血液微循环的测量研究有着非常重要的临床诊断价值。现有的可用于血液微循环测量的光学多普勒技术可分为三大类: 激光多普勒技术、相干层析多普勒技术和光声多普勒技术。在介绍这三类技术的基本工作原理和主要特点的基础上, 简要分析了各类中最具代表性的前沿技术, 分别为激光多普勒宽场实时成像技术、光学相干层析多普勒微血管造影术和光声多普勒流速测量技术。对这些前沿技术的进一步发展和实际应用进行了展望。

Cancer (malignant tumor) is one of the serious threats to human life, causing 13% of all human deaths. A crucial step in the metastasis cascade of cancer is hematogenous spreading of tumor cells from a primary tumor. Thus, isolation and identification of cells that have detached from the primary tumor and circulating in the bloodstream (circulating tumor cells, CTCs) is considered to be a potential alternation to detect, characterize, and monitor cancer. Current methods for isolating CTCs are limited to complex analytic approaches that generate very low yield and purity. Here, we propose a high throughput 3D structured microfluidic chip integrated with surface plasmon resonance (SPR) sensor to isolate and identify CTCs from peripheral whole blood sample. The microfluidic velocity-field within the channel of the chip is mediated by an array of microposts protruding from upper surface of the channel. The height of microposts is shorter than that of the channel, forming a gap between the microposts and the lower surface of the channel. The lower surface of the channel also acts as the SPR sensor which can be used to identify isolated CTCs. Microfluidic velocity-field under different parameters of the arrayed microposts is studied through numerical simulation based on finite element method. Measurement on one of such fabricated microchips is conducted by our established optical Doppler tomography technique benefiting from its noninvasive, noncontact, and high-resolution spatialresolved capabilities. Both simulation and measurement of the microfluidic velocity-field within the structured channel demonstrates that it is feasible to introduce fluidic mixing and causes perpendicular flow component to the lower surface of the channel by the 3D structured microposts. Such mixing and approaching capabilities are especially desirable for isolation and identification of CTCs at the coated SPR sensor.

光学多普勒层析术(ODT)是一种高分辨、非侵入的生物医学成像手段,能同时得到组织的结构信息和组织内血管的流速信息。提出了一种新型的基于相位分辨技术的ODT三维矢量测速方法。在ODT系统样品臂的准直镜和聚焦透镜之间加入窄带相位片,形成三个不同的相位延迟,通过计算多普勒频移和不同相位延迟下的多普勒展宽,可得到毛细管内的三维矢量流场分布。对已知浓度的聚苯乙烯溶液进行了一系列不同角度和不同流速的实验,结果证明这种新型的ODT矢量测速方法可以较精确的实现三维矢量流速的测量。

谱域光学多普勒层析(ODT)技术相对于传统的时域ODT技术,具有更快的成像速度和更大的测速动态范围。发展了基于谱域ODT技术的绝对速度测量方法,该方法综合运用多普勒频移和多普勒展宽信息实现多普勒夹角的确定,进而实现流体绝对速度的测量。给出了谱域ODT中计算多普勒频移和多普勒展宽的理论分析,并对毛细玻璃管内聚苯乙烯小球水溶液的流速进行了实际测量,实验结果和期望值能很好吻合。最后展示了该方法在老鼠脑部血管流速测量中的应用。

光学多普勒成像(Optical Doppler tomography,ODT)是一种结合了光学相干层析成像技术(Optical coherence tomography,OCT)和多普勒流速仪的非侵入、非接触的成像技术,能够实现对高散介质组织内部的血管分布和血液流速的探测。阐述了基于数字希尔伯特变换的相位分离多普勒光学相干层析成像技术的工作原理,并且通过对玻璃毛细管和生物芯片微通道管中聚苯乙烯溶液流速的实验测量,准确测量管内微粒缓慢移动时的多普勒频移量,获得了玻璃管内和生物芯片微通道管中流速分布曲线,证实了所提方法的可行性。获取的多普勒图像具有较高的空间分辨力和速度分辨力,在未来的临床应用中有潜在的应用价值。