A microfluidic chip for capturing micro-nanoparticles

Abstract

The present invention discloses a microfluidic chip for capturing micro-nano particles, which belongs to the field of microfluidic chips. The chip includes a chip body, wherein a flow channel is provided inside the chip body, a capture area of ​​the flow channel is located between a sample inlet and a sample outlet, and a side wall of the flow channel in the capture area is stepped. A piezoelectric transducer is installed on the chip body and the position of the piezoelectric transducer corresponds to the capture area. The piezoelectric transducer forms a plurality of standing wave node lines in the capture area. The standing wave node lines are parallel to the flow channel and overlap with the fluid streamlines in the flow channel. The acoustic body standing waves generated by the piezoelectric transducer in the capture area fix the particles in the flow channel on the standing wave node lines. Through the above design, the deficiency of parallel flow channels is compensated. When particles between the node lines farther away from the node lines in the previous step flow through the node line position when they reach the next step, they are captured by the next step. Through this circulation or reciprocating structure, more efficient particle capture is achieved.

Description

Technical Field

[0001] The present invention relates to the field of microfluidic chips, in particular to a microfluidic chip for capturing micro-nano particles. Background Art

[0002] With the advancement of biomedical technology, nanoscale bioparticles, such as exosomes and viruses, are increasingly being recognized and utilized. As biomarkers and therapeutic vectors, exosomes and viruses play a crucial role in disease diagnosis and treatment. Due to the abundance of particles in the dispersion medium, enrichment is required to increase the concentration of bioparticles in the solution to meet detection sensitivity requirements before downstream analysis, diagnosis, or treatment.

[0003] Traditional bioparticle enrichment methods, such as ultracentrifugation and microfiltration centrifugation, suffer from inherent drawbacks such as long processing times, low yields, and high equipment costs. Microfluidic devices can largely overcome these drawbacks and are therefore gaining increasing attention for the separation and enrichment of bioparticles. Among the numerous microfluidic methods, acoustofluidics, which combines acoustic fields with microfluidics, offers advantages such as mild force fields, non-contact, label-free operation, and excellent biocompatibility, making it an ideal bioparticle manipulation technology. When using acoustofluidics for bioparticle enrichment, the acoustic field must be able to capture and release bioparticles within a continuous liquid flow. However, the primary driving force in acoustofluidics—the acoustic radiation force—is proportional to the cube of the particle size. As particle size decreases to the nanometer scale, the dominant acoustic radiation force is replaced by the acoustic flow and the Stokes force in the fluid, leading to rapid degradation of device performance. This phenomenon limits the application of acoustofluidics for nanoparticle manipulation.

[0004] Although the existing technology has introduced micron-sized seed particles to enrich nanoscale biological particles through the secondary acoustic radiation force effect, the enrichment efficiency is low, especially the enrichment efficiency of exosomes (<200nm) is less than 10%, which also leads to the need for a large amount of sample to meet the final concentration requirements. Summary of the Invention

[0005] In order to overcome the deficiencies of the prior art, one of the objectives of the present invention is to provide a microfluidic chip for capturing micro-nanoparticles with high enrichment efficiency.

[0006] One of the purposes of the present invention is achieved by the following technical solution:

[0007] A microfluidic chip for capturing micro-nanoparticles comprises a chip body, wherein a flow channel is provided inside the chip body, wherein the flow channel is provided with a sample inlet and a sample outlet, and further provided with a capture area, wherein the capture area is located between the sample inlet and the sample outlet, and the sidewall of the flow channel in the capture area is stepped. The microfluidic chip for capturing micro-nanoparticles further comprises a piezoelectric transducer, wherein the piezoelectric transducer is mounted on the chip body and the position of the piezoelectric transducer corresponds to the capture area, and the piezoelectric transducer forms a plurality of standing wave node lines in the capture area, wherein the standing wave node lines are parallel to the flow channel and overlap with the fluid streamlines in the flow channel, and the acoustic body standing waves generated by the piezoelectric transducer in the capture area fix and clamp the particles in the flow channel to the standing wave node lines.

[0008] Furthermore, the depth of the capture zone is 1 / 4 of the standing wave wavelength.

[0009] Furthermore, the step width is an integer multiple of half the wavelength of the standing wave.

[0010] Furthermore, the steps are structures in which the cross-sectional height increases continuously, decreases continuously, or increases and decreases in a cycle.

[0011] Furthermore, the side wall on one side of the capture area is stepped.

[0012] Furthermore, the side walls on both sides of the capture area are stepped.

[0013] Furthermore, the difference between the width of the middle step and the width of the steps on both sides is a wavelength or an integer multiple thereof.

[0014] Furthermore, the difference between the width of the middle step and the width of the steps on both sides is half a wavelength or an odd multiple thereof.

[0015] Furthermore, the steps are structures whose cross-sectional height increases or decreases randomly, and the sidewalls on one side or both sides of the capture area are in a stepped shape.

[0016] Furthermore, the length of each step is greater than the axial distance that the particle moves to the node line of the standing wave.

[0017] Furthermore, the thickness resonance frequency of the piezoelectric transducer is equal to the standing wave frequency.

[0018] Compared with the prior art, the flow channel of the microfluidic chip for capturing micro-nanoparticles of the present invention is further provided with a capture area, which is located between the sample inlet and the sample outlet. The side wall of the flow channel in the capture area is stepped. The microfluidic chip for capturing micro-nanoparticles also includes a piezoelectric transducer, which is installed on the chip body and the position of the piezoelectric transducer corresponds to the capture area. The piezoelectric transducer forms multiple standing wave node lines in the capture area. The standing wave node lines are parallel to the flow channel, and the standing wave node lines overlap with the fluid streamlines in the flow channel. The acoustic standing waves generated by the piezoelectric transducer in the capture area fix the particles in the flow channel on the standing wave node lines. Through the above design, the shortcomings of the parallel flow channels are compensated. The particles between the node lines farther away from the node lines in the previous step will flow through the node line position when they reach the next step, and are thereby captured by the next step. Through this circulating or reciprocating structure, more efficient particle capture is achieved. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 is a cross-sectional view of a microfluidic chip for capturing micro-nanoparticles according to the present invention;

[0020] Figure 2 A top view of the flow channel according to the first embodiment of the present invention;

[0021] Figure 3 for Figure 2 A sound pressure simulation diagram of the first embodiment when the step width is an integer multiple of half the wavelength of the standing wave;

[0022] Figure 4 for Figure 2 Streamline simulation diagram of the first embodiment when the step width is an integer multiple of half the wavelength of the standing wave;

[0023] Figure 5 for Figure 2 The flow velocity simulation distribution diagram of the first embodiment when the step width is an integer multiple of half the wavelength of the standing wave;

[0024] Figure 6 for Figure 2 A sound pressure simulation diagram of the first embodiment when the step width is not an integer multiple of half the wavelength of the standing wave;

[0025] Figure 7 A top view of the flow channel according to a second embodiment of the present invention;

[0026] Figure 8 for Figure 7 A sound pressure simulation diagram when the difference between the width of the middle step and the width of the steps on both sides of the second embodiment is one wavelength or an integer multiple thereof;

[0027] Figure 9 for Figure 7 A streamline simulation diagram of the second embodiment in which the difference between the width of the middle step and the width of the steps on both sides is a wavelength or an integer multiple thereof;

[0028] Figure 10 for Figure 7 The flow velocity simulation distribution diagram of the second embodiment in which the difference between the width of the middle step and the width of the steps on both sides is a wavelength or an integer multiple thereof;

[0029] Figure 11 for Figure 7 A sound pressure simulation diagram when the difference between the width of the middle step and the width of the steps on both sides of the second embodiment is half a wavelength or an odd multiple thereof;

[0030] Figure 12 for Figure 7 A streamline simulation diagram of the second embodiment in which the difference between the width of the middle step and the width of the steps on both sides is half a wavelength or an odd multiple thereof;

[0031] Figure 13 for Figure 7 The difference between the width of the middle step and the width of the steps on both sides of the second embodiment is half a wavelength or an odd multiple thereof;

[0032] Figure 14 This is a simulation diagram of the sound pressure when the bilateral steps change in the same direction;

[0033] Figure 15 This is a streamline simulation diagram of the double-sided steps changing in the same direction;

[0034] Figure 16 This is a simulation diagram of the flow velocity when the bilateral steps change in the same direction;

[0035] Figure 17 A top view of a flow channel according to a third embodiment of the present invention;

[0036] Figure 18 This is a diagram showing the particle enrichment effect of the parallel flow channel.

[0037] In the figure: 10, chip body; 11, substrate; 12, cover plate; 13, flow channel; 130, sample inlet; 131, capture area; 132, sample outlet; 133, side wall; 20, piezoelectric transducer. DETAILED DESCRIPTION

[0038] The following will clearly and completely describe the technical solutions in the embodiments of the present invention in conjunction with the accompanying drawings. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. All other embodiments obtained by ordinary technicians in this field based on the embodiments of the present invention without making any creative efforts shall fall within the scope of protection of the present invention.

[0039] It should be noted that when a component is referred to as being "fixed to" another component, it may be directly on the other component or there may be another intermediate component through which it is fixed. When a component is considered to be "connected to" another component, it may be directly connected to the other component or there may be another intermediate component at the same time. When a component is considered to be "set on" another component, it may be directly set on the other component or there may be another intermediate component at the same time. The terms "vertical", "horizontal", "left", "right" and similar expressions used herein are for illustrative purposes only.

[0040] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art to which this invention pertains. The terms used in this specification of the present invention are for the purpose of describing specific embodiments only and are not intended to limit the present invention. The term "and / or" as used herein includes any and all combinations of one or more of the associated listed items.

[0041] See also Figure 1 The present invention provides a microfluidic chip for capturing micro-nanoparticles, which is used to achieve the enrichment of micro-nanoparticles with high efficiency and high throughput. The micro-nanoparticles include but are not limited to cells, exosomes, viruses, microplastics, microspheres, etc.

[0042] A microfluidic chip for capturing micro-nanoparticles includes a chip body 10 and a piezoelectric transducer 20 mounted on the chip body 10 .

[0043] The chip body 10 includes a substrate 11 and a cover plate 12. The substrate 11 is provided with a groove. The cover plate 12 is sealed and attached to the substrate 11, so that the groove between the cover plate 12 and the substrate 11 forms a flow channel 13. The piezoelectric transducer 20 is bonded to the lower surface of the capture area 131 of the substrate 11. When voltage is applied to the piezoelectric transducer 20, an acoustic body standing wave is generated. The thickness resonance frequency of the piezoelectric transducer 20 is equal to the standing wave frequency. The acoustic body standing wave fixes the particles to a specific standing wave node line. Multiple standing wave node lines are generated in the flow channel 13 to increase the capture flux; the standing wave node lines overlap with the fluid streamlines at a certain angle, thereby ensuring that the particles flowing along the flow channel 13 can flow through the standing wave node lines and be captured, thereby improving the capture efficiency.

[0044] Please continue reading Figures 2 to 5, which is the first embodiment of the flow channel 13 of the microfluidic chip for capturing micro-nanoparticles of the present invention. The flow channel 13 is provided with a sample inlet 130, a capture area 131 and a sample outlet 132, and the capture area 131 is located between the sample inlet 130 and the sample outlet 132. The capture area 131 uses acoustic wave capture to fix the particles in the continuous flow, and the particles are released after the acoustic field is closed, thereby achieving the effect of enrichment and concentration. The capture area 131 is located between the two side walls 133 of the flow channel 13, and the cross-sectional height of the side wall 133 of the capture area 131 is continuously increasing, continuously decreasing, or continuously increasing and continuously decreasing in a cycle. In the first embodiment, the side wall 133 on one side of the capture area 131 is stepped and the other side is straight, which is a single-sided stepped structure. The step widths are all integer multiples of half the wavelength of the standing wave.

[0045] from Figure 3 It can be seen that when the step widths are all integer multiples of half the wavelength of the standing wave, the sound pressure node lines are continuous and of uniform intensity, showing a higher sound pressure gradient change, and the resulting sound radiation force is also stronger; the number of sound pressure node lines increases with the increase in the width of the flow channel 13, and the capture flux can be increased by increasing the width of the flow channel 13. Figure 3 and Figure 4 It can be seen that the streamlines and the sound pressure node lines overlap at a certain angle, thus ensuring that particles flowing along the streamlines can flow through the standing wave node lines and be captured, thereby improving the capture efficiency. Figure 5 It can be seen that when the width of the flow channel 13 increases, the flow velocity decreases, which reduces the fluid drag force and is beneficial to acoustic capture.

[0046] If there is a step width that is not an integer multiple of the half wavelength of the standing wave, the sound pressure simulation for the step structure is as follows Figure 6 As shown by Figure 6 It can be seen that since the width of the second step does not meet the integer multiple of half the wavelength, the sound pressure distribution at the frequency where a large sound pressure gradient is generated between the front and rear steps has a certain irregularity, and the intensity also has a large attenuation, which is not conducive to particle capture at this position.

[0047] Please continue reading Figure 7 , which is a second embodiment of the flow channel 13 of the microfluidic chip for capturing micro-nanoparticles according to the present invention. In this second embodiment, the cross-sectional height of the sidewalls 133 of the capture zone 131 increases continuously, decreases continuously, or cycles between increasing and decreasing continuously. The sidewalls 133 on either side of the capture zone 131 are stepped, forming a bilateral staircase structure. The step widths are all integer multiples of half the wavelength of the standing wave.

[0048] When the width of the middle step differs from the width of the steps on both sides by a wavelength or an integer multiple thereof, a continuous sound pressure distribution can be formed between the steps. The simulation diagram is shown in the figure below. Figures 8 to 10As shown, it can be seen that the middle width area of ​​the sound pressure node line and the streamline diagram has a high degree of overlap, which is not conducive to improving the capture efficiency of particles flowing through the middle area.

[0049] When the width difference between the middle step and the width of the steps on both sides is half a wavelength or an odd multiple thereof, a plurality of standing wave node lines of sound pressure distribution can be formed in each step area. The standing wave sound pressure node lines in each step area are relatively staggered. The simulation diagram is as follows Figures 11 to 13 As shown, it can be seen that the sound pressure node lines and streamline diagrams are staggered with each other, which is not likely to cause the problem that particles flowing along a specific streamline cannot reach any standing wave node line, which is beneficial to the improvement of the overall capture efficiency.

[0050] When the bilateral steps change in the same direction, the standing wave node line and the fluid streamline are highly coincident, such as Figures 14 to 16 As shown, it is very easy to cause particles that are not at the standing wave node line of the first step to also be unable to reach the standing wave node line in subsequent steps, which easily leads to a decrease in capture efficiency.

[0051] Please continue reading Figure 17 , which is the third embodiment of the flow channel 13 of the microfluidic chip for capturing micro-nanoparticles of the present invention. In the third embodiment, the step width can vary randomly, but it should be noted that the width of each step is an integer multiple of half the wavelength of the standing wave. Specifically, the cross section has a step structure with randomly increased or decreased height, and the step height varies unilaterally or symmetrically on both sides. Similar to the previous two embodiments, the width difference between the steps will affect the distribution of the standing wave node line, and the direction of the streamline needs to be comprehensively considered for structural design. Avoid the situation where the standing wave node line and the streamline height coincide. The angle between the standing wave node line and the streamline is preferably less than 45 degrees, at which point the drag force of the fluid has less effect on the capture. In addition, in order to ensure the capture action time, the length of each step should be greater than the axial distance the particle moves to the node line.

[0052] The particle enrichment effect in the parallel flow channel in the prior art is as follows Figure 18 If the particle flows close to the node line of the standing wave, it is easy to capture. If it is far away from the node line, it will not be captured due to insufficient acoustic radiation force. If a parallel flow channel is used, the particles between the node lines far away from the node line may be difficult to capture due to the increased flow rate. The use of a stepped flow channel can make up for the shortcomings of the parallel flow channel. The particles between the node lines far away from the node line in the previous step will flow through the node line position when they reach the next step and are captured by the next step. Through this cyclic or reciprocating structure, more efficient particle capture is achieved.

[0053] This application uses sound waves to propel particles in a fluid. Because the mechanical force acting on the particles does not affect their activity, it offers excellent biocompatibility. The simple structure of the flow channel 13 and its small number of openings facilitate the removal of bubbles and impurities, ensuring a stable fluid environment. The overall structure is sterile and sealed, making it suitable for biohazardous samples. The chip can be discarded after a single use.

[0054] The above embodiments merely illustrate several implementations of the present invention, and while their descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the patented invention. It should be noted that those skilled in the art would be able to make numerous variations and improvements without departing from the spirit of the present invention. These variations and improvements are equivalent modifications and improvements to the above embodiments based on the essential technology of the present invention and fall within the scope of protection of the present invention.

Claims

1. A microfluidic chip for capturing micro-nanoparticles, comprising a chip body, a flow channel disposed within the chip body, the flow channel having a sample inlet and a sample outlet, characterized in that: The flow channel is also provided with a capture area, which is located between the sample inlet and the sample outlet. The side wall of the flow channel in the capture area is stepped. The microfluidic chip for capturing micro-nanoparticles also includes a piezoelectric transducer, which is installed on the chip body and the position of the piezoelectric transducer corresponds to the capture area. The piezoelectric transducer forms a plurality of standing wave node lines in the capture area. The standing wave node lines are parallel to the flow channel and overlap with the fluid streamlines in the flow channel. The acoustic standing waves generated by the piezoelectric transducer in the capture area fix the particles in the flow channel on the standing wave node lines. The step width is an integer multiple of half the wavelength of the standing wave, and the difference between the width of the middle step and the width of the steps on both sides is one wavelength or an integer multiple thereof, or the difference between the width of the middle step and the width of the steps on both sides is half a wavelength or an odd multiple thereof.

2. The microfluidic chip for capturing micro-nanoparticles according to claim 1, characterized in that: The depth of the capture zone is 1 / 4 of the standing wave wavelength.

3. The microfluidic chip for capturing micro-nanoparticles according to any one of claims 1 to 2, characterized in that: The length of each step is greater than the axial distance the particle moves to the node line of the standing wave.

4. The microfluidic chip for capturing micro-nanoparticles according to any one of claims 1 to 2, characterized in that: The thickness resonance frequency of the piezoelectric transducer is equivalent to the standing wave frequency.

5. The microfluidic chip for capturing micro-nanoparticles according to any one of claims 1 to 2, characterized in that: The steps are structures in which the cross-sectional width increases continuously, decreases continuously, or increases and decreases continuously in a cycle.

6. The microfluidic chip for capturing micro-nanoparticles according to claim 5, characterized in that: The side wall on one side of the capture area is in a stepped shape.

7. The microfluidic chip for capturing micro-nanoparticles according to claim 5, characterized in that: The side walls on both sides of the capture area are both stepped.

8. The microfluidic chip for capturing micro-nanoparticles according to any one of claims 1-2, characterized in that: The steps are structures whose cross-sectional width increases or decreases randomly, and the sidewalls on one side or both sides of the capture area are in a step shape.

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