Maxwell coil in-hole type preparation method of microbead chip

Abstract

According to the Maxwell coil in-hole type preparation method of the microbead chip, based on the characteristic that a Maxwell coil can generate a stable parallel magnetic field within a certain range, magnetic beads are placed in the parallel magnetic field, and due to the action of the magnetic field, the magnetic beads are sequentially arranged in the direction of a magnetic induction line and are regularly arranged. The silicon-based chip is placed below a parallel magnetic field generated by the Maxwell coil, and when the chip moves left and right and the regularly arranged magnetic beads encounter the small holes, the magnetic beads enter the small holes under the action of gravity and vibration, so that the magnetic bead loading operation is completed. By the adoption of the Maxwell coil hole entering type, the hole entering rate of the microbeads reaches 90%-99%.

Description

Technical Field

[0001] The invention belongs to the technical field of chips, relates to the preparation of a microbead chip, and specifically relates to a Maxwell coil-in-hole preparation method of a microbead chip. Background Art

[0002] Biochip (biochip or bioarray) integrates the biochemical analysis process on the chip surface based on the principle of specific interactions between biological molecules, thereby achieving high-throughput rapid detection of DNA, RNA, peptides, proteins and other biological components. As a low-cost, high-throughput and high-accuracy detection method, chip detection has become a powerful detection tool for large-scale analysis, providing strong technical support for research in the fields of genetic research and analysis, personalized medicine and agricultural breeding.

[0003] The main methods of fixing materials in gene chip preparation include in-situ synthesis, spotting and microsphere loading, among which the microsphere loading method is the lowest cost and most efficient method for preparing high-density gene detection chips. The usual preparation method is to use a silicon substrate as the matrix, with hundreds of thousands, millions or even hundreds of millions of small holes on the surface. Each small hole is used to fix a magnetic bead microsphere, and the surface of the microsphere is covalently coupled with a nucleic acid probe for detection. The loading of microspheres on the silicon substrate is a key step in the preparation of gene chips. Usually, hundreds of thousands of microspheres modified with different nucleic acid probes are mixed evenly in proportion and then randomly loaded into the small holes of the silicon substrate.

[0004] Magnetic beads can be moved or transferred by external strong magnetic devices, such as magnets or electromagnets, but these conventional ways of moving magnetic beads are prone to the effect of external uneven magnetic forces on the magnetic beads. The collision of the magnetic beads themselves and the collision of the magnetic beads with the support will cause damage to the surface of the magnetic beads, especially the magnetic beads that have been surface-modified. For magnetic bead chips, how to ensure the loading rate of the magnetic beads and ensure that the magnetic beads are not damaged is one of the key difficulties in the production and manufacturing process of biochips.

[0005] Maxwell coil is a device used to generate a uniform magnetic field or a uniform gradient magnetic field. The uniform magnetic field can effectively prevent the magnetic beads from being affected by other external forces and reduce the mutual collision of the magnetic beads themselves, thereby improving the practicality of the microbead chip based on magnetic beads. Summary of the invention

[0006] The present invention is directed to the above problems and provides a microbead chip and a Maxwell coil hole-entry preparation method thereof, in order to solve the technical problems in the prior art of low hole-entry rate, poor stability and easy damage of modified magnetic beads in microbead chips based on magnetic beads.

[0007] The technical principle of the present invention is as follows: Maxwell coils are used to produce large-volume, almost constant (or constant gradient) magnetic fields. Based on the characteristic of Maxwell coils that they can generate stable parallel magnetic fields within a certain range, magnetic beads are placed in the parallel magnetic field. Due to the effect of the magnetic field, the magnetic beads will be arranged in sequence along the direction of the magnetic flux lines, presenting a regular arrangement. A silicon-based chip is placed under the parallel magnetic field generated by the Maxwell coil. When the chip moves left and right, the regularly arranged magnetic beads encounter a small hole and enter the small hole due to gravity and vibration, completing the magnetic bead loading operation.

[0008] The specific technical solutions of the present invention are as follows:

[0009] The first aspect of the present invention provides a Maxwell coil-in-hole preparation method for a microbead chip, comprising the following steps:

[0010] A. Magnetic microsphere loading

[0011] The magnetic beads are injected into a buffer solution containing a dispersant, and are dispersed by shaking to prepare a monodisperse magnetic beads solution with a concentration of 5 mg / mL to 50 mg / mL;

[0012] C. Microspheres entering the hole

[0013] A certain number of single crystal silicon plates with micropores are placed on the chip placement platform of a magnetic bead loading device equipped with a Maxwell coil, and the device is turned on. The Maxwell coil generates a parallel magnetic field within the range of the magnetic bead restraint device. After adding the magnetic bead microsphere solution, the magnetic bead microspheres are regularly arranged along the direction of the magnetic flux lines; the chip is shaken, and the magnetic bead microspheres enter the holes under the action of gravity and vibration, completing the magnetic bead loading operation; after loading is completed, the silicon plate is cleaned to remove excess magnetic bead microspheres and buffer solution on the surface to obtain a microbead chip.

[0014] The preferred technical scheme of these two steps is as follows:

[0015] 1. Step A:

[0016] (1) The magnetic microspheres are magnetic microspheres covalently bound to oligonucleotide chains, and the preparation method thereof comprises the following steps ac:

[0017] a. Magnetic beads surface modified with amino groups

[0018] Magnetic microspheres (CV<5.0%) with a particle size of 500nm to 5um (preferably 3um) are prepared into a 10mg / mL to 200mg / mL xylene suspension; a silanization agent (3-aminopropyltrimethoxysilane, 3-aminopropyltriethoxysilane) is added, and the volume concentration of the silanization agent in the mixed solution is less than 10% (preferably 0.1% to 2.5%), and the reaction is sufficient to modify the surface of the magnetic microspheres with amino groups;

[0019] b. Activate magnetic microspheres

[0020] The amino-modified magnetic microspheres obtained in step a are suspended in acetonitrile, with a mass concentration of 10 mg / mL to 200 mg / mL; 0.3 M diisopropylethylamine and 0.1 M cyanuric chloride are added, and the reaction is shaken; the excess reactants are removed by washing with acetonitrile, and the magnetic microspheres are suspended in sodium borate buffer (0.05 M to 2 M), and the pH value is adjusted to 7.5 to 8.5;

[0021] c. Covalently linked oligonucleotide chains to magnetic microspheres

[0022] Dissolve 100 nmol of the oligonucleotide chain dry powder to be connected in 2M sodium chloride solution, mix with the sodium borate suspension of magnetic beads obtained in step B, wherein the content of the magnetic beads is 10-100 mg, shake and react for 5-8 hours, centrifuge at 1000-3000 rpm, and retain the supernatant; wash and dry.

[0023] (2) The buffer containing a dispersant preferably contains a polymer, including but not limited to polyethylene glycol, polyvinyl alcohol, polyacrylamide, and mixtures thereof.

[0024] (3) After the magnetic beads are injected into the buffer solution containing the dispersant, the shaking dispersion conditions are 30 minutes and 2500 rpm.

[0025] Step B

[0026] (1) About single crystal silicon panels with micropores

[0027] The preparation method belongs to the prior art, and micropores of a specified depth are set on a single crystal silicon plate by etching, such as: evenly spin-coating a photoresist on the surface of the single crystal silicon plate to form a uniform thin film, using a photolithography machine to transfer the pattern on the mask plate to the photoresist, and using plasma etching technology to etch densely arranged small holes with a diameter similar to that of magnetic beads on the surface of the silicon plate in the hollowed-out part of the photoresist, and the depth of the small holes is about 1μm to 2μm, and the photoresist on the surface of the single crystal silicon plate is removed by a chemical solvent. The surface of the silicon plate is washed three times with a large amount of deionized water to obtain a silicon plate with regularly arranged small holes.

[0028] (2) About magnetic bead loading equipment

[0029] The magnetic bead loading device includes a device body, in which a chip placement platform, a magnetic bead restraint device and a Maxwell coil are arranged from bottom to top. The chip placement platform is provided with a plurality of chip placement slots and a chip fixing assembly; the magnetic bead restraint device is installed on the chip placement platform and is hollow inside; and the Maxwell coil is installed above the magnetic bead restraint device.

[0030] Specifically, four silicon wafer placement frames are arranged on the chip placement platform, and three chip placement slots are evenly arranged in each frame; that is, the number of 75mm*25mm chips that can be placed is 3, 9, and 12.

[0031] The chip fixing component is selected from a clamp or a vacuum adsorption mechanism; the clamp is C-shaped and buckled on both ends of the silicon wafer where the microbead holes are not set to fix the silicon plate. The vacuum adsorption mechanism includes a vacuum tube set on the bottom plate of the chip placement groove and a vacuum pumping device set outside the device, and the silicon plate is fixed by vacuum adsorption.

[0032] In addition, in order to realize the reciprocating motion of the chip placement platform, a chip pushing component is also provided in the device body, including a slider provided at the bottom of the chip placement platform and a slide rail and a motor provided on the device body. By setting the moving speed and moving range, the reciprocating motion of the silicon plate within the magnetic field range is realized.

[0033] Furthermore, the diameter of the Maxwell coil is 100-1000mm; the winding specification of the coil copper wire is 0.5-5mm; the central magnetic field size is 0.01-360Gs, and the magnetic field uniformity area is from 10*10*10mm to 100*100*100mm; the magnetic field uniformity error is less than 1%.

[0034] (3) About the operation of magnetic beads entering the hole

[0035] Place the silicon plates one by one on the chip placement platform, place the chip placement platform on a conveyor rack that matches the inner diameter of the coil, and transfer the chip placement platform to the central area of ​​the magnetic bead loading device; turn on the device switch, control the current at 5A, use a Tesla meter to confirm that the center is perpendicular to the coil and the magnetic field strength is 35-40mT, and the magnetic beads are arranged in sequence along the direction of the magnetic flux lines under the action of the magnetic field, showing a regular arrangement. Then click the transmission device of the chip placement platform, and the chip placement platform reciprocates in the coil at 100mm / s. After running for 10 minutes, stop the coil power supply and transmission device. Take out the chip placement platform, take out the silicon plates one by one, use buffer and water to wash, and obtain a group of silicon plates loaded with magnetic bead microspheres. The silicon plate obtained by this method can achieve a hole penetration rate of microspheres in the small holes on the silicon plate of 90% to 99%, and 12 silicon plates can be laid in a single time.

[0036] The second aspect of the present invention provides a microbead chip prepared by the method described in the first aspect.

[0037] The third aspect of the present invention provides a use of the microbead chip as described above in the preparation of a biochip.

[0038] Functions and Effects of the Invention

[0039] In terms of effect, the Maxwell coil hole-entry method of the present invention can achieve a hole-entry rate of microbeads of 90% to 99%.

[0040] Improve chip quality: The conventional method of using strong magnetic movement to insert magnetic beads into the wells will cause damage to the surface modification of the magnetic beads. The use of Maxwell coils can avoid damage to the surface of the magnetic beads caused by strong magnetic movement and improve the quality of the magnetic bead chip. BRIEF DESCRIPTION OF THE DRAWINGS

[0041] Figure 1 A schematic structural diagram of the magnetic bead loading device of the present invention is shown.

[0042] Figure 2 A partial structural schematic diagram of the magnetic bead loading device of the present invention is shown;

[0043] Figure 3 A schematic diagram of the Maxwell coil magnetic field is shown;

[0044] Figure 4 The image shows that when no magnetic field is applied, the magnetic beads are stacked on the surface of the silicon wafer, causing signal abnormality.

[0045] Figure 5 It shows that under the microscope, there is no stacking of magnetic beads on the surface of silicon wafer under the magnetic field of Maxwell coil;

[0046] Figure 6 It shows that under the fluorescence microscope, the microspheres are damaged by the common spreading method, and the bright beads show the phenomenon of hollow spheres (the gray scale of the inner circle is less than the gray scale of the outer circle);

[0047] Figure 7 It shows that under fluorescence microscope, the Maxwell coil laying method shows that the microspheres are not damaged and there is no hollow sphere phenomenon in the bright beads (inner circle grayscale > outer circle grayscale). DETAILED DESCRIPTION

[0048] The present invention is described in detail below in conjunction with the embodiments and the accompanying drawings. However, the following embodiments should not be considered as limiting the scope of the present invention.

[0049] The experimental methods in the following examples without specifying specific conditions are usually carried out under conventional conditions or under conditions recommended by the manufacturers.

[0050] 1. Preparation of magnetic microspheres with covalently bound oligonucleotide chains

[0051] a. Magnetic beads surface modified with amino groups

[0052] The raw material is solid magnetic microspheres with silanol groups on the surface, with a particle size of 3μm, which are prepared into a 100mg / mL xylene suspension. 3-aminopropyltrimethoxysilane, a silanization reagent that can amino-aminolate the surface, is added, and the concentration of the silanization reagent in the mixed solution is 1.0%. The mixed solution is shaken at room temperature for 1 hour. After the reaction is fully completed, the surface of the microspheres will be amino-grouped.

[0053] b. Activate magnetic microspheres

[0054] The microspheres with amino groups on the surface are suspended in acetonitrile, and the mass concentration of the microspheres is 100 mg / mL. Diisopropylethylamine and cyanuric chloride are added, and the concentration of diisopropylethylamine in the mixed solution is 0.3M, and the concentration of cyanuric chloride is 0.1M. The mixed solution is shaken at room temperature for 1 hour, and cyanuric chloride reacts with the amino groups on the surface of the microspheres to greatly enhance the activity of the surface groups of the microspheres. After washing with acetonitrile 3 to 5 times to remove excess reactants and products, rinse with 2M sodium borate buffer 3 to 5 times, and finally suspend the microspheres in sodium borate buffer, and add an appropriate amount of hydrochloric acid to adjust the pH value of the suspension to 7.5 to 8.5.

[0055] c. Covalently linked oligonucleotide chains to magnetic microspheres

[0056] Dissolve 100 nmol of the oligonucleotide chain powder to be connected in 2M sodium chloride solution (the length of the oligonucleotide chain is 15mer, and the terminal is modified with an amino group), mix it with an appropriate amount of sodium borate microsphere suspension, wherein the microsphere content is 50 mg, and shake the mixture at room temperature for 5 to 8 hours to allow the oligonucleotide chain to fully contact the microspheres and react with the active groups on the surface of the microspheres. After the connection reaction is completed, centrifuge the mixture at 1000 to 3000 rpm and retain the supernatant. Wash the microspheres with ultrapure water 3 to 5 times to remove excess reactants and products, dry them into dry powder form, and store them for use.

[0057] The microspheres coupled with the oligonucleotide chain were hybridized with the target (the target is complementary to the oligonucleotide chain and has a FAM fluorescent group at the end), incubated for 30 minutes at a temperature 20°C lower than the melting temperature of the corresponding oligonucleotide chain, and the fluorescence intensity was detected. The concentration of the microspheres during the detection was 2 mg / mL, and the excitation / emission filters used were 488 nm / 520 nm.

[0058] All fluorescence intensities mentioned in the present invention are measured under the above conditions. The conversion of fluorescence intensity and concentration uses a standard curve (obtained by measuring the fluorescence value of the prepared standard substance): C=8.797e-7*I-0.0055. Wherein C is the concentration of the fluorescent group, the unit is nmol / mL, and I is the fluorescence intensity. The concentration of the fluorescent group can be obtained from the fluorescence intensity, and the amount of microspheres is known, so the number of fluorescent groups per unit surface area can be calculated. Thus, the amount of oligonucleotide chains involved in the connection reaction and the connection efficiency of the microspheres and the oligonucleotide chains are calculated. After multiple experimental verifications, the connection efficiency can reach about 8000 to 10500 oligonucleotide chains / square micron (microsphere particle size 3um, multiple measurements of fluorescence intensity of 38956, 41256, 41235).

[0059] 2. Preparation method of Maxwell coil entry hole of microbead chip

[0060] A. Etching

[0061] The photoresist is evenly spin-coated onto the surface of the single crystal silicon plate to form a uniform thin film. The pattern on the mask is transferred to the photoresist using a photolithography machine. The plasma etching technology is used to etch densely arranged small holes with a diameter similar to that of the magnetic beads on the surface of the silicon plate in the hollowed-out part of the photoresist. The depth of the small holes is about 1 μm. The photoresist on the surface of the single crystal silicon plate is removed using a chemical solvent, and the surface of the silicon plate is cleaned 3 times with a large amount of deionized water.

[0062] B. Magnetic beads and microspheres Maxwell coil entry hole

[0063] according to Figure 1 and Figure 2 The magnetic bead loading device 100 includes a device body, in which a chip pushing component 1, a chip placement platform 2, a magnetic bead restraining device 3 and a Maxwell coil 4 are arranged from bottom to top. The chip pushing component 1 is used to drive the chip placement platform 2 to reciprocate; the chip placement platform 2 is provided with a plurality of chip placement slots and a chip fixing component 5; the magnetic bead restraining device 3 is rectangular, installed on the chip placement platform, and is hollow inside; the Maxwell coil 4 is installed above the magnetic bead restraining device.

[0064] Specifically, the chip pushing component 1 can be selected from the prior art, such as a micro linear slide structure, including a slider arranged at the bottom of the chip placement platform and a slide rail and a motor arranged on the device body. By setting the moving speed and moving range, the reciprocating motion of the silicon plate within the magnetic field range is achieved.

[0065] The chip placement platform 2 is provided with four silicon wafer placement frames 21, and each frame is evenly provided with three chip placement slots 21; that is, the number of chips of 75mm*25mm that can be placed is 3, 9, and 12.

[0066] There are two ways to fix the chip assembly 5, which can be selected from a clamp or a vacuum adsorption mechanism. Figure 2 The clamp is C-shaped and buckled on both ends of the silicon wafer where no microbead holes are set to fix the silicon plate. The vacuum adsorption mechanism includes a vacuum tube set on the bottom plate of the chip placement slot and a vacuum pumping device set outside the device, and the silicon plate is fixed by vacuum adsorption.

[0067] The diameter of the Maxwell coil 4 is 100-1000mm; the coil copper wire winding specification is 0.5-5mm; the central magnetic field size is 0.01-360Gs, the magnetic field uniformity area is from 10*10*10mm to 100*100*100mm; the magnetic field uniformity error is less than 1%. See the magnetic field schematic diagram Figure 3 .

[0068] In this embodiment, 12 silicon wafers are coated simultaneously to prepare microbead chips. The specific steps are as follows:

[0069] (1) A certain amount of monodisperse magnetic beads coupled with oligonucleotides was injected into a buffer containing a dispersant, and a monodisperse magnetic bead solution with a concentration of 5 mg / mL was prepared by oscillating and dispersing (30 min, 2500 rpm).

[0070] (2) Place the silicon plates one by one on the homemade chip placement platform, place the chip placement platform on a conveyor rack that matches the inner diameter of the coil, and transfer the chip placement platform to the central area of ​​the magnetic bead loading device; turn on the device switch, control the current at 5A, use a Tesla meter to confirm that the magnetic field strength of the center perpendicular to the coil is 35-40mT, and the magnetic beads are arranged in order along the direction of the magnetic flux lines under the action of the magnetic field, showing a regular arrangement. Then click the transmission device of the chip placement platform, and the chip placement platform reciprocates in the coil at 100mm / s. After running for 10 minutes, stop the coil power supply and transmission device. Take out the chip placement platform, take out the silicon plates one by one, use buffer and water to wash, and obtain a group of silicon plates loaded with magnetic bead microspheres. The silicon plate obtained by this method has a microsphere penetration rate in the small holes on the silicon plate of 90% to 99%, and a group of 12 silicon plates loaded with magnetic bead microspheres are obtained. The product results are summarized in Table 1.

[0071] Table 1 Summary of penetration rate of magnetic beads in 12 silicon plates

[0072] Silicon board number 1 2 3 4 5 6 7 8 9 10 11 12 Porosity 90.3％ 92.2％ 94.5％ 98.7％ 99.1％ 97.5％ 95.4％ 98.4％ 97.8％ 95.8％ 96.2％ 92.5％

[0073] 3. Analyze the chip using a microscope

[0074] The inlet chip was observed using a VHX-7000 microscope. Figure 4 and Figure 5As shown in the figure, the chip prepared by conventional hole-entry method has obvious magnetic beads accumulation on the surface, which is difficult to remove, affecting the detection and use of the hole-entry magnetic beads ( Figure 4 ); Maxwell coil hole entry method is adopted, the magnetic beads are evenly distributed on the chip surface, and there is no obstruction to the magnetic beads entering the hole ( Figure 5 ).

[0075] 4. Testing of chips prepared by the Maxwell coil hole method

[0076] 1. Add 0.01% to 0.5% Tween-20 and 25% to 45% formamide to the phosphate buffer solution to prepare a buffer solution; prepare the fluorescently modified oligonucleotide chain complementary to the covalently linked oligonucleotide chain and the buffer solution to prepare a decoding solution, dilute it to 0.05 to 0.1 nmol / mL with the decoding buffer solution, and take an appropriate amount of the decoding solution and add it to the sample area of ​​the chip. At room temperature, shake it slightly and react for 5 to 8 minutes. Rinse with the decoding buffer solution for 1 to 3 minutes to remove the excess decoding solution that does not participate in the reaction.

[0077] 2. Scan

[0078] The chip hybridized with the decoding sequence in the last step is dried at room temperature, and then placed in a chip scanner for scanning and photographing to obtain a picture corresponding to each excitation channel.

[0079] 3. Analyze the image

[0080] The chip sample position was scanned using a fluorescence scanner (GCS-100).

[0081] Conventional magnetic beads into the hole method, scanned image schematic diagram see Figure 6 , the bright beads have obvious hollowness.

[0082] Maxwell coil magnetic bead insertion method, see the scanned image schematic diagram Figure 7 , bright beads without hollow phenomenon.

[0083] Use hollowness software to calculate, the calculation results are as follows Table 2:

[0084] Table 2 Comparison of hollowness of two magnetic bead insertion methods

[0085]

[0086] The Maxwell coil hole entry method is adopted to effectively load the magnetic beads into the silicon wafer holes, and can effectively reduce the damage of the magnetic beads during the loading process, thereby improving the quality of the microbead chip.

[0087] The above shows and describes the basic principles, main features and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited to the above embodiments. The above embodiments and descriptions are only for explaining the principles of the present invention. The present invention may be subject to various changes and improvements without departing from the spirit and scope of the present invention. These changes and improvements fall within the scope of the present invention. The scope of protection of the present invention is defined by the attached claims and their equivalents.

Claims

1. A Maxwell coil-in-hole preparation method for a microbead chip, characterized in that: The steps include: A. Magnetic microsphere loading The magnetic beads are injected into a buffer solution containing a dispersant, and are dispersed by shaking to prepare a monodisperse magnetic beads solution with a concentration of 5 mg / mL to 50 mg / mL; B. Microspheres entering the hole A certain number of single crystal silicon plates with micropores are placed on the chip placement platform of a magnetic bead loading device equipped with a Maxwell coil, and the device is turned on. The Maxwell coil generates a parallel magnetic field within the range of the magnetic bead restraint device. After adding the magnetic bead microsphere solution, the magnetic bead microspheres are regularly arranged along the direction of the magnetic flux lines; the chip is shaken, and the magnetic bead microspheres enter the holes under the action of gravity and vibration, completing the magnetic bead loading operation; after loading is completed, the silicon plate is cleaned to remove excess magnetic bead microspheres and buffer solution on the surface to obtain a microbead chip.

2. The Maxwell coil-in-hole preparation method of a microbead chip according to claim 1, characterized in that: in, In step A, the dispersant is selected from any one or more of polyethylene glycol, polyvinyl alcohol, and polyacrylamide.

3. The Maxwell coil-in-hole preparation method of a microbead chip according to claim 1, characterized in that: in, In step A, the concentration of the monodisperse magnetic microsphere solution is 5 mg / mL.

4. The Maxwell coil-in-hole preparation method of a microbead chip according to claim 1, characterized in that: in, In step B, the depth of the microholes on the single crystal silicon plate is 1 μm to 2 μm.

5. The Maxwell coil-in-hole preparation method of a microbead chip according to claim 1, characterized in that: in, In step B, the magnetic bead loading device includes a device body, in which a chip placement platform, a magnetic bead restraining device and a Maxwell coil are arranged from bottom to top. The chip placement platform is provided with a plurality of chip placement slots and a chip fixing assembly; the magnetic bead restraining device is installed on the chip placement platform and is hollow inside; the Maxwell coil is installed above the magnetic bead restraining device.

6. The Maxwell coil-in-hole preparation method of a microbead chip according to claim 5, characterized in that: in, The chip placement platform is provided with 4 silicon wafer placement frames, and each frame is evenly provided with 3 chip placement slots; The chip fixing component is selected from a clamp or a vacuum adsorption mechanism; The device body is also provided with a chip pushing component, which includes a slider arranged at the bottom end of the chip placement platform and a slide rail and a motor arranged on the device body.

7. The Maxwell coil-in-hole preparation method of a microbead chip according to claim 1, characterized in that: in, In step B, the diameter of the Maxwell coil is 100-1000mm; the specification of the coil copper wire winding is 0.5-5mm; the central magnetic field size is 0.01-360Gs, and the magnetic field uniformity area is from 10*10*10mm to 100*100*100mm; the magnetic field uniformity error is less than 1%.

8. The Maxwell coil-in-hole preparation method of a microbead chip according to claim 7, characterized in that: in, The magnetic field strength at the center perpendicular to the coil is 35-40 mT, and the chip placement platform reciprocates in the coil at 100 mm / s.

9. A microbead chip, characterized in that: The method is prepared by any one of claims 1 to 8.

10. Use of the microbead chip according to claim 9 in preparing a biochip.

Images