Microfluidic chip based on nanometer drug delivery system screening 3D solid tumor model and preparation method and application thereof

A microfluidic chip and three-dimensional entity technology, which is applied in drug screening, biochemical equipment and methods, compound screening, etc., can solve the problems of accuracy and reliability of analysis results, simple models, and poor integration of drug screening, etc., to achieve easy The effect of mass production, high-throughput detection, and miniaturization

Active Publication Date: 2017-11-21
SHENZHEN GRADUATE SCHOOL TSINGHUA UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] In summary, the introduction of the international cutting-edge microfluidic chip technology into the drug efficacy evaluation research of nano-medicine can overcome t

Method used

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  • Microfluidic chip based on nanometer drug delivery system screening 3D solid tumor model and preparation method and application thereof
  • Microfluidic chip based on nanometer drug delivery system screening 3D solid tumor model and preparation method and application thereof
  • Microfluidic chip based on nanometer drug delivery system screening 3D solid tumor model and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Example Embodiment

[0074] Embodiment 1 The structure of the chip of the present invention

[0075] The chip of the present invention is composed of a PDMS substrate and a cover sheet which are bonded together. Its structure is figure 1 As shown, the structure of the cover sheet is three parallel channels, and the parallel channels are connected by connecting channels. Among them, there are microchannels formed by drug perfusion and monolayer blood vessels (1), connecting channels of extracellular matrix (2), and microchannels with 14 "U"-shaped groove structures formed by three-dimensional tumor multicellular spheroids (3) ; The substrate has a shallower parallel channel that facilitates cell capture. The micro-tissue formed by the invention is very similar to the solid tumor micro-environment in the body, and the penetration of the drug in the micro-tissue can be observed in real time. Toxicity study. Cells that have undergone drug toxicity studies can flow out of the microchannels for subs...

Example Embodiment

[0076] Example 2 Production of a chip of the present invention with PDMS as a substrate and a cover sheet

[0077] (1) Put the silicon wafer into concentrated H 2 SO 4 / H 2 O 2 (3 / 1) The solution was slightly boiled for 30 minutes, taken out after cooling, rinsed with deionized water until neutral, sonicated with ethanol for 5 minutes, and heated on a heating plate for 30 minutes.

[0078] (2) A thin layer of SU-8 photoresist is applied on the silicon wafer, and the thickness of the adhesive layer is about 50 μm by controlling the speed of the glue rejection. will have figure 2 The mask of the structure is attached to the silicon wafer, and ultraviolet light passes through the mask to expose the photoresist. Another spin on this silicon wafer with a thickness of about 50 μm will have image 3 The mask of the structure is attached to the silicon wafer, and is subjected to secondary exposure with ultraviolet rays, and the unexposed part is dissolved with a developing solu...

Example Embodiment

[0081] Example 3 Using the chip prepared in Example 2 to form three-dimensional solid tumor microtissues

[0082] (1) If figure 1 , the channel (2) of the chip obtained by the present invention is perfused with basement membrane extract (BME) gel to simulate extracellular matrix, and then the channels (1) and (3) are modified with 1% (w / v) polyvinyl alcohol (PVA). ), preventing cells from sticking to PDMS.

[0083] (2) Set the concentration to 1×10 5 tumor cells / mL are perfused into the channel (3), so that the cells are uniformly and effectively captured in the "U"-shaped groove, and uniform tumor multicellular microspheres are formed after culturing for 48 hours.

[0084] (3) Set the concentration to 5×10 4 1 / mL human umbilical vein endothelial cells (HUVECs) flow into channel (1), place the chip vertically to make the cells grow on the BME glue, and place the chip horizontally after 2 hours to remove excess cells in the channel. Since BME has adhesion factors and growth f...

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Abstract

The invention discloses a microfluidic chip based on a nanometer drug delivery system screening 3D solid tumor model and a preparation method and the application thereof. The microfluidic chip consists of a substrate and a cover plate which are bonded together, wherein the cover plate structurally comprises three parallel microchannels, which are mutually connected and include a microchannel (1) for drug infusion and monolayer angiogenesis, an extracellular matrix connecting channel (2), and a microchannel (4) formed by three-dimensional tumor multicellular spheres and having many U-shaped groove structures (3); the substrate has a parallel channel (5) which facilitates cell capture. The microfluidic chip can achieve real-time monitoring of targeted delivery of the nanometer drug delivery system and online evaluation of drug toxicity at the same time, so that the drug evaluating efficiency is greatly improved; in addition, the microfluidic chip has better tumor simulating capability and provides more accurate data for preclinical drug evaluation; furthermore, the microfluidic chip platform has the advantages of small reagent dosage, low cost, simultaneous analysis of a large number of samples and the like, and has a relatively good drug screening application prospect.

Description

technical field [0001] The invention relates to the technical field of microfluidic chips, in particular to a microfluidic chip for a three-dimensional solid tumor microenvironment for nano drug delivery system screening. Background technique [0002] Malignant tumors are major diseases that seriously threaten human life and health. According to recent data, there are 10 million new cases worldwide each year, and more than 6 million people die of malignant tumors. In 2015, the number of cancer patients in my country was nearly 4.3 million, ranking first in the world, and the mortality rate accounted for 22.3% of the global total, and showed a continuous growth trend [1]. The emergence of nano drug delivery system provides a new gospel for the treatment of malignant tumors. The nano drug delivery system can effectively solve the problems of poor water solubility and easy degradation during the transportation process in the body. It can effectively improve the circulation ti...

Claims

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Application Information

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IPC IPC(8): B01L3/00C12M1/34C12M3/00
CPCB01L3/502707B01L2300/0887B01L2300/12C12M23/12C12N2503/02G01N33/5011G01N2500/10
Inventor 蒋宇扬高丹陈永丽
Owner SHENZHEN GRADUATE SCHOOL TSINGHUA UNIV
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