Microfluidic chip for manipulating particles to enable static detection in a flowing fluid

Abstract

The application discloses a microfluidic chip for controlling particles to realize static detection in flowing fluid, which comprises a chip body and a flow channel structure arranged in the chip body, and a clamping detection area and a sorting area are sequentially arranged on a main flow channel of the flow channel structure along a particle flow direction; the main flow channel has a circulation structure formed by a plurality of clamping units which are linearly and spacedly arranged along the particle flow direction; at least one clamping piezoelectric transducer is arranged on the clamping detection area to generate acoustic standing waves in three-dimensional directions, so as to fix and clamp the particles at specific standing wave nodes. The microfluidic chip for controlling particles to realize static detection in flowing fluid can fix a single particle at a position in the continuous flowing fluid through the acoustic standing waves in three directions generated by the at least one piezoelectric transducer and the circulation structure formed by the clamping units with specific shaped sections arranged on the main flow channel, so that the detection of the single particle in the continuous flow can be realized.

Description

Technical Field

[0001] This invention relates to the field of microfluidics, and in particular to a microfluidic chip for static detection of particles in flowing fluid. Background Technology

[0002] Microfluidic chips are widely used for particle detection and manipulation. Acoustic tweezers, based on the principle of particle movement towards nodes in a standing wave acoustic field, can fix particle positions, facilitating related detection. Currently, tunable surface acoustic waves (SAWs) are commonly used for microfluidic manipulation and particle sorting. Their main structure involves coating two pairs of mutually perpendicular interdigital electrodes onto a lithium niobate wafer, with the flow channel covering the lithium niobate wafer. Under the influence of a two-dimensional acoustic field, particles form an array and are fixed in position, as illustrated in patent 201380013827X. This type of solution has the following drawbacks: it is difficult to clamp individual particles; particles distributed throughout the flow channel often aggregate under the influence of the acoustic field; and in some detection fields, such as Raman detection, the particles need to be kept relatively stationary. To achieve Raman detection in a continuous flow, a manipulation scheme is needed to clamp the particles in the continuous flow for a certain period of time, keeping them stationary. To address this issue, patent CN111054454A discloses a microfluidic chip for particle manipulation, which can fix a single particle at a certain position in a continuous flow microchannel, providing time for detection and facilitating particle detection, thus solving the above problem to some extent. However, it still has the following shortcomings: it uses a focusing area and a detection area arranged sequentially. The focusing area requires focusing interdigital electrodes or piezoelectric transducers for focusing, and then a pair of clamping interdigital electrodes are needed in the detection area for clamping, which increases the complexity of the device structure, manufacturing process, and cost.

[0003] Therefore, it is now necessary to further improve the existing technology to provide a more reliable solution. Summary of the Invention

[0004] The technical problem to be solved by the present invention is to provide a microfluidic chip for static detection of particles in a flowing fluid, addressing the shortcomings of the prior art.

[0005] To solve the above-mentioned technical problems, the technical solution adopted by the present invention is: a microfluidic chip for controlling particles in a flowing fluid to achieve static detection, comprising a chip body and a flow channel structure disposed in the chip body, wherein a clamping detection area and a sorting area are sequentially disposed on the main flow channel of the flow channel structure along the particle flow direction.

[0006] The clamping detection area enables the clamping and detection of particles in the main channel in three-dimensional space, and the sorting area is used to separate target particles from non-target particles.

[0007] The main channel has a circulation structure formed by several clamping units arranged at linear intervals along the particle flow direction. At least one clamping piezoelectric transducer is provided on the clamping detection area. The piezoelectric transducer generates acoustic standing waves in three dimensions to fix and clamp the particles to a specific standing wave node, which is the geometric center of the cross section of the clamping unit in the XY plane.

[0008] The X direction is the flow direction of the main channel, i.e., the length direction; the Y direction is the width direction of the main channel; and the Z direction is the depth direction of the main channel.

[0009] Preferably, the clamping unit has a rectangular cross-sectional shape in the XY plane.

[0010] Preferably, the length of the clamping unit is an integer multiple of its width, and the width of the clamping unit is greater than or equal to its depth.

[0011] Preferably, the clamping unit has a circular cross-sectional shape in the XY plane, and the diameter of the circle is greater than or equal to the depth of the clamping unit.

[0012] Preferably, adjacent clamping units are connected by a narrow flow channel, the width of which is smaller than the width or diameter of the clamping unit.

[0013] Preferably, the chip body includes a substrate and a cover plate, the bottom surface of the substrate has a channel groove, and the cover plate is sealed and attached to the substrate, so that the channel groove between the cover plate and the substrate forms the flow channel structure.

[0014] Preferably, the clamping piezoelectric transducer is bonded to the lower surface of the substrate, and the excitation wavelength of the clamping piezoelectric transducer is twice the width or diameter of the clamping unit.

[0015] Preferably, the sorting area is provided with a sorting piezoelectric transducer, which is attached to the lower surface of the substrate in the sorting area.

[0016] Preferably, the flow channel structure further includes an inlet, a waste outlet, and a collection outlet, with the inlet located upstream of the main flow channel and the waste outlet and collection outlet both located downstream of the main flow channel.

[0017] Preferably, the downstream of the main channel is divided into three branches, two of which are connected to a collection port, and the other branch is connected to the waste liquid port. The two collection ports are located on both sides of the waste liquid port along the Y direction.

[0018] The beneficial effects of this invention are:

[0019] The microfluidic chip provided by this invention for manipulating particles in a flowing fluid to achieve static detection uses a piezoelectric transducer to generate acoustic standing waves in three directions. Combined with a cyclic structure formed by clamping units with specific cross-sections set on the main flow channel, it can fix a single particle in a continuous flow fluid at a certain position, thereby realizing the detection of a single particle in a continuous flow.

[0020] This invention uses sound waves to drive the movement of particles in a fluid. Since mechanical force is applied to the particles, their activity is not affected when the particles are biological cells.

[0021] This invention has a small number of outlets, which is beneficial for removing air bubbles and maintaining a stable fluid environment. It has a simple structure, low cost, and good application prospects.

[0022] The present invention has a simple manufacturing process, is easy to mass-produce, and reduces chip costs. Attached Figure Description

[0023] Figure 1 This is a top view of the microfluidic chip of the present invention for manipulating particles in a flowing fluid to achieve static detection.

[0024] Figure 2 This is a schematic diagram of the structure of a microfluidic chip in the XY plane (top view) for manipulating particles in a flowing fluid to achieve static detection, according to one embodiment of the present invention.

[0025] Figure 3 This is a schematic diagram of the structure of a microfluidic chip in the XY plane (top view) for manipulating particles in a flowing fluid to achieve static detection, according to another embodiment of the present invention.

[0026] Figure 4 This is a side view of the microfluidic chip of the present invention for static detection of particles in a flowing fluid;

[0027] Figure 5 This is an application example of the microfluidic chip of the present invention for static detection of particles in a flowing fluid.

[0028] Explanation of reference numerals in the attached figures:

[0029] 1—Chip body; 2—Flow channel structure; 10—Substrate; 11—Cover plate; 20—Sample inlet; 21—Main flow channel; 22—Clamping detection area; 23—Sorting area; 24—Branch; 25—Collection port; 26—Waste liquid port; 220—Clamping unit; 221—Narrow flow channel; 222—Clamping piezoelectric transducer; 223—Detection point; 230—Sorting piezoelectric transducer. Detailed Implementation

[0030] The present invention will be further described in detail below with reference to embodiments, so that those skilled in the art can implement it based on the description.

[0031] It should be understood that terms such as “having,” “comprising,” and “including” as used herein do not exclude the presence or addition of one or more other elements or combinations thereof.

[0032] Example 1

[0033] Reference Figure 1-4 This embodiment provides a microfluidic chip for static detection of particles in a flowing fluid. It includes a chip body 1 and a flow channel structure 2 disposed in the chip body 1. The main channel 21 of the flow channel structure 2 is provided with an inlet 20, a clamping detection area 22, a sorting area 23, a waste liquid outlet 26 and a collection outlet 25 in sequence along the particle flow direction. The downstream of the main channel 21 is divided into branches 24, which are respectively connected to the collection outlet 25 and the waste liquid outlet 26.

[0034] The clamping detection zone 22 enables the clamping and detection of particles in the main channel 21 in three-dimensional space, while the sorting zone 23 is used to separate target particles from non-target particles. This invention uses acoustic clamping to temporarily fix particles in a continuous flow, which is beneficial for Raman spectroscopy detection or microscopic imaging. Targeted screening is achieved by judging the detection results.

[0035] The main channel 21 has a loop structure formed by several clamping units 220 arranged linearly along the particle flow direction. The clamping detection area 22 is provided with at least one clamping piezoelectric transducer 222. The clamping piezoelectric transducer 222 generates acoustic standing waves in three dimensions to fix the particles to a specific standing wave node (detection point 223). The specific standing wave node is the geometric center of the cross section of the clamping unit 220 in the XY plane.

[0036] The X direction is the flow direction of the main channel 21, i.e., the length direction; the Y direction is the width direction of the main channel 21; and the depth direction of the main channel 21 is the Z direction.

[0037] Reference Figure 1 and Figure 2 In a preferred embodiment, the clamping unit 220 has a circular cross-sectional shape in the XY plane, and the diameter of the circle is greater than or equal to the depth of the clamping unit 220. Under the excitation of the clamping piezoelectric transducer 222, the circular flow channel vibrates in both the diametrical direction and the depth Z, establishing a standing wave within the flow channel. The particles then move towards the standing wave nodal line. In the diametrical direction, since the transducer excitation wavelength is twice the diameter, a standing wave nodal line is established at the center of the circular flow channel, causing the particles to move towards the center. In the depth direction, a nodal line is formed, and the particles move towards the nodal line, thereby fixing the depth position of the particles.

[0038] Reference Figure 3 In another preferred embodiment, the clamping unit 220 has a rectangular cross-sectional shape in the XY plane. The length of the clamping unit 220 is an integer multiple of its width, and the width of the clamping unit 220 is greater than or equal to its depth. The excitation wavelength of the clamping piezoelectric transducer 222 is twice the width or diameter of the clamping unit 220. Under the excitation of the clamping piezoelectric transducer 222, the rectangular flow channel vibrates in the length (X), width (Y), and depth (Z) directions, establishing a standing wave within the flow channel. The particles then move towards the standing wave nodal line. In the width direction, since the transducer excitation wavelength is twice the width dimension, a standing wave nodal line is established at the center of the flow channel width, causing the particles to move towards the width center, thus fixing their width position. In the length direction, one (length = width) or several nodal lines (length = n × width, particles are equally spaced in the X direction within the main channel 21) will be generated. Particles will move towards the nodal lines to form one or several aggregation points, thus fixing the length position. In the depth direction, a nodal line is formed, and particles move towards the nodal line, thus fixing the depth position of the particles.

[0039] The adjacent clamping units 220 are connected by a narrow channel 221, the width of which is smaller than the width or diameter of the clamping unit 220.

[0040] A continuous intermittent voltage signal (a square wave signal with a certain duty cycle) is applied to the clamping piezoelectric transducer 222. When a particle passes through the flow channel, if the signal is high, it will move towards the nodal line due to the ultrasonic radiation force of the standing wave nodal line; if the signal is 0, it will move with the fluid. Since the shear force of the fluid movement mainly exists in the flow direction (X-axis), even if the level returns to 0 in the width and depth directions, the particle's position will not shift again. In this invention, the circulation structure is mainly considered in the X-axis direction. Since the fluid does not stop flowing, it is necessary to overcome the fluid shear force to make the particle stop. The circulation structure can decelerate the particle in the X-axis direction until it stops.

[0041] After being decelerated by the cyclic structure, the particles are eventually clamped at a standing wave node (detection point 223), thus achieving a temporary fixation of the particle's position. During this fixation, spectral detection or imaging can be performed. This temporary fixation provides time for detection. The particles include microparticles made of inorganic materials or biological cells.

[0042] In a preferred embodiment, the chip body 1 includes a substrate 10 and a cover plate 11. The substrate 10 is a silicon wafer. A channel groove is formed on the bottom surface of the substrate 10. The cover plate 11 is sealed and attached to the substrate 10, so that the channel groove between the cover plate 11 and the substrate 10 forms a flow channel structure 2. The clamped piezoelectric transducer 222 is bonded to the lower surface of the substrate 10. The cover plate 11 can be made of glass, plastic, or polymer. The fluid in the flow channel structure 2 always maintains a laminar flow state. The waste liquid outlet 26 and the collection outlet 25 are both located downstream of the main channel 21. Downstream of the main channel 21, it is divided into three branches 24, two of which are connected to one collection outlet 25, and the other branch 24 is connected to the waste liquid outlet 26. The two collection outlets 25 are located on both sides of the waste liquid outlet 26 along the Y direction.

[0043] In a preferred embodiment, a sorting piezoelectric transducer 230 is provided in the sorting area 23 and is attached to the lower surface of the substrate 10 in the sorting area 23.

[0044] In a preferred embodiment, when the microfluidic chip for manipulating particles in a flowing fluid for static detection is working, a voltage is applied to the clamping piezoelectric transducer 222, generating acoustic standing waves in three dimensions, clamping the particle position to the standing wave nodes, thereby fixing the particle position. (Refer to...) Figure 5 This is an application example of a microfluidic chip used to manipulate particles for static detection in flowing fluid. When a particle is detected at the clamping point, spectral detection or imaging is performed. The detection time must be less than the clamping duration of a single cycle (the duration when the piezoelectric ceramic driving square wave is high). After detection, the fixed particles continue to flow downstream. Analysis is performed after particle detection at the detection point. When the detected particle is the target particle, a sorting pulse signal is generated and sent to the sorting piezoelectric transducer 230 in the sorting zone 23 to activate it and achieve the sorting of the target particle. It should be understood that the above detection function is implemented using conventional solutions in conventional products and is not the focus of this invention. For example, after briefly fixing particles in a continuous flow, Raman spectroscopy or microscopic imaging can be used to detect and target the particles based on the detection results. The sorting zone 23 can use a standing wave with two nodal lines in the width direction for sorting. The sorting function can also be implemented using other existing solutions, such as dielectric sorting or mechanical switch sorting. For example, in one embodiment, the detection function is implemented through a detection module, which includes a light spot excitation modulation system, a light signal detection system, a data acquisition, analysis and control module, and a piezoelectric drive module. This solution can refer to the microfluidic chip system for rare cell screening disclosed in patent CN201721059781.7.

[0045] Although the embodiments of the present invention have been disclosed above, they are not limited to the applications listed in the specification and embodiments. They can be applied to various fields suitable for the present invention. For those skilled in the art, other modifications can be easily made. Therefore, without departing from the general concept defined by the claims and their equivalents, the present invention is not limited to the specific details.

Claims

1. A microfluidic chip for static detection of particles in a flowing fluid, comprising a chip body and a flow channel structure disposed in the chip body, characterized in that, The main channel of the flow channel structure is provided with a clamping detection area and a sorting area in sequence along the particle flow direction; The clamping detection area enables the clamping and detection of particles in the main channel in three-dimensional space, and the sorting area is used to separate target particles from non-target particles. The main channel has a circulation structure formed by several clamping units arranged at linear intervals along the particle flow direction. At least one clamping piezoelectric transducer is provided on the clamping detection area. The piezoelectric transducer generates acoustic standing waves in three dimensions to fix and clamp the particles to a specific standing wave node, which is the geometric center of the cross section of the clamping unit in the XY plane. The X direction is the flow direction of the main channel, i.e., the length direction; the Y direction is the width direction of the main channel; and the depth direction of the main channel is the Z direction. The clamping unit has a rectangular cross-sectional shape in the XY plane, or the clamping unit has a circular cross-sectional shape in the XY plane, and the diameter of the circle is greater than or equal to the depth of the clamping unit. The length of the clamping unit is an integer multiple of its width, and the width of the clamping unit is greater than or equal to its depth. The adjacent clamping units are connected by a narrow flow channel, the width of which is smaller than the width or diameter of the clamping unit.

2. The microfluidic chip for static detection of particles in a flowing fluid according to claim 1, characterized in that, The chip body includes a substrate and a cover plate. A channel groove is formed on the bottom surface of the substrate, and the cover plate is sealed and attached to the substrate, so that the channel groove between the cover plate and the substrate forms the flow channel structure.

3. The microfluidic chip for static detection of particles in a flowing fluid according to claim 2, characterized in that, The clamping piezoelectric transducer is bonded to the lower surface of the substrate, and the excitation wavelength of the clamping piezoelectric transducer is twice the width or diameter of the clamping unit.

4. The microfluidic chip for static detection of particles in a flowing fluid according to claim 2, characterized in that, The sorting area is equipped with a sorting piezoelectric transducer, which is attached to the lower surface of the substrate in the sorting area.

5. The microfluidic chip for static detection of particles in a flowing fluid according to claim 1, characterized in that, The flow channel structure includes an inlet, a waste outlet, and a collection outlet. The inlet is located upstream of the main flow channel, and the waste outlet and collection outlet are both located downstream of the main flow channel.

6. The microfluidic chip for static detection of particles in a flowing fluid according to claim 5, characterized in that, The main channel is divided into three branches downstream, two of which are connected to a collection port, and the other branch is connected to the waste liquid port. The two collection ports are located on both sides of the waste liquid port along the Y direction.

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