CN115895883A - Device and method for controlling movement and rotation of tiny targets driven by acoustic flow tweezers - Google Patents

Abstract

The invention proposes a device and method for controlling the movement and rotation of tiny targets driven by acoustic flow tweezers. Sound waves generated by piezoelectric transducers cause the hammer-shaped end glass needles to resonate. Rotation and movement are realized under the joint action of field force and secondary radiation force; the present invention avoids the physical contact between the operating end and the particle during the entire operation, so it will not cause any damage to the target, and the hammer-shaped end enables the particle to maintain Rotating in situ, it is easy to control it well within the scope of observation; 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 the movement, orientation and fixation of particles through a Executors are used to complete the operation, avoiding the problems of high operational complexity, low success rate, and low efficiency caused by traditional multi-actuators.

Description

Device and method for controlling movement and rotation of tiny targets driven by acoustic flow tweezers

technical field

The invention belongs to the technical field of micro-nano operation, and in particular relates to a movement and rotation control device and control method of a micro target driven by acoustic flow tweezers.

Background technique

As the basic unit of the structure and function of organisms, cells have the ability to independently carry out various life activities. Therefore, the related research of cytology has attracted extensive attention in the field of modern biological sciences. In the past 30 years, the rapid progress of micromanipulation technology has provided a very important tool for the development of the biomedical field. basis for related issues. In the fields of biomedical analysis and clinical research, the controllable and precise operation of single cells is particularly important. This technology has been widely used in specific processes such as genetic engineering, embryo transfer, cloning technology and in vitro fertilization. During these procedures, doctors often need to move, position, fix, inject and other operations on oocytes under a microscope. The positioning of the cells is mainly to adjust the posture of the cells through rotation, and position them in the direction required for later operations. After the cells are located, operations such as sperm injection or genetic material extraction can be performed. For example, for oocytes injected with sperm, the nuclei are located at the edge of the cells and are distributed asymmetrically. During the cell injection process, it needs to be repositioned to a suitable position by rotating operations. The same plane can be observed under the microscope at the same time, so as to ensure the successful realization of cell injection. In addition, embryonic cells need multiple 3D image evaluations before implantation to ensure that their morphological structure meets the requirements. Precise control of the position and orientation of the cell is required in these steps, among which, the omnidirectional rotational positioning of the cell involves two main basic movements—rotation in the focal plane and rotation perpendicular to the focal plane, respectively defined are in-plane and out-of-plane rotations. The success or failure of cell micromanipulation is determined by the process of cell movement, positioning and fixation. Therefore, it is urgent to create a multi-mode switchable, efficient, accurate and safe micromanipulation device and method.

So far, high-spatial-resolution microactuators have greatly facilitated the precise movement of cells through contact or non-contact methods, however, the controlled high-precision cell rotation technology remains a challenge, especially with cell capture, Micromanipulation techniques for movement and rotation. At present, most clinical practice still stays in the way of physical contact, using the tip of traditional microneedles to directly poke cells to achieve position control. Although this method is relatively straightforward in use, it has many disadvantages. The fine glass needle used as the operation terminal will inevitably cause mechanical damage such as local negative pressure and puncture injury to the cells during the operation process, and the requirement of high precision makes the manipulator too complicated to achieve high stability. Micromanipulation success rate is low. With the development of micromanipulation technology, people no longer rely on the contact operation method, but by controlling multiple physical fields. In recent years, a series of driving methods based on physical field energy (such as optical tweezers, magnetic tweezers , acoustic tweezers, dielectrophoresis, and hydrodynamic fields, etc.) have been established for cell movement and rotation. These processes do not have direct mechanical contact, which overcomes some disadvantages of contact physical operations, but there are still risks. Magnetic fields, electric fields or high temperatures may cause potential damage to cells, and such methods are complex and expensive, and the threshold for promotion is high. In contrast, hydrodynamic fields generate directional fluid forces to alter cell motion by mapping the distribution of pressure gradients in a manner that is often considered nondestructive. However, this method is often implemented in closed and narrow microfluidic channels, which cannot achieve flexible access to cells. It is generally only suitable for cell observation and is not suitable for further cell operations, such as injection and enucleation.

To sum up, the existing micromanipulation technology is increasingly difficult to meet the needs of complex operations such as oocyte injection, such as movement, positioning and fixation.

Contents of the invention

In order to overcome the existing defects of the above-mentioned technologies, the present invention proposes a device and method for controlling the movement and rotation of tiny targets driven by acoustic flow tweezers. The end of the hammer-shaped glass is excited by sound waves to oscillate, and a time-averaged flow field and a secondary flow field are generated around it. The radiation force realizes the movement, rotation and orientation operation of the target, and effectively solves the problems of single function, damage to the target, complex system, and poor flexibility in the micro-manipulation methods at the present stage.

A movement and rotation control device for tiny targets driven by acoustic flow tweezers, comprising a micro glass needle (3), a clamping mechanism, a glass dish (4) and a piezoelectric transducer (5);

The front end of the microglass needle (3) is fixed by a clamping mechanism, and the end of the microglass needle (3) is placed in the liquid contained in the glass dish (4);

The piezoelectric transducer (5) is used to generate a sound wave with a certain set frequency and amplitude, and through the transmission of the liquid in the glass dish (4), the micro glass needle (3) is resonated, thereby generating a sound wave in the surrounding liquid. The time-averaged flow field and the secondary radiation force 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 includes a three-axis moving platform (1) and a fine-tuning platform (2); the fine-tuning platform (2) is fixed on the three-axis moving platform (1), and the microglass needle (3) It is fixed on the fine-tuning platform (2), wherein the three-axis moving platform (1) is used to adjust the position of the fine-tuning platform (2), and the fine-tuning platform (2) is used to adjust the direction and pose of the microglass needle (3).

Preferably, the piezoelectric transducer (5) is fixed on the glass dish (4).

Preferably, the piezoelectric transducer (5) includes a piezoelectric transducer and a piezoelectric driver; the piezoelectric driver is used to input a sinusoidal signal to the piezoelectric transducer, so that the piezoelectric transducer generates a set A sound wave with a fixed frequency and amplitude; the piezoelectric transducer is fixed on the bottom of the glass dish (4).

A control method for a movement and rotation control device of a tiny target driven by acoustic flow tweezers, comprising:

S401: placing the particle (6) in the liquid in the glass dish (4), and placing it in the field of view of the microscope through the glass slide;

S402: adjust the three-axis motion platform (1) and the fine-tuning platform (2), and immerse the micro glass needle (3) in the liquid of the glass dish (4);

S403; turn on the piezoelectric transducer (5), adjust the frequency and amplitude of its output sound wave, when the sound wave frequency is close to the resonance frequency of the micro glass needle (3), the micro glass needle (3) oscillates, thereby generating Vertically distributed flow field;

S404: Adjust the three-axis motion platform (1), so that the needle body of the microglass needle (3) is close to the particle (6), and under the action of the secondary radiation force, the particle (6) approaches the microglass needle (3), The high-speed flowing liquid on the surface of the needle body makes the particles (6) close to but not in contact with the needle body, thereby realizing the capture of the particles (6);

S405: adjust the three-axis moving platform (1), so that the microglass needle (3) generates a displacement, and drives the particle (6) to move under the action of the secondary radiation force;

S406: After reaching the target position, the particle (6) rotates in the plane under the action of the flow field force and the secondary radiation force;

S407: Adjust the position of the glass dish (4), so as to move the particle (6) to the end port of the micro glass needle (3), and the particle (6) rotates 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 rotational speed of the particle (6) is slowly reduced to the lowest rotational speed, and when the rotation reaches the expected position, immediately cut off the input signal of the piezoelectric transducer (5), Particle (6) stops rotating immediately.

The present invention has following beneficial effects:

The present invention proposes a device and method for controlling the movement and rotation of tiny targets driven by acoustic flow tweezers. Sound waves generated by piezoelectric transducers cause the hammer-shaped end glass needles to resonate. Rotation and movement are realized under the joint action of field force and secondary radiation force; compared with the existing micro-manipulator system, the present invention avoids the physical contact between the operating end and the particles during the entire operation process, so it will not cause any damage to the target. damage, and the hammer-shaped end keeps the particle in situ rotation, and it is easy to control it well within the observation range; compared with the existing non-contact operation that uses magnetism, electricity, light, etc. as indirect effects of external fields, the present invention It has better safety; compared with the existing system for performing cell micromanipulation in the microfluidic chip, the present 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 the movement, orientation and fixation of particles through one actuator, avoiding the problems of high operation complexity, low success rate, and low efficiency caused by traditional multiple actuators.

Description of drawings

1 is a schematic structural diagram of a device for controlling the movement and rotation of a tiny target driven by acoustic flow tweezers according to an embodiment of the present invention;

Fig. 2 is a schematic diagram of terminal flow field distribution in an embodiment of the present invention;

Fig. 3 is a schematic diagram of the force of particles rotating and capturing in a plane in the embodiment of the present invention;

Fig. 4 is a schematic diagram of the characteristic size of the operation object in the embodiment of the present invention;

FIG. 5 is a flow chart of particle capture, movement and rotation implemented in an embodiment of the present invention.

Among them, 1-three-axis moving platform, 2-fine-tuning platform, 3-micro glass needle, 4-glass dish, 5-piezoelectric transducer, 6-particles.

Detailed ways

In order to enable those skilled in the art to better understand the solutions of the present application, the technical solutions in the embodiments of the present application will be clearly and completely described below in conjunction with the drawings in the embodiments of the present application.

Embodiment one:

Referring to Fig. 1, this figure is a structural schematic diagram of a movement and rotation control device for a tiny target driven by acoustic flow tweezers according to an embodiment of the present invention, including a three-axis moving platform 1, a fine-tuning platform 2, a micro glass needle 3, and a glass dish 4 , piezoelectric transducer 5; the fine-tuning platform 2 is fixed on the three-axis mobile platform 1, wherein the three-axis mobile platform 1 is used to adjust the position of the fine-tuning platform 2; the micro glass needle 3 is fixed on the fine-tuning platform 2, The end of the micro glass needle 3 is placed in the liquid contained in the glass dish 4 .

It should be noted that the three-axis mobile platform 1 can be fixed on a horizontal plane. Among them, the three-axis moving platform 1 is used to support the entire operating device and roughly adjust its working position, for example, the end of the microglass needle 3 and the particle 6 can be adjusted to the field of view of the microscope. The micro-glass needle 3 is fixed on the fine-tuning platform 2, and the direction and posture adjustment of the micro-glass needle 3 can be realized by adjusting the fine-tuning platform 2. For example, it can rotate within a range of 360° along its installation axis on the three-axis motion platform 1 to adjust the distance and angle of the micro glass needle 3 , the glass dish 4 and the particle 6 .

The piezoelectric transducer 5 includes a piezoelectric transducer and a piezoelectric driver; the piezoelectric driver is used to input a sinusoidal signal to the piezoelectric transducer to make the piezoelectric transducer generate sound waves of a certain frequency and amplitude.

It should be noted that the sinusoidal voltage signal causes the piezoelectric actuator and the microglass needle 3 to form a resonance, thereby generating a time-averaged flow field and a secondary radiation force around the microglass needle 3, which act together on the particle 6 to drive Particles 6 rotate and move.

It should be noted that the piezoelectric transducer 5 can be bonded to any appropriate part of the glass vessel 4, and the installation positions of the piezoelectric transducer sheet and the piezoelectric driver can be independent of each other. The installation position in the whole device is not limited, as long as the piezoelectric driver can provide a sinusoidal signal for the piezoelectric transducer to make the piezoelectric transducer generate sound waves of a certain frequency and amplitude.

Optionally, the size of the microglass needle 3 used in the embodiment of the present invention is as shown in Figure 3, and the diameter of the particle 6 is 130 μm; in other embodiments, the microglass needle 3 can also adopt other sizes to adapt to other objects, This embodiment will not be described in detail.

The micro glass needle 3 is used to vibrate itself to form a vortex in the water, and drive the particle 6 to move and rotate by the flow field force and the secondary acoustic radiation force.

The working principle of the movement and rotation control device of a tiny target driven by acoustic flow tweezers provided by the embodiment of the present invention is as follows:

When a sinusoidal voltage signal of a certain frequency and amplitude is input into the piezoelectric transducer, the piezoelectric transducer emits sound waves of the corresponding frequency and intensity. When the frequency of the sound wave is close to the resonant frequency of the microglass needle 3, the microglass needle 3 will vibrate obviously under its excitation, and this high-speed periodic oscillation will drive the liquid nearby to flow locally, thereby generating a time-averaged flow. field. Referring to Fig. 2, this figure is a schematic diagram of flow field distribution at the operating end of a device and method for acoustically driven hammer-shaped end resonance and micro-eddy current excitation according to an embodiment of the present invention. Around the micro glass needle 3, a focal plane and vertical Two vertically distributed eddies at the focal plane.

On the other hand, due to the scattering of sound waves, the micro glass needle 3 will generate a near-field force on its surrounding objects, which is called secondary radiation force or Bjerknes force, and the direction of this force on the object is related to the density of the object relative to the surrounding liquid Relatedly, the density of the particle 6 in this embodiment is slightly greater than the density of the liquid in the glass dish 5 , so the particle 6 is attracted by the secondary radiation force of the micro glass needle 3 .

Under the action of the secondary radiation force, the particle 6 approaches the microglass needle 3, and when it is near the microglass needle 3, the resultant force is zero. At the same time, the high-speed flowing liquid on the surface of the microglass needle 3 prevents the particle 6 from contacting and sticking to the surface. Together, the particle 6 can be stabilized at a certain position near the micro glass needle 3, realizing the capture of the particle 6. When the micro glass needle 3 is moved, the particle 6 also moves with it under the attraction of the secondary radiation force. At the same time, the particle 6 is also affected by a torque decomposed by the force of the flow field. Under this action, after the rotation reaches a certain speed, it balances with the viscous force generated by the rotation, and then keeps rotating at a constant speed to achieve in-plane rotation. Referring to FIG. 3 , this figure is a schematic diagram of the force applied to the in-plane rotation and trapping of particles by an acoustic wave-driven hammer-shaped end resonance and micro-vortex excitation device and method according to an embodiment of the present invention. Afterwards, by adjusting the position of the glass vessel 4, the particle 6 is adjusted to the end port of the micro glass needle 3. Under the action of the flow field torque generated at the end port of the micro glass needle 3, the particle 6 realizes out-of-plane rotation. Under the action of two vertically distributed flow fields, the particle 6 can realize omnidirectional rotation. When the rotation reaches the expected position, the input signal of the piezoelectric transducer 6 is cut off to stop the particle 6 from rotating.

In this embodiment, the end of the microglass needle 3 is designed to be hammer-shaped, that is, the end has a spherical crown protrusion, and this shape can keep the particle 6 rotating in situ, and it is easy to control it well within the observation range .

It can be seen that the device of the embodiment of the present invention is composed of 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, and only the piezoelectric transducer 5 can provide power. Capturing, moving and rotating cells is realized, and the structure is simple and the operation is convenient.

Embodiment two:

Based on the device in Embodiment 1 above, this embodiment provides a control method. See Figure 4, which is a flow diagram for trapping, moving and rotating particles.

A control method for a movement and rotation control device of a tiny target driven by acoustic flow tweezers, which is applied to the capture, movement and rotation of particles, and specifically includes the following steps:

S401: placing the particle 6 in the liquid in the glass dish 4, and placing it in the field of view of the microscope through the glass slide;

S402: adjusting the three-axis motion platform 1 and fine-tuning the platform 2, immersing the microglass needle 3 in the liquid of the glass dish 4, and the microglass needle 3 does not touch the particle 6;

S403; turn on the piezoelectric transducer 5, adjust the frequency and amplitude of the sound wave output, when the frequency of the sound wave is close to the resonance frequency of the micro glass needle 3, the micro glass needle 3 vibrates obviously, thereby generating a vertically distributed flow field around it ;

Optionally, the piezoelectric transducer 5 includes a piezoelectric transducer and a piezoelectric driver, through which a sinusoidal voltage signal is input to the piezoelectric transducer to cause the piezoelectric transducer to vibrate and emit sound waves;

S404: Adjust the three-axis motion platform 1 so that the needle body of the microglass needle 3 is close to the particle 6. Under the action of the secondary radiation force, the particle 6 approaches the microglass needle 3, and the liquid flowing at a high speed on the surface of the needle body makes the particle 6 Close to but not in contact with the needle body to achieve cell capture;

S405: adjust the three-axis moving platform 1, so that the microglass needle 3 is displaced, and the particle 6 is driven to move under the action of the secondary radiation force;

S406: After reaching the target position, the particle 6 rotates in the plane under the action of the flow field force and the secondary radiation force;

S407: Adjust the position of the glass dish 4, so as to move the particle 6 to the end port of the micro glass needle 3, and the particle 6 rotates 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 speed of the particle 6 is slowly reduced to the lowest speed. When the rotation reaches the expected position, the input signal of the piezoelectric transducer 5 is immediately cut off, and the particle 6 stops rotating immediately.

The invention provides a device and method for acoustically driven hammer-shaped terminal resonance and micro-eddy current excitation. The sound wave generated by the piezoelectric transducer causes the glass needle 3 at the hammer-shaped end to resonate, and the particles 6 rotate and move under the joint action of the flow field force and the secondary radiation force generated by the glass needle 3 at the hammer-shaped end; Some use the micro-manipulator system. The present invention avoids the physical contact between the operating end and the particle during the entire operation process, so it will not cause any damage to the particle, and the hammer-shaped end enables the particle to remain in place and rotate, making it easy to move it. It is well controlled within the scope of observation; compared with the existing non-contact operation that uses magnetism, electricity, light, etc. as indirect effects of external fields, the present invention has better security; The system for cell micromanipulation is not limited by the operation task and the size of the operation object, and has strong operation flexibility. In addition, the invention realizes the capture, movement and rotation of particles through one actuator, avoiding the problems of high operation complexity, low success rate and low efficiency caused by traditional multiple actuators.

To sum up, the present invention can effectively solve the problems of complex motion control, single function, poor safety, low efficiency, and poor flexibility faced in some relatively complex micro-operation processes. The non-contact micro-operating system provided by the invention shows strong superiority and great potential in micro-target movement, positioning and fixing.

Although this example describes the embodiment of the present invention in conjunction with the accompanying drawings, for those skilled in the art, without departing from the principle of the present invention, some modifications and improvements can also be made, and these should also be regarded as belonging to the present invention. protection scope of the invention.

Claims (6)

1. A mobile and rotation control device for tiny targets driven by acoustic flow tweezers, characterized in that it comprises a microglass needle (3), a clamping mechanism, a glass dish (4) and a piezoelectric transducer (5); The front end of the microglass needle (3) is fixed by a clamping mechanism, and the end of the microglass needle (3) is placed in the liquid contained in the glass dish (4); The piezoelectric transducer (5) is used to generate a sound wave with a certain set frequency and amplitude, and through the transmission of the liquid in the glass dish (4), the micro glass needle (3) is resonated, thereby generating a sound wave in the surrounding liquid. The time-averaged flow field and the secondary radiation force act on the particles (6) together to drive the particles (6) to rotate and move. 2. The movement and rotation control device of a tiny target driven by acoustic flow tweezers as claimed in claim 1, characterized in that the end of the micro glass needle (3) is designed as a hammer. 3. the movement and the rotation control device of the tiny target driven by a kind of acoustic flow tweezers as claimed in claim 1, is characterized in that, described clamping mechanism comprises three-axis moving platform (1) and fine-tuning platform (2); The fine-tuning platform (2) is fixed on the three-axis moving platform (1), and the micro glass needle (3) is fixed on the fine-tuning platform (2), wherein the three-axis moving platform (1) is used to adjust the fine-tuning platform (2) position, the fine-tuning platform (2) is used to adjust the direction and pose of the microglass needle (3). 4 . The device for controlling the movement and rotation of a tiny target driven by acoustic flow tweezers according to claim 1 , wherein the piezoelectric transducer ( 5 ) is fixed on the glass dish ( 4 ). 5. the movement and rotation control device of the tiny target driven by a kind of acoustic flow tweezers as claimed in claim 4, is characterized in that, described piezoelectric transducer (5) comprises piezoelectric transducer plate and piezoelectric driver; The piezoelectric driver is used to input a sinusoidal signal to the piezoelectric transducer, so that the piezoelectric transducer generates sound waves with a set frequency and amplitude; the piezoelectric transducer is fixed on the bottom of the glass dish (4). 6. A control method based on the movement and rotation control device according to any one of claims 1 to 5, characterized in that it comprises: S401: placing the particle (6) in the liquid in the glass dish (4), and placing it in the field of view of the microscope through the glass slide; S402: adjust the three-axis motion platform (1) and the fine-tuning platform (2), and immerse the micro glass needle (3) in the liquid of the glass dish (4); S403; turn on the piezoelectric transducer (5), adjust the frequency and amplitude of its output sound wave, when the sound wave frequency is close to the resonance frequency of the micro glass needle (3), the micro glass needle (3) oscillates, thereby generating Vertically distributed flow field; S404: Adjust the three-axis motion platform (1), so that the needle body of the microglass needle (3) is close to the particle (6), and under the action of the secondary radiation force, the particle (6) approaches the microglass needle (3), The high-speed flowing liquid on the surface of the needle body makes the particles (6) close to but not in contact with the needle body, thereby realizing the capture of the particles (6); S405: adjust the three-axis moving platform (1), so that the microglass needle (3) generates a displacement, and drives the particle (6) to move under the action of the secondary radiation force; S406: After reaching the target position, the particle (6) rotates in the plane under the action of the flow field force and the secondary radiation force; S407: Adjust the position of the glass dish (4), so as to move the particle (6) to the end port of the micro glass needle (3), and the particle (6) rotates 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 rotational speed of the particle (6) is slowly reduced to the lowest rotational speed, and when the rotation reaches the expected position, immediately cut off the input signal of the piezoelectric transducer (5), Particle (6) stops rotating immediately.

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