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On-line cell micro observation instrument for biochemical reactor

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

Active Publication Date: 2009-11-18
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, and the contrast and resolution of the image formed by the transparent cells are not good; and because the stirring speed of the reaction tank is fast, a high-speed camera must be used, and there is no sampling device to limit the depth of field, so it is different from the figure 1 As shown in the scheme, the effect on the depth of field cannot be eliminated; 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
Comparison scheme
Effect test

Embodiment 1

[0039] In order to verify the present invention, an online cell microscopic observer for biochemical reactors of the present invention is used to observe the fermentation process of recombinant yeast in microbial reactors.

[0040] During the culture process, samples were taken every 2 hours for cell optical density (OD600) measurement, cell dry weight, off-line microscope hemocytometer 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 with the off...

example 2

[0053] In order to verify the present invention, the on-line cell microscopic observer for biochemical reactors of the present invention is used to observe the culture process of recombinant animal cells (HEK293) in mammalian cell reactors.

[0054] 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.

[0055] Table 5L Mechanically Stirred Reactor Culture HEK293 Cell Density Comparison

[0056]

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PUM

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Abstract

The invention relates to an on-line cell microscopic observer for a biochemical reactor, comprising an observer main body, an objective lens, an observation incident window, a sampling device, and an external light source system; the feature is that a reflective prism is arranged between the external light source system and the objective lens , behind the objective lens, a reflector is arranged in front of the observation entrance window, an annular diaphragm is placed in front of the reflective prism, and a CCD or area array image sensor is arranged on the upper part of the reflective prism side; the sampling device is composed of a sampling block, an elastic element, and a mobile device, wherein, An elastic element is connected between the sampling block and the driving shaft of the moving device, and the gap between the front end of the sampling block and the observation incident window forms a sampling pool. The external light source system of the present invention can easily replace the wavelength by replacing different color filters; at the same time, the dark field illumination can improve the contrast and resolution of the image formed by the observer for cells; and it has simple structure, convenient use, and low manufacturing cost. low-level features.

Description

technical field [0001] The invention relates to an on-line cell microscope observer, in particular to an on-line cell morphology 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 in poor ob...

Claims

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Application Information

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Patent Type & Authority Patents(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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