CN115895883A - Device and method for controlling movement and rotation of tiny target driven by acoustic flow forceps - Google Patents
Device and method for controlling movement and rotation of tiny target driven by acoustic flow forceps Download PDFInfo
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- CN115895883A CN115895883A CN202211438567.8A CN202211438567A CN115895883A CN 115895883 A CN115895883 A CN 115895883A CN 202211438567 A CN202211438567 A CN 202211438567A CN 115895883 A CN115895883 A CN 115895883A
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Abstract
The invention provides a device and a method for controlling the movement and rotation of a tiny target driven by acoustic flow forceps, wherein a piezoelectric transducer generates acoustic waves to cause a hammer-shaped tail end micro glass needle to resonate, and particles rotate and move under the combined action of flow field force and secondary radiation force generated by the hammer-shaped tail end micro glass needle; the invention avoids the physical contact between the operation tail end and the particles in the whole operation process, thereby not causing any damage to the target, and the hammer-shaped tail end enables the particles to keep rotating in situ, thereby being easy to control the particles in an observation range; the invention is not limited by the size of the operation task and the operation object, and has strong operation flexibility; in addition, the invention realizes that the movement, the orientation and the fixation of the particles are completed by one actuator, thereby avoiding the problems of high operation complexity, low success rate, low efficiency and the like caused by the traditional multiple actuators.
Description
Technical Field
The invention belongs to the technical field of micro-nano operation, and particularly relates to a device and a method for controlling movement and rotation of a micro target driven by acoustic streaming forceps.
Background
Since cells have the ability to independently perform various vital activities as a basic unit of organism structure and function, research on cytology has attracted much attention in the field of modern bioscience. In recent thirty years, the micromanipulation technology has rapidly advanced, which provides a very important tool for the development of the biomedical field, and the micromanipulation technology related to cells has become the basis for exploring the essence of life and solving the related problems by using methods such as microscopic observation and microsurgery, etc. In the fields of biomedical analysis, clinical research and the like, the controllable accurate operation of single cells is very important, and the technology is widely applied to specific processes such as genetic engineering, embryo transplantation, cloning technology, in vitro fertilization and the like. In these procedures, the physician often needs to move, position, fix, inject, etc. the oocyte under the microscope. The positioning of the cells is mainly to adjust the posture of the cells through rotation and position the cells in the direction required by later operation. After the cells are located, operations such as sperm injection or genetic material extraction can be performed. For example, for the injection of sperm into oocyte, the nucleus is located at the edge of the cell and asymmetrically distributed, and during the cell injection process, the nucleus, the injection needle and the fixing needle need to be repositioned to a proper position through rotation operation, and the nucleus, the injection needle and the fixing needle are adjusted to be in the same plane to ensure that the nucleus, the injection needle and the fixing needle can be observed simultaneously under a microscope, thereby ensuring that the cell injection is successfully realized. In addition, embryonic cells require multiple three-dimensional image evaluations prior to implantation to ensure their morphological structure is satisfactory. In both of these steps, the position and orientation of the cell needs to be precisely controlled, wherein the omni-directional rotational positioning of the cell involves two main fundamental motions — rotation in the focal plane and rotation in the perpendicular to the focal plane, defined as in-plane rotation and out-of-plane rotation, respectively. Whether the moving, positioning and fixing processes of the cell successfully determine the success or failure of the cell micromanipulation is urgent, and therefore, there is a need to create a micromanipulation apparatus and method which can be switched in multiple modes, and is efficient, accurate and safe.
To date, high spatial resolution microactuators have greatly facilitated precise movement of cells by contact or non-contact means, but controlled high precision cell rotation techniques remain a challenge, particularly micromanipulation techniques with simultaneous cell capture, movement and rotation. At present, most of clinical practices still stay in a physical contact mode, and the tip of the traditional microneedle is used for directly poking cells so as to realize position control. Although this method is relatively straightforward to use, it has many disadvantages. The thin glass needle as the operation terminal inevitably causes mechanical damage such as local negative pressure, puncture wound and the like to cells in the operation process, and the requirement of high precision makes the manipulator too complicated to realize higher stability, which causes low success rate of cell micromanipulation. With the development of micromanipulation techniques, people are not dependent on contact type operation mode any more, but by controlling a plurality of physical fields, and in recent years, a series of driving methods based on physical field energy (for example, optical tweezers, magnetic tweezers, acoustic tweezers, dielectrophoresis, hydrodynamic field, and the like) have been established for moving and rotating cells. These processes do not have direct mechanical contact, overcome some disadvantages of contact physical operation, but still have risks that magnetic fields, electric fields or high temperatures may cause potential damage to cells, and such methods are complex and expensive in equipment and have high popularization thresholds. In contrast, hydrodynamic fields are often considered lossless by plotting a pressure gradient profile, creating directional fluid forces to alter the movement of cells. However, this method is often implemented in a closed and narrow microfluidic channel, and flexible cell taking and placing cannot be achieved, and is generally only suitable for cell observation and is not suitable for further cell surgery, such as injection, enucleation, and the like.
In summary, the existing micromanipulation techniques are increasingly difficult to satisfy the requirement of moving, positioning and fixing the oocyte, etc.
Disclosure of Invention
In order to overcome the defects of the prior art, the invention provides a device and a method for controlling the movement and rotation of a tiny target driven by acoustic flow tweezers.
A device for controlling the movement and rotation of a tiny target driven by acoustic flow tweezers comprises a tiny glass needle (3), a clamping mechanism, a glass dish (4) and a piezoelectric transducer (5);
the front end of the micro glass needle (3) is fixed by a clamping mechanism, and the tail end of the micro glass needle (3) is placed in the liquid contained in the glass dish (4);
the piezoelectric transducer (5) is used for generating sound waves with certain set frequency and amplitude, and the micro glass needle (3) generates resonance through the transmission of liquid in the glass dish (4), so that a uniform flow field and secondary radiation force are generated in the surrounding liquid and act on the particles (6) together to drive the particles (6) to rotate and move.
Preferably, the end of the micro glass needle (3) is designed to be hammer-shaped.
Preferably, the clamping mechanism comprises a three-axis moving platform (1) and a fine adjustment platform (2); fine setting platform (2) are fixed on triaxial moving platform (1), little glass needle (3) are fixed on fine setting platform (2), and wherein triaxial moving platform (1) is used for adjusting the position of fine setting platform (2), and fine setting platform (2) are used for adjusting the direction and the position appearance of little glass needle (3).
Preferably, the piezoelectric transducer (5) is fixed on the glass dish (4).
Preferably, the piezoelectric transducer (5) comprises a piezoelectric transducer piece and a piezoelectric driver; the piezoelectric driver is used for inputting sinusoidal signals to the piezoelectric transduction piece, so that the piezoelectric transduction piece generates sound waves with set frequency and amplitude; the piezoelectric transduction piece is fixed at the bottom of the glass dish (4).
A control method of a device for controlling the movement and rotation of a tiny target driven by acoustic streaming forceps comprises the following steps:
s401: placing the microparticles (6) in the liquid of a glass dish (4) and placing them in the field of view of a microscope through a glass slide;
s402: adjusting the three-axis motion platform (1) and the fine adjustment platform (2), and immersing the micro glass needle (3) in the liquid in the glass vessel (4);
s403; turning on the piezoelectric transducer (5), adjusting the frequency and amplitude of the output sound wave, and oscillating the micro glass needle (3) when the frequency of the sound wave is close to the resonance frequency of the micro glass needle (3), so as to generate a flow field vertically distributed around the micro glass needle;
s404: adjusting the three-axis motion platform (1) to enable the needle body of the micro glass needle (3) to be close to the particles (6), enabling the particles (6) to be close to the micro glass needle (3) under the action of secondary radiation force, enabling the particles (6) to be close to but not in contact with the needle body through liquid flowing on the surface of the needle body at a high speed, and achieving capture of the particles (6);
s405, adjusting the three-axis moving platform (1) to enable the micro glass needle (3) to generate displacement and drive the particles (6) to move under the action of secondary radiation force;
s406: after reaching the target position, the particles (6) rotate in the plane under the action of the flow field force and the secondary radiation force;
s407: adjusting the position of the glass dish (4) so as to move the particles (6) to the end port of the micro glass needle (3), wherein the particles (6) rotate out of plane under the action of flow field force and secondary radiation force;
s408: the rotating speed of the particles (6) is slowly reduced to the lowest rotating speed by reducing the input voltage of the piezoelectric transducer (5), when the particles rotate to the expected pose, the input signal of the piezoelectric transducer (5) is cut off immediately, and the particles (6) stop rotating immediately.
The invention has the following beneficial effects:
the invention provides a device and a method for controlling the movement and rotation of a tiny target driven by acoustic flow tweezers, wherein a piezoelectric transducer generates acoustic waves to cause a hammer-shaped tail end micro glass needle to resonate, and particles rotate and move under the combined action of flow field force and secondary radiation force generated by the hammer-shaped tail end micro glass needle; compared with the existing micro-operation manipulator system, the invention avoids the physical contact between the operation tail end and the particles in the whole operation process, thereby not causing any damage to the target, and the hammer-shaped tail end enables the particles to keep rotating in situ, thereby being easy to control the particles in an observation range; compared with the existing non-contact operation taking magnetism, electricity, light and the like as external field indirect effects, the invention has better safety; compared with the existing system for carrying out cell micromanipulation in the microfluidic chip, the invention is not limited by operation tasks and the size of an operation object, and has strong operation flexibility. In addition, the invention realizes that the movement, the orientation and the fixation of the particles are completed by one actuator, thereby avoiding the problems of high operation complexity, low success rate, low efficiency and the like caused by the traditional multiple actuators.
Drawings
Fig. 1 is a schematic structural diagram of a device for controlling the movement and rotation of a tiny target driven by acoustic streaming forceps according to an embodiment of the present invention;
FIG. 2 is a schematic view of a terminal flow field distribution in an embodiment of the present invention;
FIG. 3 is a force diagram illustrating in-plane rotation and trapping of particles in an embodiment of the present invention;
FIG. 4 is a diagram illustrating feature sizes of operation objects according to an embodiment of the present invention;
FIG. 5 is a flow chart of the particle capture, movement and rotation implemented in an embodiment of the present invention.
Wherein, the device comprises a 1-triaxial moving platform, a 2-fine tuning platform, a 3-micro glass needle, a 4-glass vessel, a 5-piezoelectric transducer and a 6-particle.
Detailed Description
In order to make the technical solutions better understood by those skilled in the art, the technical solutions in the embodiments of the present application will be clearly and completely described below with reference to the drawings in the embodiments of the present application.
The first embodiment is as follows:
referring to fig. 1, the figure is a schematic structural diagram of a movement and rotation control device of a micro target driven by acoustic flow tweezers according to an embodiment of the present invention, and the structure includes a three-axis moving platform 1, a fine tuning platform 2, a micro glass needle 3, a glass dish 4, and a piezoelectric transducer 5; the fine adjustment platform 2 is fixed on the three-axis moving platform 1, wherein the three-axis moving platform 1 is used for adjusting the position of the fine adjustment platform 2; the micro glass needle 3 is fixed on the fine adjustment platform 2, and the tail end of the micro glass needle 3 is arranged in the liquid contained in the glass dish 4.
It should be noted that the three-axis mobile platform 1 may be fixed on a horizontal plane. Wherein the three-axis moving platform 1 is used to support the whole operation device and roughly adjust its working position, for example, the end of the micro glass needle 3 and the micro particle 6 can be adjusted in the field of view of the microscope. The micro glass needle 3 is fixed on the fine adjustment platform 2, and the direction and the pose of the micro glass needle 3 can be adjusted by adjusting the fine adjustment platform 2. For example, it is possible to rotate the micro-glass needle 3 within 360 ° along its mounting axis on the three-axis motion stage 1 to adjust the distance and angle of the micro-glass needle 4 from the glass dish 4 and the particles 6.
The piezoelectric transducer 5 comprises a piezoelectric transducer piece and a piezoelectric driver; the piezoelectric driver is used for inputting sinusoidal signals to the piezoelectric transduction piece, so that the piezoelectric transduction piece generates sound waves with certain frequency and amplitude.
It should be noted that the sinusoidal voltage signal causes the piezoelectric actuator and the micro glass needle 3 to resonate, so that a uniform flow field and a secondary radiation force are generated around the micro glass needle 3, and act on the particles 6 together to drive the particles 6 to rotate and move.
It should be noted that the piezoelectric transducer 5 may be adhered to any suitable portion of the glass dish 4, and the installation positions of the piezoelectric transducer sheet and the piezoelectric actuator may be independent of each other.
Alternatively, the micro glass needles 3 used in the embodiment of the present invention have a size as shown in fig. 3, and the particles 6 having a diameter of 130 μm are used; in other embodiments, the micro glass needles 3 may also have other sizes to accommodate other objects, and this embodiment is not described in detail.
The micro glass needle 3 is used for forming a vortex in water by self-vibration, and driving the particle 6 to move and rotate by a flow field force and a secondary sound radiation force.
The working principle of the device for controlling the movement and rotation of the tiny target driven by the acoustic flow forceps provided by the embodiment of the invention is as follows:
when a sinusoidal voltage signal with certain frequency and amplitude is input into the piezoelectric transduction piece, the piezoelectric transduction piece emits sound waves with corresponding frequency and intensity. When the frequency of the sound wave is close to the resonance frequency of the micro glass needle 3, the micro glass needle 3 can obviously oscillate under the excitation of the sound wave, and the high-speed periodic oscillation can drive the liquid nearby to locally flow, so that a time-averaged flow field is generated. Referring to fig. 2, which is a schematic diagram of the operating end flow field distribution of an acoustically-driven hammer-shaped tip resonance and micro-vortex excitation device and method according to an embodiment of the present invention, two vertically-distributed vortices are formed in the focal plane and perpendicular to the focal plane around the micro-glass needle 3.
On the other hand, due to the scattering of the sound wave, the micro glass needle 3 will generate a near field force, called secondary radiation force or Bjerknes force, to the object around it, and the acting direction of this force to the object is related to the density of the object relative to the liquid around it, in this embodiment, the density of the micro particles 6 is slightly greater than that of the liquid in the glass dish 5, so the micro particles 6 are attracted by the secondary radiation force of the micro glass needle 3.
Under the action of secondary radiation force, the particles 6 approach to the micro glass needles 3, the resultant force is zero when the particles are near the micro glass needles 3, and meanwhile, the liquid flowing on the surfaces of the micro glass needles 3 at high speed prevents the particles 6 from being contacted and adhered with the surfaces of the particles 6, so that the particles 6 can be stabilized at a certain position near the micro glass needles 3, and the particles 6 are captured. When the micro glass needle 3 is moved, the fine particles 6 are also moved by the attraction of the secondary radiation force. Meanwhile, the particles 6 are also subjected to the action of a torque decomposed by the flow field force, and the rotation is balanced with the viscous force generated by the rotation after reaching a certain rotation speed under the action, and then the uniform rotation is kept, so that the in-plane rotation is realized. Referring to fig. 3, a force diagram of the apparatus and method for resonance and excitation of micro-eddy currents with a hammer-shaped end driven by sound waves according to the embodiment of the present invention for in-plane rotation and capture of particles is shown. Then, the position of the glass plate 4 is adjusted to adjust the particles 6 to the end port of the micro glass needle 3. The particles 6 realize out-of-plane rotation under the action of flow field torque generated at the end ports of the micro glass needles 3. Under the action of two vertically distributed flow fields, the particles 6 can realize omnidirectional rotation, and when the particles rotate to an expected pose, the input signals of the piezoelectric transducer 6 are cut off, so that the particles 6 can stop rotating.
In this embodiment, the end of the micro-glass needle 3 is designed to be hammer-shaped, i.e. the end has a spherical crown-shaped projection, which can keep the micro-particles 6 in place for rotation, and is easy to control well within the observation range.
Therefore, the device provided by the embodiment of the invention comprises the three-axis moving platform 1, the fine adjustment platform 2, the micro glass needle 3, the glass dish 4 and the piezoelectric transducer 5, and the cells can be captured, moved and rotated only by the power provided by the piezoelectric transducer 5, so that the device is simple in structure and convenient and fast to operate.
The second embodiment:
based on the apparatus of the first embodiment, the present embodiment provides a control method. Referring to fig. 4, a flow chart for capturing, moving, and rotating particles is shown.
A control method of a device for controlling the movement and rotation of a tiny target driven by acoustic flow tweezers is applied to the capture, movement and rotation of particles, and specifically comprises the following steps:
s401: the microparticles 6 are placed in the liquid in the glass dish 4 and placed in the field of view of the microscope through the slide;
s402: adjusting the fine adjustment platform 2 of the three-axis movement platform 1, and immersing the micro glass needle 3 in the liquid in the glass dish 4, wherein the micro glass needle 3 is not contacted with the particles 6;
s403; turning on the piezoelectric transducer 5, adjusting the frequency and amplitude of the output sound wave, and when the frequency of the sound wave is close to the resonance frequency of the micro glass needle 3, obviously oscillating the micro glass needle 3, thereby generating a flow field which is vertically distributed around the micro glass needle;
optionally, the piezoelectric transducer 5 includes a piezoelectric transducer sheet and a piezoelectric driver, and a sinusoidal voltage signal is input to the piezoelectric transducer sheet through the piezoelectric driver, so that the piezoelectric transducer sheet vibrates to emit sound waves;
s404: adjusting the three-axis motion platform 1 to enable the needle body of the micro glass needle 3 to be close to the particle 6, enabling the particle 6 to be close to the micro glass needle 3 under the action of secondary radiation force, enabling the particle 6 to be close to but not to be in contact with the needle body through liquid flowing on the surface of the needle body at a high speed, and achieving capture of cells;
s405, adjusting the three-axis moving platform 1 to enable the micro glass needle 3 to generate displacement and drive the particles 6 to move under the action of secondary radiation force;
s406: after reaching the target position, the particles 6 rotate in the plane under the action of the flow field force and the secondary radiation force;
s407: adjusting the position of the glass dish 4, so that the particles 6 move to the end port of the micro glass needle 3, and the particles 6 rotate out of plane under the action of the flow field force and the secondary radiation force;
s408: by reducing the input voltage of the piezoelectric transducer 5, the rotation speed of the fine particles 6 is slowly reduced to the minimum rotation speed, and when the fine particles are rotated to the expected pose, the input signal of the piezoelectric transducer 5 is immediately cut off, and the fine particles 6 immediately stop rotating.
The invention provides a device and a method for exciting hammer-shaped tail end resonance and micro eddy current driven by sound wave. The piezoelectric transducer generates sound waves to cause the hammer-shaped tail end micro glass needle 3 to resonate, and the particles 6 rotate and move under the combined action of flow field force and secondary radiation force generated by the hammer-shaped tail end micro glass needle 3; compared with the existing micro-operation manipulator system, the invention avoids the physical contact between the operation tail end and the particles in the whole operation process, thereby not generating any damage to the particles, and the hammer-shaped tail end enables the particles to keep rotating in situ, thus being easy to control the particles in an observation range; compared with the existing non-contact operation taking magnetism, electricity, light and the like as external field indirect effects, the invention has better safety; compared with the existing system for carrying out cell micromanipulation in the microfluidic chip, the invention is not limited by the operation task and the size of the operation object, and has strong operation flexibility. In addition, the invention realizes that the capture, the movement and the rotation of the particles are completed by one actuator, and avoids the problems of high operation complexity, low success rate, low efficiency and the like caused by the traditional multiple actuators.
In conclusion, the invention can effectively solve the problems of complex motion control, single function, poor safety, low efficiency, poor flexibility and the like in the micro-operation process with relatively complex process. The non-contact micro-operation system provided by the invention shows strong superiority in moving, positioning and fixing the micro-target and shows huge potential.
Although the embodiments of the present invention have been described in conjunction with the accompanying drawings, it will be apparent to those skilled in the art that various changes and modifications may be made without departing from the principles of the invention, and these should be considered as falling within the scope of the invention.
Claims (6)
1. A movement and rotation control device of a tiny target driven by acoustic flow tweezers is characterized by comprising a micro glass needle (3), a clamping mechanism, a glass vessel (4) and a piezoelectric transducer (5);
the front end of the micro glass needle (3) is fixed by a clamping mechanism, and the tail end of the micro glass needle (3) is placed in the liquid contained in the glass dish (4);
the piezoelectric transducer (5) is used for generating sound waves with certain set frequency and amplitude, and the micro glass needle (3) generates resonance through the transmission of liquid in the glass dish (4), so that a uniform flow field and secondary radiation force are generated in the surrounding liquid and act on the particles (6) together to drive the particles (6) to rotate and move.
2. A device for controlling the movement and rotation of a micro-object driven by acoustic streaming forceps as claimed in claim 1, characterized in that the tip of the micro-glass needle (3) is designed as a hammer.
3. The device for controlling the movement and rotation of a tiny target driven by acoustic flow tweezers according to claim 1, wherein the clamping mechanism comprises a three-axis moving platform (1) and a fine tuning platform (2); fine setting platform (2) are fixed on triaxial moving platform (1), little glass needle (3) are fixed on fine setting platform (2), and wherein triaxial moving platform (1) is used for adjusting the position of fine setting platform (2), and fine setting platform (2) are used for adjusting the direction and the position appearance of little glass needle (3).
4. The device for controlling the movement and rotation of a minute object driven by acoustic tweezers according to claim 1, wherein the piezoelectric transducer (5) is fixed to the glass plate (4).
5. The device for controlling the movement and rotation of a tiny target driven by acoustic tweezers according to claim 4, wherein the piezoelectric transducer (5) comprises a piezoelectric transducer piece and a piezoelectric driver; the piezoelectric driver is used for inputting sinusoidal signals to the piezoelectric transduction piece, so that the piezoelectric transduction piece generates sound waves with set frequency and amplitude; the piezoelectric transduction piece is fixed at the bottom of the glass dish (4).
6. A control method of a movement and rotation control apparatus according to any of claims 1 to 5, comprising:
s401: placing the microparticles (6) in the liquid of a glass dish (4) and placing them in the field of view of a microscope through a glass slide;
s402: adjusting the three-axis motion platform (1) and the fine adjustment platform (2), and immersing the micro glass needle (3) in the liquid in the glass vessel (4);
s403; turning on the piezoelectric transducer (5), adjusting the frequency and amplitude of the output sound wave, and oscillating the micro glass needle (3) when the frequency of the sound wave is close to the resonance frequency of the micro glass needle (3), so as to generate a flow field vertically distributed around the micro glass needle;
s404: adjusting the three-axis motion platform (1) to enable the needle body of the micro glass needle (3) to be close to the particles (6), enabling the particles (6) to be close to the micro glass needle (3) under the action of secondary radiation force, enabling the particles (6) to be close to but not in contact with the needle body through liquid flowing on the surface of the needle body at a high speed, and achieving capture of the particles (6);
s405, adjusting the three-axis moving platform (1) to enable the micro glass needle (3) to generate displacement and drive the particles (6) to move under the action of secondary radiation force;
s406: after reaching the target position, the particles (6) rotate in the plane under the action of the flow field force and the secondary radiation force;
s407: adjusting the position of the glass dish (4) so as to move the particles (6) to the end port of the micro glass needle (3), wherein the particles (6) rotate out of plane under the action of flow field force and secondary radiation force;
s408: the rotating speed of the particles (6) is slowly reduced to the lowest rotating speed by reducing the input voltage of the piezoelectric transducer (5), when the particles rotate to the expected pose, the input signal of the piezoelectric transducer (5) is cut off immediately, and the particles (6) stop rotating immediately.
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| Application Number | Priority Date | Filing Date | Title |
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| CN202211438567.8A CN115895883A (en) | 2022-11-17 | 2022-11-17 | Device and method for controlling movement and rotation of tiny target driven by acoustic flow forceps |
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| CN202211438567.8A CN115895883A (en) | 2022-11-17 | 2022-11-17 | Device and method for controlling movement and rotation of tiny target driven by acoustic flow forceps |
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