Broadband microfluidic dielectrometry of biochemical liquids based on microwave precision measurement technique

高损耗材料复介电常数的精确测量，特别是在微波范围内，对生物流体的监测至关重要。尽管有许多可用的测量技术，但缺乏可靠的方法来对小体积生物流体进行微波表征。因此，开发新的方法是非常重要的，这些方法允许i)直接测量液体的电磁特性，ii)开发一种方法来表征温度低于0°C的最小体积从1 μ L到1 nL的液体，以及iii)表征具有高损耗切线的液体。解决这一问题具有很高的科学性和应用价值。然而，对此类有损流体测量的准确性和灵敏度的关键挑战尚未得到解决。因此，直接测量复介电常数具有特殊的意义。目前，基于同轴线或金属波导的非谐振方法得到了广泛的应用。然而，与谐振方法所需的非常小的体积相比，它们的灵敏度低，需要大量的流体。该项目旨在发展生物流体微波介电测量的科学原理，以便在低于0°C的温度下灵敏、直接地测量小体积损耗流体的复杂介电常数。这里的重点是一种能够实现高度精确测量的技术。我们之前的研究表明，这些问题可以通过特殊设计的低语通道模式（WGM）介质谐振器和微流体/纳米流体来解决。此外，将开发一种基于微流体的宽带方法作为参考方法，其特点是灵敏度优化，同时测量体积最小。本文的主要任务是：1)研究设计和制造用于小体积损耗液体微波研究的新型测量单元的理论基础；2)解决从测量结果确定复介电常数的反电磁问题。在这里，将开发具有新测量细胞的介电计原型，并将对最重要的生物液体（白蛋白，葡萄糖，细胞色素C， DNA水溶液等）进行测试测量。该项目的成功完成为生物和医学领域的新型介电测量开辟了前景。

The precise measurement of the complex permittivity of highly lossy materials, especially in the microwave range, is of central importance for the monitoring of biological fluids. Despite a multitude of measurement techniques available, there is a lack of reliable approaches for microwave characterization of biological fluids in small volumes. Therefore, it is extremely important to develop novel methods that allow i) direct measurements of the electromagnetic properties of the liquids, ii) to develop a method to characterize liquids in smallest volumes from 1 µL to 1 nL at temperatures below 0°C, and iii) to characterize liquids with a high loss tangents. The solution of this problem is of high scientific and application-oriented importance. Nevertheless, the crucial challenges to the accuracy and sensitivity of such measurements of lossy fluids have not been solved yet. Therefore, direct measurements of complex permittivity is of special significance. Today, the non-resonant methods based on coaxial lines or metal waveguides are widely used. However, they have low sensitivity and require large amounts of fluid compared to the very small volumes that is required for resonant methods.This project aims to develop scientific principles of microwave dielectrometry on biological fluids that allow sensitive, direct measurements of the complex permittivity of small volume lossy fluids at temperatures below 0°C. The focus here is on a technique that enables highly accurate measurements. Our previous studies show that the problems can be solved using specially designed whispering gallery mode (WGM) dielectric resonators and microfluidics/nanofluidics. In addition, a broadband method based on microfluidics will be developed as a reference method, which is characterized by optimized sensitivity while minimizing the measurement volume. Here the main tasks are explained: i) study of the theoretical basis for the design and fabrication of new types of measurement cells for microwave studies of lossy liquids of small volumes, ii) solving the inverse-electromagnetic problem in determining the complex permittivity from the measurement results. Here, a dielectrometer prototype with new measuring cells will be developed and test measurements will be performed on the most important biological fluids (albumin, glucose, cytochromes C, aqueous solutions of DNA, etc.).The successful completion of this project opens perspectives for a new type of dielectrometry in biology and medicine.