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Micro-fluidic chip for preparation of liposome by multiple emulsion method, and manufacturing method of micro-fluidic chip

A chip and emulsion technology, applied in the field of biomedicine, can solve the problems that cannot meet the size requirements of nano-drug carriers, and achieve the effects of good economy and practicability, high encapsulation efficiency, and easy processing and preparation

Active Publication Date: 2017-01-25
SHANGHAI JIAO TONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] The existing chip design is limited to the preparation of micron-scale particles, which cannot meet the size requirements of nano-drug carriers

Method used

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  • Micro-fluidic chip for preparation of liposome by multiple emulsion method, and manufacturing method of micro-fluidic chip

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0057] The preparation method of double emulsion preparation chip

[0058] The preparation method of double emulsion preparation chip of the present invention may comprise the following steps:

[0059] (1) Transfer the microchannel structure of the double emulsion preparation chip to the film mask plate, which is divided into a first layer mask plate and a second layer mask plate; wherein, the first layer includes a filter structure 1 and a first layer mask plate The mixing part 2; the second layer includes an outer water phase pipeline 3, an intermediate phase pipeline 4, an inner water phase pipeline 5, a W / O emulsion forming cavity 6, an outer water phase sampling part 7, an intermediate phase sampling part 8, an inner Water phase sampling part 9, second mixing part 10, W / O / W emulsion forming channel 11, double emulsion collecting part 12;

[0060] (2) Carry out the first layer of photolithography, control the height of the first layer, and obtain the template after the fi...

Embodiment 1

[0088] Embodiment 1 double emulsion preparation chip and its obtaining method

[0089] 1-1: The chip prepared by double emulsion of the present invention, the structural diagram can be found in figure 1 .

[0090] 1-2: The preparation method of the double emulsion preparation chip may include the following steps:

[0091] (1) Transfer the microchannel structure of the microfluidic chip to a film mask, which is divided into a first layer mask and a second layer mask; wherein, the first layer includes a filter structure 1 and a first layer The mixing part 2; the second layer includes an outer water phase pipeline 3, an intermediate phase pipeline 4, an inner water phase pipeline 5, a W / O emulsion forming cavity 6, an outer water phase sampling part 7, an intermediate phase sampling part 8, an inner Water phase sampling part 9, second mixing part 10, W / O / W emulsion forming channel 11, double emulsion collecting part 12;

[0092] (2) The first layer of photolithography:

[009...

Embodiment 2

[0123] The preparation of embodiment 2 liposomes

[0124] 2-1: Prepare double emulsion chips with reference to the method in Example 1. The height of each channel structure in the first layer is 5 microns. Therefore, the height of the first mixing part 2 is 5 microns, and the height of the first mixing part 2 is 5 microns. The width is 40 microns. The height of each channel in the second layer is 50 microns, therefore, the height of the W / O emulsion forming channel 6 is 50 microns.

[0125] 2-2: Configuration of three-phase solution:

[0126] (1) Inner water phase: 2mM calcein, 50mg / ml poloxamer (molecular weight 8350) dissolved in PBS buffer;

[0127] (2) Intermediate phase: Dissolve EPC and cholesterol in chloroform at a molar ratio of 2:1, blow dry with nitrogen, and dry at room temperature for at least 2 hours; dissolve phospholipids in ethanol to prepare a 50mg / ml stock solution, and place it at -20°C For storage, when experiments are required, dissolve the stock solut...

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Abstract

The invention belongs to the technical field of biomedicine, and in particular relates to a micro-fluidic chip for preparation of liposome by a multiple emulsion method, and a manufacturing method of the micro-fluidic chip. The multiple emulsion preparation chip provided by the invention comprises a first mixing part and a W / O emulsifier forming cavity channel, wherein the first mixing part is used for mixing an inner aqueous phase and an intermediate phase; the height of the W / O emulsifier forming cavity channel is more than that of the first mixing part; liposome with different grain sizes can be obtained by directly controlling the height of the first mixing part and the height of the W / O emulsifier forming cavity channel and without specially controlling the flow velocity of the intermediate phase and the inner aqueous phase; when the height of the first mixing part and the height of the W / O emulsifier forming cavity channel are controlled in a proper range, the liposome with nano-scale grain size can be obtained. Furthermore, by adoption of the multiple emulsion preparation chip, the liposome with uniform grain size and high encapsulation efficiency can be obtained, processing preparation is facilitated, and high economic property and practicability are achieved.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and in particular relates to a microfluidic chip for preparing liposomes by double emulsion method and a manufacturing method thereof. Background technique [0002] Liposome is an artificial carrier similar to the structure of biological membrane. Phospholipid molecules have oil-water amphiphilicity. In water, the hydrophilic end faces outward and the hydrophobic end faces inward, forming spherical vesicles with bilayer membranes, with diameters ranging from tens of nanometers to tens of microns. Liposomes can be used as drug carriers, loaded with chemical drugs, gene drugs and proteins, etc., to achieve the purpose of slow release, targeting or improving drug stability. Traditional liposome preparation methods such as thin film dispersion method and ethanol injection method have very low encapsulation efficiency of water-soluble drugs. Although double emulsion method and reverse phase evapo...

Claims

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Application Information

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IPC IPC(8): B01L3/00A61K9/127B82Y40/00
CPCA61K9/1277B82Y40/00B01L3/5027B01L3/502707B01L3/50273B01L3/502753B01L2200/10B01L2200/0631B01L2300/166B01L2300/0861B01F33/30
Inventor 成玉莹陈剑徐宇虹李真珍
Owner SHANGHAI JIAO TONG UNIV