A single-cell orderly arrangement and encapsulation device driven by an acoustic field mechanical potential well

Through the microfluidic control device driven by the acoustic field mechanical potential well, the Archimedes spiral interdigital transducer and microfluidic channel structure is used to realize the orderly arrangement and precise wrapping of suspended cells, solving the problem of low single-cell wrapping rate in the prior art, with high integration and small size.

CN115678770BActive Publication Date: 2025-07-25ZHENGZHOU UNIVERSITY OF LIGHT INDUSTRY
View PDF 2 Cites 0 Cited by

Patent Information

Application Number
CN202211320817.8
Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Filing Date
2022-10-26
Publication Date
2025-07-25
Estimated Expiration
2042-10-26

AI Technical Summary

Technical Problem

In the prior art, single-cell wrapping micro droplet technology has problems such as low random wrapping rate, cell agglomeration and uneven arrangement, making it difficult to achieve efficient single-cell wrapping and accurate micro droplet generation.

Method used

The matching design of the Archimedes spiral interdigit transducer and the microfluidic channel structure is adopted to drive the suspended cells into a single row arrangement through the acoustic field mechanical potential well, and the micro droplet generation process is combined to achieve accurate wrapping.

Benefits of technology

The orderly arrangement and precise packaging of suspended cells are achieved, the single-cell packaging rate is improved, the device is highly integrated and small in size.

✦ Generated by Eureka AI based on patent content.

Smart Images

  • Figure CN115678770B_ABST
    Figure CN115678770B_ABST
Patent Text Reader

Abstract

A single-cell orderly arrangement and encapsulation device driven by an acoustic field mechanical potential well, comprising an Archimedean spiral interdigital transducer, on which an Archimedean spiral interdigital electrode is fabricated, a microarray layer is fabricated on the upper part of the Archimedean spiral interdigital transducer, a microfluidic channel system is fabricated on the upper part of the microarray layer, and the Archimedean spiral interdigital transducer, the microarray layer and the microfluidic channel system cooperate; through the matching design of the Archimedean spiral interdigital transducer and the microfluidic channel structure of the microfluidic chip, the present invention constructs an acoustic field mechanical potential well to drive the orderly arrangement of cells and can achieve the precise encapsulation of single cells; by adopting the spiral structure design of the Archimedean spiral interdigital transducer and the microfluidic channel structure, the device has high integration and a small volume.
Need to check novelty before this filing date? Find Prior Art

Description

Technical Field

[0001] The present invention relates to the field of microfluidic technology, and particularly relates to a single-cell orderly arrangement and encapsulation device and method driven by an acoustic field mechanical potential well. Background Art

[0002] At present, major diseases typified by cancer (malignant tumor) are still challenging problems in terms of thorough treatment research due to their characteristics such as difficult detection, difficult diagnosis, and easy metastasis. Conducting single-cell research to reveal the essence of life activities and explore the causes of major diseases at the single-cell level is the key support for the early diagnosis and thorough treatment of major diseases.

[0003] How to encapsulate a single cell in an independent microenvironment is the basic premise for conducting single-cell research. Microdroplets, as natural microenvironments, are ideal structures for single-cell encapsulation. With the development of micro-nano processing technology, microfluidic technology has become an important technical means for microdroplet generation and single-cell encapsulation due to its advantages such as high analysis efficiency, high precision, and integration. Scholars at home and abroad have carried out a large number of studies on single-cell encapsulation in microdroplets from aspects of cell pre-arrangement and droplet generation control.

[0004] To improve the encapsulation efficiency and encapsulation rate, through the efforts of many scholars at home and abroad, passive and active methods have carried out a large number of studies respectively from the pre-alignment of cells (Kamalakshakurup G, Lee A P. High-efficiency single cell encapsulation and size selective capture of cells in picoliter droplets based on hydrodynamic micro-vortices[J].Lab on a Chip,2017,17:4324–4333; Harrington J,Esteban L B,Butement J,et al.Dual dean entrainment with volume ratio modulation for efficient droplet co-encapsulation:Extreme single-cell indexing[J].Lab on a Chip,2021,21(17):3378–3386; Li L,Wu P,Luo Z,et al.Dean Flow Assisted Single Cell and Bead Encapsulation for High Performance Single Cell Expression Profiling[J].ACS Sensors,2019,4(5):1299– 1305.) and droplet generation control (Wang H,Zhang W,Dai Z.A novel approach for encapsulating cells into monodisperse picolitre droplets actuated by microfluidic pulse inertia force[J].Analytical Methods,2014,6: 9754–9760). The single-cell encapsulation microdroplet technology has achieved rapid development.However, the following problems mainly need to be solved at present: 1) Challenges from random encapsulation. To prevent cell aggregation and improve the single-cell encapsulation rate, cells need to be highly diluted, resulting in the number of empty droplets far exceeding that of micro-droplets encapsulating cells; 2) Passive encapsulation methods can achieve the focused single-row arrangement of cell samples by relying on the channel structure or the action of inertial fluids, but they cannot effectively adjust the arrangement spacing between cells. Therefore, there are still deficiencies in ensuring the synchronization of cell supply and droplet generation rate and achieving precise encapsulation of single cells in micro-droplets; 3) Existing active encapsulation methods can adjust the number of encapsulated cells by controlling the size and rate of droplet generation through electrical parameters. However, since the supply of cell samples is still random, the final single-cell encapsulation rate is still limited by the Poisson distribution and remains low.

[0005] It can be seen that due to the fundamental problem of random encapsulation of suspended cells, the supply of cell samples is still random, the preparation rate of single-cell encapsulated micro-droplets is low, and it is difficult to meet the needs of single-cell research. It is urgent to explore new methods and approaches. Summary of the Invention

[0006] In order to overcome the deficiencies of the above technical methods and promote the development of single-cell encapsulation technology, the purpose of the present invention is to provide a device and method for single-cell orderly arrangement and encapsulation driven by an acoustic field mechanical potential well. By using the matching design of an Archimedean spiral interdigital transducer and a microchannel structure on a microfluidic chip, an acoustic field mechanical potential well is constructed through the coupling of acoustic-solid-liquid multi-physical fields. A non-contact vibration "acoustic sieve" acts on suspended cells, inducing the suspended cells to form a single-row arrangement tending to the acoustic field mechanical potential well during the traveling process, realizing the single-row orderly arrangement of suspended cells, and then relying on the process of generating micro-droplets to achieve precise encapsulation of single cells.

[0007] In order to achieve the above purpose, the present invention adopts the following technical solutions:

[0008] A device for single-cell orderly arrangement and encapsulation driven by an acoustic field mechanical potential well, the device includes an Archimedean spiral interdigital transducer, an Archimedean spiral interdigital electrode is arranged on the Archimedean spiral interdigital transducer, a microarray layer is arranged above the Archimedean spiral interdigital transducer, a microchannel system is arranged above the microarray layer, and the Archimedean spiral interdigital transducer, the microarray layer and the microchannel system cooperate; a suspended cell inlet joint, a continuous phase inlet joint and a collection outlet joint are installed on the microchannel system; after the microchannel system is bonded to the microarray layer, a closed microchannel is formed to accommodate the suspended cell solution and the continuous phase solution sample, providing an environment for the orderly arrangement of suspended cells and the generation of micro-droplets encapsulating cells and transporting the generated droplets to the collection outlet; the Archimedean spiral interdigital transducer is a surface acoustic wave excitation device for generating surface acoustic waves and then inducing the construction of an acoustic field mechanical potential well.

[0009] Further, the microchannel system includes a suspension cell inlet, an Archimedean spiral channel, a straight channel, a continuous phase channel, a continuous phase inlet, and a collection outlet. The inlet end of the Archimedean spiral channel is the suspension cell inlet, and the outlet end of the Archimedean spiral channel is connected and communicated with the inlet end of the straight channel; the outlet end of the straight channel is the collection outlet; the inlet end of the continuous phase channel is the continuous phase inlet, and the outlet end of the continuous phase channel is connected and communicated with the middle part of the straight channel; the microchannel system is provided with a first through groove and a second through groove for connecting with the electrode and the input wire.

[0010] Further, preferably, the channel height of the microchannel system is 100 microns, and the suspension cell inlet, the continuous phase inlet, and the collection outlet are all through holes.

[0011] Further, the material of the microchannel system is polydimethylsiloxane.

[0012] Further, the microarray layer is composed of a PDMS film and a photosensitive resin microcolumn array distributed in an Archimedean spiral shape, and the photosensitive resin microcolumn array is fabricated by 3D printing.

[0013] Further, the Archimedean spiral interdigital transducer includes a piezoelectric substrate, and Archimedean spiral interdigital electrodes arranged at equal intervals are fabricated on the piezoelectric substrate.

[0014] Further, the material of the piezoelectric substrate is a piezoelectric wafer with a high electromechanical coupling coefficient.

[0015] Further, the material of the Archimedean spiral interdigital electrode is a conductive photosensitive resin containing nano silver and can be fabricated by 3D printing.

[0016] Further, the lower surface of the channel of the microchannel system is bonded to the upper surface of the microcolumn of the microarray layer; the lower surface of the microarray layer without microcolumn is bonded to the upper surface of the Archimedean spiral interdigital transducer with electrodes; the continuous phase inlet joint is coaxially fitted and connected and communicated with the continuous phase inlet; the suspension cell inlet is coaxially fitted and connected and communicated with the suspension cell inlet joint; the collection outlet joint is coaxially fitted and connected and communicated with the collection outlet; the polar coordinate center of the Archimedean spiral channel coincides with the polar coordinate center of the Archimedean spiral interdigital electrode; the Archimedean spiral channel and the Archimedean spiral interdigital electrode are staggered, and the distances between the channel walls on both sides of the Archimedean spiral channel and the nearest electrode are equal.

[0017] Further, an operation method of a single-cell orderly arrangement and encapsulation device driven by an acoustic field mechanical potential well includes the following steps:

[0018] 1) First, fix the cell orderly arrangement and encapsulation microfluidic device for acoustic field regulation on the microscope stage equipped with a high-speed camera. Observe through the eyepiece to ensure that the Archimedean spiral flow channel 302 is within the microscope field of view and is not tilted.

[0019] 2) Connect the suspension cell inlet joint and the continuous phase inlet joint to the suspension cell syringe and the continuous phase solution syringe on the micro-injection pump respectively through Teflon hoses, and connect the collection outlet joint. The collection outlet joint is used to collect the cell-encapsulating droplets through a Teflon hose.

[0020] 3) Turn on and adjust the micro-injection pump. The syringe presses the suspension cell solution into the suspension cell inlet joint under the drive of the micro-injection pump, and enters and fills the Archimedean spiral flow channel and the straight flow channel through the suspension cell inlet.

[0021] 4) Connect the positive and negative poles of the output signal of the signal generator amplified by the power amplifier to the two poles of the Archimedean spiral interdigital electrode respectively, and adjust the output signal of the signal generator to be a continuous sine output.

[0022] 5) Press the "Output" buttons of the signal generator and the power amplifier, and set the corresponding sine AC voltage output value. The Archimedean spiral interdigital transducer generates surface acoustic waves under the excitation of the AC voltage signal. Under the regulation of the microarray on the propagation path of the surface acoustic wave in the microchannel, the applied acoustic field will couple with the microfluid to form a single-column mechanical potential well, which acts on the suspended cells as a non-contact vibration "acoustic sieve", inducing the suspended cells to form a single-row arrangement tending to the mechanical potential well of the acoustic field during the traveling process, and thus the suspended cells are arranged in a single row orderly.

[0023] 6) Move the stage, observe through the eyepiece to ensure that the connection between the straight flow channel and the continuous phase flow channel is within the microscope field of view and is not tilted. By adjusting the output parameters of the micro-injection pump, make the fluids in the straight flow channel and the continuous phase flow channel form an immiscible oil-water interface at the connection between the straight flow channel and the continuous phase flow channel, and stably generate micro-droplets. The orderly arranged cells are precisely encapsulated by the micro-droplets in the process of micro-droplet generation.

[0024] 7) The micro-droplets encapsulating cells flow out through the collection outlet and the collection outlet joint and are collected.

[0025] Furthermore, the continuous phase solution uses electronic fluorinated oil, and the suspension cell solution is an aqueous solution.

[0026] Compared with the prior art, the present invention has the following beneficial effects:

[0027] (1) Through the matching design of the Archimedean spiral interdigital transducer and the microchannel structure of the microfluidic chip, the present invention constructs a mechanical potential well of the acoustic field to drive the orderly arrangement of cells and can achieve the precise encapsulation of single cells.

[0028] (2) The present invention adopts a spiral structure design of an Archimedean spiral interdigital transducer and a microchannel structure, with high device integration and small volume.

[0029] (3) The material of the interdigital electrodes of the present invention is a conductive photosensitive resin of nano silver, and can be rapidly fabricated by 3D printing. Description of the Drawings

[0030] Figure 1 is an isometric view of the single-cell orderly arrangement and encapsulation device driven by the acoustic field mechanical potential well of the present invention;

[0031] Figure 2 is a top view of the microchannel system;

[0032] Figure 3 is a bottom view of the microchannel system;

[0033] Figure 4 is a top view of the microarray layer;

[0034] Figure 5 is a front view of the microarray layer;

[0035] Figure 6 is a top view of the Archimedean spiral interdigital transducer;

[0036] Figure 7 is a bottom view of the Archimedean spiral interdigital transducer;

[0037] Figure 8 is a schematic diagram of the present application.

[0038] In the figure:

[0039] 100 Archimedean spiral interdigital transducer, 200 microarray layer, 300 microchannel system, 400 continuous phase inlet joint, 500 collection outlet joint, 600 suspended cell inlet joint;

[0040] 101 Archimedean spiral interdigital electrode, 102 piezoelectric substrate;

[0041] 201 photosensitive resin microcolumn array, 202 PDMS film;

[0042] 301 suspended cell inlet, 302 Archimedean spiral channel, 303 continuous phase inlet, 304 continuous phase channel, 305 collection outlet, 306 straight channel, 307 second through groove, 308 first through groove. Detailed Embodiments

[0043] Next, the technical solutions in the embodiments of the present invention will be clearly and completely described in conjunction with the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts shall fall within the protection scope of the present invention.

[0044] Referring to Figure 1-8 , a single-cell ordered arrangement and encapsulation device driven by a sound field mechanical potential well, the device includes an Archimedean spiral interdigital transducer 100, an Archimedean spiral interdigital electrode is arranged on the Archimedean spiral interdigital transducer 100, a microarray layer 200 is arranged above the Archimedean spiral interdigital transducer 100, a microchannel system 300 is arranged above the microarray layer 200, and the Archimedean spiral interdigital transducer 100, the microarray layer 200 and the microchannel system 300 cooperate; a suspension cell inlet joint 600, a continuous phase inlet joint 400 and a collection outlet joint 500 are installed on the microchannel system 300; after the microchannel system 300 is bonded to the microarray layer 200, a closed microchannel is formed for accommodating a suspension cell solution and a continuous phase solution sample, providing an environment for the ordered arrangement of suspension cells and the generation of microdroplets for encapsulating cells, and transporting the generated droplets to the collection outlet; the Archimedean spiral interdigital transducer 100 is a surface acoustic wave excitation device for generating surface acoustic waves, thereby inducing the construction of a sound field mechanical potential well.

[0045] The microchannel system 300 includes a suspension cell inlet 301, an Archimedean spiral channel 302, a straight channel 306, a continuous phase channel 304, a continuous phase inlet 303 and a collection outlet 305. The inlet end of the Archimedean spiral channel 302 is the suspension cell inlet 301, and the outlet end of the Archimedean spiral channel 302 is connected and communicated with the inlet end of the straight channel 306; the outlet end of the straight channel 306 is the collection outlet 305; the inlet end of the continuous phase channel 304 is the continuous phase inlet 303, and the outlet end of the continuous phase channel 304 is connected and communicated with the middle part of the straight channel 306; first through grooves 308 and second through grooves 307 are arranged on the microchannel system 300 for connecting the electrodes and the input wires; the purpose of adopting the Archimedean spiral channel is to rely on the centrifugal force suffered by the cells during the movement process to assist the sound field mechanical potential well to better achieve the ordered arrangement of suspension cells.

[0046] Preferably, the channel height of the microchannel system 300 is 100 microns, and the suspension cell inlet 301, the continuous phase inlet 303 and the collection outlet 305 are all through holes.

[0047] Preferably, the material of the microchannel system 300 is polydimethylsiloxane.

[0048] The microarray layer 200 is composed of a PDMS thin film 202 and a photosensitive resin microcolumn array 201 distributed along an Archimedean spiral, and the photosensitive resin microcolumn array 201 is fabricated by 3D printing.

[0049] Preferably, the Archimedean spiral interdigital transducer 100 includes a piezoelectric substrate 102, and Archimedean spiral interdigital electrodes 101 arranged at equal intervals are fabricated on the piezoelectric substrate 102.

[0050] Preferably, the piezoelectric substrate 102 is made of a piezoelectric wafer with a high electromechanical coupling coefficient.

[0051] Preferably, the Archimedean spiral interdigital electrodes 101 are made of a conductive photosensitive resin containing nano silver and can be fabricated by 3D printing.

[0052] Preferably, the lower surface of the flow channel of the microfluidic channel system 300 is bonded to the upper surface of the microarray layer 200 with microcolumns; the lower surface of the microarray layer 200 without microcolumns is bonded to the upper surface of the Archimedean spiral interdigital transducer 100 with electrodes; the continuous phase inlet joint 400 is coaxially fitted and connected through the continuous phase inlet 303; the suspended cell inlet 301 is coaxially fitted and connected through the suspended cell inlet joint 600; the collection outlet joint 500 is coaxially fitted and connected through the collection outlet 305; the polar coordinate center of the Archimedean spiral flow channel 302 coincides with the polar coordinate center of the Archimedean spiral interdigital electrodes 101; the Archimedean spiral flow channel 302 and the Archimedean spiral interdigital electrodes 101 are staggered, and the distances between the flow channel walls on both sides of the Archimedean spiral flow channel 302 and the nearest electrode are equal.

[0053] Preferably, an operation method of a single-cell orderly arrangement and encapsulation device driven by acoustic field mechanical potential well includes the following steps:

[0054] 1) First, fix the microfluidic device for acoustic field-regulated single-cell orderly arrangement and encapsulation on the microscope stage equipped with a high-speed camera, and ensure through the eyepiece observation that the Archimedean spiral flow channel 302 is within the microscope field of view and has no inclination;

[0055] 2) Connect the suspended cell inlet joint 600 and the continuous phase inlet joint 400 to the suspended cell syringe and the continuous phase solution syringe on the micro-injection pump respectively through Teflon hoses, and collect the cell-encapsulating droplets through the collection outlet joint 500 and a Teflon hose.

[0056] 3) Turn on and adjust the micro-injection pump. Driven by the micro-injection pump, the syringe presses the suspension cell solution into the suspension cell inlet connector 600, and enters and fills the Archimedes spiral flow channel 302 and the straight flow channel 306 through the suspension cell inlet 301;

[0057] 4) Connect the positive and negative poles of the output signal of the signal generator amplified by the power amplifier to the two poles of the Archimedes spiral interdigital electrode 101 respectively, and adjust the output signal of the signal generator to be a continuous sine output;

[0058] 5) Press the "Output" buttons of the signal generator and the power amplifier, and set the corresponding sine AC voltage output value. The Archimedes spiral interdigital transducer 100 generates surface acoustic waves under the excitation of the AC voltage signal. Under the regulation of the microarray on the propagation path of the surface acoustic wave in the microchannel, the applied sound field will couple with the microfluid to form a single-column mechanical potential well, which acts on the suspended cells as a non-contact vibration "acoustic sieve", inducing the suspended cells to form a single-row arrangement tending to the mechanical potential well of the sound field during the movement process, and thus the suspended cells are arranged in a single row in an orderly manner;

[0059] 6) Move the stage, and ensure through the eyepiece observation that the connection between the straight flow channel 306 and the continuous phase flow channel 304 is placed within the microscope field of view and is not tilted. By regulating the output parameters of the micro-injection pump, the fluids in the straight flow channel 306 and the continuous phase flow channel 304 form an immiscible oil-water interface at the connection between the straight flow channel 306 and the continuous phase flow channel 304, and micro-droplets are stably generated. The orderly arranged cells are accurately wrapped by the micro-droplets in an orderly manner during the generation process of the micro-droplets;

[0060] 7) The micro-droplets wrapped with cells flow out through the collection outlet 305 and the collection outlet connector 500 and are collected.

[0061] Preferably, the continuous phase solution uses electronic fluorinated oil, and the suspension cell solution is an aqueous solution.

[0062] Refer to Figure 1-8The process of orderly arrangement and packaging of single cells driven by acoustic field mechanical potential well is as follows: under the drive of the microinjection pump, the suspended cell solution passes through the suspended cell inlet connector 600 and the suspended cell inlet 301, and the suspended cell solution fills the Archimedean spiral flow channel 302; the continuous phase solution passes through the continuous phase inlet connector 400 and the continuous phase inlet 303, and the continuous phase solution fills the continuous phase flow channel 304 and the direct current channel 306; the positive and negative poles of the output signal of the signal generator after amplification by the power amplifier are respectively connected to the two poles of the Archimedean spiral interdigital electrode 101, and the output signal of the signal generator is adjusted to a sinusoidal continuous output; the "output" button of the signal generator and the power amplifier is pressed, and the corresponding sinusoidal AC voltage output value is set, and the Archimedean spiral interdigital electrode 101 is connected to the Archimedean spiral interdigital electrode 101. The transducer 100 generates surface acoustic waves under the stimulation of an AC voltage signal. Under the regulation of the propagation path of the surface acoustic waves by the microarray in the microchannel, the applied acoustic field will couple with the microfluid to form a single-row mechanical potential well, which acts as a non-contact vibration "acoustic sieve" on the suspended cells, inducing the suspended cells to form a single-row arrangement tending to the mechanical potential well of the acoustic field during the movement, so that the suspended cells are orderly arranged in a single row; the input pressure of the suspended cell solution and the continuous phase solution is adjusted by a microinjection pump to achieve shearing of the dispersed phase solution by the continuous phase solution, thereby stably generating microdroplets, and the orderly arranged cells are orderly and accurately wrapped by the microdroplets during the microdroplet generation process; finally, the microdroplets wrapped with cells flow out through the collection outlet 305 and the collection outlet connector 500 and are collected.

[0063] It should be noted that, in this article, relational terms such as first and second, etc. are only used to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Moreover, the terms "include", "comprise" or any other variants thereof are intended to cover non-exclusive inclusion, so that a process, method, article or device including a series of elements includes not only those elements, but also other elements not explicitly listed, or also includes elements inherent to such process, method, article or device. In the absence of further restrictions, the elements defined by the sentence "comprise a ..." do not exclude the existence of other identical elements in the process, method, article or device including the elements.

Claims

1. A single-cell orderly arrangement and encapsulation device driven by an acoustic field mechanical potential well, characterized in that The device includes an Archimedean spiral interdigital transducer (100). An Archimedean spiral interdigital electrode is provided on the Archimedean spiral interdigital transducer (100). A microarray layer (200) is provided above the Archimedean spiral interdigital transducer (100). A microchannel system (300) is provided above the microarray layer (200). The Archimedean spiral interdigital transducer (100), the microarray layer (200) and the microchannel system (300) cooperate with each other. A suspension cell inlet joint (600), a continuous phase inlet joint (400) and a collection outlet joint (500) are installed on the microchannel system (300). After the microchannel system (300) is bonded to the microarray layer (200), a closed microchannel is formed to accommodate a suspension cell solution and a continuous phase solution sample, providing an environment for the orderly arrangement of suspension cells and the generation of microdroplets encapsulating cells and transporting the generated droplets to the collection outlet. The Archimedean spiral interdigital transducer (100) is a surface acoustic wave excitation device for generating surface acoustic waves to induce the construction of an acoustic field mechanical potential well. The lower surface of the microchannel system (300) with channels is bonded to the upper surface of the microarray layer (200) with microcolumns. The lower surface of the microarray layer (200) without microcolumns is bonded to the upper surface of the Archimedean spiral interdigital transducer (100) with electrodes. The continuous phase inlet joint (400) is coaxially fitted and connected to the continuous phase inlet (303) in a penetrating manner. The suspension cell inlet (301) is coaxially fitted and connected to the suspension cell inlet joint (600) in a penetrating manner. The collection outlet joint (500) is axially fitted and connected to the collection outlet (305) in a penetrating manner. The polar coordinate center of the Archimedean spiral channel (302) coincides with the polar coordinate center of the Archimedean spiral interdigital electrode (101). The Archimedean spiral channel (302) and the Archimedean spiral interdigital electrode (101) are staggered, and the distances from the channel walls on both sides of the Archimedean spiral channel (302) to the nearest electrode are equal.

2. The single-cell orderly arrangement and encapsulation device driven by the acoustic field mechanical potential well according to claim 1, characterized in that The microchannel system (300) includes a suspension cell inlet (301), an Archimedean spiral channel (302), a straight channel (306), a continuous phase channel (304), a continuous phase inlet (303) and a collection outlet (305). The inlet end of the Archimedean spiral channel (302) is the suspension cell inlet (301). The outlet end of the Archimedean spiral channel (302) is connected and communicated with the inlet end of the straight channel (306). The outlet end of the straight channel (306) is the collection outlet (305). The inlet end of the continuous phase channel (304) is the continuous phase inlet (303). The outlet end of the continuous phase channel (304) is connected and communicated with the middle part of the straight channel (306). First through slots (308) and second through slots (307) are provided on the microchannel system (300) for connecting with electrodes and input wires.

3. The single-cell orderly arrangement and encapsulation device driven by the acoustic field mechanical potential well according to claim 2, wherein The flow channel height of the microchannel system (300) is 100 microns, and the suspension cell inlet (301), continuous phase inlet (303) and collection outlet (305) are all through holes; the material of the microchannel system (300) is polydimethylsiloxane.

4. The single-cell orderly arrangement and encapsulation device driven by the sound field mechanical potential well according to claim 1, characterized in that, The microarray layer (200) is composed of a PDMS film (202) and a photosensitive resin microcolumn array (201) distributed along an Archimedean spiral. The photosensitive resin microcolumn array (201) is fabricated by 3D printing; the Archimedean spiral interdigital transducer (100) includes a piezoelectric substrate (102), and on the piezoelectric substrate (102), Archimedean spiral interdigital electrodes (101) are fabricated in equally spaced arrangement.

5. The single-cell ordered arrangement and encapsulation device driven by the acoustic field mechanical potential well according to claim 1, wherein The material of the piezoelectric substrate (102) is a piezoelectric wafer with a high electromechanical coupling coefficient; the material of the Archimedean spiral interdigital electrodes (101) is a conductive photosensitive resin containing nano silver and is fabricated by 3D printing.

6. A method for operating a single-cell orderly arrangement and encapsulation device according to any one of claims 1-5, characterized in that, It includes the following steps: 1) First, fix the cell orderly arrangement and encapsulation microfluidic device regulated by the sound field on the microscope stage equipped with a high-speed camera, and ensure through the eyepiece observation that the Archimedean spiral channel (302) is within the microscope field of view and has no inclination. 2) Connect the suspension cell inlet joint (600) and the continuous phase inlet joint (400) to the suspension cell syringe and the continuous phase solution syringe on the micro-injection pump respectively through Teflon hoses, and the collection outlet joint (500) is used to collect the cell encapsulation droplets through a Teflon hose. 3) Turn on and adjust the micro-injection pump. The syringe presses the suspension cell solution into the suspension cell inlet joint (600) under the drive of the micro-injection pump, and it enters and fills the Archimedean spiral channel (302) and the straight channel (306) through the suspension cell inlet (301). 4) Connect the positive and negative poles of the output signal of the signal generator amplified by the power amplifier to the two poles of the Archimedean spiral interdigital electrodes (101) respectively, and adjust the output signal of the signal generator to be a sinusoidal continuous output. 5) Press the "Output" buttons of the signal generator and the power amplifier, and set the corresponding sinusoidal AC voltage output value. The Archimedean spiral interdigital transducer (100) generates surface acoustic waves under the excitation of the AC voltage signal. Under the regulation of the microarray on the propagation path of the surface acoustic wave in the microchannel, the applied sound field will couple with the microfluid to form a single-column mechanical potential well, which acts on the suspension cells as a non-contact vibration "acoustic sieve", inducing the suspension cells to form a single-row arrangement tending to the mechanical potential well of the sound field during the traveling process, and thus the suspension cells are arranged in a single row orderly. 6) Move the stage. Ensure through the eyepiece observation that the penetration of the DC channel (306) and the continuous phase channel (304) is placed within the microscope field of view and without inclination. By adjusting the output parameters of the micro-injection pump, make the fluids in the DC channel (306) and the continuous phase channel (304) form an immiscible oil-water interface at the connection and penetration of the DC channel (306) and the continuous phase channel (304), and stably generate micro-droplets. The orderly arranged cells are precisely and orderly wrapped by the micro-droplets during the micro-droplet generation process; 7) The micro-droplets wrapped with cells flow out through the collection outlet (305) and the collection outlet connector (500) and are collected.

7. An operating method as claimed in claim 6, characterized in that, The continuous phase solution uses electronic fluorinated oil, and the cell suspension solution is an aqueous solution.

Citation Information

Patent Citations

  • Surface acoustic wave acceleration droplet-droplet micro-extraction device and method

    CN102940978A

  • Single-cell wrapped micro-droplet generation device and method based on surface acoustic wave arrangement

    CN114832872A