Apparatus and method for moving and rotating micro-objects driven by acoustic streaming tweezers

Abstract

The present application provides a kind of sound flow tweezers driven micro target movement and rotation control device and method, resonance is caused to hammer-shaped end micro glass needle by piezoelectric transducer to generate sound wave, and micro particle realizes rotation and movement under the joint action of flow field force and secondary radiation force generated by hammer-shaped end micro glass needle;The present application avoids the physical contact between the operating end and the micro particle during the entire operation process, so it will not cause any damage to the target, and the hammer-shaped end allows the micro particle to rotate in place, making it easy to control within the observation range;The present application is not limited by the operation task and the size of the operating object, and has strong operation flexibility;In addition, the present application realizes the movement, orientation and fixation of the micro particle through one actuator, avoiding the high complexity, low success rate and low efficiency caused by traditional multiple actuators.

Description

Technical Field

[0001] This invention belongs to the field of micro-nano manipulation technology, and particularly relates to a control device and method for the movement and rotation of a micro-target driven by acoustic tweezers. Background Technology

[0002] As the basic structural and functional unit of organisms, the cell possesses the ability to independently perform various life activities, thus cell biology research has attracted widespread attention in the modern bioscience field. Over the past three decades, micromanipulation techniques have advanced rapidly, providing a crucial tool for the development of the biomedical field. Cell-related micromanipulation techniques have become fundamental to exploring the essence of life and solving related problems using methods such as microscopic observation and microsurgery. In biomedical analysis and clinical research, the controlled and precise manipulation of single cells is particularly important. This technology has been widely applied in specific processes such as genetic engineering, embryo transfer, cloning, and in vitro fertilization. In these processes, doctors often need to perform operations such as moving, positioning, fixing, and injecting oocytes under a microscope. Cell positioning mainly involves rotating the cell to adjust its posture and position it in the direction required for later operations. Only after the cell is positioned can operations such as sperm injection or genetic material extraction be performed. For example, in the case of sperm injection into oocytes, the cell nucleus is located at the edge of the cell and is asymmetrically distributed. During cell injection, rotational manipulation is required to reposition the cell to a suitable location, adjusting the nucleus, injection needle, and fixation needle to be on the same plane to ensure simultaneous observation under a microscope, thus guaranteeing successful cell injection. Furthermore, embryonic cells require multiple three-dimensional image assessments before implantation to ensure their morphology and structure meet requirements. Precise control of cell position and orientation is necessary in all these steps. Omnidirectional rotational positioning of the cell involves two main basic movements—rotation in the focal plane and rotation perpendicular to the focal plane, defined as in-plane rotation and out-of-plane rotation, respectively. The success of cell micromanipulation hinges on the smoothness of cell movement, positioning, and fixation. Therefore, there is an urgent need to develop a multi-mode, efficient, precise, and safe micromanipulation device and method.

[0003] To date, high spatial resolution microactuators have greatly facilitated precise cell movement through contact or non-contact methods. However, controlled, high-precision cell rotation remains a challenge, especially micromanipulation techniques that simultaneously capture, move, and rotate cells. Currently, most clinical practices still rely on physical contact, using the tip of a traditional microneedle to directly manipulate the cell for position control. While this method is straightforward, it has many drawbacks. The fine glass needle, as the manipulation terminal, inevitably causes mechanical damage to the cell during the operation, such as local negative pressure and puncture wounds. Furthermore, the high precision requirements make robotic arms overly complex and difficult to maintain high stability, resulting in low success rates in cell micromanipulation. With the development of micromanipulation techniques, researchers have begun to move away from contact-based manipulation methods and instead control multiple physical fields. In recent years, a series of energy-based methods (e.g., optical tweezers, magnetic tweezers, acoustic tweezers, dielectrophoresis, and hydrodynamic fields) have been developed for cell movement and rotation. These processes avoid direct mechanical contact, overcoming some of the drawbacks of contact-based physical manipulation. However, risks remain; magnetic fields, electric fields, or high temperatures can potentially damage cells. Furthermore, such methods require complex and expensive equipment, making widespread adoption difficult. In contrast, hydrodynamic fields, by mapping pressure gradients and generating directional fluid forces to alter cell movement, are often considered non-invasive. However, this approach is typically implemented in closed, narrow microfluidic channels, limiting the flexibility of cell handling and generally limiting its application to cell observation rather than further cell surgery, such as injection or enucleation.

[0004] In summary, existing micromanipulation techniques are increasingly unable to meet the needs of complex procedures such as oocyte injection, which involve movement, positioning, and fixation. Summary of the Invention

[0005] To overcome the shortcomings of the existing technologies, this invention proposes a device and method for controlling the movement and rotation of a micro-target driven by acoustic tweezers. By exciting the end of a hammer-shaped glass with sound waves to oscillate, a time-averaged flow field and secondary radiation force are generated around it to achieve the movement and rotation orientation of the target object. This effectively solves the problems of single function, damage to the target object, system complexity and poor flexibility in the current micro-manipulation methods.

[0006] A device for controlling the movement and rotation of a micro-target driven by acoustic tweezers includes a micro glass needle (3), a clamping mechanism, a glass dish (4), and a piezoelectric transducer (5).

[0007] The front end of the micro glass needle (3) is fixed by a clamping mechanism, and the end of the micro glass needle (3) is placed in the liquid contained in the glass dish (4);

[0008] The piezoelectric transducer (5) is used to generate sound waves with a certain set frequency and amplitude. Through the transmission of the liquid in the glass dish (4), the micro glass needle (3) resonates, thereby generating a time-averaged flow field and secondary radiation force in the surrounding liquid, which together act on the microparticle (6) and drive the microparticle (6) to rotate and move.

[0009] Preferably, the end of the microglass needle (3) is designed to be hammer-shaped.

[0010] 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 micro glass needle (3) 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 posture of the micro glass needle (3).

[0011] Preferably, the piezoelectric transducer (5) is fixed on the glass dish (4).

[0012] Preferably, the piezoelectric transducer (5) includes a piezoelectric transducer and a piezoelectric actuator; the piezoelectric actuator is used to input a sinusoidal signal to the piezoelectric transducer so that the piezoelectric transducer generates a sound wave with a set frequency and amplitude; the piezoelectric transducer is fixed to the bottom of the glass dish (4).

[0013] A control method for a device for controlling the movement and rotation of a micro-target driven by acoustic tweezers includes:

[0014] S401: Place the particles (6) in the liquid in the glass dish (4) and place them in the field of view of the microscope through a slide;

[0015] S402: Adjust the three-axis motion platform (1) and the fine-tuning platform (2) to immerse the micro glass needle (3) in the liquid in the glass dish (4);

[0016] S403; Turn on the piezoelectric transducer (5) and adjust the frequency and amplitude of its output sound wave. When the frequency of the sound wave is close to the resonant frequency of the micro glass needle (3), the micro glass needle (3) oscillates, thereby generating a vertically distributed flow field around it.

[0017] S404: Adjust the three-axis motion platform (1) to bring the micro glass needle (3) close to the microparticle (6). Under the action of secondary radiation force, the microparticle (6) moves closer to the micro glass needle (3). The liquid flowing at high speed on the surface of the needle makes the microparticle (6) approach but does not contact the needle, thus capturing the microparticle (6).

[0018] S405: Adjust the three-axis moving platform (1) to make the micro glass needle (3) move, and drive the microparticle (6) to move under the action of secondary radiation force;

[0019] 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;

[0020] S407: Adjust the position of the glass dish (4) to move the microparticles (6) to the end port of the micro glass needle (3). The microparticles (6) rotate out of plane under the action of the flow field force and the secondary radiation force.

[0021] S408: By reducing the input voltage of the piezoelectric transducer (5), the rotation speed of the particle (6) is slowly reduced to the minimum speed. When it rotates to the expected position, the input signal of the piezoelectric transducer (5) is immediately cut off, and the particle (6) stops rotating immediately.

[0022] The present invention has the following beneficial effects:

[0023] This invention proposes a device and method for controlling the movement and rotation of micro-targets driven by acoustic tweezers. Sound waves generated by a piezoelectric transducer induce resonance in a hammer-shaped microglass needle. The microparticle rotates and moves under the combined influence of the flow field force and secondary radiation force generated by the hammer-shaped microglass needle. Compared to existing micromanipulation manipulator systems, this invention avoids physical contact between the manipulator tip and the microparticle throughout the operation, thus preventing any damage to the target. Furthermore, the hammer-shaped tip allows the microparticle to rotate in situ, making it easy to control within the observation range. Compared to existing non-contact manipulation methods using magnetic, electrical, or optical fields as indirect external fields, this invention offers better safety. Compared to existing systems performing cell micromanipulation within microfluidic chips, this invention is not limited by the size of the task or object being manipulated, offering high operational flexibility. Moreover, this invention achieves the movement, orientation, and fixation of microparticles through a single actuator, avoiding the high complexity, low success rate, and inefficiency associated with traditional multi-actuator systems. Attached Figure Description

[0024] Figure 1 This is a schematic diagram of the structure of a micro-target movement and rotation control device driven by acoustic tweezers according to an embodiment of the present invention.

[0025] Figure 2 This is a schematic diagram of the terminal flow field distribution in an embodiment of the present invention;

[0026] Figure 3 This is a schematic diagram of the forces acting on the particles as they rotate and are captured in a plane according to an embodiment of the present invention.

[0027] Figure 4 This is a schematic diagram showing the characteristic dimensions of the object to be operated in an embodiment of the present invention;

[0028] Figure 5 This is a flowchart illustrating the particle capture, movement, and rotation implemented in an embodiment of the present invention.

[0029] Among them, 1-three-axis moving platform, 2-fine adjustment platform, 3-micro glass needle, 4-glass dish, 5-piezoelectric transducer, 6-microparticle. Detailed Implementation

[0030] To enable those skilled in the art to better understand the present application, the technical solutions in the embodiments of the present application will be clearly and completely described below with reference to the accompanying drawings.

[0031] Example 1:

[0032] See Figure 1 The figure is a schematic diagram of the structure of a micro-target movement and rotation control device driven by acoustic 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, a glass dish 4, and a piezoelectric transducer 5; the fine-tuning platform 2 is fixed on the three-axis moving platform 1, wherein the three-axis moving 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, and the end of the micro glass needle 3 is placed in the liquid contained in the glass dish 4.

[0033] It should be noted that the three-axis motion platform 1 can be fixed on a horizontal plane. The three-axis motion platform 1 supports the entire operating device and allows for rough adjustment of its working position, such as adjusting the tip of the microglass needle 3 and the microparticle 6 into the microscope's field of view. The microglass needle 3 is fixed on the fine-tuning platform 2, allowing for adjustment of its direction and orientation. For example, it can be rotated 360° along its mounting axis on the three-axis motion platform 1 to adjust the distance and angle between the microglass needle 3 and the glass dish 4 and the microparticle 6.

[0034] The piezoelectric transducer 5 includes a piezoelectric transducer and a piezoelectric actuator; the piezoelectric actuator is used to input a sinusoidal signal to the piezoelectric transducer, so that the piezoelectric transducer generates sound waves of a certain frequency and amplitude.

[0035] It should be noted that the sinusoidal voltage signal causes the piezoelectric actuator and the micro glass needle 3 to resonate, thereby generating a time-averaged flow field and secondary radiation force around the micro glass needle 3, which together act on the microparticle 6, driving the microparticle 6 to rotate and move.

[0036] It should be noted that the piezoelectric transducer 5 can be attached to any suitable part of the glass dish 4. The installation positions of the piezoelectric transducer and the piezoelectric actuator can be independent of each other. In this embodiment of the invention, the installation position of the piezoelectric actuator in the whole device is not limited, as long as the piezoelectric actuator can provide a sinusoidal signal to the piezoelectric transducer so that the piezoelectric transducer generates sound waves of a certain frequency and amplitude.

[0037] Optionally, the microglass needle 3 used in the embodiments of the present invention has the following dimensions: Figure 3 As shown in the figure, the particle 6 has a diameter of 130 μm; in other embodiments, the micro glass needle 3 can also be of other sizes to adapt to other target objects, which will not be described in detail in this embodiment.

[0038] The microglass needles 3 are used to form eddies in the water by vibrating themselves, and drive the particles 6 to move and rotate by flow field force and secondary acoustic radiation force.

[0039] The working principle of the acoustic tweezers-driven micro-target movement and rotation control device provided in this embodiment of the invention is as follows:

[0040] When a sinusoidal voltage signal of a certain frequency and amplitude is input into the piezoelectric transducer, the transducer emits sound waves of corresponding frequency and intensity. When the frequency of the sound wave approaches the resonant frequency of the microglass needle 3, the microglass needle 3 will exhibit significant oscillations under its excitation. This high-speed periodic oscillation will drive localized flow in the nearby liquid, thereby generating a time-averaged flow field. See also Figure 2 The figure is a schematic diagram of the flow field distribution at the operating end of a device and method for acoustically driven hammer-shaped end resonance and micro-vortex excitation according to an embodiment of the present invention. Two vertically distributed vortices are formed around the micro glass needle 3, one in the focal plane and the other perpendicular to the focal plane.

[0041] On the other hand, due to the scattering of sound waves, the micro glass needle 3 will generate a near-field force on the surrounding objects, called the secondary radiation force or Bjerknes force. The direction of this force on the object is related to the density of the object relative to the liquid around it. In this embodiment, the density of the microparticle 6 is slightly greater than the density of the liquid in the glass dish 5. Therefore, the microparticle 6 is attracted by the secondary radiation force of the micro glass needle 3.

[0042] Under the influence of secondary radiation force, particle 6 approaches the microglass needle 3. Near the microglass needle 3, the net force is zero, and the high-speed flowing liquid on the surface of the microglass needle 3 prevents particle 6 from contacting and sticking to its surface. Therefore, particle 6 can be stably positioned near the microglass needle 3, achieving particle 6 capture. When the microglass needle 3 is moved, particle 6 also moves under the attraction of the secondary radiation force. Simultaneously, particle 6 is also subjected to a torque decomposed from the flow field force. Under this action, it rotates to a certain speed and then balances with the viscous force generated by the rotation, subsequently maintaining uniform rotation, achieving in-plane rotation. See also Figure 3This figure is a schematic diagram illustrating the forces acting on the in-plane rotation and capture of microparticles using a device and method for acoustically driven hammer-shaped end resonance and micro-eddy current excitation according to an embodiment of the present invention. Subsequently, by adjusting the position of the glass dish 4, the microparticle 6 is positioned at the end of the microglass needle 3. Under the action of the flow field torque generated at the end of the microglass needle 3, the microparticle 6 achieves out-of-plane rotation. Under the action of two vertically distributed flow fields, the microparticle 6 can achieve omnidirectional rotation. When it reaches the desired orientation, cutting off the input signal to the piezoelectric transducer 6 stops the rotation of the microparticle 6.

[0043] In this embodiment, the end of the micro glass needle 3 is designed as a hammer shape, that is, the end has a spherical crown-shaped protrusion. This shape can keep the microparticle 6 rotating in place and make it easy to control it well within the observation range.

[0044] As can be seen, the device of this embodiment consists 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. The capture, movement, and rotation of cells can be achieved by the piezoelectric transducer 5 alone, which is simple in structure and convenient to operate.

[0045] Example 2:

[0046] Based on the apparatus of Embodiment 1 above, this embodiment provides a control method. See also... Figure 4 The diagram shows a flowchart of capturing, moving, and rotating particles.

[0047] A control method for a device for controlling the movement and rotation of a micro-target driven by acoustic tweezers, applied to the capture, movement, and rotation of particles, specifically includes the following steps:

[0048] S401: Place the particles 6 in the liquid in the glass dish 4 and place them in the field of view of the microscope through a glass slide;

[0049] S402: Adjust the three-axis motion platform 1 and the fine-tuning platform 2 to immerse the micro glass needle 3 in the liquid of the glass dish 4, ensuring that the micro glass needle 3 does not contact the microparticle 6.

[0050] S403; Turn on the piezoelectric transducer 5 and adjust the frequency and amplitude of its output sound wave. When the sound wave frequency is close to the resonant frequency of the micro glass needle 3, the micro glass needle 3 will oscillate significantly, thereby generating a vertically distributed flow field around it.

[0051] Optionally, the piezoelectric transducer 5 includes a piezoelectric transducer and a piezoelectric actuator. A sinusoidal voltage signal is input to the piezoelectric transducer through the piezoelectric actuator, causing the piezoelectric transducer to vibrate and emit sound waves.

[0052] S404: Adjust the three-axis motion platform 1 to bring the micro glass needle 3 close to the microparticle 6. Under the action of secondary radiation force, the microparticle 6 moves closer to the micro glass needle 3. The high-speed flowing liquid on the surface of the needle brings the microparticle 6 closer but does not contact the needle, thus achieving cell capture.

[0053] S405: Adjust the three-axis moving platform 1 to make the micro glass needle 3 displace, and drive the microparticle 6 to move under the action of secondary radiation force;

[0054] S406: After reaching the target position, particle 6 rotates in the plane under the action of flow force and secondary radiation force;

[0055] S407: Adjust the position of the glass dish 4 to move the microparticles 6 to the end port of the micro glass needle 3. The microparticles 6 rotate out of plane under the action of the flow field force and the secondary radiation force.

[0056] S408: By reducing the input voltage of the piezoelectric transducer 5, the rotation speed of the particle 6 is slowly reduced to the minimum speed. When it rotates to the expected position, the input signal of the piezoelectric transducer 5 is immediately cut off, and the particle 6 stops rotating immediately.

[0057] This invention proposes a device and method for acoustically driven hammer-shaped end resonance and micro-eddy current excitation. Acoustic waves generated by a piezoelectric transducer induce resonance in the hammer-shaped end microglass needle 3. The microparticle 6 rotates and moves under the combined action of the flow field force and secondary radiation force generated by the hammer-shaped end microglass needle 3. Compared to existing micromanipulation manipulator systems, this invention avoids physical contact between the manipulator end and the microparticle throughout the operation, thus preventing any damage to the microparticle. Furthermore, the hammer-shaped end allows the microparticle to remain in place and rotate, making it easy to control within the observation range. Compared to existing non-contact operations using magnetic, electrical, or optical fields as indirect external fields, this invention offers better safety. Compared to existing systems for cell micromanipulation within microfluidic chips, this invention is not limited by the size of the operation task or object, offering high operational flexibility. Moreover, this invention achieves the capture, movement, and rotation of microparticles through a single actuator, avoiding the high complexity, low success rate, and inefficiency associated with traditional multi-actuator systems.

[0058] In summary, this invention effectively solves the problems of complex motion control, limited functionality, poor safety, inefficiency, and poor flexibility encountered in some relatively complex micro-operations. The non-contact micro-operating system provided by this invention demonstrates strong advantages and great potential in the movement, positioning, and fixation of micro-targets.

[0059] Although this example describes the embodiments of the present invention in conjunction with the accompanying drawings, those skilled in the art can make various modifications and improvements without departing from the principles of the present invention, and these should also be considered to fall within the scope of protection of the present invention.

Claims

1. A device for controlling the movement and rotation of a micro-target driven by acoustic tweezers, characterized in that, It includes a micro 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 end of the micro glass needle (3) is placed in the liquid contained in the glass dish (4); the end of the micro glass needle (3) is hammer-shaped. The piezoelectric transducer (5) is used to generate sound waves with a certain set frequency and amplitude. The piezoelectric transducer (5) is fixed on the glass dish (4). The piezoelectric transducer (5) includes a piezoelectric transducer sheet and a piezoelectric actuator. The piezoelectric actuator is used to input a sinusoidal signal to the piezoelectric transducer sheet, so that the piezoelectric transducer sheet generates sound waves with a set frequency and amplitude. The piezoelectric transducer is fixed to the bottom of the glass dish (4); through the transmission of the liquid in the glass dish (4), the micro glass needle (3) resonates, thereby generating a time-averaged flow field and secondary radiation force in the surrounding liquid, which together act on the microparticle (6), causing the microparticle (6) to rotate and move.

2. The acoustic tweezers-driven movement and rotation control device for a micro-target as described in claim 1, characterized in that, 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 micro glass needle (3) is fixed on the fine-tuning platform (2). 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 posture of the micro glass needle (3).

3. A control method based on the control device according to claim 1 or 2, characterized in that, include: S401: Place the particles (6) in the liquid in the glass dish (4) and place them in the field of view of the microscope through a slide; S402: Adjust the three-axis moving platform (1) and the fine-tuning platform (2) to immerse the micro glass needle (3) in the liquid in the glass dish (4); S403； Turn on the piezoelectric transducer (5) and adjust the frequency and amplitude of its output sound wave. When the frequency of the sound wave is close to the resonant frequency of the micro glass needle (3), the micro glass needle (3) oscillates, thereby generating a vertically distributed flow field around it. S404: Adjust the three-axis moving platform (1) to bring the micro glass needle (3) close to the microparticle (6). Under the action of secondary radiation force, the microparticle (6) moves closer to the micro glass needle (3). The liquid flowing at high speed on the surface of the needle makes the microparticle (6) approach but not contact the needle, thus capturing the microparticle (6). S405: Adjust the three-axis moving platform (1) to make the micro glass needle (3) move, and drive the microparticle (6) to move under the action of 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) to move the microparticles (6) to the end port of the micro glass needle (3). The microparticles (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 particle (6) is slowly reduced to the minimum speed. When it rotates to the expected position, the input signal of the piezoelectric transducer (5) is immediately cut off, and the particle (6) stops rotating immediately.

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