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Integrated terahertz superstructure nano-biochip and its application and method

A biochip and superstructure technology, applied in the field of medical detection, can solve the problems of inability to determine cell survival or apoptosis, limiting the clinical application of CTCs, lack of single-cell level detection sensitivity, etc., to improve sorting efficiency and sorting. Speed, effect of automated CTCs detection, portable CTCs detection

Active Publication Date: 2019-08-06
THE FIRST AFFILIATED HOSPITAL OF ARMY MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
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AI Technical Summary

Problems solved by technology

However, due to the small number of CTCs in peripheral blood, it is very difficult to accurately separate and detect them, thus limiting the clinical application of CTCs-related detection.
At present, traditional CTCs detection methods including immunomagnetic bead method, membrane filtration method, density gradient centrifugation method, flow cytometry, etc. have good detection sensitivity, but they also have complex sample processing, cumbersome operation process, and detection time. longer technical flaws
In order to solve the above problems, the CTCs detection chip technology based on the principle of microfluidics has recently appeared, that is, the inertial focusing effect in fluid dynamics is used for rapid CTCs sorting and detection. Although the detection speed is improved, the detection sensitivity is low.
To sum up, the current CTCs detection strategy often can only adopt a compromise solution, the high sensitivity method is usually not fast enough, and the fast analysis method is often not sensitive enough
In addition, the more critical problem faced by CTCs detection is that it is impossible to determine whether the detected cells are alive or apoptotic, and only functional cells can contribute to the formation of metastases
[0005] Aiming at problem 1: The microfluidic CTCs detection chip technology with higher sorting speed can be used for pretreatment of blood samples, but its sorting principle based on hydrodynamics makes its sorting efficiency low, and at the same time it plays a role in sorting The mismatch between the structure of the fluid pipeline and the detection spot diameter of the THz wave leads to the separation of the early sample pretreatment and subsequent THz detection steps, which makes it difficult to guarantee the authenticity of the judgment of the survival status of CTCs
[0006] For problem 2: the existing THz metamaterial sensing technology does not have the detection sensitivity at the single-cell level, and there is no conventional method to match the CTCs detection chip technology

Method used

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Embodiment 1

[0048] Embodiment 1. Integrated terahertz superstructure nano-biochip

[0049] An integrated terahertz superstructured nanobiochip for detection of circulating tumor cells with a structure such as figure 1 As shown, it includes a microfluidic filter membrane sorting chip structure 1 and a THz superstructure signal detection module 2, wherein the microfluidic filter membrane sorting chip structure 1 and the THz superstructure signal detection module 2 are connected through a channel 3, and in the channel A barrier valve II10 is arranged in the middle; the microfluidic filter membrane sorting chip structure 1 includes a filtration and incubation chamber 5, an inlet channel 9 arranged on the upper part of the filtration and incubation chamber 5 and an inlet channel arranged on the lower part of the filtration and incubation chamber. The outlet channel I8, the inlet channel 9 and the outlet channel I8 are respectively provided with a filter valve 4 and a barrier valve I7. The filt...

Embodiment 2

[0063] Embodiment 2, the detection of breast cancer cell suspension of different concentrations

[0064] For the detection of breast cancer cell suspensions with different concentrations, the specific steps are as follows:

[0065](1) Use cultured breast cancer MDA-MB-231 cells and normal human peripheral blood to configure tumor cell samples with different concentrations as CTCs model samples, and set the concentration gradient to 10-10 5 cell / ml;

[0066] (2) Open the filter membrane valve and barrier valve I, close the barrier valve II; inject the sample into the filtration and incubation chamber at a flow rate of 50 μl / min with a fluid injection pump, and filter out red blood cells;

[0067] (3) Close the filter membrane valve, open the barrier valve I, inject the gold nanoparticle solution containing the labeled antibody from the outlet channel I at a flow rate of 30 μl / min, and incubate the chip at 37°C for 60 minutes, so that the labeled antibody on the nanoparticle L...

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Abstract

The invention relates to an integrated terahertz superstructure nano-biochip as well as an application and a method thereof. The integrated terahertz superstructure nano-biochip comprises a micro-fluidic filter membrane sorting chip structure and a THz superstructure signal detection module, wherein the micro-fluidic filter membrane sorting chip structure and the THz superstructure signal detection module are connected by virtue of a channel which is provided with a barrier valve; the chip, which combines the principles of filter membrane sorting and antibody capture immobilization, has the advantages of being high in sorting efficiency and high in sorting speed; and by designing a micro-fluidic lumen and a terahertz superstructure detection array of specific size, and through a method of displacing ambient water molecules by fluorocarbon oil, the sensitivity of detection can be greatly improved, and the chip is applicable to THz detection of circulating tumor cells (CTCs); and the chip has important significance to integrated, automatic and portable detection of the CTCs.

Description

technical field [0001] The invention belongs to the field of medical detection, relates to an integrated terahertz superstructure nano biological chip, and also relates to the application and method of the biological chip. Background technique [0002] In the early stage of the formation and growth of primary epithelial tumors, tumor cells can spread to distant organs through the bloodstream. Such tumor cells in peripheral blood are collectively called circulating tumor cells (CTCs). Current studies believe that CTCs are the main biological basis for hematological metastasis of malignant tumors, and the number of CTCs is closely related to the prognosis of patients. When the number of circulating tumor cells in peripheral blood reaches a certain threshold, the probability of malignant tumor metastasis will increase greatly. If it is possible to predict that patients will develop metastases before metastases appear, more proactive treatment measures can be taken to greatly i...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12M1/34C12M1/12C12M1/00C12Q1/02G01N21/3581
CPCC12M23/16C12M33/14C12M41/36C12M47/04G01N21/3581G01N33/5005
Inventor 杨柯府伟灵杨翔
Owner THE FIRST AFFILIATED HOSPITAL OF ARMY MEDICAL UNIV
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