CN116121063B - Biochip for realizing magnetic field regulation and temperature monitoring and preparation method thereof - Google Patents
Biochip for realizing magnetic field regulation and temperature monitoring and preparation method thereof Download PDFInfo
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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
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
The statements in this section merely provide background information related to the present disclosure and may not necessarily constitute prior art.
In the field of bio-based research, techniques or devices capable of generating a local micro-magnetic field of micrometer scale are required in the course of performing experimental research on magnetic induction properties of a few single cells or cell clusters.
The conventional magnetic field generating device often uses an iron core, a coil, a pole head and the like 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 an external coil magnetic field so as to increase magnetic flux. When the magnitude and direction of the power supply current are controlled, the generated magnetic field is changed, so that a magnetic field with strong controllability and stability is provided. The magnetic field generated under the mode is mostly a strong magnetic field, the occupied space of the device is too large, the control of the direction and the intensity is too complicated, the magnetic field gradient regulation and control is lacked, the formed local magnetic field is often in a cm or even larger range, the performances of the direction, the intensity, the gradient and the like of the magnetic field cannot be accurately and rapidly regulated, and the magnetic induction device is not suitable for the field of magnetic induction performance research of single cells or a small number of cell clusters.
Currently, few magnetic field chips are mainly made of hard magnetic materials: for example, nd-FeB and the like are processed and manufactured into permanent magnets which are arranged externally or integrated on a chip, or a chip is magnetized by adding a plurality of soft magnets which are easy to magnetize such as nickel, iron powder and the like into the chip, and an externally applied magnetic field is placed outside the chip. The mode meets the advantages of small volume and easiness in integration in the chip, but the accuracy and speed of adjusting the self-defined intensity, direction and the like of the magnetic field are still to be improved; more importantly, the current magnetic field chip does not have the function of realizing multiple magnetic fields in millimeter scale, and can not observe the difference of cell behaviors in different magnetic fields in a single optical microscopic field at the same time, so that the magnetic field chip can not be applied to biomedical researches such as single cell or cell cluster magnetic induction performance researches.
In addition, the behavior of the corresponding magnetic field of the cells is often reflected in metabolism, and meanwhile, the generation of the magnetic field of the chip is often accompanied with the generation of heat, so that the real-time temperature monitoring is also a necessary function of researching the magnetic induction performance of single cells or cell clusters, but the conventional magnetic field generating device of the chip does not have the function of temperature real-time monitoring.
Disclosure of Invention
In order to solve the problems, the invention provides a biochip for realizing magnetic field regulation and temperature monitoring and a preparation method thereof, which can realize the adjustment of the direction, intensity and gradient of a local magnetic field on a micrometer scale, and can monitor local temperature change to determine cell metabolism change, and is used for biomedical fields such as magnetic induction performance research of single cells or cell clusters.
In order to achieve the above purpose, the present invention adopts the following technical scheme:
in a first aspect, the present invention provides a biochip for implementing magnetic field regulation and temperature monitoring, comprising: 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.
Alternatively, the substrate is a silicon wafer coated with silicon nitride layers on both sides.
Alternatively, the silicon nitride layer has a thickness of 20 μm to 500 μm.
Alternatively, the silicon wafer has a thickness of 0.5mm.
As an alternative embodiment, the heat insulating layer and the insulating layer both adopt HfO 2 The thickness of the insulating layer is 5-10nm.
As an alternative embodiment, the on-chip local magnetic field regulating device is used for generating a uniform magnetic field or a gradient magnetic field, and the direction, the magnitude and the gradient of the magnetic field are regulated by changing the spatial position of the metal wire and the direction and the magnitude of the current passing through the metal wire.
Alternatively, the magnitude of the current in the metal wire is changed by changing the thickness of the metal wire and changing the magnitude of the voltage applied to the metal wire.
Alternatively, the magnetic field is generated in a scale ranging from sub-micron to millimeter scale.
As an alternative embodiment, the magnetic field generated by the on-chip local magnetic field regulating device is a local steady magnetic field or a local alternating magnetic field.
As an alternative embodiment, the direction, the field strength and the gradient of the local steady magnetic field are respectively adjusted by changing the direction, the magnitude and the configuration of the metal wire current.
Alternatively, the amplitude and frequency of the local alternating magnetic field are adjusted by varying the magnitude and frequency of the metal wire current, respectively.
As an alternative implementation mode, the metal wires are symmetrically distributed on the microscopic observation window and are arranged in parallel according to the verification distance without contacting each other.
Alternatively, the configuration of the metal wire includes a symmetrical double loop type, a loop double loop type, and a parallel wire type.
As an alternative embodiment, the thermocouple is a Pd-Cr thermocouple.
In a second aspect, the present invention provides a method for preparing a biochip for implementing magnetic field regulation and temperature monitoring, comprising:
preparing an on-chip local magnetic field regulating device by using metal wires with submicron and micron dimensions;
preparing an on-chip local temperature monitoring device by using a submicron-scale thermocouple array;
a microscopic observation window is arranged on the substrate, and an on-chip local magnetic field regulating device and an on-chip local temperature monitoring device are prepared in the microscopic observation window;
a heat insulation layer is clamped between the local magnetic field regulating device and the on-chip local temperature monitoring device;
covering an insulating layer on the local temperature monitoring device on the chip;
a cell culture pond is arranged on the insulating layer.
Compared with the prior art, the invention has the beneficial effects that:
the invention provides a biochip for realizing integration of magnetic field regulation and temperature monitoring on micro-nano scale, which comprises a plurality of groups of metal wires for generating local micro-magnetic fields, and the functions of fine-tuning the direction, the size and the gradient of the magnetic field with high precision are realized by changing the space position of the metal wires and the direction and the size of the current passing through the metal wires, so that the micro-nano scale micro-magnetic field is generated, the direction, the intensity and the gradient of the magnetic field can be finely regulated, and the real-time monitoring of single cell temperature and surrounding environment temperature with high precision and high space-time resolution is realized.
The invention reduces the space range of the adjustable magnetic field, can observe the behavior mode of single cells/clusters under different magnetic field distribution in the same optical window, can obtain the physiological change of the single cells/clusters in response to the action of the magnetic field through in-situ high-time-space and high-precision thermocouple temperature monitoring, and is suitable for the micro-fluidic chip of single cell/cluster magnetic induction research in the biomedical field.
The invention realizes the functions of local magnetic field generation, regulation and control and temperature field monitoring on the micro-nano scale, avoids complicated process, reduces the cost and the area of the magnetic field generation device, and can be widely applied to biomedical research such as magnetic induction performance research of single cells or cell clusters.
Additional aspects of the invention will be set forth in part in the description which follows and, in part, will be obvious from the description, or may be learned by practice of the invention.
Drawings
The accompanying drawings, which are included to provide a further understanding of the invention and are incorporated in and constitute a part of this specification, illustrate embodiments of the invention and together with the description serve to explain the invention.
FIG. 1 is a top view of a biochip according to example 1 of the present invention;
FIG. 2 is a side view of a biochip according to example 1 of the present invention;
FIG. 3 is a diagram showing a biochip manufactured by the embodiment 1 of the invention;
FIG. 4 is a schematic diagram of the principles of the parallel-line design of the micro-magnetic field distribution and gradient control according to embodiment 1 of the present invention;
FIGS. 5 (a) -5 (b) are schematic diagrams of the principle of uniform distribution of the micro magnetic field and calculation of the field intensity for the toroidal design provided in example 1 of the present invention;
FIG. 6 (a) is a schematic diagram showing the distribution of the loop dual-ring type micro magnetic field and thermocouple provided in embodiment 1 of the present invention;
fig. 6 (b) -6 (c) are schematic diagrams of the loop double-loop design provided in embodiment 1 of the present invention, and simultaneously construct a uniform magnetic field with variable strength and a blank magnetic field;
FIG. 7 (a) is a schematic diagram showing the distribution of the symmetrical double-ring type micro-magnetic field and thermocouple according to the embodiment 1 of the present invention;
fig. 7 (b) -7 (d) are schematic diagrams of the symmetrical double-loop design provided in embodiment 1 of the present invention, which simultaneously constructs a reverse, variable-strength uniform magnetic field and a blank magnetic field;
FIG. 8 (a) is a schematic diagram showing the distribution of parallel linear micro-magnetic fields and thermocouples according to example 1 of the present invention;
FIGS. 8 (b) -8 (c) are schematic diagrams of the parallel line design provided in example 1 of the present invention, while constructing a uniform magnetic field with variable reverse and intensity and a blank magnetic field;
the device comprises a substrate 1, a substrate 2, PDMS (polydimethylsiloxane), a cell culture pond 3, a silicon nitride suspension platform 4, a silicon nitride suspension platform 5, an HfO2 insulating layer 6, a thermocouple 7, a Cr submicron strip 8, a Pd submicron strip 9, a magnetic field generating device 10, a Cr lead of the thermocouple 11, a magnetic field generating device lead 12, a Pd lead of the thermocouple 13, a symmetrical double-ring type micro-magnetic field device 14, a parallel linear type micro-magnetic field device 15 and a loop double-ring type micro-magnetic field device.
Detailed Description
The invention is further described below with reference to the drawings and examples.
It should be noted that the following detailed description is exemplary and is intended to provide further explanation of the 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 is noted that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of exemplary embodiments according to the present invention. As used herein, unless the context clearly indicates otherwise, the singular forms also are intended to include the plural forms, and furthermore, it is to be understood that the terms "comprises" and "comprising" and any variations thereof are intended to cover non-exclusive inclusions, such as, for example, processes, methods, systems, products or devices that comprise a series of steps or units, are not necessarily limited to those steps or units that are expressly listed, but may include other steps or units that are not expressly listed or inherent to such processes, methods, products or devices.
Embodiments of the invention and features of the embodiments may be combined with each other without conflict.
Example 1
As shown in fig. 1-3, the present embodiment provides a biochip for implementing magnetic field regulation and temperature monitoring on micro-nano scale, which is used for single-cell or clustered magnetic induction research in biomedical field, etc.; the method specifically comprises the following steps: culture chip based on micro-fluidic technology, on-chip local magnetic field regulation and control device and on-chip local temperature monitoring device;
the on-chip local magnetic field regulating and controlling device is prepared by metal lines 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.
As shown in FIG. 1, the circle where the dotted line is located is a calibration line, and the functional area of magnetic field generation and temperature monitoring is located in the dotted line, so that the local micro magnetic field and the local micro magnetic field are generated and the temperature is monitored, the number of devices in the calibration line is adjustable, and a plurality of biochips can be arranged to form a matrix to realize high-precision large-scale adjustment of the micro magnetic field and the temperature. As shown in fig. 2, the functional device was fabricated on a transparent microscopic observation window of a silicon nitride suspended platform and operated in a cell culture pond surrounded by PDMS.
In this embodiment, the substrate 1 is a silicon wafer coated with silicon nitride layers on both sides.
Alternatively, the silicon nitride layer has a thickness of 20 μm to 500 μm.
Alternatively, the silicon wafer has a thickness of 0.5mm.
In this embodiment, a plurality of millimeter-scale silicon nitride suspended platforms 4 are etched on the substrate 1 to be used as transparent microscopic observation windows for observing cell behaviors; the silicon nitride suspended platform 4 provides a window for optically observing the behavior of cells, and reduces heat dissipation to improve 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 micrometer range magnetic field with controllable intensity, gradient and direction are prepared in the microscopic observation window, a heat insulation layer is sandwiched between the on-chip local magnetic field regulating device and the on-chip local temperature monitoring device, an insulating layer is covered above the on-chip local temperature monitoring device, interference to device functions in a culture solution environment is prevented, leakage of a device conductor is reduced, and a cell culture pond 3 prepared from PDMS is arranged above the insulating layer.
As an alternative embodiment, the heat insulating layer and the insulating layer both adopt HfO 2 An insulating layer 5 made of HfO 2 Molecular deposition to form the polymer with the thickness of 5-10nm;
as a heat insulating layer, the distance between the functional element (magnetic field generating device and temperature monitoring device) and the cells is as close as possible under the condition of ensuring electric insulation, so that the cells (clusters) to be detected are positioned at the magnetic field center as much as possible;
as an insulating layer, the device can prevent the intervention of the culture solution on the functions of the device, and improve the temperature resolution of thermocouple temperature measurement and shorten the response time while avoiding the electric leakage of the conductor of the device.
In this embodiment, the on-chip local magnetic field regulating device is prepared from submicron and micron-scale metal wires, and comprises a plurality of groups of metal wire configuration designs for generating local magnetic fields, the metal wire configuration designs are regularly distributed on a silicon nitride suspension platform, uniform magnetic fields or gradient magnetic fields required by various experiments are generated when current passes through the metal wire, and high-precision fine adjustment of the direction, the magnitude and the gradient of the magnetic field is realized by changing the spatial position of the metal wire and the direction and the magnitude of the current passing through the metal wire.
As an alternative embodiment, the change of the current level of the metal wire is achieved by changing the thickness of the metal wire, changing the voltage level applied to the metal wire, and the like.
As an alternative implementation mode, the metal wire is a stable low-resistance metal conductive material such as gold, platinum, palladium, chromium and the like; such as Cr submicron stripes 7 and Pd submicron stripes 8 in fig. 2.
As an alternative implementation mode, the metal wires are symmetrically distributed on the silicon nitride suspension platform, and the metal strips are arranged in parallel according to the verification distance and are not contacted with each other, so that mutual interference of current is avoided, and meanwhile, the regulation and control of a magnetic field are facilitated.
As an alternative implementation mode, the on-chip local magnetic field regulating device can realize the construction of two or more different magnetic field distributions in the millimeter range, and can generate different magnetic fields according to different experimental requirements; the design of the metal wire configuration for generating the local magnetic field comprises, but is not limited to, symmetrical double-ring type, loop double-ring type, parallel line type and the like, and can realize different magnetic field distributions in a smaller area at the same time, thereby being beneficial to experimental variable control and result comparison.
Alternatively, the local magnetic field is a local steady magnetic field or a local alternating magnetic field.
Furthermore, the direction, the field intensity and the gradient of the local steady magnetic field are adjustable and characterizable, and the local steady magnetic field is realized by changing the direction, the size and the configuration of the metal wire current.
Furthermore, the amplitude and the frequency of the local alternating magnetic field are adjustable and characterizable, and the local alternating magnetic field is realized by changing the magnitude and the frequency of the current of the metal wire.
As an alternative, the local magnetic field may have dimensions ranging down to sub-micron levels, up to millimeter levels.
In this embodiment, the on-chip local temperature monitoring device is made of a submicron-scale thermocouple array, and is located on the upper layer of the magnetic field generating device, so that the temperature at the thermocouple can be converted into voltage output between metal strips, and the purpose of temperature measurement is achieved.
As an alternative embodiment, the thermocouples 6 are distributed around the magnetic field generating device 9 to monitor the temperature variation of the respective representative locations and the cell metabolism.
As an alternative embodiment, the thermocouple 6 is a pd—cr thermocouple.
As an alternative embodiment, the temperature measurement accuracy of the thermocouple 6 is up to 20mK.
As an alternative embodiment, the thermocouple 6 has 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 regulation of each micro magnetic field configuration, the embodiment designs a simulation calculation software model of the magnetic field intensity, direction and gradient of the local magnetic field for each micro magnetic field configuration so as to regulate the local micro magnetic field according to actual requirements, and as shown in fig. 4 and fig. 5 (a) -fig. 5 (b), schematic diagrams of the micro magnetic field distribution and gradient regulation principles designed for parallel line type and circular ring type respectively. Wherein, FIG. 4 shows the distribution of magnetic fields at different heights h on the vertical section of the parallel wires when the distance between the two parallel wires is 20 μm, the line width is 10 μm, and the current in the wires is 10 milliamperes; in fig. 5 (a) -5 (b), the magnetic field strength increases to 4%, 24% and 90% respectively at distances of 1/4, 1/2 and 3/4 from the center point, i.e. the magnetic field distribution in the coil center area is relatively uniform, and the magnetic field gradient at different positions near the wire can be adjusted.
Fig. 6 (a) -6 (c), fig. 7 (a) -7 (d), and fig. 8 (a) -8 (c) are three typical micro-magnetic field configurations and schematic diagrams of multiple magnetic fields formed by the same, and the symmetrical double-loop type design of fig. 7 (a) -7 (d) is taken as an example to illustrate the principle and application of the simultaneous implementation of multiple magnetic fields.
In the research of magnetic induction characteristics of a certain cell, the behavior and physiological changes of the same cell under different magnetic field intensities, directions and gradients are explored. The above study requires that the following conditions be met: (1) Besides directly observing the cell behavior, the chip is provided with a sensor capable of reflecting the cell metabolic change in real time; (2) To ensure a strict single variable, it is required to simultaneously realize multiple magnetic field distributions, real-time magnetic field regulation and control and blank magnetic fields as control groups under the same observation field (within the range of not more than 1 square millimeter).
The symmetrical dual-ring type of micro-magnetic field design shown in fig. 7 (a) -7 (d) meets the above requirements:
(1) FIG. 7 (a) shows the design configuration and thermocouple profile of a symmetrical double-loop type micromagnetic field, wherein 4 thin-film thermocouples are respectively prepared in four typical areas of the micromagnetic field to monitor the temperature changes of cells in different areas, and the temperature changes reflect the metabolic conditions of the cells.
(2) Fig. 7 (b) -7 (d) show the principle of implementation of local multiple magnetic field distributions in the case of 3-directional combinations of currents. When the current direction is shown in fig. 7 (b) and fig. 7 (c), 3 different magnetic field regions can be simultaneously realized, as shown in fig. 7 (b), region 1 is a quasi-uniform magnetic field in a downward direction, region 2 is a non-magnetic field region as a blank group, region 3 is a quasi-uniform magnetic field in an upward magnetic field direction, and the intensity is weaker than that of region 1; when the current directions are reversed as shown in fig. 7 (d), the magnetic field distribution of the regions 1-3 is changed, i.e., the magnetic field direction is regulated by the current direction, the magnetic field strength is regulated by the current magnitude, and the magnetic field gradient is regulated by both the current direction and the current magnitude.
Example 2
The embodiment provides a preparation method of the biochip for realizing magnetic field regulation and temperature monitoring, which comprises the following steps:
preparing an on-chip local magnetic field regulating device by using metal wires with submicron and micron dimensions;
preparing an on-chip local temperature monitoring device by using a submicron-scale thermocouple array;
a microscopic observation window is arranged on the substrate, and an on-chip local magnetic field regulating device and an on-chip local temperature monitoring device are prepared in the microscopic observation window;
a heat insulation layer is clamped between the local magnetic field regulating device and the on-chip local temperature monitoring device;
covering an insulating layer on the local temperature monitoring device on the chip;
a cell culture pond is arranged on the insulating layer.
While the foregoing description of the embodiments of the present invention has been presented in conjunction with the drawings, it should be understood that it is not intended to limit the scope of the invention, but rather, it is intended to cover all modifications or variations within the scope of the invention as defined by the claims of the present invention.
Claims (8)
1. A biochip for implementing magnetic field regulation and temperature monitoring, comprising: 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, wherein 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 prepared in the microscopic observation window, a heat insulation layer is arranged 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 on-chip local magnetic field regulating and controlling device is used for generating a uniform magnetic field or a gradient magnetic field, and regulating the direction, the size and the gradient of the magnetic field by changing the space position of the metal wire and the current direction and the size of the metal wire;
the magnetic field generated by the on-chip local magnetic field regulating device is a local steady magnetic field or a local alternating magnetic field; the direction, the field intensity and the gradient of the local steady magnetic field are respectively adjusted by changing the direction, the size and the configuration of the metal wire current; the amplitude and the frequency of the local alternating magnetic field are respectively adjusted by changing the magnitude and the frequency of the current of the metal wire; the metal wires are symmetrically distributed on the microscopic observation window and are arranged in parallel according to the verification distance without contact;
the on-chip local magnetic field regulating device can realize the construction of two kinds of different magnetic field distribution in a millimeter range, and can generate different magnetic fields according to different experimental requirements.
2. The biochip for realizing magnetic field control and temperature monitoring according to claim 1, wherein the substrate is a silicon wafer coated with silicon nitride layers on both sides.
3. A biochip for implementing magnetic field regulation and temperature monitoring according to claim 2,
the thickness of the silicon nitride layer is 20-500 mu m;
or the thickness of the silicon wafer is 0.5mm.
4. The biochip for realizing magnetic field control and temperature monitoring according to claim 1, wherein the heat insulating layer and the insulating layer are made of HfO 2 The thickness of the insulating layer is 5-10nm.
5. A biochip for implementing magnetic field regulation and temperature monitoring according to claim 1,
changing the current of the metal wire by changing the thickness of the metal wire and changing the voltage applied to the metal wire;
or, the scale of the generated magnetic field ranges from submicron to millimeter.
6. A biochip for implementing magnetic field regulation and temperature monitoring according to claim 1,
the configuration of the metal wire comprises symmetrical double-ring type, loop double-ring type and parallel line type.
7. The biochip for realizing magnetic field control and temperature monitoring according to claim 1, wherein the thermocouple is a Pd-Cr thermocouple.
8. The preparation method of the biochip for realizing magnetic field regulation and temperature monitoring is characterized by comprising the following steps:
preparing an on-chip local magnetic field regulating device by using metal wires with submicron and micron dimensions;
preparing an on-chip local temperature monitoring device by using a submicron-scale thermocouple array;
a microscopic observation window is arranged on the substrate, and an on-chip local magnetic field regulating device and an on-chip local temperature monitoring device are prepared in the microscopic observation window;
a heat insulation layer is clamped between the local magnetic field regulating device and the on-chip local temperature monitoring device;
covering an insulating layer on the local temperature monitoring device on the chip;
a cell culture pond is arranged on the insulating layer;
the on-chip local magnetic field regulating and controlling device is used for generating a uniform magnetic field or a gradient magnetic field, and regulating the direction, the size and the gradient of the magnetic field by changing the space position of the metal wire and the current direction and the size of the metal wire;
the magnetic field generated by the on-chip local magnetic field regulating device is a local steady magnetic field or a local alternating magnetic field; the direction, the field intensity and the gradient of the local steady magnetic field are respectively adjusted by changing the direction, the size and the configuration of the metal wire current; the amplitude and the frequency of the local alternating magnetic field are respectively adjusted by changing the magnitude and the frequency of the current of the metal wire; the metal wires are symmetrically distributed on the microscopic observation window and are arranged in parallel according to the verification distance without contact;
the on-chip local magnetic field regulating device can realize the construction of two kinds of different magnetic field distribution in a millimeter range, and can generate different magnetic fields according to different experimental requirements.
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