Magnetic bead monodispersion chip and operation method

Abstract

A magnetic bead monodispersion chip and an operation method. The magnetic bead monodispersion chip comprises a droplet generation array (103) located in a housing. The droplet generation array (103) is located between a droplet storage cavity (102) and a sample inlet. The droplet generation array (103) comprises a plurality of micro-droplet generation channels. Each channel comprises a narrow channel region (I) and a bell-mouth region (II) connected to the narrow channel region (I). A channel bottom surface (103d) is higher than the bottom surface of the droplet storage cavity (102). The narrow channel region (I) is communicated with the sample inlet, and the bell-mouth region (II) is communicated with the droplet storage cavity (102). The channel has a first height. The ratio of the first height to the particle size of a magnetic bead is 1.5 to 3. The bell-mouth region (II) has a first width adjacent to the narrow channel region (I) and a second width adjacent to the droplet storage cavity (102), the second width being greater than the first width. By dispersing magnetic beads by means of micro-droplets, monodispersion of the magnetic beads can be achieved.

Description

Magnetic bead monodisperse chip and operation method

[0001] This application claims priority to the Chinese patent application filed with the China Patent Office on December 1, 2023, with application number 202311663599.2 and invention name “Magnetic Bead Monodisperse Chip and Operation Method”, the entire contents of which are incorporated by reference into this application. Technical Field

[0002] The present invention relates to the field of bioanalysis technology, and in particular to a magnetic bead monodisperse chip and an operating method. Background Art

[0003] Digital ELISA is used to detect and measure the concentration of specific biomolecules (such as IL-6 antigen) in biological fluids. Compared to traditional ELISA, digital ELISA offers higher sensitivity and accuracy, allowing for the detection and measurement of very low concentrations of molecules. Single-molecule immunoassay technology based on digital ELISA generally consists of three steps: reagent reaction, magnetic bead monodispersion, and fluorescence detection.

[0004] In the currently commercialized digital enzyme-linked immunosorbent assay (ELISA), there are two methods for magnetic bead monodispersion: magnetic bead drop-in-hole and magnetic bead tiling. Magnetic bead drop-in-hole uses gravity to capture magnetic beads in femtoliter-sized microwells. However, since gravity is not significant at the microscale, the capture efficiency of magnetic bead drop-in-hole is low and unstable, resulting in the loss of a large number of magnetic beads. Magnetic bead tiling uses gravity sedimentation to spread magnetic beads on a smooth glass surface. However, due to interactions such as nonspecific adsorption and van der Waals forces between individual magnetic beads, magnetic bead aggregation is inevitable after tiling, resulting in poor and unstable magnetic bead monodispersion.

[0005] In summary, the existing magnetic bead monodispersion effect is poor, and the existing magnetic bead monodispersion method needs to be further improved. Summary of the Invention

[0006] The technical problem solved by the present invention is to provide a magnetic bead monodisperse chip and an operation method to improve the monodisperse performance of the magnetic beads.

[0007] In order to solve the above technical problems, the technical solution of the present invention provides a magnetic bead monodisperse chip, comprising: a shell, the shell is respectively provided with an inlet and an outlet communicating with the inside and outside of the shell, the inlet is used to inject a magnetic bead suspension into the shell, the magnetic bead suspension comprises a plurality of magnetic beads to be processed, and the magnetic beads to be processed have a first particle size; a droplet storage chamber located in the shell, the droplet storage chamber having a storage chamber bottom surface and a storage chamber side wall perpendicular to the storage chamber bottom surface; a droplet generation array located in the shell, the droplet generation array is also located between the droplet storage chamber and the inlet, the droplet generation array comprises a plurality of micro-droplet generation channels, each of the channels comprises a narrow channel area, a trumpet area connected to the narrow channel area, the channel having a channel bottom surface and a storage chamber side wall perpendicular to the channel bottom surface The side wall of the channel is higher than the bottom surface of the storage chamber, the narrow channel area is connected to the sample inlet, and the bell-mouth area is connected to the droplet storage chamber. In a first direction perpendicular to the bottom surface of the channel, the channel has a first height, and the ratio of the first height to the first particle size ranges from 1.5 to 3. In a second direction parallel to the bottom surface of the channel and perpendicular to the extension direction of the channel, the bell-mouth area has a first width adjacent to the narrow channel area and a second width adjacent to the droplet storage chamber, and the second width is greater than the first width; an oil storage chamber is located in the shell, and the oil storage chamber is also located between the droplet storage chamber and the sample outlet, and is communicated with the sample outlet, and is used to store the oil phase reagent flowing out of the droplet storage chamber.

[0008] Optionally, the structure of the monodisperse magnetic bead chip further includes: a droplet filtration structure located between the droplet storage chamber and the oil storage chamber, the droplet filtration structure having a plurality of gaps connecting the droplet storage chamber and the oil storage chamber, the width of each gap being smaller than the target droplet particle size; the width of each gap ranges from 10 μm to 40 μm.

[0009] Optionally, each of the channels further includes an inlet area, the two ends of which are respectively connected to the narrow channel area and the injection port; the inlet area has a third width adjacent to the narrow channel area, and a fourth width adjacent to the injection port, and the fourth width is greater than the third width.

[0010] Optionally, the droplet generation array is fan-shaped, and a plurality of the channels are arranged along the circumferential direction.

[0011] Optionally, the number of the plurality of channels includes one of 8, 16, 24, 32 and 48.

[0012] Optionally, the structure of the monodisperse magnetic bead chip also includes: the first height ranges from 5 μm to 20 μm; the ratio of the width of the narrow channel area in the second direction to the first particle size ranges from 2 to 10; the width of the narrow channel area in the second direction ranges from 10 μm to 25 μm; the angle between the channel side wall of the bell-mouth area and the channel side wall of the narrow channel area ranges from 10 degrees to 20 degrees; the length of the bell-mouth area in the extension direction of the channel ranges from 50 μm to 500 μm; the ratio of the height difference between the bottom surface of the channel and the bottom surface of the storage cavity to the first height ranges from 4 to 15.

[0013] Optionally, the shell includes an upper shell and a lower shell, the upper shell and the lower shell are encapsulated at the edges, and the sample inlet and the sample outlet are located in the upper shell; the magnetic bead monodisperse chip also includes: a plurality of support columns located between the bottom surface of the storage cavity and the upper shell; the plurality of support columns are also located between the bottom surface of the oil storage cavity and the upper shell; the radius range of each of the support columns is 100μm to 500μm; the plurality of support columns are arranged in an array in a direction parallel to the bottom surface of the storage cavity, and the spacing between two adjacent support columns is in the range of 1mm to 2.5mm; the thickness range of the upper shell is 0.5mm to 2mm; the thickness range of the lower shell is 0.5mm to 2mm.

[0014] Optionally, the material of the monodisperse magnetic bead chip includes one or more of glass, silicon wafer and polymer material; the polymer material includes one or more of polydimethylsiloxane, polyurethane, epoxy resin, polymethyl methacrylate, polycarbonate, cycloolefin copolymer, polystyrene, polyethylene and fluoroplastic.

[0015] Correspondingly, the technical solution of the present invention also provides a method for operating monodisperse magnetic beads, comprising: providing a monodisperse magnetic bead chip, the monodisperse magnetic bead chip comprising: a shell, the shell being respectively provided with an inlet and an outlet connected to the inside and outside of the shell, the inlet being used to inject a magnetic bead suspension into the shell, the magnetic bead suspension comprising a plurality of magnetic beads to be processed, the magnetic beads to be processed having a first particle size; a droplet storage chamber located in the shell, the droplet storage chamber having a storage chamber bottom surface and a storage chamber side wall perpendicular to the storage chamber bottom surface; a droplet generation array located in the shell, the droplet generation array also being located between the droplet storage chamber and the inlet, the droplet generation array comprising a plurality of micro-droplet generation channels, each of the channels comprising a narrow channel area and a trumpet-mouth area connected to the narrow channel area, the channel having a channel bottom surface and a channel side wall perpendicular to the channel bottom surface, the channel bottom surface being higher than the storage chamber bottom surface, the narrow channel area being perpendicular to the inlet The bell-mouth area is connected to the droplet storage chamber, and in a first direction perpendicular to the bottom surface of the channel, the channel has a first height, and the ratio of the first height to the first particle size ranges from 1.5 to 3. In a second direction parallel to the bottom surface of the channel and perpendicular to the extension direction of the channel, the bell-mouth area has a first width adjacent to the narrow channel area and a second width adjacent to the droplet storage chamber, and the second width is greater than the first width; an oil storage chamber is located in the shell, and the oil storage chamber is also located between the droplet storage chamber and the sample outlet, and is interconnected with the sample outlet, and is used to store the oil phase reagent flowing out of the droplet storage chamber; providing the magnetic bead suspension; injecting the oil phase reagent into the magnetic bead monodisperse chip through the sample inlet until there is no gas residual inside the magnetic bead monodisperse chip; after injecting the oil phase reagent, injecting the magnetic bead suspension into the magnetic bead monodisperse chip.

[0016] Optionally, the method for injecting the magnetic bead suspension into the magnetic bead monodisperse chip includes: using a segmented suction method to pre-encapsulate the magnetic bead suspension to be processed in a hose, the segmented suction method includes allowing the hose to at least suck in a first section of oil phase reagent, and after sucking in the first section of oil phase reagent, sucking in the magnetic bead suspension to be processed; air-tightly connecting the suction port end of the hose to the injection port of the magnetic bead monodisperse chip, and ensuring that there are no bubbles at the connection; after the air-tight connection, injecting the magnetic bead suspension to be processed and the first section of oil phase reagent in the hose into the magnetic bead monodisperse chip.

[0017] Optionally, the segmented suction method further comprises: after sucking the magnetic bead suspension to be treated, sucking the second oil phase reagent

[0018] Optionally, the method for obtaining a magnetic bead suspension includes: obtaining a target magnetic bead concentration according to a target droplet particle size; and preparing a magnetic bead suspension having the target magnetic bead concentration.

[0019] Optionally, the method for obtaining the target magnetic bead concentration according to the target droplet particle size includes: obtaining the target droplet particle size D1; obtaining the boundary particle size D2 of the magnetic bead suspension to be configured according to the target droplet particle size D1, D2>D1 / 90%; according to the relationship between the magnetic bead concentration C in the magnetic bead suspension and the boundary particle size D2 and the boundary particle size D2, and obtain the target magnetic bead concentration C of the magnetic bead suspension.

[0020] Optionally, the method for configuring a magnetic bead suspension having the target magnetic bead concentration further includes: obtaining an initial suspension, wherein the initial suspension contains the plurality of magnetic beads to be processed; adding a surfactant to the initial suspension, resuspending the initial suspension, and obtaining the suspension; the resuspension method includes: one or more of vortexing, stirring, and shaking; the surfactant includes one or more of Tween 20, SDS, Span 80, Triton, and EM90.

[0021] Optionally, the structure of the monodisperse magnetic bead chip includes: the first height ranges from 5 μm to 20 μm; the ratio of the width of the narrow channel area in the second direction to the first particle size ranges from 2 to 10; the width of the narrow channel area in the second direction ranges from 10 μm to 25 μm; the angle between the channel side wall of the bell-mouth area and the channel side wall of the narrow channel area ranges from 10 degrees to 20 degrees; the length of the bell-mouth area in the extension direction of the channel ranges from 50 μm to 500 μm; the ratio of the height difference between the bottom surface of the channel and the bottom surface of the storage cavity to the first height ranges from 4 to 15.

[0022] Optionally, the method for obtaining the monodisperse magnetic bead chip includes: establishing a model of the droplet particle size and the setting parameters of the monodisperse magnetic bead chip, the setting parameters of the monodisperse magnetic bead chip include one or more of the first height, the width of the narrow channel area in the second direction, the first width and the second width of the bell-mouth area, the angle at which the side wall of the bell-mouth area is inclined relative to the side wall of the narrow channel area, the length of the bell-mouth area in the extension direction of the channel, and the height difference between the bottom surface of the channel and the bottom surface of the storage cavity; according to the target droplet particle size, obtaining the setting parameter value of the monodisperse magnetic bead chip; according to the setting parameter value of the monodisperse magnetic bead chip, preparing the monodisperse magnetic bead chip.

[0023] Optionally, the structure of the monodisperse magnetic bead chip further includes: a droplet filtration structure located between the droplet storage chamber and the oil storage chamber, the droplet filtration structure having a plurality of gaps connecting the droplet storage chamber and the oil storage chamber, the width of each gap being smaller than the target droplet particle size; the width of each gap ranges from 10 μm to 40 μm.

[0024] Optionally, the droplet generation array is fan-shaped, and a plurality of the channels are arranged along the circumferential direction.

[0025] Optionally, the shell includes an upper shell and a lower shell, the upper shell and the lower shell are encapsulated at the edges, and the sample inlet and the sample outlet are located in the upper shell; the magnetic bead monodisperse chip also includes: a plurality of support columns located between the bottom surface of the storage cavity and the upper shell; the plurality of support columns are also located between the bottom surface of the oil storage cavity and the upper shell; the radius range of each of the support columns is 100μm to 500μm; the plurality of support columns are arranged in an array in a direction parallel to the bottom surface of the storage cavity, and the spacing between two adjacent support columns is in the range of 1mm to 2.5mm; the thickness range of the upper shell is 0.5mm to 2mm; the thickness range of the lower shell is 0.5mm to 2mm.

[0026] Compared with the existing technology, the technical solution of the embodiment of the present invention has the following beneficial effects:

[0027] In the magnetic bead monodisperse chip provided by the technical solution of the present invention, the droplet generation array includes a plurality of micro-droplet generation channels, the bottom surface of the channel is higher than the bottom surface of the storage cavity, so that a step is formed between the channel and the droplet storage cavity. After the magnetic bead suspension enters the droplet generation array, droplets are generated at the step due to the sudden change in surface tension; at the same time, the channel has a first height, which limits the ratio between the first height and the first particle size of the magnetic beads to be processed, so that only a single magnetic bead is allowed to pass through a single channel at a time, which is conducive to encapsulating a single magnetic bead in a single droplet to form micro-droplets. The magnetic beads are dispersed by the micro-droplets, which reduces the probability of the magnetic beads re-aggregating after dispersion, and is conducive to achieving monodisperse magnetic beads.

[0028] Furthermore, the droplet generation array is in a fan-shaped ring shape. The fan-shaped ring structure makes it more difficult for the generated micro-droplets to accumulate, which is beneficial to improving the uniformity of the particle size of the micro-droplets.

[0029] In the operating method of the magnetic bead monodisperse chip provided by the technical solution of the present invention, the droplet generation array includes a plurality of micro-droplet generation channels, the bottom surface of the channel is higher than the bottom surface of the storage cavity, so that a step is formed between the channel and the droplet storage cavity. After the magnetic bead suspension enters the droplet generation array, droplets are generated at the step due to the sudden change in surface tension; at the same time, the channel has a first height, which limits the ratio between the first height and the first particle size of the magnetic beads to be processed, so that only a single magnetic bead is allowed to pass through a single channel at a time, which is conducive to encapsulating a single magnetic bead in a single droplet to form micro-droplets. The magnetic beads are dispersed by the micro-droplets, which reduces the probability of the magnetic beads re-aggregating after dispersion, and is conducive to achieving monodisperse magnetic beads.

[0030] Furthermore, by obtaining the target magnetic bead concentration based on the target droplet particle size, a magnetic bead concentration that is conducive to achieving monodispersity of the magnetic beads can be obtained, thereby increasing the single-package ratio of the magnetic beads finally obtained.

[0031] Furthermore, the segmented suction method is conducive to improving the utilization rate of magnetic beads, achieving a magnetic bead utilization rate close to 100%. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the embodiments or the description of the prior art. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0033] 1 to 4 are schematic structural diagrams of a monodisperse magnetic bead chip according to an embodiment of the present invention;

[0034] 5 to 9 are schematic flow charts of an operating method of a monodisperse magnetic bead chip according to an embodiment of the present invention;

[0035] FIG10 is a schematic diagram of a segmented suction method in an operation method of a monodisperse magnetic bead chip according to an embodiment of the present invention;

[0036] 11 to 13 are schematic diagrams of magnetic bead droplets obtained in a method for operating a magnetic bead monodisperse chip according to an embodiment of the present invention;

[0037] FIG14 is a schematic structural diagram of a monodisperse magnetic bead chip according to another embodiment of the present invention. DETAILED DESCRIPTION

[0038] As described in the background art, the existing magnetic bead monodispersion effect is poor, and the existing magnetic bead monodispersion method needs to be further improved.

[0039] In order to solve the above problems, the present invention provides a magnetic bead monodisperse chip and operation method, in which a droplet generation array includes a plurality of micro-droplet generation channels, the bottom surface of the channel is higher than the bottom surface of the storage cavity, so that a step is formed between the channel and the droplet storage cavity. After the magnetic bead suspension enters the droplet generation array, droplets are generated at the step due to the sudden change in surface tension; at the same time, the channel has a first height, which limits the ratio between the first height and the first particle size of the magnetic beads to be processed, so that only a single magnetic bead is allowed to pass through a single channel at a time, which is conducive to encapsulating a single magnetic bead in a single droplet to form micro-droplets. The magnetic beads are dispersed by the micro-droplets, which reduces the probability of the magnetic beads reaggregating after dispersion, and is conducive to achieving monodisperse magnetic beads.

[0040] In order to make the above-mentioned objects, features and beneficial effects of the present invention more obvious and easy to understand, specific embodiments of the present invention are described in detail below with reference to the accompanying drawings.

[0041] 1 to 4 are schematic structural diagrams of a monodisperse magnetic bead chip according to an embodiment of the present invention.

[0042] Please refer to Figures 1 to 4. Figure 1 is a schematic diagram of the top view of the magnetic bead monodisperse chip omitting the upper shell. Figure 2 is a partial enlarged view of the droplet generation array in Figure 1. Figure 3 is a partial enlarged view of the dotted frame in Figure 2. Figure 4 is a schematic diagram of the cross-sectional structure along the DD1 direction in the dotted frame in Figure 2. The magnetic bead monodisperse chip includes: a shell, the shell is respectively provided with an inlet (not shown in the figure) and an outlet (not shown in the figure) communicating with the inside and outside of the shell, the inlet is used to inject a magnetic bead suspension into the shell, and the magnetic bead suspension includes a plurality of The processing magnetic beads have a first particle size; a droplet storage chamber 102 is located in the housing, the droplet storage chamber 102 has a storage chamber bottom surface 102d and a storage chamber sidewall 102c perpendicular to the storage chamber bottom surface 102d; a droplet generation array 103 is located in the housing, the droplet generation array 103 is also located between the droplet storage chamber 102 and the injection port, the droplet generation array 103 includes a plurality of micro-droplet generation channels, each of the channels includes a narrow channel area I and a channel connected to the narrow channel area I. The channel has a channel bottom surface 103d and a channel sidewall 103c perpendicular to the channel bottom surface 103d, the channel bottom surface 103d is higher than the storage chamber bottom surface 102d, the narrow channel area I is connected to the injection port, and the bell-mouth area II is connected to the droplet storage chamber 102. In a first direction X perpendicular to the channel bottom surface 103d, the channel has a first height h, and the ratio of the first height h to the first particle size ranges from 1.5 to 3. In a direction parallel to the channel, the channel has a first height h, and the ratio of the first height h to the first particle size ranges from 1.5 to 3. The bottom surface 103d of the channel is perpendicular to the second direction Y in the extension direction of the channel. The bell-mouth area II has a first width d1 adjacent to the narrow channel area I and a second width d2 adjacent to the droplet storage chamber 102, and the second width d2 is greater than the first width d1. The oil storage chamber 104 is located in the shell, and the oil storage chamber 104 is also located between the droplet storage chamber 102 and the sample outlet, and is communicated with the sample outlet for storing the oil-phase reagent flowing out of the droplet storage chamber 102.

[0043] Here, the droplet generation array 103 includes a plurality of micro-droplet generation channels, wherein the bottom surface 103d of the channel is higher than the bottom surface 102d of the storage chamber, so that a step is formed between the channel and the droplet storage chamber 102. After the magnetic bead suspension enters the droplet generation array 103, it is subjected to the action of the sudden change in surface tension at the step to generate droplets. The shape of the bell-mouth region II is conducive to improving the monodispersity between the droplets. In addition, the channel has a first height h, which defines the ratio between the first height h and the first particle size of the magnetic beads to be processed. This is conducive to allowing only a single magnetic bead to pass through a single channel at a time, and is conducive to encapsulating a single magnetic bead in a single droplet to form micro-droplets. The dispersion of the magnetic beads by micro-droplets reduces the probability of the magnetic beads reaggregating after dispersion, thereby achieving monodispersity of the magnetic beads.

[0044] In this embodiment, the housing includes an upper housing (not shown in the figure) and a lower housing 10. The upper housing and the lower housing 10 are sealed at the edges, and the sample inlet and the sample outlet are located in the upper housing.

[0045] The packaging method of the monodisperse magnetic bead chip can be one or more of thermal bonding, adhesive bonding, plasma bonding, and anodic bonding. Specifically, the position of the auxiliary sealing hole 105 is also shown in FIG1 .

[0046] In this embodiment, the droplet generation array 103 , the droplet storage chamber 102 , and the oil storage chamber 104 are all disposed on the lower housing 10 .

[0047] In this embodiment, the monodisperse magnetic bead chip further includes: an injection chamber 100 located in the shell, the injection chamber 100 is located between the injection port and the droplet generation array 103, and is interconnected with the injection port and the droplet generation array 103; an oil drainage chamber 101 located in the shell, the oil drainage chamber 101 is located between the sample outlet and the oil storage chamber 104, and is interconnected with the sample outlet and the oil storage chamber 104.

[0048] In this embodiment, the structure of the monodisperse magnetic bead chip further includes a droplet filtration structure 106 located between the droplet storage chamber 102 and the oil storage chamber 104. The droplet filtration structure 106 has a plurality of gaps (not shown) connecting the droplet storage chamber 102 and the oil storage chamber 104. The width of each gap is smaller than the target droplet size and ranges from 10 μm to 40 μm. The purpose of making each gap smaller than the target droplet size is to ensure that all droplets that meet the required size remain within the droplet storage chamber 102.

[0049] In this embodiment, each channel further includes an inlet region III, the ends of which are connected to the narrow channel region II and the injection port, respectively. The inlet region III has a third width adjacent to the narrow channel region II and a fourth width adjacent to the injection port, the fourth width being greater than the third width. The inlet region III has a trumpet-shaped structure, facilitating injection of samples into the droplet generation array.

[0050] In this embodiment, the droplet generation array is fan-shaped, and the plurality of channels are arranged along the circumference. The fan-shaped structure makes it less likely for the generated micro-droplets to accumulate, which helps to improve the uniformity of the micro-droplet particle size.

[0051] In this embodiment, the number of the plurality of channels includes one of 8, 16, 24, 32 and 48.

[0052] In this embodiment, the structure of the monodisperse magnetic bead chip further includes: the first height h ranges from 5 μm to 20 μm; the ratio of the width of the narrow channel region I in the second direction Y to the first particle size ranges from 2 to 10; the width of the narrow channel region I in the second direction Y ranges from 10 μm to 25 μm; the angle α between the channel sidewall 103c of the bell-mouth region II and the channel sidewall 103c of the narrow channel region I ranges from 10 degrees to 20 degrees; the length L of the bell-mouth region II in the direction of extension of the channel ranges from 50 μm to 500 μm; and the ratio of the height difference H between the channel bottom surface 103d and the storage chamber bottom surface 102d to the first height h ranges from 4 to 15. By adjusting the above-mentioned setting parameters of the monodisperse magnetic bead chip, a reasonable droplet size can be obtained.

[0053] In this embodiment, the monodisperse magnetic bead chip further includes: a plurality of support pillars 107 located between the bottom surface 102d of the storage cavity and the upper housing. The plurality of support pillars 107 are used to prevent the monodisperse magnetic bead chip structure from collapsing.

[0054] In this embodiment, the plurality of support columns 107 are also located between the bottom surface of the oil storage cavity 104 and the upper shell. In another embodiment, the oil storage cavity is smaller and the plurality of support columns may not be provided between the bottom surface of the oil storage cavity and the upper shell.

[0055] In this embodiment, the radius of each support column 107 ranges from 100 μm to 500 μm; the support columns 107 are arranged in an array in a direction parallel to the bottom surface 102d of the storage cavity, and the spacing between two adjacent support columns 107 ranges from 1 mm to 2.5 mm; the thickness of the upper shell ranges from 0.5 mm to 2 mm; and the thickness of the lower shell ranges from 0.5 mm to 2 mm.

[0056] In this embodiment, the material of the monodisperse magnetic bead chip includes one or more of glass, silicon wafer and polymer material; the polymer material includes one or more of polydimethylsiloxane, polyurethane, epoxy resin, polymethyl methacrylate, polycarbonate, cycloolefin copolymer, polystyrene, polyethylene, and fluoroplastic.

[0057] It should be noted that there is no limitation on the shape of the droplet storage chamber 102. In this embodiment, the droplet storage chamber 102 is fan-shaped; in another embodiment, the droplet storage chamber 102 may be rectangular or in other shapes.

[0058] 5 to 9 are schematic flow charts of an operating method of a magnetic bead monodisperse chip according to an embodiment of the present invention.

[0059] Accordingly, an embodiment of the present invention further provides an operating method using the above-mentioned magnetic bead monodisperse chip, as shown in FIG5 , comprising the following steps:

[0060] Step S301, providing a monodisperse magnetic bead chip;

[0061] Step S302, providing a magnetic bead suspension, wherein the magnetic bead suspension includes a plurality of magnetic beads to be processed;

[0062] Step S303, injecting the oil phase reagent into the magnetic bead monodisperse chip through the injection port until no gas remains in the magnetic bead monodisperse chip;

[0063] Step S304: After injecting the oil phase reagent, inject the magnetic bead suspension into the magnetic bead monodisperse chip.

[0064] The following is a detailed description with reference to the accompanying drawings.

[0065] Please continue to refer to Figures 1 to 4, which provide a monodisperse magnetic bead chip.

[0066] The magnetic bead monodisperse chip includes: a shell, the shell is respectively provided with an injection port (not shown in the figure) and an outlet port (not shown in the figure) communicating with the inside and outside of the shell, the injection port is used to inject a magnetic bead suspension into the shell, the magnetic bead suspension includes a plurality of magnetic beads to be processed, and the magnetic beads to be processed have a first particle size; a droplet storage chamber 102 located in the shell, the droplet storage chamber 102 having a storage chamber bottom surface 102d and a storage chamber side wall 102c perpendicular to the storage chamber bottom surface 102d; a droplet generation array 103 located in the shell, the droplet generation array 103 is also located between the droplet storage chamber 102 and the injection port, the droplet generation array 103 includes a plurality of micro-droplet generation channels, each of the channels includes a narrow channel area I and a bell-mouth area II connected to the narrow channel area I, the channel has a channel bottom surface 103d and a channel side wall 103c perpendicular to the channel bottom surface 103d, The channel bottom surface 103d is higher than the storage chamber bottom surface 102d. The narrow channel region I is connected to the sample inlet, and the bell-mouth region II is connected to the droplet storage chamber 102. In a first direction X perpendicular to the channel bottom surface 103d, the channel has a first height h, and the ratio of the first height h to the first particle size ranges from 1.5 to 3. In a second direction Y parallel to the channel bottom surface 103d and perpendicular to the extension direction of the channel, the bell-mouth region II has a first width d1 adjacent to the narrow channel region I and a second width d2 adjacent to the droplet storage chamber 102, wherein the second width d2 is greater than the first width d1. An oil storage chamber 104 is located within the housing. The oil storage chamber 104 is also located between the droplet storage chamber 102 and the sample outlet and is interconnected with the sample outlet, and is used to store the oil-phase reagent flowing out of the droplet storage chamber 102.

[0067] In this embodiment, the first height h ranges from 5 μm to 20 μm; the ratio of the width of the narrow channel area I in the second direction Y to the first particle size ranges from 2 to 10; the width of the narrow channel area I in the second direction Y ranges from 10 μm to 25 μm; the angle α between the channel side wall 103c of the bell-mouth area II and the channel side wall 103c of the narrow channel area I ranges from 10 degrees to 20 degrees; the length L of the bell-mouth area II in the extension direction of the channel ranges from 50 μm to 500 μm; the ratio of the height difference H between the channel bottom surface 103d and the storage cavity bottom surface 102d to the first height h ranges from 4 to 15.

[0068] In this embodiment, the structure of the monodisperse magnetic bead chip further includes: a droplet filtration structure 106 located between the droplet storage chamber 102 and the oil storage chamber 104, wherein the droplet filtration structure 106 has a plurality of gaps (not shown in the figure) connecting the droplet storage chamber 102 and the oil storage chamber 104, and the width of each of the through holes is smaller than the target droplet particle size; the width of each of the gaps ranges from 10 μm to 40 μm.

[0069] It should be noted that the gap has two opposite side walls that are perpendicular to the storage cavity bottom surface 102d, and the width refers to the distance between the two side walls.

[0070] In this embodiment, the droplet generation array is fan-shaped, and the plurality of channels are arranged along the circumferential direction.

[0071] In this embodiment, the housing includes an upper housing (not shown in the figure) and a lower housing 10. The upper housing and the lower housing 10 are sealed at the edges, and the sample inlet and the sample outlet are located in the upper housing.

[0072] In this embodiment, the magnetic bead monodisperse chip also includes: a plurality of support columns 107 located between the bottom surface 102d of the storage cavity and the upper shell; the plurality of support columns 107 are also located between the bottom surface of the oil storage cavity 104 and the upper shell; the radius of each support column 107 ranges from 100 μm to 500 μm; the plurality of support columns 107 are arranged in an array in a direction parallel to the bottom surface 102d of the storage cavity, and the spacing between two adjacent support columns 107 ranges from 1 mm to 2.5 mm; the thickness of the upper shell ranges from 0.5 mm to 2 mm; the thickness of the lower shell ranges from 0.5 mm to 2 mm.

[0073] In this embodiment, the method for obtaining the monodisperse magnetic bead chip is shown in FIG6 , and includes the following steps:

[0074] Step S3011, establishing a model of droplet particle size and setting parameters of the monodisperse magnetic bead chip, wherein the setting parameters of the monodisperse magnetic bead chip include one or more of the first height, the width of the narrow channel region in the second direction, the first width and the second width of the bell-mouth region, the angle at which the sidewall of the bell-mouth region is inclined relative to the sidewall of the narrow channel region, the length of the bell-mouth region in the extension direction of the channel, and the height difference between the bottom surface of the channel and the bottom surface of the storage chamber;

[0075] Step S3012, obtaining the setting parameter values ​​of the magnetic bead monodisperse chip according to the target droplet particle size;

[0076] Step S3013: setting parameter values ​​according to the monodisperse magnetic bead chip to prepare the monodisperse magnetic bead chip.

[0077] Continuing to refer to FIG. 5 , a magnetic bead suspension is provided, wherein the magnetic bead suspension includes a plurality of magnetic beads to be processed.

[0078] In this embodiment, the method for obtaining the magnetic bead suspension is shown in FIG7 , and includes the following steps:

[0079] Step S3021, obtaining a target magnetic bead concentration according to the target droplet size;

[0080] Step S3022: preparing a magnetic bead suspension having the target magnetic bead concentration.

[0081] In this embodiment, the method for obtaining the target magnetic bead concentration according to the target droplet particle size is shown in FIG8 , and includes the following steps:

[0082] Step S30211, obtaining the target droplet size D1;

[0083] Step S30212, according to the target droplet size D1, obtaining the boundary particle size D2 of the magnetic bead suspension to be prepared, D2>D1 / 90%;

[0084] Step S30212, based on the relationship between the magnetic bead concentration C in the magnetic bead suspension and the boundary particle size D2 and the boundary particle size D2, and obtain the target magnetic bead concentration C of the magnetic bead suspension.

[0085] Based on practical experience, controlling the droplet size to less than 90% of the boundary particle size is beneficial for achieving 100% single-bead encapsulation. This allows for a magnetic bead concentration that is conducive to achieving monodispersity and increases the final single-bead encapsulation ratio. The single-bead encapsulation ratio refers to the ratio of the number of magnetic beads encapsulated in a single droplet to the total number of magnetic beads.

[0086] In this embodiment, the method for preparing a magnetic bead suspension having the target magnetic bead concentration further includes: obtaining an initial suspension containing the plurality of magnetic beads to be processed; adding a surfactant to the initial suspension, resuspending the initial suspension, and obtaining the suspension.

[0087] In this embodiment, the resuspension treatment method includes: one or more of vortexing, stirring, and shaking; the surfactant includes one or more of Tween 20 (polysorbate 20), SDS (Sodium Dodecyl Sulfate), Span 80 (Span-80), Triton (Span-80), and EM90.

[0088] In this embodiment, the method of injecting the magnetic bead suspension into the magnetic bead monodisperse chip is shown in FIG9 , and includes the following steps:

[0089] Step S3041, pre-encapsulating the magnetic bead suspension to be processed in a hose using a segmented suction method, wherein the segmented suction method includes causing the hose to suck in at least a first section of an oil phase reagent, and then sucking in the magnetic bead suspension to be processed after sucking in the first section of the oil phase reagent;

[0090] Step S3042, air-tightly connecting the suction port of the hose to the sampling port of the monodisperse magnetic bead chip, and ensuring that there are no bubbles at the connection;

[0091] Step S3043: After the airtight connection, the magnetic bead suspension to be processed and the first oil phase reagent in the hose are injected into the magnetic bead monodisperse chip.

[0092] FIG. 10 is a schematic diagram of a segmented suction method in an operation method of a magnetic bead monodisperse chip according to an embodiment of the present invention.

[0093] Please continue to refer to Figure 9 and Figure 10. A segmented suction method is used to pre-encapsulate the magnetic bead suspension 200 to be treated in the hose 20. The segmented suction method includes allowing the hose 20 to suck in at least the first section of the oil phase reagent 201, and after sucking in the first section of the oil phase reagent 201, sucking in the magnetic bead suspension 200 to be treated.

[0094] Specifically, the suction operation can be completed with the aid of a syringe pump or a pressure pump.

[0095] In this embodiment, the segmented aspiration method further includes: after aspirating the magnetic bead suspension 200 to be processed, aspirating the second-stage oil phase reagent 202 .

[0096] In this embodiment, the hose 20 may be made of polytetrafluoroethylene (PTFE) or other materials.

[0097] 9 and 10 , the suction port of the hose 20 is airtightly connected to the injection port of the magnetic bead monodisperse chip, and no bubbles are present at the connection.

[0098] Here, ensuring that there are no bubbles at the joints is beneficial to improving the monodispersity of the magnetic beads and the uniformity of the microdroplet size.

[0099] Please continue to refer to FIG. 9 and FIG. 10 . After the airtight connection, the magnetic bead suspension to be processed and the first oil phase reagent 201 in the hose 20 are injected into the magnetic bead monodisperse chip.

[0100] Here, the segmented suction method allows the first section of oil phase reagent to continue to be injected into the magnetic bead monodisperse chip after the magnetic bead suspension is injected, so as to push all the magnetic bead suspension in the droplet generation array 103 into the droplet storage chamber 102, thereby improving the utilization rate of the magnetic beads and achieving a magnetic bead utilization rate close to 100%.

[0101] The effect of monodispersity of magnetic beads in this embodiment is described below.

[0102] 11 to 13 are schematic diagrams of magnetic bead droplets obtained in the magnetic bead monodisperse chip operation method according to an embodiment of the present invention.

[0103] Specifically, the following conditions are taken as an example:

[0104] The obtained magnetic bead monodisperse chip setting parameter values ​​include: the width of the narrow channel region I is 25 μm, the angle α is 19°, the length L of the bell-mouth region II is 150 μm, the first height difference h of the channel is 10 μm, and the height difference H is 90 μm;

[0105] The surfactant was monodispersed using Tween 20 at a concentration of 0.1%, and resuspended by vortexing;

[0106] The segmented suction method includes: allowing the hose 20 to suck in a first section of the oil phase reagent 201, then sucking in the magnetic bead suspension 200 to be processed, and then sucking in a second section of the oil phase reagent 202 after sucking in the magnetic bead suspension 200 to be processed;

[0107] In order to control the droplet size to be less than 51.8 μm, the volume concentration of the magnetic bead suspension was 10,000 beads / μl.

[0108] Please refer to Figures 11 to 13 for the monodisperse effects of magnetic beads obtained under the above conditions.

[0109] Please refer to Figures 11 to 13. Figure 11 is a schematic diagram of magnetic bead droplets, Figure 12 is a partial enlarged view of area A in Figure 11, and Figure 13 is a partial enlarged view of area B in Figure 11. The obtained magnetic bead droplets are as follows: the droplet particle size is about 48μm, CV=1.2%, the proportion of single-package magnetic beads in the field of view is close to 100%, and there is only one magnetic bead retained in the generation port channel, accounting for nearly 0% of the total amount of magnetic beads input.

[0110] FIG14 is a schematic structural diagram of a monodisperse magnetic bead chip according to another embodiment of the present invention.

[0111] The main differences between this embodiment and the previous embodiment are:

[0112] The droplet storage chamber has different shapes and the support columns are distributed at different positions.

[0113] In this embodiment, the droplet storage chamber is rectangular, and no support column is provided between the bottom surface of the oil storage chamber and the upper shell.

[0114] Please refer to Figure 14, which is a schematic diagram of the top structure of the magnetic bead monodisperse chip omitting the upper shell. The magnetic bead monodisperse chip includes: a shell, the shell includes an upper shell (not shown in the figure) and a lower shell 40, the upper shell is provided with an inlet (not shown in the figure) and an outlet (not shown in the figure) communicating with the inside and outside of the shell, the inlet is used to inject a magnetic bead suspension into the shell, the magnetic bead suspension contains a plurality of magnetic beads to be processed, and the magnetic beads to be processed have a first particle size; a droplet storage chamber 402 located in the shell, the droplet storage chamber 402 having a storage chamber bottom surface (not shown in the figure) and a storage chamber sidewall perpendicular to the storage chamber bottom surface (not shown in the figure); a droplet generation array 403 located in the shell, the droplet generation array 403 is also located between the droplet storage chamber 402 and the inlet, the droplet generation array 403 includes a plurality of micro-droplet generation channels, each of the channels includes a narrow channel area (not shown in the figure), a flared mouth connected to the narrow channel area The housing further comprises an oil storage chamber 404, wherein the oil storage chamber 404 is located between the droplet storage chamber 402 and the sample outlet. The oil storage chamber 404 is located between the droplet storage chamber 402 and the sample outlet. The oil storage chamber 404 is connected to the sample outlet, and the bell-mouth region is connected to the droplet storage chamber 402. In a first direction perpendicular to the channel bottom 403d, the channel has a first height, and the ratio of the first height to the first particle size is in a range of 1.5 to 3. In a second direction parallel to the channel bottom and perpendicular to the extension direction of the channel, the bell-mouth region has a first width adjacent to the narrow channel region and a second width adjacent to the droplet storage chamber 402, the second width being greater than the first width.

[0115] Specifically, the magnetic bead monodisperse chip also includes: an injection chamber 400 located in the shell, the injection chamber 400 is located between the injection port and the droplet generation array 403, and is interconnected with the injection port and the droplet generation array 403; an oil drainage chamber 401 located in the shell, the oil drainage chamber 401 is located between the sample outlet and the oil storage chamber 404, and is interconnected with the sample outlet and the oil storage chamber 404; a droplet filtering structure 406 located between the droplet storage chamber 402 and the oil storage chamber 404, the droplet filtering structure 406 has a plurality of gaps (not shown in the figure) connecting the droplet storage chamber 402 and the oil storage chamber 404, and the width of each gap is smaller than the target droplet particle size; and a plurality of support columns 407 located between the bottom surface of the storage chamber and the upper shell.

[0116] Although the present invention is disclosed as above, the present invention is not limited thereto. Any person skilled in the art can make various changes and modifications without departing from the spirit and scope of the present invention. Therefore, the scope of protection of the present invention should be based on the scope defined by the claims.

Claims

1. A magnetic bead monodisperse chip, characterized in that: include: A shell, wherein the shell is provided with an inlet and an outlet respectively connected to the inside and outside of the shell, the inlet is used to inject a magnetic bead suspension into the shell, the magnetic bead suspension includes a plurality of magnetic beads to be processed, and the magnetic beads to be processed have a first particle size; A liquid drop storage chamber located in the housing, the liquid drop storage chamber having a storage chamber bottom surface and a storage chamber side wall perpendicular to the storage chamber bottom surface; A droplet generation array located in the housing, the droplet generation array is also located between the droplet storage chamber and the injection port, the droplet generation array includes a plurality of micro-droplet generation channels, each of the channels includes a narrow channel area and a bell-mouth area connected to the narrow channel area, the channel has a channel bottom surface and a channel sidewall perpendicular to the channel bottom surface, the channel bottom surface is higher than the storage chamber bottom surface, the narrow channel area is connected to the injection port, the bell-mouth area is connected to the droplet storage chamber, in a first direction perpendicular to the channel bottom surface, the channel has a first height, the ratio of the first height to the first particle size ranges from 1.5 to 3, in a second direction parallel to the channel bottom surface and perpendicular to the extension direction of the channel, the bell-mouth area has a first width adjacent to the narrow channel area and a second width adjacent to the droplet storage chamber, the second width is greater than the first width; An oil storage chamber is located in the shell, and the oil storage chamber is also located between the liquid drop storage chamber and the sample outlet, and is interconnected with the sample outlet, and is used to store the oil phase reagent flowing out of the liquid drop storage chamber.

2. The monodisperse magnetic bead chip according to claim 1, characterized in that: The structure of the magnetic bead monodisperse chip also includes: a droplet filtration structure located between the droplet storage chamber and the oil storage chamber, the droplet filtration structure having a plurality of gaps connecting the droplet storage chamber and the oil storage chamber, the width of each gap being smaller than the target droplet particle size; the width of each gap ranges from 10 μm to 40 μm.

3. The monodisperse magnetic bead chip according to claim 1, characterized in that: Each of the channels also includes an inlet area, and both ends of the inlet area are respectively connected to the narrow channel area and the injection port; the inlet area has a third width adjacent to the narrow channel area and a fourth width adjacent to the injection port, and the fourth width is greater than the third width.

4. The monodisperse magnetic bead chip according to claim 1, characterized in that: The droplet generation array is in a fan-shaped ring shape, and a plurality of the channels are arranged along the circumferential direction.

5. The monodisperse magnetic bead chip according to claim 1, characterized in that: The number of some of the channels includes one of 8, 16, 24, 32 and 48.

6. The monodisperse magnetic bead chip according to claim 1, characterized in that: The structure of the monodisperse magnetic bead chip also includes: the first height ranges from 5μm to 20μm; the ratio of the width of the narrow channel area in the second direction to the first particle size ranges from 2 to 10; the width of the narrow channel area in the second direction ranges from 10μm to 25μm; the angle between the channel side wall of the bell-mouth area and the channel side wall of the narrow channel area ranges from 10 degrees to 20 degrees; the length of the bell-mouth area in the extension direction of the channel ranges from 50μm to 500μm; the ratio of the height difference between the bottom surface of the channel and the bottom surface of the storage cavity to the first height ranges from 4 to 15.

7. The monodisperse magnetic bead chip according to claim 1, characterized in that: The shell includes an upper shell and a lower shell, the upper shell and the lower shell are encapsulated at the edge, and the sample inlet and the sample outlet are located in the upper shell; the magnetic bead monodisperse chip also includes: a plurality of support columns located between the bottom surface of the storage cavity and the upper shell; the plurality of support columns are also located between the bottom surface of the oil storage cavity and the upper shell; the radius of each support column ranges from 100μm to 500μm; the plurality of support columns are arranged in an array in a direction parallel to the bottom surface of the storage cavity, and the spacing between two adjacent support columns ranges from 1mm to 2.5mm; the thickness of the upper shell ranges from 0.5mm to 2mm; the thickness of the lower shell ranges from 0.5mm to 2mm.

8. The monodisperse magnetic bead chip according to claim 1, characterized in that: The material of the magnetic bead monodisperse chip includes one or more of glass, silicon wafer and polymer material; the polymer material includes one or more of polydimethylsiloxane, polyurethane, epoxy resin, polymethyl methacrylate, polycarbonate, cycloolefin copolymer, polystyrene, polyethylene and fluoroplastic.

9. A method for operating a monodisperse magnetic bead chip, characterized in that: include: A magnetic bead monodisperse chip is provided, the magnetic bead monodisperse chip comprising: A shell, wherein the shell is provided with an inlet and an outlet respectively connected to the inside and outside of the shell, the inlet is used to inject a magnetic bead suspension into the shell, the magnetic bead suspension includes a plurality of magnetic beads to be processed, and the magnetic beads to be processed have a first particle size; A liquid drop storage chamber located in the housing, the liquid drop storage chamber having a storage chamber bottom surface and a storage chamber side wall perpendicular to the storage chamber bottom surface; A droplet generation array located in the housing, the droplet generation array is also located between the droplet storage chamber and the injection port, the droplet generation array includes a plurality of micro-droplet generation channels, each of the channels includes a narrow channel area and a bell-mouth area connected to the narrow channel area, the channel has a channel bottom surface and a channel sidewall perpendicular to the channel bottom surface, the channel bottom surface is higher than the storage chamber bottom surface, the narrow channel area is connected to the injection port, the bell-mouth area is connected to the droplet storage chamber, in a first direction perpendicular to the channel bottom surface, the channel has a first height, the ratio of the first height to the first particle size ranges from 1.5 to 3, in a second direction parallel to the channel bottom surface and perpendicular to the extension direction of the channel, the bell-mouth area has a first width adjacent to the narrow channel area and a second width adjacent to the droplet storage chamber, the second width is greater than the first width; An oil storage chamber located in the housing, the oil storage chamber is also located between the liquid drop storage chamber and the sample outlet, and is interconnected with the sample outlet, and is used to store the oil phase reagent flowing out of the liquid drop storage chamber; Providing the magnetic bead suspension; Injecting the oil phase reagent into the magnetic bead monodisperse chip through the injection port until no gas remains inside the magnetic bead monodisperse chip; After the oil phase reagent is injected, the magnetic bead suspension is injected into the magnetic bead monodisperse chip.

10. The method for operating the monodisperse magnetic bead chip according to claim 9, characterized in that: The method for injecting the magnetic bead suspension into the magnetic bead monodisperse chip comprises: pre-packaging the magnetic bead suspension to be treated in a hose by adopting a segmented suction method, wherein the segmented suction method comprises allowing the hose to at least suck in a first section of an oil phase reagent, and after sucking in the first section of an oil phase reagent, sucking in the magnetic bead suspension to be treated; air-tightly connecting the suction port end of the hose to the injection port of the magnetic bead monodisperse chip, and ensuring that there are no bubbles at the connection; after the air-tight connection, injecting the magnetic bead suspension to be treated and the first section of an oil phase reagent in the hose into the magnetic bead monodisperse chip.

11. The method for operating a monodisperse magnetic bead chip according to claim 10, characterized in that: The segmented suction method further comprises: after suctioning the magnetic bead suspension to be treated, suctioning a second stage oil phase reagent.

12. The method for operating a monodisperse magnetic bead chip according to claim 9, characterized in that: The method for obtaining a magnetic bead suspension comprises: obtaining a target magnetic bead concentration according to a target droplet diameter; and configuring a magnetic bead suspension having the target magnetic bead concentration.

13. The method for operating a monodisperse magnetic bead chip according to claim 12, characterized in that: According to the target droplet particle size, the method for obtaining the target magnetic bead concentration includes: obtaining the target droplet particle size D1; according to the target droplet particle size D1, obtaining the boundary particle size D2 of the magnetic bead suspension to be configured, D2>D1 / 90%; according to the relationship between the magnetic bead concentration C in the magnetic bead suspension and the boundary particle size D2 and the boundary particle diameter D2, to obtain the target magnetic bead concentration C of the magnetic bead suspension.

14. The method for operating a monodisperse magnetic bead chip according to claim 12, characterized in that: The method for configuring a magnetic bead suspension having the target magnetic bead concentration also includes: obtaining an initial suspension, wherein the initial suspension contains the plurality of magnetic beads to be processed; adding a surfactant to the initial suspension, resuspending the initial suspension, and obtaining the suspension; the resuspending method includes: one or more of vortexing, stirring, and shaking; the surfactant includes one or more of Tween 20, SDS, Span 80, Triton, and EM90.

15. The method for operating a monodisperse magnetic bead chip according to claim 9, characterized in that: The structure of the monodisperse magnetic bead chip includes: the first height ranges from 5μm to 20μm; the ratio of the width of the narrow channel area in the second direction to the first particle size ranges from 2 to 10; the width of the narrow channel area in the second direction ranges from 10μm to 25μm; the angle between the channel side wall of the bell-mouth area and the channel side wall of the narrow channel area ranges from 10 degrees to 20 degrees; the length of the bell-mouth area in the extension direction of the channel ranges from 50μm to 500μm; the ratio of the height difference between the bottom surface of the channel and the bottom surface of the storage cavity to the first height ranges from 4 to 15.

16. The method for operating a monodisperse magnetic bead chip according to claim 15, characterized in that: The method for obtaining the monodisperse magnetic bead chip comprises: establishing a model of droplet particle size and setting parameters of the monodisperse magnetic bead chip, wherein the setting parameters of the monodisperse magnetic bead chip comprise one or more of the first height, the width of the narrow channel area in the second direction, the first width and the second width of the bell-mouth area, the angle at which the side wall of the bell-mouth area is inclined relative to the side wall of the narrow channel area, the length of the bell-mouth area in the extension direction of the channel, and the height difference between the bottom surface of the channel and the bottom surface of the storage cavity; obtaining the setting parameter value of the monodisperse magnetic bead chip according to the target droplet particle size; and preparing the monodisperse magnetic bead chip according to the setting parameter value of the monodisperse magnetic bead chip.

17. The method for operating a monodisperse magnetic bead chip according to claim 9, characterized in that: The structure of the magnetic bead monodisperse chip also includes: a droplet filtration structure located between the droplet storage chamber and the oil storage chamber, the droplet filtration structure having a plurality of gaps connecting the droplet storage chamber and the oil storage chamber, the width of each gap being smaller than the target droplet particle size; the width of each gap ranges from 10 μm to 40 μm.

18. The method for operating a monodisperse magnetic bead chip according to claim 9, characterized in that: The droplet generation array is in a fan-shaped ring shape, and a plurality of the channels are arranged along the circumferential direction.

19. The method for operating a monodisperse magnetic bead chip according to claim 9, characterized in that: The shell includes an upper shell and a lower shell, the upper shell and the lower shell are encapsulated at the edge, and the sample inlet and the sample outlet are located in the upper shell; the magnetic bead monodisperse chip also includes: a plurality of support columns located between the bottom surface of the storage cavity and the upper shell; the plurality of support columns are also located between the bottom surface of the oil storage cavity and the upper shell; the radius of each support column ranges from 100μm to 500μm; the plurality of support columns are arranged in an array in a direction parallel to the bottom surface of the storage cavity, and the spacing between two adjacent support columns ranges from 1mm to 2.5mm; the thickness of the upper shell ranges from 0.5mm to 2mm; the thickness of the lower shell ranges from 0.5mm to 2mm.

Images