Micro-fluidic chip for high-throughput screening of blood brain barrier drug permeability and preparation method of micro-fluidic chip

Abstract

The invention relates to a micro-fluidic chip, which is applicable to researches on blood brain barrier drug permeability and high-throughput screening. The chip is prepared from elastic polydimethylsiloxane by virtue of a molding method. The chip, which is of a three-layer structure, comprises an array of nine groups of parallel micro-reaction units, wherein each of the micro-reaction units is composed of an upper cell culture chamber layer, a lower cell culture chamber layer and a microporous membrane layer, and each of the micro-reaction units comprises a chip micro-electrode and a fluid circulating pipeline. By continuously injecting a culture solution to the cell culture chambers, a fluid state in blood vessels can be simulated, so that a fluid environment is closer to a real internal environment of human body. By virtue of the chip micro-electrodes, electrical impedance signals are collected, and the physiological activity situations of the cell layers in the chip are monitored in real time. Drug molecules, which penetrate through the microporous membranes and the cell layers, deposit in the fluid circulating pipeline on the lower part of the chip and are eluted by virtue of the pipeline, and then membrane-permeable drugs can be collected for subsequent analysis. The micro-fluidic chip disclosed by the invention, compared with an existing method, can reflect blood brain barrier permeability of drugs, and the micro-fluidic chip can conduct high-throughput screening on nine drugs in a targeted mode in one time.

Description

technical field [0001] The invention belongs to the field of biomedical detection and analysis, in particular to a microfluidic chip used for high-throughput screening of blood-brain barrier drug permeability. Background technique [0002] The Blood Brain Barrier (BBB) ​​is a layer between blood and brain tissue that is selective for the permeability of substances. It is composed of endothelial cells, continuous basement membrane and astrocyte foot plate. Intermittent film formation. Normally, the blood-brain barrier acts as a hindrance to substances, allowing only gas molecules and fat-soluble molecules with relatively small molecular weights to pass through, which is beneficial to protecting brain tissue from damage and stabilizing the internal environment of the nervous system. However, this feature also makes it difficult for more than 95% of drugs to penetrate the blood brain and enter the central nervous system, making it difficult to exert drug effects, which greatly...

AI Technical Summary

Problems solved by technology

Currently available drug permeability assay methods mainly include in vivo evaluation and in vitro evaluation, both of which have many defects (1) In vivo evaluation, that is, in vivo analysis of drug molecules that pass through the blood-brain barrier The concentration of drugs in the blood-brain barrier is low, making it difficult to carry out accurate quantitative analysis, and the operation of detection in vivo is extremely complicated

(2) In vitro evaluation, that is, using a cell model that has common characteristics with the blood-brain barrier structure as the research object, but the existing models are often difficult to simulate the real internal environment in vivo (such as the fluid environment in the vascular lumen), and it is difficult to analyze The physiological activity of the model is monitored

At present, microfluidic chips and electrical impedance signal acquisition methods are used to simulate the real physiological environment of the human blood-brain barrier, especially the research on the dynamic blood-brain barrier with three-dimensional functional structure and the ability to screen high-throughput drug permeability still blank

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