CN116121063B - Biochip for realizing magnetic field regulation and temperature monitoring and preparation method thereof - Google Patents

Abstract

The invention discloses a biochip for realizing magnetic field regulation and temperature monitoring and a preparation method thereof, comprising the following steps: a culture chip, an on-chip local magnetic field regulating device and an on-chip local temperature monitoring device; the on-chip local magnetic field regulating and controlling device is prepared by metal wires with submicron and micron dimensions, and the on-chip local temperature monitoring device is prepared by a thermocouple array with submicron dimensions; the culture chip comprises a substrate, a microscopic observation window is arranged on the substrate, an on-chip local magnetic field regulating device and an on-chip local temperature monitoring device are arranged in the microscopic observation window, a heat insulation layer is clamped between the on-chip local magnetic field regulating device and the on-chip local temperature monitoring device, an insulating layer is covered on the on-chip local temperature monitoring device, and a cell culture pond is arranged on the insulating layer. The method realizes the adjustability of the direction, intensity and gradient of the local magnetic field on the micrometer scale, can monitor the local temperature change at the same time to determine the cell metabolism change, and is used in biomedical fields such as the study of the magnetic induction performance of single cells or cell clusters.

Description

A biochip for realizing magnetic field regulation and temperature monitoring and its preparation method

technical field

The invention relates to the technical field of biochip research and development, in particular to a biochip for realizing magnetic field regulation and temperature monitoring and a preparation method thereof.

Background technique

The statements in this section merely provide background information related to the present invention and do not necessarily constitute prior art.

In the field of biological basic research, in the process of experimental research on the magnetic induction performance of some single cells or cell clusters, technologies or devices that can generate local micro-magnetic fields at the micron scale are needed.

Traditional magnetic field generators often use iron cores, coils, poles, etc. to form a closed magnetic circuit. The energized coil can generate a magnetic field, and the iron core surrounded by the coil can be magnetized under the action of the magnetic field of the external coil to increase the magnetic flux. When the magnitude and direction of the power supply current are controlled, the generated magnetic field will also change accordingly, thus providing a highly controllable and stable magnetic field. The magnetic field generated in this way is mostly a strong magnetic field, and the device occupies too much space, the control of direction and intensity is too complicated, and the magnetic field gradient is lacking. The local magnetic field formed is often in the range of centimeters or even larger, which cannot be adjusted accurately and quickly. The direction, strength, gradient and other properties of the magnetic field are not suitable for the research field of magnetic induction properties of single cells or a small number of cell clusters.

At present, the rare magnetic field chips are mainly processed by some hard magnetic materials: such as Nd-FeB, etc. to make permanent magnets external or integrated in the chip, or by adding some soft magnets such as nickel and iron powder inside the chip, which are easy to be magnetized. An external magnetic field is placed outside the chip to magnetize the chip, etc. This type of method satisfies the advantages of small size and easy integration inside the chip, but the adjustment accuracy and speed of customizing the strength and direction of the magnetic field need to be improved; more importantly, the current magnetic field chip does not have the ability to adjust the magnetic field at the millimeter scale. The function of realizing multiple magnetic fields within a single optical microscope field cannot simultaneously observe the difference in cell behavior in different magnetic fields, so it cannot be applied to biomedical research such as the study of the magnetic induction performance of single cells or cell clusters.

In addition, the behavior of cells corresponding to the magnetic field is often reflected in the metabolism. At the same time, the generation of the magnetic field of the chip is often accompanied by the generation of heat. Therefore, real-time temperature monitoring is also an essential function of the chip for the study of the magnetic induction performance of single cells or cell clusters. However, the existing chips The magnetic field generating device does not have the function of real-time temperature monitoring.

Contents of the invention

In order to solve the above problems, the present invention proposes a biochip and its preparation method for magnetic field regulation and temperature monitoring, which can realize the adjustment of the direction, intensity and gradient of the local magnetic field on the micron scale, and can also monitor the local temperature change at the same time. To clarify changes in cell metabolism, it is used in biomedical fields such as the study of magnetic induction properties of single cells or cell clusters.

In order to achieve the above object, the present invention adopts the following technical solutions:

In the first aspect, the present invention provides a biochip for magnetic field control and temperature monitoring, including: a culture chip, an on-chip local magnetic field control device, and an on-chip local temperature monitoring device;

The on-chip local magnetic field regulation device is made of sub-micron and micron-scale metal wires, and the on-chip local temperature monitoring device is made of sub-micron-scale thermocouple arrays;

The culture chip includes a base, the base is provided with a microscopic observation window, and an on-chip local magnetic field regulating device and an on-chip local temperature monitoring device are prepared in the microscopic observation window, with a heat insulating layer sandwiched between the two, and the local temperature monitoring on the chip The device is covered with an insulating layer, and a cell culture pool is arranged on the insulating layer.

As an optional embodiment, the substrate is a silicon wafer covered with silicon nitride layers on both sides.

As an optional implementation manner, the thickness of the silicon nitride layer is 20 μm-500 μm.

As an optional implementation manner, the thickness of the silicon wafer is 0.5mm.

As an optional implementation manner, both the heat insulating layer and the insulating layer are HfO ₂ insulating layers with a thickness of 5-10 nm.

As an optional implementation, the on-chip local magnetic field regulating device is used to generate a uniform magnetic field or a gradient magnetic field, and adjust the direction, magnitude and gradient of the magnetic field by changing the spatial position of the metal wire and the direction and magnitude of the current passing through the metal wire .

As an optional embodiment, the current of the metal wire is changed by changing the thickness of the metal wire and changing the voltage applied to the metal wire.

As an optional implementation, the generated magnetic field has a scale ranging from a submicron level to a millimeter level.

As an optional implementation manner, the magnetic field generated by the on-chip local magnetic field regulating device is a local constant magnetic field or a local alternating magnetic field.

As an optional implementation, the direction, field strength and gradient of the local steady-state magnetic field are respectively adjusted by changing the direction and magnitude of the metal wire current and the configuration of the metal wire.

As an alternative embodiment, the magnitude and frequency of the local alternating magnetic field are adjusted respectively by changing the magnitude and frequency of the metal wire current.

As an optional implementation manner, the metal wires are symmetrically distributed on the microscopic observation window, arranged in parallel at a predetermined distance, and do not touch each other.

As an optional implementation manner, the configurations of the metal wires include symmetrical double ring type, loop double ring type and parallel line type.

As an optional implementation, the thermocouple is a Pd-Cr thermocouple.

In a second aspect, the present invention provides a method for preparing a biochip for magnetic field regulation and temperature monitoring, including:

An on-chip local magnetic field control device is prepared from sub-micron and micron-scale metal wires;

An on-chip local temperature monitoring device is prepared from a submicron-scale thermocouple array;

A microscopic observation window is provided on the substrate, and an on-chip local magnetic field regulation device and an on-chip local temperature monitoring device are prepared in the microscopic observation window;

An insulating layer is sandwiched between the local magnetic field regulating device and the on-chip local temperature monitoring device;

An insulating layer is covered on the on-chip local temperature monitoring device;

A cell culture pool is arranged on the insulating layer.

Compared with prior art, the beneficial effect of the present invention is:

The present invention proposes a biochip that integrates magnetic field regulation and temperature monitoring at the micro-nano scale, including multiple sets of metal wire designs that generate local micro-magnetic fields. By changing the spatial position of the metal wires and the direction and size of the current passing through the metal wires, Realize the function of fine-tuning the direction, size and gradient of the magnetic field with high precision. It not only realizes the generation of micro-nano-scale micro-magnetic field, but also fine-tunes the direction, strength and gradient of the magnetic field. It also realizes the temperature control of single cells and the surrounding environment. Carry out real-time monitoring with high precision and high temporal and spatial resolution.

The invention reduces the spatial range of the adjustable magnetic field, can observe the behavior patterns of single cells/clusters under different magnetic field distributions in the same optical window, and can obtain single cells through in-situ high-temporal and high-precision thermocouple temperature monitoring /cluster responds to the physiological changes of the magnetic field, and is suitable for microfluidic chips in the study of single cell/cluster magnetic induction in the field of biomedicine.

The invention realizes the functions of local magnetic field generation, regulation and temperature field monitoring on the micro-nano scale, avoids cumbersome processes, reduces the cost and area of the magnetic field generation device, and can be widely used in the study of magnetic induction properties of single cells or cell clusters and other biomedical research.

Advantages of additional aspects of the invention will be set forth in the description which follows, and in part will be obvious from the description, or may be learned by practice of the invention.

Description of drawings

The accompanying drawings constituting a part of the present invention are used to provide a further understanding of the present invention, and the schematic embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute improper limitations to the present invention.

Fig. 1 is the top view of the biochip provided by Embodiment 1 of the present invention;

Fig. 2 is a side view of the biochip provided by Embodiment 1 of the present invention;

Fig. 3 is the finished product picture of the biochip provided by Embodiment 1 of the present invention;

Fig. 4 is a schematic diagram of the principle of micro-magnetic field distribution and gradient regulation of the parallel linear design provided by Embodiment 1 of the present invention;

Fig. 5 (a)-Fig. 5 (b) is the micro-magnetic field uniform distribution principle and the schematic diagram of field strength calculation of the annular design provided by embodiment 1 of the present invention;

Figure 6(a) is a schematic diagram of the loop double-ring micro-magnetic field and thermocouple distribution provided by Embodiment 1 of the present invention;

Figure 6(b)-Figure 6(c) is a schematic diagram of the principle of simultaneously constructing a variable-intensity uniform magnetic field and a blank magnetic field in the loop double-loop design provided by Embodiment 1 of the present invention;

Figure 7(a) is a schematic diagram of the symmetrical double-ring micro-magnetic field and thermocouple distribution provided by Embodiment 1 of the present invention;

Figure 7(b)-Figure 7(d) is a schematic diagram of the principle of simultaneously constructing a reverse, variable-intensity uniform magnetic field and a blank magnetic field in the symmetrical double-ring design provided by Embodiment 1 of the present invention;

Figure 8(a) is a schematic diagram of the distribution of parallel linear micro-magnetic fields and thermocouples provided in Example 1 of the present invention;

Figure 8(b)-Figure 8(c) is a schematic diagram of the principle of parallel line design provided by Embodiment 1 of the present invention to simultaneously construct a reverse, variable-intensity uniform magnetic field and a blank magnetic field;

Among them, 1. Substrate, 2. PDMS, 3. Cell culture pool, 4. Silicon nitride suspended platform, 5. HfO2 insulating layer, 6. Thermocouple, 7. Cr submicron strips, 8. Pd submicron strips , 9, magnetic field generating device, 10, Cr lead wire of thermocouple, 11, lead wire of magnetic field generating device, 12, Pd lead wire of thermocouple, 13, symmetrical double-ring micro-magnetic field device, 14, parallel linear micro-magnetic field device, 15, Loop double ring micro-magnetic field device.

Detailed ways

The present invention will be further described below in conjunction with the accompanying drawings and embodiments.

It should be noted that the following detailed description is exemplary and intended to provide further explanation of the present invention. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

It should be noted that the terminology used here is only for describing specific embodiments, and is not intended to limit exemplary embodiments according to the present invention. As used herein, unless the context clearly dictates otherwise, the singular is intended to include the plural, and it should also be understood that the terms "comprising" and "having" and any variations thereof are intended to cover a non-exclusive Comprising, for example, a process, method, system, product, or device comprising a series of steps or units is not necessarily limited to those steps or units explicitly listed, but may include steps or units not explicitly listed or for these processes, methods, Other steps or units inherent in a product or equipment.

In the case of no conflict, the embodiments and the features in the embodiments of the present invention can be combined with each other.

Example 1

As shown in Figures 1 to 3, this embodiment provides a biochip that integrates magnetic field regulation and temperature monitoring at the micro-nano scale, and is used for single-cell or cluster magnetic induction research in the biomedical field; specifically includes: micro-based Fluidic technology culture chip, on-chip local magnetic field control device and on-chip local temperature monitoring device;

The on-chip local magnetic field regulation device is made of sub-micron and micron-scale metal lines, and the on-chip local temperature monitoring device is made of sub-micron-scale thermocouple arrays;

The culture chip includes a base, the base is provided with a microscopic observation window, and an on-chip local magnetic field regulating device and an on-chip local temperature monitoring device are prepared in the microscopic observation window, with a heat insulating layer sandwiched between the two, and the local temperature monitoring on the chip The device is covered with an insulating layer, and a cell culture pool is arranged on the insulating layer.

As shown in Figure 1, the circle where the dotted line is located is the calibration line, and the dotted line is the functional area of magnetic field generation and temperature monitoring, which is used to generate local micro-magnetic fields and temperature monitoring. The number of devices in the calibration line is adjustable, and multiple biochips It can be arranged to form a matrix to achieve high-precision and large-scale adjustment of micro-magnetic field and temperature. As shown in Figure 2, the functional devices are prepared on the transparent microscopic observation window of the silicon nitride suspended platform, and work in the cell culture pool surrounded by PDMS.

In this embodiment, the substrate 1 is a silicon wafer coated with a silicon nitride layer on both sides.

As an optional implementation manner, the thickness of the silicon nitride layer is 20 μm-500 μm.

As an optional implementation manner, the thickness of the silicon wafer is 0.5 mm.

In this embodiment, several millimeter-scale silicon nitride suspended platforms 4 are etched on the substrate 1 as transparent microscopic observation windows for observing cell behavior; on the one hand, the silicon nitride suspended platforms 4 provide optical observation of cells The behavior of the window on the one hand reduces heat dissipation and improves the sensitivity of the temperature sensing element.

In this embodiment, an on-chip local magnetic field regulating device and an on-chip local temperature monitoring device for generating a micron-range magnetic field with controllable intensity, gradient and direction are prepared in the microscopic observation window, and an on-chip local magnetic field regulating device and an on-chip local temperature monitoring device are prepared. There is a thermal insulation layer in the middle of the monitoring device, and an insulating layer is covered above the local temperature monitoring device on the chip to prevent the interference of the device function in the culture medium environment and reduce the leakage of the device conductor. Cells prepared by PDMS are arranged above the insulating layer. Culture pool 3.

As an optional implementation mode, both the heat insulating layer and the insulating layer are made of HfO ₂ insulating layer 5, deposited by HfO ₂ molecules, with a thickness of 5-10 nm;

As a thermal insulation layer, under the condition of ensuring electrical insulation, the distance between the functional elements (magnetic field generating device and temperature monitoring device) and the cells is shortened as much as possible, so that the cells (clusters) to be tested are located in the center of the magnetic field as much as possible;

As an insulating layer, it can prevent the culture medium from interfering with the device function, avoid device conductor leakage, improve the temperature resolution of the thermocouple temperature measurement, and shorten the response time.

In this embodiment, the on-chip local magnetic field control device is made of sub-micron and micron-scale metal wires, including multiple sets of metal wire configuration designs that generate local magnetic fields, and are regularly distributed on the silicon nitride suspended platform, When the current passes through, the uniform magnetic field or gradient magnetic field required for various experiments is generated, and by changing the spatial position of the metal wire and the direction and magnitude of the current passing through the metal wire, high-precision fine-tuning of the direction, magnitude and gradient of the magnetic field is realized.

As an alternative embodiment, the current magnitude of the metal wire can be changed by changing the thickness of the metal wire, changing the voltage applied to the metal wire, and other methods.

As an optional implementation, the metal wires are stable and low-resistance metal conductive materials such as gold, platinum, palladium, chromium, etc.; as shown in Cr submicron strips 7 and Pd submicron strips 8 in FIG. 2 .

As an optional implementation, the metal wires are symmetrically distributed on the silicon nitride suspended platform, and the metal strips are arranged in parallel according to the approved distance without contacting each other, which avoids mutual interference of currents and facilitates the regulation of the magnetic field. .

As an optional implementation, the on-chip local magnetic field control device can realize the construction of two to multiple different magnetic field distributions within the millimeter range, and can generate different magnetic fields for different experimental requirements; wherein, the metal wires that generate the local magnetic field The configuration design includes but is not limited to symmetrical double ring type, loop double ring type, parallel line type, etc., which can realize different magnetic field distributions in a small area at the same time, which is helpful for experimental variable control and result comparison.

As an optional implementation manner, the local magnetic field is a local steady magnetic field or a local alternating magnetic field.

Furthermore, the direction, field strength and gradient of the local steady magnetic field are all adjustable and characterizable, which is realized by changing the direction, magnitude and configuration of the metal wire current respectively.

Furthermore, the amplitude and frequency of the local alternating magnetic field are both adjustable and characterizable, which is realized by changing the magnitude and frequency of the metal wire current.

As an optional implementation manner, the scale range of the local magnetic field is as small as a submicron level and as large as a millimeter level.

In this embodiment, the on-chip local temperature monitoring device is made of a submicron-scale thermocouple array, which is located on the upper layer of the magnetic field generating device, and can convert the temperature at the thermocouple into the voltage output between the metal strips, so as to achieve the measurement warm purpose.

As an optional implementation, the thermocouples 6 are distributed around the magnetic field generating device 9 to monitor the temperature changes of representative locations and cell metabolism.

As an optional implementation, the thermocouple 6 is a Pd-Cr thermocouple.

As an optional implementation, the temperature measurement accuracy of the thermocouple 6 is up to 20mK.

As an optional implementation manner, the thermocouple 6 has a high time resolution and can monitor the temperature change near the metal wire in real time.

In order to better calculate and control the local magnetic field adjustment of each micro-magnetic field configuration, this embodiment designs a simulation calculation software model of the magnetic field strength, direction, and gradient of the local magnetic field for each micro-magnetic field configuration, so as to regulate the local magnetic field according to actual requirements. Micro-magnetic fields, as shown in Fig. 4 and Fig. 5(a)-Fig. 5(b), are schematic diagrams of micro-magnetic field distribution and gradient control principles designed for parallel linear and circular types, respectively. Wherein, Fig. 4 shows that the distance between two parallel conductors is 20 μm, the line width is 10 μm, and when the current in the conductor is 10 mA, the magnetic field distribution on different heights h on the vertical section of the parallel conductors; Fig. 5 (a) - Fig. 5 In (b), at the distances of 1/4, 1/2, and 3/4 from the center point, the magnetic field strength increases to 4%, 24%, and 90% respectively, that is, the magnetic field distribution in the central area of the coil is relatively uniform, close to the wire The magnetic field gradient at different positions is adjustable.

Figure 6(a)-Figure 6(c), Figure 7(a)-Figure 7(d), Figure 8(a)-Figure 8(c) are three typical micro-magnetic field configurations and the multi- The schematic diagram of the magnetic field, taking the symmetrical double-ring design in Figure 7(a)-Figure 7(d) as an example, illustrates the principle and application of simultaneous realization of multiple magnetic fields.

In a study of the magnetic induction characteristics of cells, the behavior and physiological changes of the same kind of cells were explored under different magnetic field strengths, directions, and gradients. The above research requirements need to meet the following conditions: (1) In addition to direct observation of cell behavior, the chip should have sensors that can reflect changes in cell metabolism in real time; In the range of square millimeters), various magnetic field distributions can be realized simultaneously, the magnetic field can be adjusted in real time, and a blank magnetic field is used as a control group.

The symmetrical double-ring micro-magnetic field design shown in Figure 7(a)-Figure 7(d) can meet the above requirements:

(1) Figure 7(a) shows the design configuration and thermocouple distribution diagram of the symmetrical double-ring micro-magnetic field. Four thin-film thermocouples are prepared in four typical areas of the micro-magnetic field to monitor the temperature of cells in different areas. Changes in temperature reflect cell metabolism.

(2) Fig. 7(b)-Fig. 7(d) show the realization principle of various local magnetic field distributions under the combination of three directions of current. When the current direction is shown in Figure 7(b) and Figure 7(c), three different magnetic field regions can be realized at the same time, as shown in Figure 7(b), region 1 is a quasi-uniform magnetic field facing downward, and region 2 is a non-magnetic field area as a blank control group, and area 3 is a quasi-uniform magnetic field with an upward magnetic field direction, and its strength is weaker than that of area 1; when the current direction is opposite as shown in Figure 7 (d), then area 1-3 The distribution of the magnetic field will change, that is, the direction of the magnetic field is regulated by the direction of the current, the strength of the magnetic field is regulated by the magnitude of the current, and the gradient of the magnetic field is regulated by the direction and magnitude of the current.

Example 2

This embodiment proposes a preparation method of the aforementioned biochip for magnetic field regulation and temperature monitoring, including:

An on-chip local magnetic field control device is prepared from sub-micron and micron-scale metal wires;

An on-chip local temperature monitoring device is prepared from a submicron-scale thermocouple array;

A microscopic observation window is provided on the substrate, and an on-chip local magnetic field regulation device and an on-chip local temperature monitoring device are prepared in the microscopic observation window;

An insulating layer is sandwiched between the local magnetic field regulating device and the on-chip local temperature monitoring device;

An insulating layer is covered on the on-chip local temperature monitoring device;

A cell culture pool is arranged on the insulating layer.

Although the specific implementation of the present invention has been described above in conjunction with the accompanying drawings, it is not a limitation to the protection scope of the present invention. Those skilled in the art should understand that on the basis of the technical solution of the present invention, those skilled in the art do not need to pay creative work Various modifications or variations that can be made are still within the protection scope of the present invention.

Claims (8)

1. A biochip for realizing magnetic field regulation and temperature monitoring, characterized in that it comprises: a culture chip, an on-chip local magnetic field regulation device and an on-chip local temperature monitoring device; The on-chip local magnetic field regulation device is made of sub-micron and micron-scale metal wires, and the on-chip local temperature monitoring device is made of sub-micron-scale thermocouple arrays; The culture chip includes a base, the base is provided with a microscopic observation window, and an on-chip local magnetic field regulating device and an on-chip local temperature monitoring device are prepared in the microscopic observation window, with a heat insulating layer sandwiched between the two, and the local temperature monitoring on the chip The device is covered with an insulating layer, and a cell culture pool is arranged on the insulating layer; The on-chip local magnetic field regulating device is used to generate a uniform magnetic field or a gradient magnetic field, and adjust the direction, magnitude and gradient of the magnetic field by changing the spatial position of the metal wire and the direction and magnitude of the current passing through the metal wire; The magnetic field generated by the on-chip local magnetic field control device is a local steady magnetic field or a local alternating magnetic field; the direction, field strength and gradient of the local steady magnetic field are adjusted respectively by changing the direction, magnitude and configuration of the metal wire current; Adjust the amplitude and frequency of the local alternating magnetic field by changing the magnitude and frequency of the metal wire current; the metal wires are symmetrically distributed on the microscopic observation window, arranged in parallel according to the approved distance, and do not touch each other; The on-chip local magnetic field control device can realize the construction of two or more different magnetic field distributions within a millimeter range, and can generate different magnetic fields for different experimental requirements. 2 . A biochip for magnetic field regulation and temperature monitoring as claimed in claim 1 , wherein the substrate is a silicon chip coated with a silicon nitride layer on both sides. 3 . 3. A kind of biological chip that realizes magnetic field regulation and temperature monitoring as claimed in claim 2, is characterized in that, The thickness of the silicon nitride layer is 20 μm-500 μm; Or, the thickness of the silicon wafer is 0.5mm. 4. A biochip for realizing magnetic field regulation and temperature monitoring as claimed in claim 1, characterized in that, both the heat insulating layer and the insulating layer are made of HfO ₂ insulating layer with a thickness of 5-10nm. 5. A kind of biological chip that realizes magnetic field regulation and temperature monitoring as claimed in claim 1, is characterized in that, Change the current of the metal wire by changing the thickness of the metal wire and changing the voltage applied to the metal wire; Alternatively, the generated magnetic field has a scale ranging from a submicron level to a millimeter level. 6. A kind of biological chip that realizes magnetic field regulation and temperature monitoring as claimed in claim 1, is characterized in that, The configurations of the metal wires include symmetrical double ring type, loop double ring type and parallel line type. 7. A biochip for magnetic field regulation and temperature monitoring as claimed in claim 1, wherein the thermocouple is a Pd-Cr thermocouple. 8. A method for preparing a biochip for magnetic field regulation and temperature monitoring, characterized in that it comprises: An on-chip local magnetic field control device is prepared from sub-micron and micron-scale metal wires; An on-chip local temperature monitoring device is prepared from a submicron-scale thermocouple array; A microscopic observation window is provided on the substrate, and an on-chip local magnetic field regulation device and an on-chip local temperature monitoring device are prepared in the microscopic observation window; An insulating layer is sandwiched between the local magnetic field regulating device and the on-chip local temperature monitoring device; An insulating layer is covered on the on-chip local temperature monitoring device; A cell culture pool is arranged on the insulating layer; The on-chip local magnetic field regulating device is used to generate a uniform magnetic field or a gradient magnetic field, and adjust the direction, magnitude and gradient of the magnetic field by changing the spatial position of the metal wire and the direction and magnitude of the current passing through the metal wire; The magnetic field generated by the on-chip local magnetic field control device is a local steady magnetic field or a local alternating magnetic field; the direction, field strength and gradient of the local steady magnetic field are adjusted respectively by changing the direction, magnitude and configuration of the metal wire current; Adjust the amplitude and frequency of the local alternating magnetic field by changing the magnitude and frequency of the metal wire current; the metal wires are symmetrically distributed on the microscopic observation window, arranged in parallel according to the approved distance, and do not touch each other; The on-chip local magnetic field control device can realize the construction of two or more different magnetic field distributions within a millimeter range, and can generate different magnetic fields for different experimental requirements.