Flexible Microbeam Force Sensor for Myocardial Tissue Based on Liquid Metal, Its Array and Preparation Method

Abstract

The present invention discloses a flexible microbeam force sensor for myocardial tissue based on liquid metal, an array thereof and a preparation method. The flexible microbeam force sensor for myocardial tissue includes a flexible microbeam, a microchannel and a cell culture area; a sensitive material is filled in the microchannel; a fiber scaffold formed by ordered fibers is arranged in the cell culture area, and myocardial cells are cultured in the cell culture area; the contraction of the myocardial cells causes the flexible microbeam to be deformed by force, and further causes the sensitive material in the microchannel to generate an electrical signal. The flexible microbeam force sensor has good biocompatibility and stretchability, can be adapted to the modulus of myocardial tissue through size design, and can be used for in-situ sensing of the contractile force of myocardial tissue. The preparation process of the sensor is simple, and arraying can be realized, which is used for high-throughput testing of the mechanical properties of myocardial tissue.

Description

Technical Field

[0001] The present invention belongs to the technical field of cell detection, and particularly relates to a flexible microbeam force sensor for myocardial tissue and a preparation method thereof. Background Art

[0002] Cardiovascular diseases (CVDs) are the world's leading killers. According to estimates by the World Health Organization (WHO), approximately 17.9 million people die from CVDs each year, accounting for 31% of the total global deaths. In addition, drug-induced cardiotoxicity has been the main reason for drug withdrawals and losses in the past few decades. On the one hand, drug-induced cardiotoxicity also threatens people's health and even lives. On the other hand, drug development is a long and low-success-rate process. It usually takes an average of 12 years and costs over $1 billion from preclinical testing to final FDA approval. However, once there is a case of sudden death caused by drug-induced cardiotoxicity, the drug will be immediately withdrawn by the FDA, resulting in huge economic losses and waste of resources. Establishing in vitro heart models for cardiovascular disease research and drug screening is of great significance for simulating the structure and function of the heart and its basic unit, cardiomyocytes. The heart is one of the core organs of the human body, responsible for pumping blood throughout the body through the blood vessels of the circulatory system. By regulating the movement of calcium ions inside and outside the cell, electrical excitation and mechanical contraction can be coupled together. Therefore, the force signal of the in vivo heart model is a crucial research parameter.

[0003] According to the unique mechanical properties of cardiomyocytes, many tools or methods have been developed to characterize the physiological parameters of cardiomyocytes. Currently, typical detection techniques include optical detection and indirect electrical detection. Direct optical detection methods include video analysis, traction force microscopy (TFM), calcium imaging, laser sensing, atomic force microscopy (AFM), and colorimetric sensing, etc.; indirect electrical detection methods detect the deformation of a flexible structure adhered to myocardial tissue, convert the corresponding deformation into an electrical signal, and calculate the contraction characteristics of myocardial tissue. Currently, this method is mainly used for detecting the contractile force of two-dimensional planar myocardial tissue, and the three-dimensional structural force detection method has always been a difficult point for HOC (Heart-On-Chip). Therefore, it is of great significance to establish a sensing function with high resolution, low hysteresis, long fatigue life, suitable for 3D myocardial models, enabling in-situ acquisition of mechanical parameters and facilitating integration with myocardial chips.

[0004] For myocardial tissue sensors, it is crucial to be able to adapt to the stent for in-situ detection of the contractile force signal of myocardial tissue and have a modulus adapted to the tissue. Currently, there is no sensor that can be used for in-situ detection of the force signal of myocardial tissue with fibers as the stent. Summary of the Invention

[0005] The object of the present invention is to overcome the deficiencies of the prior art, and provide a flexible microbeam force sensor for myocardial tissue based on liquid metal, its array and preparation method, thus solving the problems in the above-mentioned background art.

[0006] One of the technical solutions adopted by the present invention to solve its technical problems is:

[0007] A flexible microbeam force sensor for myocardial tissue, comprising a flexible microbeam, a microchannel and a cell culture area; the microchannel is filled with a sensitive material; a fiber scaffold formed by ordered fibers is provided in the cell culture area, and myocardial cells are cultured in the cell culture area; the contraction of the myocardial cells causes the flexible microbeam to be deformed by force, and further causes the sensitive material in the microchannel to generate an electrical signal.

[0008] Preferably, the microchannel is located between the flexible microbeam and the cell culture area.

[0009] Preferably, the flexible microbeam force sensor for myocardial tissue comprises a flexible substrate and a flexible encapsulation layer, the flexible substrate and the flexible encapsulation layer are bonded to form a flexible microbeam and a cell culture area capable of accommodating a fiber scaffold, and the microchannel is formed between the flexible substrate and the flexible encapsulation layer. For example, corresponding protrusions and depressions are provided on the flexible substrate, so that after being laminated and bonded with the flexible encapsulation layer, the flexible microbeam and the cell culture area are formed, and the microchannel is formed therebetween.

[0010] Preferably, the resistance of the sensitive material changes with the change of its structure; after the flexible microbeam is deformed by force, the microchannel also deforms, and the resistance value of the sensitive material in the microchannel changes, generating an electrical signal, so that the magnitude of the contraction force of the myocardial cells can be measured.

[0011] Preferably, the sensitive material is liquid metal, but not limited thereto, and other conductive flexible materials can also be used.

[0012] Preferably, the liquid metal includes gallium-indium-tin alloy liquid metal.

[0013] Preferably, the direction of the ordered fibers is perpendicular to the flexible microbeam. That is, the ordered fibers can induce the cells to grow along the direction perpendicular to the flexible microbeam, so that the cell contraction force can be maximally converted into the force that deforms the flexible microbeam, and further the test result is more accurate.

[0014] Preferably, the ordered fibers are prepared by roller spinning, and the fibers obtained thereby have a certain degree of order, which can make the myocardial cells grow directionally, so that the contraction force directions are consistent, and persuasive data can be obtained.

[0015] Preferably, it further comprises a flexible electrode, the flexible electrode is connected to the sensitive material, and the electrical signal is led out by connecting the flexible electrode with a lead wire.

[0016] Preferably, there are two flexible electrodes at each end of the sensitive material filled in the microchannel, and a four-wire resistance measurement mode is adopted to reduce the influence of the test of the electrode leads.

[0017] Preferably, the flexible electrode and the sensitive material are made of the same material, which makes the material unified and convenient for preparation. The lead wire is directly in contact with the flexible electrode, so as to lead out the resistance signal and connect to an external device to measure data.

[0018] Preferably, the thickness of the sensor is 0.1 - 1 mm; the side length of the cross-section of the flexible microbeam is 0.1 - 1 mm, and the length is 5 - 16 mm; the area of the cell culture area is 5 - 20 mm 2 ; the side length of the cross-section of the microchannel is 10 - 500 μm, and the side length of the electrodes at both ends is 0.1 - 1 mm.

[0019] Preferably, the material of the flexible substrate is PDMS, Ecoflex, hydrogel or other flexible materials.

[0020] Preferably, the material of the flexible encapsulation layer is PDMS, Ecoflex, hydrogel or other flexible materials.

[0021] The second technical solution adopted by the present invention to solve its technical problems is:

[0022] A flexible microbeam force sensor array for myocardial tissue, comprising a plurality of the above-mentioned flexible microbeam force sensors for myocardial tissue.

[0023] The third technical solution adopted by the present invention to solve its technical problems is:

[0024] A preparation method of a flexible microbeam force sensor for myocardial tissue, comprising the following steps:

[0025] 1) Prepare a mold, and use injection molding to demold and prepare a flexible substrate and a flexible encapsulation layer;

[0026] 2) Irreversibly bond the flexible substrate and the flexible encapsulation layer to form a flexible microbeam and a cell culture area capable of accommodating a fiber scaffold, and form a microchannel between the flexible substrate and the flexible encapsulation layer;

[0027] 3) Cover the only inlet of the microchannel with a sensitive material, and use a vacuum filling method to pour the sensitive material into the microchannel;

[0028] 4) Place the product prepared in 3) on a roller for electrospinning to prepare ordered fibers to form a fiber scaffold as the cell culture area.

[0029] Preferably, step 1) includes the following steps: preparing a mold by using a stereolithography 3D printer, machining, or other means, clamping and fixing the mold and the silicon wafer with a fixture, injecting the mixed raw materials of the flexible substrate and the flexible encapsulation layer such as polymers into the mold cavity by using a syringe, curing at a temperature of 80-90°C for 20-30 min, and demolding to obtain the flexible substrate and the flexible encapsulation layer.

[0030] Preferably, step 2) includes the following steps: treating the demolded flexible substrate and flexible encapsulation layer with oxygen plasma for 80-200 s, then aligning and bonding the two layers, placing the bonded device in an incubator at 80-120°C for 30-50 min under the pressing of an appropriate heavy object to seal the flexible substrate and the flexible encapsulation layer.

[0031] Preferably, step 3) includes the following steps:

[0032] ① Covering a water-soluble sealant at one open end of the microchannel, leaving only the other open end of the microchannel as the inlet for the sensitive material;

[0033] ② Taking a certain amount of sensitive material and covering it at the other open end of the microchannel;

[0034] ③ Placing it in a vacuum chamber for 20-30 min, opening the vent to restore the air pressure in the vacuum chamber, and standing for 10-15 min to completely fill the microchannel with the sensitive material;

[0035] ④ Removing the excess sensitive material;

[0036] ⑤ Immersing it in deionized water to remove the water-soluble sealant.

[0037] Preferably, step 4) includes the following steps: placing the product prepared in 3) on a roller, grounding the roller, preparing ordered fibers by electrospinning, and making the direction of the ordered fibers consistent with the rotation direction of the roller and the vertical direction of the flexible microbeam, that is, inducing the cells to grow along the direction perpendicular to the flexible microbeam, so that the cell contraction force can be maximally converted into the force that deforms the flexible microbeam, thereby making the test results more accurate.

[0038] The equipment, reagents, processes, parameters, etc. involved in the present invention are all conventional equipment, reagents, processes, parameters, etc. unless otherwise specified, and no embodiments will be given again.

[0039] All ranges listed in the present invention include all point values within the range.

[0040] Compared with the background technology, this technical solution has the following advantages:

[0041] 1. The present invention uses a flexible conductive material as a flexible sensitive material and an electrode material, and a flexible polymer as a substrate and a packaging layer to realize the preparation of a fully flexible microbeam sensor. It has excellent biocompatibility and tensile resistance, and can adjust the stiffness of the stent structure through size design to match the modulus of myocardial tissue, so that the myocardial tissue can obtain appropriate strain, and can be used for long-term real-time in-situ recording of mechanical signals of myocardial tissue such as in-situ sensing of myocardial tissue contractile force on a myocardial chip.

[0042] 2. The present invention adopts a drum electrospinning process to integrally manufacture an organ chip array with an integrated three-dimensional ordered fiber scaffold. Different from adherent topography induction, the myocardial tissue induced by ordered fibers has directivity and can greatly restore the in-vivo myocardial tissue structure, thus obtaining mechanical signals closer to those of in-vivo myocardial tissue. Different from the step-by-step manufacturing of the stent and the chip in the chip, by in-situ electrospinning on a PDMS film, it can be ensured that the ordered fiber scaffolds of each chip are prepared under the same environment, the same process parameters, and the same time, greatly improving the consistency and stability between chips, and at the same time avoiding the positioning problem of the stent in the chip.

[0043] 3. The present invention adopts a vacuum filling technology. Preparing a flexible polymer with an internal microchannel array in advance alleviates problems such as difficult positioning, low precision, and complex steps in layer-by-layer manufacturing of the substrate - electrode - insulating layer.

[0044] 4. The preparation process of the present invention is simple, can be arrayed, and is used for high-throughput testing of the mechanical properties of myocardial tissue. Description of the Drawings

[0045] Figure 1 is an exploded structural schematic diagram of the myocardial tissue flexible microbeam force sensor of Example 1.

[0046] Figure 2 is Figure 1 a side view of each layer structure of the myocardial tissue flexible microbeam force sensor.

[0047] Figure 3 is a structural schematic diagram of the myocardial tissue flexible microbeam force sensor of Example 1.

[0048] Figure 4 is is Figure 3 a top-down perspective view of.

[0049] Figure 5 (a) - (f) are schematic diagrams of the preparation process flow of the myocardial tissue flexible microbeam force sensor of Example 1.

[0050] Figure 6 is a structural schematic diagram of the myocardial tissue flexible microbeam force sensor array of Example 3.

[0051] Figure 7 It is a schematic diagram of the integration of the peripheral system of the flexible microbeam force sensor array of myocardial tissue in Example 3.

[0052] Figure 8 It is a schematic structural diagram of another array mode of the flexible microbeam force sensor of myocardial tissue in Example 4.

[0053] Figure 9 It is a performance test diagram of the flexible microbeam force sensor of myocardial tissue in Example 1.

[0054] Reference numerals: 1 - flexible substrate, 2 - sensitive layer formed by liquid metal filled in the microchannel, 3 - fiber scaffold formed by electrospun ordered fibers, 4 - flexible encapsulation layer, 5 - flexible electrode, 6 - flexible microbeam, 7 - microchannel, 8 - sensor frame, 9 - cell culture area, 10 - perfusion inlet, 11 - terminal, 12 - lead solder joint, 13 - platinum wire lead, 14 - perfusion outlet, 15 - high-precision digital multimeter, 16 - PC, 17 - cell suspension / culture medium, 18 - pressure regulator, 19 - air pressure source. Detailed implementation manners

[0055] The present invention will be further described below with reference to the drawings and embodiments.

[0056] In the description of the present invention, it should be understood that the orientation or positional relationships indicated by the terms "upper", "lower", "front", "rear", "left", "right", "horizontal", "vertical", "top", "bottom", "inner", "outer", etc. are based on the orientation or positional relationships shown in the three-dimensional view in the drawings, and are only for the convenience of describing the present invention and simplifying the description, rather than indicating or implying that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and thus should not be construed as a limitation of the present invention. In addition, the terms "first" and "second" are only used for descriptive purposes and cannot be construed as indicating or implying relative importance.

[0057] Example 1

[0058] As Figures 1 to 4 shown, a flexible microbeam force sensor of myocardial tissue in this embodiment Figure 1 is an exploded view of the structure, Figure 2 is Figure 1 a side view of Figure 3 is an isometric view, Figure 4 is a top view. In the figure, 1 is a flexible substrate made of PDMS containing microstructures, 2 is a sensitive layer formed by liquid metal with variable resistance filled in the microchannel, 3 is a fiber scaffold formed by PCL ordered fibers obtained by electrospinning, 4 is a flexible encapsulation layer made of PDMS, 5 is a flexible electrode made of liquid metal, 6 is a flexible microbeam, 7 is a microchannel, 8 is the frame of the sensor, and 9 is the cell culture area.

[0059] Bond the flexible substrate 1 with the preset flexible microbeam 6 structure and the preset cell culture area 9 structure and the flexible encapsulation layer 4 through oxygen plasma to form a microchannel 7 therebetween. The liquid metal, as the sensitive material, is located in the microchannel 7, that is, the liquid metal fills the microchannel 7 between the flexible substrate 1 and the flexible encapsulation layer 4; a fiber scaffold 3 is arranged in the cell culture area 9 between the flexible microbeam 6 and the outer frame 8 of the frame.

[0060] Estimate the magnitude of the contractile force generated by the myocardial tissue in the cell culture area 9. The deformation generated by the cell contraction on the flexible microbeam 6 needs to be within the range that the liquid metal can sense, so as to complete the size design of the flexible microbeam 6. For the size design of the cell culture area 9, on the premise of considering the above factors, it is also necessary to consider the corresponding strain range during the contraction process of the myocardial tissue. In this embodiment, the thickness of the sensor is 0.1 - 1 mm; the cross-sectional side length of the flexible microbeam is 0.1 - 1 mm, and the length is 5 - 16 mm; the area of the cell culture area is 5 - 20 mm 2 ; the cross-sectional side length of the microchannel is 10 - 500 μm, and the side lengths of the two end electrodes are 0.1 - 1 mm.

[0061] During the cell culture process, the cells contract. The size design of the sensor can meet the strain requirements of the cells without generating additional constraints; at the same time, the induction of the ordered fibers can make the cells grow orderly along the fiber direction, so as to obtain cardiomyocytes with a contractile force closer to that of the in vivo myocardial tissue. The microchannel 7 is located between the flexible microbeam 6 and the cell culture area 9. When the cardiomyocytes in the cell culture area 9 contract, it will drive the flexible microbeam 6 to deform, thereby changing the volume of the microchannel 7, and further causing the resistance value of the sensitive layer formed by the liquid metal in the microchannel 7 to change. By calibrating the relationship between the tissue change and the contractile force, the contractile force of the myocardium can be evaluated through the resistance value change obtained by the external device.

[0062] At the same time, several myocardial tissue flexible microbeam force sensors of this embodiment can also form an array, such as Figure 6 and Figure 7 , and the arrayed chip design can meet the high-throughput requirements.

[0063] A myocardial tissue flexible microbeam force sensor of this embodiment can be upgraded from two-dimensional culture to a dynamic three-dimensional culture chip, more closely simulating the cell growth environment, so as to test the mechanical properties closer to those of the in vivo myocardial tissue. The high-resolution flexible microbeam force sensor can obtain more accurate and real cell mechanical information. The dimensions of the microbeam, the culture area, and the microchannel can adjust the corresponding characteristics of the liquid metal sensitive layer by modifying the microchannel dimensions and the dimensions of the micro-protrusions of the mold. The process of vacuum filling the sensitive material can well adapt to different trajectory requirements, and the design is flexible.

[0064] Example 2

[0065] As Figure 5 shown, this embodiment also provides a preparation method for a flexible microbeam force sensor, including the following steps:

[0066] a) Use a Nanoscribe two-photon polymerization 3D printer. Immerse the mold in isopropyl alcohol for 8 - 10 hours to remove the photosensitive resin, and then rinse the mold with alcohol to remove the residual isopropyl alcohol on the mold surface.

[0067] b) Spray release agent on the mold and the silicon wafer respectively, bond them together, fix them with a clamp, and slowly inject PDMS (10:1) into the mold with a syringe, taking care not to leave any air bubbles.

[0068] c) Place the mold in an incubator at 80 °C for 30 minutes. After taking it out, demold the PDMS to obtain a PDMS film with a sensing structure (preset flexible microbeam structure, preset cell culture area structure) as the flexible substrate.

[0069] d) Bond a thin film on the PDMS film with the sensing structure through oxygen plasma as the flexible encapsulation layer to achieve the purpose of encapsulating and forming a microchannel.

[0070] e) Cover the opening at one end of the microchannel with liquid metal, place the device in a vacuum chamber for 30 minutes, take it out and remove the surface liquid metal to obtain the original device, and lead out the device signal with a platinum wire to obtain a myocardial tissue flexible microbeam force-electricity sensor.

[0071] f) Place the prepared sensor on a roller for electrospinning to form ordered fibers as the cell culture area.

[0072] Example 3

[0073] This embodiment provides a myocardial tissue flexible microbeam force sensor array, as Figure 6 and Figure 7 , which is composed of several myocardial tissue flexible microbeam force sensors combined. As Figure 6 shown, 10 is the perfusion inlet, 11 is the wiring terminal, 12 is the lead solder joint, 13 is the platinum wire lead, and 14 is the perfusion outlet. During cultivation, inject the cell suspension from the perfusion inlet. Wait for the cells to enter the fiber culture area, let it stand for 4 hours, and then pass the culture medium through the perfusion inlet, and the waste liquid flows out from the perfusion outlet. The platinum wire is connected to the electrode to lead out the resistance signal to the wiring terminal.

[0074] As Figure 7As shown, 15 is a precision digital multimeter, 16 is a computer PC, 17 is a cell suspension / nutrient solution, 18 is a pressure regulator, and 19 is a gas source. The perfusion rate is adjusted by regulating the air pressure, and the cell suspension / culture solution is perfused into the culture area. The precision digital multimeter is connected by a terminal to collect resistance data, and the data is exported to the PC side for data processing to obtain the specific parameters of the contractile force.

[0075] Example 4

[0076] As Figure 8 shown, another array property of the microbeam sensor is demonstrated. Only the microbeams are arrayed, which also falls within the scope of protection of the content of this invention patent.

[0077] As Figure 9 shown, the resolution characteristics of the myocardial tissue flexible microbeam force sensor in Example 1 under the action of the corresponding contractile force of the myocardial tissue are demonstrated, aiming to illustrate that this sensor can meet the test requirements of the contractile force of the myocardial tissue and does not limit the data test of the present invention.

[0078] The above is only a preferred embodiment of the present invention, and thus the scope of implementation of the present invention cannot be limited thereby. That is, equivalent changes and modifications made according to the scope of the present invention patent and the content of the specification should still fall within the scope covered by the present invention.

Claims

1. A flexible microbeam force sensor for myocardial tissue, characterized in that: It includes a flexible microbeam, a microchannel, and a cell culture area; a sensitive material is filled in the microchannel; a fiber scaffold formed by ordered fibers is provided in the cell culture area, and cardiomyocytes are cultured in the cell culture area; the contraction of the cardiomyocytes causes the flexible microbeam to be deformed by force, thereby causing the sensitive material in the microchannel to generate an electrical signal; The microchannel is located between the flexible microbeam and the cell culture area; a fiber scaffold is arranged in the cell culture area between the flexible microbeam and the outer frame of the frame.

2. The flexible microbeam force sensor for myocardial tissue according to claim 1, wherein: The cardiomyocyte tissue flexible microbeam force sensor includes a flexible substrate and a flexible encapsulation layer. The flexible substrate and the flexible encapsulation layer are bonded to form a flexible microbeam and a cell culture area capable of accommodating a fiber scaffold, and the microchannel is formed between the flexible substrate and the flexible encapsulation layer.

3. The flexible microbeam force sensor for myocardial tissue according to claim 1, wherein: The sensitive material is liquid metal.

4. The flexible microbeam force sensor for myocardial tissue according to claim 1, wherein: The direction of the ordered fibers is perpendicular to the flexible microbeam.

5. The flexible microbeam force sensor for myocardial tissue according to claim 1, wherein: It further includes a flexible electrode. The flexible electrode is connected to the sensitive material, and the electrical signal is led out by connecting the flexible electrode with a lead wire.

6. The flexible microbeam force sensor for myocardial tissue according to claim 1, characterized in that: The thickness of the sensor is 0.1 - 1 mm; the side length of the cross-section of the flexible microbeam is 0.1 - 1 mm, and the length is 5 - 16 mm; the area of the cell culture region is 5 - 20 mm 2 ; the side length of the cross-section of the microchannel is 10 - 500 μm, and the side length of the electrodes at both ends is 0.1 - 1 mm.

7. A flexible microbeam force sensor array for myocardial tissue, characterized in that: It includes the cardiomyocyte tissue flexible microbeam force sensor according to any one of claims 1 to 6.

8. A method for preparing the flexible microbeam force sensor for myocardial tissue according to any one of claims 1 to 6, characterized in that: It includes the following steps: 1) Prepare a mold, use injection molding, and demold to prepare a flexible substrate and a flexible encapsulation layer; 2) Irreversibly bond the flexible substrate and the flexible encapsulation layer to form a flexible microbeam and a cell culture area capable of accommodating a fiber scaffold, and form a microchannel between the flexible substrate and the flexible encapsulation layer; 3) Cover the only inlet of the microchannel with a sensitive material, and pour the sensitive material into the microchannel by means of vacuum filling; 4) Place the product prepared in 3) on a roller for electrospinning to prepare ordered fibers to form a fiber scaffold as the cell culture area.

9. The preparation method according to claim 8, characterized in that: The step 1) includes the following steps: Prepare a mold by means including a photocuring 3D printer and machining, clamp the mold and a silicon wafer with a fixture, inject the mixed raw materials of the flexible substrate and the flexible encapsulation layer into the mold cavity with a syringe, cure at a temperature of 80-90 °C for 20-30 min, and demold to obtain a flexible substrate and a flexible encapsulation layer; The step 2) includes the following steps: Treat the demolded flexible substrate and flexible encapsulation layer with oxygen plasma for 80-200 s, then align and bond the two layers, place the bonded device in an oven at 80-120 °C for 30-50 min under the pressure of an appropriate heavy object to seal the flexible substrate and the flexible encapsulation layer; The step 3) includes the following steps: ① Cover the opening at one end of the microchannel with a water-soluble sealant, and only leave the opening at the other end of the microchannel as the inlet for the sensitive material; ② Cover the opening at the other end of the microchannel with the sensitive material; ③ Place it in a vacuum chamber for 20-30 min, open the vent to restore the air pressure in the vacuum chamber, and let it stand for 10-15 min to completely fill the microchannel with the sensitive material; ④ Remove the excess sensitive material; ⑤ Immerse it in water to remove the water-soluble sealant; The step 4) includes the following steps: Place the product prepared in 3) on a roller, ground the roller, and electrospin to prepare ordered fibers. The direction of the ordered fibers is consistent with the rotation direction of the roller and the perpendicular direction of the flexible microbeam.

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