CN112345524A - Execution and sensing integrated method and system based on micro-scale bubbles - Google Patents

Execution and sensing integrated method and system based on micro-scale bubbles Download PDF

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CN112345524A
CN112345524A CN202011260751.9A CN202011260751A CN112345524A CN 112345524 A CN112345524 A CN 112345524A CN 202011260751 A CN202011260751 A CN 202011260751A CN 112345524 A CN112345524 A CN 112345524A
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target object
bubble
bubbles
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刘吉晓
严珺嘉
周一笛
郭士杰
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Hebei University of Technology
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Abstract

The invention discloses an execution and sensing integrated method and a system based on micro-scale bubbles, wherein the method comprises the steps of 1) generating a stable bubble at the tail end of a capillary tube, and applying force to a target object through the bubble; 2) adjusting the position of the capillary by using the three-degree-of-freedom micro-operation platform, moving the bubbles to a target object, and pressing the target object to serve as a force actuator; 3) determining the current action positions of the bubbles and the target object in the vertical direction by using a CCD microscope, acquiring a video stream when the bubbles and the target object interact under the current action position in the horizontal direction by using a camera while the bubbles execute force on the target object, and performing image processing on the video stream to acquire the contact area of the bubbles and the target object at the current position so as to acquire the contact force between the bubbles and the target object; the air bubbles serve as an actuator and simultaneously realize the function of the sensor, and the two functions are simultaneously carried out to realize the integration of execution and sensing.

Description

Execution and sensing integrated method and system based on micro-scale bubbles
Technical Field
The invention relates to the technical field of micro-operation, in particular to an execution and sensing integrated method and system based on micro-scale bubbles.
Background
The research on the mechanical properties of the cells not only can understand the composition structure and the functions of the cells, but also can find a new direction for disease treatment and provide a theoretical basis for developing personalized medicine. The micromanipulation technology is an indispensable technology in the field of cell research, and at present, there are many methods for researching mechanical properties of cells through the micromanipulation technology, one of which is to apply force to a cell sample directly through a capillary, and since the capillary is rigid, the cell is damaged by direct contact with the cell, and further research results are influenced. When the existing method is used for obtaining the contact force between the capillary and the cell, a reference object is required to be added or a PVDF membrane is connected at the tail end of the capillary to obtain an electric signal, so that the magnitude of the contact force is calculated, the operation process is complex, and the result accuracy is low.
Xinyu Liu et al (see literature "Xinyu Liu, Yu Sun, Wenhui Wang and Bob Lansdorp. Vision-based cellular for measuring an electronic microscopic device [ J ]. Journal of microorganisms and microorganisms, 17(2007): 1281-1288.) in manipulating an egg cell of a mouse with a capillary, the magnitude of the contact force is calculated by measuring the deformation of a columnar structure, the capillary acting directly on the cell damages the cell, resulting in a low cell survival rate, and the process of fabricating the cell holder and measuring the deformation of the columnar structure is complicated and difficult to implement.
Yu Xie et al (see "AFORCE CONTROL BASED CELL INJECTION APPROACH IN A Bio-layers System [ J ]. IEEE International Conference on layers and analysis, 2009.) adopt a method of adding a PVDF membrane at the end of a capillary tube, and obtain a contact force by receiving an electric signal and measuring the deformation of the PVDF membrane.
Disclosure of Invention
Aiming at the defects of the prior art, the technical problem to be solved by the invention is to provide an execution and sensing integrated method and system based on micro-scale bubbles; the method uses the bubbles as a medium to flexibly apply force to the target object without damaging the target object, calculates the force through the parameters of the bubbles, and can calculate the force while applying the force, thereby realizing the function of integrating execution and sensing.
The technical scheme adopted by the invention for solving the technical problems is as follows:
an integrated execution and sensing method based on micro-scale bubbles is characterized by comprising the following steps:
1) generating a stable bubble at the end of the capillary tube, and applying force to the target object through the bubble;
2) adjusting the position of the capillary by using the three-degree-of-freedom micro-operation platform, moving the bubbles to a target object, and pressing the target object to serve as a force actuator;
3) determining the current action position of the bubble and the target object in the vertical direction by using a CCD microscope, acquiring a video stream when the bubble and the target object interact with each other in the current action position from the horizontal direction by using a camera while executing force on the target object by the bubble, performing image processing on the video stream to acquire a contact area A of the bubble and the target object in the current position, acquiring a contact force between the bubble and the target object according to formulas (1) and (2), further realizing the function of taking the bubble as a sensor, realizing the function of the sensor while taking the bubble as an actuator, and simultaneously performing the two functions to realize the integration of execution and sensing;
A=π(d/2)2
(1)
F=pA
(2)
in the formulas (1) to (2), d is the diameter of the contact surface; p is the gas pressure.
The radius of the generated bubbles is 5-500 microns, the air pressure is controlled by a bubble generator, and the bubble generator is an air pump.
The target object is a cell.
The invention also provides an execution and sensing integrated system based on the micro-scale bubbles, which comprises a capillary tube, a three-degree-of-freedom micro-operation platform and a CCD microscope; the system is characterized by also comprising an air pump, a coaxial light microscope, a microscope focusing moving platform and a camera;
a culture dish provided with a target object is placed on an objective table of the CCD microscope, a coaxial light microscope is arranged on a microscope focusing moving platform, a camera is arranged on the coaxial light microscope, and the coaxial light microscope acts on the side surface of the target object;
the three-degree-of-freedom micro-operation platform is provided with a connecting plate, a supporting rod extends out of the side face of the connecting plate, and the tail end of the supporting rod is hinged with a clamping rod; the capillary tube is clamped in the mounting groove of the clamping rod; one end of the capillary tube is connected with the output end of the air pump through the air feed pipe, and the tail end of the capillary tube generates bubbles.
One end of the capillary tube, which is used for giving out air, is of a conical structure, and the pipe diameter of the conical structure is gradually reduced from the air inlet to the air outlet.
The inner diameter of the tail end of the capillary tube is 10-900 micrometers.
Compared with the prior art, the invention has the beneficial effects that:
1. according to the invention, a single micro-scale bubble with controllable size is generated at the tail end of the capillary tube, the bubble is used as a gas-liquid flexible interface to act on a target object, and based on the surface tension of the gas-liquid flexible interface and the compressibility of gas, the interaction between the bubble and the target object is realized, so that the target object is prevented from being directly contacted with a rigid actuator (capillary tube) to cause damage to the target object; the method is suitable for researching the mechanical property of the cells, and the cells are forced by the bubbles, so that the defect of low cell survival rate caused by damage to the cells due to direct contact of the capillaries and the cells is avoided. The invention provides the method for using the bubbles as media to realize the functions of force application and force calculation for the first time, and deeply excavates the functions of the bubbles in the field of micro-operation.
2. The generated bubbles are stable, the size and the action position with a target object are controllable, the violent change of the cell or organism environment caused by the introduction of foreign matters is avoided, and the accuracy of research results is improved; the magnitude of acting force borne by the target object is obtained through the product of the gas pressure and the contact area of the bubbles and the target object, the calculation method is simple and easy to implement, and the bubbles can be used as a force actuator and a force sensor to perform simultaneously when interacting with the target object, so that the integrated function of execution and sensing is realized.
3. The system observes the action positions of the bubbles and the target object and the deformation of the upper surface of the target object through the CCD microscope, and additionally increases the observation direction along the horizontal direction through the coaxial light microscope and the camera, so that the target object is observed at multiple angles, the observation result is more accurate, and the visual information of the target object in multiple directions provides a basis for subsequent mechanical analysis. Although the three-dimensional microscope can realize multi-angle observation of the target object, the three-dimensional microscope is expensive, and the system has a simple structure and low cost.
Drawings
FIG. 1 is a schematic view of the overall structure of the present invention;
FIG. 2 is a schematic diagram of the structure of the capillary tube of the present invention;
FIG. 3 is a schematic view of the structure of the capillary action end of the present invention with a bubble;
FIG. 4 is a schematic diagram of the state of the present invention when bubbles interact with a target object;
FIG. 5 is a schematic diagram of the principle of the present invention as a bubble interacts with a target object;
FIG. 6 is a comparison of experimental validation results of the present invention;
in the figure, 1, a capillary; 2. a three-degree-of-freedom micro-operation platform; 3. an air pump; 4. a coaxial light microscope; 5. a CCD microscope; 6. a connecting plate; 7. a microscope focusing moving platform; 8. an air supply pipe; 9. a culture dish; 10. a camera; 11. a support bar; 12. and a clamping rod.
Detailed Description
Specific examples of the present invention are given below. The specific examples are only intended to illustrate the invention in further detail and do not limit the scope of protection of the claims of the present application.
The invention provides an execution and sensing integrated system (for short, see fig. 1-5) based on micro-scale bubbles, which comprises a capillary tube 1, a three-degree-of-freedom micro-operation platform 2, an air pump 3, a coaxial light microscope 4, a CCD microscope 5, a microscope focusing moving platform 7 and a camera 10;
the CCD microscope 5, the microscope focusing moving platform 7 and the three-degree-of-freedom micro-operation platform 2 are all placed on a test bed, a culture dish 9 is placed on an object stage of the CCD microscope 5, a target object (a cell in the embodiment) is placed in the culture dish 9, the target object is located in a visual field range of the CCD microscope 5, and the CCD microscope 5 is used for observing the specific position of the capillary 1 acting on the target object and the deformation condition of the upper surface of the target object; the coaxial light microscope 4 is arranged on the microscope focusing moving platform 7, the camera 10 is arranged on the coaxial light microscope 4, and the coaxial light microscope 4 is arranged on the side surface of a target object;
the top of the three-degree-of-freedom micro-operation platform 2 is provided with a connecting plate 6, a supporting rod 11 extends from the side surface of the connecting plate 6, the tail end of the supporting rod 11 is hinged with a clamping rod 12, and the clamping rod 12 and the supporting rod 11 can be relatively fixed; the clamping rod 12 is provided with a mounting groove (not shown in the figure), and the capillary tube 1 is clamped in the mounting groove; one end of the capillary 1 is connected with the output end of the air pump 3 through the air supply pipe 8, the tail end of the capillary is used for generating air bubbles, and the air pump 3 is placed on the test bed; the position of the capillary 1 in the space is adjusted by manually rotating an X-direction adjusting stud, a Y-direction adjusting stud and a Z-direction adjusting stud on the three-degree-of-freedom micro-operation platform 2, so that the tail end of the capillary 1 can extend into a culture dish 9; the air pump 3 is used for ventilating the capillary tube 1 through the air feed pipe 8, air and liquid in the culture dish 9 act on each other to form bubbles at the tail end of the capillary tube 1, the target object is forced through the bubbles, and the size of the bubbles can be controlled by adjusting the air output of the air pump 3.
The air outlet end of the capillary tube 1 is of a conical structure, the pipe diameter of the conical structure is gradually reduced from the air inlet along the tail end direction, the inner diameter of the tail end of the capillary tube 1 is 10-900 micrometers, the system is provided with capillary tubes of different specifications, and the capillary tubes of different specifications can generate bubbles of different sizes; the capillary tube 1 is drawn by a glass sampling tube with the diameter of 900mm in a needle drawing instrument, one end of the glass sampling tube is made to form a needle-shaped slender point, then the slender point is perpendicular to thinner abrasive paper (2000 meshes), the abrasive paper is ground, after the slender point is ground for a period of time, a microscope is used for observing whether the inner diameter of the slender point reaches the size required by an experiment, the slender point is connected with a syringe after the requirement is met, the syringe is used for washing residual fine scraps in the tube, and the capillary tube is obtained.
The model of the three-degree-of-freedom micro-operation platform 2 is LD 60-LM; the CCD microscope 5 is an Olympus microscope with model number BX 53F; the air pump 3 is a micro air pump with the model number AF 1-Dual-12789; the coaxial light microscope 4 adopts a Lapsun coaxial light microscope with the model number of 2000; the model of the camera 10 is PSC 600-03C; the focusing moving platform 7 of the moving microscope adopts an RSLOA horizontal focusing two-in-one platform of an acute Keniu brand.
The working principle and the working process of the invention are as follows:
and (3) adjustment of the system: firstly, placing a culture dish 9 filled with target objects (cells) on an objective table of a CCD microscope 5, adjusting the position of the objective table of the CCD microscope 5, and placing the target objects in the visual field range of the CCD microscope 5; adjusting an X-direction adjusting stud, a Y-direction adjusting stud and a Z-direction adjusting stud of the three-degree-of-freedom micro-operation platform 2, adjusting the tail end of the capillary 1 to be above a target object, and ensuring that the tail end of the capillary 1 is positioned in the visual field range of the CCD microscope 5 at the same time; the moving microscope focuses the moving platform 7, so that the target object and the tail end of the capillary tube are positioned in the visual field range of the coaxial light microscope 4, and the adjustment of the system is completed.
The camera and the camera 10 of the CCD microscope 5 respectively acquire video streams; the video stream that CCD microscope 5's camera obtained is used for observing the effect position of bubble and target object, and the video stream that camera 10 obtained is used for calculating the area of contact of bubble and target object, and in the process of whole bubble and target object interact, the bubble plays power executor and sensor integration parallel function simultaneously, especially in the mechanical properties research of cell, the system of this application can provide a flexible contact for the cell, avoids destroying the cell.
Due to the surface tension of the gas-liquid interface and the compressibility of the gas, flexible contact between the capillary 1 and the target object is realized, so that the function of the bubble as a force actuator is realized (see fig. 5, the bubble is in contact with the target object in fig. 5, an interaction force occurs, the bubble is pressed and acts on the target object, and the diameter of a contact area with the target object is d), and meanwhile, the force application size is estimated through the deformation of the bubble, so that the function of the bubble as a sensor is realized. The method for generating the bubbles is simple, the size of the bubbles is controllable, the radius of the bubbles is 5-500 micrometers, the pipe diameters of the tail ends of the capillary tubes 1 are different, the air pressure required for generating the bubbles is also different, the smaller the pipe diameter is, the greater the pressure required for generating the bubbles is, for example, the inner diameter of the tail end of the capillary tube 1 is 120 micrometers, and the pressure required for generating the bubbles is 1700-2500 pa; the inner diameter of the tail end of the capillary 1 is 500 micrometers, and the pressure required by bubble production is 1000 Pa-1200 Pa; the micro-scale bubbles with different sizes are generated by replacing the capillary tubes 1 with different specifications and simultaneously controlling and inputting the gas pressure in the capillary tubes 1, so that the micro-scale bubbles with different sizes are exerted on target objects, namely, the bubbles have wide space application as actuators and sensors due to the wide size range of generated bubbles.
The invention discloses an execution and sensing integrated method based on micro-scale bubbles, which comprises the following specific steps:
1) the air pump 3 is opened, the air pressure is gradually increased to a preset range from small to small, a stable bubble is generated at the tail end of the capillary tube 1, the target object is applied with force through the bubble, and the function of the force actuator is realized in a flexible mode;
2) adjusting the position of the capillary by using the three-degree-of-freedom micro-operation platform 2, contacting the bubble with a target object, and pressing the target object;
3) determining the current action position of the bubble and the target object in the vertical direction by using a CCD microscope, acquiring a video stream when the bubble and the target object interact with each other in the current action position from the horizontal direction by using a camera while executing force on the target object by the bubble, performing image processing on the video stream to acquire a contact area A of the bubble and the target object in the current position, acquiring a contact force between the bubble and the target object according to formulas (1) and (2), further realizing the function of taking the bubble as a sensor, realizing the function of the sensor while taking the bubble as an actuator, and simultaneously performing the two functions to realize the integration of execution and sensing;
A=π(d/2)2
(1)
F=pA
(2)
in formulas (1) to (2), a represents a contact area of the bubble with the target object; p is the gas pressure, which is read directly by the gas pump.
In order to verify the accuracy of force calculation through bubble parameters, namely the force application size is obtained through the product of the contact area of the bubbles and a target object and the air pressure of the bubbles, an experiment is designed to prove the feasibility and the accuracy of the calculation method;
firstly, fixing the lower end of a rectangular transparent adhesive tape in a culture dish, suspending the other end of the rectangular transparent adhesive tape, wherein the length of the transparent adhesive tape is 5459 micrometers, the width of the transparent adhesive tape is 586 micrometers, and the thickness of the transparent adhesive tape is 82 micrometers; adjusting lenses of the CCD microscope 5 and the camera 10 to enable the tail ends of the cantilever beam and the capillary tube to be located in the visual field range of the cantilever beam and the capillary tube, then generating a stable bubble with unchanged internal pressure at the tail end of the capillary tube with the tube diameter of 500 micrometers, controlling the position of the bubble at the tail end of the capillary tube to enable the bubble to be continuously close to and push the suspended end of the transparent adhesive tape, wherein the contact surface of the bubble and the cantilever beam is the surface where the length and the width of the cantilever beam are located; adjusting an X-direction adjusting stud, a Y-direction adjusting stud and a Z-direction adjusting stud of the three-degree-of-freedom micro-operation platform 2 to enable the bubbles to be continuously pushed to the cantilever beam, wherein the cantilever beam is continuously bent and deformed in the process, and an interaction force exists between the cantilever beam and the bubble, and can be obtained by calculating a bending formula (3) of the cantilever beam;
Figure BDA0002774550050000051
wherein E is the Young modulus of the cantilever beam material, and the value is 0.013 x 1011pa; w is the deflection displacement of the cantilever beam; i is the inertia moment of the cantilever beam; l is the height of the cantilever;
according to Newton's third law, two interaction forces are equal, namely, one force is obtained by the cantilever beam, and the other force obtained by the bubble is equal, so that the interaction force between the bubble and the cantilever beam can also be obtained by calculating the parameters of the bubble, and the correctness and the effectiveness of the method calculated by the bubble are verified.
In the process of pushing the cantilever beam by the air bubble, acquiring data (deflection displacement of the cantilever beam and contact area of the air bubble and the cantilever beam) at seven moments to calculate the interaction force at the seven moments, wherein as shown in fig. 6, FA represents the force calculated by the air bubble, and FB represents the force obtained by the cantilever beam; as can be seen from the figure, the two forces are very close in magnitude, and the maximum error does not exceed 3%, thus proving the correctness of the calculation method of the force through the parameters of the air bubble.
Nothing in this specification is said to apply to the prior art.

Claims (6)

1. An integrated execution and sensing method based on micro-scale bubbles is characterized by comprising the following steps:
1) generating a stable bubble at the end of the capillary tube, and applying force to the target object through the bubble;
2) adjusting the position of the capillary by using the three-degree-of-freedom micro-operation platform, moving the bubbles to a target object, and pressing the target object to serve as a force actuator;
3) determining the current action position of the bubble and the target object in the vertical direction by using a CCD microscope, acquiring a video stream when the bubble and the target object interact with each other in the current action position from the horizontal direction by using a camera while executing force on the target object by the bubble, performing image processing on the video stream to acquire a contact area A of the bubble and the target object in the current position, acquiring a contact force between the bubble and the target object according to formulas (1) and (2), further realizing the function of taking the bubble as a sensor, realizing the function of the sensor while taking the bubble as an actuator, and simultaneously performing the two functions to realize the integration of execution and sensing;
A=π(d/2)2
(1)
F=pA
(2)
in the formulas (1) to (2), d is the diameter of the contact surface; p is the gas pressure.
2. The integrated execution and sensing method based on micro-scale bubbles according to claim 1, wherein the radius of the generated bubbles is 5-500 microns, the gas pressure is controlled by a bubble generator, and the bubble generator is an air pump.
3. The micro-scale bubble based integrated performance and sensing method of claim 1, wherein the target object is a cell.
4. An execution and sensing integrated system based on micro-scale bubbles comprises a capillary tube, a three-degree-of-freedom micro-operation platform and a CCD microscope; the system is characterized by also comprising an air pump, a coaxial light microscope, a microscope focusing moving platform and a camera;
the culture dish provided with the target object is placed on the objective table of the CCD microscope, the coaxial light microscope is installed on the microscope focusing moving platform, the camera is installed on the coaxial light microscope, and the coaxial light microscope acts on the side surface of the target object, so that the observation angle is increased, the visual information of the observation bubble and the target object is enriched, and the accurate control of the bubble position and the subsequent mechanical analysis are facilitated;
the three-degree-of-freedom micro-operation platform is provided with a connecting plate, a supporting rod extends out of the side face of the connecting plate, and the tail end of the supporting rod is hinged with a clamping rod; the capillary tube is clamped in the mounting groove of the clamping rod; one end of the capillary tube is connected with the output end of the air pump through the air feed pipe, and the tail end of the capillary tube generates bubbles.
5. The integrated micro-scale bubble-based execution and sensing system according to claim 4, wherein the outlet end of the capillary tube is of a conical structure, and the diameter of the pipe of the conical structure is gradually reduced from the inlet to the outlet.
6. The integrated microscale bubble-based implement and sense system of claim 4 wherein the capillary tip has an internal diameter of 10-900 microns.
CN202011260751.9A 2020-11-12 2020-11-12 Execution and sensing integrated method and system based on micro-scale bubbles Pending CN112345524A (en)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113189358A (en) * 2021-05-06 2021-07-30 上海迈振电子科技有限公司 Semi-contact type sample applicator and preparation method of micro-cantilever sensor chip
CN116059890A (en) * 2023-03-08 2023-05-05 北京理工大学 Micro-hybrid robot device based on sound-dispelling bubble oscillation and hybrid control method

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113189358A (en) * 2021-05-06 2021-07-30 上海迈振电子科技有限公司 Semi-contact type sample applicator and preparation method of micro-cantilever sensor chip
CN113189358B (en) * 2021-05-06 2023-05-30 上海迈振电子科技有限公司 Semi-contact sample application instrument and preparation method of micro-cantilever sensing chip
CN116059890A (en) * 2023-03-08 2023-05-05 北京理工大学 Micro-hybrid robot device based on sound-dispelling bubble oscillation and hybrid control method
CN116059890B (en) * 2023-03-08 2024-06-11 北京理工大学 Micro-hybrid robot device based on sound-dispelling bubble oscillation and hybrid control method

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