CN1316005C - System for detecting in vitro growth and metabolism status of cells - Google Patents
System for detecting in vitro growth and metabolism status of cells Download PDFInfo
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- CN1316005C CN1316005C CNB2005100245809A CN200510024580A CN1316005C CN 1316005 C CN1316005 C CN 1316005C CN B2005100245809 A CNB2005100245809 A CN B2005100245809A CN 200510024580 A CN200510024580 A CN 200510024580A CN 1316005 C CN1316005 C CN 1316005C
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Abstract
The present invention relates to a system for detecting the in-vitro growth and the metabolism state of cells, which is used for the technical field of cell engineering, and the system for detecting the in-vitro growth and the metabolism state of cells comprises a culture liquid supplying unit, a cell culture unit and a data receiving treating apparatus. The system for detecting the in-vitro growth and the metabolism state of cells has the connection mode that the culture liquid supplying unit is connected with the data receiving treating apparatus by a data transmission line, and the cell culture unit is connected with the data receiving treating apparatus by the data transmission line. The present invention provides a supplying system composed of the constant culture liquid and dissolved gas, and the system for detecting the in-vitro growth and the metabolism state of cells can quantitatively detect O2 and nutritive substances consumed by the cells within particular time and the change of pH. A plurality of biologic reactors are connected in parallel in the same detecting unit, and a detected value can be the general average value best showing the growth state of the cells. The system for detecting the in-vitro growth and the metabolism state of cells collects various detecting electrodes into a whole and provides the information of the growth of the cells as much as possible.
Description
Technical field
This invention relates to a kind of detection system that is used for the cell engineering field, specifically is a kind of system for detecting in vitro growth and metabolism status of cells.
Background technology
Cell can effectively react its growth conditions under environment in vivo at external growth metabolism, now existing increasing test is tested the situation that may take place in vivo of simulating with cell at external growth, differentiation, aging, apoptosis and pharmacological toxicology, thereby make us further understand the essential property of cell and help the pharmacology and the toxicologic detection of medicine newly developed, for a clinical trial phase provides foundation.But the now domestic external pharmacological toxicology test of carrying out mostly also adopts device static, off-line that the various data that can not provide cell to characterize in real time, and the complex steps that detects are provided.
Find by prior art documents, people such as H.G.Koebe are at " Toxicology " 2000, (the external toxicology in the liver cell bio-reactor-extracellular acidification rate in target cell system hints the substrate conversion of liver cell mediation to " In vitro toxicology in hepatocyte bioreactors-extracellularacidification rate (EAR) the in a target cell line indicates hepato-activatedtransformation of substrates " that delivers on the 154:31-44, " toxicology ") in the literary composition, proposed a kind of system that is used to detect at the cell in-vitro growth and metabolism status, this system is by airing system, cell culture system detection system three parts of unifying are formed.Though this filling system constantly has the input of nutrient solution and gas, can't provide a kind of homogeneous nutrient solution to get the hang of, be unfavorable for the gas that consumed when the detection by quantitative nutrient solution is flowed through cell and culture etc.This device does not detect pH, O behind the cell of flowing through
2, glucose, glutamine and generation the variation of amount of lactic acid, and these just are the of paramount importance parameters of reacting cells growth metabolism state.
Summary of the invention
The objective of the invention is to overcome deficiency of the prior art, a kind of system for detecting in vitro growth and metabolism status of cells is provided, make its plenum system that constant nutrient solution and gas dissolved component are provided, the O that energy detection by quantitative specified time inner cell is consumed
2And nutritive substance, and the variation of pH; A plurality of bio-reactors in parallel in same detecting unit, make the value that records be can the reacting cells growth conditions population mean; Compile multiple detecting electrode in one, the information that the cell growth is provided as much as possible.
The present invention is achieved by the following technical solutions, the present invention includes: nutrient solution feed unit, cell culture unit and data receiving processor, its mode of connection is: the nutrient solution feed unit links to each other with data receiving processor by data transmission line, and cell culture unit links to each other with data receiving processor by data transmission line.Described nutrient solution feed unit comprises: air compressor, the oxygen gas steel cylinder, the one 0.2 μ m nuclepore membrane filter, the 2 0.2 μ m nuclepore membrane filter, T tube, the 3 0.2 μ m nuclepore membrane filter, container for storing liquid, container for storing liquid water-bath layer, gas distributor, magnetic stir bar, magnetic stirring apparatus, initiating terminal detecting electrode and peristaltic pump, its mode of connection is: the oxygen gas steel cylinder, the one 0.2 μ m nuclepore membrane filter and air compressor, the 2 0.2 μ m nuclepore membrane filter links to each other with T tube by the silica gel pneumatic tube successively, and T tube is connected with the air intake of container for storing liquid by the silica gel pneumatic tube; Container for storing liquid is surrounded by container for storing liquid water-bath layer outward, inserts the initiating terminal detecting electrode on the liquid storage tank deck; The ventage of the 3 0.2 μ m nuclepore membrane filter and container for storing liquid is connected by the silica gel pneumatic tube; The air intake of container for storing liquid is terminal to link to each other with gas distributor by the silica gel pneumatic tube; Magnetic stirring apparatus is in the container for storing liquid bottom, and the container for storing liquid inner bottom part is equipped with magnetic stir bar; Numerous initiating terminal detecting electrodes are connected with data receiving processor by data transmission line; Peristaltic pump is between the liquid outlet and cell culture unit of container for storing liquid.
Perforation on the described liquid storage tank deck, the liquid storage tank deck is provided with air intake, ventage, liquid outlet.
Described initiating terminal detecting electrode or pH electrode, or dissolved oxygen electrode, or glucose electrode, or glutamine electrode, or lactic acid electrode.
Described cell culture unit comprises: water-bath base, water-bath lid, detection groove, terminal detecting electrode, waste liquid cylinder, the 4 0.2 μ m nuclepore membrane filter, reactor assembly.Detect between the liquid outlet of the liquid inlet of groove and the container for storing liquid in the nutrient solution feed unit, between the liquid inlet of reactor assembly and detection groove and detect between the liquid inlet of the liquid outlet of groove and waste liquid cylinder and all link to each other with the silica gel tubing; Outside reactor assembly, water-bath base and water-bath cover and constitute an almost airtight water-bath overcoat together, in the whole reactor system is coated on; Detecting groove is connected with the terminal detecting electrode; The ventage of waste liquid cylinder links to each other with the silica gel pneumatic tube with the 4 0.2 μ m nuclepore membrane filter.
Described reactor assembly comprises T bottle, T bottle cap and splitter box, the liquid outlet of the container for storing liquid in the inlet of splitter box and the nutrient solution feed unit links to each other by the silica gel tubing, also link to each other by the silica gel tubing between the inlet of the outlet of splitter box and T bottle and between the liquid inlet of the outlet of T bottle and detection groove, the T bottle cap is located on the T bottle.
Perforation on the described detection groove.
Described terminal detecting electrode or pH electrode, or dissolved oxygen electrode, or glucose electrode, or glutamine electrode, or lactic acid electrode.
The floorage of described T bottle is 25cm
2
The ventage of container for storing liquid makes the pressure of the inside and outside gas of container for storing liquid keep constant, and the 3 0.2 μ m nuclepore membrane filter is guaranteed can not bring external source to pollute when interior gas of container for storing liquid and ambient atmos exchange; Magnetic stirring apparatus is in the container for storing liquid bottom, and the container for storing liquid inner bottom part is equipped with magnetic stir bar, guarantees uniform gas-liquid distribution in the container for storing liquid.Oxygen gas steel cylinder and air compressor both provided a certain proportion of all gases dividing potential drop for container for storing liquid, satisfied the demand of cell to dissolved oxygen and other gases, airborne CO
2Can prevent the fluctuation of pH again within the specific limits.Numerous initiating terminal detecting electrodes provide the data of detailed nutrient solution, help some index and adjust when unusual, and provide foundation to gas and nutraceutical consumption for the final specified time inner cell of measuring.The T bottle cap is made by nontoxic plastics, covers on the T bottle, is used for cell inoculation and cell cultivation process and takes a sample temporarily; The T bottle is difficult for excessive, gets floorage 25cm
2Be advisable, help cell and cover with fast, and save substratum.The ventage of waste liquid cylinder makes the pressure of the inside and outside gas of waste liquid cylinder keep constant, and the 4 0.2 μ m nuclepore membrane filter is guaranteed inner aseptic.The terminal detecting electrode provides flow through composition behind the cell of nutrient solution, according to the data that the initiating terminal detecting electrode provides, can calculate cell to gas and nutraceutical consumption, thereby infer the upgrowth situation of cell.
When the present invention works, air and O that air compressor and oxygen gas steel cylinder produce
2Enter after filtering in the container for storing liquid nutrient solution, under agitation mixed evenly with whole nutrient solution, the data of reading pH, dissolved oxygen, glucose, glutamine and lactic acid that the initiating terminal detecting electrode records by data receiving processor.Nutrient solution is pumped in the reactor assembly by peristaltic pump, by splitter box nutrient solution is transported to respectively in several isolated relatively T bottles, nutrient solution is crossed the T bottle with controlled velocity flow very slowly, data receiving processor is read the data of pH, dissolved oxygen, glucose, glutamine and lactic acid that the terminal detecting electrode records, by the processing and the calculating of numerical value, deduce the growth conditions of cell in a certain period.Because nutrient solution constantly at stream, constantly getting by data, so finally can obtain the panorama sketch of a cell growth.If add certain medicine in nutrient solution, what then obtain is exactly the growing state of cell under this kind drug effect.
The invention has the beneficial effects as follows: provide a kind of nutrient solution of relative homogeneous to get the hang of, monitor nutrient solution in real time by numerous detecting electrodes simultaneously, make the difference of terminal detecting electrode and initiating terminal detecting electrode can accurately reflect cell, greatly reduce the chance that error produces dissolved oxygen in the nutrient solution and nutraceutical consumption; A plurality of T flask culture cells in parallel can increase difference in reactor assembly, reduce the requirement of counter electrode tolerance range, reduce cost, and the average of cell growth can be provided again, the general upgrowth situation of reflection cell; The growth metabolism situation of numerous pH, dissolved oxygen, glucose, glutamine and the comprehensive investigation cell of lactate detection electrode can obtain the data of maximum in easy test once, help efficient cheap carry out clinical before test cell line.
Description of drawings
Fig. 1 is a structural representation of the present invention
Fig. 2 is a bioreactor system structural representation of the present invention
Embodiment
Shown in Fig. 1-4, the present invention includes: nutrient solution feed unit 1, cell culture unit 2 and data receiving processor 3.Its mode of connection is: nutrient solution feed unit 1 links to each other with data receiving processor 3 by data transmission line, and cell culture unit 2 links to each other with data receiving processor 3 by data transmission line.Described nutrient solution feed unit 1 comprises: air compressor 4, oxygen gas steel cylinder 5, the one 0.2 μ m nuclepore membrane filter 6, the 2 0.2 μ m nuclepore membrane filter 7, T tube 8, the 3 0.2 μ m nuclepore membrane filter 9, container for storing liquid 10, container for storing liquid water-bath layer 11, gas distributor 14, magnetic stir bar 15, magnetic stirring apparatus 16, initiating terminal detecting electrode 17 and peristaltic pump 19, its mode of connection is: oxygen gas steel cylinder 5, the one 0.2 μ m nuclepore membrane filter 6 and air compressor 4, the 2 0.2 μ m nuclepore membrane filter 7 links to each other with T tube 8 by the silica gel pneumatic tube successively, and T tube 8 is connected with the air intake 12 of container for storing liquid 10 by the silica gel pneumatic tube; The container for storing liquid 10 outer container for storing liquid water-bath layers 11 that are surrounded by, container for storing liquid 10 tops are gone up and are inserted initiating terminal detecting electrode 17; The ventage 13 of the 3 0.2 μ m nuclepore membrane filter 9 and container for storing liquid 10 is connected by the silica gel pneumatic tube; The air intake 12 terminal silica gel pneumatic tubes that pass through of container for storing liquid 10 link to each other with gas distributor 14; Magnetic stirring apparatus 16 is in container for storing liquid 10 bottoms, and container for storing liquid 10 inner bottom parts are equipped with magnetic stir bar 15; Numerous initiating terminal detecting electrodes 17 are connected with data receiving processor 3 by data transmission line; Peristaltic pump 19 is between the liquid outlet 18 and cell culture unit 2 of container for storing liquid 10.
Perforation is gone up on described container for storing liquid 10 tops, and container for storing liquid 10 tops are provided with air intake 12, ventage 13, liquid outlet 18.
Described initiating terminal detecting electrode 17 or pH electrode, or dissolved oxygen electrode, or glucose electrode, or glutamine electrode, or lactic acid electrode.
Described cell culture unit 2 comprises: water-bath base 20, water-bath lid 21, detect groove 22, terminal detecting electrode 25, waste liquid cylinder the 26, the 4 0.2 μ m nuclepore membrane filter 29, reactor assembly 30, detect between the liquid outlet 18 of the liquid inlet 23 of groove 22 and the container for storing liquid 10 in the nutrient solution feed unit 1, reactor assembly 30 and detect between the liquid inlet 23 of groove 22 and detect the liquid outlet 24 of groove 22 and the liquid inlet 27 of waste liquid cylinder 26 between all link to each other with the silica gel tubing; Outside reactor assembly 30, water-bath base 20 and water-bath lid 21 lump together and constitute an airtight water-bath overcoat, in whole reactor system 30 is coated on; Detecting groove 22 is connected with terminal detecting electrode 25; The ventage 28 of waste liquid cylinder 26 links to each other with the silica gel pneumatic tube with the 4 0.2 μ m nuclepore membrane filter 29.
Described reactor assembly 30 comprises T bottle 33, T bottle cap 36 and splitter box 37.The liquid outlet 18 of the container for storing liquid 10 in the inlet 31 of splitter box 37 and the nutrient solution feed unit 1 links to each other by the silica gel tubing, between the outlet 32 of splitter box 37 and the inlet 34 of T bottle 33 and the outlet 35 of T bottle 33 and detecting between the liquid inlet 23 of groove 22 also link to each other by the silica gel tubing; T bottle cap 36 is located on the T bottle 33.
Perforation on the described detection groove 22.
Described terminal detecting electrode 25 or pH electrode, or dissolved oxygen electrode, or glucose electrode, or glutamine electrode, or lactic acid electrode.
The floorage of described T bottle 33 is 25cm
2
Claims (5)
1. system for detecting in vitro growth and metabolism status of cells, comprise: nutrient solution feed unit (1), cell culture unit (2) and data receiving processor (3), nutrient solution feed unit (1) links to each other with data receiving processor (3) by data transmission line, cell culture unit (2) links to each other with data receiving processor (3) by data transmission line, described nutrient solution feed unit (1) comprising: oxygen gas steel cylinder (5), peristaltic pump (19), it is characterized in that, also comprise: air compressor (4), the one 0.2 μ m nuclepore membrane filter (6), the 2 0.2 μ m nuclepore membrane filter (7), T tube (8), the 3 0.2 μ m nuclepore membrane filter (9), container for storing liquid (10), container for storing liquid water-bath layer (11), gas distributor (14), magnetic stir bar (15), magnetic stirring apparatus (16) and initiating terminal detecting electrode (17), oxygen gas steel cylinder (5), the one 0.2 μ m nuclepore membrane filter (6) and air compressor (4), the 2 0.2 μ m nuclepore membrane filter (7) links to each other with T tube (8) by the silica gel pneumatic tube successively, T tube (8) is connected with the air intake (12) of container for storing liquid (10) by the silica gel pneumatic tube, the outer container for storing liquid water-bath layer (11) that is surrounded by of container for storing liquid (10), insert initiating terminal detecting electrode (17) on container for storing liquid (10) top, the ventage (13) of the 3 0.2 μ m nuclepore membrane filter (9) and container for storing liquid (10) is connected by the silica gel pneumatic tube, the air intake (12) of container for storing liquid (10) is terminal to link to each other with gas distributor (14) by the silica gel pneumatic tube, magnetic stirring apparatus (16) is in container for storing liquid (10) bottom, container for storing liquid (10) inner bottom part is equipped with magnetic stir bar (15), numerous initiating terminal detecting electrodes (17) are connected with data receiving processor (3) by data transmission line, and peristaltic pump (19) is between the liquid outlet (18) and cell culture unit (2) of container for storing liquid (10);
Described cell culture unit (2) comprising: water-bath base (20), water-bath lid (21), detect groove (22), terminal detecting electrode (25), waste liquid cylinder (26), the 4 0.2 μ m nuclepore membrane filter (29) and reactor assembly (30), between the liquid inlet (23) of detection groove (22) and the liquid outlet (18) of container for storing liquid (10), all link to each other between the liquid inlet (23) of reactor assembly (30) and detection groove (22) and between the liquid inlet (27) of the liquid outlet (24) of detection groove (22) and waste liquid cylinder (26) with the silica gel tubing, outside reactor assembly (30), water-bath base (20) and water-bath lid (21) lump together and constitute an airtight water-bath overcoat, in whole reactor system (30) is coated on, detect groove (22) and be connected with terminal detecting electrode (25), the ventage (28) of waste liquid cylinder (26) links to each other with the silica gel pneumatic tube with the 4 0.2 μ m nuclepore membrane filter (29); Described reactor assembly (30) comprising: T bottle (33), T bottle cap (36), splitter box (37), the inlet (31) of splitter box (37) links to each other by the silica gel tubing with the liquid outlet (18) of container for storing liquid (10), also link to each other by the silica gel tubing between the outlet (32) of splitter box (37) and the inlet (34) of T bottle (33) and between the liquid inlet (23) of the outlet (35) of T bottle (33) and detection groove (22), T bottle cap (36) is located on the T bottle (33).
3. system for detecting in vitro growth and metabolism status of cells according to claim 1 is characterized in that, described initiating terminal detecting electrode (17) is a pH electrode, or dissolved oxygen electrode, or glucose electrode, or the glutamine electrode, or the lactic acid electrode.
4. system for detecting in vitro growth and metabolism status of cells according to claim 1 is characterized in that, described detection groove (22) is gone up perforation.
5. system for detecting in vitro growth and metabolism status of cells according to claim 1 is characterized in that, described terminal detecting electrode (25) is a pH electrode, or dissolved oxygen electrode, or glucose electrode, or the glutamine electrode, or the lactic acid electrode.
6. system for detecting in vitro growth and metabolism status of cells according to claim 1 is characterized in that, the floorage of described T bottle (33) is 25cm
2
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2005100245809A CN1316005C (en) | 2005-03-24 | 2005-03-24 | System for detecting in vitro growth and metabolism status of cells |
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| Application Number | Priority Date | Filing Date | Title |
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| CNB2005100245809A CN1316005C (en) | 2005-03-24 | 2005-03-24 | System for detecting in vitro growth and metabolism status of cells |
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| CN1687390A CN1687390A (en) | 2005-10-26 |
| CN1316005C true CN1316005C (en) | 2007-05-16 |
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| CNB2005100245809A Expired - Fee Related CN1316005C (en) | 2005-03-24 | 2005-03-24 | System for detecting in vitro growth and metabolism status of cells |
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| CN102199536A (en) * | 2010-03-23 | 2011-09-28 | 上海坤巨科技发展有限公司 | Apparatus and method for monitoring cell quantity or cell proportion during dynamic stem cell differentiation |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1632573A (en) * | 2004-12-23 | 2005-06-29 | 上海交通大学 | On-line biological aspect detecting system of cell reactor for terrestrial plant and seaweed |
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| CN1632573A (en) * | 2004-12-23 | 2005-06-29 | 上海交通大学 | On-line biological aspect detecting system of cell reactor for terrestrial plant and seaweed |
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Granted publication date: 20070516 Termination date: 20110324 |