基于介电特性和电磁通量研究生物标记物精确测量模型

The dielectric property of biomarker solution plays an important role in the characterization of biosensor responses for microwave sensors, and it varies with the solution's shape, volume, and environment temperature and humidity. Until now, the research work based on microwave biosensors usually relies on the detection results to analyze and characterize the performance of the sensor, neglecting the interference introduced by the change of the dielectric properties during the measurement process of biomarker solution. Moreover, there is no theoretical reference for the usage of the solution volume. In our project, we propose a new method which regards the accurate detection of dielectric properties of biomarker solution and establishment of its numerical simulation model as the breakthrough point. Then, we are focusing to study the electromagnetic radiation characteristics exactly at the sensitive region of the microwave resonator, and analyze the relationship between the sensor performance with shape and volume of the tested solution, respectively. Next, combining with micro-nano fabrication technology, the measurement condition of the solution can be achieved with fixed-shape, fixed-volume, constant temperature and constant humidity. Finally, simulation model and the equivalent circuit during the accurate detection of biomarkers based on microwave resonator can be completed based on the analysis of electrical parameters and bio sensing performance. Furthermore, the above-mentioned accurate detection model is applied to five microwave devices that have been developed by our group, aiming to realize the accurate detection models of biomarker solutions by different kind of microwave devices. This project belongs to the practical and basic research involving microwave theory, biomedical, and other disciplines. It is intended to provide novel perspectives for microwave sensors that aims to accurately detect biomarker solution.

生物标记物溶液的介电特性在微波传感器表征生物响应的过程中起重要作用，该特性会随着溶液自身形状、用量、以及外界温度和湿度的影响而改变。目前基于微波生物传感器的研究工作往往依赖检测结果去分析和表征传感器性能，忽略了生物标记物溶液在检测时由于介电特性变化所引入的误差，且对于溶液的用量缺乏理论依据。本课题拟另辟蹊径，提出以生物标记物溶液的介电特性精确检测和数值仿真模型建立为突破口，研究微波谐振器敏感区域的电磁通量辐射特性，分析传感器性能与被检溶液形状、用量之间的关系，结合微纳加工工艺实现被检溶液定形、定量、恒温、恒湿的检测环境，完成基于微波谐振器精确检测生物标记物溶液的仿真模型和等效电路。最终将上述精确检测模型应用到本课题组已开发的五种微波器件中，实现多种微波器件对生物标记物溶液的精确检测模型。本项目属于微波原理、生物医学等学科交叉的应用基础研究，拟为微波传感器精确检测生物标记物溶液提供新思路。

生物标记物溶液检测结果的精确性、可靠性是微波传感器表征生物响应并诊断待测患者是否患有疾病的前提条件，与国民的日常医疗息息相关。在认真调研国内外同行在微波生物传感器领域的研究现状后，结合申请人的前期研究经历，我们发现，虽然微波生物传感器在应用层面获得很大进展，但是仍然面临严峻挑战——精确模型表征的缺失导致微波生物传感器的仿真、被检生物标记物溶液的用量、检测结果的精确性受到极大限制。为了解决上述问题，本项目开展了如下三方面的研究内容：.第一，精确检测被检生物标记物溶液的微波介电特性。本研究团队结合Cole-Cole表达式，对生物标记物溶液的复介电常数进行了数学模型建立。基于该模型，在微波谐振器的谐振频率下，我们能够对不同浓度的生物标记物溶液进行介电常数实部和虚部的数值关系表征，完成了被检生物标记物溶液（以葡萄糖溶液为例）的精确检测和等效电路建立，实现仿真结果与实测结果的高度匹配。上述研究内容发表SCI论文2篇;.第二，建立基于IPD谐振器检测葡萄糖溶液浓度的精确检测模型和等效电路。本研究团队利用LC型谐振器、双敏感区域型谐振器、可控中心频带型谐振器、以及贴片型谐振器的敏感区域电磁通量辐射特性，得到传感器性能（灵敏度和线性度）与溶液用量之间的关系，分析实现最优的溶液容量；进而结合加工工艺实现被检生物标记物溶液的定形、定量、恒温、恒湿的检测环境，消除外界因素对被检生物标记物溶液自身介电特性的影响，保证检测结果的精确性。上述研究内容发表SCI论文3篇，EI国际会议论文2篇，授权国内发明专利3项;.第三，基于本课题组开发的集成无源巴伦、天线双工器、电阻、以及电容器件，分析了不同微波器件表征生物传感响应的物理机制和性能优缺点，为基于微波传感器精确检测各种不同类型的生物标记物溶液提供新的思路和理论依据。此外，通过基于RFID概念的微波生物传感器，为生物标记物溶液的非接触式测量提供了可行方案。上述研究内容发表SCI论文5篇。