连续血糖监测中非均匀介质人体组织的射频动态响应机制研究

Diabetes, which is caused by deficiency of insulin secretion or impaired biological function, is a worldwide epidemic disease and it has become a serious threat to human health. Thus far, there is no cure for diabetes. To avoid diabetic complications, maintenance of blood glucose concentration within the physiological range through antidiabetic drugs or diet/sport adjustment is of great importance. Therefore, the frequent monitoring of blood glucose is an essential part of diabetic management. Noninvasive blood glucose monitoring (NBGM) based on radio-frequency (RF) signals provides a promising solution for glucose measurement with the advantages of painless, convenience, low cost and continuous monitoring. However, the RF sensing signal is affected by both the glucose and human tissues of sensing path. Therefore, the critical element of influencing the accuracy of glucose monitoring is that the blood component is complicated and the dynamic response mechanism of RF sensing signal to human tissues is ambiguous. In this proposal, we mainly focus on the response mechanism of blood to RF sensing signal based on our previous studies. Specifically, the Cole-Cole blood model with different glucose concentrations which considered other components of blood as the error factor will be established when the dielectric properties of different components of blood are measured, respectively. Subsequently, the blood component electromagnetic model will be built, and response characteristics of RF sensing signals will be explored based on the aforementioned electromagnetic model. In addition, the function between blood glucose concentration and response characteristics of RF will be investigated. We will clarify the dynamic response mechanism of blood component to RF sensing signals for continuous glucose monitoring. The contribution of this research proposal includes not only the electromagnetic models of blood component will be comprehensive studied, but also the significant theory of physiological signal sensing based on RF signals will be provided. We believe that this research proposal will promote the development of blood glucose monitoring technology and it will play an important role in diabetes screening and diagnosis.

糖尿病是由于体内胰岛素分泌缺陷或其生物作用受损所引起的代谢紊乱性疾病，是严重威胁人类健康的世界性公共卫生问题。目前，糖尿病尚无切实可行的根治方法，糖尿病患者被建议通过连续监测血糖浓度变化来及时调整口服降糖药物和胰岛素的用量或调整饮食运动等，进而控制血糖浓度在合理范围，预防或减轻并发症。基于射频的血糖监测技术具有无创、低成本、便捷、可连续监测等优势，是血糖连续监测发展的重要方向。然而，射频传感信号受血糖与传感路径上的非均匀介质人体组织的共同影响，血液成分的复杂性以及传感信号动态响应机制不明确是影响血糖浓度变化监测精度的关键因素。本项目在前期射频信号与人体生物效应研究的基础上，拟通过研究血液各成分的介电特性，建立一个以血液其他成分为误差因子的不同血糖浓度的血液介电特性Cole-Cole模型，根据所建立的Cole-Cole模型，有利于分析血液其他成分浓度变化引起的测量误差；结合Cole-Cole模型，建立血液成分电磁模型，探索基于该模型的射频传感信号的响应特性，明确血糖浓度与射频传感信号的函数表达式，为基于射频的血糖传感的研究提供更完善的建模基础。本项目的意义在于不仅对基于射频的连续血糖浓度变化监测技术中的血液成分进行了全面深入的电磁建模，还为基于射频的人体生理信号传感分析提供了重要的理论基础和学术价值。随着血糖监测在糖尿病患者日常生活中的日趋重要性，本项目的研究将有利于推动血糖监测技术的发展，在糖尿病的前期筛查、糖尿病诊断、血糖的实时检测等领域具有重要的研究意义。

无创血糖监测具有无疼痛、可连续监测、低成本等优势，是血糖监测技术发展的重要方向。无创血糖检测技术中，传感信号受血糖与传感路径上的人体组织的共同影响，传感信号响应机制不明确是影响无创血糖检测精度的关键因素。考虑到人体组织非均匀介质特性和时变特性，本项目对基于射频传感信号的无创血糖监测技术进行了研究，1）研究并建模了不同葡萄糖浓度的Cole-Cole模型，探索葡萄糖浓度以及血液容积变化对射频传感信号的影响；2）建立基于非均匀介质(血液、血管以及其他组织)的无创血糖监测模型，并采用时域有限差分法分析了模型中的电流密度分布情况；3）研究了一种高灵敏度的射频传感器结构。研究发现，在1kHz至1MHz频率，水溶液的相对介电常数对葡萄糖浓度变化不敏感。然而，水溶液的电导率与葡萄糖浓度具有良好的相关性。随着葡萄糖浓度的增加，水溶液的电导率几乎线性减少；通过体外和在体实验发现随着葡萄糖浓度的增大，阻抗差值在逐渐减小，初步验证了基于血液容积阻抗差对无创血糖监测的影响；数值仿真发现：随着血糖浓度的增大，血液中电流密度将减少；项目组设计了多种具有高场限制、灵敏度高、结构紧凑、灵活性好、尺寸小型化的新型传感器，所设计的高灵敏度高场约束的封闭式裂环传感器的敏感性达到82MHz/mgmL-1，血糖监测精度达到＜0.05 wt%。本项目的科学意义在于揭示了基于射频传感的无创血糖监测中，不同的组织会对血糖有不同的响应，人体的生理活动（血液容积变化）会带来血糖监测误差；通过高场约束提高射频传感器的血糖变化灵敏度能显著提高血糖监测精度。.在项目执行期内，发表学术论文9篇，其中SCI论文7篇，EI论文1篇，中文核心及其他1篇；申请发明专利2项，已培养硕士研究生1名，本科生2名，正在培养学生5名。本项目的顺利实施有利于促进无创血糖监测技术的发展，具有显著的社会和经济效益。