well cell culture plate device system 15 during irradiation.

[0075] In order to realize high-precision positioning of the diaphragm device system 13 and the 96-well cell culture plate device system 15 relative to the accelerator proton beam flow axis, a diaphragm moving device 16 and a culture plate moving device 17 are respectively arranged in the device. The diaphragm moving device 16 comprises a diaphragm lifting mechanism 161 for adjusting the vertical height, and a diaphragm front-to-back guiding mechanism 162 and a diaphragm left-to-right guiding mechanism 163 for adjusting the horizontal direction position; the culture plate moving device 17 comprises a culture plate lifting mechanism 171 for adjusting the vertical height, and a culture plate front-to-back guiding mechanism 172 and a culture plate left-to-right guiding mechanism 173 for adjusting the horizontal direction position. Through the above structural configuration, independent adjustment of the diaphragm device system 13 and the 96-well cell culture plate device system 15 in the vertical direction, the front-to-back direction and the left-to-right direction can be realized respectively, so as to support the accurate collinear arrangement of the diaphragm device system 13, the 96-well cell culture plate device system 15 and the accelerator proton beam flow axis.

[0076] A dose monitoring device 14 is arranged between the diaphragm device system 13 and the 96-well cell culture plate device system 15 or coaxially with the 96-well cell culture plate device system 15 along the proton beam flow propagation direction. The dose monitoring device 14 comprises a left end semiconductor detector 141 and a right end semiconductor detector 142, which have consistent structural parameters and are used for real-time monitoring of the dose of the proton beam flow regulated by the diaphragm device system 13 during irradiation. The dose information obtained by the dose monitoring device 14 is transmitted to a computer equipment 18 for display, recording and serving as a basis for beam flow regulation and calibration.

[0077] Through the above structural configuration, the accelerator proton beam flow is limited, diffused, accurately positioned and dose monitored before entering the cell culture plate, so that the regulated proton beam flow can be stably and uniformly incident to the cell sample in the cell culture hole, thereby providing reliable physical condition basis for subsequent radiation biology experiments.

[0078] In a specific embodiment, as described in the background, the accelerator is the core equipment for generating high-energy and high-purity proton beam flow, which can reveal the quantitative law of radiation dose-biological effect in cell radiation biology research, and provide key experimental data for clinical tumor proton radiotherapy. The 96-well cell culture plate is the mainstream carrier of batch experiments due to its high standardization advantage, and its design can be directly adapted to subsequent experiments such as CCK8, without cell transplantation, which can avoid operation errors, but there are many technical defects in the existing accelerator irradiation equipment when adapting to 96-well plates: first, the accelerator usually outputs a high flux of ≥10 9 particles / (cm²·s), while cell experiments only require 10 3 –10 5 particles / (cm 2 ·s), and the existing metal sheet or straight-hole diaphragm can only rely on empirical adjustment, with an error often exceeding ±20%, which can easily cause excessive cell apoptosis or excessive experimental time consumption; second, secondary particle pollution is serious, and Fe, Al, Cu and other metal diaphragms will produce a large amount of secondary neutrons and gamma rays under high-energy proton bombardment, which will interfere with the analysis of the dose-effect relationship, and if additional shielding is added, it will significantly increase the volume and weight of the device; third, the positioning accuracy is insufficient, and the traditional manual structure cannot achieve sub-millimeter alignment of the diaphragm and the 96-well plate, which can cause significant dose differences in different hole positions, thereby reducing the experimental repeatability.

[0079] Therefore, before actual application, in order to ensure the requirements of stable proton flux and uniform dose distribution when the accelerator irradiates cells, the Monte Carlo simulation needs to be performed in advance, i.e., to determine the optimal thickness of the required diaphragm, the geometric shape and arrangement of the diaphragm through-hole, and the optimal spatial position of the diaphragm, the 96-well cell culture plate and the proton beam flow source, and other parameters. Figure 2

[0080] In the embodiments of the present application, further mathematical calculations need to be performed on the basis of the Monte Carlo simulation data to convert the statistical particle flux into simulated dose rate. For example, Figure 8 , the calculation can include the following steps: Step 1: Based on the Monte Carlo output data, determine the number of particles counted at the bottom of each cell culture hole in the 96-well cell culture plate.

[0081] ​In specific implementation, the bottom surface of each cell culture hole can be divided into a plurality of tiny voxels with a size much smaller than the area of the hole bottom, and each voxel can be regarded as a point source. According to the actual inner diameter size of each cell culture hole of the used 96-hole cell culture plate, corresponding region division is performed through a program such as python. Taking the cell culture hole 152152 of the 96-hole cell culture plate as an example, when the effective particle number inside is obtained N effect The following formula (1) can be used to calculate the collection efficiency of the Monte Carlo simulation according to the total number of simulated particles N0: (2) Step 2, according to the actual number of protons emitted per unit time by the accelerator actually used in the later stage , the actual fluence rate in each cell hole during the actual experiment is calculated: (3) Where dt is the unit time.

[0082] Then the fluence rate and dose rate can be converted according to the mass stopping power S. The mass stopping power is the stopping power corrected by the material density, and its formula is as follows: (4) Where dE is the particle deposition energy, dx is the unit depth, which can be understood as the rate of kinetic energy of a single proton hole. In specific calculation, since the energy of protons emitted by the accelerator in cell irradiation experiment is usually not more than 10 MeV, and the cells in the experiment are in culture solution, the material is mainly H2O, and the protons usually deposit in the range of 0.03~0.05g / cm 2 Therefore, in the calculation, the energy of the used protons can be defaulted to be completely deposited in the culture solution.

[0083] According to the absorbed dose formula, formula decomposition and symbol replacement are performed to convert it into a calculation formula related to fluence rate, assuming that there are dN protons in a cylinder with cross section dA and thickness dx: (5) Where p represents the density of the object through which the protons pass.

[0084] Step 3, the data calculated in formula (5) is in MeV / g / s, which needs to be brought into Avogadro's constant N A, according to the actual proton energy of the accelerator, through the PSTAR database disclosed by the National Institute of Standards and Technology (NIST) to look up and substitute. Finally, the calculation formula for converting the proton fluence rate into the dose rate can be obtained: (6) In the actual simulation, the calculation of the diaphragm and diaphragm through hole geometric parameters and the spatial position between the 96-well cell culture plate for improving the proton beam intensity and irradiation dose rate can be carried out by the above method to realize the optimal diaphragm overall design and the determination of the placement position.

[0085] After the above particle transport simulation and dose rate conversion based on the Monte Carlo method, the thermal effect of the diaphragm material under the irradiation of the proton beam needs to be further evaluated. Since the diaphragm material can be Al, Cu, Fe or PMMA, among which PMMA has the highest risk of damage after proton irradiation, therefore, this embodiment focuses on the heat estimation of PMMA material. For ease of analysis, the irradiation process of the PMMA plate can be regarded as an extreme case of adiabatic condition, in which the kinetic energy of the protons is completely deposited inside the PMMA. The calculation can include the following steps: Step one, according to the proton beam intensity and the irradiation time, the absorbed heat Q of the PMMA plate can be estimated, and the calculation is carried out under the limit condition of 23nA and irradiation time of 240s, as shown in the following formula (7): (7) The number of protons N corresponding to the absorbed heat is p : (8) Where q represents the elementary charge, i.e. the charge amount carried by one proton. Adding the proton energy Ep=5.2MeV, the total heat absorbed by PMMA is: (9) Step two, in this embodiment, the beam action area diameter of the PMMA diaphragm plate is 1.5cm, and the plate thickness is 4mm. According to the PSTAR database, the range of protons in this energy range is about 393.02μm (about 0.039cm). The specific heat capacity of PMMA is taken as c=1.5J / (g·K), and the density is taken as 1.19g / cm³. The irradiation area can be regarded as a cylinder, and its volume is: (10) The corresponding mass is: (11) Therefore, the temperature rise of PMMA under the adiabatic assumption is: (12) Since the diaphragm will have natural convection heat dissipation in actual situation, its heating power becomes: (13) Because the convection heat transfer coefficient of the diaphragm is h = 10 W / (m 2 / K), the surface area is S = 5.423 x 10 4 m 2 , and thus its natural convection heat dissipation power is: (14) Step three, assuming that the room temperature is 25°C = 298.15K, when the temperature change reaches a steady state, at this time p = p conv , according to the formula p = p conv x Δt, Δt = 22K can be calculated, that is, the temperature of the diaphragm plate at a steady state is 47°C. Similarly, if only the upper and lower surfaces of the diaphragm are considered for natural convection heat dissipation, Δt1 = 34K, that is, the temperature of the diaphragm plate at a steady state is 59°C. Table 1 lists the steady-state temperatures of different diaphragm materials under adiabatic, full-surface heat dissipation, and two-surface heat dissipation conditions, as well as their typical thermal conductivity ranges.

[0086] Table 1 Comparison of steady-state temperatures and thermal conductivities of different diaphragm materials under different heat dissipation conditions

[0087] From the calculation results, it can be seen that under the condition of room temperature 25°C, even if only two-surface natural heat dissipation is considered, the temperature of each type of diaphragm material at a steady state is still significantly lower than its melting point, which can meet the safety and structural stability requirements of proton beam irradiation experiments.

[0088] Figure 9 is a method flowchart of an accelerator proton beam intensity regulation method provided by an embodiment of the present application. As shown in Figure 9 , the present application provides an accelerator proton beam intensity regulation method, which comprises the following steps: Step S10: obtaining a proton beam output by an accelerator, and making the proton beam enter a diaphragm body along a preset beam path.

[0089] Specifically, the accelerator system is started, and the accelerator is made to enter a stable running state and output a proton beam. The proton beam output by the accelerator propagates along a preset beam transmission path, which is determined by a beam transport structure inside the accelerator, and is used to ensure that the proton beam is emitted in a stable direction and a given axis. Before the beam enters a subsequent regulation device, the initial beam particle fluence is set by an accelerator control system to meet the basic needs of cell irradiation experiments.

[0090] After the proton beam is emitted, the proton beam is made to enter the incident end of the diaphragm body along the accelerator beam center axis. To ensure that the beam can smoothly enter the diaphragm body, the initial position of the diaphragm body is pre-adjusted by the high-precision moving adjustment module before entering the diaphragm body, so that the center position of the diaphragm body is consistent with the accelerator beam center axis, thereby avoiding the deviation or irregular scattering of the proton beam in the incident stage. In the above manner, stable acquisition of the accelerator output proton beam is realized, and reliable incident conditions are provided for the subsequent flow limiting and diffusion regulation process.

[0091] Step S20: The diaphragm body performs flow limiting and diffusion regulation on the entering proton beam to form a regulated proton beam.

[0092] Specifically, after the proton beam enters the diaphragm body, the proton beam first passes through the incident hole structure of the diaphragm body to realize flow limiting control of the number of beam particles. The cross-sectional area of the beam is constrained by the incident hole, so that the proton beam particle flux entering the diaphragm body is effectively limited, thereby adjusting the original high-flux beam of the accelerator to a range suitable for cell irradiation experiments. Subsequently, the proton beam continues to propagate along the through-hole structure inside the diaphragm body and is emitted from the exit hole of the diaphragm body. In this process, the structure design of the exit hole enables the proton beam to obtain a certain degree of spatial expansion after passing through the diaphragm. After leaving the diaphragm body, the proton beam enters the air propagation section and scatters naturally in the air, thereby gradually expanding the lateral distribution of the beam. Through the combination of flow limiting and diffusion regulation, the proton beam regulated by the diaphragm body has a suitable beam distribution state for hole plate irradiation while maintaining the stability of the propagation direction.

[0093] Step S30: Under the action of the high-precision moving adjustment module, the relative spatial position of the diaphragm body and the cell culture plate is adjusted, so that the diaphragm body is aligned with the accelerator proton beam axis, and the regulated proton beam is incident to the cell culture plate.

[0094] Specifically, after completing the flow limiting and diffusion regulation of the proton beam, the spatial position of the diaphragm body and the 96-well cell culture plate is accurately adjusted by the high-precision moving adjustment module. First, the vertical height of the diaphragm body and the cell culture plate is adjusted by the mechanical cross-lifting table respectively, so that the center positions of the two are aligned with the accelerator proton beam center axis in the vertical direction. This process is used to eliminate the influence of height deviation on the beam incident position.

[0095] Further, the relative positions of the diaphragm body and the cell culture plate are finely adjusted in the horizontal direction by a ball screw guide rail sliding table, so that the diaphragm through hole and the hole of the cell culture plate are kept aligned in the front-rear direction and the left-right direction. At the same time, the distance between the diaphragm outlet and the upper surface of the cell culture plate is adjusted to a preset value, so as to ensure that the proton beam flow regulated by the diaphragm can stably enter the cell culture plate after completing the necessary scattering process in the air. Through the above multi-direction independent adjustment, the regulated proton beam flow is incident to the irradiation area of the cell culture plate along the predetermined axis.

[0096] Step S40: In the process of the proton beam incident to the cell culture plate, the dose monitoring device is used to monitor the dose of the proton beam regulated by the diaphragm body, and the corresponding dose monitoring data is obtained.

[0097] Specifically, in the process of the proton beam incident to the cell culture plate and irradiating the cell sample, the dose monitoring device is started to monitor the dose of the proton beam in real time. The dose monitoring device is arranged between the diaphragm body and the cell culture plate or coaxially arranged with the cell culture plate along the propagation direction of the accelerator proton beam, for obtaining the dose information of the proton beam regulated by the diaphragm body.

[0098] In the monitoring process, the real-time proton beam detection data is obtained by the semiconductor dose rate monitor, and the data is used as the basis for reflecting the actual irradiation dose level at the cell culture plate. When the dose rate deviates from the preset value, the real-time calibration mechanism is started according to the monitoring result, the position of the front-rear guide rail sliding table is finely adjusted by the motion controller, or the initial beam particle flux is adjusted by the accelerator control system, so that the dose rate at the bottom of the hole plate is restored to the set range. Through the above monitoring and calibration process, the stability and controllability of the proton beam dose in the cell irradiation experiment are ensured.

[0099] The embodiment of the present application also provides a computer readable storage medium, which stores instructions, and the instructions make the computer execute the above functions when the computer runs.

[0100] Those skilled in the art can understand that all or part of the steps in the method for implementing the above embodiment can be completed by programs instructing related hardware, the programs are stored in a storage medium, and the programs include a plurality of instructions for making a single-chip microcomputer, a chip or a processor execute all or part of the steps of the method described in each embodiment of the present application. The foregoing storage medium includes a U disk, a mobile hard disk, a read-only memory (ROM), a random access memory (RAM), a magnetic disk or an optical disk and various program code storage media.

[0101] The optional embodiments of the present application are described in detail above with reference to the drawings, but the embodiments of the present application are not limited to the specific details in the above-described embodiments. Within the technical concept of the embodiments of the present application, various simple modifications can be made to the technical solutions of the embodiments of the present application, and these simple modifications all belong to the protection scope of the embodiments of the present application. In addition, it should be noted that, in the above-described specific embodiments, various specific technical features can be combined in any appropriate manner without contradiction. In order to avoid unnecessary repetition, various possible combinations are not described again in the embodiments of the present application.

[0102] In addition, various different embodiments of the present application can also be combined in any appropriate manner, as long as it does not deviate from the idea of the embodiments of the present application, and it should also be considered as disclosed by the embodiments of the present application.

Claims

1. A device for controlling the intensity of a proton beam in an accelerator, characterized in that, The device includes: The aperture body is used for current limiting and diffusion control of the proton beam in the accelerator; Cell culture plates are used to hold cell samples that have been irradiated by proton beams. A high-precision motion adjustment module is connected to the aperture body and the cell culture plate respectively, and is used to adjust the relative spatial position of the aperture body and the cell culture plate so that the aperture body is aligned with the proton beam axis of the accelerator; A clamping mechanism is used to fix the aperture body and the cell culture plate. A dose monitoring device is used to monitor the proton beam dose after it has been regulated by the aperture body.

2. The accelerator proton beam intensity control device according to claim 1, characterized in that, The aperture body is positioned on the exit path of the accelerator proton beam and arranged upstream of the cell culture plate along the propagation direction of the accelerator proton beam. A spatial segment for the propagation of the proton beam is formed between the aperture body and the cell culture plate, so that the proton beam is incident on the cell culture plate after passing through the aperture body.

3. The accelerator proton beam intensity control device according to claim 2, characterized in that, The space between the aperture body and the cell culture plate is continuously arranged along the propagation direction of the accelerator proton beam; No structural components are provided within the space segment to block or guide the proton beam, so that the proton beam reaches the cell culture plate along its original propagation direction after leaving the aperture body.

4. The accelerator proton beam intensity control device according to claim 1, characterized in that, The high-precision motion adjustment module includes an aperture moving device and a culture plate moving device; The aperture moving device is connected to the aperture body and is used to drive the aperture body to adjust its position relative to the accelerator proton beam axis. The culture plate moving device is connected to the cell culture plate and is used to drive the cell culture plate to adjust its position relative to the accelerator proton beam axis. The aperture moving device and the culture plate moving device are set independently to complete the spatial positioning of the aperture body and the cell culture plate, respectively.

5. The accelerator proton beam intensity control device according to claim 4, characterized in that, The aperture moving device and the culture plate moving device each include a lifting mechanism for adjusting the vertical height and a guide moving mechanism for adjusting the horizontal position. The guiding and moving mechanism includes a front-back guiding mechanism arranged in the front-back direction and a left-right guiding mechanism arranged in the left-right direction, so as to realize the independent adjustment of the aperture body and the cell culture plate in the vertical, front-back and left-right directions, so as to support the collinear arrangement of the aperture body, the cell culture plate and the accelerator proton beam axis.

6. The accelerator proton beam intensity control device according to claim 1, characterized in that, The clamp fixing mechanism includes an aperture clamp and a culture plate clamp; The aperture clamp is fixedly connected to the high-precision movement adjustment module and is used to detachably fix the aperture body, so as to limit the attitude change of the aperture body during the adjustment process of the high-precision movement adjustment module. The culture plate clamp is fixedly connected to the high-precision movement adjustment module and is used to detachably fix the cell culture plate to limit the relative displacement of the cell culture plate during irradiation.

7. The accelerator proton beam intensity control device according to claim 1, characterized in that, The dose monitoring device is disposed on the irradiation path of the cell culture plate and is located between the aperture body and the cell culture plate or coaxially with the cell culture plate along the direction of the accelerator proton beam propagation, for acquiring proton beam dose information after being regulated by the aperture body.

8. The accelerator proton beam intensity control device according to claim 7, characterized in that, The dose monitoring device is configured as follows: Based on the proton beam dose monitored at the location of the dose monitoring device, and in accordance with the collinear arrangement of the cell culture plate along the direction of the accelerator proton beam propagation, the monitored proton beam dose is used as a characterization basis for reflecting the dose level of the proton beam incident on the cell culture plate after being regulated by the aperture body.

9. A method for controlling the intensity of a proton beam in an accelerator, characterized in that, The method is implemented based on the accelerator proton beam intensity control device according to any one of claims 1-8, and the method includes: Acquire the proton beam output from the accelerator and guide the proton beam into the aperture body along a preset beam path; The incoming proton beam is controlled by the aperture body to perform current limiting and diffusion regulation, forming a regulated proton beam; Under the action of the high-precision motion adjustment module, the relative spatial position of the aperture body and the cell culture plate is adjusted so that the aperture body is aligned with the axis of the accelerator proton beam and the regulated proton beam is injected into the cell culture plate. During the process of proton beam infusion into cell culture plates, a dose monitoring device is used to monitor the proton beam dose after it is regulated by the aperture body, and the corresponding dose monitoring data is obtained.

10. A computer-readable storage medium, characterized in that, The computer-readable storage medium stores instructions that, when executed on a computer, cause the computer to perform the accelerator proton beam intensity control method of claim 9.

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