CN104946523A - Measuring apparatus and measuring method of cell mechanics - Google Patents
Measuring apparatus and measuring method of cell mechanics Download PDFInfo
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- CN104946523A CN104946523A CN201510282272.XA CN201510282272A CN104946523A CN 104946523 A CN104946523 A CN 104946523A CN 201510282272 A CN201510282272 A CN 201510282272A CN 104946523 A CN104946523 A CN 104946523A
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/02—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving viable microorganisms
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/483—Physical analysis of biological material
- G01N33/487—Physical analysis of biological material of liquid biological material
- G01N33/48707—Physical analysis of biological material of liquid biological material by electrical means
- G01N33/48728—Investigating individual cells, e.g. by patch clamp, voltage clamp
Abstract
The present invention relates to a measuring apparatus, and discloses a measuring apparatus and a measuring method of cell mechanics. The measuring apparatus comprises: a sample tray (1) for placing a cell sample, a measuring unit (2) for contacting the cell sample in the sample tray (1) to acquire the mechanical parameters of the cell sample, and a control unit (3) connected with the measuring unit (2) and used for controlling the measuring unit (2) to vertically move according to the mechanical parameters so as to change the contacting degree of the measuring unit (2) and the sample cell and make the measuring unit (2) acquire the mechanical parameters of the cell sample within the contacting degree change period. With the measuring apparatus, the mechanical parameters of the cell can be accurately acquired.
Description
Technical field
The present invention relates to a kind of measuring apparatus, particularly, relate to a kind of measuring apparatus and measuring method of cyto-mechanics.
Background technology
The mechanics parameter of cell comprises the rigidity, viscosity etc. of cell, and the state of described mechanics parameter and cytoskeleton is closely related, and cytoskeleton in cell migration, breed, engulf and played keying action in associated molecule intracellular signaling process.Pathophysiological process in each organ-tissue of human body is along with the change of cyto-mechanics parameter, particularly tumour cell, because the abilities such as its propagation, migration and metabolism are all different from normal cell, its mechanics parameter is different from the cell of normal physiological tissue all significantly.Such as, the rigidity coming from normal bladder tissue clone (Hu609 and HCV29) is ten times of clone (Hu456, T24, the BC3726) rigidity coming from Bladder Cancer; The rigidity coming from normal galactophore tissue's clone (MCF-10A) is 1.4 ~ 1.8 times that come from breast cancer tissue's clone (MCF-7) rigidity.In addition, the mechanics parameter of tumour cell can also react its susceptibility to chemotherapeutics.Research finds, green tea crude extract (Green Tea Extract, GTE) optionally produces cytotoxicity to tumour cell, do not affect normal cell simultaneously, after GTE effect, tumour cell increases due to expression of actin, and stiffness by itself also increases; And normal cell after GTE effect rigidity without significant change.
Therefore, not only can be applied to the early diagnosis of clinical middle cancer and the selection of personalized chemotherapeutic medicine to the detection of tumour cell self mechanics parameter, also can be the screening of high-throughout chemotherapeutics simultaneously and quantitative foundation is provided.
Atomic force microscopy is the common technology means measuring cell rigidity, but traditional atomic force microscope can only detect the carrying out of viable cell in liquid phase physiological environment, obtains cell image, and technical parameter requires strict; Because piezoelectric ceramics tubular type scanning device resonant frequency is low, cause that efficiency of measurement is low, accuracy of detection is poor, limit its further application in high-flux cell mechanical test.
Summary of the invention
The object of this invention is to provide a kind of cyto-mechanics measuring apparatus, accurately can obtain the mechanics parameter of cell.
To achieve these goals, the invention provides a kind of measuring apparatus of cyto-mechanics, described measuring apparatus comprises sample disc, for placing cell sample; Measuring unit, for contacting with the cell sample in described sample disc, obtains the mechanics parameter of described cell sample; And control unit, be connected with described measuring unit, for controlling described measuring unit vertical movement according to described mechanics parameter, to change the exposure level of described measuring unit and described cell sample, described measuring unit is made to obtain the mechanics parameter of described cell sample in described exposure level During.
The measuring apparatus of cyto-mechanics of the present invention is by the setting of control unit, the exposure level in measuring unit and sample disc between cell sample can be adjusted as required, to obtain the mechanics parameter of exposure level During inner cell sample, useful range is wide, accuracy is high.
Another object of the present invention is to the measuring method that a kind of cyto-mechanics is provided, accurately can obtain the mechanics parameter of cell.
For achieving the above object, technical scheme of the present invention is achieved in that
A measuring method for cyto-mechanics, described measuring method comprises: be positioned over by cell sample in sample disc; Use measuring unit to measure to contact with the cell sample in described sample disc, obtain the mechanics parameter of described cell sample; Control described measuring unit vertical movement according to described mechanics parameter, to change the exposure level of described measuring unit and described cell sample, make described measuring unit obtain the mechanics parameter of described cell sample in described exposure level During.
The Dominant Facies that the measuring method of described cyto-mechanics and the measuring apparatus of above-mentioned cyto-mechanics have relative to prior art is same, does not repeat them here.
Other features and advantages of the present invention are described in detail in embodiment part subsequently.
Accompanying drawing explanation
Accompanying drawing is used to provide a further understanding of the present invention, and forms a part for specification sheets, is used from explanation the present invention, but is not construed as limiting the invention with embodiment one below.In the accompanying drawings:
Fig. 1 is the measuring apparatus three-dimensional arrangement block diagram of cyto-mechanics of the present invention;
Fig. 2 is the modular structure schematic diagram of the control unit in the measuring apparatus of cyto-mechanics of the present invention;
Fig. 3 is the structural representation of sample disc in the measuring apparatus of cyto-mechanics of the present invention;
Fig. 4 is the schema of the measuring method of cyto-mechanics of the present invention;
Fig. 5 is the closed-loop control schematic diagram of positioning table in the measuring method of cyto-mechanics of the present invention;
Fig. 6 is an embodiment of the measuring method of cyto-mechanics of the present invention.
Description of reference numerals
1 sample disc 2 measuring unit
21 laser apparatus 22 photoelectric conversion modules
23 probe detector 24 piezoelectric ceramic stacks
25 image capture module 3 control units
31 adjustment of displacement module 32 control modules
33 photoelectric processing module 34 positioning table control modules
35 displacement platform control module 4 positioning tables
5 displacement platforms
Embodiment
Below in conjunction with accompanying drawing, the specific embodiment of the present invention is described in detail.Should be understood that, embodiment described herein, only for instruction and explanation of the present invention, is not limited to the present invention.
In the present invention, when not doing contrary explanation, the direction term mentioned, such as " on ", D score, "front", "rear", "left", "right" etc., be only the direction with reference to accompanying drawing.Therefore, the direction term of use is used to illustrate and is not used for limiting the scope of the invention.
As depicted in figs. 1 and 2, cyto-mechanics measuring apparatus of the present invention comprises sample disc 1, for placing cell sample; Measuring unit 2, for contacting with the cell sample in described sample disc 1, obtains the mechanics parameter of described cell sample; And control unit 3, be connected with described measuring unit 2, for controlling the vertical movement of described measuring unit 2 according to described mechanics parameter, to change described measuring unit 2 and the exposure level of described cell sample, described measuring unit 2 is made to obtain the mechanics parameter of described cell sample in described exposure level During.
The measuring apparatus of cyto-mechanics of the present invention is by the setting of control unit, the exposure level in measuring unit and sample disc between cell sample can be adjusted as required, to obtain the mechanics parameter of exposure level During inner cell sample, useful range is wide, accuracy is high; And to measurement environment without particular requirement, efficiency of measurement is high.
Described control unit 3 controls the vertical movement of described measuring unit 2 according to described mechanics parameter and comprises: the mechanics parameter that described measuring unit 2 obtains by described control unit 3 and set(ting)value compare, for: when described mechanics parameter > set(ting)value, control described measuring unit 2 upward vertical movement, described measuring unit 2 is weakened, until stop motion during the mechanics parameter again obtained=described set(ting)value with the exposure level of described cell sample; When described mechanics parameter < set(ting)value, control described measuring unit 2 vertical downward movement, described measuring unit 2 is strengthened, until stop motion during the mechanics parameter again obtained=described set(ting)value with the exposure level of described cell sample.
Wherein, described mechanics parameter comprises at least one in cell rigidity, viscosity and the interaction force between measuring unit and cell sample etc.
As shown in Figure 1, described measuring unit 2 comprises laser apparatus 21, for perpendicular to described sample disc 1 transmitted beam; Detection module, can vertical movement, and for contacting with the cell sample in described sample disc 1 and interact, the beam reflection of simultaneously being launched by described laser apparatus 21 becomes to characterize the spot signal of mechanics parameter; And photoelectric conversion module 22, be sent to described control unit 3 for receiving described spot signal and being converted to the electrical signal characterizing described mechanics parameter; Described control unit 3 connects described photoelectric conversion module 22 and detection module respectively, for receiving the electrical signal characterizing mechanics parameter, and control described detection module vertical movement according to described mechanics parameter, to change the exposure level of described detection module and described cell sample.In the present embodiment, described photoelectric conversion module 22 is four-quadrant photo-sensor.
Wherein, described detection module comprises probe detector 23, for contacting with cell sample and interacting, becomes to characterize the spot signal of mechanics parameter by beam reflection simultaneously; And piezoelectric ceramic stack 24, be connected with described probe detector 23; For being controlled by described control unit 3, and drive the vertical movement of described probe detector 23.
In the present embodiment, described probe detector 23 comprises probe, and described probe is installed on probe base, and described probe and described piezoelectric ceramic stack 24 are rigidly connected.
For described mechanics parameter for interaction force: the interaction force that described probe obtains by described control unit 3 and set(ting)value compare, when described interaction force > set(ting)value, described control unit 3 controls described piezoelectric ceramic stack 24 at upward vertical movement, the exposure level of described probe and cell sample is weakened, until again obtain interaction force=set(ting)value time stop; When interaction force < set(ting)value, control unit 3 controls described piezoelectric ceramic stack 24 at vertical downward movement, and the exposure level of described probe and cell sample is strengthened, until again obtain interaction force=set(ting)value time stop.Described piezoelectric ceramic stack 24 by vertical direction up and down motion make probe complete measurement to a cell sample surface, obtain the many groups mechanics parameter in exposure level During, form mechanics parameter curve, and record storage related data by described control unit 3.
Described measuring unit 2 also comprises fine setting module (not shown), is connected, for adjusting the position of described photoelectric conversion module 22 to receive described spot signal with described photoelectric conversion module 22.
Preferred version, described measuring unit 2 also comprises image capture module 25, shows the image of the position relationship of described detection module and cell sample for Real-time Collection, to guarantee that described detection module is vertical corresponding with described cell sample.In the present embodiment, described image capture module 25 is CCD (Charge-coupled Device, charge coupled cell).By the setting of CCD, can the position relationship of probe described in Real-time Obtaining and cell sample, can adjust in time when deviation appears in the position of described probe and cell sample, guarantee the accuracy that mechanics parameter is measured.
As Fig. 2, described control unit 3 comprises adjustment of displacement module 31, for controlling described detection module vertical movement; And control module 32, connect described photoelectric conversion module 22 and described adjustment of displacement module 31 respectively, determine corresponding mechanics parameter for receiving the electrical signal characterizing described mechanics parameter, and export vertical translation signal to described adjustment of displacement module 31 according to described mechanics parameter.
The electrical signal characterizing mechanics parameter is accurately received for making described control module 32, described electrical signal is also needed to process further, that is: described control unit 3 also comprises photoelectric processing module 33, be arranged between described control module 32 and photoelectric conversion module 22, after the electrical signal of described photoelectric conversion module 22 is amplified process, input to described control module 32.
As shown in Figure 1, the measuring apparatus of cyto-mechanics of the present invention also comprises: positioning table 4, be connected with described control unit 3, and described positioning table 4 is provided with described sample disc 1, for being controlled by described control unit 3, and drive described sample disc 1 level and/or vertical movement, with the different cell samples making described measuring unit 2 measure same measured zone in described sample disc 1.
Corresponding, described control unit 3 also comprises positioning table control module 34 (as shown in Figure 2), connects described control module 32 and positioning table 4 respectively, for: controlled by described control module 32, control described positioning table 4 level and/or vertical movement; Or by the horizontal shift signal feedback of described positioning table to described control module 32, described control module 32 positioning table 4 according to the horizontal shift signal control of described positioning table 4 continues to move horizontally or stop.
Wherein, the described positioning table of described control continues method that is mobile or that stop and comprises: calculate the horizontal shift of described positioning table and the difference of setting displacement, judges described difference whether in setting difference range; If in setting difference range, then control described positioning table and stop mobile; Otherwise, control described positioning table and continue to move horizontally.
In positioning table 4 pointwise position fixing process, stopping as early as possible after arriving target location to make described positioning table 4, in the control in the present invention to described positioning table 4, have employed the PID closed-loop control (as shown in Figure 5) in band adjustable dead band.According to the needs used, can set when positioning table goes to distance objective position ± n nanometer, positioning table control module 34 stops servocontrol, makes positioning table 4 keep current position motionless.
When the control signal r (k) of positioning table control module output is through conversion as shown in Figure 5, after completing one-time positioning control, by displacement sensor, displacement signal c (k) is fed back to control module through positioning table control module.R (k) and c (k) are carried out subtraction process by described control module, obtain difference e (k), and judge that whether described e (k) is at setting difference range [-e further
0, e
0] in: when setting difference range in (namely | e (k) |≤e
0) time, stop servocontrol, i.e. described positioning table stop motion, start the measurement carrying out mechanics parameter; Otherwise, when not setting difference range in (namely | e (k) | >e
0) time, then continue servocontrol, namely described positioning table continues tangential movement, until | e (k) |≤e
0.
By above-mentioned closed-loop control, not only shorten setting time, and avoid in mechanical meaurement process, the sample caused due to above-mentioned positioning table servo action moves, and improves mechanical meaurement precision.
In addition, positioning table control module 34 can also control the motion that positioning table 4 carries out vertical direction (i.e. Z-direction), for compensating the measuring error that cell sample or measuring unit 2 tilt to cause.
In the present embodiment, described positioning table 4 is flexible hinge nanometer positioning platform.Wherein, described flexible hinge nanometer positioning platform can realize the quick position of the power of nano level high resolution among a small circle in horizontal direction (i.e. X, Y-direction), as 200 μm × 200 μm, Z-direction stroke is several μm, as 4 μm, resolving power reaches sub-nanometer scale, and described flexible hinge nanometer positioning stylobate drives in piezoelectric ceramic stack, mechanical lever amplification principle, exports high-pressure activated by control unit.
Further, the measuring apparatus of cyto-mechanics of the present invention also comprises displacement platform 5, be connected with described control unit 3, and described displacement platform 5 is provided with described positioning table 4, for being controlled by described control unit 3, drive described positioning table 4 level and/or vertical movement, measure the cell sample of measured zone different in described sample disc to make described measuring unit 2.
Corresponding, described control unit 3 also comprises displacement platform control module 35 (as shown in Figure 2), connects described control module 32 and displacement platform 5 respectively, for: controlled by described control module 32, control described displacement platform 5 level and/or vertical movement; Or by the horizontal shift signal feedback of described displacement platform 5 to described control module 32, described control module 32 displacement platform 5 according to the horizontal shift signal control of described displacement platform 5 continues to move horizontally or stop.
Wherein, the control method that described control module 32 displacement platform 5 according to the horizontal shift signal control of described displacement platform 5 continues method and the positioning table described above 4 moving horizontally or stop is similar, does not repeat them here.
Described displacement platform 5 can drive the positioning table 4 on it to carry out X, Y-direction are moved, and with handover measurement region, range of movement is 1 × 1cm
2-50 × 50cm
2, and carry out Z-direction motion, with realize behind handover measurement region again sample disc to probe approach and Z-direction away from action is moved, range of movement is 1-50cm.
Described control unit 3 in the measuring apparatus of cyto-mechanics of the present invention also can connect upper computer, to realize the control of instruction, the collection of data and output.Wherein, described control module 32 can be PC104 embedded main board, described PC104 embedded main board is connected by network with described upper computer, connects described adjustment of displacement module 31, photoelectric processing module 33, positioning table control module 34 and displacement platform control module 35 respectively by PC104 bus.
As shown in Figure 3, described sample disc 1 comprises multiple measured zone, and each described measured zone all becomes the checker of dot matrix to distribute.The useful range of each described measured zone is 1 × 1mm
2to 30 × 30mm
2, each described tessellated region be 10 × 10 μm
2to 50 × 50 μm
2; Adjacently tessellatedly be spaced apart 0-10 μm.Further, each described checker inside has the promoting layer promoting cell attachment, described promoting layer can be made up of the material of any one or the combination such as collagen protein, ln, fibronectin, gelatin and poly-lysine, and also can be other has the protein material of correlation properties to make; Have the inhibition layer that T suppression cell is adherent between adjacent checker, described inhibition layer can be made up of the such as material such as bovine serum albumin, polyoxyethylene glycol and F127.Described sample disc 1 is fastened on positioning table 4 by screw, vacuum suck or magnetic-adsorption.
The measuring apparatus of cyto-mechanics of the present invention utilize positioning table to have locating speed is fast, precision is high advantage, carry out X, Y-direction among a small circle in fast and resetting, make rapidly detection module aim at the middle position of the cell sample to be measured in sample disc; Utilize displacement platform to have moving range is large, precision is high, carrying capacity is strong advantage, makes it drive positioning table on it and sample disc automatic switchover sample measurement region, avoids because positioning table moving range is little, the drawback of manual switchover measured zone length consuming time; Utilize the advantage that piezoelectric ceramic stack resonant frequency is high, positioning precision is high, the test of high-precision mechanics parameter can be carried out fast; Sample disc checker alignment technology is utilized to make cell sample ordered arrangement, make the process of the cell measurement in whole sample disc, only need search out first cell sample and probe alignment by CCD and displacement platform, then remaining cell is quick and precisely located with regard to realizing by simple control positioning table and displacement platform, easy to operate, efficiency of measurement is high.
As shown in Figure 4, the measuring method of cyto-mechanics of the present invention comprises: step 401: be positioned over by cell sample in sample disc; Step 402: measuring unit is contacted with the cell sample in described sample disc, obtains the mechanics parameter of described cell sample; Step 403: control described measuring unit vertical movement according to described mechanics parameter, to change the exposure level of described measuring unit and described cell sample, makes described measuring unit obtain the mechanics parameter of described cell sample in described exposure level During.
Wherein, the described method controlling described measuring unit vertical movement according to described mechanics parameter comprises: described mechanics parameter and set(ting)value are compared: when described mechanics parameter > set(ting)value, control described measuring unit upward vertical movement, the exposure level of described measuring unit and described cell sample is weakened, until stop motion during the mechanics parameter again obtained=described set(ting)value; When described mechanics parameter < set(ting)value, control described measuring unit vertical downward movement, the exposure level of described measuring unit and described cell sample is strengthened, until stop motion during the mechanics parameter again obtained=described set(ting)value.Described mechanics parameter comprises at least one in cell rigidity, viscosity and the interaction force between measuring unit and cell sample etc.
Wherein, the measuring method of cyto-mechanics of the present invention also comprises: before step 401 operates, first should prepare sample disc, that is: a slice template is provided, described template is prepared micron post, make described micron post in silicon template, become the chessboard of dot matrix to distribute, form described sample disc, wherein, multiple checker forms a measured zone, and described sample disc comprises multiple measured zone.
Further, by described sample disc in the lower process that imposes a condition, make the upper surface of described micron post to be modified with the promoting layer promoting cell attachment, adjacent micron intercolumniation has the adherent inhibition layer of T suppression cell.
Wherein, the method preparing micron post comprises: utilize reaction coupled plasma etch technology to prepare silicon template, utilize polydimethylsiloxane (PDMS, polydimethylsiloxane) to carry out complex, obtain the structure of micron post according to template.Wherein, described micron post is cylinder or side is foursquare rectangular structure, and the diameter of micron post or size dimension are 10-50 μm, be highly 5-10 μm, the spacing of adjacent microtrabeculae is 0-10 μm, and multiple microns of posts form a measured zone, and the area of described measured zone is 1 × 1mm
2-30 × 30mm
2.
Describedly to comprise in the process that imposes a condition: described micron rod structure is carried out Cement Composite Treated by Plasma, then the collagen protein of 10-100 μ g/mL, ln, fibronectin, gelatin is soaked in, or in the dextrorotation Poly-L-Lysine Solution of 0.01%, hatch 1 hour for 37 DEG C, to have modified the micron post of mentioned component for seal, by the surface of Western blot in hydrophobic plastic ware or glass dish substrate, make the upper surface of described micron post to be modified with the promoting layer promoting cell attachment; And by above-mentioned be modified with promote that the plastic ware of promoting layer of cell attachment or glass dish substrate hatch half an hour in F-127, bovine serum albumin or polyglycol solution after, make that there is between adjacent chessboard the adherent inhibition layer of T suppression cell.Cell sample puts into above-mentioned treated sample disc, and cultivates the measurement that 0.5-12 hour carries out mechanics parameter afterwards.
The measuring method of cyto-mechanics of the present invention also comprises: be installed on positioning table by described sample disc, controls described positioning table level and/or vertically movement, makes described detecting unit aim at cell sample to be measured; After a cell sample measurement terminates, control described positioning table level and/or vertical movement, make described measuring unit measure the different cell samples of same measured zone in described sample disc.
Wherein, in described positioning table tangential movement process, according to the horizontal shift signal control of described positioning table, positioning table continues mobile or stops.
The described positioning table of described control continues method that is mobile or that stop and comprises: calculate the horizontal shift of described positioning table and the difference of setting displacement, judges described difference whether in setting difference range; If in setting difference range, then control described positioning table and stop mobile; Otherwise, control described positioning table and continue to move horizontally.
Further, the measuring method of cyto-mechanics of the present invention also comprises: be arranged on displacement platform by described positioning table, controls described displacement platform level and/or vertical movement, and described measuring unit is contacted with cell sample to be measured; After a measured zone measurement terminates, control bit moving stage level and/or vertical movement, make described measuring unit measure the cell sample in the different measuring region in described sample disc.
Move horizontally in process at described displacement platform, according to the horizontal shift signal control of described displacement platform, displacement platform continues to move horizontally or stop.Wherein, it is similar that the described displacement platform of described control continues mobile or method that is that stop and described positioning table control method, do not repeat them here.
Preferably, the measuring method of cyto-mechanics of the present invention also comprises: Real-time Collection shows the image of the position relationship of described measuring unit and described cell sample, can adjust in time when deviation appears in the position of described measuring unit and cell sample, guarantee the accuracy of metrical information.
The measuring method (as shown in Figure 6) of cyto-mechanics of the present invention is introduced below in detail with a specific embodiment.
Observe also correspondence by CCD and move horizontally displacement platform, make the middle position of first cell sample to be measured in probe perpendicular alignmnet region to be measured; Then control bit moving stage is moved in Z-direction, makes described cell sample to be measured approach probe; Controlling piezoelectric ceramic stack drives probe to move in Z-direction, to adjust the exposure level of described probe and cell sample, obtains the mechanics parameter of described cell sample in exposure level During; After a cell sample measurement terminates, control positioning table and move horizontally, make the next cell central authorities to be measured (as shown in Figure 3, sweep limit can be 200 μm × 200 μm, and step pitch is 40 μm) of probe alignment; Judge whether the maximum scan scope arriving at described positioning table, if not, repeat aforesaid operations, continue to measure the different cell samples in same measured zone, otherwise, control bit moving stage level and/or vertical movement, to measure the cell sample in next measured zone; Judge whether the scanning of all zones, if completed, end operation, otherwise repeat aforesaid operations, continue to measure.
The measuring apparatus of cyto-mechanics of the present invention utilize positioning table to have locating speed is fast, precision is high advantage, carry out X, Y-direction among a small circle in fast and resetting, make rapidly the middle position of the cell sample to be measured in probe alignment sample disc; Utilize displacement platform to have moving range is large, precision is high, carrying capacity is strong advantage, make it drive positioning table on it and sample disc automatic switchover sample detection region, avoid because positioning table moving range is little, the drawback of manual switchover Sample Scan region length consuming time, easy to operate, efficiency of measurement is high.
Below the preferred embodiment of the present invention is described in detail by reference to the accompanying drawings; but; the present invention is not limited to the detail in above-mentioned embodiment; within the scope of technical conceive of the present invention; can carry out multiple simple variant to technical scheme of the present invention, these simple variant all belong to protection scope of the present invention.
It should be noted that in addition, each concrete technical characteristic described in above-mentioned embodiment, in reconcilable situation, can be combined by any suitable mode, in order to avoid unnecessary repetition, the present invention illustrates no longer separately to various possible array mode.
In addition, also can carry out arbitrary combination between various different embodiment of the present invention, as long as it is without prejudice to thought of the present invention, it should be considered as content disclosed in this invention equally.
Claims (18)
1. a measuring apparatus for cyto-mechanics, is characterized in that, described measuring apparatus comprises:
Sample disc (1), for placing cell sample;
Measuring unit (2), for contacting with the cell sample in described sample disc (1), obtains the mechanics parameter of described cell sample; And
Control unit (3), be connected with described measuring unit (2), for controlling described measuring unit (2) vertical movement according to described mechanics parameter, to change described measuring unit (2) and the exposure level of described cell sample, described measuring unit (2) is made to obtain the mechanics parameter of described cell sample in described exposure level During.
2. the measuring apparatus of cyto-mechanics according to claim 1, is characterized in that, described control unit (3) controls described measuring unit (2) vertical movement according to described mechanics parameter and comprises:
The mechanics parameter that described measuring unit (2) obtains by described control unit (3) and set(ting)value compare, for:
When described mechanics parameter > set(ting)value, control described measuring unit (2) upward vertical movement, described measuring unit (2) is weakened, until stop motion during the mechanics parameter again obtained=described set(ting)value with the exposure level of described cell sample;
When described mechanics parameter < set(ting)value, control described measuring unit (2) vertical downward movement, described measuring unit (2) is strengthened, until stop motion during the mechanics parameter again obtained=described set(ting)value with the exposure level of described cell sample.
3. the measuring apparatus of cyto-mechanics according to claim 1, is characterized in that, described measuring unit (2) comprising:
Laser apparatus (21), for perpendicular to described sample disc (1) transmitted beam;
Detection module, can vertical movement, and for contacting with the cell sample in described sample disc (1) and interact, the beam reflection of simultaneously being launched by described laser apparatus (21) becomes to characterize the spot signal of mechanics parameter; And
Photoelectric conversion module (22), for receiving described spot signal and being converted to the electrical signal of sign mechanics parameter and being sent to described control unit (3);
Described control unit (3) connects described photoelectric conversion module (22) and detection module respectively, for receiving the electrical signal of described sign mechanics parameter, and control described detection module vertical movement according to described mechanics parameter, to change the exposure level of described detection module and described cell sample.
4. the measuring apparatus of cyto-mechanics according to claim 3, is characterized in that, described detection module comprises:
Probe detector (23), for contacting with cell sample and interacting, becomes to characterize the spot signal of mechanics parameter simultaneously by beam reflection; And
Piezoelectric ceramic stack (24), is connected with described probe detector (23); For being controlled by described control unit (3), and drive described probe detector (23) vertical movement.
5. the measuring apparatus of cyto-mechanics according to claim 3, is characterized in that, described measuring unit also comprises:
Fine setting module, is connected with described photoelectric conversion module (22), for adjusting the position of described photoelectric conversion module (22) to receive described spot signal.
6. the measuring apparatus of cyto-mechanics according to claim 3, is characterized in that, described measuring unit (2) also comprises:
Image capture module (25), shows the image of described detection module and cell sample position relationship for Real-time Collection.
7. the measuring apparatus of the cyto-mechanics according to any one of claim 1-6, is characterized in that, described sample disc (1) comprises multiple measured zone, and each described measured zone all becomes the checker of dot matrix to distribute.
8. the measuring apparatus of cyto-mechanics according to claim 7, is characterized in that, each described checker inside has the promoting layer promoting cell attachment, has the inhibition layer that T suppression cell is adherent between adjacent checker.
9. the measuring apparatus of cyto-mechanics according to claim 7, is characterized in that, described measuring apparatus also comprises:
Positioning table (4), be connected with described control unit (3), and described positioning table (4) is provided with described sample disc (1), for being controlled by described control unit (3), and drive described sample disc (1) level and/or vertical movement, with the different cell samples making described measuring unit (2) measure same measured zone in described sample disc (1).
10. the measuring apparatus of cyto-mechanics according to claim 9, is characterized in that, described measuring apparatus also comprises:
Displacement platform (5), be connected with described control unit (3), and described displacement platform (5) is provided with described positioning table (4), for being controlled by described control unit (3), drive described positioning table (4) level and/or vertical movement, with the cell sample making described measuring unit (2) measure measured zone different in described sample disc.
The measuring method of 11. 1 kinds of cyto-mechanics, is characterized in that, described measuring method comprises:
Cell sample is positioned in sample disc;
Measuring unit is contacted with the cell sample in described sample disc, obtains the mechanics parameter of described cell sample;
Control described measuring unit vertical movement according to described mechanics parameter, to change the exposure level of described measuring unit and described cell sample, make described measuring unit obtain the mechanics parameter of described cell sample in described exposure level During.
The measuring method of 12. cyto-mechanics according to claim 11, is characterized in that, the described method controlling described measuring unit vertical movement according to described mechanics parameter comprises:
The mechanics parameter obtain described measuring unit and set(ting)value compare:
When described mechanics parameter > set(ting)value, control described measuring unit upward vertical movement, the exposure level of described measuring unit and described cell sample is weakened, until stop motion during the mechanics parameter again obtained=described set(ting)value;
When described mechanics parameter < set(ting)value, control described measuring unit vertical downward movement, the exposure level of described measuring unit and described cell sample is strengthened, until stop motion during the mechanics parameter again obtained=described set(ting)value.
The measuring method of 13. cyto-mechanics according to claim 11, it is characterized in that, described measuring method also comprises: provide a slice template, described template is prepared micron post, make described micron post in silicon template, become the checker of dot matrix to distribute, form described sample disc, wherein, multiple checker forms a measured zone, and described sample disc comprises multiple measured zone.
The measuring method of 14. cyto-mechanics according to claim 13, is characterized in that,
By described sample disc in the lower process that imposes a condition, make the upper surface of described micron post to be modified with the promoting layer promoting cell attachment, adjacent micron intercolumniation has the adherent inhibition layer of T suppression cell.
The measuring method of 15. cyto-mechanics according to claim 13, is characterized in that, described measuring method also comprises:
Described sample disc is installed on positioning table, controls described positioning table level and/or vertically movement, make described detecting unit aim at cell sample to be measured;
After a cell sample measurement terminates, control described positioning table level and/or vertical movement, make described measuring unit measure the different cell samples of same measured zone in described sample disc.
The measuring method of 16. cyto-mechanics according to claim 15, is characterized in that, in described positioning table tangential movement process, according to the horizontal shift signal control of described positioning table, positioning table continues mobile or stops.
The measuring method of 17. cyto-mechanics according to claim 16, is characterized in that, the described positioning table of described control continues method that is mobile or that stop and comprises:
The difference of the horizontal shift calculating described positioning table and setting displacement, judges described difference whether in setting difference range; If in setting difference range, then control described positioning table and stop mobile; Otherwise, control described positioning table and continue to move horizontally.
The measuring method of 18. cyto-mechanics according to any one of claim 15-17, it is characterized in that, described measuring method also comprises:
Described positioning table is arranged on displacement platform, controls described displacement platform level and/or vertical movement, described measuring unit is contacted with the cell sample in region to be measured;
After a measured zone measurement terminates, control bit moving stage level and/or vertical movement, make described measuring unit measure the cell sample in the different measuring region in described sample disc.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107209199A (en) * | 2016-01-07 | 2017-09-26 | 瑞尔赛特股份有限公司 | The detection of base material |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090205089A1 (en) * | 2005-10-13 | 2009-08-13 | Jaehnke Torsten | Method for Examining a Measurement Object, and Apparatus |
| US20100263098A1 (en) * | 2007-07-24 | 2010-10-14 | Mueller Torsten | Method and apparatus for the combined analysis of a sample with objects to be analyzed |
| CN104419642A (en) * | 2013-08-22 | 2015-03-18 | 中国科学院沈阳自动化研究所 | Cell physiological information detection system and detection method |
| CN204714807U (en) * | 2015-05-28 | 2015-10-21 | 三捷生物科技（北京）有限公司 | A kind of measuring apparatus of cyto-mechanics |
-
2015
- 2015-05-28 CN CN201510282272.XA patent/CN104946523B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090205089A1 (en) * | 2005-10-13 | 2009-08-13 | Jaehnke Torsten | Method for Examining a Measurement Object, and Apparatus |
| US20100263098A1 (en) * | 2007-07-24 | 2010-10-14 | Mueller Torsten | Method and apparatus for the combined analysis of a sample with objects to be analyzed |
| CN104419642A (en) * | 2013-08-22 | 2015-03-18 | 中国科学院沈阳自动化研究所 | Cell physiological information detection system and detection method |
| CN204714807U (en) * | 2015-05-28 | 2015-10-21 | 三捷生物科技（北京）有限公司 | A kind of measuring apparatus of cyto-mechanics |
Non-Patent Citations (1)
| Title |
|---|
| 韩文波等: "《光电探测、制导与控制技术实验教程》", 31 May 2014 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107209199A (en) * | 2016-01-07 | 2017-09-26 | 瑞尔赛特股份有限公司 | The detection of base material |
| CN107209199B (en) * | 2016-01-07 | 2022-04-08 | 瑞尔赛特股份有限公司 | Detection of substrates |
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|---|---|
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