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A method for preparing monodisperse freeze-dried microbubbles based on microfluidic technology and its application

A microfluidic, monodisperse technology, which is used in preparations for in vivo experiments, pharmaceutical formulations, echo/ultrasonic imaging agents, etc. effect, low efficiency of micro-bubble preparation, etc., to achieve the effect of green production process, reduce Oswald ripening effect, and reduce the risk of blocking capillaries

Active Publication Date: 2022-03-11
湖州里应生物科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Compared with this patent, their limitations are (1) the operation and maintenance of the microfluidic chip requires the user to have a certain professional knowledge and technical background and technical operation ability, (2) the preparation efficiency of the microbubbles of the single-channel microfluidic chip is low , according to literature reports, the production rate of a single-channel microfluidic chip for preparing microbubbles with a diameter of 5 microns is one million per second (Lab on a Chip 11(12), 2023-2029), then prepare 1mL containing 10 9 The solution of each microbubble needs 15~20 minutes, is difficult to respond to the instant demand of clinical application; It is negatively correlated with the flow rate of the fluid. To prepare smaller microbubbles, a higher liquid flow rate is required, resulting in a lower bubble concentration. However, in actual ultrasound contrast applications, it is usually difficult to provide a lower bubble concentration. Effective acoustic reflection; (4) In view of the low rate of microfluidic actual production of microbubbles, the stability of microbubbles is usually affected during the long process of preparation, collection, transfer and transportation, further reducing the The yield and use effect

Method used

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  • A method for preparing monodisperse freeze-dried microbubbles based on microfluidic technology and its application
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  • A method for preparing monodisperse freeze-dried microbubbles based on microfluidic technology and its application

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Embodiment 1

[0057] A method for preparing monodisperse freeze-dried microbubbles based on microfluidic technology, the preparation steps are as follows:

[0058] (1) Drawing: Use the engineering drawing software AutoCAD to design the microfluidic pipeline, which has a water phase inlet, an oil phase inlet, and a product collection outlet. The diameter of the inlet and outlet is 1 mm, the depth of the pipeline is 50 microns, and the width is 100 microns. ; The structure of the microfluidic pipeline is as figure 2 shown;

[0059] (2) Mold making: The lithographic template obtained in step (1) is projected and printed on the silicon wafer substrate in equal proportions using soft lithography, with a size ratio of 1:1. The pipeline is made of SU-8 2100 photoresist, the depth of the pipeline is 50 microns, and the width is controlled to 100 microns;

[0060] (3) Remove the mold: After mixing the dimethylsiloxane monomer and the curing agent in a ratio of 10:1, pour it on the silicon wafer t...

Embodiment 2

[0067] A glass capillary microfluidic technology method for preparing monodisperse freeze-dried microbubbles based on microfluidic technology. The preparation steps are as follows: (1) tube making: we use a round tube with a length of 2 cm, an inner diameter of 0.5 mm, and an outer diameter of 0.7 mm. Type glass capillary (CM Scientific) was used as the inner tube, and one end was stretched using a capillary stretching machine (P-97, Sutter Instrument Company) to form a streamlined constriction port with a port size of 0.1 mm; we used another one with a length of 5 cm, a square glass capillary (CM Scientific) with an inner side length of 0.7 mm and an outer side length of 1 mm was used as the outer tube. The inner and outer tubes are fully cleaned and dried before use.

[0068] (2) Assembly: Carefully insert the inner tube obtained in step (1) into the outer tube by about 5 mm, and connect the distal end of the inner tube, the junction of the inner and outer tubes, and the dis...

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Abstract

The invention discloses a method for preparing monodisperse freeze-dried microbubbles based on microfluid technology and its application. The method obtains a size-controllable monodisperse emulsion through microfluid rapid emulsification technology; after the obtained monodisperse emulsion is freeze-dried, the obtained hollow microspheres are the precursors of microbubbles; after the hollow microspheres are mixed with a buffer solution, the A monodisperse microbubble solution was obtained. This method utilizes microfluidic emulsification technology to prepare hollow microspheres as the precursor of microbubbles, and the obtained microbubble freeze-dried powder is convenient for transportation and storage. When used, it is not limited by the requirements of instruments, sites, and technical backgrounds of users. The size of the microbubbles is uniform, and the size of the microbubbles and the type of gas in the inner core can be adjusted by microfluidic technology. In animal clinical experiments, the monodisperse freeze-dried microbubbles of the present invention exhibit a stronger contrast effect than traditional polydisperse microbubble contrast agents. The experiment controllability of the present invention is strong, and the application field of the obtained microbubble is wide.

Description

technical field [0001] The invention belongs to the technical field of biological material application, and in particular relates to a method for preparing monodisperse freeze-dried microbubbles based on microfluid technology and its application. Background technique [0002] Micron-sized microbubbles (1-10m in diameter) have been widely used in the diagnosis of cardiovascular system and superficial visceral diseases and tumors (Kanaka Hettiarachchi et al Lab Chip, 7, 463-468 (2007)). Compared with traditional chemical-based ultrasonic contrast agents, microbubbles are not only non-toxic and have no side effects, but also provide clearer imaging contrast and higher signal-to-noise ratio. In some special cases, such as the diagnosis of ventricular fissures, it is difficult to find lesions with traditional chemical ultrasound contrast agents, but microbubble ultrasound contrast agents can provide obvious contrast effects (Mehmet Kaya et al, BubbleSci Eng Technol.2( 2), 33–40 ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K49/22
CPCA61K49/223
Inventor 徐江张磊
Owner 湖州里应生物科技有限公司