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CN-121991781-A - Physical and chemical sieve for circulating tumor cells and application thereof

CN121991781ACN 121991781 ACN121991781 ACN 121991781ACN-121991781-A

Abstract

The invention discloses a circulating tumor cell physicochemical sieve and application thereof, wherein the circulating tumor cell physicochemical sieve comprises a body, a reaction tank is arranged in the body, at least two liquid inlets are arranged at one end of the reaction tank, a liquid outlet is arranged at the other end of the reaction tank, a plurality of reaction areas are arranged between the liquid inlets and the liquid outlet, a plurality of microcolumns are arranged in each reaction area, and the intervals among the microcolumns in each reaction area are gradually reduced along the direction from the liquid inlet to the liquid outlet. The invention adopts a mode of combining physical blocking and chemical adsorption to sort the circulating tumor cells, the space between microcolumns in each reaction zone is gradually reduced, the screening of CTC cells is facilitated, the further observation and discrimination are also facilitated, the compatibility to various colorants is good, and the application range is wide.

Inventors

  • XIAO LEYI
  • SONG WENHUI
  • LI DONG
  • LIU YUANZHU
  • XU YUANHONG
  • HU GE
  • PAN HUIYUN
  • WANG NA
  • LI MAOLIN
  • WANG JUNLI

Assignees

  • 青岛言鼎生物医疗科技有限公司

Dates

Publication Date
20260508
Application Date
20241101

Claims (10)

  1. 1. A circulating tumor cell physicochemical sieve is characterized by comprising a body, wherein a reaction groove is arranged in the body, at least two liquid inlets are formed in one end of the reaction groove, a liquid outlet is formed in the other end of the reaction groove, a plurality of reaction areas are arranged between the liquid inlets and the liquid outlet, a plurality of microcolumns are arranged in each reaction area, and the distance between the microcolumns in each reaction area is gradually reduced along the direction from the liquid inlet to the liquid outlet.
  2. 2. The circulating tumor cell physicochemical sieve of claim 1, wherein the microcolumn spacing of the downstream reaction zone is 66% -80% of the microcolumn spacing of the upstream reaction zone in the adjacent two reaction zones in the direction from the liquid inlet to the liquid outlet.
  3. 3. The circulating tumor cell physicochemical sieve of claim 2, wherein the reaction zones comprise six reaction zones, and the micro-column spacing in each reaction zone is respectively 30-40 microns, 20-30 microns, 15-20 microns, 10-15 microns, 8-10 microns and 6-8 microns in sequence along the direction from the liquid inlet to the liquid outlet.
  4. 4. The circulating tumor cell physicochemical sieve of claim 3, wherein the micropillar spacing in each reaction zone is 30 microns, 20 microns, 15 microns, 10 microns, 8 microns, 6 microns, respectively, in sequence along the direction from the liquid inlet to the liquid outlet.
  5. 5. The circulating tumor cell physicochemical sieve of any one of claims 1-4, wherein the microcolumns in each reaction zone have a circular, or triangular, or hexagonal cross section.
  6. 6. The circulating tumor cell physicochemical sieve of any one of claims 1-4, wherein the cross-sectional shape and/or height of the microcolumns in each reaction zone are the same.
  7. 7. The circulating tumor cell physicochemical sieve according to any one of claims 1 to 4, wherein a support table is arranged at the bottom of the liquid inlet, a hollow space is arranged in the support table and is communicated with the reaction tank, the liquid inlet is communicated with the hollow space of the support table, and liquid entering through the liquid inlet enters the reaction tank through the hollow space of the support table.
  8. 8. The circulating tumor cell physicochemical sieve of any one of claims 1-4, wherein the liquid inlet comprises a first liquid inlet and a second liquid inlet, and a central line of the first liquid inlet and the second liquid inlet is parallel or coincident with a central line of the reaction tank in the length direction.
  9. 9. The circulating tumor cell physicochemical sieve of any one of claims 1-4, wherein the liquid outlet is provided with a driving device for driving the liquid to move from the liquid inlet to the liquid outlet.
  10. 10. Use of a circulating tumor cell physicochemical sieve according to any of claims 1-9 for sorting enriched circulating tumor cells.

Description

Physical and chemical sieve for circulating tumor cells and application thereof Technical Field The invention belongs to the field of analysis of circulating tumor cells, and particularly relates to a circulating tumor cell physicochemical sieve and application thereof. Background Circulating tumor cells (circulating tumor cell) are abbreviated CTCs, and tumor cells that enter human peripheral blood are generally referred to as circulating tumor cells. CTC detection measures CTCs existing in peripheral blood by capturing and detecting, and monitors the trend of CTC type and quantity change, so that tumor dynamics can be monitored in real time, treatment effects can be evaluated, and real-time individual treatment can be realized. However, the number of CTCs in peripheral blood is very small, and the number of CTCs in whole blood per milliliter of tumor metastasis patient is only 1-10, so how to sort and enrich CTCs from millions of white blood cells and billions of red blood cells becomes a main problem of analysis and identification. Along with the continuous deepening of the influence of the microfluidic technology on the cell biology and the advantages of the microfluidic technology in integrated sample pretreatment and blood component analysis, living cells can be controlled and sorted more gently, rapidly and consistently, the method is favorable for extracting information in liquid samples such as blood more accurately and efficiently, and is very suitable for detecting cells such as blood cells and cancer cells. In recent years, scholars at home and abroad acquire a series of achievements in the field of micro-fluidic sorting of tumor cells, and a micro-fluidic chip technology is becoming a main tool for cell sorting, so that the application of the micro-fluidic chip is expected to realize high-efficiency and high-purity detection of circulating tumor cells. The structure of the microfluidic chip directly influences the screening efficiency of the circulating tumor cells, and the current method for detecting the circulating tumor cells by using the microfluidic chip mainly comprises two steps of 1) a biological method based on different expression of specific proteins on the surfaces of CTCs and blood cells and using affinity recognition and capture, and 2) a physical method based on physical characteristic differences and using differences of some physical properties between the CTCs and the blood cells to separate, such as cell size, density, dielectric property, deformability and the like. For example, by circulating tumor cells and other cells using microfiltration, or by determining the lateral shift pattern and separating cells based on cell size. Due to the influence of chip structural design and the like, the existing mode still has the problems of low screening rate of circulating tumor cells, nonspecific adsorption of non-target cells, damage of the circulating tumor cells, poor enrichment effect, poor cell activity and the like, and the next culture and related experiments cannot be performed. In addition, in the existing microfluidic chip, the front end of the chip is blocked earlier by cell clusters formed by cell aggregation, so that the problem of influencing the dispersion of subsequent materials can interfere with subsequent observation, and a technician can hardly distinguish CTC cells. The present invention has been made in view of this. Disclosure of Invention The invention aims to solve the technical problem of overcoming the defects of the prior art and providing a circulating tumor cell physicochemical sieve and application thereof. The invention adopts a mode of combining physical blocking and chemical adsorption to sort the circulating tumor cells, the distance between microcolumns in each reaction area is gradually reduced, the effects of dispersing and screening the cells step by step can be achieved, the blocking of a stacked fuzzy observation field of view is avoided, the screening of CTC cells is facilitated, the further observation and the discrimination are also facilitated, the compatibility of various colorants is good, and the application range is wide. In order to solve the technical problems, the invention adopts the basic conception of the technical scheme that: The invention provides a circulating tumor cell physicochemical sieve which comprises a body, wherein a reaction groove is arranged in the body, at least two liquid inlets are arranged at one end of the reaction groove, a liquid outlet is arranged at the other end of the reaction groove, a plurality of reaction areas are arranged between the liquid inlets and the liquid outlet, a plurality of microcolumns are arranged in each reaction area, and the intervals among the microcolumns in each reaction area are gradually reduced along the direction from the liquid inlet to the liquid outlet. Further, in the direction from the liquid inlet to the liquid outlet, the distance between the microcolumns in the downs