CN111773545A - Magnetic-thermal integrated device - Google Patents
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Abstract
The invention relates to a magnetic-thermal integrated device which comprises a low-frequency rotating magnetic field generating unit, a high-frequency alternating magnetic field generating unit and a sample operating area, wherein the sample operating area is positioned above the low-frequency rotating magnetic field generating unit, and the high-frequency alternating magnetic field generating unit comprises a heating coil which is positioned in the sample operating area. Compared with the prior art, the magnetic-thermal integrated device can realize the output of physical signals of force and heat on the same platform, does not need to move an action object, simplifies the research and use steps, and is convenient to popularize and apply; based on the same nano material platform, two different forms of treatment can be realized on the cell by only changing an external magnetic field on the magnetic-thermal integrated device, the two treatment modes have a synergistic effect, and the magnetic-thermal therapy has effectiveness and safety at the same time.
Description
Technical Field
The invention belongs to the technical field of nano medicine, and relates to a magnetic-thermal integrated device applied to tumor treatment.
Background
At present, the tumor treatment methods based on magnetic nano materials mainly include two methods, namely magnetocaloric therapy and magnetic therapy, and the corresponding magnetic field devices are also divided into two methods: a high frequency alternating magnetic field and a low frequency rotating magnetic field.
The existing high-frequency alternating magnetic field equipment can cover solution, cells, small animals, large animals and even human bodies, and tests are already carried out in the clinical stage. Magnetic induction thermotherapy based on high-frequency alternating magnetic field means that magnetic nanoparticles can convert energy of high-frequency alternating magnetic field into heat energy, and act on tumor cells to cause tumor cell death. It has been studied systematically and comprehensively in germany, the united states and china, and especially germany has pushed it to clinical trials and developed large-scale instruments suitable for human body, showing good application prospects in both brain glioma and prostate cancer treatment, but also exposing some problems. For example, in clinical magnetic thermal treatment of brain glioma, the injected dose of material is large, causing the highest temperature at the tumor site to be as high as 81.2 ℃, and local hyperthermia and heat diffusion cause a series of side reactions, such as headache, twitch, dyskinesia, tachycardia and the like.
The existing low-frequency rotating magnetic field equipment can meet the experiment of solution, cells and small animals. The magnetic mechanical force therapy based on the low-frequency rotating magnetic field is an international emerging tumor therapy method, and damages to a tumor cell substructure and a cell structure are caused by rotation after magnetic nanoparticles are self-assembled under the low-frequency rotating magnetic field to form a magnetic knife. Although magnetic treatment achieves good killing at the cellular level, tumor elimination in vivo models is less effective.
Disclosure of Invention
The invention aims to provide a magnetic-thermal integrated device which can provide a double-frequency magnetic field, can be used for double-physical magnetic thermal therapy of tumors by combining the double-frequency magnetic field responsiveness of a magnetic nano material, and overcomes the defects of single magnetic-thermal therapy and single magnetic-thermal therapy.
The purpose of the invention can be realized by the following technical scheme:
the utility model provides a magnetic force magnetism heat integrated device, the device includes that low frequency rotating magnetic field takes place unit, high frequency alternating magnetic field and takes place unit and sample operation district, and this sample operation district is located the top that low frequency rotating magnetic field takes place the unit, high frequency alternating magnetic field take place the unit and include heating coil, this heating coil is located sample operation district. The magnetic force generating device and the magnetic heat generating device are integrated on the same platform, so that the low-frequency rotating magnetic field and the high-frequency alternating magnetic field are converged in the sample operation area and are overlapped in the sample operation area, and the magnetic treatment and the magnetic heat treatment are respectively carried out on the sample in the sample operation area.
Wherein, the low-frequency rotating magnetic field is used for magnetic therapy, and the frequency range is 0-40 Hz; the high-frequency alternating magnetic field is used for performing the magnetocaloric therapy, and the frequency range is 200-700 kHz.
Further, the low-frequency rotating magnetic field generating unit comprises a fixed chassis, a rotating platform arranged on the fixed chassis, a rotating disk arranged on the top of the rotating platform and a magnet arranged on the rotating disk, wherein the sample operating area is positioned above the magnet and in the magnetic field of the magnet. The rotating disc and the magnet are driven by the rotating table to rotate, so that an alternating magnetic field is formed in the sample operation area.
Furthermore, a motor is arranged in the rotating table and is in transmission connection with the rotating disc. The motor drives the rotating disc to rotate.
Furthermore, the low-frequency rotating magnetic field generating unit also comprises a rotating speed regulator electrically connected with the motor. The rotation speed regulator is used for regulating the rotation speed of the motor. The rotating speed display screen is arranged on the rotating speed regulator, and can monitor the rotating speed in real time.
Further, the device also comprises a sample fixing mechanism, wherein the sample fixing mechanism comprises a fixing frame arranged on the fixing chassis, a fixing sleeve arranged at the top of the fixing frame and a sample cavity arranged on the fixing sleeve, and the sample cavity is positioned in the sample operation area. The sample is placed in the sample chamber, thereby immobilizing the sample in the sample manipulation zone. The holder is preferably a portal holder. The sample cavity is positioned right above the low-frequency rotating magnetic field generating unit.
Further, the heating coil is a multi-layer spiral coil, and the sample cavity is located in the heating coil.
Furthermore, the heating coil is a multilayer spiral coil with a hollow interior, the cross section of the heating coil is circular, and a cooling medium is arranged in the hollow portion. The cooling medium can be selected from water and the like.
Furthermore, the high-frequency alternating magnetic field generating unit further comprises a high-frequency heating host, wherein a positive connecting end and a negative connecting end are respectively arranged at two ends of the heating coil, and the heating coil is connected with the high-frequency heating host through the positive connecting end and the negative connecting end.
A preparation method of a functional magnetic nano material for the magnetic and magnetocaloric integrated device is characterized by comprising the following steps: the magnetic nano material is converted into a water phase with good biocompatibility through L-cysteine, and then polyethyleneimine and RGD molecules are sequentially modified on the surface of the magnetic nano material. The prepared functional magnetic nano material has excellent magnetic response and magnetocaloric conversion performance, and can be used for processing samples, so that the samples can realize magnetic treatment and magnetocaloric treatment in the magnetic magnetocaloric integrated device.
Further, the magnetic nano material is a zinc-doped iron oxide material.
The preparation method of the functional magnetic nano material specifically comprises the following steps:
(1) preparing a magnetic nano material:
reference (j.am. chem. soc.2009,131,454) synthesizes a 60nm block-type zinc-doped iron oxide material (Zn)0.4Fe2.6O4)；
(2) Preparing a functional magnetic nano material:
(2-1) adding the magnetic nano material into L-cysteine, converting the magnetic nano material into a water phase by probe ultrasonic treatment, and washing the water phase for the second time for purification;
(2-2) modifying polyethyleneimine on the surface of the magnetic nanoparticles under the catalytic action of EDC/NHS to improve the stability and dispersibility of the magnetic nanoparticles, and washing with water for the second time for purification;
(2-3) under the catalytic action of EDC/NHS, modifying RGD molecules outside the polypeptide, so that the polypeptide targets tumor cells with high integrin expression, and the endocytosis efficiency of the polypeptide is improved.
The EDC is 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride, and the NHS is N-hydroxysuccinimide.
In the step (2-1), the mass ratio of the magnetic nano material to the cysteine is 1:5, and the probe performs ultrasonic treatment for 1 hour at 48W.
In the step (2-2), the carboxyl activating process comprises the following steps: EDC/NHS (1:1.1, W%), probe sonication for 0.5h, 48W. Every 5mg of magnetic nano-particles corresponds to 0.1mmol of EDC and 50mg of polyethyleneimine, and the probe performs ultrasonic treatment for 1h at 48W.
In the step (2-3), the carboxyl activating process comprises the following steps: EDC/NHS (1:1.1, W%), probe sonication for 0.5h, 48W. Every 5mg of magnetic nano particles corresponds to 0.2mmol of EDC and 2.4mg of RGD, and the probe performs ultrasonic treatment for 1h and 48W.
The effect of L-cysteine is: the surface of the magnetic nano particle is converted into a water phase, so that the biocompatibility of the magnetic nano particle is improved; the polyethyleneimine has the function of improving the stability of the magnetic nanoparticles; the functional magnetic nano material has the function of targeting tumor cells by modifying the targeting molecule RGD on the surface of the magnetic nano material. The magnetic force and the magnetocaloric performance of the synthesized magnetic nanoparticles are characterized in series, so that the magnetic nanoparticles have good magnetic force response and magnetocaloric conversion capability and can be used as response media of different types of magnetic fields.
The functional magnetic nano material has excellent magnetic response and magnetocaloric conversion capability, and can convert magnetic field energy into mechanical energy and heat energy. Under the low-frequency rotating magnetic field, the magnetic nano particles are self-assembled to form a magnetic knife, the structure of the tumor cells is damaged under the rotating magnetic field, and biochemical signals in the cells are up-regulated to make the cells sensitive to heat; and then, the second stage of magnetic heat treatment is applied, the magnetic nano particles in the cells generate heat to further damage the cell substructure and the cell structure, and finally the tumor cells are killed, so that the effective heat treatment at low temperature is realized, the effectiveness and the safety of the treatment are ensured, and the defects existing in a single treatment means are overcome.
The application of the integrated device combined with the magnetic nano material in tumor treatment mainly comprises the application at a cellular level and/or the application at an animal level.
(1) Cellular level:
(1-1) dispersing the tumor cells in a confocal dish, and incubating for 24h to spread the tumor cells; each 35mm2The number of cells in the confocal dish was 5 × 104。
(1-2) adding a magnetic nano material, and incubating the material and cells together to ensure that the cells are endocytosed; each 35mm2The amount of Fe of the magnetic material added to the confocal dish of (1) was 25. mu.g, and the magnetic material was incubated with the cells for 24 hours.
(1-3) washing away materials which are not endocytosed, placing the confocal dish in a sample operation area of the magnetic and magnetocaloric integrated device, sequentially starting a low-frequency rotating magnetic field and a high-frequency alternating magnetic field to perform magnetic therapy and magnetocaloric therapy, and counting cell activity. The parameters of the treatment process are: low-frequency rotating magnetic field: 40mT, 15Hz, 15 min; high-frequency alternating magnetic field: 150Oe, 375kHz, 6 min. The results show that the magnetic therapy can enhance the magnetic heat therapy, and the two treatment modes have certain synergistic effect.
(2) On animal level:
(2-1) establishing a nude mouse tumor model; the volume of the subcutaneous tumor of the nude mouse is 80-100mm3Subsequent tests were performed.
(2-2) carrying out intratumoral injection on the magnetic nano material; the amount of the magnetic nano material injected in each time is 5mg/kg, and the magnetic nano material is injected three times every other day.
(2-3) placing the tumor part of the nude mouse in a sample operation area of the magnetic and magnetocaloric integrated device, sequentially starting a low-frequency rotating magnetic field and a high-frequency alternating magnetic field to perform magnetic therapy and magnetocaloric therapy, and observing the volume change of the tumor after the therapy. Each treatment was performed according to a pattern sequence of first magnetic force (40mT, 15Hz, 30min) and then magnetic heat (150Oe, 375kHz, 6min), seven times in sequence, once a day. Eventually, the mouse tumor was completely eliminated.
In view of the fact that magnetic treatment and magnetic heat treatment both use magnetic nano materials as media, the invention designs a magnetic and magnetic heat integrated platform for realizing the combination of the magnetic treatment and the magnetic heat treatment, namely, a single magnetic nano material is used as a magnetic induction medium, and two different physical treatments can be realized on tumors without moving an experimental object.
The magnetic heat integrated experimental device designed by the invention is combined with magnetic nano particles to be used for double-physical magnetic heat treatment of tumors, and mainly comprises the following contents: (1) constructing a magnetic and magnetocaloric integrated device; (2) preparing a functional magnetic nano material with excellent magnetic response and magnetocaloric conversion capability; (3) the integrated device is combined with the application of the magnetic nano material in tumor treatment. The invention integrates the low-frequency rotating magnetic field and the high-frequency alternating magnetic field into the same platform, and the two magnetic fields share the sample operation area and are independently controlled by different systems. The integrated device can induce the magnetic induction medium to generate different forces or thermal physical signals by changing the input signal of the external magnetic field, thereby realizing two different forms of killing on tumor cells and giving consideration to the safety and the effectiveness of treatment. The magnetic-thermal integrated device can adjust the frequency of a magnetic field through a switch, so that the magnetic nano material generates force and thermal physical signals in situ, a sample does not need to be moved, the experimental steps can be simplified, the complex treatment mode is realized, the compliance of a patient is improved, and the application and the popularization are facilitated.
In the invention, the therapeutic effect of the functional magnetic nano material depends on the magnetic field. The magnetic thermotherapy is suitable for deep tumor therapy because the magnetic field has the advantages of no penetration limitation and the like. The application time and space of the external magnetic field are controllable, the local action of the treatment site is also ensured, and the damage to the surrounding normal tissues is reduced.
Compared with the prior art, the invention has the following characteristics:
1) the magnetic-thermal integrated device can output physical signals of force and heat on the same platform, does not need to move an action object, simplifies research and use steps, and is convenient to popularize and apply.
2) The functional magnetic nano material prepared by the invention has excellent magnetic performance, can be self-assembled into a magnetic knife under a low-frequency rotating magnetic field, and generates magnetic force; heat can be generated under a high frequency alternating magnetic field. Based on the dual response capability of the magnetic nanoparticles, by varying the applied magnetic field, embodiments of magnetocaloric therapy are available. Therefore, based on the same nano material platform, two different forms of treatment can be realized on the cell by only changing the external magnetic field on the magnetic-thermal integrated device, the two treatment modes have a synergistic effect, and the magnetic-thermal therapy has effectiveness and safety at the same time.
3) The treatment based on the magnetic field has the advantages of space-time controllability, no penetration limitation and the like, so that the magnetic-thermal integrated device is combined with the magnetic nanoparticle-mediated magnetic-thermal therapy and is suitable for accurate treatment of deep tumors.
Drawings
FIG. 1 is a schematic structural view of a magneto-magnetocaloric integrated device according to example 1;
FIG. 2 is a TEM spectrum of the functional magnetic nanomaterial prepared in example 1;
FIG. 3 is a graph showing the magnetic properties of the functional magnetic nanomaterial prepared in example 1;
FIG. 4 is a graph showing the effect of magnetic hyperthermia mediated by the integrated device combined with magnetic nanoparticles in example 1, wherein (a) is a cell motility diagram and (b) is a photograph of a tumor site.
The notation in the figure is:
1-sample operation area, 2-heating coil, 3-fixed chassis, 4-rotating table, 5-rotating disc, 6-magnet, 7-speed regulator, 8-fixed mount, 9-fixed sleeve, 10-sample cavity, 11-high frequency heating host, 12-positive pole connecting end, 13-negative pole connecting end.
Detailed Description
The invention is described in detail below with reference to the figures and specific embodiments. The present embodiment is implemented on the premise of the technical solution of the present invention, and a detailed implementation manner and a specific operation process are given, but the scope of the present invention is not limited to the following embodiments.
Example 1:
(I) construction of magnetic force and magnetocaloric integrated device
The magnetic force generating device and the magnetic heat generating device are integrated on the same platform and controlled by independent operating systems. Magnetic force generating means, i.e. a low frequency rotating magnetic field; a magnetocaloric generating device, i.e. a high-frequency alternating magnetic field. The coil of the magnetocaloric generating device is integrated with the sample placement section of the magnetic force generating device, i.e., they share the sample manipulation section 1.
The magnetic force generating device is arranged below a heating coil 2 of the magnetic heat generating device, wherein the heating coil 2 is arranged right above the center of the magnetic force generating device, and the sample is arranged in the magnetic heat coil, and the position of the sample away from the magnetic platform is adjustable. Different magnetic fields are started according to requirements, so that the magnetic nanoparticles generate different physical signals. The concrete structure is as follows:
fig. 1 shows a magnetic magnetocaloric integrated device, which includes a low-frequency rotating magnetic field generating unit, a high-frequency alternating magnetic field generating unit, and a sample operating area 1, where the sample operating area 1 is located above the low-frequency rotating magnetic field generating unit, and the high-frequency alternating magnetic field generating unit includes a heating coil 2, and the heating coil 2 is located in the sample operating area 1.
Wherein, the low-frequency rotating magnetic field generating unit comprises a fixed chassis 3, a rotating platform 4 arranged on the fixed chassis 3, a rotating disk 5 arranged on the top of the rotating platform 4 and a magnet 6 arranged on the rotating disk 5, and the sample operating area 1 is positioned above the magnet 6 and in the magnetic field of the magnet 6. The rotating platform 4 is internally provided with a motor which is in transmission connection with the rotating disk 5. The low frequency rotating magnetic field generating unit further comprises a rotational speed regulator 7 electrically connected to the motor.
The device also comprises a sample fixing mechanism, wherein the sample fixing mechanism comprises a fixing frame 8 arranged on the fixing base plate 3, a fixing sleeve 9 arranged at the top of the fixing frame 8 and a sample cavity 10 arranged on the fixing sleeve 9, and the sample cavity 10 is positioned in the sample operation area 1. The heating coil 2 is a multi-layer spiral coil, and the sample chamber 10 is located in the heating coil 2. The heating coil 2 is a multi-layer spiral coil having a hollow interior, and a cooling medium is provided in the hollow interior.
The high-frequency alternating magnetic field generating unit further comprises a high-frequency heating host 11, a positive connecting end 12 and a negative connecting end 13 are respectively arranged at two ends of the heating coil 2, and the heating coil 2 is connected with the high-frequency heating host 11 through the positive connecting end 12 and the negative connecting end 13.
(II) a functional magnetic nano material with excellent magnetic response and magnetic-thermal conversion performance, which is prepared by the following steps:
(1) preparing a magnetic nano material:
reference (j.am. chem. soc.2009,131,454) synthesizes a 60nm block-type zinc-doped iron oxide material (Zn)0.4Fe2.6O4)；
(2) Preparing a functional magnetic nano material:
(2-1) dispersing 5mg of magnetic nano material in 13mL of absolute ethyl alcohol, weighing 2mg of cysteine, dissolving the cysteine in 2mL of secondary water, adding the cysteine solution into a magnetic nano particle system under the ultrasonic condition of a probe, carrying out magnetic separation and washing for three times with ultrasonic power of 48W and ultrasonic power of 60min for 5s and 2s at intervals, and finally fixing the volume to 10mL of secondary water, wherein the mark is lcMC;
(2-2) weighing EDC 19.17mg, NHS 12.66mg and PEI 50mg respectively in three 5mL centrifuge tubes, adding 1mL, 1mL and 3mL of secondary water respectively, and dissolving by ultrasound; uniformly ultrasonically dispersing the 10mL of lcMC, placing the mixture under an ultrasonic probe, setting parameters of 0.5h,48W, working for 5s and intermittent 2s, sequentially adding EDC and NHS into a reaction bottle in an ultrasonic opening state, and activating-COOH for 0.5 h; after the activation process is finished, adding PEI into the reaction system, and continuing to react for 1h with the same strength to finish amidation modification; after the reaction is finished, carrying out magnetic separation and washing for three times, and finally fixing the volume to 10mL of secondary water, wherein the mark is lcMCP;
(2-3) weighing EDC 38.34mg, NHS 25.32mg and RGD 2.4mg respectively in 5mL, 5mL and 15mL centrifuge tubes, adding 2mL, 2mL and 4mL secondary water respectively, and dissolving by ultrasound; placing the RGD solution under an ultrasonic probe, and activating-COOH0.5h; after the activation process is finished, taking out the RGD centrifugal tube, placing an lcMCP glass bottle under probe ultrasound, setting parameters to be 1h, 48W, working for 5s and intermittent 2s, adding an RGD solution into a reaction bottle in an ultrasonic starting state, continuing to react for 1h, and finishing amidation modification; after the reaction was completed, the mixture was washed by magnetic separation for three times, and finally the volume was adjusted to 10mL in secondary water, which was labeled as lcMCPR.
Characterization of functional magnetic nanomaterials: fig. 2 and fig. 3 are TEM spectra and magnetization curves of the prepared functional magnetic nano material. As can be seen from FIG. 2, the average particle size of the synthesized magnetic nanoparticles is 60nm, and the magnetic nanoparticles have uniform particle size and stable morphology; as can be seen from FIG. 3, the saturation magnetization of the magnetic nanoparticles is 98emu/g, indicating that it can be used as an excellent magnetic induction medium for mediating magnetic therapy and magnetocaloric therapy.
(III) application of integrated device combined with magnetic induction medium in tumor treatment
(1) Cell level
(1-1) digestion of tumor cells and dispersion in 35mm2In the confocal dish, the number of cells in each dish was 5 × 104Incubating for 24h to spread the mixture;
(1-2) adding magnetic nano materials into a confocal dish, adding a magnetic material containing 25 mu g of iron into each dish, and incubating the materials and cells for 24 hours to ensure that the cells are endocytosed;
(1-3) washing the materials which are not endocytosed by PBS, placing the cells in a magnetic-thermal integrated experimental device, sequentially starting a low-frequency rotating magnetic field (15Hz, 40mT, 15min) for magnetic therapy, and carrying out magnetic-thermal therapy by a high-frequency alternating magnetic field (375kHz, 150Oe, 6 min);
(1-4) after the culture is continued for 24 hours, the cell viability is counted by CCK-8. As can be seen from (a) of fig. 4, the cell viability of the magnetocaloric unit is only 9.6%, which is much lower than the cell viability of the magnetocaloric unit (62.3%) and the magnetic unit alone (67.1%), and it can be calculated that the magnetic force and the magnetocaloric heat in the magnetocaloric therapy have a synergistic effect.
(2) Animal bedding
U87 subcutaneous tumor model
Establishing a nude mouse tumor model, injecting U87 cells into the right back of the nude mouse, wherein the cell amount is 5 × 106Injection volume was 100 μ L/body; the tumor volume is 80-100mm3Then, the magnetic nano particles are injected into the tumor with the material amount of 25 mug/particle and the injection volume of 25 mug/particle, and the material is firstly injectedThree post injections, injections were given on days 0, 2, 4; the mice are placed on a magnetic thermal integration platform for magnetic thermal treatment on days 1, 3, 5, 6, 7, 8 and 9, the treatment mode is firstly magnetic treatment (15Hz, 40mT, 30min) and then magnetic thermal treatment (375kHz, 150Oe and 6min) every time, the weight and the tumor volume of the mice are recorded till 21d, the mice are dissected at the 21d, and the tumor parts of the mice are photographed, as shown in figure 4 (b), the tumors of the mice in the magnetic thermal group completely disappear, and the magnetic thermal integration device is proved to have good treatment effect on the animal level by combining the magnetic thermal treatment mediated by a magnetic induction medium.
Example 2:
(I) construction of magnetic magnetocaloric integrated device
The magnetic device and the magnetocaloric device are controlled by different operating systems, and their relative positions, such as the coil orientations, can be changed. The generation of magnetic force and magnetocaloric heat includes, but is not limited to, the specific structure in example 1.
And (II) preparation of a functional magnetic nano material with excellent magnetic performance.
(III) application of integrated device combined with magnetic induction medium in tumor treatment
(1) Cellular level: the dosage, cell types and number of the magnetic nano material can be adjusted.
(1-1) digestion of tumor cells and dispersion in 35mm2In the confocal dish, the number of cells in each dish was 1 × 105Incubating for 24h to spread the mixture;
(1-2) adding magnetic nano materials into a confocal dish, adding the magnetic materials containing 50 mu g of iron into each dish, and incubating the materials and cells for 24 hours to ensure that the cells are endocytosed;
(1-3) washing the material which is not endocytosed with PBS, putting the cells under a low-frequency rotating magnetic field (15Hz, 40mT, 15min) for magnetic treatment, and then putting the cells under a high-frequency alternating magnetic field for magnetic heat treatment (375kHz, 150Oe, 6 min);
(1-4) after the culture is continued for 24 hours, the cell viability is counted by CCK-8.
(2) Animal level
The magnetic thermotherapy can be applied to U87 in-situ brain glioma, prostatic cancer and other tumors, and especially has extremely high application value to deep tumors.
Example 3:
(I) construction of magnetic magnetocaloric integrated device
The invention emphasizes that the magnetic equipment and the magnetic-thermal equipment are integrated into a whole, the control system of the magnetic-thermal equipment can be changed, and the magnetic field frequency can be adjusted by the same system.
(II) preparation of functional magnetic nano material with excellent magnetic property
(III) application of integrated device combined with magnetic induction medium in tumor treatment
Cellular level
The invention emphasizes that the magnetic-thermal dual-physical therapy is implemented based on a magnetic nano material platform, and the sequence and the magnetic field parameters (frequency, intensity and time) of the two physical therapy means can be changed.
(1-1) digestion of tumor cells and dispersion in 35mm2In the confocal dish, the number of cells in each dish was 1 × 105Incubating for 24h to spread the mixture;
(1-2) adding magnetic nano materials into a confocal dish, adding the magnetic materials containing 50 mu g of iron into each dish, and incubating the materials and cells for 24 hours to ensure that the cells are endocytosed;
(1-3) washing the material which is not endocytosed by PBS, firstly placing the cells in a high-frequency alternating magnetic field for magnetic heat treatment (375kHz, 150Oe, 15min), and then placing the cells in a low-frequency rotating magnetic field (15Hz, 40mT, 30min) for magnetic treatment;
(1-4) after the culture is continued for 24 hours, the cell viability is counted by CCK-8.
The embodiments described above are described to facilitate an understanding and use of the invention by those skilled in the art. It will be readily apparent to those skilled in the art that various modifications to these embodiments may be made, and the generic principles described herein may be applied to other embodiments without the use of the inventive faculty. Therefore, the present invention is not limited to the above embodiments, and those skilled in the art should make improvements and modifications within the scope of the present invention based on the disclosure of the present invention.
Claims (10)
1. The magnetic and thermal integrated device is characterized by comprising a low-frequency rotating magnetic field generating unit, a high-frequency alternating magnetic field generating unit and a sample operating area (1), wherein the sample operating area (1) is positioned above the low-frequency rotating magnetic field generating unit, the high-frequency alternating magnetic field generating unit comprises a heating coil (2), and the heating coil (2) is positioned in the sample operating area (1).
2. A magnetocaloric integrated unit according to claim 1, wherein the low frequency rotating magnetic field generating unit comprises a fixed chassis (3), a rotating platform (4) disposed on the fixed chassis (3), a rotating disk (5) disposed on top of the rotating platform (4), and a magnet (6) disposed on the rotating disk (5), the sample manipulation zone (1) is located above the magnet (6) and in the magnetic field of the magnet (6).
3. A magneto-caloric integrated magnetic-thermal device as claimed in claim 2, characterized in that said rotary table (4) has a motor therein, said motor being in driving connection with said rotary table (5).
4. A magnetocaloric integrated unit according to claim 3, wherein the low frequency rotating magnetic field generating unit further comprises a speed regulator (7) electrically connected to the motor.
5. A magnetocaloric integrated device according to claim 2, characterized in that it further comprises a sample holding means comprising a holder (8) arranged on the holding chassis (3), a holding pouch (9) arranged on top of the holder (8) and a sample chamber (10) arranged on the holding pouch (9), the sample chamber (10) being located in the sample manipulation zone (1).
6. A magnetocaloric integrated unit according to claim 5, characterized in that the heating coil (2) is a multi-layer spiral coil and the sample chamber (10) is located in the heating coil (2).
7. A magnetocaloric integrated unit according to claim 6, characterized in that the heating coil (2) is a multi-layer helical coil with a hollow interior, and the hollow interior is filled with a cooling medium.
8. A magnetic magnetocaloric integrated device according to claim 6, wherein the high-frequency alternating magnetic field generating unit further comprises a high-frequency heating main unit (11), the two ends of the heating coil (2) are respectively provided with a positive connecting end (12) and a negative connecting end (13), and the heating coil (2) is connected with the high-frequency heating main unit (11) through the positive connecting end (12) and the negative connecting end (13).
9. A method for preparing a functional magnetic nanomaterial for a magnetic magnetocaloric integrated device according to any one of claims 1 to 8, the method comprising: the magnetic nano material is converted into a water phase with good biocompatibility through L-cysteine, and then polyethyleneimine and RGD molecules are sequentially modified on the surface of the magnetic nano material.
10. The method for preparing the functional magnetic nanomaterial for the integrated magnetocaloric device according to claim 9, wherein the magnetic nanomaterial is a zinc-doped iron oxide material.
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| WO2023207384A1 (en) * | 2022-04-29 | 2023-11-02 | 同济大学 | Multi-modal magnetic treatment apparatus combined with permanent magnet and electromagnetism |
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