A cell high-recovery sorting chip based on cooperation of magnetic field source and microfluidics

Abstract

The utility model embodiment provides a kind of cell high recovery rate sorting chip based on magnetic field source and microfluidic coordination, which comprises: microfluidic chip, magnetic field source and the capture interface being arranged between microfluidic chip and magnetic field source;The first end of microfluidic chip along the first direction is provided with one sheath liquid inlet and one sample inlet, and the second end of microfluidic chip along the first direction is provided with one outlet, and the sheath liquid inlet, sample inlet and outlet are respectively communicated with the fluid channel of microfluidic chip;The capture interface seals the fluid channel;Magnetic field source applies the magnetic force towards capture interface to target cell marked by magnetic bead in fluid channel, and target cell is pulled to capture interface by magnetic force.The utility model adds sheath liquid in microfluidic chip, forms a stable flow protection layer on the both sides of sample, so that fluid flow environment is more stable, and fluid pulsation is small under low flow, more stable.

Description

Technical Field

[0001] This utility model relates to the field of cell sorting technology, and more specifically, to a cell sorting chip with high recovery rate based on the synergy of magnetic field source and microfluidics. Background Technology

[0002] Magnetic-Activated Cell Sorting (MACS) technology has been widely used in cell isolation, immunoassay, and clinical diagnostics due to its ease of operation and high throughput. Traditional MACS relies on the random collision and adsorption of target cells labeled with magnetic beads in a magnetic field, but its capture efficiency and specificity still have room for improvement due to hydrodynamic limitations. The combination of MACS technology and microfluidics has become a hot area in biomedical engineering in recent years. Its core technology lies in forming an optimized magnetic field that generates a magnetic force on the target cells. This magnetic force, along with the fluid drag and the frictional force between the cell and the capture interface, achieves a balance, thereby realizing the purpose of cell capture.

[0003] The combination of MACS and microfluidics has shown significant potential in cell sorting, clinical diagnosis, and treatment. For example, microfluidic chips, through precise fluid control, allow magnetically modified target cells to flow through a capture interface controlled by a magnetic field source, resulting in a significantly higher cell capture probability than the random collision mechanism of conventional MACS. The microchannels of microfluidic chips have extremely low shear forces, leading to a higher cell viability retention rate compared to traditional MACS. Furthermore, due to the micro-manipulation characteristics of microfluidics, reagents and samples required for experiments can be greatly reduced.

[0004] While this technology is relatively mature, certain bottlenecks remain, posing challenges to its integration: First, at low flow rates, both centrifugal and volumetric pumps generate fluid pulsations within the flow channel, potentially causing a sudden increase in the fluid drag force on the cells. Second, magnetic field sources typically employ high relative permeability materials to generate the induced magnetic field, resulting in a limited magnetic field range, usually on the order of hundreds of micrometers. This makes them particularly sensitive to the thickness of the capture interface, leading to a sharp decrease in magnetic force when thickness deviations exist at the capture interface. Both of these situations can cause captured target cells to escape, reducing the cell capture rate. Therefore, a cell sorting chip is urgently needed to overcome at least one of the aforementioned problems in the existing technology to improve the target cell capture rate of magnetic sorting chips. Utility Model Content

[0005] This application provides a cell sorting chip with high recovery rate based on the synergy of magnetic field source and microfluidics, in order to solve at least one of the technical problems in the prior art.

[0006] According to an embodiment of this application, a cell sorting chip with high recovery rate based on the collaboration of a magnetic field source and microfluidics is provided. The cell sorting chip with high recovery rate includes: a microfluidic chip, a magnetic field source, and a capture interface disposed between the microfluidic chip and the magnetic field source. The microfluidic chip has a sheath fluid inlet and a sample inlet at its first end along a first direction, and an outlet at its second end along the first direction. The sheath fluid inlet, the sample inlet, and the outlet are all connected to the fluid channel of the microfluidic chip. The capture interface seals the fluid channel. The magnetic field source applies a magnetic force toward the capture interface to the target cells labeled with magnetic beads in the fluid channel, thereby pulling the target cells toward the capture interface. The first direction is the fluid flow direction of the fluid channel.

[0007] In some embodiments of this application, the high cell recovery rate sorting chip further includes: multiple cell cards; Multiple cell cards are arranged on the capture interface, with the opening of each cell card facing the sheath fluid inlet and the sample inlet along the first direction to immobilize target cells.

[0008] In some embodiments of this application, each of the cell cards is in the form of an open semi-circular ring.

[0009] In some embodiments of this application, each cell card includes two quarter-ring structures, which are symmetrically arranged to form the open semi-ring shape, and a flow gap is provided between the two quarter-ring structures.

[0010] In some embodiments of this application, the diameter and height of the open semi-circular inner ring are both 5 to 20 micrometers.

[0011] In some embodiments of this application, the magnetic field source includes a permanent magnet and a plurality of amorphous alloys. The permanent magnet is disposed away from the capture interface, and the plurality of amorphous alloys are disposed close to the capture interface. The plurality of amorphous alloys and the permanent magnet form an alternating stacked structure.

[0012] In some embodiments of this application, the fluid channel includes a central channel, two side transition sections, and an edge connecting section. The two ends of the central channel are integrally connected to one of the two side transition sections. The sample inlet and the outlet are respectively connected to the central channel through two of the two side transition sections. The sheath fluid inlet is connected to the central channel through two of the edge connecting sections.

[0013] In some embodiments of this application, the central channel is rectangular in cross-section perpendicular to the second direction, and the two side transition sections are isosceles triangles in cross-section perpendicular to the second direction. The base of the two side transition sections is connected to the short side of the central channel, and the sample inlet and the outlet are respectively connected to the apex of the two side transition sections; wherein, the second direction is perpendicular to the first direction.

[0014] In some embodiments of this application, the two edge connecting segments are respectively connected to the two bottom corners of the two transition segments located on one side of the sample inlet.

[0015] In some embodiments of this application, the edge connecting segment includes a first straight segment, an arc segment, and a second straight segment. The two ends of the first straight segment are respectively connected to the midpoint of the arc segment and the sheath fluid inlet. The two ends of the arc segment are respectively connected to one end of the two second straight segments. The other ends of the two second straight segments are respectively connected to the two bottom corners of the two transition segments located on the side of the sample inlet.

[0016] The beneficial effects of the embodiments of this application are as follows: By incorporating sheath fluid into the microfluidic chip and employing a chip design that synchronizes the flow of sheath fluid and the sample, a stable flow protective layer is formed by the sheath fluid on both sides of the sample, resulting in a more stable fluid flow environment with less fluid pulsation and smoother flow at low flow rates. Simultaneously, a cell card is added to the cell capture interface to effectively immobilize the captured target cells, solving the problem of target cell escape after capture. Furthermore, the synergy between amorphous alloy with high magnetic permeability and a permanent magnet with high remanence optimizes the magnetic field gradient. This high-recovery-rate cell sorting chip effectively overcomes the effects of fluid pulsation and thickness deviations at the capture interface, achieving effective cell immobilization and improving the target cell capture rate of the magnetic sorting chip. Attached Figure Description

[0017] To more clearly illustrate the technical solutions in the embodiments of this application or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of this utility model. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0018] Figure 1 A schematic diagram of the overall structure of a cell sorting chip with high recovery rate based on the synergy of magnetic field source and microfluidics, provided for an embodiment of this application; Figure 2 A cross-sectional schematic diagram of the fluid channel in a cell sorting chip with high recovery rate based on the synergy of magnetic field source and microfluidics, provided for an embodiment of this application; Figure 3A schematic diagram of the cell card structure in a high-recovery-rate cell sorting chip based on the synergy of a magnetic field source and microfluidics, provided in an embodiment of this application; Explanation of reference numerals in the attached figures: 1 is the microfluidic chip, 11 is the sheath fluid inlet, 12 is the sample inlet, 13 is the outlet, 14 is the fluid channel, 141 is the central channel, 142 is the transition section on both sides, 143 is the edge connection section, 1431 is the first straight segment, 1432 is the arc segment, 1433 is the second straight segment, 2 is the magnetic field source, 21 is the permanent magnet, 22 is the amorphous alloy, 3 is the capture interface, 4 is the cell card, 41 is the quarter-circular ring structure, and 42 is the flow gap. Detailed Implementation

[0019] The technical solutions of the embodiments of this application will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of this utility model, and not all embodiments. Based on the embodiments of this utility model, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the protection scope of this utility model.

[0020] It should be noted that the terms "comprising" and "having," and any variations thereof, in the embodiments and accompanying drawings of this application are intended to cover non-exclusive inclusion. For example, it may include a series of structures, without being limited to the structures listed, but may optionally include structures not listed, or may optionally include other components inherent to these structures.

[0021] This application discloses a cell sorting chip with high recovery rate based on the synergy of a magnetic field source and microfluidics. These will be described in detail below.

[0022] Figure 1 This illustration shows a cell sorting chip with high recovery rate based on the synergy of a magnetic field source and microfluidics, according to an embodiment of this application. Figure 1 As shown, the high cell recovery sorting chip includes: a microfluidic chip 1, a magnetic field source 2, and a capture interface 3 disposed between the microfluidic chip 1 and the magnetic field source 2.

[0023] The microfluidic chip 1 in this embodiment employs a chip design where sheath fluid and sample flow synchronously. Specifically, the microfluidic chip 1 has a sheath fluid inlet 11 and a sample inlet 12 at its first end along a first direction, and an outlet 13 at its second end along the first direction. The sheath fluid inlet 11, sample inlet 12, and outlet 13 are all connected to the fluid channel 14 of the microfluidic chip 1. In other words, the microfluidic chip 1 has two inlets: one is the sheath fluid inlet 11, and the other is the sample inlet 12, with both inlets corresponding to the same outlet 13. When this high-recovery-rate cell sorting chip is applied, an external pump is connected to the outlet 13. When the external pump creates negative pressure at the outlet, guiding the fluid to flow in the fluid channel 14, the sheath fluid forms a stable flow protection layer on both sides of the sample. This maintains stable flow dynamics even if sample parameters change, reducing fluid pulsation fluctuations. This solves the technical problems in the prior art where it cannot effectively cope with the sudden increase in fluid drag caused by fluid pulsation in the flow channel at low flow rates, and where the deviation requirements are extremely stringent due to sensitivity to the thickness parameters of the capture interface.

[0024] In this embodiment, the capture interface 3 also serves as the sealing surface of the fluid channel 14. On one hand, the capture interface 3 is a specially functionalized surface area in the microfluidic chip 1, which specifically binds to target cells (such as circulating tumor cells, pathogens, etc.) labeled with magnetic beads through physical or chemical action, thereby achieving enrichment or separation from complex samples (such as blood, saliva). On the other hand, the capture interface 3 seals the fluid channel 14 and is also a functional layer in the microfluidic chip 1 used to close the fluid channel 14 and prevent leakage or contamination.

[0025] In this embodiment, the magnetic field source 2 is a physical device that generates a magnetic field and provides the magnetic field energy required for sorting. It applies a magnetic force toward the capture interface 3 to the target cells labeled with magnetic beads in the fluid channel 14. The magnetic force pulls the target cells toward the capture interface 3, and the target cells are captured under the combined action of magnetic force, friction force, and fluid drag force.

[0026] In this embodiment, the second direction is perpendicular to the first direction. The first direction is the fluid flow direction of the fluid channel 14, and the second direction is the direction of the central axis of the sheath fluid inlet 11, the sample inlet 12, and the outlet 13. It should be noted and understood that the perpendicularity in this embodiment is not absolute and can be 90° ± 10°.

[0027] In some specific embodiments, such as Figure 1 and Figure 3As shown, the high-recovery-rate cell sorting chip also includes multiple cell cards 4. Specifically, multiple cell cards 4 are arranged on the capture interface 3, and the opening of each cell card 4 faces the sheath fluid inlet 11 and the sample inlet 12 along the first direction, so that the target cells are well fixed after being pulled to the capture interface 3 by the magnetic field source 2. Each cell card 4 is an open semi-circular ring, that is, the cross-section of the cell card 4 perpendicular to the second direction is an open semi-circular ring, and its opening faces the incoming flow direction. Further, each cell card 4 includes two quarter-circular ring structures 41, which are symmetrically arranged to form an open semi-circular ring, and a flow gap 42 is provided between the two quarter-circular ring structures 41. After the cells enter the cell card 4, the fluid flows out from the flow gap 42 between the two quarter-circular ring structures 41, thereby fixing the cells. In the specific implementation, the inner ring diameter and height of the open semi-circular ring are both 5~20 micrometers. In the application, the inner ring diameter and height of the cell card 4 can be adaptively adjusted according to the different cell sizes.

[0028] In other specific embodiments, such as Figure 1 As shown, the magnetic field source 2 includes a permanent magnet 21 and multiple amorphous alloys 22. The permanent magnet 21 is positioned away from the capture interface 3, while the multiple amorphous alloys 22 are positioned close to the capture interface 3. The multiple amorphous alloys 22 and the permanent magnet 21 form an alternating stacked structure. The amorphous alloys 22 are used in combination with the permanent magnet 21 as magnetic flux conduction / reinforcing materials to achieve high-frequency magnetic field enhancement.

[0029] In other specific embodiments, the microfluidic chip 1 employs a trapezoidal expansion-contraction channel, such as... Figure 2 As shown, the fluid channel 14 includes a central channel 141, two side transition sections 142, and an edge connecting section 143. The two ends of the central channel 141 are integrally connected to one of the two side transition sections 142. The sample inlet 12 and the outlet 13 are connected to the central channel 141 through the two side transition sections 142, respectively. The sheath fluid inlet 11 is connected to the central channel 141 through the two edge connecting sections 143, so as to achieve smooth flow rate switching through the two side transition sections 142 and achieve synchronous flow of sheath fluid and sample through the edge connecting sections 143.

[0030] Furthermore, the central channel 141 is rectangular in cross-section perpendicular to the second direction, and the two side transition sections 142 are isosceles triangles in cross-section perpendicular to the second direction. The base of the two side transition sections 142 is connected to the short side of the central channel 141, and the sample inlet 12 and outlet 13 are respectively connected to the apex corners of the two side transition sections 142. Furthermore, the two edge connecting sections 143 are respectively connected to the two base corners of the two side transition sections 142 located on the side of the sample inlet 12. In addition, the edge connecting section 143 includes a first straight section 1431, an arc section 1432, and a second straight section 1433. The two ends of the first straight section 1431 are respectively connected to the midpoint of the arc section 1432 and the sheath fluid inlet 11, the two ends of the arc section 1432 are respectively connected to one end of the two second straight sections 1433, and the other ends of the two second straight sections 1433 are respectively connected to the two base corners of the two side transition sections 142 located on the side of the sample inlet 12. This allows the sheath fluid to form a stable boundary layer inside the chip, minimizing fluid pulsation.

[0031] In summary, this application discloses a high-recovery-rate cell sorting chip based on the synergy of a magnetic field source and microfluidics. A sheath fluid is added to the microfluidic chip, and a chip design is adopted in which the sheath fluid and sample flow synchronously. The sheath fluid forms a stable flow protective layer on both sides of the sample, resulting in a more stable fluid flow environment with less fluid pulsation and smoother flow at low flow rates. Simultaneously, a cell card is added to the cell capture interface to effectively fix the captured target cells, solving the problem of target cell escape after capture. Furthermore, the high-permeability amorphous alloy and the high-remanence permanent magnet work together to optimize the magnetic field gradient. This high-recovery-rate cell sorting chip can effectively overcome the effects of fluid pulsation and thickness deviation at the capture interface, achieving effective cell fixation and improving the target cell capture rate of the magnetic sorting chip.

[0032] It will be understood by those skilled in the art that the accompanying drawings are merely schematic diagrams of one embodiment, and the components shown in the drawings are not necessarily essential for implementing this invention. It should also be noted that similar reference numerals and letters in the following drawings denote similar items; therefore, once an item is defined in one drawing, it does not need to be further defined and explained in subsequent drawings.

[0033] In the description of the embodiments of this application, unless otherwise expressly specified and limited, the terms "installation," "connection," and "linking" should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral connection; they can refer to a mechanical connection or an electrical connection; they can refer to a direct connection or an indirect connection through an intermediate medium; and they can refer to the internal connection of two components. Those skilled in the art can understand the specific meaning of the above terms in this utility model based on the specific circumstances. Furthermore, in the description of the embodiments of this application, it should be noted that the terms "center," "upper," "lower," "left," "right," "vertical," "horizontal," "inner," and "outer," etc., indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings. They are only for the convenience of describing this utility model and simplifying the description, and do not indicate or imply that the device or component referred to must have a specific orientation, or be constructed and operated in a specific orientation. Therefore, they should not be construed as limitations on this utility model.

[0034] Finally, it should be noted that the above-described embodiments are merely specific implementations of this utility model, used to illustrate the technical solution of this utility model, and not to limit it. The protection scope of this utility model is not limited thereto. Although this utility model has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that any person skilled in the art can still modify or easily conceive of changes to the technical solutions described in the foregoing embodiments, or make equivalent substitutions for some of the technical features, within the technical scope disclosed in this utility model. These modifications, changes, or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of this utility model, and should all be covered within the protection scope of this utility model. Therefore, the protection scope of this utility model should be determined by the protection scope described in the claims.

Claims

1. A cell sorting chip with high recovery rate based on the synergy of a magnetic field source and microfluidics, characterized in that, The high cell recovery rate sorting chip includes: a microfluidic chip, a magnetic field source, and a capture interface disposed between the microfluidic chip and the magnetic field source; The microfluidic chip has a sheath fluid inlet and a sample inlet at its first end along a first direction, and an outlet at its second end along the first direction. The sheath fluid inlet, the sample inlet, and the outlet are all connected to the fluid channel of the microfluidic chip. The capture interface seals the fluid channel. The magnetic field source applies a magnetic force toward the capture interface to the target cells labeled with magnetic beads in the fluid channel, thereby pulling the target cells toward the capture interface. The first direction is the fluid flow direction of the fluid channel.

2. The cell sorting chip with high recovery rate based on the synergy of magnetic field source and microfluidics as described in claim 1, characterized in that, The high-recovery-rate cell sorting chip also includes: multiple cell cards; Multiple cell cards are arranged on the capture interface, with the opening of each cell card facing the sheath fluid inlet and the sample inlet along the first direction to immobilize target cells.

3. The cell sorting chip with high recovery rate based on the synergy of magnetic field source and microfluidics as described in claim 2, characterized in that, Each of the cell cards is an open semi-circular ring.

4. The cell sorting chip with high recovery rate based on the synergy of magnetic field source and microfluidics as described in claim 3, characterized in that, Each of the cell cards includes two quarter-ring structures, which are symmetrically arranged to form the open semi-circular shape, and a flow gap is provided between the two quarter-ring structures.

5. The cell sorting chip with high recovery rate based on the synergy of magnetic field source and microfluidics as described in claim 3, characterized in that, The diameter and height of the open semi-circular inner ring are both 5-20 micrometers.

6. The cell sorting chip with high recovery rate based on the synergy of magnetic field source and microfluidics as described in claim 1, characterized in that, The magnetic field source includes a permanent magnet and a plurality of amorphous alloys. The permanent magnet is disposed away from the capture interface, and the plurality of amorphous alloys are disposed close to the capture interface. The plurality of amorphous alloys and the permanent magnet form an alternating stacked structure.

7. The cell sorting chip with high recovery rate based on the synergy of magnetic field source and microfluidics as described in claim 1, characterized in that, The fluid channel includes a central channel, two side transition sections, and an edge connecting section. The two ends of the central channel are integrally connected to one of the two side transition sections. The sample inlet and the outlet are respectively connected to the central channel through the two side transition sections. The sheath fluid inlet is connected to the central channel through the two edge connecting sections.

8. The cell sorting chip with high recovery rate based on the synergy of magnetic field source and microfluidics as described in claim 7, characterized in that, The central channel is rectangular in cross-section perpendicular to the second direction, and the two side transition sections are isosceles triangles in cross-section perpendicular to the second direction. The base of the two side transition sections is connected to the short side of the central channel. The sample inlet and the outlet are respectively connected to the apex of the two side transition sections. The second direction is perpendicular to the first direction.

9. The cell sorting chip with high recovery rate based on the synergy of magnetic field source and microfluidics as described in claim 8, characterized in that, The two edge connecting segments are respectively connected to the two bottom corners of the two transition segments located on one side of the sample inlet.

10. The cell sorting chip with high recovery rate based on the synergy of magnetic field source and microfluidics as described in claim 9, characterized in that, The edge connecting segment includes a first straight segment, an arc segment, and a second straight segment. The two ends of the first straight segment are respectively connected to the midpoint of the arc segment and the sheath fluid inlet. The two ends of the arc segment are respectively connected to one end of the two second straight segments. The other ends of the two second straight segments are respectively connected to the two bottom corners of the two transition segments located on one side of the sample inlet.

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