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On-line cell micro observation instrument for biochemical reactor

A technology of biochemical reactors and observers, applied in the field of online cell microscopic observers, can solve problems such as poor contrast and resolution, high cost of switching excitation wavelengths, complex light source drive controllers, etc., to improve contrast and resolution , simple structure and low manufacturing cost

Active Publication Date: 2007-11-14
SHANGHAI GUOQIANG BIOCHEMICAL ENG EQUIP CO LTD +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This scheme adopts the bright field illumination method, which has poor contrast and resolution of the image formed by the transparent cells; and because the high-speed camera must be used when the stirring speed of the reaction tank is fast, and there is no sampling device to limit the depth of field, so it is different from that in the figure. The solution shown in 1 cannot eliminate the effect on the depth of field; at the same time, because the light source uses a complex SLD (Super Light Diode), the light source drive controller is relatively complicated, so it is costly and difficult to replace the light source and switch the excitation wavelength

Method used

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  • On-line cell micro observation instrument for biochemical reactor
  • On-line cell micro observation instrument for biochemical reactor
  • On-line cell micro observation instrument for biochemical reactor

Examples

Experimental program
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Effect test

Embodiment 1

[0039] In order to verify the present invention, use a kind of on-line cell microscope observer for biochemical reactor of the present invention in microbial reactor to the observation application of recombinant yeast fermentation process

[0040] During the culture process, samples were taken every 2 hours for cell optical density (OD600) measurement, cell dry weight, off-line microscope blood cell count, and online cell microscope observer for automatic observation and counting. The results are shown in Table 1.

[0041] It can be seen from Table 1 that the online cell counting result of the online cell microscope is basically consistent with the cell optical density (OD600) and the cell hemocytometer counting results, but it is slightly larger in the later stage of culture. Each cell concentration and fermentation time were fitted with an exponential equation, and the linear correlation coefficient was the highest in the online cell microscope, which was basically consistent...

example 2

[0045] For verifying the present invention, use the on-line cell microscopic observer for biochemical reactor of the present invention to observe the application of the culture process of recombinant animal cells (HEK293) in mammalian cell reactors

[0046] During the fermentation process, samples were taken every 24 hours for off-line cell hemocytometer. The cell count results of the two are shown in Table 2. It can be seen from Table 2 that the results of the off-line blood cell count and the cell number count of the on-line cell microscopic observer are basically the same.

[0047] Table 5L Mechanically Stirred Reactor Culture HEK293 Cell Density Comparison

[0048] Time

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PUM

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Abstract

This invention involves an online cell microscopic observation instrument for biochemical reactor, including the main instrument of the observation, the objective lens, the observation window incident, sampling devices, external light source system. Its characteristics are: reflectance prism is installed between external light source and lens system. There is a reflecting mirror behind the objective lens and in the front of entrance window. Reflecting prism is placed in the front of annular aperture films. the upper side of the reflecting prism has a home or area array CCD image sensor. Sampling device includes sampling block, elastic components, a mobile device. The elastic element is installed between sampling block and the drive shaft of mobile devices. the gab between the front face of sampling block and observation entrance window develops the sampling pool. The external light source system of this invention can easily replace wavelength through different filter replacement; dark field of view at the same time lighting can improve resolution of observation instrument for the cells into the contrast of the image and resolution; and it is simple in structure, easy-to-use, manufacturing costs low.

Description

technical field [0001] The invention relates to an on-line cell microscopic observer, in particular to an on-line cell micromorphological observer applied to a biochemical reaction tank. Background technique [0002] When living cell culture is used for product production in the biological reaction process, cell growth and morphological changes are extremely important monitoring parameters. For a long time, the method of sampling from the tank was obtained by offline microscope observation. In recent years, with the advancement of electronic technology, images can be converted into digital signals for computer processing, thereby obtaining quantitative information on growth and morphological changes. However, the above method is only off-line interval sampling, lack of dynamic observation, especially in the large-scale cultivation process of animal cells, anti-bacterial contamination is the primary problem of process operation, so frequent sampling is impossible, resulting i...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N21/84C12Q1/04
Inventor 张嗣良张岳芳刘健王绍娟郭美锦贺莉清张恂张明袁旭军马文峰
Owner SHANGHAI GUOQIANG BIOCHEMICAL ENG EQUIP CO LTD
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