基于微流控芯片的微光电检测系统研究

发布时间：2018-01-13 05:28

本文关键词：基于微流控芯片的微光电检测系统研究　出处：《浙江大学》2016年博士论文　论文类型：学位论文

【摘要】：微流控芯片技术日益成熟,已经由科研阶段进入到实际的应用领域,相应的微流控检测技术随之得到了快速发展。本文主要是借助微流控技术平台,以生物样品为例,探讨开发适用于微弱生物信号检测的微光电检测系统。本文首先研究了微流控技术相关的检测手段和方法,针对荧光和吸光度这两种生物样品的常规检测方法,文中创新性提出了将荧光检测和吸光度检测联合应用在同一台设备内的系统方案。荧光和吸光度同台设备联合检测,能够最大限度的扩展微流控使用范围,在进行未知病毒或者生物样本进行检测时,可以使用吸光度扫描与荧光检测结合的方法,通过此方法,可以更加准确的进行生物分析和样本身份验证。此外,由于荧光和吸光度两种检测方式在可以在同一台设备上实现,不需要更换检测仪器,从而避免了人为操作误差。为了能够剔除微流控芯片材料本身产生的荧光和吸光度信号误差,本文又提出了对比光路检测方案。根据对比光路设计方案,在进行光学系统设计时,本文采取了系统分光与远心光学系统相结合的设计思路；在进行吸光度和荧光联合检测时,采用了变化工作距离的方法。此外,吸光度检测是基于特征波长特征吸收的原理,激发波长要求与检测物质相对应,所以系统需要动态改变波长,此系统改变波长是采用光机电结合技术,通过动态调整镜组间距的方法来实现。另外一方面,在进行吸光度时,由于微流控芯片光程超短,往往只有微米级,所以针对微流控芯片的吸光度检测,本文提出了将二次谐波检测技术应用于微流控生物检测领域,并为此进行了理论设计和实验验证。本文的另外一部分,主要是进行整体实验与结果分析,在实验装置中,从光学系统搭建过程研究到电路系统框架系统的研究都进行了相关介绍与说明。同时,关于与灵敏度患息相关的二次谐波技术,经过了多次的分析和改进。在进行激光诱导荧光样品实验中,由于扣除的材料本底等误差信号,与传统的微流控激光诱导荧光仪器相比,本文中的对比通道检测系统能使仪器的检测灵敏度提高2到3个数量级。此外,由于对比通道的检测能够剔除激光光源的光强变化,从而在提高灵敏度的同时提高了系统的检测基线稳定性。另外一方面,对于二次谐波技术应用于微流控吸光度检测进行了多次理论计算和样品测试。根据样品测试结果来看,在进行吸光度检测时,直接吸收不能检测出信号的情况下,此系统采用二次谐波频率检测的方法,仍然能够检测出很强的信号,从而验证了系统方案的可行性。整体实验结果表明,此系统拥有了激光诱导荧光与吸光度联合检测的能力,同时微流控芯片上的荧光检测技术和吸光度检测技术都得到了很大改善。
[Abstract]:Microfluidic chip technology has become more mature, from the stage of research into practical application, corresponding with microfluidic detection technology has been rapid development. This paper is mainly using microfluidic technology platform in biological samples, to explore the development of micro optical detection system for weak signal detection. Organisms are studied in this paper. Microfluidic technology related testing methods and methods for routine detection of fluorescence and absorbance of the two biological samples, this paper proposes innovative system scheme combined with fluorescence detection and absorbance detection in the same device. The combined detection of fluorescence and absorbance with the equipment, can be extended to maximize the use of microfluidic in the range of unknown viruses or biological samples, can use absorbance method combined with scanning and fluorescence detection, through this method, can be more With accurate biological analysis and sample authentication. In addition, the two ways of detecting fluorescence and absorbance can be achieved on the same machine, do not need to replace the testing instruments, so as to avoid human errors. In order to eliminate the microfluidic chip material producing fluorescence and absorbance signal error of this the comparison of optical detection scheme. According to the comparison of optical design scheme in optical system design, this paper adopts the design idea of the system combining light and telecentric optical system; the absorbance and fluorescence joint detection, using the method of changing working distance. In addition, the absorbance detection is the principle of absorption characteristics based on the characteristics of wavelength, excitation wavelength and detection of substances should be relative, so the system needs to dynamically change the wavelength, the wavelength is changed by optical electromechanical system combined with the technology, through the Method of dynamic adjustment of mirror group spacing to achieve. On the other hand, the absorbance, microfluidic chip optical ultrashort, often only micron, so for absorbance detection of microfluidic chip, this paper put forward two harmonic detection technology used in microfluidic detection field, and the theory of design and experimental verification. Another part of this thesis, mainly analysis the whole experiment and the results were in the experimental setup, build from the optical system research process research to the circuit system of the system are introduced in detail. At the same time, with about two harmonic sensitivity with related technology, through analysis and improvement for many times the laser induced fluorescence samples. In the experiment, the deduction of material of the bottom of the error signal, compared with the traditional micro fluidic laser-induced fluorescence instrument, compared in this paper Channel detection system can make the detection sensitivity of the instrument is increased by 2 to 3 orders of magnitude. In addition, the contrast detection channel can eliminate the intensity change of the laser light source, in order to improve the sensitivity and improve the detection of baseline stability system. On the other hand, the two harmonic technology conducted a number of theoretical calculation and test in microfluidic absorbance detection. According to the test result, the absorbance detection, direct absorption can not detect signal, this system uses two harmonic frequency detection method is still able to detect a strong signal, in order to verify the feasibility of the system. The experimental results show that this system have the ability of laser induced fluorescence detection and absorbance, and fluorescence detection technology and absorbance detection technology on microfluidic chip have been great Improve.

【学位授予单位】：浙江大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：TN492

【相似文献】