Dynamic sound field modulation and particle control method based on digital microfluidics

Abstract

The invention discloses a dynamic sound field modulation and particle control method based on digital microfluidics, modulation of a sound field is achieved through liquid drops, the liquid drops are located between an upper pole plate and a lower pole plate, air is around the liquid drops, sound waves are located on the paths of the lower pole plate, the liquid drops and the upper pole plate, and due to the fact that the acoustic impedance difference between liquid and glass is not large, the sound field is modulated. Most of energy of sound waves can be transmitted through transmission, most of the energy of the sound waves is difficult to transmit due to the fact that acoustic impedance difference between air and glass is large and most of the energy of the sound waves is reflected at an interface of the air and the glass, the sound waves selectively penetrate at specific positions by controlling the number and arrangement of the liquid drops, so that a specific sound field is formed, and real-time movement of the liquid drops is controlled. The sound field formed by penetration is changed in real time, so that the dynamic modulation of the sound field is achieved, the sound field obtained by modulation acts on the solution, the specific movement of the particles is obtained through the sound field, the control of the particles is realized, and the application prospect in the aspects of micro-assembly and cell control is very good.

Description

Technical Field

[0001] The present invention relates to the field of microfluidics technology, and in particular to a dynamic acoustic field modulation and particle manipulation method based on digital microfluidics technology. Background Art

[0002] Acoustic manipulation has the advantages of non-contact and remote operation, and its application fields are very wide, including drug delivery, cell screening, in vitro diagnosis, etc. The main component of the ultrasonic particle manipulation system is the ultrasonic transducer, which converts electrical energy into mechanical vibrations and can generate sound waves in the fluid medium. When the sound waves interact with the fluid medium, two forces are generated: acoustic streaming force (ASF) and acoustic radiation force (ARF).

[0003] Acoustic streaming is a steady fluid flow formed by the viscous attenuation of sound waves. When sound waves propagate in a fluid, the state of the fluid volume unit is characterized by the fluctuations of pressure and velocity. In an ideal fluid, the time average of the displacement of the fluid unit, that is, the net flow of the fluid, is zero everywhere. However, in real fluids, viscous attenuation causes the net displacement of the fluid unit in each oscillation cycle to be non-zero. This local effect leads to the formation of flow on a global scale, thus generating acoustic streaming.

[0004] The generation of acoustic radiation force is due to the transfer of wave momentum to absorbing or scattering objects in the attenuating medium. Its generation mechanism includes the dissipation of acoustic energy, reflection of the incident wave, gradient change of compression wave velocity, and spatial inhomogeneity of energy density in the standing wave.

[0005] Ultrasonic waves can directly manipulate particles by applying acoustic radiation force, or they can indirectly drive particle motion by generating acoustic flow through the acoustic pressure field. Particles are also affected by viscous drag when moving in a fluid. ARF is proportional to the cube of the particle radius, while ASF is proportional to the particle radius. Therefore, as the particle radius decreases, ARF decreases faster than ASF. At the submicron scale, ASF begins to play a dominant role in particle motion.

[0006] With the help of acoustic radiation forces, suspended cells can be actively guided and precisely arranged on nodes or antinodes according to their compressibility and density characteristics. These cell patterns can remain fixed or dynamically reconstructed by changing the frequency or phase. For example, Armstrong et al. used sound waves to align myoblasts in hydrogels to form muscle tissue with bundled myotubes. These acoustically arranged high-density tissue structures better replicate the structure in natural muscle tissue and exhibit anisotropic tensile mechanical properties. Acoustic manipulation combined with microfluidic systems can also achieve the sorting of cells of different types or sizes.

[0007] The acoustic metasurface can be used to modulate the sound field of bulk acoustic waves. By designing and manufacturing physical microstructures, the reflection, absorption, and transmission of sound waves can be effectively controlled to achieve effects such as directional transmission of sound waves, energy convergence, and ultrasonic particle suspension. For example, ultrasound can be focused transcranially by using an acoustic holographic lens to perform non-invasive deep brain neuromodulation. Kai Melde et al. can generate a three-dimensional holographic sound field by combining three orthogonally arranged bulk acoustic wave resonators and three acoustic metasurfaces, and perform three-dimensional patterning of particles and cells.

[0008] The above-mentioned method of using acoustic metasurfaces to modulate the sound field, or by arranging multiple acoustic devices to generate acoustic standing waves, can already achieve patterned arrangement of particles and cells. However, this technology basically produces a static modulated sound field, or only generates a regular linear or dot array pattern. If the sound field changes, different metasurface structures need to be redesigned and manufactured. Therefore, real-time dynamic modulation of the sound field can give acoustic operations more flexibility and has broader application prospects. Summary of the invention

[0009] The present invention discloses a dynamic sound field modulation method based on digital microfluidics, which can realize dynamic modulation of the sound field. At the same time, the present invention also discloses a dynamic particle manipulation method based on digital microfluidics, which can realize dynamic manipulation of particles.

[0010] A dynamic acoustic field modulation method based on digital microfluidics realizes modulation of the acoustic field through droplets. The droplets are located between the upper electrode and the lower electrode, and the droplets are surrounded by air. The acoustic resonator is connected to the lower electrode through an ultrasonic coupling agent or water. The acoustic waves generated by the acoustic resonator are on the path of the lower electrode, the droplets, and the upper electrode. Since the acoustic impedance of the liquid and the glass is not much different, most of the energy of the sound waves can be transmitted. Since the acoustic impedance of the air and the glass is very different on the path of the lower electrode, the air, and the upper electrode, most of the sound wave energy is reflected at the interface between the air and the glass and is difficult to transmit. By controlling the number and arrangement of the droplets, the sound waves can be selectively penetrated at a specific position, thereby forming a specific sound field. By controlling the real-time movement of the droplets between the upper electrode and the lower electrode, the sound field formed by the penetration changes in real time, thereby achieving dynamic modulation of the sound field.

[0011] Preferably, the distribution and movement of the droplets are controlled by a digital microfluidic chip.

[0012] Preferably, the upper electrode plate is a glass plate.

[0013] Preferably, the lower electrode plate is a glass plate.

[0014] Preferably, the liquid droplets are water droplets.

[0015] The particle manipulation method based on digital microfluidics obtains the sound field through the above modulation method and acts on the solution. There are particles in the solution. The solution is connected to the upper electrode through an ultrasonic coupling agent. The acoustic flow, acoustic radiation force and viscous resistance of the particles moving in the solution generated by the body acoustic wave work together to drive the movement of the particles in the solution. The sound field is modulated by controlling the movement of the droplets, and the specific movement of the particles is obtained through the sound field to achieve the manipulation of the particles.

[0016] Furthermore, the microparticles are carbon particles, polystyrene microspheres or cells.

[0017] Further, the particle movement includes patterning of particles, capturing of particles, or transfer of particles.

[0018] Beneficial effects of the present invention:

[0019] (1) A single sound field can be modulated to become a controllable dynamically changing sound field. The rapid movement of droplets can achieve rapid changes in the sound field transmitted to the next level.

[0020] (2) The dynamic modulation method of the acoustic field proposed in the present invention has been experimentally verified to have the ability to capture and manipulate microparticles, realize the patterning of microparticles deposited on the bottom layer of the solution, and realize the controllable aggregation and capture of polystyrene microspheres suspended in the solution. The movement of droplets can also control the movement of microparticles, which has very good application prospects in microassembly and cell manipulation. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 It is a schematic diagram of the principle of droplet control of acoustic field in digital microfluidics;

[0022] Figure 2 It is an experiment and schematic diagram of double droplet-controlled acoustic field patterning;

[0023] Figure 3 The modulated acoustic field was used to conduct the suspension aggregation experiment of polystyrene microspheres;

[0024] Figure 4 This is an experimental picture of the movement of droplets regulating the sound field, driving the aggregated polystyrene microspheres to move over a large range;

[0025] Figure 5 This is an experiment to adjust the frequency of the bulk acoustic wave resonator and control the small-range movement of aggregated polystyrene microspheres. DETAILED DESCRIPTION

[0026] In order to make the technical problems solved by the present invention, the technical solutions adopted and the technical effects achieved clearer, the technical solutions of the present invention are further described below in conjunction with the accompanying drawings and through specific implementation methods. It is understood that the specific embodiments described herein are only used to explain the present invention, rather than to limit the present invention. It should also be noted that, for the convenience of description, only the parts related to the present invention are shown in the accompanying drawings, not all.

[0027] Sound field modulation principle:

[0028] Due to the different acoustic impedance matching between solids, liquids and gases, the propagation ability of sound waves at the solid-liquid interface and the solid-gas interface varies greatly. The calculation formula for acoustic impedance is: .

[0029] When sound waves propagate from one medium to another at an acoustic interface, some reflection and some transmission will occur. The acoustic reflection coefficient R of the interface between two materials can be calculated from their acoustic impedance.

[0030] Assuming that the acoustic impedance of medium 1 is Z1 and the acoustic impedance of medium 2 is Z2, the formula for the acoustic reflection coefficient 𝑅 is: ;

[0031] This formula represents the reflection of sound waves at the interface of two media with different acoustic impedances. The value of the reflection coefficient R is between -1 and 1: when R=0, it means that the acoustic impedances of the two media are equal, there is no reflection, and all sound waves are transmitted to the second medium. When R=1 or R=-1, it means complete reflection, and the sound waves cannot be transmitted to the second medium. When R is between -1 and 1, part of the sound wave is reflected and part of the sound wave is transmitted.

[0032] like Figure 1 As shown, the droplets in the middle layer are in contact with the glass plates in the up and down directions, and the rest of the area around the droplets is air. There are two different paths in the process of sound waves transmitting upward. One path passes through the air 23, and the other passes through the droplets 21. Due to the large difference in acoustic impedance between air and glass, a large amount of sound wave energy will be reflected between the two media of glass and air, hindering the propagation of sound wave energy. The difference in acoustic impedance between liquids and solids is not large, so more sound wave energy can be transmitted upward. As a result, a large-scale sound field 25 can be transformed into a small-scale sound field 20 by passing through the droplets and transmitted to the top, completing the modulation of the sound field.

[0033] Digital microfluidic acoustic field modulation principle. With the help of the principle of dielectric electrowetting, the digital microfluidic (DMF) system can achieve highly flexible and precise droplet manipulation on a picoliter scale. The digital microfluidic chip consists of two glass plates with electrodes arranged on them. Between the upper and lower plates are droplets that can be controlled to move. By switching the electrodes on or off and changing the voltage applied to the droplet position, it can easily control the movement of the droplet.

[0034] The movement of droplets in digital microfluidic chips is very flexible and fast. The movement and distribution of droplets can dynamically control whether the sound wave energy at different positions can be transmitted to the next level, thereby changing the state of the sound field transmitted to the solution tank.

[0035] The modulated small-scale sound field is transmitted to the solution tank above. The acoustic flow, acoustic radiation force generated by the body sound wave and the viscous resistance of the particles moving in the solution work together to drive the movement of the particles in the solution tank.

[0036] The microparticles may be carbon particles, polystyrene microspheres or cells. According to an embodiment of the present invention, the particles are in an aqueous medium.

[0037] Figure 1 The principle of dynamic modulation of the acoustic field by a digital microfluidic system is demonstrated. The digital microfluidic chip consists of an upper plate 22, a droplet 21, and a lower plate 24. The upper plate 22 is ITO glass, and the lower plate 24 is provided with electrodes. The surfaces of both plates are coated with hydrophobic materials. By switching the on and off of the electrode of the lower plate 24, the applied voltage can change the hydrophilicity and hydrophobicity of the droplet 21, thereby controlling the movement of the droplet 21.

[0038] The bulk acoustic wave resonator at the bottom of the digital microfluidic chip generates a large-scale uniform sound field 25. The upper and lower plates of the digital microfluidic chip are both made of glass, and the droplets are surrounded by air 23. Due to the different matching degrees of acoustic impedance, in the process of the sound field 25 at the bottom being transmitted upward, the sound waves transmitted to the air 23 interface are almost all reflected, and the sound field can only pass through the position where the droplets 21 are. Therefore, the large-scale sound field can be converted into a small-scale sound field 20 after being modulated by the droplets 21. As the droplets 21 move, the modulated sound field 20 will also change with the droplets. In addition, multiple droplets 21 can modulate the sound field at the same time.

[0039] The solution tank is arranged above the digital microfluidic chip and connected to the digital microfluidic chip through water or ultrasonic coupling agent. The solution tank contains a solution. The particles are in the solution. The particles can be carbon particles, polystyrene or cells. The acoustic field modulated by the dynamic modulation method of the body acoustic wave acoustic field acts on the solution in the solution tank. The acoustic flow, acoustic radiation force and viscous resistance of the particles when moving in the solution work together to drive the movement of the particles in the solution, so as to achieve the capture, transfer and patterning of the particles.

[0040] Example 1: Patterning of Carbon Particles

[0041] like Figure 1 As shown in the figure, the movement of droplets in digital microfluidics is very flexible and fast, and it can dynamically control whether the acoustic wave energy at different positions can be transmitted to the next level. The combined effect of acoustic flow, acoustic radiation force and viscous resistance can drive the movement of particles in the solution layer. Based on the above-mentioned acoustic field dynamic modulation method and principle, by driving the carbon particles deposited at the bottom of the solution tank, it is verified that this system has the ability to drive deposited particles with a density greater than that of water.

[0042] Figure 2 The carbon particle patterning experiment is shown. The left picture is the experimental picture, and the right picture is a schematic diagram of the droplet drive at the corresponding moment. The droplet is located in the digital microfluidic chip. The black area is the carbon particles in the upper solution tank. After the bulk acoustic wave resonator is turned on, sound waves appear in the droplet area and repel the carbon particles to the surroundings. From turning on the acoustic device to the carbon particles being pushed out to the largest area, the whole process takes about 1 second. By using a digital microfluidic chip to drive the droplet to move, a concave carbon particle pattern can be left in the area where the droplet passes. The large-scale uniform sound field at the bottom remains unchanged, and the separate control of multiple droplets allows the drawing of patterns at different locations at the same time. By planning the movement path of the droplet, any target pattern can be generated.

[0043] Example 2: Manipulation of polystyrene microspheres

[0044] The aggregation experiment of suspended polystyrene microspheres can verify the ability of the acoustic field obtained by the acoustic field modulation method of the present invention to control suspended particles. The present invention can also be extended to the control of suspended particles such as cells.

[0045] Figure 3 , Figure 4 , Figure 5 The experiments on suspension aggregation of 20-micron polystyrene microspheres, large-range movement of droplets controlled after aggregation, and small-range movement controlled by frequency were demonstrated respectively.

[0046] The specific preparation method of the polystyrene microsphere suspension solution is as follows: first, prepare a 10 mg / ml bovine human albumin solution with deionized water, and then add an appropriate amount of polystyrene high concentration dispersion solution for vibration dispersion. The microsphere aggregation effect can be achieved by dispersing only with deionized water, but the viscosity of the solution is adjusted with bovine human albumin, which can make the aggregated microspheres more stably suspended.

[0047] Take 3 ml of the ball suspension solution and add it to the solution tank. Adjust the control signal frequency of the BAW resonator to 960kHz. Turn on the BAW resonator and you can see Figure 3 The microspheres achieved a aggregation effect in about half a minute, and the microspheres can be stably aggregated in the center area of ​​the controlled droplet. Figure 4 As shown in the figure, after the aggregation is completed, the digital microfluidic system is used to control the acoustic field in the chip to modulate the movement of the droplets, and the aggregated microspheres can be controlled to follow the droplets to transfer over a large range. By adjusting the frequency of the sound wave within a range of about 10 kHz, Figure 5 The captured particles are shown to have a small controllable movement, the range of movement being modulated by the droplet size.

[0048] The particle control method proposed in the present invention is not limited to the particles proposed in the above case. According to the method proposed in the present invention, the suspended particles not mentioned above or the particles settled at the bottom of the solution can be controlled.

[0049] In the description of the present invention, it should be noted that the directions or positional relationships indicated by terms such as “up”, “down”, “left”, “right”, “clockwise” and “counterclockwise” are based on the directions or positional relationships shown in the accompanying drawings. They are only for the convenience of describing the present invention and simplifying the description. They do not indicate or imply that the device or element referred to must have a specific direction, be constructed and operated in a specific direction. Therefore, they cannot be understood as limitations on the present invention.

[0050] The above embodiments are only to illustrate the basic principles and characteristics of the present invention. The present invention is not limited by the above embodiments. Without departing from the spirit and scope of the present invention, the present invention may be subject to various changes and modifications, which are within the scope of the present invention. The scope of protection of the present invention is defined by the attached claims and their equivalents.

Claims

1. A dynamic acoustic field modulation method based on digital microfluidics, characterized in that: The modulation of the sound field is achieved through droplets. The droplets are located between the upper electrode and the lower electrode. The droplets are surrounded by air. On the path of the lower electrode, the droplets, and the upper electrode, since the acoustic impedance of the liquid and the glass are not much different, most of the energy of the sound waves can be transmitted. On the path of the lower electrode, the air, and the upper electrode, since the acoustic impedance of the air and the glass are very different, most of the sound wave energy is reflected at the interface between the air and the glass and is difficult to transmit. By controlling the number and arrangement of the droplets, the sound waves can be selectively penetrated at specific positions, thereby forming a specific sound field. By controlling the real-time movement of the droplets between the upper electrode and the lower electrode, the sound field formed by the penetration changes in real time, thereby achieving dynamic modulation of the sound field.

2. The dynamic sound field modulation method based on digital microfluidics according to claim 1, characterized in that: The distribution and movement of droplets are controlled by digital microfluidics chips.

3. The dynamic sound field modulation method based on digital microfluidics according to claim 1, characterized in that: The upper electrode plate is a glass plate.

4. The dynamic sound field modulation method based on digital microfluidics according to claim 1, characterized in that: The lower electrode plate is a glass plate.

5. The dynamic sound field modulation method based on digital microfluidics according to claim 1, characterized in that: The liquid droplets are water droplets.

6. A particle manipulation method based on digital microfluidics, characterized in that: The modulation method of weights 1-5 is used to obtain an acoustic field and act on a solution, wherein the solution contains particles. The solution container is connected to the upper electrode plate through an ultrasonic coupling agent. The acoustic flow and acoustic radiation force generated by the body acoustic wave and the viscous resistance of the particles when moving in the solution work together to drive the movement of the particles in the solution. The acoustic field is modulated by controlling the movement of the droplets, and the specific movement of the particles is controlled by the acoustic field to achieve manipulation of the particles.

7. The particle manipulation method based on digital microfluidics according to claim 6, characterized in that: The microparticles are carbon particles, polystyrene microspheres or cells.

8. The particle manipulation method based on digital microfluidics according to claim 6, characterized in that: The particle movement includes patterning of particles, trapping of particles, or transfer of particles.

9. The microparticle manipulation method based on digital microfluidics according to claim 6, characterized in that: By adjusting the frequency of the sound waves, the captured particles can be controlled to move in a small range.

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