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题名	用于微针经皮给药测试的光学相干层析成像技术研究
作者	宋思雨
文献子类	硕士
导师	李中梁
关键词	微针经皮给药 transdermal drug delivery by microneedles 光学相干层析成像 optical coherence tomography 贝塞尔光束 Bessel beams 圆环达曼光栅 circular Dammann grating
其他题名	Research on Optical Coherence Tomography for Transdermal Drug Delivery by Microneedles
英文摘要	微针经皮给药是提高药物经皮吸收效率的给药方式之一， 它使用微米尺度的 针刺入皮肤，在皮肤上产生药物运输的通道。 微针的穿刺深度不会接触到神经末 梢和血管， 无痛无血就可以使药物实现皮内释放， 且针体尺寸较小，几乎不会对 皮肤造成损害， 是近年来经皮给药领域的研究热点。然而，此技术仍处于发展阶 段，需要利用成像手段对微针刺入皮肤的深度、 微通道的关闭时间、 药物颗粒的 释放行为等进行研究。 光学相干层析成像（OCT） 可以实时、 在体检测样品的内 部结构信息， 是对微针经皮给药测试的常用技术手段之一。然而，利用 OCT 对 微针经皮给药测试也存在一些问题。微针的长度一般在 50~1500μm 之间，药物 颗粒的粒径为数微米， 要求成像系统同时具有高分辨率和大焦深。 而传统的 OCT 系统采用高斯光束照射样品， 虽然采用短焦物镜可以获得小的光斑尺寸，但相应 的焦深很短，超出焦深区域的光斑尺寸会迅速增大， 降低成像质量。 贝塞尔光束 可以在远大于瑞利距离的范围内保持与高斯光束相同的光斑尺寸，能够同时满足 高横向分辨率和大焦深的要求。 本论文从微针经皮给药的测试需求出发， 利用圆 环达曼光栅产生的贝塞尔光束照射样品， 解决了传统 OCT 系统横向分辨率与焦 深相互制约的问题。 主要工作包括以下两个方面： 1. 优化了基于圆环达曼光栅产生贝塞尔光束的方法。 将圆环达曼光栅与空间滤 波器、 4f 透镜系统相结合，利用圆环达曼光栅的一级衍射光产生贝塞尔光束， 具有入射光能量利用率高等优点。 利用光学仿真软件 VirtualLab 对上述贝塞 尔光束的产生过程进行仿真， 通过优化空间滤波器的环缝宽度等参数，改变 贝塞尔光束中心光斑沿轴向的光强分布， 提高了贝塞尔光束的质量，为实现 在大成像深度范围内保持高横向分辨率的 OCT 系统奠定了基础。 2. 设计并搭建了一套基于圆环达曼光栅产生的贝塞尔光束照明的扫频 OCT 系 统。 经测试， 该系统的 A-scan 成像速率为 50kHz， 纵向分辨率约为 7.3μm （组织内）， 有效焦深为 1.68mm，焦深区域内的横向分辨率均高于 4μm。 利用该 系统对实心微针、 可溶性微针刺入皮肤后成像。 从获得的 OCT 图像中可清 晰观察到微针的边缘、刺入皮肤的深度和产生的微通道，并观察到了微通道 的关闭过程以及可溶性微针的溶解过程。 实验结果表明， 该系统能够满足微 针经皮给药的测试需求。; Transdermal drug delivery by microneedles is one of the ways to increase the efficiency of transdermal absorption of drugs. It uses micron-scale needles to penetrate the skin and create channels for drug delivery. In the process of drug delivering, the microneedles will not reach the nerve endings and blood vessels, so the process is painless and non-bleeding. And the microneedles are so small that they can hardly cause damage to skin. This technology has become a research hotspot in the field of transdermal drug delivery in recent years. However, there are still some details that need to be further studied, such as the penetration depth of microneedles, the closing time of microchannels and the release behavior of drug particles. Optical coherence tomography (OCT) is a commonly used technique for testing the transdermal drug delivery by microneedles. It can detect the internal structure of the sample in real time and in vivo. However, there are some problems when OCT is used to image the progress of drug delivery. In general, the length of a microneedle is between 50μm and 1500μm, and the diameter of a drug particle is several micrometers. That means the imaging system needs to have both high resolution and large depth of focus. The traditional OCT system uses Gaussian beams to illuminate the sample and uses a short-focus objective lens to obtain a small spot size. But the corresponding depth of focus is very short, so the spot size beyond this area will increase rapidly, which will reduce the image quality. Bessel beams can maintain the same spot size as Gaussian beams in a range far larger than the Rayleigh distance, and thus can simultaneously meet the requirements of high lateral resolution and large depth of focus. In this dissertation, an OCT system with Bessel beams illumination is proposed to image transdermal drug delivery by microneedles. The Bessel beams are generated by a circular Dammann grating (CDG). And the problem that the lateral resolution and depth of focus in the traditional OCT system are mutually restricted is solved. The main contents of this dissertation are as follows: 1. The method of generating Bessel beams based on a CDG is optimized. The first-order diffracted light of CDG is used to generate Bessel beams by combining the grating with a spatial filter and a 4f lens system. It has an advantage of high energy efficiency of the incident light. The optical simulation software VirtualLab is used to simulate the above generation process of Bessel beams. By optimizing parameters such as the width of the annular slit of the spatial filter, the axial intensity distribution of the central spot of Bessel beams is changed, and the quality of Bessel beams is improved. This analysis lays the foundation for realizing an OCT system with high lateral resolution over large range of imaging depth. 2. A swept-source OCT system based on Bessel beams illumination generated by the CDG is proposed. The measured A-scan imaging rate in this system is 50kHz, the measured axial resolution is 7.3μm (in tissue), the effective depth of focus is 1.68mm and the lateral resolution in the depth of focus area is better than 4μm. The proposed system is used to image the solid microneedles and dissolving microneedles after inserted into the skin. The obtained OCT images show that the edge of microneedles, the penetration depth and the microchannels can be clearly observed. Besides, the closing progress of microchannels and the dissolving progress of dissolving microneedles are observed. The experimental results demonstrate that this system can meet the test requirements of transdermal drug delivery by microneedles
学科主题	光学工程
内容类型	学位论文
源URL	[http://ir.siom.ac.cn/handle/181231/31063]
专题	中国科学院上海光学精密机械研究所
作者单位	中国科学院上海光学精密机械研究所
推荐引用方式 GB/T 7714	宋思雨. 用于微针经皮给药测试的光学相干层析成像技术研究[D].

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