CN101221166B - Cell strain loading device under three-dimensional cultivation condition - Google Patents
Cell strain loading device under three-dimensional cultivation condition Download PDFInfo
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- CN101221166B CN101221166B CN2008100173679A CN200810017367A CN101221166B CN 101221166 B CN101221166 B CN 101221166B CN 2008100173679 A CN2008100173679 A CN 2008100173679A CN 200810017367 A CN200810017367 A CN 200810017367A CN 101221166 B CN101221166 B CN 101221166B
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Abstract
The invention discloses a cell strain loading device under a three-dimensional culture condition, a power supply is connected to an electrode of a driving part of a piezoelectric ceramic plate by a drive line, and the electrode is connected with the piezoelectric ceramic plate; the piezoelectric ceramic plate is fixed on a base bottom by a fixed device of the ceramic plate, the back end of a displacement transfer plunger and a displacement output end of the piezoelectric ceramic plate are fixed together, a three-dimensional complex which is composed of a cell-scaffold is positioned at the central position of the bottom part of a culture small chamber, the left and the right are respectively connected with porous fixed material, one side of the porous fixed material is fixed on the wall of the culture small chamber, the other side of the porous fixed material is fixedly connected with the displacement transfer plunger; a laser probe is non-contact arranged at the back end of the transfer plunger and is connected with a computer for the detection of the front and back displacement of the transfer plunger. The invention can load amplitude and frequency and facilitate regulation without machine shutdown; the invention has good operability, high repeat precision, smooth mechanical loading and small error; furthermore, the invention can avoid magnetic field interference.
Description
Technical field
The present invention relates to a kind of determinator that is used for biomechanics Research, cell is accepted the loading experimental apparatus of mechanical stress stimulation under particularly a kind of three-dimensional cultivation condition.
Background technology
In recent years, increasing along with crossing research between life science and other subjects, the new branch of science that biomechanics is carried out quantitative examination as applied mechanics principle and method to the mechanics problem in the biosome becomes the focus of field of biology research gradually.Wherein cell is one of field, forward position of present biomechanics Research to the response investigations of mechanical stimulation.Yet because the human body internal milieu is extremely complicated, the comparatively difficulty that research also becomes in the body of this aspect.And multiple isolated cells culture technique provides possibility for the biological effect of studying mechanical stimulation on the cell aspect.Studies show that mechanical stimulation can cause cytoskeleton to produce deformation, cause the variation of skeleton arrangement, and then influence the many aspects such as mechanical property, adhesive force, propagation, differentiation of cellular morphology, cell self.
Many isolated cells Experiments of Machanics methods have been studied personnel's proposition and have been used for the research of biosome to the mechanism aspects such as response of mechanics factor, as substrate tension, four-point bending stretching, hydrostatic pressure and fluid shear stress stimulation separately, the combination of fluid shear stress etc.Also set up simultaneously the model that many mechanics load.Publication number is a kind of cyto-mechanics loading system that the Chinese patent of CN 1847847 discloses, this system is made of the culture chamber that the bottom is fixed with pellosil, can inoculating cell on the pellosil, hoisting gasbag is arranged at the pellosil bottom, by adjusting how many generation distortion of air bag internal gas,, pellosil produces planar equal-biaxial periodical pull stress or compressive stress thereby being out of shape.Though this device is simple to operate, volume is little, the distortion that external force produces air bag is closely related with the original pressure of its internal gas, is difficult to accomplish therefore that very accurate control air bag is out of shape; Secondly the deformation that cell receives in this device does not have direct detection system.Publication number be CN 1425905 patented invention a kind of four point bending cell mechanics loader, this device is by the rotation of stepper motor, drive drive screw and produce the front and back displacement, promote pressure head (two contact points respectively being arranged up and down) and load the culture plate that inoculation has cell, make culture plate and cell produce distortion with Tissue Culture Plate.This device controllability is good, the repeatable accuracy height, owing to need to use but device is comparatively complicated, and because the deformation difference of culture plate diverse location produces identical deformation so can not guarantee cell.Publication number be CN 1932510 patent disclosure a kind of charger of cell tensile, it passes through controller, the driver control stepper motor rotates, rotation is changed into the displacement of horizontal direction by screw mandrel, the pulling inoculation has the culture membrane of cell, make cell be subjected to the stretcher strain of horizontal direction, this device can make cell stressed comparatively even, accurately control stretching amplitude and frequency, stretching distance also can be regulated easily, but use stepper motor in this device as drive source, inevitably bring the interference in magnetic field, and magnetic field is still indeterminate at present as a kind of influence of physical factor pair cell, studies cell for us the response of mechanical stimulation is brought disturbing factor.
Above-mentioned three disclosed devices of patent all are based upon cell monolayer and cultivate on the basis, the cultured cell monolayer growth, comparatively convenient when carrying out as experiments such as morphologic observation, cell dyeings, but the residing solid space of cell under the shortage internal milieu, weakened influencing each other and acting on of iuntercellular autocrine, paracrine, therefore and the environment of body cell when being subjected to mechanical stimulation is 3 D stereo, should set up the research model of cell under the 3 D stereo condition during research aspect carrying out this.Publication number be CN 1567399 patent disclosure cardiac muscle cell's mechanical stimulation device under a kind of three-dimensional cultivation condition, this device utilizes method of tissue engineering to make up cell--the complex of collagen, form the dimensional culture environment of cell, by motor, flywheel, connecting rod and slide block the rotation of motor is become motion on the horizontal direction again, periodic cell--the complex of collagen that loads makes cell be subjected to mechanical stimulation.Though this device has been realized the three dimensional growth environment of cell, it drives the motor that produces magnetic field when still using work, and its adjusting that loads amplitude is needed to shut down, and brings inconvenience to operation; In addition, this device adopts too much mechanical drive, and also there is the wear problem in the long-term work in unavoidable noise and the heat of producing during work.
Summary of the invention
For overcome the prior art complex structure, have magnetic field, the deficiency of aspects such as disturbing factor such as heat; the invention provides cell or tissue strain loading device under a kind of three-dimensional cultivation condition; simple in structure; can not shut down and change parameters such as loading amplitude, frequency; avoid magnetic interference; the generation heat is low, is applicable to the mechanics loading experimental apparatus of cell under the three-dimensional cultivation condition.
The technical solution adopted for the present invention to solve the technical problems is: adopt piezoelectric ceramic piece as drive source, the three-dimensional complex that pair cell--porous support constitutes carries out mechanical stimulation.The present invention is primarily aimed at that pair cell carries out mechanical stimulation under the three-dimensional cultivation condition, comprises drive power supply for piezoelectric ceramics, piezoelectric ceramic piece drive part, cell culture unit and laser displacement sensor deformation test section.The piezoelectric ceramic piece drive part mainly is made of its core component piezoelectric ceramic piece, electrode, potsherd stationary installation, transmission plunger, porous immobilization material; Cell culture unit is made of substrate and cultivation cell; Laser displacement sensor deformation test section is made up of laser probe and computing machine.Power supply is connected to by drive wire on the electrode of piezoelectric ceramic piece drive part, and electrode links to each other with piezoelectric ceramic piece.By the potsherd stationary installation piezoelectric ceramic piece is fixed in the substrate, the displacement output terminal that plunger back-end and piezoelectric ceramic piece are transmitted in displacement is fixed together, front end be connected cell--the porous immobilization material that props up the three-dimensional complex that is configured to is fixed.Cell--a three-dimensional complex that is configured to is positioned at cultivates cell bottom center position, about connect the porous immobilization material respectively, the porous immobilization material of a side is fixed on to be cultivated on the little locular wall, the porous immobilization material of opposite side is fixedlyed connected with displacement transmission plunger.The laser probe noncontact is installed on the transmission plunger back-end, links to each other with computing machine, detects the front and back displacement of transmitting plunger.
As a preferred embodiment of the present invention, described piezoelectric ceramic piece adopts the bimorph of technology maturation, exportable big displacement.The electrode of piezoelectric ceramic piece drive part is positioned at the both sides of bimorph, closely is connected with potsherd, and the 3rd electrode drawn from potsherd middle layer copper sheet, and electrode is connected with drive power supply for piezoelectric ceramics.
As second kind of preferred version of the present invention, described piezoelectric ceramic piece adopts technology maturation, the convenient piezo-electric stack driver of buying, and can realize the cell bigger to hardness--the loading of porous support complex.The piezo-electric stack driver is fixed on the cell culture unit, and the displacement output terminal that plunger one end is fixed on driver is transmitted in displacement, the other end with is connected cell--prop up the porous immobilization material connection of the three-dimensional complex that is configured to.
Described porous immobilization material is not for producing Cytotoxic porosint, as porous polyethylene etc.
Cell culture unit adopts organic glass or polytetrafluoroethylmaterial material to make among the present invention, is easy to processing, also can sterilize easily simultaneously, prevents that possible pollution from taking place.
Principle of work of the present invention: drive power supply for piezoelectric ceramics provides the voltage of sinusoidal wave or other waveforms of piezoelectric ceramic piece or piezo-electric stack driver needs, the flexural deformation that piezoelectric ceramic piece produces or the anteroposterior position Mobile Communication of piezo-electric stack driver cross displacement transmission plunger and are delivered to cell--on the porous support complex, cell--porous support complex two ends condense together with the porous immobilization material respectively, so that can produce compression or stretcher strain when plunger seesaws, and then make cell produce periodic deformation.By with transmit the laser probe that the plunger noncontact is installed, detect the displacement that transmits plunger, data transfer by the processing of computer software, shows the displacement waveform to computing machine in real time.
The invention has the beneficial effects as follows: the present invention can pair cell applies the deformation of waveforms such as sine wave or triangular wave, frequency range is 0-100Hz, amplitude of deformation is that maximum can reach 1mm, and adopt the method that makes up porous support and cell conjugate to provide the cell growth required three-dimensional environment, farthest simulated the growing environment in the cell body.This device adopts novel drive source piezoelectric ceramics as the power that loads cell, can load amplitude, frequency under non-stop-machine situation, and can regulate easily.
Stretching, compressive strain that the output of cyto-mechanics loading experimental apparatus among the present invention produces various ways, it is good to have operability, the repeatable accuracy height, mechanics loads steadily, and error is little, the magnetic interference of having brought when having avoided stepper motor as drive source.The characteristics such as 3 D stereo culture environment of cell growth needs can be provided, the deformation that cell is produced, the experiment under the same terms has good consistance.Can be used as pair cell in the biomechanics and carry out the experimental provision of mechanical stimulation response investigations.
The present invention is further described below in conjunction with drawings and Examples.
Description of drawings
The cell three-dimensional of Fig. 1 embodiment one of the present invention is cultivated the synoptic diagram of strain loading device;
Fig. 2 is cell culture unit and the piezoelectric ceramic piece drive part side view of embodiment one of the present invention;
Among the figure, the 1-substrate; The 2-lead-in wire picks out end; The 3-lead-in wire; 4-piezoelectric ceramics cutting ferrule; The 5-bimorph; 6-cultivates cell; The 7-driving ram; The complex of 8-collagen scaffold and cell; 9-porous immobilization material; The 10-laser probe; The 11-computing machine; The 12-drive power supply for piezoelectric ceramics;
Fig. 3 is the schematic three dimensional views that the cell three-dimensional of embodiment one of the present invention is cultivated strain loading device;
Fig. 4 is that the piezo-electric stack driver of embodiment two of the present invention is cultivated the strain loading device synoptic diagram with cell three-dimensional;
Among the figure, the 13-driver rack; 14-driver set bolt; 15-piezo-electric stack driver; 16-driver driving ram; The 17-plunger is connected and fixed pin;
Fig. 5 is that the piezo-electric stack driver of embodiment two of the present invention is cultivated the unit three-dimensional synoptic diagram with cell three-dimensional.
Embodiment
Embodiment one, bimorph are as the cell strain loading device of driver
With reference to Fig. 1, Fig. 2 and Fig. 3, apparatus of the present invention comprise drive power supply for piezoelectric ceramics, piezoelectric ceramic piece drive part, cell culture unit and laser displacement sensor deformation test section.Drive power supply for piezoelectric ceramics 12 provides on-load voltage; The piezoelectric ceramic piece drive part mainly is made of its core component piezoelectric ceramic piece 5, electrode, potsherd stationary installation, transmission plunger 7, porous immobilization material; Cell culture unit is made of substrate 1 and cultivation cell 6; Laser displacement sensor deformation test section is made up of laser probe 10 and computing machine 11.Wherein electrode picks out end 2 for lead-in wire, the potsherd stationary installation is selected piezoelectric ceramics cutting ferrule 4 for use, the porous immobilization material uses porous polyethylene 9, and substrate 1, piezoelectric ceramics cutting ferrule 4, cellular incubation cell 6 are pmma material, and driving ram 7 materials are teflon.Substrate 1 is the base of this device, and lead-in wire picks out end 2 and cultivates cell 6 and is fixed in the substrate 1.Bimorph 5 is fixed on cultivation cell 6 front sides by piezoelectric ceramics cutting ferrule 4, and lead-in wire 3 is connected to lead-in wire and picks out on the end 2, and power supply 12 applies voltage by the 3 pairs of bimorphs 5 that go between, and makes it produce front and back deformation.Polymerization can take place when raising in the collagen temperature, is condensed into one with porous polyethylene 9, and the deformation that driving ram 7 transmits is loaded on the complex 8 of collagen scaffold and cell.When needs carry out the cyto-mechanics loading, regulate power supply 12 earlier, output needs the voltage of waveform, voltage 3 is loaded on the bimorph 5 by going between, because bimorph 5 two ends are fixed on the cellular incubation cell 6, so the position, intermediate portion can produce maximum deformation, is delivered to porous polyethylene 9 by driving ram 7, and then make the complex 8 of collagen scaffold and cell produce distortion.
Embodiment two, piezo-electric stack driver are as the cell strain loading device that drives
With reference to Fig. 4 and Fig. 5, the device among apparatus of the present invention and the embodiment one is basic identical, and difference is that this device uses piezo-electric stack driver 15 as drive source, provides driving force.The transmission of displacement realizes by driving ram 16.Piezo-electric stack driver 15 usefulness set bolts 14 are fixed in the driver rack 13, driver is connected piezo-electric stack driver 15 vibration output terminals with driving ram 16.Driver connects with fixed pin 17 with the each several part of driving ram 16.When pair cell applies mechanical stimulation in the experiment, at first regulate power supply 12 output required voltage signals, the corresponding deformation of drive pressure electroceramics device 15 outputs, similar to embodiment one, transmit the complex 8 that makes collagen scaffold and cell by driver with driving ram 16 and produce distortion, pick-up unit is identical with embodiment one, realizes by laser probe 10 and computing machine 11.
Claims (3)
1. cell strain loading device under three-dimensional cultivation condition, comprise drive power supply for piezoelectric ceramics, piezoelectric ceramic piece drive part, cell culture unit and laser displacement sensor deformation test section, it is characterized in that: described piezoelectric ceramic piece drive part comprises piezoelectric ceramic piece, electrode, potsherd stationary installation, transmits plunger, porous immobilization material; Cell culture unit is made of substrate and cultivation cell; Laser displacement sensor deformation test section comprises laser probe and computing machine; Power supply is connected to by drive wire on the electrode of piezoelectric ceramic piece drive part, and electrode links to each other with piezoelectric ceramic piece; By the potsherd stationary installation piezoelectric ceramic piece is fixed in the substrate, the displacement output terminal that plunger back-end and piezoelectric ceramic piece are transmitted in displacement is fixed together, front end be connected cell--the porous immobilization material that props up the three-dimensional complex that is configured to is fixed; Cell--a three-dimensional complex that is configured to is positioned at cultivates cell bottom center position, and both sides connect the porous immobilization material respectively, and the porous immobilization material of a side is fixed on to be cultivated on the little locular wall, and the porous immobilization material of opposite side transmits plunger with displacement fixedlys connected; The laser probe noncontact is installed on the transmission plunger back-end, links to each other with computing machine, detects the front and back displacement of transmitting plunger.
2. according to utilizing the described cell strain loading device under three-dimensional cultivation condition of claim 1, it is characterized in that: described porous immobilization material is not for producing Cytotoxic porosint.
3. according to utilizing the described cell strain loading device under three-dimensional cultivation condition of claim 1, it is characterized in that: described cell culture unit adopts organic glass or polytetrafluoroethylmaterial material to make.
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| CN2008100173679A CN101221166B (en) | 2008-01-22 | 2008-01-22 | Cell strain loading device under three-dimensional cultivation condition |
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| CN101221166B true CN101221166B (en) | 2011-09-14 |
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Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101899393B (en) * | 2010-08-10 | 2011-12-28 | 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 |
| CN102373154B (en) * | 2010-08-19 | 2013-04-24 | 西北工业大学 | Novel cell culturing apparatus |
| CN102268360B (en) * | 2011-04-27 | 2013-01-30 | 南开大学 | Supersonic vibration microscopic cell penetrating system based on piezoelectric ceramic driving |
| CN103173355A (en) * | 2013-04-18 | 2013-06-26 | 中国医学科学院生物医学工程研究所 | Cell culture incubator with low-level laser environment |
| CN110305787A (en) * | 2018-03-27 | 2019-10-08 | 华东理工大学 | A kind of internal mechanical environment simulator |
| CN110577895B (en) * | 2019-10-14 | 2021-03-02 | 东华大学 | Dynamic cell culture method and culture device for simulating in-vivo dynamic environment |
| CN111057640A (en) * | 2019-12-09 | 2020-04-24 | 西北工业大学 | Experimental device for in-situ research cell mechanical characteristics |
| CN115074314A (en) * | 2022-03-28 | 2022-09-20 | 北京大学口腔医学院 | Material for regulating and controlling osteogenic differentiation of stem cells and preparation method and application thereof |
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