CN111073948A - Non-contact cell weak magnetic determination method - Google Patents
Non-contact cell weak magnetic determination method Download PDFInfo
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Abstract
The invention discloses a non-contact cell weak magnetic determination method, which comprises the steps of placing cells in a non-magnetic environment, giving an external stimulus to the cells, and detecting a weak magnetic field of the cells subjected to the external stimulus by using a magnetic sensor. The invention excites the action potential or local potential change of the cell by applying external stimulation to the cell in a non-magnetic environment, thereby generating a weak magnetic field, and then detects the weak magnetic field of the cell in a non-contact condition by a high-sensitivity magnetic sensor. The invention discovers the method for detecting the cell magnetism in a non-contact way for the first time, has the characteristics of non-contact, high sensitivity and cell friendliness, overcomes the defect of irreparable damage to cells when the cell activity is measured at present, and provides a new idea for magnetic research on the cell level in the future.
Description
Technical Field
The invention relates to a method for measuring weak magnetism (namely weak magnetic field or extremely weak magnetic field of cells), in particular to a non-contact high-sensitivity cell weak magnetism measuring method friendly to cells, belonging to the technical field of medical instruments.
Background
The cells are the basic activity units of life, the human body has more than 200 cells, and the total cell number is 1012To 1016Each cell has a unique structure to perform a different function. The living cells of a living organism have electrical activity in both a resting state and an active state, and the electrical activity is called bioelectricity. The weak electrical activity and changes of cells may be fundamental characteristics and forms of realization of their different biological activities. In recent years, it has been found that various excitable cells, when excited, share a common, first-appearing characteristic, although they may have different external manifestations: it is the action potential change on both sides of the cell membrane of the excitable cell.
When living cells and organisms are subjected to mechanical stimuli in the environment, the mechanical signals are then converted into biological signals, which cause the cells to respond, a process known as mechanotransduction, a feature common to all living organisms from bacteria to humans. Mechanical stimuli include high frequency vibrations, changes in osmotic pressure, hydrostatic pressure, shear forces of the fluid, and the like. In the mechanical signal transduction process, mechanosensitive ion channels (MS channels) play an important role. The opening of mechanosensitive ion channels of cells causes the change of action potential (also called membrane potential) of cells, and at present, the data such as membrane potential of cells are tested, and the biological activity of cells is studied more deeply through the membrane potential. However, cell membrane potential is currently tested by using a contact method such as patch clamp, and the test method needs to be in contact with cells, so that irreparable influences such as damage and death of the cells are caused.
Research shows that the action potential change is accompanied with the change of the extremely weak magnetism of the cells, the action potential change of the cells can be well reflected through the change of the extremely weak magnetism of the cells, and no related method for testing the extremely weak magnetism of the cells is reported at present.
Disclosure of Invention
Aiming at the defects in the prior art, the invention provides a non-contact cell weak magnetic determination method, which can perform non-contact determination on a very weak magnetic field of a cell, has the advantages of high sensitivity, cell friendliness and the like, cannot cause irreparable influence on the cell, can well reflect the excitation degree of the cell, and provides a new research idea for the detection of the biological activity of the cell.
The invention provides a non-contact cell weak magnetic determination method, which comprises the following steps: the method comprises the steps of placing cells in a non-magnetic environment, giving an external stimulus to the cells, and detecting weak magnetic fields of the cells subjected to the external stimulus by using a magnetic sensor.
Furthermore, the method realizes the non-contact measurement of weak magnetism of the cells through three steps of construction of a non-magnetic environment, stimulation of the cells and detection of a magnetic field of the cells. The non-magnetic environment can be realized by any feasible method reported in the prior art, and the cells are ensured to be in an environment with zero magnetic field during detection, so that errors in the detection process are avoided, and the detection accuracy is ensured. For example, the cells may be placed in a magnetic shield device capable of isolating an external magnetic field, or the cells may be placed in an operation room capable of isolating an external magnetic field, and it is preferable to place the cells in the magnetic shield device to create a non-magnetic environment in consideration of convenience of use.
Further, the magnetic shielding device comprises a shell and a cavity formed by the shell, and a cover body is arranged on the shell. The cavity formed by the shell and the cover body is in a non-magnetic environment, and cells are placed in the cavity, so that weak magnetic detection in the non-magnetic environment can be realized. In addition, in order to facilitate the placement of cells and the realization of external stimulation, a component for placing cells and a device for realizing external stimulation can be arranged in the cavity.
Further, the shell can be of a single-layer structure or a multi-layer structure, and is preferably of a multi-layer structure, so as to improve the magnetic shielding effect. In a specific embodiment of the present invention, the housing is formed by a plurality of shells coaxially or concentrically arranged, each shell is provided with a shell cover, and each shell cover forms a cover body. Each layer of shell and shell cover forms a cavity. The shells of each layer are not contacted with each other, and the shells of each layer are arranged concentrically or coaxially.
Further, the non-magnetic environment can be realized by various materials capable of shielding a magnetic field, preferably by iron-nickel alloy, that is, a magnetic shielding device or an operation room capable of isolating an external magnetic field is made of or built up of iron-nickel alloy. The iron-nickel alloy is preferably permalloy, the permalloy is soft magnetic alloy, the nickel content is 30-90%, the weak magnetic field permeability is very high, and magnetic field shielding is convenient to achieve. When the magnetic shielding device is used, the magnetic shielding device or the operating room can be made of single-layer iron-nickel alloy or multi-layer iron-nickel alloy, the thickness of each layer of iron-nickel alloy, the number of layers selected by the iron-nickel alloy and other conditions can be adjusted according to the condition of an external magnetic field in the actual use process, and the zero magnetic field environment is guaranteed to be realized. When the iron-nickel alloy uses a plurality of layers, the layers can be simply nested and overlapped for use, and the layers can also be manufactured into an integral structure for use in a certain way.
Preferably, the shell and the cover of the magnetic shielding device are made of iron-nickel alloy, the iron-nickel alloy can be a single layer or multiple layers, and the multiple layers of iron-nickel alloy can be integrated by pressing, bonding and other means, or can be simply stacked and nested together. The iron-nickel alloy is preferably permalloy.
Further, the shape of the magnetic shield device may be arbitrary, and may be, for example, a barrel shape, a square shape, a rectangular parallelepiped shape, a spherical shape, an irregular shape, or the like.
Furthermore, a compensation coil can be arranged in the magnetic shielding device and used for offsetting an internal magnetic field which cannot be shielded by the magnetic shielding device and ensuring a zero magnetic environment in the magnetic shielding device. The compensation coil is a coil made of a conducting wire, can be in various shapes such as a spiral shape, a branch line shape, a U shape, an S shape, a snake shape and the like, and aims to generate a magnetic field under the condition of electrifying so as to counteract the internal magnetic field in the magnetic shielding device and realize a zero magnetic environment. When the case is a single layer, the compensation coil may be provided on the inner surface of the case of the magnetic shield device, and when the case is composed of a plurality of layers of shells, the compensation coil may be provided on the shell of the innermost layer. The shape, number, and distribution position of the compensation coils in the magnetic shield device can be adjusted and set according to the condition of the internal magnetic field.
Further, at least one through hole is arranged on the shell of the magnetic shielding device, so that the magnetic sensor can be conveniently installed and used, signals can be conveniently transmitted, and cells can be conveniently observed. The shape of the hole can be random, and the diameter of the hole is about 1-5 cm.
Further, the purpose of giving the external stimulus to the cell is to change the action potential or local potential of the cell, and therefore any stimulus that can open the ion channel of the cell, cause the change in the action potential or local potential of the cell, can be used in the present invention as the external stimulus to the cell. Such external stimuli may be physical stimuli, chemical stimuli, biological stimuli or other kinds of stimuli that can achieve the purpose of opening cellular ion channels, causing cellular action potentials or local potential changes.
Further, the physical stimulation includes mechanical stimulation, pressure stimulation, electrical stimulation, optical stimulation, temperature stimulation, osmotic pressure change stimulation, stirring stimulation, fluid shear force stimulation and the like, wherein the mechanical stimulation can be in a mode of high-frequency vibration, shaking, rotation, swinging and the like, for example, a non-magnetic platform is arranged in the magnetic shielding device, a high-frequency vibration device is arranged on the non-magnetic platform, and a culture bottle containing cells is placed on the high-frequency vibration device to give a vibration stimulation to the cells; for another example, the culture bottle containing the cells is fixed by a rope and does simple pendulum motion to provide a physical stimulation of fluid shear force for the cells.
Further, the chemical stimulus may act to stimulate the cell by applying certain chemicals to the cell. The chemical substances can be an opening agent of an ion channel such as minoxidil and diazoxide for stimulating cells, a blocker of an ion channel such as nifedipine, mexiletine and amiodarone for blocking the ion channel, and other chemical substances such as potassium chloride, sodium chloride, calcium chloride or tetrodotoxin for stimulating cells.
Further, the biostimulation may be accomplished by applying to the cells biologically active substances, including hormones, enzymes, antigen-antibodies, viruses, etc., that cause the cells to produce a change in membrane potential.
Further, since the magnetic field generated by the cell is extremely weak, the magnetic sensor used is a magnetic sensor having a sensitivity of 10-12The high-sensitivity magnetic sensor above T can detect pT magnetic field or even fT magnetic field. For example, the magnetic sensor may be a high-sensitivity fiber optic magnetic field sensor or a high-sensitivity atomic magnetometer. The optical fiber magnetic field sensor calculates the magnetic field signal of the measured area or the measured cell by utilizing different influences on laser transmitted in light caused by different reactions of magnetic powder in the cavity to the magnetic field. The atomic magnetometer realizes the measurement of the magnetic field of the cell by utilizing the movement condition of the atoms in the magnetic field generated by the cell. The high-sensitivity fiber-optic magnetic field sensor or the high-sensitivity atomic magnetometer can be purchased from the market.
Further, since the detection range of the magnetic sensor is limited, the magnetic sensor is placed close to the cell.
Further, the cells are contained in a container such as a culture bottle or a petri dish, and in order to maintain the living state of the cells, the cells are placed in an environment suitable for the living of the cells, for example, various culture solutions suitable for the cells, and the like.
The invention excites the action potential or local potential change of the cell by applying external stimulation to the cell in a non-magnetic environment, thereby generating a weak magnetic field, and then detects the weak magnetic field of the cell in a non-contact condition by a high-sensitivity magnetic sensor. The invention discovers the method for detecting the cell magnetism in a non-contact way for the first time, has the characteristics of non-contact, high sensitivity and cell friendliness, overcomes the defect of irreparable damage to cells when the cell activity is measured at present, and provides a new idea for magnetic research on the cell level in the future.
Drawings
FIG. 1 is a schematic view of a cylindrical magnetic shielding device, wherein A is a schematic cross-sectional view of the device and B is a schematic cross-sectional view of the device;
FIG. 2 is a schematic view of a built-in compensation coil of the magnetic shield apparatus shown in FIG. 1;
FIG. 3 is a schematic diagram of a weak magnetic cell test method;
FIG. 4 is a diagram showing the weak magnetic test process of the cell and the test result;
FIG. 5 is a graph of the magnetic field versus time for the experimental group (fibroblasts);
FIG. 6 is a graph of the variation of magnetic field with time for the blank control group (MEM medium);
FIG. 7 is a graph of the change of the magnetic field of the experimental group (Schwann cells) with time;
FIG. 8 is a graph of magnetic field versus time for the blank control (DMEM medium);
FIG. 9 is a graph of the magnetic field versus time for murine fibroblasts without any external stimulus.
Detailed Description
The examples are intended to further illustrate the content of the invention and do not limit the scope of protection of the invention. The techniques described herein may be applied to any method or apparatus for magnetic measurement of cells.
The invention provides a non-contact weak magnetic measuring method for cells, which comprises the steps of placing the cells in a non-magnetic environment, then giving an external stimulus to the cells to enable the cells to generate action potential or local potential, enabling the change of the potential to bring the change of extremely weak magnetic field of the cells, and detecting the weak magnetic field of the cells after being stimulated by the external stimulus through a magnetic sensor.
The method is realized by combining the construction of a non-magnetic environment, the external stimulation of cells and the detection of a cell magnetic field. In the actual operation process, a set of test system for weak magnetic field measurement of cells can be designed for measuring the weak magnetic field of the cells.
The non-magnetic environment can be realized in any non-magnetic mode, and the cell detection process can be ensured to be in an external zero-magnetic environment, for example, a non-magnetic environment can be constructed by some magnetic shielding materials, the cell is placed in the non-magnetic environment for detection, and the non-magnetic environment can also be constructed in a magnetic field counteracting mode to facilitate the weak magnetic detection of the cell. In one embodiment of the present invention, a magnetic shielding device is provided for providing a zero magnetic environment for cell detection, and the magnetic shielding device includes a housing and a cover, wherein the cover is disposed on the housing, and the cover and the housing can be connected as a whole or separated from the housing. A cavity may be formed by the housing and the cover. The housing and cover are made of an iron-nickel alloy, preferably permalloy. The shell can be of a single-layer structure or a multi-layer structure. Preferably, the shell is of a multilayer structure and is formed by a plurality of layers of shells, a shell cover is arranged on each layer of shell, and each layer of shell cover forms the cover body. The shells are coaxially or concentrically arranged and are not in contact with each other, and a cavity is formed by each shell and the shell cover.
Further, the shell and the cover body can be made of a layer of iron-nickel alloy or a plurality of layers of iron-nickel alloy, the plurality of layers of iron-nickel alloy can be integrated by a certain processing means, and can also be in a separated state, preferably, the plurality of layers of iron-nickel alloy are coaxially or concentrically arranged, and the layers of iron-nickel alloy are separated from each other and do not contact each other. In order to better ensure the zero magnetic field in the magnetic shielding device, a compensation coil is arranged in the magnetic shielding device, the compensation coil is positioned on the shell, and the cover body is not provided with the compensation coil. The compensation coil may be of any shape, such as a spiral, a branch, a U, an S, a serpentine, etc. When the case is a single layer, the compensation coil may be provided on the inner surface of the case of the magnetic shield device, and when the case is composed of a plurality of layers of shells, the compensation coil may be provided on the shell of the innermost layer. The shape, number, and distribution position of the compensation coils in the magnetic shield device can be adjusted and set according to the condition of the internal magnetic field. The compensation coil is a coil made of a conductive wire, and is intended to generate a magnetic field in the case of energization for canceling an internal magnetic field in the magnetic shield apparatus, achieving a zero magnetic environment. In addition, at least one through hole can be arranged on the shell of the magnetic shielding device, so that the magnetic sensor can be installed and used, signals can be transmitted, and cells can be observed conveniently. The shape, number and size of the through holes are sufficient for the purposes of installation, observation and signal transmission.
In addition, the shape of the magnetic shielding device is not particularly required, and may be any shape which is convenient for cell detection and for realizing a zero magnetic environment, such as a barrel shape, a spherical shape, a columnar shape, a rectangular parallelepiped shape, a square shape, a random shape, and the like.
In a specific embodiment of the invention, the magnetic shielding device is composed of a shell and a cover body, wherein the shell and the cover body are both made of permalloy with high magnetic permeability, the whole magnetic shielding device is in a cylindrical shape, and the cover body and the shell are detachably arranged, so that the installation of a detection system and the acquisition of data are facilitated. The shell is formed by nesting and combining a plurality of layers of cylindrical permalloy shells which are coaxially arranged, each shell is identical in shape and different in size, the shells are combined together according to the coaxial nesting to form the shell, and the permalloy shells are fixed through three or a plurality of fixing clamping teeth, so that the plurality of cylindrical permalloy shells are ensured to be coaxially placed. And a shell cover matched with the permalloy shell is arranged on each layer of permalloy shell, and the shell cover of each layer can form a closed cavity. The compensation coil is wound on the barrel-shaped outer wall of the permalloy shell at the innermost layer, the winding directions of the compensation coils can be the same direction or different directions, the compensation coil is also arranged on the outer wall at the side corresponding to the shell cover, and the compensation coil is a thread-shaped or multi-branch-shaped (i.e. branch-line-shaped) compensation coil.
Further, a structure for placing cells and a device or a structure for externally stimulating cells may be provided inside the magnetic shield device. In one embodiment of the invention, a non-magnetic platform is arranged in the magnetic shielding device, a high-frequency vibration device is arranged on the platform to provide high-frequency vibration stimulation for the cell culture bottle, and the magnetic sensor is connected to the inner wall of the shell or fixed on the non-magnetic platform through a fixed rod. In another embodiment of the present invention, a simple pendulum device is disposed in the magnetic shielding device, one end of the simple pendulum is fixed on the inner wall of the housing, the other end is used for placing a cell culture flask, the fluid shear force is provided by periodic oscillation to perform physical stimulation on the cells, and the magnetic sensor is connected to the inner wall of the housing through a fixing rod and fixed.
After a nonmagnetic environment is created, cells are placed in the nonmagnetic environment, then external stimulation is carried out on the cells to enable the cells to generate action potential or local potential change, and the external stimulation can be physical stimulation, chemical stimulation, biological stimulation or other types of stimulation which can achieve the purposes of opening cell ion channels and causing the action potential or the local potential change of the cells. The physical stimulation comprises mechanical stimulation, pressure stimulation, electric stimulation, optical stimulation, temperature stimulation, osmotic pressure change stimulation, stirring stimulation, fluid shear force stimulation and the like, wherein the mechanical stimulation can be in a mode of high-frequency vibration, shaking, rotation, swing and the like. The chemical stimulation can stimulate the cells by applying certain chemical substances to the cells, wherein the chemical substances can be an ion channel opener such as minoxidil and diazoxide for stimulating the cells, an ion channel blocker such as nifedipine, mexiletine and amiodarone for blocking the ion channels, and other chemical substances such as potassium chloride, sodium chloride, calcium chloride or tetrodotoxin for stimulating the cells. The biostimulation may be accomplished by applying to the cells biologically active substances, including hormones, enzymes, antigen-antibodies, viruses, etc., that cause the cells to produce a change in membrane potential.
After the cells are stimulated, the action potential or local potential change causes a very weak magnetic field, and the detection of the magnetic field can be realized by a high-sensitivity magnetic sensor, wherein the high-sensitivity magnetic sensor can be a high-sensitivity optical fiber magnetic field sensor or a high-sensitivity atomic magnetometer. The magnetic sensor is placed close to the cell, so that the magnetic field change of the cell under the external stimulation can be conveniently captured. When the external stimulation is continuously carried out or the external stimulation is carried out with different strengths, the magnetic field change of the cell can be continuously detected to obtain the magnetic field change condition of the cell under the condition of different external stimulation, so that the relationship between the cell activity and the magnetic field change can be conveniently researched, and a foundation is laid for the magnetic research on a cell layer.
Example 1
Fig. 1 is a schematic view of a magnetic shield device according to the present invention, fig. 1A is a schematic sectional view of the device, and fig. 1B is a schematic sectional view of the device. The device comprises casing and lid, the casing comprises a plurality of cylindric shells not of uniform size, and each shell is coaxial to be arranged, and is fixed through three fixed latch between each shell, and three fixed latch alternate arrangement, two adjacent shells are each other not contact, can effectively improve the magnetic screen effect. Each shell is provided with an opening, each opening is provided with a corresponding detachable shell cover, the plurality of shell covers form a cover body, and the shell covers are made of permalloy or other substances with high magnetic permeability. Through the matching of the shell and the cover body, a non-magnetic cavity can be formed inside the magnetic shielding device.
The magnetic shield device is provided with a compensation coil therein, and the arrangement of the compensation coil is as shown in fig. 2. The compensation coil is arranged on the innermost shell and can be divided into two parts, one part is spirally wound on the outer cylinder wall of the innermost shell and can be called as a winding coil, and the other part is arranged on the inner side wall or the outer side wall of one side opposite to the shell cover and can be called as a bottom coil. The compensating coil which is spirally wound on the cylinder wall of the innermost shell is an electric lead, a plurality of electric leads can be spirally wound on the cylinder wall in one direction, uniform current can be generated, so that a uniform magnetic field can be generated, the plurality of electric leads can be spirally wound in two directions, the current on the coil can be respectively regulated and controlled in the two directions, and the better shielding effect of the residual magnetic field in the inner part can be achieved.
The bottom coil may be spiral or multi-branched. The spiral coil can be communicated with current with uniform magnitude, each part has the same current magnitude, the effect of uniform current distribution is achieved, and a relatively uniform compensation magnetic field can be generated. The multi-branch coil is provided with a plurality of direct currents (8 direct currents in the figure), each direct current can be independently distributed with the current of each direct current through the current distributor, the multi-branch coil has the characteristic that the current part can be regulated, and each direct current can be regulated to different currents, so that magnetic fields with different sizes are generated to adapt to the complex and variable magnetic field conditions.
Example 2
As shown in fig. 3, in addition to the structure described in embodiment 1, the magnetic shielding device has a small hole above the housing, and a simple pendulum device is mounted on the hole for external stimulation of the cells. The prepared cell culture solution is connected to the simple pendulum device through a nonmagnetic lead. The lead is set to be of a fixed length, and the distance between the cell culture solution and the lower high-sensitivity magnetic sensor is guaranteed to be 0.5-1 cm. The cell culture solution is guided by the simple pendulum device to do periodic simple pendulum motion by taking the sensor as the center. The high-sensitivity magnetic sensor is fixed to the housing of the magnetic shield device by a fixing lever.
The simple pendulum device can be any device which provides simple pendulum motion for the cell culture solution, and the simple pendulum motion can provide fluid shear force for the cell culture solution, and the fluid shear force is one of the physical stimuli. The non-magnetic lead can be made of non-magnetic materials such as polyethylene and the like, so that the lead is ensured not to interfere with an internal magnetic field. The high-sensitivity magnetic sensor is a high-sensitivity optical fiber magnetic field sensor or a high-sensitivity atomic magnetometer, and the cell culture solution is a specific culture medium required by the tested cells.
Example 3
Using murine fibroblasts as an example, the field weakening of murine fibroblasts was measured using the apparatus described in example 2, murineThe culture medium required for fibroblasts is a nonmagnetic MEM culture medium. Two groups of experiments are set, one group is an experiment group, the other group is a blank group, and the experiment group is prepared by adding MEM culture medium and 2 x 10 medium into a cell culture bottle5cells/ml mouse fibroblasts, blank group added only equal amount of MEM medium. As shown in FIG. 4, which is a schematic diagram of the testing process of murine fibroblasts, MEM medium and 2X 10 medium were placed in a cell culture flask5Mouse fibroblasts of cells/ml are connected to a simple pendulum device arranged above a magnetic shielding device through an opening of the magnetic shielding device by a nonmagnetic polyethylene connecting line, and the distance between a cell culture bottle and a high-sensitivity magnetic sensor at the lower part is ensured to be 0.5-1 cm. Under the traction of the simple pendulum device, the cell culture bottle does periodic simple pendulum motion above the sensor, and continuously collects signals sent by the sensor in the process of swinging. After the collection of the signals of the murine fibroblasts was completed, the cell culture flasks to which only the MEM medium was added were tested according to the same method.
The signals obtained from the two experiments are analyzed and processed to obtain a cell extremely-low magnetic field signal diagram, as shown in fig. 5 and 6, fig. 5 is an extremely-low magnetic field signal diagram of mouse fibroblasts, fig. 6 is an extremely-low magnetic field signal diagram of the MEM medium, and as can be seen from the diagrams, the magnetic field test data of the mouse fibroblasts have obvious peaks, and the magnetic field test data of the MEM medium is closer to the data of noise. It can be shown that the method of the present invention can detect very weak magnetic fields of cells well.
Example 4
Taking rat nerve cells, namely schwann cells as an example, the weak magnetism of the rat schwann cells is measured by adopting the device described in the embodiment 2, and the culture solution required by the rat schwann cells is nonmagnetic DMEM culture solution. The experiment is set up in two groups, one group is experiment group, the other group is blank group, the experiment group is added with DMEM culture medium and 2 x 10 culture medium in cell culture bottle5cells/ml rat Schwann cells, blank group added only equivalent amount of DMEM medium. Placing the cell culture bottle into a DMEM medium and 2 x 105Mouse nerve cells of cells/ml are connected to a simple pendulum device arranged above the magnetic shielding device through an opening of the magnetic shielding device by a nonmagnetic polyethylene connecting wire, so that fineness is guaranteedThe distance between the cell culture bottle and the high-sensitivity magnetic sensor at the lower part is 0.5-1 cm. Under the traction of the simple pendulum device, the cell culture bottle does periodic simple pendulum motion above the sensor, and continuously collects signals sent by the sensor in the process of swinging. After completion of signal collection of rat schwann cells, cell culture flasks added with DMEM medium only were tested according to the same method.
And (3) analyzing and processing the signals obtained in the two groups of experiments to obtain a cell extremely-weak magnetic field signal diagram, wherein as shown in fig. 7 and 8, fig. 7 is the extremely-weak magnetic field signal diagram of the rat schwann cells, and fig. 8 is the extremely-weak magnetic field signal diagram of the DMEM culture medium. Therefore, the method can well detect the extremely weak magnetic field of different cells.
Comparative example
Taking mouse fibroblasts as an example, the weak magnetism of the mouse fibroblasts is measured by the device described in example 2, and the culture solution required for the mouse fibroblasts is a nonmagnetic MEM culture solution. MEM Medium and 2X 10 cells were placed in a cell culture flask5Mouse fibroblasts of cells/ml are connected to a simple pendulum device arranged above a magnetic shielding device through an opening of the magnetic shielding device by a nonmagnetic polyethylene connecting line, and the distance between a cell culture bottle and a high-sensitivity magnetic sensor at the lower part is ensured to be 0.5-1 cm. The simple pendulum device is guaranteed to stand, external stimulation is not carried out on cells in any mode, and collected magnetic field signals are observed and collected.
The signals obtained from the experiment are subjected to data analysis and processing to obtain a very weak magnetic field signal diagram of the cell, as shown in fig. 9, it can be seen from the diagram that the magnetic field signals are closer to the data of noise, and therefore, it can be seen that the magnetic field signals are not generated when the cell does not receive any external stimulation.
Claims (10)
1. A non-contact cell weak magnetic determination method is characterized in that: the cell is placed in a non-magnetic environment, then an external stimulus is given to the cell, and the weak magnetic field of the cell after the external stimulus is detected by the magnetic sensor.
2. The method of measuring according to claim 1, wherein: an external stimulus given to a cell refers to any stimulus that is capable of opening the cell's ion channel, causing a change in the cell's action potential or local potential; preferably, the external stimulus administered to the cell comprises a physical stimulus, a chemical stimulus or a biological stimulus.
3. The method of measuring according to claim 2, wherein: the physical stimulation comprises mechanical stimulation, pressure stimulation, electric stimulation, optical stimulation, temperature stimulation, osmotic pressure change stimulation, stirring stimulation and fluid shear force stimulation; the chemical stimulation is achieved by applying a chemical to the cell, the chemical comprising an ion channel opener, an ion channel blocker, potassium chloride, sodium chloride, calcium chloride, or tetrodotoxin; the biostimulation is achieved by applying to the cells a biologically active substance that causes the cells to produce a change in membrane potential, the biologically active substance comprising a hormone, an enzyme, an antigen antibody or a virus.
4. The method of measuring according to claim 1, wherein: the sensitivity of the magnetic sensor is 10-12A high-sensitivity magnetic sensor of T or more; preferably, the magnetic sensor is a high-sensitivity optical fiber magnetic field sensor or a high-sensitivity atomic magnetometer.
5. The method according to claim 1 or 4, wherein: the magnetic sensor is placed in proximity to the cell.
6. The method according to any one of claims 1 to 5, wherein: the non-magnetic environment is achieved by placing the cells in a magnetic shielding device that can isolate the external magnetic field.
7. The method according to claim 6, wherein: the magnetic shielding device comprises a shell and a cavity formed by the shell, and a cover body is arranged on the shell.
8. The method of measuring according to claim 7, wherein: the shell is composed of a plurality of layers of shells which are coaxially or concentrically arranged, each layer of shell is provided with a shell cover, and each layer of shell cover forms a cover body; preferably, the case and the lid of the magnetic shield device are made of an iron-nickel alloy, preferably permalloy.
9. The method according to claim 6, 7 or 8, wherein: and a compensation coil is arranged in the magnetic shielding device and used for offsetting an internal magnetic field which cannot be shielded by the magnetic shielding device and ensuring the zero magnetic environment in the magnetic shielding device.
10. The method according to claim 7, 8 or 9, wherein: the shell of the magnetic shielding device is also provided with at least one through hole so as to facilitate the installation and the use of the magnetic sensor, the transmission of signals and the observation of cells.
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| PCT/CN2020/095711 WO2021000714A1 (en) | 2019-07-04 | 2020-06-12 | Non-contact cell flux-weakening determination method |
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| CN116482591A (en) * | 2023-04-28 | 2023-07-25 | 华中科技大学 | Device for measuring residual magnetism of object and rapidly demagnetizing |
| CN117147004A (en) * | 2023-10-30 | 2023-12-01 | 之江实验室 | High-precision temperature and magnetic field signal measuring device used in weak magnetic field environment |
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