CN103966091A - Devices for cell composite force-electric load measurement - Google Patents

Devices for cell composite force-electric load measurement Download PDF

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CN103966091A
CN103966091A CN201410204746.4A CN201410204746A CN103966091A CN 103966091 A CN103966091 A CN 103966091A CN 201410204746 A CN201410204746 A CN 201410204746A CN 103966091 A CN103966091 A CN 103966091A
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cell
piezoelectric
generating unit
placement platform
measuring
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CN103966091B (en
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谢瑜
刘翀
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Xiamen University
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    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M35/00Means for application of stress for stimulating the growth of microorganisms or the generation of fermentation or metabolic products; Means for electroporation or cell fusion
    • C12M35/02Electrical or electromagnetic means, e.g. for electroporation or for cell fusion
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    • C12M35/00Means for application of stress for stimulating the growth of microorganisms or the generation of fermentation or metabolic products; Means for electroporation or cell fusion
    • C12M35/04Mechanical means, e.g. sonic waves, stretching forces, pressure or shear stimuli
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    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M41/00Means for regulation, monitoring, measurement or control, e.g. flow regulation

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Abstract

The invention belongs to the technical field of cell engineering, and particularly relates to a cytomechanic-electrical joint loading and analyzing device in a biomedical experimental instrument. The invention discloses a device for cell composite force-electric load measurement. The device comprises a mechanical drive system, a mechanical drive control system, an electrode probe, a cell placement platform, an electric signal generation system and a piezoelectric measurement system. The invention also discloses a device for cell composite force-electric load measurement. The device for cell composite force-electric load measurement comprises a mechanical drive system, a mechanical drive control system, an electrode probe, a cell placement platform, an electric signal measuring system and a piezoelectric measurement system. The devices disclosed by the invention are applied to an application prospect for cytomechanic-electrical load measurement on cells.

Description

Cell composite force-electricity loads the device of measuring
Technical field
The invention belongs to cell engineering field, particularly cyto-mechanics-electricity combination loading and the analytical equipment in biomedicine experiment instrument.
Background technology
Cyto-mechanics is to develop an advanced subject rapidly in several years biomechanics fields, mainly studies the change of cell on structure and function under mechanical stimulation.The mechanical characteristic of research biomass cells is significant to aspects such as the Clinics and Practices of cell physiological, pathologic process research, disease, cell quality evalution and analyses.Normal by the structural changes in the Changeement cell development process of ovum zona pellucida coefficient of elasticity and biochemical variation in reproductive medicine and developmental biology field.The coefficient of elasticity of ovum zona pellucida is considered to an important indicator of cell grade estimation.In robot assisted micromanipulation, also need cell to carry out mechanical modeling, to realize the accurate manipulation of end effector to cell.In existing cyto-mechanics deceleration loading device, be mainly to the simulating at mechanics environment of cell, by substrate tension method, realize the mechanical stimulation to cell.As providing a kind of, the grant number patent that is CN 1932510B and CN 101892154B stretches to being attached with the Elastic Foundation counterdie of cell, by the change of the stretch range of film, frequency is formed to extrusion stretching to cell.There are two limitation in this deceleration loading device: the one, and cell need to be to grow or to be fixed on the attached cell on basilar membrane, and class suspension cells such as ovum are existed to fixing and the inhomogeneous problem of Mechanical loading; Another is to be to realize by the stretching to basilar membrane to the Mechanical loading of cell, cannot determine, and this device cannot provide the Mechanical loading experiment of the known power of applying to being finally applied to the size of the power on cell.
Except power stimulates, electricity irritation is also the conventional stimulating method in cell engineering field.Because bioelectricity is the base attribute of body activity, by the research to cell biological electricity characteristic, contribute to understand the mechanism of vital movement and produce rule.The membrane potential of ovum is the electrophysiology sign of oocyte maturation and fertilization, and detecting ovocyte membrane potential is the whether normal important indicator of judgement ovocyte function.Thereby ovum produces the variation of egg membrane current potential in natural fertilization process due to intracellular calcium ion continued jitters.In monosperm microinjection experiment and animal nuclear transplantation experiment, the method of electricity irritation can make the moment increase of ovocyte membrane permeability, thereby make exogenous calcium enter in ovocyte or by activating the release of IP3 system induction calcium stores calcium ion, cause intracellular free calcium level to increase, make activation of oocytes, improve embryo's developmental rate.
As known from the above, force characteristic and electrical characteristic are simultaneous two key properties of cell, and the developmental mechanism that two characteristics is integrated to research ovum is very important.For example, by electrode catheter, measure the electrical signal of cell, also need force transducer to obtain the coefficient of elasticity of ovum zona pellucida simultaneously, thereby assess the development quality of ovum.While applying electrical stimulation signal to cell, when electrode catheter is when cell specific position applies electricity irritation, need force transducer monitoring electrode catheter to act on the power on cell, to guarantee that electrode probe touches stimulation location, and this position is not produced to excessive destruction.On the other hand, when cell electricity irritation, control the elastic force pressure of electrode probe, can guarantee that the electricity irritation at every turn cell being applied has repeatability.
Visible, in some application scenario, be to need to adopt to adopt composite force-electricity to load measurement to cell.And existing mechanical loading unit and electricity stimulating apparatus provide separately stimulation mostly.Granted patent CN 101892154b provides a kind of pressure-electricity co-stimulation cell culture device, need to will after cell suspension and biomaterial composite molding, to cell, provide indirectly power electricity combined stimulation.This device only can provide pressure-electricity combined stimulation, needs by other laboratory facilities, to analyze and stimulate rear result again after having stimulated, and cannot measure in real time cell under pressure-electricity combined stimulation, the real-time stress response situation of cell.In addition, this device must be realized fixing, stretching and the electricity irritation of cell by matrix material, cannot directly to individual cells, implement accurate power electricity irritation, has very big limitation.Separately, this case contriver also once proposed that cell was carried out to simple physics and visited the technical scheme of pressing the improvement stimulating, but still cannot be adapted to composite force-electricity, loaded under the sight of measuring.
Summary of the invention
The object of the invention is can not provide to class suspension cells such as ovum the technical problem of accurate power electricity combined stimulation in order to solve existing apparatus, thereby proposes a kind ofly can carry test set for single celled power-electricity united heating.
The present invention is concrete adopts following technical scheme to realize:
Cell composite force-electricity loads a device of measuring, and comprising: machine driven system, mechanical transmission Controlling System, electrode catheter, cell placement platform, electrical signal generation systems and piezoelectric measurement system, wherein,
This machine driven system comprises mechanical action generating unit and the motion arm that is connected in this mechanical action generating unit, and this mechanical action generating unit is for driving this motion arm to carry out the displacement action on space;
This mechanical transmission Controlling System and this mechanical action generating unit control linkage, for driving this mechanical action generating unit running, thereby make this mechanical action generating unit drive this motion arm to carry out the displacement action of setting;
This electrode catheter is to be connected with the motion arm of this machine driven system, thereby drives this electrode catheter to carry out displacement action with respect to this cell placement platform by this motion arm;
The electrical signal of this electrical signal generation systems is connected in this electrode catheter, for generation of the electrical stimulation signal that loads on cell;
This cell placement platform is to comprise a upright piezoelectric sensing substrate arranging and place plate with this piezoelectric sensing substrate cell connected vertically, and this piezoelectric sensing substrate is drawn measure traverse line;
This piezoelectric measurement system is electrically connected to the measure traverse line of this cell placement platform, for the piezoelectric signal of the piezoelectric sensing substrate of this cell placement platform is carried out to real-time survey record; This piezoelectric measurement system is also connected with this mechanical transmission Controlling System, and the piezoelectric signal of measuring is in real time fed back to this mechanical transmission Controlling System.
Cell composite force-electricity loads a device of measuring, and comprising: machine driven system, mechanical transmission Controlling System, electrode catheter, cell placement platform, electric signal measurement system and piezoelectric measurement system, wherein,
This machine driven system comprises mechanical action generating unit and the motion arm that is connected in this mechanical action generating unit, and this mechanical action generating unit is for driving this motion arm to carry out the displacement action on space;
This mechanical transmission Controlling System and this mechanical action generating unit control linkage, for driving this mechanical action generating unit running, thereby make this mechanical action generating unit drive this motion arm to carry out the setting displacement action on space;
This electrode catheter is to be connected with the motion arm of this machine driven system, thereby drives this electrode catheter to carry out displacement action with respect to this cell placement platform by this motion arm;
The signals collecting end input of this electric signal measurement system is connected in this electrode catheter, for measuring the bioelectrical signals of the cell irriate feedback of this electrode catheter collection;
This cell placement platform is to comprise a upright piezoelectric sensing substrate arranging and place plate with this piezoelectric sensing substrate cell connected vertically, and this piezoelectric sensing substrate is drawn measure traverse line;
This piezoelectric measurement system is electrically connected to the measure traverse line of this cell placement platform, for the piezoelectric signal of the piezoelectric sensing substrate of this cell placement platform is carried out to real-time survey record; This piezoelectric measurement system is also connected with this mechanical transmission Controlling System, and the piezoelectric signal of measuring is in real time fed back to this mechanical transmission Controlling System.
Further, it is a continuous lines frid that the cell of this cell placement platform is placed plate, and one of them side wall surface of this continuous lines frid and this piezoelectric sensing substrate bonding arrange.
Further, this cell placement platform is to adopt two U-shaped supports, a crossbeam and a PVDF piezoelectric membrane to build, these two U-shaped supports are separately positioned on the two ends of this crossbeam, and by the U word slotted eye of these two U-shaped supports, this crossbeam clamping is also open and flat fixing, this PVDF piezoelectric membrane is pasted on this crossbeam.One of them of these two U-shaped supports is also provided with a through hole, for the setting that stretches through for this measure traverse line.
Further, also comprise a bearing base, this bearing base is used for placing a Tissue Culture Dish, and this cell placement platform is placed in this Tissue Culture Dish.
Further, the mechanical action generating unit of this mechanical transmission Controlling System is a three-dimensional motion generating unit.
Further, this three-dimensional motion generating unit is to comprise: one is positioned at the first straight-line displacement assembly of X-axis, a second straight-line displacement assembly that is positioned at Y-axis and a 3rd straight-line displacement assembly that is positioned at Z axis, this the second straight-line displacement assembly is vertically fixedly installed on the driver plate of this first straight-line displacement assembly, and the 3rd straight-line displacement assembly is vertically fixedly installed on the driver plate of this second straight-line displacement assembly.
Further, this first, second, third straight-line displacement assembly includes by two end seats, two guide rails, a rhizoid bar, an electric controlled rotating device and the straight-line displacement assemblies that driver plate forms, wherein these two guide rail parallel settings, two ends are fixed in these two end seats, this screw mandrel is arranged at the centre of these two guide rails, this driver plate socket and these two guide rails and a rhizoid bar, this electric controlled rotating device is arranged at one of them end seat and drives this screw mandrel to rotate, thereby drives this driver plate along straight-line displacement.Preferably, this electric controlled rotating device is a direct-current machine, and installation arranges an encoder.
It is by machine driven system, mechanical transmission Controlling System, electrode catheter to be controlled that cell composite force of the present invention-electricity loads the device of measuring, cell is loaded to polytype mechanical force signal: as visited pressure, visit pressure speed, visit pressure amplitude degree, visit voltage-frequency rate etc.; This device is provided with cell placement platform, can realize the single or continuous loading of a plurality of cells simultaneously; Electrode catheter is connected with electricity irritation or electrical measuring systems, can be by manoeuvring platform to the loading of cell realizable force-electrical signal and detection.
Accompanying drawing explanation
Fig. 1 is the schematic diagram of the physical construction part of a preferred embodiment of the present invention.
Fig. 2 is the schematic diagram of the cell placement platform of the preferred embodiment.
Embodiment
The present invention proposes a kind of cell composite force-electricity and loads the device of measuring, and comprising: machine driven system, mechanical transmission Controlling System, electrode catheter, cell placement platform, electronic system (electrical signal generation systems/electric signal measurement system) and piezoelectric measurement system.The device that the loading of this cell composite force-electricity is measured utilizes mechanical transmission Controlling System to order about machine driven system drive electrode catheter the cell on cell placement platform is visited and pressed or load electricity irritation, piezoelectric measurement system is the piezoelectric signal of the cell of this cell placement platform of survey record in real time, and the piezoelectric signal of measuring is in real time fed back to this mechanical transmission Controlling System, thereby the displacement action that spy that can accuracy controlling electrode catheter is pressed.Like this, the device that the loading of cell composite force of the present invention-electricity is measured can be realized cell record electricity irritation and accurate pressure spy are being depressed, cell real-time stress situation is carried out to Measurement and analysis, and can realize the accurate pressure of cell is being visited and depressed, cell real-time stress situation and cell irriate feedback bioelectrical signals is carried out to Measurement and analysis, thereby the composite force-electricity that can realize the individual cells that cannot realize in current technique means (also can a plurality of cells) loads measurement.
Now the present invention is further described for by reference to the accompanying drawings with 2 embodiments.
Embodiment 1:
Consult shown in Fig. 1 and Fig. 2, the cell of this embodiment composite force-electricity loads the device of measuring, and comprising: machine driven system, mechanical transmission Controlling System, electrode catheter, cell placement platform, electrical signal generation systems and piezoelectric measurement system.Wherein:
This machine driven system comprises mechanical action generating unit and the motion arm 5 that is connected in this mechanical action generating unit, and this mechanical action generating unit is the displacement action for driving this motion arm 5 to carry out on spaces.This mechanical action generating unit is a three-dimensional motion generating unit (can adopt one dimension or two dimensional motion generating unit according to actual needs).As shown in Figure 1, this three-dimensional motion generating unit is to comprise: one is positioned at the first straight-line displacement assembly of X-axis, a second straight-line displacement assembly that is positioned at Y-axis and a 3rd straight-line displacement assembly that is positioned at Z axis, this the second straight-line displacement assembly is vertically fixedly installed on the driver plate of this first straight-line displacement assembly, and the 3rd straight-line displacement assembly is vertically fixedly installed on the driver plate of this second straight-line displacement assembly.
Concrete, the first straight-line displacement assembly comprises that (the electric controlled rotating device of this embodiment is a direct-current machine 15 preferably, and installs an encoder 16 is set by 11,12, two guide rails of two end seats 13, a rhizoid bar 14, electric controlled rotating device; Electric controlled rotating device also can adopt piezoelectric motor, stepper-motor, servomotor to coordinate corresponding acceleration mechanism and function unit to realize) and a straight-line displacement assembly that driver plate 17 forms, wherein these two guide rails 13 be arranged in parallel, two ends are fixed in these two end seats 11,12, this screw mandrel 14 is arranged at the centre of these two guide rails 13, these driver plate 17 sockets and these two guide rails 13 and a rhizoid bar 14, this electric controlled rotating device is arranged at one of them end seat 11 and drives this screw mandrel to rotate, thereby drives this driver plate 17 along straight-line displacement.Same, this the second straight-line displacement assembly also adopts same straight-line displacement unit construction, by 21,22, two guide rails of two end seats 23, a rhizoid bar 24, a direct-current machine 25 and install and an electric controlled rotating device and the driver plate 27 that an encoder 26 forms is set forms, difference is, for the ease of this second straight-line displacement assembly is vertically fixedly installed on the driver plate 17 of this first straight-line displacement assembly, hold between seat 21,22 by base plate 28 connections and for being fixed to the driver plate 17 of this first straight-line displacement assembly for two.The 3rd straight-line displacement assembly is also to adopt same straight-line displacement unit construction, has by 31,32, two guide rails of two end seats 33, a rhizoid bar 34, a direct-current machine 35 and install an electric controlled rotating device and the driver plate 37 that an encoder 36 forms is set forms.Because the 3rd straight-line displacement assembly is vertically fixedly installed on the driver plate 27 of this second straight-line displacement assembly by its end seat 32, thereby base plate can be set.The motion arm 5 of this machine driven system is fixedly mounted on the driver plate 37 of the 3rd straight-line displacement assembly by an installation portion 4.Like this, the second straight-line displacement assembly that the first straight-line displacement assembly that this motion arm 5 can be positioned at X-axis by this is positioned at Y-axis comes implementation space three-D displacement to move with the 3rd straight-line displacement assembly that is positioned at Z axis.
This mechanical transmission Controlling System (not shown) and this mechanical action generating unit control linkage, for driving this mechanical action generating unit running, thereby make this mechanical action generating unit drive this motion arm to carry out the displacement action of setting.This mechanical transmission Controlling System can adopt corresponding with it transmission control circuit to realize according to the difference of mechanical action generating unit.For example, for above-mentioned mechanical action generating unit, be to adopt three-dimensional motion generating unit, can adopt to there are three groups of output control signals and connect the first straight-line displacement assembly that is positioned at X-axis that is connected to respectively this mechanical action generating unit, be positioned at the second straight-line displacement assembly of Y-axis and be positioned at the control inputs port of electric controlled rotating device of the 3rd straight-line displacement assembly of Z axis.
For example, this mechanical transmission Controlling System is provided with hardware circuit and built-in control algolithm, in order to realize the spy pressure of probe to cell, visits pressure speed, visits pressure amplitude degree, visits the adjustment of the cell loading mode of voltage-frequency rate.Described hardware circuit part, comprise DSP control module, motor drive module, supplying unit, described supplying unit connects DSP control module and motor drive module, described DSP control module connects motor drive module, and described motor drive module connects 3 direct-current machine 15,25,35 of this first, second, third straight-line displacement assembly.The module of control algolithm forms speed detection and rate control module and the Man Machine Interface module that is provided with the position detection visiting pressure detection and visit pressure-controlling module, probe and position control module, probe; The detection hardware of visiting pressure consists of described PVDF piezoelectric membrane 84 and the modulate circuit that is fixed on cell placing platform 8.Described spy pressure detection module is converted to spy pressure signal by voltage signal.By described spy pressure-controlling module and Man Machine Interface module, visit pressing and can accurately be set by user the loading force size of cell and frequency.By described position control module, rate control module and Man Machine Interface module, probe is visited and is pressed the degree of depth, spy pressure speed and frequency accurately to be set by user cell.The current techique that this mechanical transmission Controlling System is well known to those skilled in the art, launches explanation no longer in detail in this.
This electrode catheter 6 is to be connected with the motion arm 5 of this machine driven system, thereby drives this electrode catheter 6 to carry out displacement action with respect to this cell placement platform 8 by this motion arm 5, thereby the cell 9 on this cell placement platform 8 is visited to press operation.
Preferably, also comprise a bearing base, this bearing base is used for placing a Tissue Culture Dish 7, and this cell placement platform 8 is placed in this Tissue Culture Dish 7.Preferred, thereby one of them end seat 12 of the first straight-line displacement assembly of this mechanical action generating unit can change structure design directly substitute the function of this bearing base, be about to the height design get Geng Gao of this end seat 12, for supporting this Tissue Culture Dish 7.
The electrical signal of this electrical signal generation systems (not shown) is connected in this electrode catheter 6, for generation of the electrical stimulation signal that loads on cell; This electrical signal generation systems can adopt the adjustable electrical signal generating circuit devices of establishing of electrical property feature such as voltage, frequency, electric current that can produce setting to realize, as adopts the conventional signal generator using, so that direct current constant voltage and pulsed voltage to be provided.The current techique that this electrical signal generation systems is well known to those skilled in the art, no longer describes in detail in this.
This cell placement platform 8 is to comprise a upright piezoelectric sensing substrate arranging and place plate with this piezoelectric sensing substrate cell connected vertically, this piezoelectric sensing substrate is drawn measure traverse line, thereby prevent that the cell of placing on plate at this cell is subject to after electrode catheter 6 spy pressures, according to Newton's third law, stressed the conducting to of cell 9 placed on the piezoelectric sensing substrate that plate is vertical with this cell, this piezoelectric sensing substrate can convert pressure to electrical signal, draws measure traverse line by piezoelectric measurement system institute acquisition process.
Preferably, it is that (this embodiment adopts the continuous V-shaped line frid shown in Fig. 2 to a continuous lines frid that the cell of this cell placement platform 8 is placed plate 86, also can adopt continuous U-shaped trunking plate or Continuous Rectangular taps frid etc.), one of them side wall surface of this continuous lines frid and this piezoelectric sensing substrate bonding arrange.This piezoelectric sensing substrate can adopt PVDF piezoelectric membrane, pressure resistance type MEMS vane, capacitive MEMS vane, PTC piezoelectric ceramic piece etc.
It should be noted that, although the piezoelectric sensing substrate of this cell placement platform 8 can adopt prior art to realize, as the patented technology of CN 102589760A, CN 102967394 A, and existing pressure resistance type MEMS vane, capacitive MEMS vane, PTC piezoelectric ceramic piece etc., but for cell composite force of the present invention-electricity, load the difference (cell is visited and pressed) of the application scenarios of the device of measuring, the piezoelectricity collection of this cell placement platform 8 need to be carried out suitable optimization, to improve its accuracy of detection and stability.
Concrete, to consult shown in Fig. 2, the cell placement platform 8 of this embodiment is to adopt 81,82, crossbeams 83 of two U-shaped supports and a PVDF piezoelectric membrane 84 to build as piezoelectric sensing substrate.These two U-shaped supports 81,82 are separately positioned on the two ends of this crossbeam 83, and by the U word slotted eye of these two U-shaped supports 81,82, these crossbeam 83 clampings are also open and flat fixing, and this PVDF piezoelectric membrane 84 is pasted on this crossbeam 83.A side wall surface and this PVDF piezoelectric membrane 84 bondings that the cell of this continuous V-shaped line frid is placed plate 86 arrange.PVDF piezoelectric membrane 84 is drawn measure traverse line 85.And one of them U-shaped support 81 is also provided with logical 811 holes, for the setting that stretches through for this measure traverse line 85.This cell is placed plate 86 and can be adopted synthetic glass or acryl to make, and this crossbeam 83 is to adopt flexible material, as PC sheet material, PA sheet material etc.
The above-mentioned preferred structure design of the cell placement platform 8 of this embodiment; compared with patent CN 102589760A, a kind of structure with flexible support beam Bonding pressure sensitive material is disclosed; its U-shaped groove structure adopting can effectively be protected the destruction of excessive pressure to pressure sensitive material, makes sensor have higher robustness.Compared with the patent CN 102967394 fixing pressure sensitive material fixed sturctures in disclosed a kind of four limits of A, U-shaped structure authorized pressure sensitive material has larger deformation space, has expanded the useful range of force transducer; And according to the moment of flexure of beam and shearing equilibrium equation, derive, this structure can guarantee pressure sensitive material pressure and should become exact linear relationship, improve the stated accuracy of force transducer.Structure than the sensing triangular support sensitive material used of some PVDF piezoelectric membranes, also has more excellent characteristic.For example also to have overcome existing this structure too simple for this preferred structure, effective fixation pressure sensitive material, and when being subject to external force, due to the unstable of this structure, easily cause the disturbance of tested External Force Acting overdraft sensitive material itself, make sensor produce the deficiency of mistake output.
This piezoelectric measurement system (not shown) is electrically connected to the measure traverse line 85 of this cell placement platform, for the piezoelectric signal of the piezoelectric sensing substrate of this cell placement platform (i.e. the PVDF piezoelectric membrane 84 of this embodiment) is carried out to real-time survey record; This piezoelectric measurement system is also connected with this mechanical transmission Controlling System, the piezoelectric signal of measuring is in real time fed back to this mechanical transmission Controlling System, thereby the electrode catheter 6 that this mechanical transmission Controlling System can be connected this motion arm 5 of this machine driven system is accurately visited pressure-controlled.This piezoelectric measurement system comprises conventional signal amplification module, signal condition module, signal output module etc., and according to the difference of connected piezoelectric sensing substrate, and slightly different, the current techique being well known to those skilled in the art, no longer describes in detail in this.
The cell composite force of this embodiment-electricity loads the device of measuring, and to carry out the sight of a detection as follows: the cell that one or more zebra fish ovum 9 is placed on to the continuous V-shaped groove of this cell placement platform 8 is placed on plate 86, electrode catheter 6 is arranged on motion arm 5, electrode catheter 6 is connected with the electrical signal modulation circuit of this electrical signal generation systems, the measure traverse line 85 of the PVDF piezoelectric membrane 84 of this cell placement platform 8 is connected with the electrical signal modulate circuit of this piezoelectric measurement system, respectively and by this mechanical transmission Controlling System, after piezoelectric measurement system connects, Access Control center is (as PC, industrial computer etc.), and open respectively this mechanical transmission Controlling System, the power supply of electrical signal generation systems and piezoelectric measurement system, electrical signal generation systems human-computer interaction interface by control center is set the amplitude that 6 pairs of cells 9 of electrode catheter apply electrical signal, pulse width and frequency, by mechanical transmission Controlling System human-computer interaction interface, set the loading position of 6 pairs of cells of electrode catheter, click the electrical signal load button of electrical signal generation systems human-computer interaction interface, this machine driven system drives electrode catheter 6, according to the parameters of electrical stimulation of input, cell 9 is applied to electrical signal and loads, cell pressurized in stimulating course, PVDF piezoelectric membrane 84 by this cell placement platform 8 carries out real-time survey record by cell pressurized generation force signal, and feed back to control center and adjust this mechanical transmission Controlling System.The electric stimulation pulse amplitude that this electrical signal generation systems is implemented is 500 millivolts, and pulse width is 2 milliseconds, and frequency is 2 hertz.
Embodiment 2:
This embodiment is substantially the same manner as Example 1, and difference is: electrode catheter is not to be connected in electrical signal generation systems, but is connected to an electric signal measurement system, thereby can gather the bioelectrical signals of cell irriate feedback.Concrete, this embodiment comprises: machine driven system, mechanical transmission Controlling System, electrode catheter, cell placement platform, electric signal measurement system and piezoelectric measurement system.Wherein:
This machine driven system comprises mechanical action generating unit and the motion arm that is connected in this mechanical action generating unit, and this mechanical action generating unit is for driving this motion arm to carry out the displacement action on space.
This mechanical transmission Controlling System and this mechanical action generating unit control linkage, for driving this mechanical action generating unit running, thereby make this mechanical action generating unit drive this motion arm to carry out the setting displacement action on space.
This electrode catheter is to be connected with the motion arm of this machine driven system, thereby drives this electrode catheter to carry out displacement action with respect to this cell placement platform by this motion arm.
The signals collecting end input of this electric signal measurement system is connected in this electrode catheter, for measuring the bioelectrical signals of the cell irriate feedback of this electrode catheter collection; This electric signal measurement system realizes amplification, filtering and the AD conversion etc. of weak bioelectrical signals by its electrical signal collection modulate circuit, the current techique that this electric signal measurement system is well known to those skilled in the art, no longer describes in detail in this.
This cell placement platform is to comprise a upright piezoelectric sensing substrate arranging and place plate with this piezoelectric sensing substrate cell connected vertically, and this piezoelectric sensing substrate is drawn measure traverse line.
This piezoelectric measurement system is electrically connected to the measure traverse line of this cell placement platform, for the piezoelectric signal of the piezoelectric sensing substrate of this cell placement platform is carried out to real-time survey record; This piezoelectric measurement system is also connected with this mechanical transmission Controlling System, and the piezoelectric signal of measuring is in real time fed back to this mechanical transmission Controlling System.
The cell composite force of this embodiment-electricity loads the device of measuring, and to carry out the sight of a detection as follows: the cell that one or more zebra fish ovum is placed on to the continuous V-shaped groove of this cell placement platform is placed on plate, electrode catheter is arranged on motion arm, electrode catheter is connected with the electrical signal collection modulate circuit of this electric signal measurement system, the measure traverse line of the PVDF piezoelectric membrane of this cell placement platform is connected with the electrical signal modulate circuit of this piezoelectric measurement system, respectively and by this mechanical transmission Controlling System, after piezoelectric measurement system connects, Access Control center is (as PC, industrial computer etc.), and open respectively this mechanical transmission Controlling System, the power supply of electric signal measurement system and piezoelectric measurement system, by mechanical transmission Controlling System human-computer interaction interface, set the loading position of electrode catheter to cell, click the electrical signal load button of electrical signal generation systems human-computer interaction interface, this machine driven system drives electrode catheter, according to the parameters of electrical stimulation of input, cell is applied to probe physics and visits pressure, for example physics spy pressure loading velocity is 1.7 mm/second, frequency is 2 hertz, at physics, visit cell pressurized in pressure stimulating course, PVDF piezoelectric membrane by this cell placement platform carries out real-time survey record by cell pressurized generation force signal, and feed back to control center and adjust this mechanical transmission Controlling System.Now, this electrode catheter is visited while being pressed onto cell different sites, and cell irriate can feed back bioelectrical signals, by this electric signal measurement system, carries out real-time survey record.
As fully visible, the invention has the advantages that: 1, by this device, can study the physiology reflection of single or continuous a plurality of cells under accurate mechanical signal, electrical signal stimulate; 2, by this device, can study the physiology reflection of unicellular or continuous a plurality of cells under accurate mechanics-electrical signal stimulates; 3, by this device, can study variation and the reflection of other physiology of the membrane potential of unicellular or continuous a plurality of cells under accurate mechanical signal stimulates; 4, the present invention is simple in structure, use, good stability, and the evaluation of the research of cyto-mechanics and cell quality provides a new thinking and new research means.
Although specifically show and introduced the present invention in conjunction with preferred embodiment; but those skilled in the art should be understood that; within not departing from the spirit and scope of the present invention that appended claims limits; can make a variety of changes the present invention in the form and details, be protection scope of the present invention.

Claims (10)

1. cell composite force-electricity loads a device of measuring, and it is characterized in that, comprising: machine driven system, mechanical transmission Controlling System, electrode catheter, cell placement platform, electrical signal generation systems and piezoelectric measurement system, wherein,
This machine driven system comprises mechanical action generating unit and the motion arm that is connected in this mechanical action generating unit, and this mechanical action generating unit is for driving this motion arm to carry out the displacement action on space;
This mechanical transmission Controlling System and this mechanical action generating unit control linkage, for driving this mechanical action generating unit running, thereby make this mechanical action generating unit drive this motion arm to carry out the displacement action of setting;
This electrode catheter is to be connected with the motion arm of this machine driven system, thereby drives this electrode catheter to carry out displacement action with respect to this cell placement platform by this motion arm;
The electrical signal of this electrical signal generation systems is connected in this electrode catheter, for generation of the electrical stimulation signal that loads on cell;
This cell placement platform is to comprise a upright piezoelectric sensing substrate arranging and place plate with this piezoelectric sensing substrate cell connected vertically, and this piezoelectric sensing substrate is drawn measure traverse line;
This piezoelectric measurement system is electrically connected to the measure traverse line of this cell placement platform, for the piezoelectric signal of the piezoelectric sensing substrate of this cell placement platform is carried out to real-time survey record; This piezoelectric measurement system is also connected with this mechanical transmission Controlling System, and the piezoelectric signal of measuring is in real time fed back to this mechanical transmission Controlling System.
2. cell composite force-electricity loads a device of measuring, and it is characterized in that, comprising: machine driven system, mechanical transmission Controlling System, electrode catheter, cell placement platform, electric signal measurement system and piezoelectric measurement system, wherein,
This machine driven system comprises mechanical action generating unit and the motion arm that is connected in this mechanical action generating unit, and this mechanical action generating unit is for driving this motion arm to carry out the displacement action on space;
This mechanical transmission Controlling System and this mechanical action generating unit control linkage, for driving this mechanical action generating unit running, thereby make this mechanical action generating unit drive this motion arm to carry out the setting displacement action on space;
This electrode catheter is to be connected with the motion arm of this machine driven system, thereby drives this electrode catheter to carry out displacement action with respect to this cell placement platform by this motion arm;
The signals collecting end input of this electric signal measurement system is connected in this electrode catheter, for measuring the bioelectrical signals of the cell irriate feedback of this electrode catheter collection;
This cell placement platform is to comprise a upright piezoelectric sensing substrate arranging and place plate with this piezoelectric sensing substrate cell connected vertically, and this piezoelectric sensing substrate is drawn measure traverse line;
This piezoelectric measurement system is electrically connected to the measure traverse line of this cell placement platform, for the piezoelectric signal of the piezoelectric sensing substrate of this cell placement platform is carried out to real-time survey record; This piezoelectric measurement system is also connected with this mechanical transmission Controlling System, and the piezoelectric signal of measuring is in real time fed back to this mechanical transmission Controlling System.
3. cell composite force according to claim 1 and 2-electricity loads the device of measuring, and it is characterized in that: it is a continuous lines frid that the cell of this cell placement platform is placed plate, and one of them side wall surface of this continuous lines frid and this piezoelectric sensing substrate bonding arrange.
4. cell composite force according to claim 3-electricity loads the device of measuring, it is characterized in that: this cell placement platform is to adopt two U-shaped supports, a crossbeam and a PVDF piezoelectric membrane to build, these two U-shaped supports are separately positioned on the two ends of this crossbeam, and by the U word slotted eye of these two U-shaped supports, this crossbeam clamping is also open and flat fixing, this PVDF piezoelectric membrane is pasted on this crossbeam.
5. cell composite force according to claim 4-electricity loads the device of measuring, and it is characterized in that: one of them of these two U-shaped supports is also provided with a through hole, for the setting that stretches through for this measure traverse line.
6. cell composite force according to claim 1 and 2-electricity loads the device of measuring, and it is characterized in that: also comprise a bearing base, this bearing base is used for placing a Tissue Culture Dish, and this cell placement platform is placed in this Tissue Culture Dish.
7. cell composite force according to claim 1 and 2-electricity loads the device of measuring, and it is characterized in that: the mechanical action generating unit of this mechanical transmission Controlling System is a three-dimensional motion generating unit.
8. cell composite force according to claim 7-electricity loads the device of measuring, it is characterized in that: this three-dimensional motion generating unit is to comprise: one is positioned at the first straight-line displacement assembly of X-axis, a second straight-line displacement assembly that is positioned at Y-axis and a 3rd straight-line displacement assembly that is positioned at Z axis, this the second straight-line displacement assembly is vertically fixedly installed on the driver plate of this first straight-line displacement assembly, and the 3rd straight-line displacement assembly is vertically fixedly installed on the driver plate of this second straight-line displacement assembly.
9. cell composite force according to claim 8-electricity loads the device of measuring, it is characterized in that: this is first years old, second, the 3rd straight-line displacement assembly includes by two end seats, two guide rails, one rhizoid bar, an electric controlled rotating device and a straight-line displacement assembly that driver plate forms, wherein these two guide rail parallel settings, two ends are fixed in these two end seats, this screw mandrel is arranged at the centre of these two guide rails, this driver plate socket and these two guide rails and a rhizoid bar, this electric controlled rotating device is arranged at one of them end seat and drives this screw mandrel to rotate, thereby drive this driver plate along straight-line displacement.
10. cell composite force according to claim 9-electricity loads the device of measuring, and it is characterized in that: this electric controlled rotating device is a direct-current machine, and installation arranges an encoder.
CN201410204746.4A 2014-05-15 2014-05-15 Cell composite force-electricity loads the device measured Expired - Fee Related CN103966091B (en)

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