Particle patterning control device and method based on in-capillary multi-mode sound field

Abstract

The invention discloses a particle patterning control device and method based on a multi-mode sound field in a capillary tube. Comprising the steps that particle suspension liquid is injected into a capillary tube, a piezoelectric transducer is arranged on the outer side of the capillary tube, and the piezoelectric transducer is acoustically coupled with the outer surface of the capillary tube; applying an electric signal to the piezoelectric transducer, using the piezoelectric transducer to excite the two-dimensional acoustic resonance mode of the capillary tube, so that a corresponding bulk acoustic wave field is generated in the capillary tube, and the particles in the capillary tube are distributed according to the sound field gradient of the bulk acoustic wave field to form a particle pattern; and manipulating the particle pattern by modulating the excitation frequency or the structure of the capillary. According to the device and the method disclosed by the invention, various complex and stable particle aggregation patterns including circles, ellipses, other high-order modes and the like can be formed in the capillary tube.

Description

Technical Field

[0001] This invention relates to the fields of microfluidics and acoustic fluid control, and more specifically, to a method and apparatus for non-contact, precise, and reconfigurable manipulation and patterning of micron-sized particles, nano-sized particles, or biological cells suspended in a fluid by selectively exciting multiple different bulk acoustic wave (BAW) resonant modes in a capillary resonator. Background Technology

[0002] Acoustic fluid manipulation, utilizing the interaction between sound fields and fluids and suspended particles within them, has become a powerful manipulation tool in "lab-on-a-chip" systems. This technology boasts significant advantages such as being non-contact, label-free, biocompatible, and versatile, showing broad application prospects in fields like biomedicine, chemical analysis, and materials science. The physical basis of acoustic manipulation primarily stems from two acoustic effects: acoustic radiation force (ARF) and acoustic streaming. Acoustic radiation force, the time-averaged force generated when sound waves scatter on the particle surface, is the main force driving precise particle manipulation.

[0003] Existing acoustic manipulation devices can be mainly divided into two categories: bulk acoustic wave (BAW) and surface acoustic wave (SAW). Conventional BAW devices typically attach a piezoelectric transducer to a microfluidic chip, achieving particle manipulation by exciting the fundamental frequency or half-wavelength resonance within the cross-section of the chip's channels. The limitation of this method is that it can usually only produce simple sound field distributions, such as forming a center line at sound pressure nodes or two parallel lines at antinodes. It is difficult to achieve complex two-dimensional particle patterning, limiting its potential in advanced applications such as constructing complex microstructures or biomimetic tissues.

[0004] To achieve more complex particle patterns, existing technologies have proposed several solutions. One mainstream approach uses complex transducer arrays, actively generating the desired sound field shape by independently controlling the phase and amplitude of the driving signal for each transducer unit in the array. However, this method significantly increases the hardware complexity, manufacturing cost, and control difficulty of the system, hindering the miniaturization and integration of the device. Another approach utilizes multi-frequency excitation, programming the generation of specific patterns by superimposing sound fields of different frequencies. However, these methods often rely on complex waveform synthesis algorithms or fail to stably excite and switch multiple discrete higher-order sound field modes using a single transducer in a simple cylindrical capillary resonator.

[0005] Therefore, there is an urgent need in the field for a new technical solution that can generate and control a variety of complex and stable two-dimensional particle patterns within a simple microfluidic structure (such as a standard capillary) using simple driving hardware (such as a single transducer). Furthermore, how to efficiently integrate multi-step, different-mode particle patterning processes into a continuous flow system is also a major challenge currently facing the technology. This invention is proposed precisely to overcome the limitations of the prior art. Summary of the Invention

[0006] This invention aims to overcome the shortcomings of existing technologies and provide a device and method for microparticle patterning manipulation based on multimodal sound fields within a capillary. The device and method of this invention can generate and control multiple different high-order sound field modes within a simple capillary using a single piezoelectric transducer, thereby achieving complex two-dimensional patterning manipulation of microparticles.

[0007] The technical solution adopted in this invention is as follows: I. A Particle Patterning Manipulation Method Based on Multimodal Sound Fields in Capillaries The microparticle patterning manipulation method includes the following steps: injecting a microparticle suspension into a capillary; placing a piezoelectric transducer on the outside of the capillary, with the piezoelectric transducer acoustically coupled to the outer surface of the capillary; applying an electrical signal to the piezoelectric transducer to excite the two-dimensional acoustic resonance mode of the capillary, thereby generating a corresponding bulk acoustic wave field within the capillary; and arranging the microparticles within the capillary according to the acoustic field gradient of the bulk acoustic wave field to form a microparticle pattern.

[0008] As an optional specific embodiment of the present invention, the particle pattern is manipulated by modulating the excitation frequency, including: for capillaries with consistent structural parameters along the axial direction, adjusting the frequency of the electrical signal to the excitation frequency corresponding to different higher-order two-dimensional acoustic resonance modes of the capillaries, thereby realizing the manipulation of the particle pattern.

[0009] As another optional specific embodiment of the present invention, the particle pattern is manipulated by adjusting the structure of the capillary, including: for a composite capillary formed by connecting at least two capillary segments with different structural parameters along the axial direction, applying an electrical signal with a fixed excitation frequency to the piezoelectric transducer, wherein the fixed excitation frequency is configured to enable each capillary segment to generate different high-order two-dimensional acoustic resonance modes, thereby realizing the manipulation of the particle pattern; the structural parameters are inner diameter and wall thickness.

[0010] Furthermore, the structural parameter is the ratio of inner diameter to wall thickness.

[0011] Furthermore, under the higher-order two-dimensional acoustic resonance mode, the capillary exhibits elliptical, micro-triangular, circular, or triangular strain modes.

[0012] Furthermore, on the capillary cross-section at the sound pressure node or antinode, the particles form a two-dimensional pattern, which can be a double arc (double circular arc), a dot matrix, a ring, a hexagram, or a triple circular arc.

[0013] Furthermore, the particles include cells, cell spheres, and organoids.

[0014] II. A microparticle patterning manipulation device based on multimodal sound field within a capillary tube The particle patterning manipulation device is applied to the above-mentioned particle patterning manipulation method based on multimodal sound fields within capillaries, including: A capillary tube contains fluid and particles suspended in the fluid. A single piezoelectric transducer is acoustically coupled to the outer surface of the capillary. A signal generating circuit is used to provide a variable frequency electrical signal to the piezoelectric transducer; A controller is used to control the frequency of electrical signals.

[0015] Optionally, the capillary is made of borosilicate glass, fused silica, silicon, stainless steel, aluminum, or resin.

[0016] Optionally, the structural parameters of the capillary are consistent along the axial direction.

[0017] Optionally, the capillary is a composite capillary formed by connecting at least two capillary segments with different structural parameters along the axial direction.

[0018] The present invention has the following beneficial effects: 1. Versatile Functionality: It can generate a variety of complex two-dimensional micro-particle patterns as needed, far exceeding the capabilities of traditional single-line focusing.

[0019] 2. Simplified structure: It only requires a capillary tube and a standard piezoelectric transducer, which greatly reduces the hardware complexity and cost of the system and makes it easy to integrate and miniaturize.

[0020] 3. Programmability: Through frequency modulation, particle patterns can be dynamically and in real time, enabling reconfigurable particle manipulation. Through geometric modulation, specific manipulation sequences can be "fixed" into the chip's physical structure, making it suitable for high-throughput continuous stream processing.

[0021] 4. High-value application prospects: It can precisely arrange biological cells, cell spheres or organoids, providing a new and powerful tool for the construction of biomimetic structures, cell co-culture research and bottom-up preparation of micro composite materials in tissue engineering. Attached Figure Description

[0022] Figure 1 This is a schematic diagram of the microparticle patterning manipulation device in this invention; Figure 2 This is a simulation diagram of the sound field modes in Embodiment 1 of the present invention; Figure 3 The elliptical particle distribution in Embodiment 1 of the present invention; Figure 4 These are the simulation results of the double circular arc mode in this invention; Figure 5 These are the results of the lattice modal simulation in this invention; Figure 6 These are the simulation results of the elliptical lattice mode in this invention; Figure 7 These are the simulation results of the toroidal modal in this invention; Figure 8 The simulation results of the hexagram mode in this invention; Figure 9 The results are the simulation results of the three-circular-arc modal in this invention. Detailed Implementation

[0023] The present invention will be further described in detail below with reference to the accompanying drawings and specific embodiments.

[0024] The first aspect of this invention provides a method for microparticle patterning manipulation based on multimodal acoustic fields within a capillary. The core physical mechanism of this invention lies in the excitation and control of higher-order bulk acoustic (BAW) modes within a capillary resonant cavity. The capillary, as a hollow cylindrical structure, receives acoustic energy from the fluid inside when vibrated by an external piezoelectric transducer. This energy is then constrained by the capillary wall to form standing waves, making the entire system an acoustic resonator.

[0025] The method of the present invention includes the following steps: Step 1: Inject a microparticle suspension into the capillary and place a single piezoelectric transducer on the outside of the capillary. The piezoelectric transducer is acoustically coupled to the outer surface of the capillary. Step 2: Apply an electrical signal with a specific excitation frequency to the piezoelectric transducer to excite the higher-order two-dimensional acoustic resonance mode of the capillary, thereby generating a corresponding bulk acoustic wave (BAW) field within the capillary. The particles within the capillary are distributed according to the acoustic field gradient of the bulk acoustic wave field, forming a particle pattern. That is, the acoustic radiation force generated by the acoustic field gradient of the bulk acoustic wave standing wave field drives the particle movement, which gathers at the sound pressure node and then arranges itself on the capillary cross-section at the sound pressure node to form a two-dimensional pattern.

[0026] Unlike traditional one-dimensional half-wavelength resonators used for particle focusing along the channel width, the cross-section of a cylindrical resonant cavity supports a rich array of two-dimensional resonant modes. The acoustic pressure field p1 of these modes exhibits a complex distribution of nodal (p1=0) and anti-nodal (p1=max) patterns in the two-dimensional plane, resembling the classic Cranny diagram. Particles suspended in the acoustic field are primarily acted upon by acoustic radiation forces. For particles much smaller than the wavelength of the sound wave, this force can be expressed as a function of the acoustic radiation potential U. The acoustic radiation potential U is related to the time-averaged square of the acoustic pressure p1 and the sound velocity v1. Ultimately, the acoustic radiation force pushes the particles toward the nodal or antinode of the acoustic pressure, the specific direction depending on the difference in density and compressibility between the particle and the surrounding fluid, i.e., the acoustic contrast factor. For common polystyrene microspheres or cells in aqueous solution, they are typically pushed toward the acoustic pressure nodal. Therefore, by controlling the modes of the acoustic pressure field, the final arrangement pattern of the particles can be controlled.

[0027] The key to this invention lies in the fact that the resonant frequency *f* of a given cylindrical resonant cavity is not a single value, but rather possesses a discrete spectrum, related to the number of nodes in both the circumferential and radial directions. These resonant frequencies are determined by the boundary conditions of the Helmholtz equation in cylindrical coordinates, and are functions of the capillary's material properties (such as Young's modulus, Poisson's ratio, and density) and geometric dimensions (inner diameter *a*, wall thickness 2t = *ba*), where *b* is the outer diameter. Theoretical analysis and numerical simulations both show that the frequencies of higher-order modes exhibit a high sensitivity to structural parameters, particularly the ratio of wall thickness to inner diameter. This invention utilizes this physical dependence, employing either active selection of the resonant frequency or preset structural dimensions to "address" and excite specific modes, thereby achieving precise control over the particle pattern.

[0028] Specifically: Optionally, particle patterns can be manipulated by modulating the excitation frequency, including: for capillaries with uniform structural parameters along the axial direction, adjusting the frequency of the electrical signal to the excitation frequency corresponding to different higher-order two-dimensional acoustic resonant modes of the capillary to achieve particle pattern manipulation. The principle of frequency modulation is: the capillary is regarded as a cylindrical acoustic resonant cavity. In addition to its fundamental frequency resonance, this resonant cavity also has a series of discrete higher-order resonant frequencies. Each higher-order resonant frequency corresponds to a unique, stable two-dimensional standing wave mode (i.e., mode shape) within the cross-section of the capillary, whose sound pressure distribution is similar to the Cranny pattern observed on a vibrating plate. By precisely selecting and applying an electrical signal of a specific higher-order resonant frequency to a piezoelectric transducer, the corresponding acoustic field mode can be selectively excited within the capillary. Under the action of acoustic radiation force, particles suspended in the fluid will rapidly move to the nodes or antinodes of the sound pressure (depending on the acoustic contrast factor between the particles and the fluid), thus spontaneously arranging themselves into complex two-dimensional patterns corresponding to the acoustic field mode, such as lattices, elliptical rings, or hexagrams.

[0029] Optionally, the particle pattern can be manipulated by adjusting the structure of the capillary, including: for a composite capillary formed by connecting at least two capillary segments with different structural parameters axially, applying an electrical signal with a fixed excitation frequency to a piezoelectric transducer. The fixed excitation frequency is configured to generate different high-order two-dimensional acoustic resonant modes in each capillary segment, thereby allowing the particles to simultaneously form different two-dimensional patterns in different sections of the composite capillary, thus achieving particle pattern manipulation; the structural parameters are the inner diameter and wall thickness. The principle of structural modulation is to transfer the control of the acoustic field mode selection from the dynamic electrical signal frequency to the static device geometry. According to the vibration theory of thick-walled hollow cylinders, their resonant frequency spectrum is a strong function of their geometric dimensions (inner diameter a, outer diameter b, i.e., wall thickness (ba) / 2) and material physical properties (elastic modulus, density). In particular, the resonant frequencies of high-order modes are extremely sensitive to the ratio of wall thickness to inner diameter. Therefore, while maintaining a constant driving frequency, it is possible to pre-design and select capillaries with specific geometries to ensure they resonate strongly with a desired higher-order mode at that fixed frequency. Based on this principle, a continuous microfluidic channel comprising multiple tube segments with different geometries (such as wall thickness or inner diameter) can be fabricated. As fluid flows sequentially through these tube segments, although the entire device is driven by a single, fixed-frequency sound source, different sound field modes are sequentially excited within different tube segments, thereby achieving continuous, multi-step patterned rearrangement of particles.

[0030] Preferably, in the composite capillary, each capillary segment has the same outer diameter.

[0031] Optionally, the excitation frequency corresponding to the higher-order resonant mode is determined using finite element simulation. This includes: first, constructing a model using finite element simulation, which includes a piezoelectric ceramic (piezoelectric transducer), a capillary tube, and its internal solution. A fixed voltage is applied to the piezoelectric ceramic, and scanning is performed at 10kHz intervals within a frequency range of 1.8MHz to 4MHz. The acoustic field within the capillary tube and the stress on the capillary wall corresponding to each scanned frequency are statistically analyzed to determine the correspondence between the excitation frequency, stress mode, and acoustic field mode.

[0032] Preferably, the structural parameter is the ratio of inner diameter to wall thickness.

[0033] Preferably, the inner diameter of the capillary is 100~1000µm and the outer diameter is 600~5000µm.

[0034] Preferably, applying electrical signals of different frequencies to the piezoelectric transducer can induce different strains in the tube wall, including elliptical strain, micro-triangular strain, circular strain, and triangular strain. These strain patterns of the tube wall represent different resonant modes, ultimately generating different sound fields inside the tube wall.

[0035] Preferably, on the capillary cross-section at the sound pressure node or antinode, the particles form a two-dimensional pattern. The strain mode determines the shape of the two-dimensional pattern, which can be a double arc (double circular arc), a lattice, a ring, a hexagram, or a triple circular arc.

[0036] like Figure 4 As shown, when the pipe wall exhibits elliptical strain, the corresponding two-dimensional pattern formed is a double arc (double circular arc).

[0037] like Figure 5 and Figure 6 As shown, when the pipe wall exhibits elliptical strain, the corresponding two-dimensional pattern formed is a dot matrix.

[0038] like Figure 7 As shown, when the pipe wall exhibits circular strain, the corresponding two-dimensional pattern formed is a ring.

[0039] like Figure 8 and Figure 9 As shown, when the pipe wall exhibits micro-triangular strain, the corresponding two-dimensional pattern is a hexagram or a three-circular arc. When the triangular strain intensity is low, the two-dimensional pattern is a three-circular arc; the higher the triangular strain intensity, the closer it is to a hexagram pattern.

[0040] Preferably, the microparticles are biological entities, including cells, cell spheres, and organoids.

[0041] Preferably, the piezoelectric transducer is lead zirconate titanate (PZT) ceramic.

[0042] A second aspect of the present invention provides a microparticle patterning manipulation device based on a multimodal sound field within a capillary.

[0043] like Figure 1 As shown, the apparatus of the present invention includes: A capillary tube contains fluid and particles suspended in the fluid. A single piezoelectric transducer is acoustically coupled to the outer surface of a capillary. The signal generation circuit is used to provide a variable frequency electrical signal to the piezoelectric transducer; A controller is used to control the frequency of electrical signals.

[0044] Capillary tubes are made of materials such as borosilicate glass, fused silica, silicon, stainless steel, aluminum, or resin.

[0045] The structural parameters of a capillary are consistent along the axial direction, or it is composed of at least two capillary segments with different structural parameters connected along the axial direction.

[0046] The technical solution of the present invention will be further illustrated below through specific embodiments.

[0047] Example 1 This embodiment demonstrates a method for generating different particle patterns in the same capillary by changing the driving frequency. First, the frequencies corresponding to the generation of different particle patterns in the same capillary are calculated using finite element simulation. Figure 2 To verify the results, the elliptical pattern within it was observed.

[0048] The device is configured as follows: Capillary tube: A 316L stainless steel capillary tube with an inner diameter of 0.3 mm and a wall thickness of 0.2 mm is selected. A glass capillary tube of the same size is connected to the end for easy observation.

[0049] Transducer: A PZT-53 piezoelectric ceramic sheet with dimensions of 4mm×50mm×0.9mm is firmly bonded to the middle of the outer wall of the capillary using epoxy resin as the acoustic coupling agent.

[0050] Drive and observation system: A drive circuit capable of generating 25V to drive the piezoelectric transducer in a frequency range of 2MHz to 4MHz. A high-speed camera equipped with a microscope lens for real-time observation of particle distribution within the capillary cross-section.

[0051] The specific operation method is as follows: 1. The concentration is approximately 10 6 An aqueous suspension of 4 µm polystyrene microspheres per mL was injected into the capillary.

[0052] 2. Starting from 2MHz, the driving frequency was slowly scanned in 10kHz steps, while the dynamic behavior of the particles was observed through a microscope.

[0053] 3. At most frequencies, the particles exhibit random Brownian motion. However, at certain specific discrete frequency points, it can be observed that the particles are rapidly captured by acoustic radiation forces and converge into stable, ordered one-dimensional line patterns within seconds.

[0054] 4. Observing the state of the particles from two directions, as the particles flow, the particles in one direction are basically in a straight line, while the particles in the other direction are distributed as thicker lines, proving that the particles are elliptical in distribution. Figure 3 ).

[0055] Example 2 This embodiment demonstrates how multi-level, continuous particle patterning can be achieved by changing the geometry of the capillary at a fixed driving frequency.

[0056] The device is configured as follows: Drive source: A PZT transducer driven by a signal source at a fixed frequency.

[0057] Capillary tube: Three steel needles with the same outer diameter are connected together, and the inner diameter is designed to have three sections with different geometric dimensions (A, B, C). The entire steel needle is acoustically coupled to the single transducer mentioned above.

[0058] Section A: Inner diameter = 200µm, wall thickness = 250µm.

[0059] Section B: Inner diameter = 300µm, wall thickness = 200µm.

[0060] Section C: Inner diameter = 400µm, wall thickness = 150µm.

[0061] The specific operation method is as follows: 1. Pump the particulate suspension into the steel needle at a constant flow rate (e.g., 120 µL / min) and let it flow through sections A, B and C in sequence.

[0062] 2. Starting from 2MHz, the driving frequency was slowly scanned in 10kHz steps, while the dynamic behavior of the particles was observed through a microscope.

[0063] 3. Record the frequencies of the dot array formed inside the three steel needles respectively, and record the corresponding frequencies.

[0064] 4. Results Analysis: This embodiment successfully demonstrates how acoustic field modal control capabilities can be "encoded" into the physical structure of a steel needle chip. The table below summarizes the correspondence between the geometric parameters of each section and the acoustic field modes and particle patterns:

[0065] The above specific embodiments are used to explain and illustrate the present invention, but not to limit the present invention. Any modifications and changes made to the present invention within the spirit and scope of the claims shall fall within the protection scope of the present invention.

[0066] The above description is only a preferred embodiment of the present invention. Therefore, all equivalent changes or modifications made to the structure, features and principles described in the claims of this patent application are included in the scope of this patent application.

Claims

1. A method for microparticle patterning manipulation based on multimodal sound fields within a capillary tube, characterized in that, Includes the following steps: A microparticle suspension is injected into a capillary, and a piezoelectric transducer is placed on the outside of the capillary, acoustically coupled to the outer surface of the capillary. An electrical signal is applied to the piezoelectric transducer to excite the two-dimensional acoustic resonant mode of the capillary, thereby generating a corresponding bulk acoustic wave field inside the capillary. The microparticles inside the capillary are arranged according to the acoustic field gradient of the bulk acoustic wave field to form a microparticle pattern.

2. The microparticle patterning manipulation method based on multimodal sound field within a capillary tube according to claim 1, characterized in that: Manipulating the particle pattern by modulating the excitation frequency includes: for capillaries with consistent structural parameters along the axial direction, adjusting the frequency of the electrical signal to the excitation frequency corresponding to different two-dimensional acoustic resonance modes of the capillaries, thereby realizing the manipulation of the particle pattern.

3. The microparticle patterning manipulation method based on multimodal sound field within a capillary tube according to claim 1, characterized in that: Manipulating the particle pattern by adjusting the structure of the capillary includes: for a composite capillary formed by connecting at least two capillary segments with different structural parameters along the axial direction, applying an electrical signal with a fixed excitation frequency to the piezoelectric transducer, wherein the fixed excitation frequency is configured to enable each capillary segment to generate different two-dimensional acoustic resonance modes, thereby realizing the manipulation of the particle pattern; the structural parameters are inner diameter and wall thickness.

4. The microparticle patterning manipulation method based on multimodal sound field within a capillary tube according to claim 3, characterized in that: The structural parameter is the ratio of inner diameter to wall thickness.

5. The microparticle patterning manipulation method based on multimodal sound field within a capillary tube according to claim 1, characterized in that: Under the two-dimensional acoustic resonance mode, the capillary exhibits elliptical, micro-triangular, circular, or triangular strain modes.

6. The microparticle patterning manipulation method based on multimodal sound field within a capillary tube according to claim 1, characterized in that: On the capillary cross-section at the sound pressure node or antinode, the particles form a two-dimensional pattern, which can be a double arc, a dot matrix, a ring, a hexagram, or a triple arc.

7. The microparticle patterning manipulation method based on multimodal sound field within a capillary tube according to claim 1, characterized in that: The particles include cells, cell spheres, and organoids.

8. A particle patterning manipulation device based on a multimodal sound field within a capillary tube, applied to the particle patterning manipulation method based on a multimodal sound field within a capillary tube as described in any one of claims 1 to 7, characterized in that, include: A capillary tube contains fluid and particles suspended in the fluid. A single piezoelectric transducer is acoustically coupled to the outer surface of the capillary. A signal generating circuit is used to provide a variable frequency electrical signal to the piezoelectric transducer; A controller is used to control the frequency of electrical signals.

9. The microparticle patterning manipulation device based on capillary multimodal sound field according to claim 8, characterized in that: The capillary is made of borosilicate glass, fused silica, silicon, stainless steel, aluminum, or resin.

10. The microparticle patterning manipulation device based on multimodal sound field within a capillary tube according to claim 8, characterized in that: The capillary has consistent structural parameters along the axial direction, or is formed by connecting at least two capillary segments with different structural parameters along the axial direction.

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