CN114983610A - A measuring device for animal experiments of tumor electric field therapy - Google Patents
A measuring device for animal experiments of tumor electric field therapy Download PDFInfo
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Abstract
Description
技术领域technical field
本发明涉及实验器材技术领域,尤其涉及一种用于肿瘤电场治疗动物实验的测量装置。The invention relates to the technical field of experimental equipment, in particular to a measuring device for animal experiments of tumor electric field therapy.
背景技术Background technique
肿瘤电场治疗(Tumor-Treating Fields,TTFields)是一种新型的无创、抗有丝分裂治疗肿瘤的技术,利用中频(100-500kHz)、低强度(1-3V/cm)的交流电场作用于肿瘤细胞,抑制其有丝分裂过程,达到治疗肿瘤的效果。2020年5月肿瘤电场治疗在国内获批上市。但是TTFields抑制肿瘤细胞增殖的机制还不清楚,使得相关治疗技术在肿瘤治疗方面存在较大的局限性,特别是其他不同类型的肿瘤治疗,还在进一步探索中。Tumor-Treating Fields (TTFields) is a new type of non-invasive, anti-mitotic tumor treatment technology. Inhibit its mitotic process to achieve the effect of tumor treatment. In May 2020, tumor electric field therapy was approved for marketing in China. However, the mechanism by which TTFields inhibit the proliferation of tumor cells is still unclear, which makes the related treatment technologies have great limitations in tumor treatment, especially for other different types of tumor treatments, which are still being further explored.
为了研究TTFields对不同肿瘤细胞的作用效果和机制,除了肿瘤细胞实验外,动物实验是重要的实验环节,针对不同肿瘤动物模型,进行不同参数的TTFields实验;TTFields通过刺激电极将交流电场施加在动物体内,为了保证有足够的电场强度,需要对整个刺激电路进行分析和计算,保证在动物身上具有1-2V/cm的电场强度,传统的计算方法只能以整个实验动物为单位,即根据实际动物体长去调整电压大小,至于动物体内是否产生满足要求的电场强度一直没有相关测量。另一方面由于生物组织具有特殊的电气性质,电导率、相对介电常数、密度等参数差异很大,再加上血液和组织液流动,肌肉收缩蠕动等原因的影响,TTFields在体内的产生的电场强度大小和分布必然有着巨大差异。目前针对于生物体内电场强度的大小和分布,一般采用计算机建模仿真分析,该方法根据不同生物组织建立分层模型,并赋予不同组织适宜的电导率和相对介电常数,最后得到仿真的电场强度分布。至于生物体内实际的电场强度大小和分布和计算机建模仿真的结果是否一致,一直未得到确认,同时由于生物组织特殊的电气性质,各个参数值变化范围大,建模过程中参数选择是否准确也是一个未解决的问题。In order to study the effect and mechanism of TTFields on different tumor cells, in addition to tumor cell experiments, animal experiments are an important experimental link. TTFields experiments with different parameters are carried out for different tumor animal models; TTFields stimulate electrodes to apply an AC electric field to animals. In vivo, in order to ensure sufficient electric field strength, it is necessary to analyze and calculate the entire stimulation circuit to ensure an electric field strength of 1-2V/cm in animals. The length of the animal is used to adjust the voltage, and there has been no relevant measurement on whether the required electric field intensity is generated in the animal. On the other hand, due to the special electrical properties of biological tissues, parameters such as conductivity, relative permittivity, and density are very different, coupled with the influence of blood and tissue fluid flow, muscle contraction and peristalsis, etc., the electric field generated by TTFields in vivo The magnitude and distribution of intensities are bound to vary enormously. At present, computer modeling and simulation analysis are generally used for the magnitude and distribution of electric field in vivo. This method establishes a layered model according to different biological tissues, and assigns appropriate electrical conductivity and relative permittivity to different tissues. Finally, the simulated electric field is obtained. intensity distribution. Whether the magnitude and distribution of the actual electric field in vivo is consistent with the results of computer modeling and simulation has not been confirmed. At the same time, due to the special electrical properties of biological tissues, the value of each parameter varies widely, and whether the parameter selection in the modeling process is accurate is also an issue. an unresolved issue.
因此,一种可以可靠测量生物体体内肿瘤电场治疗强度的装置,将对肿瘤电场治疗相关的动物实验、计算机精确建模仿真产生重要的积极意义。Therefore, a device that can reliably measure the treatment intensity of tumor electric field in vivo will have important positive significance for animal experiments and computer accurate modeling and simulation related to tumor electric field treatment.
发明内容SUMMARY OF THE INVENTION
本发明的目的是提供一种用于肿瘤电场治疗动物实验的测量装置,是一种肿瘤电场治疗实验中动物体内电场强度的测量装置。可解决目前TTFields动物实验和计算机建模仿真中,无法确定动物体内实际电场强度的大小和分布问题,为进一步优化实验方式和参数提供必要的真实数据。The purpose of the present invention is to provide a measuring device for animal experiments of tumor electric field treatment, which is a measuring device of electric field intensity in animals in tumor electric field treatment experiments. It can solve the problem that the size and distribution of the actual electric field intensity in the animal body cannot be determined in the current TTFields animal experiment and computer modeling simulation, and provide necessary real data for further optimization of experimental methods and parameters.
本发明解决其问题所采取的技术手段是:所述的一种用于肿瘤电场治疗动物实验的测量装置,主要包括多通道等距测量探针、定位器和通道选择器三个部分,所述多通道等距测量探针穿过定位器的测量孔,进入待测动物体内测量电场强度,通道选择器选择打开多通道等距测量探针上的测量通道,将测量信号传输至显示记录端。The technical means adopted by the present invention to solve its problems are as follows: the described measurement device for animal experiments on tumor electric field treatment mainly includes three parts: a multi-channel isometric measurement probe, a locator and a channel selector. The multi-channel equidistant measurement probe passes through the measurement hole of the locator and enters the body of the animal to be measured to measure the electric field strength. The channel selector selects to open the measurement channel on the multi-channel equidistant measurement probe, and transmits the measurement signal to the display and recording end.
所述多通道等距测量探针主要由导电位点、探针主体和传输导线构成,多通道等距测量探针整体呈现为圆锥柱形,根据探针主体的不同材料,分为中空和实体两种结构,探针直径根据待测动物大小和组织的不同,可以选取范围为0.5mm到4mm,多通道等距测量探针头端为尖头设计,可以穿破待测组织;探针主体是整个探针的主要刚体结构,可以由经过绝缘的高强度金属材料和高强度的绝缘塑料制成,当采用经过绝缘的高强度金属材料(如:不锈钢)制备探针主体时,探针为中空结构,传输导线走线在探针主体中间腔体,穿过导电位点覆盖区域下的预留孔隙,并和导电位点焊接连接;当采用高强度绝缘塑料制备探针主体时,探针整体为浇注实体结构,先将导电位点和传输导线焊接好并固定在制备探针主体的模具内,然后浇注塑料制成;探针主体尾部具有刻度标线,可测得探针探入定位器的深度;导电位点由导电性能优越且易加工成箔片的材料制成,如:金、银、铜等,采用粘贴或浇注一体方法固定在探针主体表面,且相邻位点等距,根据不同体型动物,可间隔1mm-5mm的距离;传输导线为外表做过绝缘的导电性能优越的材料,连接导电位点和通道选择器,传输导线在探针主体内部走线,在出口处转变为独立导线,和通道选择器输入端口连接。The multi-channel equidistant measurement probe is mainly composed of a conductive site, a probe body and a transmission wire. The multi-channel equidistant measurement probe is in the shape of a conical cylinder as a whole, and is divided into hollow and solid according to different materials of the probe body. There are two structures. The diameter of the probe can be selected from 0.5mm to 4mm according to the size of the animal to be tested and the tissue. It is the main rigid body structure of the entire probe, which can be made of insulated high-strength metal materials and high-strength insulating plastics. When the probe body is made of insulated high-strength metal materials (such as stainless steel), the probe is Hollow structure, the transmission wire is routed in the middle cavity of the probe body, passes through the reserved pores under the coverage area of the conductive site, and is connected to the conductive site by welding; when the probe body is made of high-strength insulating plastic, the probe The whole is a cast solid structure. The conductive sites and transmission wires are first welded and fixed in the mold for preparing the probe body, and then made of plastic; The depth of the probe; the conductive sites are made of materials with superior conductivity and easy to process into foil, such as: gold, silver, copper, etc., which are fixed on the surface of the probe body by sticking or pouring, and the adjacent sites, etc. The distance between them can be 1mm-5mm according to different size animals; the transmission wire is a material with excellent electrical conductivity that has been insulated on the surface, connecting the conductive point and the channel selector, and the transmission wire is routed inside the probe body and at the exit It is converted into a separate wire and connected to the channel selector input port.
所述定位器由透明塑料材料制成,分为上定位器和下定位器,上定位器和下定位器中间有对应的凹槽,该凹槽在定位器组合固定后,形成容纳动物躯干的空间,凹槽形状与动物躯干形状契合,凹槽大小根据不同种类的实验动物变化,一般设置为待测动物的平均躯干大小。上定位器和下定位器通过四组榫卯结构组合,榫卯结构对接表面嵌有两个对应的磁吸装置,上定位器表面有十字刻度线,标明毫米级刻度;上定位器在中心十字刻度线设有若干相互间距5mm的等距测量孔,等距测量孔贯穿上定位器,等距测量孔直径略大于多通道等距测量探针主体的直径,多通道等距探针穿过等距测量孔,实现定位定量测量,等距测量孔数量在躯干长轴方向最少5个,躯干横轴方向最少3个,最多数量根据实验动物大小变化;在下定位器22中间凹槽的两侧设有刺激电极契合槽28,用于安装固定施加电场的电极。The locator is made of transparent plastic material and is divided into an upper locator and a lower locator. There is a corresponding groove in the middle of the upper locator and the lower locator. Space, the shape of the groove fits the shape of the animal's trunk, and the size of the groove varies according to different types of experimental animals, and is generally set to the average trunk size of the animal to be tested. The upper locator and the lower locator are combined by four groups of tenon-and-mortise structures. Two corresponding magnetic suction devices are embedded on the butting surface of the mortise-and-mortise structure. The surface of the upper locator has a cross scale line indicating a millimeter scale; the upper locator is crossed in the center. The scale line is provided with a number of equidistant measurement holes with a mutual distance of 5mm. The equidistant measurement holes pass through the upper locator. The diameter of the equidistant measurement holes is slightly larger than the diameter of the main body of the multi-channel equidistant measurement probe. The multi-channel equidistant probe passes through the equidistant. Distance measurement holes to achieve quantitative measurement of positioning. The number of isometric measurement holes is at least 5 in the direction of the long axis of the torso, and at least 3 in the direction of the transverse axis of the torso. The maximum number varies according to the size of the experimental animal; There is a stimulating
所述通道选择器为电路设计模块,主要包含电源模块、控制模块、输入模块、输出模块和显示模块,其中电源模块将直流5v供电转换为不同电压,供其他模块使用;控制模块实现主要的定时、选通功能;输入模块连接探针多通道信号;输出模块将选通的信号传输至显示记录端,可通过有线传输和无线传输两种不同传输模式;显示模块显示当前记录时间和选通通道号。The channel selector is a circuit design module, which mainly includes a power supply module, a control module, an input module, an output module and a display module, wherein the power supply module converts the DC 5v power supply into different voltages for use by other modules; the control module realizes the main timing , gating function; the input module is connected to the multi-channel signal of the probe; the output module transmits the gating signal to the display and recording terminal, which can be transmitted in two different transmission modes: wired transmission and wireless transmission; the display module displays the current recording time and the gating channel No.
本发明所述多通道等距测量探针具有:(1)质地坚韧,无生物毒副作用,具有良好的生物相容性;(2)探针细小,针上探测位点导电性能好;(3)各个通道探测位点间隔等距,可观测探入深度。The multi-channel isometric measurement probe of the present invention has: (1) tough texture, no biological toxicity and side effects, and good biocompatibility; (2) the probe is small, and the detection site on the needle has good electrical conductivity; (3) ) The detection sites of each channel are equidistant, and the penetration depth can be observed.
本发明所述定位器具有:(1)透明结构,可观测到测量探针和动物体表特征;(2)具有等距测量孔,供多通道等距测量探针插入测量;(3)具有中心标记线,对齐动物体位;(4)具有产生电场的电极槽,契合安装刺激电极;(5)具有榫卯结构,精确稳定组合;(6)无实际大小限制,可根据实验动物大小等比例调整。The positioner of the present invention has: (1) a transparent structure, which can observe the measurement probe and the surface features of the animal; (2) has an equidistant measurement hole for insertion and measurement of multi-channel equidistant measurement probes; (3) has The center mark line is aligned with the animal body position; (4) It has an electrode groove that generates an electric field, and is suitable for installing stimulating electrodes; (5) It has a tenon-and-mortise structure, which can be combined accurately and stably; (6) There is no actual size limit, and it can be proportional to the size of the experimental animal Adjustment.
本发明所述的通道选择器具有:(1)循环选通多通道等距探针中的某一个测量通道;(2)可设定测量时长,并无损传输至显示记录端;(3)显示当前选通通道与记录时长。The channel selector of the present invention has: (1) cyclically selects a certain measurement channel in the multi-channel equidistant probe; (2) can set the measurement time length, and transmit it to the display and record end without damage; (3) display The current gated channel and recording duration.
相对于目前以整个实验动物为单位的整体电场强度计算法和计算机建模仿真分析电场强度法,本发明具有以下优点:(1)可直接测得真实的实验动物体内电场强度大小;(2)利用定位器的测量孔和多通道等距测量探针,可测得体表和体内电场强度的空间分布;(3)定位器适用性广,可用于不同种类和大小的实验动物(4)通道选择器定时选通测量不同通道,资源利用高效;(5)整套测量装置结构设计合理,适用性强,可靠性高,对促进科学问题深入研究有重要意义。Compared with the current overall electric field strength calculation method and computer modeling simulation analysis electric field strength method based on the whole experimental animal, the present invention has the following advantages: (1) the electric field strength in the body of the real experimental animal can be directly measured; (2) Using the measuring holes of the positioner and the multi-channel equidistant measurement probes, the spatial distribution of the electric field intensity on the body surface and in the body can be measured; (3) The positioner has wide applicability and can be used for experimental animals of different types and sizes (4) Channel selection (5) The whole set of measuring device has reasonable structure design, strong applicability and high reliability, which is of great significance for promoting in-depth research on scientific issues.
附图说明Description of drawings
图1为本发明结构示意图。Figure 1 is a schematic structural diagram of the present invention.
图2为多通道等距测量探针结构示意图。FIG. 2 is a schematic structural diagram of a multi-channel equidistant measurement probe.
图3为定位器结构示意图。Figure 3 is a schematic diagram of the structure of the positioner.
图4为通道选择器结构示意图。FIG. 4 is a schematic diagram of the structure of the channel selector.
图5为本发明实际应用示例图。FIG. 5 is a diagram showing an example of practical application of the present invention.
具体实施方式Detailed ways
本发明结合附图和实施例作进一步的说明。The present invention will be further described with reference to the accompanying drawings and embodiments.
实施例1Example 1
参见图1,为本发明的一种用于肿瘤电场治疗动物实验的测量装置,主要包括多通道等距测量探针1、定位器2和通道选择器3三个部分。Referring to FIG. 1 , it is a measurement device used for tumor electric field treatment animal experiments according to the present invention, which mainly includes three parts: a multi-channel
参见图2,多通道等距测量探针1主要由导电位点11、探针主体12和传输导线13构成,多通道等距测量探针整体呈现为圆锥柱形,根据探针主体12的不同材料,分为中空和实体两种结构,探针直径根据待测动物大小和组织的不同,可以选取范围为0.5mm到4mm,多通道等距测量探针头端为尖头设计,可以穿破待测组织;探针主体12是整个探针的主要刚体结构,可以由经过绝缘的高强度金属材料和高强度的绝缘塑料制成,当采用经过绝缘的高强度金属材料(如:不锈钢)制备探针主体12时,探针为中空结构,传输导线13走线在探针主体12中间腔体,穿过导电位点(11)覆盖区域下的预留孔隙,和导电位点11焊接连接;当采用高强度绝缘塑料制备探针主体12时,探针整体为浇注实体结构,先将导电位点11和传输导线13焊接好并固定在制备探针主体12的模具中,然后浇注塑料制成;探针主体12尾部具有刻度标线14,可测得探针探入定位器2的深度;导电位点11由导电性能优越且易加工成箔片的材料制成,如:金、银、铜等,采用粘贴或浇注一体方法固定在探针主体12表面,且相邻位点等距,根据不同体型动物,可间隔1mm-5mm的距离;传输导线13为外表做过绝缘的导电性能优越的材料,连接导电位点11和通道选择器3,传输导线13在探针主体12内部走线,在出口处转变为独立导线,和通道选择器输入端口连接。Referring to FIG. 2 , the multi-channel
参见图3,定位器2由透明塑料材料制成,分为上定位器21和下定位器22,上定位器21和下定位器22中间有对应的凹槽23,该凹槽23在定位器组合固定后,形成容纳动物躯干的空间,凹槽23形状与动物躯干形状契合,可以很好的容纳、固定实验动物,凹槽23大小根据不同种类的实验动物变化,一般设置为待测动物的平均躯干大小,在实验时,挑选躯干大小匹配的实验动物。上定位器21和下定位器22通过四组榫卯结构24组合,榫卯结构24对接表面嵌有两个对应的磁吸装置25,保证两部分结合紧密,上定位器21表面有十字刻度线26,标明毫米级刻度,便于定位动物;上定位器21在中心十字刻度线设有若干等距测量孔27,相互间距5mm,贯穿上定位器21,测量孔27直径略大于多通道等距测量探针主体12的直径,多通道等距探针1穿过等距测量孔27,实现定位定量测量,等距测量孔27数量在躯干长轴方向最少5个,躯干横轴方向最少3个,最多数量根据实验动物大小变化;在下定位器22中间凹槽的两侧设有刺激电极契合槽28,用于安装固定施加电场的电极。Referring to FIG. 3 , the positioner 2 is made of transparent plastic material, and is divided into an
参见图4,通道选择器3为电路设计模块,主要包含电源模块31、控制模块32、输入模块33、输出模块34和显示模块35,其中电源模块31将直流5v供电转换为不同电压,供其他模块使用;控制模块32实现主要的定时、选通功能;输入模块33连接探针多通道信号;输出模块34将选通的信号传输至显示记录端,可通过有线传输和无线传输两种不同传输模式;显示模块35显示当前记录时间和选通通道号。Referring to FIG. 4, the
实施例2Example 2
参见图5,为本发明一种的应用实例示意图。本发明中定位器2将实验动物定位安装好,其中,刺激电极和导线在固定动物前安装在契合槽内,导线末端通过相应的接口接入TTFields设备,动物固定时将动物以平仰姿态放入定位器2的下半部分,前后肢中间的躯干置于定位器凹槽中,四肢和其他部位位于定位器外部,并将动物躯干中心线和定位器2的刻度线对齐,对其完成后合并定位器2的上下部分,多通道等距测量探针1通过定位器2的测量孔伸入定位器2内和动物身体内部,直到预定深度;多通道等距测量探针1尾端的传输导线接入通道选择器3的输入端口,通道选择器3的输出端口和测量信号显示记录设备4(如:示波器)相连接,打开TTFields设备,调整实验参数,显示记录多通道等距测量探针1在预设位置的信号,通过不同测量孔重复测量实验动物体内不同位置和深度的电场,最终得到整体的电场强度大小分布。Referring to FIG. 5, it is a schematic diagram of an application example of the present invention. In the present invention, the locator 2 locates and installs the experimental animal, wherein the stimulating electrode and the lead wire are installed in the fitting groove before the animal is fixed, and the end of the lead wire is connected to the TTFields device through the corresponding interface. Enter the lower part of the positioner 2, the trunk between the front and rear limbs is placed in the positioner groove, the limbs and other parts are located outside the positioner, and the center line of the animal trunk and the scale line of the positioner 2 are aligned. Merging the upper and lower parts of the positioner 2, the multi-channel
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