A piezoelectric robot for precise injection of a trace amount of medicine and a method for searching for a parafocal position

Abstract

The present application relates to the technical field of robots, and in particular to a piezoelectric robot for precise injection of trace drugs and a method for searching for a parafocal position; the piezoelectric robot for precise injection of trace drugs comprises: a base, a planar three-degree-of-freedom piezoelectric platform is arranged on the base, an injection object is arranged on the planar three-degree-of-freedom piezoelectric platform, and the planar three-degree-of-freedom piezoelectric platform is used to drive the injection object to translate and rotate; a piezoelectric automatic focusing system is arranged on the base, and the piezoelectric automatic focusing system is arranged correspondingly with the planar three-degree-of-freedom piezoelectric platform, and the piezoelectric automatic focusing system is used to focus and monitor the injection object in situ; a piezoelectric injection system comprises a piezoelectric injector, a fixing support and a three-degree-of-freedom motion platform; the piezoelectric robot for precise injection of trace drugs has the characteristics of compact structure, fast focusing speed, precise control of trace drugs and high automation degree.

Description

Technical Field

[0001] This invention relates to the field of robotics, specifically to a piezoelectric robot for precise injection of micro-drugs and a method for finding the focal position. Background Technology

[0002] In recent years, with the development of biomedical technology and precision manipulation technology, cell microinjection technology has gradually matured. Cell microinjection is the delivery of exogenous substances (mRNA, proteins, drugs, etc.) into cells via injection, playing an important role in fields such as genetic engineering, protein engineering, intracytoplasmic sperm injection (ICSI), biomedicine, and pharmacological research. Currently, most microinjections are performed manually by laboratory technicians. Therefore, technicians need extensive training, proficiency, and the ability to withstand the pressure of long working hours. This not only leads to low injection efficiency but also poor stability and consistency. Furthermore, precise control of drug injection volume is a critical challenge that urgently needs to be addressed. To address these issues, a piezoelectric robot for precise micro-drug injection is needed. Summary of the Invention

[0003] Therefore, the technical problem to be solved by the present invention is to overcome the problems of low injection efficiency, difficulty in precise control of drug injection volume, and low degree of automation of the existing micro-injection robot, so as to provide a piezoelectric robot for precise injection of micro-drugs and a method for searching the focal position.

[0004] To address the aforementioned technical problems, this invention provides a piezoelectric robot for precise micro-drug injection, comprising: a base, on which a planar three-degree-of-freedom piezoelectric platform is mounted, and an injection target is mounted on the planar three-degree-of-freedom piezoelectric platform for driving the injection target to translate and rotate; a piezoelectric autofocus system mounted on the base and corresponding to the planar three-degree-of-freedom piezoelectric platform, the piezoelectric autofocus system being used for focusing and in-situ monitoring of the injection target; and a piezoelectric injection system comprising a piezoelectric injector, a fixed support, and a three-degree-of-freedom motion platform; the three-degree-of-freedom motion platform is mounted on the base, one end of the fixed support is connected to the three-degree-of-freedom motion platform, and the other end is connected to the piezoelectric injector, the piezoelectric injection system corresponding to the planar three-degree-of-freedom piezoelectric platform and the piezoelectric autofocus system.

[0005] Furthermore, the piezoelectric autofocus system includes a CCD camera, a parallel optical lens, a semi-reflective mirror, a piezoelectric focusing device, a support column, a parallel optical lens holder, a coaxial light source, a microscope objective, and a support base; the support base is connected to the base, the support column is mounted on the support base, the parallel optical lens is fixed to the support column via the parallel optical lens holder, the CCD camera is connected to one end of the parallel optical lens, the semi-reflective mirror is connected to the other end of the parallel optical lens, the coaxial light source is connected to the semi-reflective mirror, and the microscope objective is connected to the semi-reflective mirror via the piezoelectric focusing device.

[0006] Furthermore, the piezoelectric focusing device includes a focusing device connector, a bridge-type displacement amplification mechanism, a piezoelectric stack, a microscope objective lens connector, and a piezoelectric focusing device housing; the piezoelectric focusing device connector is connected to a semi-reflective mirror, the microscope objective lens connector is connected to a microscope objective lens, two symmetrically arranged bridge-type displacement amplification mechanisms are provided between the piezoelectric focusing device connector and the microscope objective lens connector, and the piezoelectric stack is disposed within the bridge-type displacement amplification mechanism.

[0007] Furthermore, the two piezoelectric stacks are arranged in parallel.

[0008] Further, the piezoelectric injector includes an injection needle, a drug cavity, a piston, a first displacement amplification mechanism, a first piezoelectric stack, an end cap, a second displacement amplification mechanism, a second piezoelectric stack, and a tailstock; the tailstock is connected to the fixed bracket, the first displacement amplification mechanism is disposed within the end cap, the first piezoelectric stack is located within the first displacement amplification mechanism, the end cap is disposed within the tailstock and close to the first displacement amplification mechanism, the second displacement amplification mechanism is disposed within the tailstock, and the second piezoelectric stack is disposed within the second displacement amplification mechanism; the piston is disposed within the drug cavity, the injection needle is connected to the drug cavity, the first displacement amplification mechanism is connected to the second displacement amplification mechanism, the end cap, and the piston, the end cap and the tailstock are not directly connected and can move relative to each other, and the drug cavity is used to store drugs.

[0009] Furthermore, the planar three-degree-of-freedom piezoelectric platform includes a piezoelectric platform base and a piezoelectric platform drive body. The piezoelectric platform base includes a platform base, a support foot, and a ball bearing roller plunger. The ball bearing roller plunger is connected to the support foot and is used to support the platform base. The platform base is used to place the injection object.

[0010] Furthermore, the piezoelectric platform drive includes a platform connector, a piezoelectric bicrystalline beam oscillator, and a clamping block; the platform connector is connected to the support platform base, the platform connector is connected to one side of the piezoelectric bicrystalline beam oscillator, and the clamping block is connected to the other side of the piezoelectric bicrystalline beam oscillator.

[0011] Further, the platform connecting member includes a body and four connecting plates. The four connecting plates and the body are integrally formed, and the four connecting plates are perpendicular to each other.

[0012] Further, the piezoelectric bimorph beam oscillator includes piezoelectric ceramic sheets, a metal substrate, and a mass block. The piezoelectric ceramic sheets are disposed on both sides of the metal substrate, and the mass block is disposed at one end of the metal substrate away from the platform connecting body.

[0013] The present invention also provides a method for searching the ortho-focus position of the piezoelectric robot for precise micro-drug injection, which is characterized by including the following steps: First, taking 4S as the movement step of the piezoelectric focusing device, collecting three images and calculating the sharpness C1, C2, and C3 of the images, and then comparing the magnitudes of C1, C2, and C3; if C1 > C2 > C3, it means that the three steps just moved are exactly on the other side of the ortho-focus position and have just crossed the ortho-focus position, and a smaller step needs to be taken for reverse search. Therefore, the step is adjusted to 2S and reverse search is performed; if C1 < C2 < C3 or C1 > C2 < C3, it means that the ortho-focus position has not been reached and the ortho-focus position is in the current movement direction of the piezoelectric focusing device. Therefore, search continues in the original direction with a step of 4S; if C1 <c2>If C3, it indicates that the ortho-focus position is within the range of the just-moved three steps. At this time, limit the search range of the ortho-focus position within three steps, and end the rough focusing stage to enter the fine focusing stage. In the fine focusing stage, first use S as the movement step of the piezoelectric focusing device, collect three images and calculate the sharpness C1, C2, and C3 of the images, and then compare the magnitudes of C1, C2, and C3. If C1 > C2 > C3, it proves that the ortho-focus position has just been crossed, and it is necessary to reduce the step size for reverse search. Therefore, adjust the step size to 0.5S and conduct reverse search. If C1 < C2 < C3 or C1 > C2 < C3, it indicates that the ortho-focus position has not been reached yet, and the ortho-focus position is in the current movement direction of the piezoelectric focusing device. Therefore, continue to search in the original direction with a step size of S. If C1 <c2>C3 indicates that the focus position has been reached, the search ends, and the piezoelectric autofocus system 1 has completed the autofocus task.

[0014] The technical solution of this invention has the following advantages:

[0015] The piezoelectric robot for precise micro-drug injection provided by this invention includes: a base, on which a planar three-degree-of-freedom piezoelectric platform is mounted, and an injection target is mounted on the planar three-degree-of-freedom piezoelectric platform for driving the injection target to translate and rotate; a piezoelectric autofocusing system mounted on the base and corresponding to the planar three-degree-of-freedom piezoelectric platform, the piezoelectric autofocusing system for focusing and in-situ monitoring of the injection target; and a piezoelectric injection system including a piezoelectric injector, a fixed support, and a three-degree-of-freedom motion platform; the three-degree-of-freedom motion platform is mounted on the base, one end of the fixed support is connected to the three-degree-of-freedom motion platform, and the other end is connected to the piezoelectric injector, the piezoelectric injection system corresponding to the planar three-degree-of-freedom piezoelectric platform and the piezoelectric autofocusing system.

[0016] By mounting a planar three-degree-of-freedom piezoelectric platform on a base, the injection target is placed on this platform. The platform can translate and rotate on the base to adjust its position, thereby moving the injection target on the platform. This facilitates rapid automatic focusing and in-situ monitoring of the injection target by the piezoelectric focusing system based on visual feedback. Once the injection target's position is determined, a micro-injection is performed using the piezoelectric injection system. Specifically, the movement of the three-degree-of-freedom motion platform on the base can be manually adjusted, thereby moving the fixed support and the piezoelectric injector to the designated position for micro-drug injection.

[0017] The piezoelectric robot for precise micro-drug injection boasts a piezoelectric focusing mechanism with advantages such as fast focusing speed and high motion resolution, significantly reducing manual focusing time and improving the accuracy of microscopic focusing. The piezoelectric injector adopts an integrated design concept, combining the syringe's puncture function with drug injection functionality into a compact structure. The combination of piezoelectric stacks and displacement amplification mechanisms gives it high motion resolution, enabling precise control of micro-drugs. Furthermore, this piezoelectric robot for precise micro-drug injection features a compact structure, fast focusing speed, precise micro-drug control, high degree of automation, and no electromagnetic interference. Through the coordinated operation of the piezoelectric focusing mechanism, piezoelectric injector, and piezoelectric platform, it can complete fully automated precise micro-drug injection tasks, making it promising for applications in fields such as genetic engineering, protein engineering, intracytoplasmic sperm injection (ICSI), biomedicine, and pharmacological research.

[0018] The summary section is provided to present the chosen concepts in a simplified form, which will be further described in the detailed description below. The summary section is not intended to identify essential or necessary features of this disclosure, nor is it intended to limit the scope of this disclosure. Attached Figure Description

[0019] To more clearly illustrate the specific embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the specific embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of the present invention. For those skilled in the art, other drawings can be obtained from these drawings without creative effort.

[0020] Figure 1 A schematic diagram of the piezoelectric robot for precise micro-drug injection provided by the present invention;

[0021] Figure 2 A schematic diagram of the piezoelectric focusing device for precise micro-drug injection provided by the present invention;

[0022] Figure 3 Flowchart of the piezoelectric robot piezoelectric focusing position search algorithm for precise micro-drug injection provided by the present invention;

[0023] Figure 4 A schematic diagram of a piezoelectric robot piezoelectric injector for precise micro-drug injection provided by the present invention;

[0024] Figure 5 A schematic diagram of the piezoelectric platform substrate of the planar three-degree-of-freedom piezoelectric platform for the piezoelectric robot for precise micro-drug injection provided by the present invention;

[0025] Figure 6 A schematic diagram of the piezoelectric platform drive body of the planar three-degree-of-freedom piezoelectric platform of the piezoelectric robot for precise micro-drug injection provided by the present invention;

[0026] Figure 7 A schematic diagram of the motion principle of the planar three-degree-of-freedom piezoelectric platform of the piezoelectric robot for precise micro-drug injection provided by the present invention;

[0027] Figure 8 The piezoelectric robot system for precise micro-drug injection provided by this invention is shown in the flowchart.

[0028] Explanation of reference numerals in the attached figures:

[0029] 1. Piezoelectric autofocus system; 1-1. CCD camera; 1-2. Parallel optical lens; 1-3. Semi-reflective mirror; 1-4. Piezoelectric focusing device; 1-4-1. Focusing device connector; 1-4-2. Bridge-type shift magnification mechanism; 1-4-3. Piezoelectric stack; 1-4-4. Microscope objective lens connector; 1-4-5. Piezoelectric focusing device housing; 1-5. Support column; 1-6. Parallel optical lens holder; 1-7. Coaxial light source; 1-8. Microscope objective lens; 1-9. Support base;

[0030] 2. Piezoelectric injection system; 2-1. Piezoelectric injector; 2-1-1. Injection needle; 2-1-2. Drug cavity; 2-1-3. Piston; 2-1-4. First displacement amplification mechanism; 2-1-5. First piezoelectric stack; 2-1-6. End cap; 2-1-7. Second displacement amplification mechanism; 2-1-8. Second piezoelectric stack; 2-1-9. Tailstock; 2-2. Fixed bracket; 2-3. Three-degree-of-freedom motion platform;

[0031] 3. Planar three-degree-of-freedom piezoelectric platform; 3-1. Piezoelectric platform base; 3-1-1. Platform base; 3-1-2. Support foot; 3-1-3. Ball bearing roller and ball head plunger; 3-2. Piezoelectric platform drive body; 3-2-1. Platform connector; 3-2-2. Piezoelectric bicrystalline beam oscillator; 3-2-2-1. Piezoelectric ceramic sheet; 3-2-2-2. Metal substrate; 3-2-2-3. Mass block; 3-2-3. Clamping block;

[0032] 4. Base. Detailed Implementation

[0033] In the following description, only certain exemplary embodiments are briefly described. As those skilled in the art will recognize, the described embodiments can be modified in various ways without departing from the spirit or scope of this disclosure. Therefore, the drawings and description are to be considered exemplary in nature and not restrictive.

[0034] In the description of this disclosure, it should be understood that the terms "center," "longitudinal," "lateral," "length," "width," "thickness," "upper," "lower," "front," "rear," "left," "right," "vertical," "horizontal," "top," "bottom," "inner," "outer," "clockwise," and "counterclockwise," etc., indicating orientations or positional relationships based on the orientations or positional relationships shown in the accompanying drawings, are only for the convenience of describing this disclosure and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation, and therefore should not be construed as a limitation of this disclosure. Furthermore, the terms "first" and "second" are used for descriptive purposes only and should not be construed as indicating or implying relative importance or implicitly specifying the number of indicated technical features. Thus, a feature defined as "first" or "second" may explicitly or implicitly include one or more of the stated features. In the description of this disclosure, "a plurality of" means two or more, unless otherwise explicitly specified.

[0035] In the description of this disclosure, it should be noted that, unless otherwise expressly specified and limited, the terms "installation," "connection," and "joint" should be interpreted broadly. For example, they can refer to fixed connections, detachable connections, or integral connections; they can refer to mechanical connections, electrical connections, or connections that allow for communication; they can refer to direct connections or indirect connections through an intermediate medium; they can refer to the internal communication of two components or the interaction between two components. Those skilled in the art can understand the specific meaning of the above terms in this disclosure according to the specific circumstances.

[0036] In this disclosure, unless otherwise expressly specified and limited, "above" or "below" the second feature can include direct contact between the first and second features, or contact between the first and second features through another feature between them. Furthermore, "above," "over," and "on top" of the second feature includes the first feature being directly above or diagonally above the second feature, or simply indicates that the first feature is at a higher horizontal level than the second feature. "Below," "below," and "under" the second feature includes the first feature being directly above or diagonally above the second feature, or simply indicates that the first feature is at a lower horizontal level than the second feature.

[0037] The following disclosure provides many different embodiments or examples for implementing various structures of this disclosure. To simplify the disclosure, specific examples of components and arrangements are described below. Of course, these are merely examples and are not intended to limit the scope of this disclosure. Furthermore, reference numerals and / or letters may be repeated in different examples; such repetition is for simplification and clarity and does not in itself indicate a relationship between the various embodiments and / or arrangements discussed. In addition, the various specific examples of processes and materials provided in this disclosure are examples of applications of other processes and / or the use of other materials that will be apparent to those skilled in the art.

[0038] The preferred embodiments of this disclosure are described below with reference to the accompanying drawings. It should be understood that the preferred embodiments described herein are for illustration and explanation only and are not intended to limit this disclosure.

[0039] Please see Figures 1 to 8 As shown, this invention provides a piezoelectric robot for precise micro-drug injection, comprising: a base 4, on which a planar three-degree-of-freedom piezoelectric platform 3 is mounted, and an injection target is mounted on the planar three-degree-of-freedom piezoelectric platform 3, which is used to drive the injection target to translate and rotate; a piezoelectric autofocusing system 1, mounted on the base 4, and correspondingly arranged with the planar three-degree-of-freedom piezoelectric platform 3, which is used for focusing and in-situ monitoring of the injection target; and a piezoelectric injection system 2, comprising a piezoelectric injector 2-1, a fixed bracket 2-2, and a three-degree-of-freedom motion platform 2-3; the three-degree-of-freedom motion platform 2-3 is mounted on the base 4, one end of the fixed bracket 2-2 is connected to the three-degree-of-freedom motion platform 2-3, and the other end is connected to the piezoelectric injector 2-1, and the piezoelectric injection system 2 corresponds to the planar three-degree-of-freedom piezoelectric platform 3 and the piezoelectric autofocusing system 1.

[0040] A planar three-degree-of-freedom piezoelectric platform 3 is mounted on the base 4. This platform 3 carries the injection target and can translate and rotate on the base 4 to adjust its position, thereby moving the injection target. This facilitates rapid automatic focusing and in-situ monitoring of the injection target by the piezoelectric focusing system based on visual feedback. Once the position of the injection target is determined, a micro-injection is performed using the piezoelectric injection system 2. Specifically, the movement of the three-degree-of-freedom motion platform 2-3 on the base 4 can be manually adjusted, thereby moving the fixed support 2-2 and the piezoelectric injector 2-1 to the designated position for micro-drug injection.

[0041] The piezoelectric focusing device 1-4 of this micro-drug precision injection piezoelectric robot has the advantages of fast focusing speed and high motion resolution, which greatly saves the time of manual focusing and improves the accuracy of microscopic focusing. The piezoelectric injector 2-1 adopts an integrated design concept, integrating the puncture function of the syringe and the drug injection function into one compact structure. The combination of piezoelectric stack and displacement amplification mechanism makes its motion resolution high, realizing precise control of micro-drugs. Furthermore, this micro-drug precision injection piezoelectric robot has the characteristics of compact structure, fast focusing speed, precise control of micro-drugs, high degree of automation, and no electromagnetic interference. Through the cooperation of the piezoelectric focusing device 1-4, the piezoelectric injector 2-1, and the planar three-degree-of-freedom piezoelectric platform 3, it can complete the task of fully automatic micro-drug precision injection, making it promising for applications in fields such as genetic engineering, protein engineering, intracytoplasmic sperm injection, biomedicine, and pharmacological research.

[0042] The three-degree-of-freedom motion platform 2-3 is used for macroscopic adjustment of the position of the piezoelectric injector 2-1, including three-degree-of-freedom motion outputs along the x-axis, y-axis, and z-axis, with the three-degree-of-freedom motion outputs being independent of each other. The three-degree-of-freedom motion platform 2-3 can be a commercially available three-degree-of-freedom platform that is manually adjustable or controlled by a servo motor, or it can be a piezoelectric platform with a wide range of motion output capabilities.

[0043] In some optional embodiments, the piezoelectric autofocus system includes a CCD camera 1-1, a parallel optical lens 1-2, a semi-reflective mirror 1-3, a piezoelectric focuser 1-4, a support column 1-5, a parallel optical lens holder 1-6, a coaxial light source 1-7, a microscope objective lens 1-8, and a support base 1-9.

[0044] Specifically, the support base 1-9 is connected to the base 4, and the support column 1-5 is disposed on the support base 1-9; specifically, the support base 1-9 is connected to the base 4 by bolts, and the support column 1-5 is fixed to the support base 1-9 by bolts.

[0045] The parallel optical lens 1-2 is fixed to the support column 1-5 via the parallel optical lens bracket 1-6. The CCD camera 1-1 is connected to one end of the parallel optical lens 1-2 for microscopic imaging of the injected object. The semi-reflective mirror 1-3 is connected to the other end of the parallel optical lens 1-2. The coaxial light source 1-7 is connected to the semi-reflective mirror 1-3 and provides illumination for microscopic observation. The microscope objective 1-8 is connected to the semi-reflective mirror 1-3 via a piezoelectric focusing device 1-4. The piezoelectric focusing device 1-4 can achieve single-degree-of-freedom motion output and is used to move the microscope objective 1-8 to complete the focusing operation.

[0046] Please see Figure 2 As shown, the piezoelectric focusing device 1-4 includes a focusing device connector 1-4-1, a bridge-type displacement amplification mechanism 1-4-2, a piezoelectric stack 1-4-3, a microscope objective lens connector 1-4-4, and a piezoelectric focusing device housing 1-4-5.

[0047] The piezoelectric focusing connector 1-4-1 is connected to the semi-reflective lens 1-3, and the microscope objective connector 1-4-4 is connected to the microscope objective 1-8. Two symmetrically arranged bridge-type displacement amplification mechanisms 1-4-2 are provided between the piezoelectric focusing connector 1-4-1 and the microscope objective connector 1-4-4. The piezoelectric stack 1-4-3 is located inside the bridge-type displacement amplification mechanism 1-4-2.

[0048] The two piezoelectric stacks 1-4-3 are connected in parallel, simultaneously driving the two bridge-type displacement amplification mechanisms 1-4-2 to complete single-degree-of-freedom motion output. When a voltage is applied to the piezoelectric stack 1-4-3, different voltage values ​​correspond to different elongations of the piezoelectric stack 1-4-3, thereby driving the bridge-type displacement amplification mechanism 1-4-2 to move. Therefore, driven by the piezoelectric stack 1-4-3, the bridge-type displacement amplification mechanism 1-4-2 can drive the microscope objective lens 1-8 to move up and down, ultimately completing the focusing task.

[0049] The piezoelectric focusing device 1-4 uses a bridge-type displacement amplification mechanism 1-4-2 and a piezoelectric stack 1-4-3 for displacement amplification and output. The displacement amplification mechanism can also be a lever-type amplification mechanism, and the piezoelectric stack can be replaced by a patch-type or sandwich-type piezoelectric actuator to complete one-dimensional motion output.

[0050] The semi-reflective mirror 1-3 and the coaxial light source 1-7 provide illumination conditions for microscopic observation. Other illumination conditions, such as a ring LED light source, can also be used instead.

[0051] Please see Figure 4 As shown, the piezoelectric injector 2-1 includes an injection needle 2-1-1, a drug cavity 2-1-2, a piston 2-1-3, a first displacement amplification mechanism 2-1-4, a first piezoelectric stack 2-1-5, an end cap 2-1-6, a second displacement amplification mechanism 2-1-7, a second piezoelectric stack 2-1-8, and a tailstock 2-1-9;

[0052] The tailstock 2-1-9 is connected to the fixed bracket. The first displacement amplification mechanism 2-1-4 is disposed inside the end cap 2-1-6. The first piezoelectric stack 2-1-5 is located inside the first displacement amplification mechanism 2-1-4. The end cap 2-1-6 is connected to the second displacement amplification mechanism 2-1-7. The second displacement amplification mechanism 2-1-7 is disposed inside the tailstock. The second piezoelectric stack 2-1-8 is disposed inside the second displacement amplification mechanism 2-1-7.

[0053] Piston 2-1-3 is disposed in the drug cavity 2-1-2. Piezoelectric injection needle 2-1-1 is connected to the drug cavity 2-1-2. The first displacement amplification mechanism 2-1-4 is connected to the second displacement amplification mechanism 2-1-7, end cap 2-1-6, and piston 2-1-3. There is no direct connection between end cap 2-1-6 and tailstock 2-1-9, and they can move relative to each other. The drug cavity 2-1-2 is used to store drugs.

[0054] The piezoelectric injector 2-1 has two functions: controlling the feeding motion of the injection needle 2-1-1 and the piston 2-1-3. The piezoelectric stack used to control the feeding motion has longitudinal movement capability and can be replaced by a patch-type or sandwich-type single-degree-of-freedom piezoelectric actuator. The amplification mechanisms 2-1-4 and 2-1-7 used for displacement amplification can be bridge-type or lever-type amplification mechanisms, etc.

[0055] The injection procedure mainly consists of two steps: the puncture of the injection needle 2-1-1 and the injection of a small amount of medication.

[0056] The first step involves the puncture movement of the injection needle 2-1-1, which is accomplished by the second piezoelectric stack 2-1-8 and the second displacement amplification mechanism 2-1-7. When the voltage across the second piezoelectric stack 2-1-8 is zero, the injection needle 2-1-1 is in its original position. When a voltage is applied to the second piezoelectric stack 2-1-8, the second piezoelectric stack 2-1-8 elongates according to the magnitude of the voltage. As the second piezoelectric stack 2-1-8 elongates, the second displacement amplification mechanism 2-1-7 drives the piezoelectric injector end cap 2-1-6 to move, thereby controlling the puncture movement of the injection needle 2-1-1. By controlling the voltage across the second piezoelectric stack 2-1-8, the movement and displacement of the injection needle 2-1-1 can be precisely controlled, thereby controlling the puncture depth of the injection needle 2-1-1 and completing the puncture task.

[0057] The second step, drug injection, is mainly accomplished by the first piezoelectric stack 2-1-5 and the first displacement amplification mechanism 2-1-4. When a voltage is applied to the first piezoelectric stack 2-1-5, the first piezoelectric stack 2-1-5 changes its elongation according to the voltage. When the first piezoelectric stack 2-1-5 elongates, the first displacement amplification mechanism 2-1-4 drives the piston 2-1-3 to push the drug to complete the injection. Therefore, by precisely controlling the voltage across the first piezoelectric stack 2-1-5, the movement and displacement of the piston 2-1-3 can be precisely controlled, thereby precisely controlling the amount of drug injected. When the voltage applied to the first piezoelectric stack 2-1-5 is reduced, the first displacement amplifier 2-1-4 pulls the piston 2-1-3, which can complete the replenishment or replacement of the drug.

[0058] Please see Figure 5 As shown, the planar three-degree-of-freedom piezoelectric platform 3 includes a piezoelectric platform base 3-1 and a piezoelectric platform drive body 3-2. The piezoelectric platform base 3-1 includes a platform base and support feet 3-1-2, as well as a ball bearing roller plunger 3-1-3.

[0059] The ball bearing roller plunger 3-1-3 is connected to the support foot 3-1-2 via threads, and the ball bearing roller plunger 3-1-3 is used to support the platform base 3-1-3;

[0060] The ball bearing roller plunger 3-1-3 is used to support the platform base 3-1-3, the platform base 3-1-1 is used to place the injection object, and the platform connector 3-2-1 is connected to the platform base 3-1-1 by screws.

[0061] Please see Figure 6 As shown, the piezoelectric platform drive body 3-2 includes a platform connector 3-2-1, a piezoelectric bicrystalline beam oscillator 3-2-2, and a clamping block 3-2-3; wherein, the platform connector 3-2-1 is connected to the support platform base 3-1-3, the platform connector is connected to one side of the piezoelectric bicrystalline beam oscillator 3-2-2, and the clamping block is connected to the other side of the piezoelectric bicrystalline beam oscillator 3-2-2.

[0062] Specifically, the piezoelectric bicrystalline beam oscillator 3-2-2 is connected to the platform connector 3-2-1 via a clamping block 3-2-3 and screws, providing the driving force required for the movement of the planar three-degree-of-freedom piezoelectric platform 3; the piezoelectric ceramic sheet 3-2-2-1 is attached to both sides of the metal substrate 3-2-2-2, enabling the metal substrate 3-2-2-2 to complete bending motion, which in turn drives the mass block 3-2-2-3 to move; the four piezoelectric bicrystalline beam oscillators 3-2-2 are arranged vertically and crosswise to drive the translational and rotational motion of the planar three-degree-of-freedom piezoelectric platform 3.

[0063] The piezoelectric bicrystalline oscillator 3-2-2 is used to generate the driving force required to drive the planar three-degree-of-freedom piezoelectric platform 3 to move. The inertial driving force is generated by an inertial impact drive scheme. One-dimensional motion output can be achieved by commercial piezoelectric stacks or sandwich piezoelectric actuators instead of piezoelectric bicrystalline oscillators 3-2-2 to generate inertial driving force.

[0064] In this embodiment, the platform connector 3-2-1 includes a body and four connecting plates. The four connecting plates are integrally formed with the body, and the four connecting plates are arranged perpendicular to each other.

[0065] In some optional embodiments, the piezoelectric bicrystalline beam oscillator 3-2-2 includes a piezoelectric ceramic sheet 3-2-2-1, a metal substrate 3-2-2-2, and a mass block 3-2-2-3; wherein the piezoelectric ceramic sheet 3-2-2-1 is disposed on both sides of the metal substrate 3-2-2-2, and the mass block 3-2-2-3 is disposed at the end of the metal substrate 3-2-2-2 away from the platform connector 3-2-1.

[0066] Specifically, the metal substrate 3-2-2-2 completes the bending motion, driving the mass block 3-2-2-3 to move. The four piezoelectric bicrystalline oscillators 3-2-2 are arranged vertically and crosswise to drive the translation and rotation of the planar three-degree-of-freedom piezoelectric platform 3.

[0067] Please see Figure 7 As shown, the specific working principle of the planar three-degree-of-freedom piezoelectric platform 3 is inertial impact type. For the sake of simplicity, the vertically intersecting piezoelectric bicrystalline beam oscillators 3-2-2 are labeled as I, II, III, and IV, respectively.

[0068] Please see Figure 7 As shown in (1), when II and IV remain in their initial state, and when I and III move slowly along the negative X-axis, the inertial force generated by the mass block 3-2-2-3 is less than the static friction force between the planar three-degree-of-freedom piezoelectric platform 3 and the contact surface. Therefore, the planar three-degree-of-freedom piezoelectric platform 3 remains stationary.

[0069] Please see Figure 7 As shown in (2), when I and III move rapidly along the positive X-axis, the inertial force generated by the mass block 3-2-2-3 is greater than the static friction between the planar three-degree-of-freedom piezoelectric platform 3 and the contact surface. Therefore, the planar three-degree-of-freedom piezoelectric platform 3 moves one step along the negative X-axis. Similarly, when I and III move slowly along the positive X-axis, the inertial force generated by the mass block 3-2-2-3 is less than the static friction between the planar three-degree-of-freedom piezoelectric platform 3 and the contact surface. Therefore, the planar three-degree-of-freedom piezoelectric platform 3 moves one step. Platform 3 remains stationary. When I and III move rapidly along the negative X-axis, the inertial force generated by the mass block 3-2-2-3 is greater than the static friction between the planar three-degree-of-freedom piezoelectric platform 3 and the contact surface. Therefore, the planar three-degree-of-freedom piezoelectric platform 3 moves one step along the positive X-axis. If the planar three-degree-of-freedom piezoelectric platform 3 is to be driven to move along the Y-axis, I and III need to be kept in their initial state, which can be achieved by controlling II and IV. The motion principle is the same as the motion principle of the planar three-degree-of-freedom piezoelectric platform 3 along the X-axis.

[0070] Please see Figure 7 As shown in (3), when I, II, III and IV bend slowly counterclockwise around the Z-axis, the inertial force generated by the mass block 3-2-2-3 is less than the static friction force between the planar three-degree-of-freedom piezoelectric platform 3 and the contact surface. Therefore, the planar three-degree-of-freedom piezoelectric platform 3 remains stationary.

[0071] Please see Figure 7 As shown in (4), when I, II, III, and IV simultaneously bend rapidly clockwise around the Z-axis, the inertial force generated by the mass block 3-2-2-3 is greater than the static friction between the planar three-degree-of-freedom piezoelectric platform 3 and the contact surface. Therefore, the planar three-degree-of-freedom piezoelectric platform 3 rotates counterclockwise around the Z-axis by an angle. Similarly, when I, II, III, and IV simultaneously bend slowly clockwise around the Z-axis, the inertial force generated by the mass block 3-2-2-3 is less than the static friction between the planar three-degree-of-freedom piezoelectric platform 3 and the contact surface. Therefore, the planar three-degree-of-freedom piezoelectric platform 3 remains stationary. When I, II, III, and IV simultaneously bend rapidly counterclockwise around the Z-axis, the inertial force generated by the mass block 3-2-2-3 is greater than the static friction between the planar three-degree-of-freedom piezoelectric platform 3 and the contact surface. Therefore, the planar three-degree-of-freedom piezoelectric platform 3 rotates clockwise around the Z-axis by an angle.

[0072] Please see Figure 3 As shown, the present invention also provides a method for searching the focal position of a piezoelectric robot for precise injection of micro-drugs, comprising the following steps:

[0073] After starting the search, first use 4S as the movement step of the piezoelectric focusing device 1-4, collect three images and calculate the sharpness C1, C2, and C3 of the images. Then compare the magnitudes of C1, C2, and C3. If C1 > C2 > C3, it means that the three steps just moved are exactly on the other side of the in-focus position and have just crossed the in-focus position, and it is necessary to reduce the step size for reverse search. Therefore, adjust the step size to 2S and conduct a reverse search. If C1 < C2 < C3 or C1 > C2 < C3, it means that the in-focus position has not been reached yet, and the in-focus position is in the current moving direction of the piezoelectric focusing device. Therefore, continue to search in the original direction with a step size of 4S. If C1 <c2>If C3 is obtained, it indicates that the orthofocus position is within the range of the just-moved three steps. At this time, the search range of the orthofocus position is limited within three steps, and the rough focusing stage ends and the fine focusing stage begins. In the fine focusing stage, first, taking S as the movement step of the piezoelectric focusing device, three images are collected and the sharpness C1, C2, and C3 of the images are calculated. Then, compare the magnitudes of C1, C2, and C3. If C1 > C2 > C3, it proves that the orthofocus position has just been crossed, and the step needs to be reduced for reverse search. Therefore, the step is adjusted to 0.5S and reverse search is carried out; if C1 < C2 < C3 or C1 > C2 < C3, it indicates that the orthofocus position has not been reached yet, and the orthofocus position is in the current movement direction of the piezoelectric focusing device. Therefore, continue to search in the original direction with the S step; if C1 <c2>C3 indicates that the focus position has been reached, the search ends, and the piezoelectric autofocus system 1 has completed the autofocus task.

[0074] The focal position refers to the position of the microscope objective 1-8 when the piezoelectric focusing device 1-4 completes the focusing task. At this position, the image sharpness value acquired by the CCD camera 1-1 is at its maximum. When the microscope objective 1-8 deviates from the focal position, the image sharpness value acquired by the CCD camera 1-1 decreases. Different positions of the microscope objective 1-8 correspond to different voltage values ​​applied to the piezoelectric stack 1-4-3. Therefore, searching for the focal position is equivalent to searching for the voltage value.

[0075] During the focus position search, the piezoelectric autofocus system 1 completes a crucial step in autofocusing; please refer to [link to relevant documentation]. Figure 3 As shown, the piezoelectric autofocus system 1 employs a coarse-fine combined focusing position search algorithm. When the voltage change applied to the piezoelectric stack 1-4-3 is one step S, the microscope objective 1-8 moves one step under the drive of the piezoelectric stack 1-4-3 and the bridge displacement amplifier 1-4-2. In the coarse adjustment stage, the microscope objective 1-8 is controlled to move with step sizes of 4S and 2S respectively. In the fine adjustment stage, the microscope objective 1-8 is controlled to move with step sizes of S and 0.5S respectively.

[0076] Please see Figure 8 As shown, the workflow of the piezoelectric robot system for precise micro-drug injection is as follows: After the control program starts, the image acquired by the piezoelectric autofocus system 1 is analyzed to determine if the image is clear. If the image is unclear, the piezoelectric focusing device 1-4 is controlled to automatically focus until the image is clear. If the image is clear, the system proceeds to determine if the orientation of the injection target is accurate. If the orientation is inaccurate, the orientation of the injection target is adjusted by controlling the translation or rotation of the planar three-degree-of-freedom piezoelectric platform 3. After the orientation adjustment of the injection target is completed, the micro-drug injection stage begins. This stage is completed in two steps: the puncture motion of the injection needle and the precise injection of the drug. First, the injection needle 2-1-1 is controlled to perform the puncture motion. Then, the piston 2-1-3 is controlled to push the drug to complete the injection. When performing single-cell microinjection or micro-drug formulation experiments, multiple injection tasks usually need to be completed. Therefore, it is necessary to determine whether all injection tasks have been completed. If not, the micro-drug injection process is repeated. If all tasks have been completed, the process ends.

[0077] Obviously, the above embodiments are merely illustrative examples for clear explanation and are not intended to limit the implementation. Those skilled in the art will recognize that other variations or modifications can be made based on the above description. It is neither necessary nor possible to exhaustively list all possible implementations here. However, obvious variations or modifications derived therefrom are still within the scope of protection of this invention.

Claims

1. A piezoelectric robot for precise injection of micro-drugs, characterized in that, include: The base (4) is provided with a planar three-degree-of-freedom piezoelectric platform (3), and the planar three-degree-of-freedom piezoelectric platform (3) is provided with an injection object. The planar three-degree-of-freedom piezoelectric platform (3) is used to drive the injection object to translate and rotate. The piezoelectric autofocus system (1) is mounted on the base (4) and is correspondingly set with the planar three-degree-of-freedom piezoelectric platform (3). The piezoelectric autofocus system (1) is used for focusing and in-situ monitoring of the injection object. The piezoelectric injection system (2) includes a piezoelectric injector (2-1), a fixed bracket (2-2), and a three-degree-of-freedom motion platform (2-3). The three-degree-of-freedom motion platform (2-3) is mounted on a base (4). One end of the fixed bracket (2-2) is connected to the three-degree-of-freedom motion platform (2-3), and the other end is connected to the piezoelectric injector (2-1). The piezoelectric injection system (2) corresponds to the planar three-degree-of-freedom piezoelectric platform (3) and the piezoelectric autofocus system (1). The planar three-degree-of-freedom piezoelectric platform (3) includes a piezoelectric platform base (3-1) and a piezoelectric platform drive (3-2). The piezoelectric platform base (3-1) includes a platform base (3-1-1), a support foot (3-1-2), and a ball bearing roller plunger (3-1-3). The ball bearing roller plunger (3-1-3) is connected to the support foot (3-1-2). The ball bearing roller plunger (3-1-3) is used to support the platform base (3-1-1), and the platform base (3-1-1) is used to place the injection object. The piezoelectric platform drive (3-2) includes a platform connector (3-2-1), a piezoelectric bicrystalline beam oscillator (3-2-2), and a clamping block (3-2-3); the platform connector (3-2-1) is connected to the support platform base (3-1-1), the platform connector (3-2-1) is connected to one side of the piezoelectric bicrystalline beam oscillator (3-2-2), and the clamping block (3-2-3) is connected to the other side of the piezoelectric bicrystalline beam oscillator (3-2-2); The platform connector (3-2-1) includes a main body and four connecting plates. The four connecting plates are integrally formed with the main body, and the four connecting plates are arranged perpendicular to each other. The piezoelectric bicrystalline beam oscillator (3-2-2) includes a piezoelectric ceramic sheet (3-2-2-1), a metal substrate (3-2-2-2), and a mass block (3-2-2-3); the piezoelectric ceramic sheet (3-2-2-1) is located on both sides of the metal substrate (3-2-2-2), and the mass block (3-2-2-3) is located at the end of the metal substrate (3-2-2-2) away from the platform connector (3-2-1).

2. The piezoelectric robot for precise micro-drug injection according to claim 1, characterized in that, The piezoelectric autofocus system (1) includes a CCD camera (1-1), a parallel optical lens (1-2), a semi-reflective mirror (1-3), a piezoelectric focuser (1-4), a support column (1-5), a parallel optical lens holder (1-6), a coaxial light source (1-7), a microscope objective lens (1-8), and a support base (1-9). The support base (1-9) is connected to the base (4), the support column (1-5) is set on the support base (1-9), the parallel optical lens (1-2) is fixed on the support column (1-5) through the parallel optical lens bracket (1-6), the CCD camera (1-1) is connected to one end of the parallel optical lens (1-2), the semi-reflective mirror (1-3) is connected to the other end of the parallel optical lens (1-2), the coaxial light source (1-7) is connected to the semi-reflective mirror (1-3), and the microscope objective (1-8) is connected to the semi-reflective mirror (1-3) through the piezoelectric focusing device (1-4).

3. The piezoelectric robot for precise micro-drug injection according to claim 2, characterized in that, The piezoelectric focusing device (1-4) includes a focusing device connector (1-4-1), a bridge-type displacement amplification mechanism (1-4-2), a piezoelectric stack (1-4-3), a microscope objective lens connector (1-4-4), and a piezoelectric focusing device housing (1-4-5). The piezoelectric focusing connector (1-4-1) is connected to the semi-reflective mirror (1-3), the microscope objective connector (1-4-4) is connected to the microscope objective (1-8), and two symmetrically arranged bridge-type displacement amplification mechanisms (1-4-2) are provided between the piezoelectric focusing connector (1-4-1) and the microscope objective connector (1-4-4). The piezoelectric stack (1-4-3) is located inside the bridge-type displacement amplification mechanism (1-4-2).

4. The piezoelectric robot for precise micro-drug injection according to claim 3, characterized in that, Two piezoelectric stacks (1-4-3) are connected in parallel.

5. The piezoelectric robot for precise micro-drug injection according to any one of claims 1-4, characterized in that, The piezoelectric injector (2-1) includes an injection needle (2-1-1), a drug cavity (2-1-2), a piston (2-1-3), a first displacement amplification mechanism (2-1-4), a first piezoelectric stack (2-1-5), an end cap (2-1-6), a second displacement amplification mechanism (2-1-7), a second piezoelectric stack (2-1-8), and a tailstock (2-1-9). The tailstock (2-1-9) is connected to the fixed bracket (2-2). The first displacement amplification mechanism (2-1-4) is located inside the end cap (2-1-6). The first piezoelectric stack (2-1-5) is located inside the first displacement amplification mechanism (2-1-4). The end cap (2-1-6) is located inside the tailstock (2-1-9) and close to the first displacement amplification mechanism (2-1-4). The second displacement amplification mechanism (2-1-7) is located inside the tailstock (2-1-9). The second piezoelectric stack is located inside the second displacement amplification mechanism (2-1-7). The piston (2-1-3) is located inside the drug cavity (2-1-2). The injection needle (2-1-1) is connected to the drug cavity (2-1-2). The first displacement amplification mechanism (2-1-4) is connected to the second displacement amplification mechanism (2-1-7), the end cap (2-1-6), and the piston (2-1-3). The end cap (2-1-6) and the tailstock (2-1-9) are not directly connected and can move relative to each other. The drug cavity (2-1-2) is used to store drugs.

6. A method for finding the focal position of a piezoelectric robot for precise micro-drug injection according to any one of claims 1-5, characterized in that, Includes the following steps: First, using 4S as the movement step size of the piezoelectric focuser (1-4), three images were acquired and the sharpness C1, C2 and C3 of the images were calculated. Then, the sizes of C1, C2 and C3 were compared. If C1 > C2 > C3, then the three steps just moved are exactly on the other side of the positive focus position and have just crossed the positive focus position. It is necessary to reduce the step size for reverse search. Therefore, adjust the step size to 2S and perform reverse search; If C1 < C2 < C3 or C1 > C2 < C3, it means that the positive focus position has not been reached yet, and the positive focus position is in the direction of the current movement of the piezoelectric focusing device. Therefore, continue to search in the original direction with a step size of 4S; If C1 <c2>C3, it means that the positive focus position is within the range of the three steps just moved. At this time, limit the search range of the positive focus position within three steps, and at this time, end the coarse adjustment stage and enter the fine adjustment stage;< / c2> In the fine adjustment stage, first use S as the movement step size of the piezoelectric focusing device (1-4), collect three images and calculate the sharpness C1, C2, and C3 of the images, and then compare the sizes of C1, C2, and C3; If C1 > C2 > C3, it proves that the positive focus position has just been crossed, and it is necessary to reduce the step size for reverse search. Therefore, adjust the step size to 0.5S and perform reverse search; If C1 < C2 < C3 or C1 > C2 < C3, it means that the positive focus position has not been reached yet, and the positive focus position is in the direction of the current movement of the piezoelectric focusing device. Therefore, continue to search in the original direction with a step size of S; If C1 <c2>C3, it means that the positive focus position has been reached, end the search, and the piezoelectric auto-focusing system (1) completes the auto-focusing task.< / c2>

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