A non-contact particle shaking device and method

Abstract

The present invention discloses a non-contact particle shaking device and method, the device includes at least two ultrasonic transducers, a microfluidic chip and an excitation power supply, the ultrasonic transducer is tightly fitted with the side wall of the microfluidic chip, and is located at the same cross section of the channel of the microfluidic chip, the main vibration direction of the ultrasonic transducer is perpendicular to the axis of the microfluidic chip channel, and the ultrasonic transducer is connected to the excitation power supply electrical signal. By simultaneously driving at least two ultrasonic transducers attached to the outer wall of the microfluidic chip, a body standing wave acoustic field is generated in the microchannel, and three-dimensional rapid capture of particles is achieved. On this basis, the frequency difference Δf of the two transducers is adjusted, and the particle's shaking frequency f and shaking amplitude A are controlled by Δf, so as to achieve precise fixed-frequency shaking control of a single particle or a particle cluster, and the fixed-frequency shaking has the advantages of precise and stable frequency output, good reliability, and easy adjustment.

Description

Technical Field

[0001] The present invention relates to the technical field of micro-nano control, and more specifically, to a non-contact particle shaking device and method. Background Art

[0002] With the rapid development of scientific fields such as biomedicine and micro-nano manufacturing, precise manipulation of microparticles has become an important direction of scientific research, and the requirements for manipulation technology are becoming increasingly higher. In addition to ultrasonic manipulation, common methods of microparticle manipulation include: optical tweezers, magnetophoresis, dielectrophoresis, etc. These manipulation methods not only have physical requirements for the controlled particles, but may also cause irreversible damage to the controlled particles. By utilizing the gentle and non-contact characteristics of ultrasonic manipulation, precise manipulation of particles can be achieved without pollution or damage; in addition, ultrasonic manipulation has no physical requirements for the controlled particles, and has the characteristics of diversified manipulation functions, simple structure of the manipulation device, easy miniaturization, easy to carry, and low production cost.

[0003] Especially in the field of tissue engineering, the use of ultrasound to capture cells in three dimensions and non-contact suspension culture has become a common technical solution. The establishment of an ultrasonic standing wave field can achieve the aggregation of free cells in a cell suspension; non-contact suspension culture can provide mild conditions for in vitro cell tissue growth and differentiation, and can also improve the survival rate of cell tissue transplantation. In addition, low-intensity periodic ultrasound stimulation is beneficial to cell differentiation and helps to improve tissue cell activity.

[0004] At present, the main technical means for the jitter control of particles in liquids is to build a thin-sheet acoustic control chamber and place an ultrasonic transducer directly below the chamber. By adjusting the driving frequency of the ultrasonic transducer, the particles in the chamber are first captured, and then the frequency is adjusted back and forth near the frequency to perform a periodic constant rate sweep operation to achieve periodic reciprocating motion of the controlled particles. The shortcomings of this particle jitter control method are that fixed-frequency jitter depends on the continuous periodic change of the piezoelectric transducer driving electrical signal. When jitter outputs of different frequencies and sizes are required, the driving frequency of the electrical signal end is required to be continuously adjustable, automatically periodically reciprocating, accurately controllable, and the output is stable and continuous, which inevitably places higher requirements on the signal end; in addition, this technology cannot achieve fixed-frequency and fixed-amplitude particle jitter. The experimental results of the inventors show that two standing waves with similar but different frequencies can generate a periodic oscillation force, which can repeatedly disturb the captured particles and cause them to oscillate spontaneously. Based on the experimental results, the inventors designed a device and method for non-contact rapid three-dimensional capture and precise fixed-frequency dithering, introducing a new mechanism for controlling the interaction between particles in a microfluidic environment, which is of great significance for creating bionic microenvironments and obtaining active bioreactors. Summary of the invention

[0005] The purpose of the present invention is to overcome the shortcomings of existing devices that require frequency sweeping operations to achieve particle jitter control and cannot achieve fixed frequency and fixed amplitude particle jitter control, and provide a non-contact particle jitter device and method, which generates a body standing wave acoustic field in the microchannel by driving an ultrasonic transducer attached to the outer wall of a microfluidic chip to achieve three-dimensional rapid capture of particles. On this basis, the frequency difference Δf of the two transducers is adjusted, and the particle jitter frequency f and jitter amplitude A are controlled by Δf, so as to achieve precise quantitative and fixed frequency jitter control of a single particle or a particle cluster.

[0006] The technical solution adopted by the present invention is:

[0007] A non-contact particle shaking device includes at least two ultrasonic transducers, a microfluidic chip and an excitation power supply. The ultrasonic transducer is tightly fitted to the side wall of the microfluidic chip and is located at the same cross-section of the channel of the microfluidic chip. The main vibration direction of the ultrasonic transducer is perpendicular to the axis of the microfluidic chip channel. The ultrasonic transducer is connected to the excitation power supply electrical signal.

[0008] The main feature of the microfluidic chip is that its effective structure (channels, reaction chambers and other certain functional components) for containing fluids is micrometer-scale at least in one dimension. Due to the micrometer-scale structure, the fluid therein displays and produces special properties that are different from those of the macroscopic scale, thus developing unique analytical performance. The microfluidic chip described in the present invention is mainly a glass capillary, and its cross section is a square outside and a circle inside (i.e., the cross section of the channel is circular) or a circle outside and a circle inside. Of course, the microfluidic chip described in the present invention can also be made of other materials that can implement the technical solution.

[0009] The working principle of the present invention is as follows: The non-contact particle shaking device described in the present invention includes at least two ultrasonic transducers and a microfluidic chip. The two ultrasonic transducers are arranged on the side walls of the microfluidic chip and fit closely with the side walls of the microfluidic chip. One of the ultrasonic transducers is used to generate radiation force and can capture particles in a three-dimensional plane, and the other is used to vibrate the particles. When an alternating electrical signal of a certain frequency is applied to the ultrasonic transducer by an excitation power supply, the ultrasonic transducer will vibrate at the same frequency to generate sound waves, and the sound waves are transmitted through the side walls of the microfluidic chip and introduced into the channel in the microfluidic chip. The incident sound wave in the channel and the reflected sound wave of the channel wall meet and overlap to form an ultrasonic standing wave field, and the microparticles in the sound field gather or shake under the action of the acoustic radiation force, etc. The interference between the two sound waves creates a vibration force field for the captured particles and causes them to oscillate at a frequency and amplitude related to the drive.

[0010] Furthermore, the excitation power supply includes a signal generator and a power amplifier connected in sequence, the signal generator is a dual-channel signal generator, and its two output ends are respectively connected to the electrodes of the two ultrasonic transducers through the power amplifier and the wire. The two ultrasonic transducers are driven by a sinusoidal signal, which is generated by the dual-channel signal generator and amplified by the dual-channel power amplifier, and then the signal is transmitted to the ultrasonic transducers through the wires.

[0011] Furthermore, the excitation power supply also includes an oscilloscope for monitoring the signal waveform, and the oscilloscope is connected in series with the power amplifier to monitor the signal waveform after being amplified by the power amplifier.

[0012] Furthermore, the non-contact particle shaking device also includes an imaging device, which is arranged on the outer wall of the microfluidic chip. The axial direction of the microfluidic chip channel is taken as the z direction, and the main vibration directions of the two ultrasonic transducers are the x and y directions respectively. The imaging device can be a CCD camera, which has a powerful self-scanning function, good image clarity, and can capture images at any time. The imaging device is arranged on the outer wall of the microfluidic chip, and two right-angled triangular prisms with cross sections are arranged between the imaging device and the outer wall of the microfluidic chip, one of the acute angles of the right-angled triangular prism is 67.5°, and the right angle side of the angle is parallel to the diagonal of the cross section of the microfluidic chip. Through the refraction of the right-angled triangular prism, the imaging device can simultaneously capture images of the xz plane and the yz plane without distortion. As one of the preferred schemes, the microfluidic chip is placed on a chip holder with a groove, and a space for placing an ultrasonic transducer is provided at the bottom of the groove. The angle formed between the two ultrasonic transducers after being placed is 90°, and the ultrasonic transducer is 45° to the surface of the chip holder. The microfluidic chip is placed on two ultrasonic transducers, and two adjacent side surfaces of the microfluidic chip are in close contact with the ultrasonic transducers. At this time, the diagonal of the cross section of the microfluidic chip is parallel to the surface of the chip holder. The short right-angled side of the right-angled triangle prism is in close contact with the surface of the chip holder, and the 67.5° angle abuts against the edge of the microfluidic chip.

[0013] Furthermore, there are two ultrasonic transducers, which are respectively arranged on two adjacent side walls of the microfluidic chip. AB glue can be used as the bonding medium between the two ultrasonic transducers and the microfluidic chip, and silver conductive paint is used to introduce the electrode on the side where the ultrasonic transducer is bonded to the outer wall of the microfluidic chip into the side wall of the ultrasonic transducer.

[0014] Furthermore, both ultrasonic transducers are thin-film piezoelectric ceramic transducers, which are relatively common, and the ultrasonic transducers have the same size and thickness, and theoretically have the same resonant frequency. The two ultrasonic transducers are preferably square in shape, and their width is the same as the width of the outer wall of the microfluidic chip to ensure that the ultrasonic transducers will not interfere with each other when they are glued to the two adjacent outer walls of the microfluidic chip.

[0015] Furthermore, each ultrasonic transducer can independently establish a three-dimensional standing wave acoustic field in the channel of the microfluidic chip and can achieve particle aggregation.

[0016] The present invention also includes a non-contact particle shaking method, comprising the following steps:

[0017] Step S1, constructing a non-contact control device based on an ultrasonic transducer, placing at least two of the ultrasonic transducers on the side wall of the microfluidic chip and closely attached thereto, and connecting each ultrasonic transducer to an excitation power supply electrical signal respectively;

[0018] Step S2, injecting the mixed solution containing the controlled particles into the channel of the microfluidic chip, and removing the air bubbles in the channel of the microfluidic chip;

[0019] Step S3, fixing the control device on the microscope workbench, turning on the excitation power supply corresponding to each ultrasonic transducer in turn, and determining the optimal operating frequency of each ultrasonic transducer according to the movement of the controlled particles in the sound field, wherein the optimal operating frequency is the resonant frequency of the system;

[0020] Step S4, adjusting the operating frequency and the operating voltage of the ultrasonic transducer, the operating voltage affects the response speed of the particles in the sound field, and the operating frequency affects the capture position of the particles in the sound field; the operating voltage and the operating frequency are continuously adjustable, and they are adjusted according to the needs to control the optimal capture position and response speed of the particles, and at the same time, the operating frequencies of the various ultrasonic transducers are equal, all being f0, while realizing the rapid three-dimensional capture of the particles;

[0021] Step S5, adjust the operating frequency of one of the ultrasonic transducers to f1, so that an operating frequency difference Δf=|f0-f1| is formed between the ultrasonic transducers. At this time, the particles in the sound field perform fixed-frequency jitter at the jitter frequency f, and the operating frequency difference Δf is adjusted to achieve precise and controllable fixed-frequency jitter of the particles.

[0022] Furthermore, in step S5, the specific operation of adjusting the operating frequency difference Δf to achieve precise and controllable fixed-frequency jitter of the particles is:

[0023] Step S51, the frequency f of the particle fixed-frequency vibration is in a ratio relationship with the working frequency difference Δf formed between the ultrasonic transducer: That is, the output frequency f of the particle fixed-frequency jitter can be controlled intuitively and stably by adjusting the working frequency difference Δf;

[0024] Step S52, the amplitude A of the particle fixed-frequency jitter is in a ratio relationship with the working frequency difference Δf formed between the ultrasonic transducer: Δf×A≈C, where C is a constant; the constant C corresponding to different sound fields has different sizes, and C is a constant value in the same sound field. Therefore, the amplitude A of the particle fixed-frequency jitter can be intuitively and stably controlled by adjusting the working frequency difference Δf.

[0025] Compared with the prior art, the present invention has the following beneficial effects:

[0026] 1. The present invention is a device and method for realizing three-dimensional rapid capture and precise fixed-frequency jitter control of microparticles in a microchannel. The device and method utilize the standing wave acoustic field characteristics generated by a single ultrasonic transducer in a microchannel, and realize rapid aggregation of particles by designing the acoustic field and simultaneously using multiple ultrasonic transducers. At the same time, by controlling the working frequency difference Δf of the two ultrasonic transducers, and combining the relationship between the particle jitter frequency f and the amplitude A changing with Δf, precise fixed-frequency jitter control of the particles is realized. The fixed-frequency jitter has the advantages of precise and stable frequency output, good reliability, and easy adjustment.

[0027] 2. The present invention is a non-contact control device and method under the action of ultrasound. The control method based on ultrasound has no physical requirements on the controlled particles. In addition, the ultrasonic non-contact control characteristics will not damage or pollute the controlled particles. In addition, based on the mildness of ultrasonic control itself, it can achieve non-destructive control of microorganisms and even cells. The present invention introduces a new mechanism for controlling the interaction between particles in a microfluidic environment. The controllable oscillation of microparticles has a good application prospect in microbial applications.

[0028] 3. The control device of the present invention is only composed of a piezoelectric transducer and a straight-through microchannel. The device has a simple structure, and the materials of each part are common, cheap and easy to obtain. There is no special requirement for automatic frequency scanning of the driving electrical signal. It has the advantages of miniaturization, convenience, good reliability and low production cost. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1 It is a structural schematic diagram of the non-contact particle shaking device of the present invention;

[0030] Figure 2 Schematic diagram of the principle of synchronous imaging in the xz and yz planes of a microchannel when ultrasonic particles oscillate;

[0031] Figure 3 It is the trend diagram of particle jitter frequency f changing with driving frequency difference Δf;

[0032] Figure 4It is the trend diagram of particle jitter displacement z changing with driving frequency difference Δf;

[0033] Figure 5 This is a graph showing the variation of the vibration amplitude A of the particle in the sound field over time when Δf = 0.6 Hz;

[0034] Figure 6 This is the two-dimensional displacement trajectory of the particle in the microchannel cross section when Δf = 0.6Hz.

[0035] In the attached figure:

[0036] 1-ultrasonic transducer; 2-microfluidic chip; 3-signal generator; 4-power amplifier; 5-oscilloscope; 6-imaging device; 7-chip holder; 8-prism. DETAILED DESCRIPTION

[0037] The present invention is further described below in conjunction with specific implementation methods. The drawings are only used for exemplary description and cannot be understood as limiting the present invention. In order to better illustrate the present embodiment, some parts of the drawings may be omitted, enlarged or reduced, and do not represent the size of the actual product. For those skilled in the art, it is understandable that some well-known structures and their descriptions in the drawings may be omitted.

[0038] The same or similar reference numerals in the drawings of the embodiments of the present invention correspond to the same or similar parts; in the description of the present invention, it should be understood that if the terms "front", "rear", "left", "right" and the like indicate an orientation or positional relationship based on the orientation or positional relationship shown in the drawings, it is only for the convenience of describing the present invention and simplifying the description, rather than indicating or implying that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation. Therefore, the terms describing the positional relationship in the drawings are only used for exemplary explanations and cannot be understood as limitations on this patent. For ordinary technicians in this field, the specific meanings of the above terms can be understood according to specific circumstances. In addition, in the present invention, the descriptions of "first", "second", etc. are only used for descriptive purposes, and cannot be understood as indicating or implying their relative importance or implicitly indicating the number of technical features indicated. Therefore, the features defined as "first" and "second" may explicitly or implicitly include at least one of the features.

[0039] Embodiment 1:

[0040] like Figure 1 or Figure 2As shown, this embodiment provides a non-contact particle shaking device and method, wherein the device includes at least two ultrasonic transducers 1, a microfluidic chip 2 and an excitation power supply, the ultrasonic transducer 1 is tightly fitted to the side wall of the microfluidic chip 2, and is located at the same cross-section of the channel of the microfluidic chip 2, the main vibration direction of the ultrasonic transducer 1 is perpendicular to the axis of the channel of the microfluidic chip 2, and the ultrasonic transducer 1 is connected to the excitation power supply electrical signal.

[0041] The microfluidic chip 2 described in this embodiment is a glass capillary tube with a square outer cross section and a circular inner cross section. The size of the glass capillary tube is 1.5×0.9×50 mm (outer width×inner diameter×tube length). c Calculation formula:

[0042]

[0043] In the formula, π is the circumference constant, d is the inner diameter of the microfluidic chip, which is 0.9 mm; the propagation speed of sound waves in aqueous solution c0 = 1480 m / s, and the resonant frequency f is calculated by substituting it into the above formula. c =963.6kHz. According to the required resonant frequency f c , select an ultrasonic transducer 1 of appropriate thickness.

[0044] The ultrasonic transducer 1 is a common thin-film piezoelectric ceramic transducer, also known as PZT. If a high-frequency electrical signal is applied to its two ends, when the frequency of the electrical signal is the same as the natural frequency of the piezoelectric transducer, its amplitude reaches the maximum, that is, the energy output efficiency is the highest. For a thin-film piezoelectric transducer, according to the resonance conditions under a high-frequency electrical signal:

[0045]

[0046] Where, the longitudinal wave velocity c in ultrasonic transducer 1 is h =4000m / s, the resonant frequency f of ultrasonic transducer 1 h =f c=963.6kHz, substitute into the above formula to calculate the thickness of ultrasonic transducer 1 h=2.076mm, so an ultrasonic transducer 1 with a thickness of 2mm can be selected. The width of ultrasonic transducer 1 is the same as the width of the outer wall of microfluidic chip 2 to ensure that when two or more ultrasonic transducers 1 are symmetrically placed relative to microfluidic chip 2, the placement position of adjacent ultrasonic transducers 1 is not affected. Therefore, the shapes of the two ultrasonic transducers 1 are both square and the same size, both 2.0×1.5×20mm (thickness×width×length); the two ultrasonic transducers 1 are partially glued to the adjacent side walls of microfluidic chip 2 by KE301AB glue, and are located at the same cross-section of the channel of microfluidic chip 2. The main vibration direction of the ultrasonic transducer 1 is perpendicular to the axis of the channel of microfluidic chip 2, and the electrodes of ultrasonic transducer 1 are led out by wires and connected to the excitation power supply.

[0047] The non-contact particle shaking method described in this embodiment takes the manipulation of polystyrene fluorescent microspheres in deionized water as an example, so the solvent is deionized water (density 1.0 g / cm 3 ), the particles in the water are polystyrene fluorescent microspheres (density 1.05g / cm 3 ), the density of the two is similar, then the gravity on the particles and the buoyancy in the aqueous solution can almost cancel each other out, so the effects of gravity and buoyancy on the particles can be ignored at the same time, and only the effect of the acoustic field force on the particles can be considered. Therefore, the method described in this embodiment includes the following steps:

[0048] Step S1, use a glass capillary with a cross-section of a square outside and a round inside as the microfluidic chip 2, the size of the glass capillary is 1.5×0.9×50mm (outer width×inner diameter×tube length); use two ultrasonic transducers 1 with a size of 2.0×1.5×20mm (thickness×width×length), and use silver conductive paint to introduce the electrode on the side of the ultrasonic transducer 1 that is glued to the outer wall of the glass capillary into the side wall of the ultrasonic transducer 1. Take an appropriate amount of KE301AB glue and stir it slowly to avoid generating too many bubbles; use the mixed AB glue to stick the ultrasonic transducer 1 to the adjacent side walls of the microfluidic chip 2, and put it in an 80°C drying oven for two hours. Then use a wire to lead out the electrode of the ultrasonic transducer 1 and connect it to the excitation power supply;

[0049] Step S2, injecting the polystyrene fluorescent microsphere solution into the channel of the microfluidic chip 2, and removing the bubbles in the channel;

[0050] Step S3, fixing the device including the ultrasonic transducer 1 and the microfluidic chip 2 on the microscope workbench, turning on the excitation power supplies corresponding to the two ultrasonic transducers 1 in turn, and finding the optimal operating frequencies of the two ultrasonic transducers 1 respectively according to the movement of the polystyrene particles in the sound field;

[0051] Step S4, adjusting the operating frequency and the operating voltage of the two ultrasonic transducers 1, so that the operating frequencies of the two ultrasonic transducers 1 are both f0=1042.000 kHz while achieving rapid three-dimensional capture of particles;

[0052] Step S5, adjust the driving frequency of one of the ultrasonic transducers 1 to f1=1042.001kHz, so that the two ultrasonic transducers form a frequency difference Δf=|f0-f1|=1Hz, and obtain the fixed-frequency dithering frequency f=Δf=1Hz of the polystyrene particles; further, Δf can be changed by changing f1, thereby achieving precise control of the fixed-frequency dithering frequency f.

[0053] Embodiment 2:

[0054] like Figure 1 or Figure 2 As shown, on the basis of the first embodiment, the excitation power supply includes a signal generator 3 and a power amplifier 4 connected in sequence through wires, and the signal generator 3 is a dual-channel signal generator, and its two output ends are respectively connected to the electrodes of the two ultrasonic transducers 1 through the power amplifier 4 and the wires. The two ultrasonic transducers 1 are driven by a sinusoidal signal, which is generated by the dual-channel signal generator 3 and amplified by the dual-channel power amplifier 4, and then the signal is transmitted to the ultrasonic transducers 1 through the wires. At the same time, the excitation power supply also includes an oscilloscope 5 for monitoring the signal waveform, and the oscilloscope 5 is connected in series with the power amplifier 4. The oscilloscope 5 presents the output signal frequency of the excitation power supply in a visual manner, which is convenient for the operator to adjust.

[0055] The axial direction of the channel of the microfluidic chip 2 is taken as the z direction, and the main vibration directions of the two ultrasonic transducers 1 are respectively the x and y directions; the x and y directions are also the radial directions of the channel of the microfluidic chip.

[0056] Furthermore, the microfluidic chip 2 is placed on a chip holder 7 with a groove, and a space for placing the ultrasonic transducer 1 is provided at the bottom of the groove. The angle formed between the two ultrasonic transducers 1 after being placed is 90°, and the ultrasonic transducer 1 is 45° to the surface of the chip holder 7. The microfluidic chip 2 is placed on the two ultrasonic transducers 1, and the two adjacent side surfaces of the microfluidic chip 2 are in close contact with the ultrasonic transducer 1. At this time, the diagonal line of the cross section of the microfluidic chip 2 is parallel to the surface of the chip holder 7.

[0057] See also Figure 2The non-contact particle shaking device described in this embodiment also includes a CCD camera, which is arranged on the side of the microfluidic chip 2, and two prisms 8 with a right-angled triangle cross section are arranged between the CCD camera and the microfluidic chip 2. The cross section of the prism 8 has an acute angle of 67.5°, and the right-angled side of the angle is in close contact with the surface of the chip bracket 7. Through the refraction of the right-angled triangle prism 8, the imaging device 6 can simultaneously capture the images of the xz plane and the yz plane in the channel of the microfluidic chip 2 without distortion.

[0058] Embodiment three:

[0059] The axial direction of the microfluidic chip channel is taken as the z direction, and the main vibration directions of the two ultrasonic transducers 1 are respectively the x and y directions; the x and y directions are also the radial directions of the microfluidic chip 2 channel.

[0060] like Figure 3 As shown, based on the first embodiment, the shaking frequency f of the polystyrene particles is proportional to the frequency difference Δf between the two ultrasonic transducers 1, that is, The output frequency f of the particle fixed-frequency jitter can be intuitively and stably controlled by adjusting the working frequency difference Δf. In addition, the same test results were obtained in different sound control devices, indicating that the ratio relationship between f and Δf is very stable.

[0061] It is worth noting that the amplitude A of the fixed-frequency jitter of the polystyrene particles changes with the operating frequency difference Δf between the ultrasonic transducers as shown in Figure 4 The vibration of particles in the acoustic field is a two-dimensional plane motion approaching the cross section of the 2-channel microfluidic chip, where A z and A y They respectively represent the variation of the particle vibration amplitude A in the z direction and in the y direction with the frequency difference Δf. It can be seen that the larger Δf is, the smaller A is. From the fitting curve, it can be found that the vibration amplitude A of the polystyrene particle is proportional to the frequency difference Δf between the two ultrasonic transducers 1: Δf×A≈C, where C is a constant; the constant C corresponding to different sound fields has different magnitudes, and C is a constant value in the same sound field. Therefore, the magnitude of the particle fixed-frequency vibration amplitude A can be intuitively and stably controlled by adjusting the working frequency difference Δf.

[0062] When the frequency difference Δf = 0.6 Hz, the variation trend of the particle shaking frequency f and shaking amplitude A in the sound field over time is as follows: Figure 5 As shown, its A z and A yThey respectively represent the variation trend of the particle's shaking amplitude A in the z direction and in the y direction over time. It can be seen that when Δf is determined, the ratio between the shaking frequency f and the shaking amplitude A remains stable. At the same time, according to the measurement results, the two-dimensional displacement trajectory of the particle in the channel cross section of the microfluidic chip 2 when Δf = 0.6 Hz is plotted as follows: Figure 6 It is worth noting that when Δf is different, there will be slight differences in the motion trajectory of the particles, but for any frequency difference Δf, the ratio between the particle's jitter frequency f and jitter amplitude A still satisfies the above conclusion.

[0063] In the specific contents of the above-mentioned specific implementation methods, the various technical features can be combined in any non-contradictory manner. In order to make the description concise, not all possible combinations of the above-mentioned technical features are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0064] Obviously, the above embodiments of the present invention are merely examples for clearly illustrating the present invention, and are not intended to limit the embodiments of the present invention. For those skilled in the art, other different forms of changes or modifications can be made based on the above description. It is not necessary and impossible to list all the embodiments here. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present invention should be included in the protection scope of the claims of the present invention.

Claims

1. A non-contact particle shaking method, characterized in that: The non-contact particle shaking method is implemented based on a non-contact control device, the control device comprising two ultrasonic transducers (1), a microfluidic chip (2) and an excitation power supply, the ultrasonic transducers (1) are tightly fitted with the side walls of the microfluidic chip (2) and are located at the same cross section of the channel of the microfluidic chip (2), the main vibration direction of the ultrasonic transducer (1) is perpendicular to the axis of the channel of the microfluidic chip (2), each ultrasonic transducer (1) can independently establish a three-dimensional standing wave sound field in the channel of the microfluidic chip (2), and can achieve particle aggregation, each ultrasonic transducer (1) is electrically connected to the excitation power supply, the excitation power supply comprises a signal generator (3) and a power amplifier (4) connected in sequence, the signal generator (3) is a dual-channel signal generator (3), and its two output ends are respectively connected to the electrodes of the two ultrasonic transducers (1) through the power amplifier (4) and a wire; The dithering method includes the following steps: Step S1, constructing a non-contact control device based on an ultrasonic transducer (1): taking a glass capillary tube with a cross section of an outer square and an inner circle as the microfluidic chip (2), the dimensions of the glass capillary tube being an outer width of 1.5 mm × an inner diameter of 0.9 mm × a tube length of 50 mm, and placing two ultrasonic transducers (1) with dimensions of thickness of 2.0 mm × width of 1.5 mm × length of 20 mm on two adjacent side walls of the microfluidic chip (2) and closely attached to and located at the same cross section of the channel of the microfluidic chip (2), and connecting each ultrasonic transducer (1) to an excitation power supply electrical signal; Step S2, injecting a mixed solution containing polystyrene particles and deionized water into the channel of the microfluidic chip (2), while removing air bubbles in the channel of the microfluidic chip (2); Step S3, fixing the non-contact control device on the microscope workbench, turning on the excitation power supplies corresponding to the two ultrasonic transducers (1) in turn, and determining the optimal operating frequencies of the two ultrasonic transducers (1) respectively according to the movement of the polystyrene particles in the sound field; Step S4, adjusting the operating frequency and the operating voltage of the ultrasonic transducer (1), wherein the operating voltage affects the response speed of the particles in the sound field, and the operating frequency affects the capture position of the particles in the sound field; the operating voltage and the operating frequency are both continuously adjustable, and are adjusted according to demand to control the optimal capture position and response speed of the particles, so that the operating frequencies of the ultrasonic transducers (1) are equal while achieving rapid three-dimensional capture of the particles. ,in, f 0 is the initial operating frequency of the two ultrasonic transducers (1); Step S5: Adjust the operating frequency of one of the ultrasonic transducers (1) to , so that the operating frequency difference between the two ultrasonic transducers (1) is formed , the frequency of the particle fixed frequency jitter f The operating frequency difference is formed between the ultrasonic transducer (1) Into a ratio relationship: , which can be achieved by adjusting the operating frequency difference Intuitively and stably control the frequency of granular fixed-frequency dithering f The output of the sound field is at a jitter frequency. f Do fixed frequency jitter, by adjusting the working frequency difference To achieve precise and controllable fixed-frequency jitter of particles, f 1 is the adjusted operating frequency of the ultrasonic transducer (1); the amplitude of the particle fixed frequency jitter A The operating frequency difference between the two ultrasonic transducers (1) is formed Into a ratio relationship: ,in: In the formula, C is a constant; the constant corresponding to different sound fields C Different size, same sound field C is a constant value, so the working frequency difference can be adjusted Intuitively and stably control the amplitude of the particle fixed frequency dither A size; The particles are z The amplitude of the jitter in the direction, in μm; The particles are y The amplitude of the jitter in the direction, in μm; where, z Direction and y The directions represent the radial directions of the microfluidic chip, and the two are perpendicular to each other.

2. The non-contact particle shaking method according to claim 1, characterized in that: The excitation power supply further comprises an oscilloscope (5) for monitoring the signal waveform, and the oscilloscope (5) is connected in series between the power amplifier (4) and the ultrasonic transducer (1).

3. The non-contact particle shaking method according to claim 2, characterized in that: The non-contact manipulation device further comprises an imaging device (6), wherein the imaging device (6) is arranged on the outer wall of the microfluidic chip (2).

4. The non-contact particle shaking method according to claim 3, characterized in that: The imaging device (6) comprises a CCD camera and a prism (8) arranged between the CCD camera and the microfluidic chip (2).

5. The non-contact particle shaking method according to claim 1, characterized in that: Two ultrasonic transducers (1) are connected to adjacent side walls of the microfluidic chip (2) by gluing.

6. The non-contact particle shaking method according to claim 5, characterized in that: Both ultrasonic transducers (1) are piezoelectric ceramic transducers.

7. The non-contact particle shaking method according to any one of claims 1 to 6, characterized in that: The non-contact control device further comprises a chip holder (7) having a groove, the microfluidic chip (2) being placed on the chip holder (7), a space for placing an ultrasonic transducer (1) being provided at the bottom of the groove, the angle formed between the two ultrasonic transducers (1) being 90° after being placed, the ultrasonic transducers (1) being at a 45° angle to the surface of the chip holder (7), and the diagonal of the cross section of the microfluidic chip (2) being parallel to the surface of the chip holder (7); It also comprises two prisms (8) with a right-angled triangle cross section, the two prisms (8) being arranged on both sides of the microfluidic chip (2), the cross section of the prism (8) having an acute angle of 67.5°, the right-angled side where the acute angle is located being in close contact with the surface of the chip holder (7).

Images