CN201817494U - Dynamic loading and circular perfusion bioreactor - Google Patents

Dynamic loading and circular perfusion bioreactor Download PDF

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Publication number
CN201817494U
CN201817494U CN2010202874750U CN201020287475U CN201817494U CN 201817494 U CN201817494 U CN 201817494U CN 2010202874750 U CN2010202874750 U CN 2010202874750U CN 201020287475 U CN201020287475 U CN 201020287475U CN 201817494 U CN201817494 U CN 201817494U
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China
Prior art keywords
piezoelectric ceramics
main body
sliding sleeve
loading
cabin
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Expired - Fee Related
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CN2010202874750U
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Chinese (zh)
Inventor
张西正
侍才洪
陈学忠
宁波
郭勇
李瑞欣
关静
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Institute of Medical Equipment Chinese Academy of Military Medical Sciences
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Institute of Medical Equipment Chinese Academy of Military Medical Sciences
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Abstract

The utility model belongs to the fields of bone tissue engineering and cell biomechanics, and relates to a dynamic loading and circular perfusion bioreactor comprising a main body, a sliding sleeve module and a three-dimensional cultivation chamber module, wherein the main body comprises a base, a lateral support plate and an upper support plate, and the lateral support plate is provided with a concaved chute; the sliding sleeve module comprises a sliding sleeve, piezoelectric ceramics, a lifting adjusting screw rod and a fastening screw rod and can stably slide up and down in the concaved chute, and the piezoelectric ceramics penetrate through the sliding sleeve; the three-dimensional cultivation chamber module comprises a cultivation chamber main body the upper surface of which is provided with a through hole through which the piezoelectric ceramics penetrate into the three-dimensional cultivation chamber, the movable end of the piezoelectric ceramics is connected with a loading rod; and the cultivation chamber main body is also provided with a liquid inlet hole and a liquid outlet hole externally connected with a peristaltic pump. The dynamic loading and circular perfusion bioreactor has the characteristics of simple operation, high practicability, good sterile sealing performance, high output accuracy of loading stress as well as timely and accurate data tracking and recording.

Description

Dynamic load and circulation perfusion bioreactor
Technical field
The utility model belongs to bone tissue engineer and cell biological mechanics field, is specifically related under a kind of dynamic cultivation that is used for tissue engineered bone and the research three-dimensional cultivation condition dynamic compressive strain to the bio-reactor of growth of cells such as mescenchymal stem cell, scleroblast, osteoclast, chondrocyte and differentiation influence.
Background technology
Studies show that of relevant in recent years biological tissue stress-growth relationship is from organ, be organized into the life movement at all levels such as cell, ubcellular and all carrying out certain mechanical environment.The pass of stress and growth ties up to and mainly shows two aspects on the cell levels: the biological behaviour of individual cells, as the influence of propagation, form and secreting function etc.; The influence of the global behavior of colony's cell tissue, as the enhancing of scleroblast and osteoclast function, osteocyte, scleroblast, osteoclast to influencing each other in the mechanical response process, mechanical signal conducts and expression of gene etc.Because internal milieu complexity, cells in vitro separation and Culture technology provides a kind of feasible research method for research cell physiological, pathological phenomenon, and utilize the organizational project principle, and under external three-dimensional cultivation condition, carry out stress to load, also be the important method in the present cyto-mechanics research.
The representational bio-reactor that uses in Tissue Engineering Study at present comprises (1) stirring type bioreactor; (2) rotating wall vessel bioreactor; (3) tubular fibre formula bio-reactor; (4) direct perfusion type bio-reactor; (5) stress loaded type bio-reactor etc., the mechanical environment under the simulation normal physiological conditions.But the real bio-reactor that is fit to tissue engineered bone is given mechanical loading in external long-term cultivation is very few, and they are very different with the patent of intending application.
Bio-reactor about the stress that is used for osseous tissue and engineered culture loads only has a small amount of document and patent report both at home and abroad; The power system that its dynamic stress or strain load also mainly is to adopt the stepper-motor class, and has many deficiencies, and is accurate inadequately as the track record of stress or strain loading and data; The perfusion that can't carry out under the real effectively long-term aseptic condition tissue culture is simultaneously cultivated; Practical Performance is poor, conventional efficient is low etc.Also all there is above-mentioned deficiency in the piezoelectric ceramics deceleration loading device of contriver's early development with the similar research and development product of external report.
The utility model content
The purpose of this utility model is the deficiency that overcomes existing mechanical stimulation type bio-reactor, and this device can be widely used in the research work of aspects such as organizational project, cell biological mechanics.
A kind of dynamic load and circulation perfusion bioreactor, comprise main body, sliding sleeve module and 3 D stereo are cultivated the cabin module, described main body comprises base, lateral bolster fagging and upper backup pad, the lower end of lateral bolster fagging is fixed on the base, the upper end is fixed with upper backup pad, on the lateral bolster fagging, offer the spill chute, described sliding sleeve module comprises sliding sleeve, piezoelectric ceramics, the lift adjustment screw rod, and fastening screw, sliding sleeve can slide up and down in described spill chute reposefully, one end of lift adjustment screw rod is installed on the upper backup pad by bearing, the lower end links to each other with sliding sleeve by screw thread, piezoelectric ceramics runs through sliding sleeve, and the rear end of piezoelectric ceramics is an inboardend, is fixed with rear end cap, fastening screw one end is connected in upper backup pad, the other end closely contacts with the piezoelectric ceramics rear end cap, and piezoelectric ceramics and piezoelectric ceramics servomechanism are electrically connected, and described piezoelectric ceramics servomechanism is used for applying frequency and the adjustable voltage of waveform to it; Described 3 D stereo cultivate the cabin module comprise upper surface offer the cultivation cabin main body of through hole, be connected cultivate the cabin bottom part body add the loading placement platform, piezoelectric ceramics extends through 3 D stereo by described through hole and cultivates in the cabin, and its movable end is connected with loading bar; Described cultivation cabin main body also offers the inlet opening and the fluid hole of external peristaltic pump.
The utility model adopts the dynamic compressive strain loading system of piezoelectric ceramics with Displacement Feedback, in conjunction with three-dimensional circulation perfused culture system, make up a kind of influence that the research trends compressive strain is grown, broken up cells such as mescenchymal stem cell, scleroblast, osteoclast, chondrocytes under the three-dimensional cultivation condition that both can be used for, can be used for the bio-reactor that the tissue engineered bone long-term dynamics is cultivated again.Whole bioreactor system has simple to operate, the practicality height, and the sterile seal performance is good, loads strain output accuracy height, timely, the characteristic of accurate of data tracking record.Technique effect is specific as follows:
(1) by the two-ways regulation of lift adjustment screw rod and fastening screw, both piezoelectric ceramics can be advanced to set position, can be locked again, eliminate loosening that backhaul because of screw rod produces, drift about when avoiding piezoelectric ceramics work;
(2) utilize bio-reactor of the present utility model, can constitute by 3 D stereo and cultivate the cabin module, cultivate the three-dimensional circulation perfused culture system of hyperchannel that liquid pool, multichannel bidirectional peristaltic pump and pipe connecting are formed, use the power unit of the adjustable multi-channel peristaltic pump of flow velocity as the circulation perfusion, can carry out perfusion to a plurality of cultivations cabin simultaneously, the long-term cultivation that both can be used for tissue culture also can be installed on carries out the stress loading on the piezoelectric ceramics deceleration loading device;
(3) loading power system adopts the intelligence encapsulation piezoelectric ceramics of configuration bit displacement sensor as loading power system, the organizational project culture that is regulated to by computer provides frequency, type (square wave, sine wave, choppy sea etc.), waveform that amplitude is adjustable, and the size of display frequency, displacement in real time, displacement accuracy reaches the thousandth of full stroke;
(4) the current limliting post has been controlled the circulating pathway of nutrient solution effectively, being used of current limliting post and loading bar, shutoff the nutrient solution path of on add loading, circulating, make nutrient solution realize circulation by the space that adds loading place, such design helps upgrading nutrient solution and control liquid level, make the cell that adds loading inside can fully absorb fresh nutrient solution and the metabolic product of eliminating, and can save the consumption of nutrient solution greatly;
(5) can avoid the weight of loading bar to be applied on the tissue culture again so that loading bar closely contacts with tissue culture by preloading spring;
(6) the piezoelectric ceramics deceleration loading device all adopts stainless material, has avoided getting rusty under the incubator environment, can reach good disinfection efficacy behind 75% alcohol wipe and ultra violet lamp, avoids polluting.
Description of drawings
Fig. 1 dynamic load and circulation perfusion bioreactor integral installation figure;
Fig. 2 main body and sliding sleeve topology view;
Fig. 33 D stereo is cultivated the cabin structure view;
Fig. 43 D stereo is cultivated the cabin sectional view.
Among Fig. 1-Fig. 4: 1 main body, 2 sliding sleeve modules, 33 D stereos are cultivated cabin module, 4 bases, 5 lateral bolster faggings, 6 threaded holes, 7 spill chutes, 8 upper backup pads, 9 lift adjustment screw rods, 10 fastening screws, 11 piezoelectric ceramics rear end caps, 12 piezoelectric ceramics, 13 piezoelectric ceramics movable ends, 14 wire casings, 15 through holes, 16 sliding sleeves, 17 open holess, 18 stainless steel press boxes, 19 glass ports, 20 gaskets, 21 stop nuts, 22 cross bars, 23 preloading springs, 24 loading bars, 25 guide paths, 26 cultivate the cabin main body, and 27 add the loading placement platform, 28 inlet openings, 29 current limliting posts, 30 add loading, 31 fluid holes.
Embodiment
The utility model is described in further detail below in conjunction with drawings and Examples.
Referring to Fig. 1, dynamic load of the present utility model and circulation perfusion bioreactor comprise: main body 1, and sliding sleeve module 2,3 D stereo is cultivated cabin module 3.
Referring to Fig. 2, main body 1 is by base 4, lateral bolster fagging 5, and upper backup pad 8 is formed.Lateral bolster fagging 5 has spill chute 7, make sliding sleeve 16 and lateral bolster fagging 5 four sides contact, and has guaranteed the structural strength and the levelness of sliding sleeve 16 traveling comforts, contact jaw.
Sliding sleeve module 2 mainly is made up of sliding sleeve 16, piezoelectric ceramics 12, lift adjustment screw rod 9, fastening screw 10.Piezoelectric ceramics 12 is cylindrical, piezoelectric ceramics rear end cap 11 links to each other with the inboardend of piezoelectric ceramics 12, piezoelectric ceramics 12 is placed in the through hole 15, piezoelectric ceramics rear end cap 11 closely contacts with the upper surface of sliding sleeve 16, moving of restriction piezoelectric ceramics 12, the supply lead of piezoelectric ceramics 12 and signal wire are connected to the piezoelectric ceramics servomechanism by wire casing 14, the piezoelectric ceramics servomechanism can apply frequency and adjustable load or displacement waveform (square wave, sine wave, the choppy sea etc.) voltage of waveform, realizes the displacement closed-loop control of piezoelectric ceramics 12 by inbuilt displacement sensor.Lift adjustment screw rod 9 one ends are installed on the upper backup pad 8 by bearing, and the other end links to each other with sliding sleeve 14 by screw thread, and rotation and lifting adjusting screw(rod) 9, its invariant position, sliding sleeve 14 are realized the adjusting of height up and down under the effect of worm drive.Fastening screw 10 1 ends link to each other with upper backup pad 8 by screw thread, and rotation fastening screw 10 can be regulated the length that it stretches out, and the other end closely contacts with piezoelectric ceramics rear end cap 11.By spill chute 7, lift adjustment screw rod 9, fastening screw 10 3 end in contact, effectively guaranteed the levelness of sliding sleeve 14, improve stability, eliminate the gap.
3 D stereo is cultivated cabin module 3 mainly by stainless steel press box 18, glass port 19, and gasket 20, stop nut 21, preloading spring 23, loading bar 24, guide path 25 is cultivated cabin main body 26, adds loading placement platform 27, inlet opening 28, current limliting post 29, fluid hole 31 is formed.Cultivate cabin main body 26 and have view port, view port is at first placed gasket 20, place glass port 19 then, put stainless steel press box 18 at last again, by being fastenedly connected of stainless steel press box 18 and cultivation cabin main body 26, realize the sealing of view port, this design helps dismounting and autoclave sterilization.Loading bar 24 is provided with cross bar 22, cross bar 22 can move up and down along guide path 25, stop nut 21 is above cross bar 22, with guide path 25 by being threaded, preloading spring 23 is installed on cross bar 22 and the upper surface of cultivating cabin main body 26, preloading spring 23 plays the effect of eliminating loading bar 24 weight, avoids the weight of loading bar 24 to be applied to and adds in the loading 30, and is particularly evident for the influence that adds loading that quality is softer.One end of loading bar 24 links to each other with piezoelectric ceramics movable end 13 by screw thread, the other end passes guide path 25 and enters and cultivate that the cabin is inner to be contacted with the upper surface that adds loading 30, rotary stopper nut 21 can be regulated loading bar 24 and add the degree that loading 30 contacts, the change in displacement of piezoelectric ceramics movable end 13 is transferred to by loading bar and adds in the loading 30, produces corresponding microstrain.Add loading placement platform 27 and the bottom of cultivating cabin main body 26 by being threaded, can be easy to place or take out and add loading by adding loading placement platform 27.Inlet opening 28 all is external to peristaltic pump with fluid hole 31, they are presented down diagonally opposing corner and distribute, current limliting post 29 and inlet opening 28 inside that is connected with fluid hole 31 offers the through hole that loading bar 24 is freely run through, through hole be inserted into cultivation when loading bar 24 during the cabin, current limliting post 29 with loading bar 24 shutoff the nutrient solution path of on add loading 30, circulating, then nutrient solution can only be realized circulation by the space that adds loading 30 places, such design helps upgrading nutrient solution and control liquid level, topmost purpose is that the cell that adds loading 30 inside can fully absorb fresh nutrient solution and get rid of metabolic product, simulation applies fluid shearing stress to adding loading 30, reaches the effect of dimensional culture.

Claims (3)

1. dynamic load and circulation perfusion bioreactor, comprise main body, sliding sleeve module and 3 D stereo are cultivated the cabin module, described main body comprises base, lateral bolster fagging and upper backup pad, the lower end of lateral bolster fagging is fixed on the base, the upper end is fixed with upper backup pad, it is characterized in that, on the lateral bolster fagging, offer the spill chute, described sliding sleeve module comprises sliding sleeve, piezoelectric ceramics, the lift adjustment screw rod, and fastening screw, sliding sleeve can slide up and down in described spill chute reposefully, one end of lift adjustment screw rod is installed on the upper backup pad by bearing, and the lower end links to each other with sliding sleeve by screw thread, and piezoelectric ceramics runs through sliding sleeve, the rear end of piezoelectric ceramics is an inboardend, be fixed with rear end cap, fastening screw one end is connected in upper backup pad, and the other end closely contacts with the piezoelectric ceramics rear end cap, piezoelectric ceramics and piezoelectric ceramics servomechanism are electrically connected, and described piezoelectric ceramics servomechanism is used for applying frequency and the adjustable voltage of waveform to it; Described 3 D stereo cultivate the cabin module comprise upper surface offer the cultivation cabin main body of through hole, be connected cultivate the cabin bottom part body add the loading placement platform, piezoelectric ceramics extends through 3 D stereo by described through hole and cultivates in the cabin, and its movable end is connected with loading bar; Described cultivation cabin main body also offers the inlet opening and the fluid hole of external peristaltic pump.
2. dynamic load according to claim 1 and circulation perfusion bioreactor, it is characterized in that, cultivating the limited fluidization tower of cabin main body internal fixing, its inside offers the through hole that loading bar is freely run through, inlet opening and fluid hole are presented down diagonally opposing corner and are distributed, and all pass the current limliting post and communicate with described through hole.
3. dynamic load according to claim 1 and circulation perfusion bioreactor, it is characterized in that, described loading bar, described cultivation cabin main body, offer guide path in it, described loading bar is provided with the cross bar that can move up and down along guide path, and the top of cross bar is provided with the fitting nut that is connected with guide path by screw thread, at cross bar and cultivate between the upper surface of cabin main body and be connected with preloading spring.
CN2010202874750U 2010-08-10 2010-08-10 Dynamic loading and circular perfusion bioreactor Expired - Fee Related CN201817494U (en)

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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101899393A (en) * 2010-08-10 2010-12-01 中国人民解放军军事医学科学院卫生装备研究所 Dynamic load and recirculating perfusion bioreactor
CN103756898A (en) * 2013-12-24 2014-04-30 浙江大学 Three-dimensional stress cell culture device capable of applying dynamic load
CN109370893A (en) * 2018-11-01 2019-02-22 刘延群 Biological culture reaction unit
CN109706079A (en) * 2018-12-11 2019-05-03 江苏理工学院 It is a kind of for simulating the flow cavity of flowing environment after bracket
CN111440717A (en) * 2020-04-26 2020-07-24 华南理工大学 Dynamic mechanical loading device based on orifice plate

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101899393A (en) * 2010-08-10 2010-12-01 中国人民解放军军事医学科学院卫生装备研究所 Dynamic load and recirculating perfusion bioreactor
CN103756898A (en) * 2013-12-24 2014-04-30 浙江大学 Three-dimensional stress cell culture device capable of applying dynamic load
CN103756898B (en) * 2013-12-24 2015-08-19 浙江大学 A kind of stressed culture apparatus of cell three-dimensional applying dynamic load
CN109370893A (en) * 2018-11-01 2019-02-22 刘延群 Biological culture reaction unit
CN109706079A (en) * 2018-12-11 2019-05-03 江苏理工学院 It is a kind of for simulating the flow cavity of flowing environment after bracket
CN109706079B (en) * 2018-12-11 2022-03-25 江苏理工学院 Flow cavity for simulating flowing environment behind bracket
CN111440717A (en) * 2020-04-26 2020-07-24 华南理工大学 Dynamic mechanical loading device based on orifice plate

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C17 Cessation of patent right
CF01 Termination of patent right due to non-payment of annual fee

Granted publication date: 20110504

Termination date: 20120810