基于净信号提取的差动式浮动基准测量方法及其在血液成分无创检测中的应用

As the variation in background is the biggest challenge in the human measurement and the floating reference can fulfill the relative measurement in vivo, it has great significance in the non-invasive sensing of blood components. However, its application is still restricted by some problems, such as the reference position varies with the wavelength and the scattering media, the reference signal is only used for simple correction. In the project, a differential floating reference measurement method is proposed based on the thorough analysis for the distribution and signal composition of diffuse reflectance. Then the net analyte signal (NAS) of component interested is extracted based on the subspace constructed by the reference signal and the two-dimensional correlation spectroscopy is combined with NAS projection to discriminate data validity. Four key questions are conducted: (1) the relationship between the reference signal in different wavelength is determined and thus the reference signal in multi-wavelength and different scattering system is received in fixed source-detector distance; (2) A differential floating reference measurement method which collect the diffuse reflectance at the reference position and its both sides simultaneously, is proposed to improve the signal noise ratio; (3) the net analyte signal of component interested is extracted based on the subspace constructed by the reference signal to improve the selectivity; (4) Two-dimensional correlation spectroscopy is combined with the net analyte signal orthogonal projection to remove the invalid data which is possible caused by the chance correlation factors in the measurement process, to further improve the specificity.

由于背景变异是在体测量最大的障碍，而浮动基准能够实现在体参考测量，因此对血液成分无创检测具有重要意义。但到目前为止，该方法的应用还存在基准位置随被测个体和波长变化、基准信息仅被用于简单修正等问题。在本课题中，通过对不同径向距离下漫反射光分布及其信息构成的深入分析，提出了一种差动式的浮动基准测量方法，并基于基准信息提取被测成分的净信号，最后结合二维相关光谱判断数据有效性。重点解决以下四个关键问题：（1）获得不同波长基准信息之间的关系，实现多波长基准信息在固定区域接收；（2）提出在基准环及其左右两侧同时检测的差动式浮动基准测量方法，提高检测信噪比；（3）研究基于基准信息构建背景变异子空间来提取被测成分净信号的方法，提高信号拾取的选择性；（4）研究二维相关光谱与净信号投影相结合剔除可能的时变偶然相关导致的无效数据，提高信号拾取的特异性。

由于背景变异是在体测量最大的障碍，而浮动基准能够实现在体参考测量，因此对血液成分检测具有重要意义。在本课题中，研究了一种差动式的浮动基准测量方法，并基于基准信息提取被测成分的净信号。研究内容包括：1）理论推导了浮动基准位置的存在性，基于同一介质中不同波长下基准信息之间的关系反推其他波长下的信息，实现在有限区域接收多波长及不同个体的基准信息。2）提出基于差动式的浮动基准参考测量方法来消除测量过程中的共性干扰，设计了相应的光纤探头、测量条件的保障措施和多波长光谱信号同步采集系统，确定了探头与参考物的最佳距离以及在体接触测量中的最佳接触压力范围。3）分析测量过程中的背景变异导致的光谱响应构成及其对葡萄糖预测精度的影响，采用基准信息构建不含被测成分变化信息的背景变异子空间，提出了一种基于NAS-VIP-SPXY-PLS的信号提取方法，并实验验证了差动浮动基准方法在消除在体测量过程中共性干扰的有效性，单人的预测误差能达到0.5-1.0mmol/L。 4）基于二维相关光谱分析了各种扰动下的二维光谱特征，提出了简化正交距离法以及三维坐标法剔除测量过程中时变偶然相关因素导致的异常光谱，并结合压力不敏感位置和温度不敏感位置等人体自身包含的内部基准消除生理背景干扰，提高了数据提取的特异性。