CN103966091B - Cell composite force-electricity loads the device measured - Google Patents

Cell composite force-electricity loads the device measured Download PDF

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CN103966091B
CN103966091B CN201410204746.4A CN201410204746A CN103966091B CN 103966091 B CN103966091 B CN 103966091B CN 201410204746 A CN201410204746 A CN 201410204746A CN 103966091 B CN103966091 B CN 103966091B
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cell
piezoelectric
generating unit
placement platform
electrode catheter
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CN103966091A (en
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谢瑜
刘翀
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Xiamen University
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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
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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
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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 cell engineering field, the cyto-mechanics particularly in biomedicine experiment instrument-electricity combination loading and analytical equipment.The present invention discloses a kind of cell composite force-electricity and loads the device measured, and comprising: machine driven system, mechanical transmission Controlling System, electrode catheter, cell placement platform, electrical signal generation systems and piezoelectric measurement system.The present invention also discloses a kind of cell composite force-electricity and loads the device measured, and comprising: machine driven system, mechanical transmission Controlling System, electrode catheter, cell placement platform, electric signal measurement system and piezoelectric measurement system.The present invention is applied in and adopts composite force-electricity to load the application scenario measured to cell.

Description

Cell composite force-electricity loads the device measured
Technical field
The invention belongs to cell engineering field, the cyto-mechanics particularly in biomedicine experiment instrument-electricity combination loading and analytical equipment.
Background technology
Cyto-mechanics developed an advanced subject rapidly in biomechanics field into several years, mainly studies the change of cell on structure and function under mechanical stimulation.The aspect such as Clinics and Practices, cell quality evaluation and application of mechanical characteristic to cell physiological, pathologic process research, disease of research biomass cells is significant.Usually through the structural changes in the Changeement cell development process of ovum zona pellucida coefficient of elasticity and Biochemical changes 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 to carry out mechanical modeling to cell, to realize the accurate manipulation of end effector to cell.In existing cyto-mechanics deceleration loading device, simulating at mechanics environment mainly to cell, realizes the mechanical stimulation to cell by substrate tension method.Stretch, by forming extrusion stretching to the stretch range of film, the change of frequency to cell as the grant number patent that is CN1932510B and CN101892154B provides a kind of elastic substrates film to being attached with cell.There are two limitation in this deceleration loading device: one is that cell needs to be can grow or be fixed on the attached cell on basilar membrane, there is fixing and that Mechanical loading is uneven problem to class suspension cells such as ovum; Another is by realizing the stretching of basilar membrane to the Mechanical loading of cell, cannot determine, and this device cannot provide the Mechanical loading of known applying power to test to the size of the power be finally applied on cell.
Except power stimulates, electricity irritation is also the stimulating method that cell engineering field is commonly used.Due to the base attribute that bioelectricity is body activities, by the research to cell biological electricity characteristic, contribute to mechanism and the generation rule of understanding vital movement.The membrane potential of ovum is the electrophysiology mark of oocyte maturation and fertilization, and detecting ovocyte membrane potential is the important indicator judging that whether normal ovocyte function is.Ovum produces the change of egg membrane current potential due to intracellular calcium ion continued jitters in natural fertilization process.In monosperm experiments Microinjection and animal nuclear transfer experiments, the method of electricity irritation can make ovocyte membrane permeability increase instantaneously, thus make exogenous calcium enter in ovocyte or pass through to activate the release of IP3 system induction cellular calcium storehouse calcium ion, intracellular free calcium level is caused to increase, make activation of oocytes, improve the developmental rate of embryo.
As known from the above, force characteristic and electrical characteristic are simultaneous two key properties of cell, and the developmental mechanism two characteristics being integrated research ovum is very important.Such as, measured the electrical signal of cell by electrode catheter, also need force transducer to obtain the coefficient of elasticity of ovum zona pellucida simultaneously, thus the development quality of assessment ovum.When applying electrical stimulation signal to cell, when electrode catheter applies electricity irritation at cell specific position, need force transducer to monitor electrode catheter and act on power on cell, to guarantee that electrode probe touches stimulation location, and excessive destruction is not produced to this position.On the other hand, control the elastic force pressure of electrode probe when cell electricity irritation, can guarantee to the electricity irritation that cell applies, to there is repeatability at every turn.
Visible, be need to adopt to adopt composite force-electricity to load measurement to cell in some application scenario.And existing mechanical loading unit and electricity stimulating apparatus provide stimulation separately mostly.Granted patent CN101892154B provides a kind of pressure-electricity co-stimulation cell culture device, and needing provides indirectly power electricity combined stimulation by after cell suspension and biomaterial composite molding to cell.This device only can provide pressure-electricity combined stimulation, has stimulated rear needs to analyze by other laboratory facilities again and has stimulated rear result, cannot measure cell in real time under pressure-electricity combined stimulation, the real-time stress response situation of cell.In addition, this device must by matrix material realize cell fixing, stretch and electricity irritation, directly cannot implement accurate power electricity irritation to individual cells, there is significant ASIC limitation.Separately, inventor also once proposed to carry out to cell the technical scheme that simple physical visits the improvement that pressure stimulates, but under still cannot being adapted to the sight of composite force-electricity loading measurement.
Summary of the invention
The object of the invention is the technical problem that accurate power electricity combined stimulation can not be provided class suspension cells such as ovum to solve existing apparatus, thus proposition one can carry test set for single celled power-electricity united heating.
The present invention specifically adopts following technical scheme to realize:
Cell composite force-electricity loads the device measured, 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 is connected to the motion arm of this mechanical action generating unit, and this mechanical action generating unit is for driving this motion arm execution displacement action spatially;
This mechanical transmission Controlling System and this mechanical action generating unit control linkage, for driving this mechanical action generating unit to operate, thus make this mechanical action generating unit drive this motion arm to perform the displacement action of setting;
This electrode catheter is connected with the motion arm of this machine driven system, thus drive this electrode catheter to carry out displacement action relative to this cell placement platform by this motion arm;
The electrical signal of this electrical signal generation systems is connected to this electrode catheter, for generation of the electrical stimulation signal loading on cell;
This cell placement platform comprises a piezoelectric sensing substrate uprightly arranged and places plate with this piezoelectric sensing substrate cell connected vertically, and measure traverse line drawn by this piezoelectric sensing substrate;
This piezoelectric measurement system is electrically connected with the measure traverse line of this cell placement platform, and the piezoelectric signal for the piezoelectric sensing substrate by this cell placement platform carries out real-time survey record; This piezoelectric measurement system is also connected with this mechanical transmission Controlling System, the piezoelectric signal measured in real time is fed back to this mechanical transmission Controlling System.
Cell composite force-electricity loads the device measured, 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 is connected to the motion arm of this mechanical action generating unit, and this mechanical action generating unit is for driving this motion arm execution displacement action spatially;
This mechanical transmission Controlling System and this mechanical action generating unit control linkage, for driving this mechanical action generating unit to operate, thus make this mechanical action generating unit drive this motion arm execution setting displacement action spatially;
This electrode catheter is connected with the motion arm of this machine driven system, thus drive this electrode catheter to carry out displacement action relative to this cell placement platform by this motion arm;
The signals collecting end input of this electric signal measurement system is connected to this electrode catheter, for measuring the bioelectrical signals of the cell irriate feedback that this electrode catheter gathers;
This cell placement platform comprises a piezoelectric sensing substrate uprightly arranged and places plate with this piezoelectric sensing substrate cell connected vertically, and measure traverse line drawn by this piezoelectric sensing substrate;
This piezoelectric measurement system is electrically connected with the measure traverse line of this cell placement platform, and the piezoelectric signal for the piezoelectric sensing substrate by this cell placement platform carries out real-time survey record; This piezoelectric measurement system is also connected with this mechanical transmission Controlling System, the piezoelectric signal measured in real time is fed back to this mechanical transmission Controlling System.
Further, it is a continuous lines frid that the cell of this cell placement platform places plate, and one of them side wall surface and this piezoelectric sensing substrate bonding of this continuous lines frid are arranged.
Further, this cell placement platform is employing two U-shaped supports, a crossbeam and a PVDF piezoelectric membrane structure, these two U-shaped supports are separately positioned on the two ends of this crossbeam, and by the U-shaped groove hole of these two U-shaped supports, the clamping of this crossbeam is 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 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 comprises: first straight-line displacement assembly being positioned at X-axis, a second straight-line displacement assembly being positioned at Y-axis and one are positioned at the 3rd straight-line displacement assembly of 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 the straight-line displacement assembly be made up of two end seats, two guide rails, a rhizoid bar, an electric controlled rotating device and driver plates, wherein these two guide rail parallels are arranged, two ends are fixed in these two end seats, this screw mandrel is arranged at the centre of these two guide rails, the socket of this driver plate and these two guide rails and a rhizoid bar, this electric controlled rotating device end seat disposed therein also drives this screw mandrel to rotate, thus drives the linearly displacement of this driver plate.Preferably, this electric controlled rotating device is a direct-current machine, and installation arranges an encoder.
It is controlled electrode catheter by machine driven system, mechanical transmission Controlling System that cell composite force of the present invention-electricity loads the device measured, polytype mechanical force signal is loaded to cell: 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 continuous loading that is single or multiple cell simultaneously; Electrode catheter is connected with electricity irritation or electrical measuring systems, then 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 mechanical structure portion 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 measured, 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.This cell composite force-electricity loads the device measured and utilizes mechanical transmission Controlling System to order about machine driven system to drive electrode catheter to carry out spys pressure or loading electricity irritation to the cell on cell placement platform, piezoelectric measurement system can the piezoelectric signal of the cell of this cell placement platform of survey record in real time, and the piezoelectric signal measured in real time is fed back to this mechanical transmission Controlling System, thus can the displacement action of spy pressure of accuracy controlling electrode catheter.Like this, cell composite force of the present invention-electricity loads the device measured and can be implemented in cell record electricity irritation and accurate pressure spy pressure, Measurement and analysis is carried out to cell real-time stress situation, and can be implemented in cell accurate pressure spy pressure, Measurement and analysis is carried out to cell real-time stress situation and cell irriate feedback bioelectrical signals, thus composite force-electricity of the individual cells that can realize cannot realizing in current technique means (also can multiple cell) 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 composite force-electricity of this embodiment loads the device measured, 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 is connected to the motion arm 5 of this mechanical action generating unit, and this mechanical action generating unit is for driving this motion arm 5 to perform displacement action spatially.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 comprises: first straight-line displacement assembly being positioned at X-axis, a second straight-line displacement assembly being positioned at Y-axis and one are positioned at the 3rd straight-line displacement assembly of 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 by two end seat 11,12, two guide rail 13, rhizoid bars, 14, electric controlled rotating device that (the electric controlled rotating device of this embodiment is preferably a direct-current machine 15, and installs and arrange an encoder 16; Electric controlled rotating device also can adopt piezoelectric motor, stepper-motor, servomotor to coordinate corresponding acceleration mechanism and function unit to realize) and the straight-line displacement assembly that forms of a driver plate 17, 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, the socket of this driver plate 17 and this two guide rails 13 and a rhizoid bar 14, this electric controlled rotating device end seat 11 disposed therein also drives this screw mandrel to rotate, thus drives this driver plate 17 linearly displacement.Same, this the second straight-line displacement assembly also adopts same straight-line displacement unit construction, installed by two end seat 21,22, two guide rail 23, rhizoid bars 24, direct-current machine 25 an electric controlled rotating device that an encoder 26 forms is set and a driver plate 27 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, to be connected by a base plate 28 between two end seats 21,22 and driver plate 17 for being fixed to this first straight-line displacement assembly.3rd straight-line displacement assembly is also adopt same straight-line displacement unit construction, has by two end seat 31,32, two guide rail 33, rhizoid bars 34, direct-current machine 35 and install to arrange an electric controlled rotating device that an encoder 36 forms and a driver plate 37 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, thus can base plate 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 namely this motion arm 5 is positioned at X-axis by this is positioned at Y-axis carrys out implementation space three-D displacement action with the 3rd straight-line displacement assembly being 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 to operate, thus make this mechanical action generating unit drive this motion arm to perform the displacement action of setting.This mechanical transmission Controlling System can adopt transmission control circuit corresponding with it to realize according to the difference of mechanical action generating unit.Such as, be adopt three-dimensional motion generating unit for above-mentioned mechanical action generating unit, then can adopt and there are three groups of control inputs ports of electric controlled rotating device of the 3rd straight-line displacement assembly exporting control signals and connect the first straight-line displacement assembly being positioned at X-axis being connected to this mechanical action generating unit respectively, the second straight-line displacement assembly being positioned at Y-axis and be positioned at Z axis.
Such as, 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, visit 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 composition of control algolithm is provided with to be visited pressure detection and visits pressure control module, the position detection of probe and position control module, the velocity measuring of probe and rate control module and Man Machine Interface module; The PVDF piezoelectric membrane 84 that the detection hardware visiting pressure is fixed on cell placing platform 8 by described and modulate circuit are formed.Voltage signal is converted to spy pressure signal by described spy pressure detection module.By described spy pressure control module and Man Machine Interface module, visit pressing and accurately can 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 the pressure degree of depth, spy pressure speed and frequency to cell and accurately can be set by user.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 connected with the motion arm 5 of this machine driven system, thus drive this electrode catheter 6 to carry out displacement action relative to this cell placement platform 8 by this motion arm 5, thus carry out spy press operation to the cell 9 on this cell placement platform 8.
Preferably, also comprise a bearing base, this bearing base is for placing a Tissue Culture Dish 7, and this cell placement platform 8 is placed in this Tissue Culture Dish 7.Preferred, one of them end seat 12 of first straight-line displacement assembly of this mechanical action generating unit can design thus directly substitute the function of this bearing base by change structure, by the height design get Geng Gao of this end seat 12, for this Tissue Culture Dish 7 of supporting.
The electrical signal of this electrical signal generation systems (not shown) is connected to this electrode catheter 6, for generation of the electrical stimulation signal loading on cell; This electrical signal generation systems can adopt the adjustable electrical signal generating circuit device established of electrical property feature such as voltage, frequency, electric current that can produce setting to realize, as adopted the conventional signal generator used, to provide direct current constant voltage and pulsed voltage.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 comprises a piezoelectric sensing substrate uprightly arranged and places plate with this piezoelectric sensing substrate cell connected vertically, measure traverse line drawn by this piezoelectric sensing substrate, thus prevent after this cell cell placed on plate is subject to electrode catheter 6 spy pressure, according to Newton's third law, stressed the conducting to of cell 9 is placed on the vertical piezoelectric sensing substrate of plate 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 places plate 86, also continuous U-shaped trunking plate or Continuous Rectangular taps frid etc. can be adopted), one of them side wall surface and this piezoelectric sensing substrate bonding of this continuous lines frid are arranged.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 CN102589760A, CN102967394A, and existing pressure resistance type MEMS vane, capacitive MEMS vane, PTC piezoelectric ceramic piece etc., but the difference (cell visits pressure) of the application scenarios of the device measured is loaded for cell composite force of the present invention-electricity, the piezoelectricity collection of this cell placement platform 8 needs to carry out suitable optimization, to improve its accuracy of detection and stability.
Concrete, consult shown in Fig. 2, the cell placement platform 8 of this embodiment is that the U-shaped support of employing two 81,82, crossbeam 83 and a PVDF piezoelectric membrane 84 build as piezoelectric sensing substrate.These two U-shaped supports 81,82 are separately positioned on the two ends of this crossbeam 83, and are clamped by this crossbeam 83 by the U-shaped groove hole of these two U-shaped supports 81,82 and open and flat fixing, and this PVDF piezoelectric membrane 84 is pasted on this crossbeam 83.A side wall surface of the cell placement plate 86 of this continuous V-shaped line frid and this PVDF piezoelectric membrane 84 bond and arrange.PVDF piezoelectric membrane 84 draws 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 synthetic glass or acryl can be adopted to make, and this crossbeam 83 adopts 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; a kind of structure of flexible support beam Bonding pressure sensitive material is disclosed compared with patent CN102589760A; the excessive pressure of the U-type groove structure energy available protecting that it adopts, to the destruction of pressure sensitive material, makes sensor have higher robustness.Compared with the pressure sensitive material fixed sturcture of a kind of Four built in boundaries disclosed in patent CN102967394A, U-shaped structure authorized pressure sensitive material has larger deformation space, expands the useful range of force transducer; And derive according to the moment of flexure of beam and floor equation, this structure can ensure pressure sensitive material pressure and should become exact linear relationship, improves the stated accuracy of force transducer.Compared to the structure of the sensing of some PVDF piezoelectric membranes triangular support sensitive material used, also there is more excellent characteristic.It is too simple that such as this preferred structure also overcomes existing this structure, can not 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 by mistake exported.
This piezoelectric measurement system (not shown) is electrically connected with the measure traverse line 85 of this cell placement platform, and the piezoelectric signal for the piezoelectric sensing substrate (i.e. the PVDF piezoelectric membrane 84 of this embodiment) by this cell placement platform carries out real-time survey record; This piezoelectric measurement system is also connected with this mechanical transmission Controlling System, the piezoelectric signal measured in real time is fed back to this mechanical transmission Controlling System, thus make this mechanical transmission Controlling System accurately can visit pressure-controlled to the electrode catheter 6 that this motion arm 5 of this machine driven system connects.This piezoelectric measurement system comprises conventional signal amplification module, Signal-regulated kinase, signal output module etc., and slightly different according to the difference of connected piezoelectric sensing substrate, the current techique be 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 measured, and to carry out the sight of a detection as follows: the cell one or more zebra fish ovum 9 being placed on 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 this mechanical transmission Controlling System respectively, the power supply of electrical signal generation systems and piezoelectric measurement system, the amplitude of electrical signal is applied by electrical signal generation systems human-computer interaction interface setting electrode catheter 6 pairs of cells 9 of control center, pulse width and frequency, by the loading position of mechanical transmission Controlling System human-computer interaction interface setting electrode catheter 6 pairs of cells, click the electrical signal load button of electrical signal generation systems human-computer interaction interface, this machine driven system drives electrode catheter 6 to apply electrical signal according to the parameters of electrical stimulation of input to cell 9 and loads, cell pressurized in stimulating course, by the PVDF piezoelectric membrane 84 of this cell placement platform 8, cell pressurized is produced force signal and carry out real-time survey record, and feed back to control center to 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 be connected to electrical signal generation systems, but is connected to an electric signal measurement system, thus 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 is connected to the motion arm of this mechanical action generating unit, and this mechanical action generating unit is for driving this motion arm execution displacement action spatially.
This mechanical transmission Controlling System and this mechanical action generating unit control linkage, for driving this mechanical action generating unit to operate, thus make this mechanical action generating unit drive this motion arm execution setting displacement action spatially.
This electrode catheter is connected with the motion arm of this machine driven system, thus drive this electrode catheter to carry out displacement action relative to this cell placement platform by this motion arm.
The signals collecting end input of this electric signal measurement system is connected to this electrode catheter, for measuring the bioelectrical signals of the cell irriate feedback that this electrode catheter gathers; This electric signal measurement system realizes amplification, the filtering and AD conversion etc. of weak bioelectrical signals by its electrical signal collection modulate circuit, and 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 comprises a piezoelectric sensing substrate uprightly arranged and places plate with this piezoelectric sensing substrate cell connected vertically, and measure traverse line drawn by this piezoelectric sensing substrate.
This piezoelectric measurement system is electrically connected with the measure traverse line of this cell placement platform, and the piezoelectric signal for the piezoelectric sensing substrate by this cell placement platform carries out real-time survey record; This piezoelectric measurement system is also connected with this mechanical transmission Controlling System, the piezoelectric signal measured in real time is fed back to this mechanical transmission Controlling System.
The cell composite force of this embodiment-electricity loads the device measured, and to carry out the sight of a detection as follows: the cell one or more zebra fish ovum being placed on 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 this mechanical transmission Controlling System respectively, the power supply of electric signal measurement system and piezoelectric measurement system, by mechanical transmission Controlling System human-computer interaction interface setting electrode catheter to the loading position of cell, click the electrical signal load button of electrical signal generation systems human-computer interaction interface, this machine driven system drives electrode catheter to apply probe physics according to the parameters of electrical stimulation of input to cell and visits pressure, it is 1.7 mm/second that such as physics visits pressure loading velocity, frequency is 2 hertz, cell pressurized in pressure stimulating course is visited at physics, by the PVDF piezoelectric membrane of this cell placement platform, cell pressurized is produced force signal and carry out real-time survey record, and feed back to control center to adjust this mechanical transmission Controlling System.Now, when this electrode catheter is visited and is pressed onto cell different sites, cell irriate can feed back bioelectrical signals, carries out real-time survey record by this electric signal measurement system.
As fully visible, the invention has the advantages that: 1, by this device, the physiology reflection of single or continuous multiple cell under accurate mechanical signal, electrical signal stimulate can be studied; 2, by this device, the physiology reflection of unicellular or continuous multiple cell under accurate mechanics-electrical signal stimulates can be studied; 3, by this device, change and the reflection of other physiology of the membrane potential of unicellular or continuous multiple cell under accurate mechanical signal stimulates can be studied; 4, structure of the present invention is simple, use, good stability, and the research of cyto-mechanics and the evaluation of cell quality provide a new thinking and new research means.
Although specifically show in conjunction with preferred embodiment and describe the present invention; but those skilled in the art should be understood that; 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 the device measured, 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 is connected to the motion arm of this mechanical action generating unit, and this mechanical action generating unit is for driving this motion arm execution displacement action spatially;
This mechanical transmission Controlling System and this mechanical action generating unit control linkage, for driving this mechanical action generating unit to operate, thus make this mechanical action generating unit drive this motion arm to perform the displacement action of setting;
This electrode catheter is connected with the motion arm of this machine driven system, thus drive this electrode catheter to carry out displacement action relative to this cell placement platform by this motion arm;
The electrical signal of this electrical signal generation systems is connected to this electrode catheter, for generation of the electrical stimulation signal loading on cell;
This cell placement platform comprises a piezoelectric sensing substrate uprightly arranged and places plate with this piezoelectric sensing substrate cell connected vertically, and it is a continuous lines frid that this cell places plate, and measure traverse line drawn by this piezoelectric sensing substrate;
This piezoelectric measurement system is electrically connected with the measure traverse line of this cell placement platform, and the piezoelectric signal for the piezoelectric sensing substrate by this cell placement platform carries out real-time survey record; This piezoelectric measurement system is also connected with this mechanical transmission Controlling System, the piezoelectric signal measured in real time is fed back to this mechanical transmission Controlling System.
2. cell composite force-electricity loads the device measured, 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 is connected to the motion arm of this mechanical action generating unit, and this mechanical action generating unit is for driving this motion arm execution displacement action spatially;
This mechanical transmission Controlling System and this mechanical action generating unit control linkage, for driving this mechanical action generating unit to operate, thus make this mechanical action generating unit drive this motion arm execution setting displacement action spatially;
This electrode catheter is connected with the motion arm of this machine driven system, thus drive this electrode catheter to carry out displacement action relative to this cell placement platform by this motion arm;
The signals collecting end input of this electric signal measurement system is connected to this electrode catheter, for measuring the bioelectrical signals of the cell irriate feedback that this electrode catheter gathers;
This cell placement platform comprises a piezoelectric sensing substrate uprightly arranged and places plate with this piezoelectric sensing substrate cell connected vertically, and it is a continuous lines frid that this cell places plate, and measure traverse line drawn by this piezoelectric sensing substrate;
This piezoelectric measurement system is electrically connected with the measure traverse line of this cell placement platform, and the piezoelectric signal for the piezoelectric sensing substrate by this cell placement platform carries out real-time survey record; This piezoelectric measurement system is also connected with this mechanical transmission Controlling System, the piezoelectric signal measured in real time is fed back to this mechanical transmission Controlling System.
3. cell composite force according to claim 1 and 2-electricity loads the device measured, and it is characterized in that: one of them side wall surface and this piezoelectric sensing substrate bonding of this continuous lines frid are arranged.
4. cell composite force according to claim 3-electricity loads the device measured, it is characterized in that: this cell placement platform is employing two U-shaped supports, a crossbeam and a PVDF piezoelectric membrane structure, these two U-shaped supports are separately positioned on the two ends of this crossbeam, and by the U-shaped groove hole of these two U-shaped supports, the clamping of this crossbeam is 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 measured, 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 measured, and it is characterized in that: also comprise a bearing base, this bearing base is 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 measured, 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 measured, it is characterized in that: this three-dimensional motion generating unit comprises: first straight-line displacement assembly being positioned at X-axis, a second straight-line displacement assembly being positioned at Y-axis and one are positioned at the 3rd straight-line displacement assembly of 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 measured, it is characterized in that: this is first years old, second, 3rd straight-line displacement assembly includes by two end seats, two guide rails, one rhizoid bar, the straight-line displacement assembly of an electric controlled rotating device and a driver plate composition, wherein these two guide rail parallels are arranged, two ends are fixed in these two end seats, this screw mandrel is arranged at the centre of these two guide rails, the socket of this driver plate and these two guide rails and a rhizoid bar, this electric controlled rotating device end seat disposed therein also drives this screw mandrel to rotate, thus drive the linearly displacement of this driver plate.
10. cell composite force according to claim 9-electricity loads the device measured, 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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