Device and method for separating circulating tumor cells and their microemboli by dual-frequency standing wave acoustic field

Abstract

The invention discloses a device and method for separating circulating tumor cells and their microemboli by using a dual-frequency standing wave sound field. It is composed of the first piezoelectric ceramic and the second piezoelectric ceramic which are in contact with and located under the two flow channels to alternately generate a dual-frequency standing wave sound field; the liquid outlet of the first flow channel extends from the three-point line to both sides Two unequal-width first liquid outlets and second liquid outlets are formed, and the liquid outlet of the second channel extends from the three-point line to both sides to form two unequal-width third liquid outlets and the fourth liquid outlet, and a smooth transition between the first liquid outlet and the fourth liquid inlet; due to the use of cascaded two-stage channels, combined with the alternating action of the dual-frequency standing wave sound field, the separation of the sound field is improved. The precision and accuracy effectively ensure the activity of cells, and the separated cells have large throughput, smooth flow, high sensitivity, strong integration, good separation effect and high separation efficiency.

Description

technical field [0001] The invention relates to the field of separation devices and separation methods for circulating tumor cells and their microembolisms, in particular to a device and method for separating circulating tumor cells and their microembolisms by using a dual-frequency standing wave sound field. Background technique [0002] Circulating tumor cells refer to tumor cells that spread from tumor lesions into the peripheral blood circulation, and can develop into tumor metastatic lesions under certain conditions; while circulating tumor cell microthrombosis (clusters) are formed by the aggregation of two or more circulating tumor cells. It has been found that more than 50% of tumor metastases are caused by circulating tumor cell microthrombosis, and the proportion in breast cancer is as high as 97%; Clinically meaningful monitoring devices provide important evidence. [0003] The diameter of circulating tumor cells involved in this paper is generally ≥10 μm, and th...

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Problems solved by technology

[0004] 1) Passive screening scheme: mainly based on cell size, density, surface markers and other attributes to separate, common passive screening methods include filtration, density gradient centrifugation, circulating tumor cell marker screening and microfluidic structure-based However, the filtration method and the microfluidic structure-based screening method usually cause blockage and cell damage, which affects the subsequent culture, phenotypic identification and toxicological analysis of the isolated circulating tumor cells and microemboli. The separation efficiency of density gradient centrifugation is relatively low; while the screening method of circulating tumor cell markers depends on the phenotype of circulating tumor cells, usually based on EpCAM (epithelial cell antigen) to capture and separate, but circulating tumors of different tumor sources There are differences in the expression of EpCAM in cells, and the expression of this protein will change dynamically, so there may be false positives

[0005] 2) Active screening scheme: mainly based on the effect of external force (such as electric field force, acoustic field force, etc.) to achieve separation, common methods include dielectrophoresis method and acoustic wave method; the advantage of dielectrophoresis method is that it can separate cells below 1 μm , but due to the limitation of the dielectric electric field strength, the available dielectric force is relatively small, and the separation flux is not as good as the acoustic wave method; the acoustic wave method generates a standing wave sound field in the microchannel to act on the cells to be separated. The method is more suitable for separating particles and cells with a diameter of several microns to tens of microns; according to the way of generating sound waves and the way of sound wave propagation, the sound wave method is subdivided into the surface acoustic wave method and the bulk acoustic wave method: the surface acoustic wave method is convenient for designing the sound field , but the relative sound field strength is small; the sound field strength of the bulk acoustic wave method is large, but the common bulk acoustic wave method has only a single acoustic node, which limits the separation ability of the bulk acoustic wave method

[0006] Regardless of the passive screening scheme or the active screening scheme, the separation process of the existing separation devices and methods has not been realized in the original environment where the circulating tumor cells are located, and it is difficult to effectively ensure the activity of the cells, and provide a basis for the subsequent detection of cell metabolic activity, Multiple protein marker detection, culture and toxicology research provide guarantee

[0007] Therefore, the existing technology still needs to be improved and developed

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