Magnetothermal microfluidic system and microfluidic method

Abstract

The application discloses a magneto-caloric micro-fluidic system and a micro-fluidic method, and the system comprises a magneto-caloric unit, a micro-fluidic chip unit and a detection unit, the magneto-caloric unit comprises an electromagnetic coil, a magnetic core, an alternating current resonance power supply and a circuit control module, the electromagnetic coil and the magnetic core are both two, each magnetic core is embedded in an electromagnetic coil to form two magnetic core coil opposite arrangements, two electromagnetic coils are connected through a circuit connecting line, and the current directions are the same, the alternating current resonance power supply provides excitation current for the two electromagnetic coils and is connected with the circuit control module, the micro-fluidic chip unit is arranged between the two magnetic cores, and the detection unit is used for detecting samples in the micro-fluidic chip unit. The magneto-caloric sample heating volume can be improved from microliters to nanoliters, and various functional applications of the magneto-caloric technology in the micro-fluidic chip are realized.

Description

TECHNICAL FIELD

[0001] The present application relates to a magnetic heating system, in particular a magnetic heating microfluidic system and a microfluidic method, and belongs to the technical field of magnetic heating applications. BACKGROUND

[0002] Magnetic heating technology has been widely used in the fields of biological magnetic hyperthermia and induction heating of metal materials. Magnetic heating effect refers to the heat generated by magnetic loss in the magnetization process of materials in an alternating magnetic field. Magnetic loss can be mainly divided into eddy current effect, magnetic hysteresis effect and magnetization relaxation effect according to its mechanism. The heat power generated by each magnetic heating effect mechanism is determined by parameters such as magnetic field (mainly magnetic field strength and frequency), material properties and volume size.

[0003] At present, the application of magnetic heating technology mainly includes two aspects of magnetic hyperthermia and induction heating of metal materials. Magnetic hyperthermia mainly uses magnetization relaxation effect to heat nanoscale ferromagnetic or superparamagnetic medium to achieve tumor magnetic hyperthermia. For example, the MagneTherm magnetic fluid hyperthermia analysis system of Nanotherics company can achieve a magnetic field frequency of 110 kHz-987 kHz and a maximum magnetic field strength of 25 mT. The DM100 series of magnetic hyperthermia effect analyzers developed by NB (Nano Scale Biomagnetics) company can generate a magnetic field strength of 0-30 mT in a frequency range of 229.3 kHz-828 kHz. In addition, a small part uses magnetic hysteresis and eddy current effect to heat micron or millimeter scale ferromagnetic medium to achieve tumor arterial embolization hyperthermia. The frequency of the current magnetic hyperthermia equipment is about 50-1000 kHz, and the magnetic field strength does not exceed 30 mT. Induction heating mainly uses eddy current effect to heat metal materials, and its frequency range is relatively wide, about 1 kHz-2 MHz, and the magnetic field generated by its induction coil is also within 30 mT. In addition, whether it is magnetic hyperthermia or metal induction heating, the volume of the heating object is relatively large, for example, the volume of the magnetic fluid heated in magnetic hyperthermia is usually in the order of milliliter (mL) or above.

[0004] At present, the research on efficient heating of small volume magnetic medium or metal medium by using magnetic heating technology is still relatively small, and there is no report on the application of magnetic heating technology to microfluidic chip. If efficient magnetic heating can be realized in microfluidic, the advantages of magnetic heating and microfluidic chip can be combined to expand the new applications of magnetic heating technology, such as on-chip polymerase chain reaction (PCR reaction, PCR instrument based on polymerase is actually a temperature control device, which can be well controlled between denaturation temperature, annealing temperature and extension temperature) [1], on-chip magnetic-thermal coupling biological and chemical sample high-throughput sorting and detection [2], and micro-nano scale metal content detection in liquid. However, the current difficulty is the lack of efficient magnetic heating technology to heat small samples.

[0005] Although the magnetic heating technology is widely used, the volume of the heated object is usually above milliliter (for liquid) or cubic centimeter (for solid). For microliter or nanoliter level volume material, the heat production power is usually less than the heat dissipation power due to fast heat dissipation, so the current magnetic heating system cannot heat the small volume material sample by magnetic heating. In the microfluidic system, the volume of the sample is usually in nanoliter or picoliter level, and there is no report on the magnetic heating microfluidic system.

[0006] The above references are as follows:

[0007] [1] Liu H. Research on polymerase chain reaction and gene chip technology and its application in major aquatic animal virus quarantine and monitoring [D]. Central China Agricultural University, 2004.

[0008] [2] Salafi T, Zeming K K, Zhang Y. Advancements in microfluidics for nanoparticle separation [J]. Lab on a Chip, 2017, 17(1): 11-33. SUMMARY

[0009] The purpose of the present application is to solve the problems of the existing magnetic heating technology in sample heating volume and application limitation in microfluidic system, and provide a magnetic heating microfluidic system, which can improve the magnetic heating sample heating volume from microliter to nanoliter level, and realize various functional applications of magnetic heating technology in microfluidic chip.

[0010] Another purpose of the present application is to provide a magnetic heating microfluidic method.

[0011] The purpose of the present application can be achieved by adopting the following technical solutions:

[0012] The application discloses a magneto-caloric micro-fluidic system, which comprises a magneto-caloric unit, a micro-fluidic chip unit and a detection unit, wherein the magneto-caloric unit comprises two electromagnetic coils, two magnetic cores, an alternating current resonance power supply and a circuit control module; each of the electromagnetic coils and the magnetic cores is two, each magnetic core is embedded in one electromagnetic coil to form two magnetic core coil pairs which are oppositely arranged; the two electromagnetic coils are connected through a circuit connecting line and have the same current direction; the alternating current resonance power supply provides excitation current for the two electromagnetic coils and is connected with the circuit control module; the micro-fluidic chip unit is arranged between the two magnetic cores; and the detection unit is used for detecting samples in the micro-fluidic chip unit.

[0013] Further, the magneto-caloric unit further comprises a circulating cooling module, and the circulating cooling module comprises a circulating cooling pump and a circulating cooling pipeline.

[0014] Each electromagnetic coil is wound on a first support, and each magnetic core is fixed on a second support; the inside of the first support and the inside of the second support form a cooling liquid channel; and the two cooling liquid channels are connected through the circulating cooling pipeline, and the circulating cooling pump is connected with the circulating cooling pipeline.

[0015] Further, the micro-fluidic chip unit comprises a micro-fluidic chip and a liquid path control module; and the liquid path control module drives samples into the micro-fluidic chip through a connecting pipeline.

[0016] Further, the micro-fluidic chip is a magneto-caloric array micro-fluidic chip, which comprises a magneto-caloric array chip upper substrate, a magneto-caloric array chip layer and a magneto-caloric array chip lower substrate; the magneto-caloric array chip lower substrate is provided with a plurality of capture micro-holes; the capture micro-holes are used for capturing magnetic media; the magneto-caloric array chip layer is arranged above the magneto-caloric array chip lower substrate; the magneto-caloric array chip layer comprises a plurality of magneto-caloric micro-chambers; the number of the magneto-caloric micro-chambers is consistent with the number of the capture micro-holes; each capture micro-hole is located at the lower center of a corresponding magneto-caloric micro-chamber; and the magneto-caloric array chip upper substrate is arranged above the magneto-caloric array chip layer.

[0017] Further, the micro-fluidic chip is a circulating heating micro-fluidic chip, which comprises a circulating heating chip layer, a circulating heating chip substrate and a circulating heating micro-fluidic module; the circulating heating chip layer is arranged above the circulating heating chip substrate; and the circulating heating micro-fluidic module is arranged in the circulating heating chip layer.

[0018] Further, the circulating heating micro-fluidic module comprises a circulating heating chip inlet, a circulating heating chip inlet micro-channel, a circulating heating and detection cavity, a circulating heating chip outlet micro-channel and a circulating heating chip outlet which are sequentially connected.

[0019] Further, the microfluidic chip is a high-throughput metal detection microfluidic chip, the high-throughput metal detection microfluidic chip comprises a metal detection chip layer, a metal detection chip substrate and a metal detection microfluidic module, the metal detection chip layer is arranged above the metal detection chip substrate, and the metal detection microfluidic module is arranged in the metal detection chip layer.

[0020] Further, the metal detection microfluidic module comprises a first metal detection chip inlet, a second metal detection chip inlet, a first metal detection chip inlet microchannel, a second metal detection chip inlet microchannel, a metal detection chip sample mixing chamber, a metal detection chip chamber connecting channel, a metal detection chip detection chamber, a metal detection chip outlet microchannel and a metal detection chip outlet.

[0021] The first metal detection chip inlet is connected with the first metal detection chip inlet microchannel, the second metal detection chip inlet is connected with the second metal detection chip inlet microchannel, the first metal detection chip inlet microchannel and the second metal detection chip inlet microchannel are respectively connected with the metal detection chip sample mixing chamber, and the metal detection chip sample mixing chamber, the metal detection chip chamber connecting channel, the metal detection chip detection chamber, the metal detection chip outlet microchannel and the metal detection chip outlet are sequentially connected.

[0022] Further, the detection unit comprises a thermal infrared detection module, a data acquisition module and a fluorescence detection module, probes of the thermal infrared detection module and the fluorescence detection module are aligned with samples in the microfluidic chip unit, and the data acquisition module is connected with the thermal infrared detection module and the fluorescence detection module through data connection lines.

[0023] Another purpose of the present application can be achieved by adopting the following technical solutions:

[0024] A microfluidic method is realized based on the above-mentioned magnetic heating microfluidic system, and the method comprises the following steps:

[0025] The output frequency, current size and power-on time of the alternating current resonance power supply are controlled through the circuit control module.

[0026] An alternating strong magnetic field is generated in a specific area of the microfluidic chip unit through cooperation of the alternating current resonance power supply, the electromagnetic coil and the magnetic core.

[0027] The sample in the microfluidic chip unit is detected through the detection unit, so that quantitative or qualitative detection of the metal sample, the magnetic sample or the biological sample is realized.

[0028] The present application has the following beneficial effects relative to the prior art:

[0029] This invention amplifies and focuses an alternating magnetic field into a specific region using a magnetocaloric unit (the magnetic field strength can reach 200mT at 400kHz). This enables highly efficient magnetocaloric processing of trace amounts of metallic or magnetic media (in nanoliters or picoliters) within a microfluidic chip unit, achieving rapid sample heating and detection. It can be applied to rapid metal content detection, thermal stress studies of single biological samples, and PCR nucleic acid amplification and detection. Furthermore, the metallic or magnetic media can achieve an arrayed magnetocaloric-thermophoretic coupling effect, enabling efficient enrichment, sorting, and detection of biochemical samples. The arrayed microfluidic chip can simultaneously enrich and detect 1-10,000 samples, achieving high-throughput sample processing compared to current thermophoretic enrichment and detection methods (single microchamber). Attached Figure Description

[0030] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on the structures shown in these drawings without creative effort.

[0031] Figure 1 This is a schematic diagram of the overall structure of the magnetothermal microfluidic system according to Embodiment 1 of the present invention.

[0032] Figure 2 This is a top view of the overall structure of the magnetothermal microfluidic system according to Embodiment 1 of the present invention.

[0033] Figure 3 This is a front view of the overall structure of the magnetothermal microfluidic system according to Embodiment 1 of the present invention.

[0034] Figure 4 This is a three-dimensional structural diagram of the magnetic core coil and microfluidic chip of Embodiment 1 of the present invention.

[0035] Figure 5 This is a side view of the magnetic core coil and microfluidic chip of Embodiment 1 of the present invention.

[0036] Figures 6a-6d This is a schematic diagram of the magnetic core coil assembly in Embodiment 1 of the present invention.

[0037] Figure 7 This is a front view of the magnetic core coil of Embodiment 1 of the present invention.

[0038] Figure 8 for Figure 7 AA cross-section view.

[0039] Figure 9 for Figure 7 BB cross-section.

[0040] Figure 10 for Figure 7 CC cross-section view.

[0041] Figure 11 This is a top view of the magnetic core coil of Embodiment 1 of the present invention.

[0042] Figure 12 for Figure 11 DD cross-sectional view.

[0043] Figure 13 for Figure 11 EE cross-section.

[0044] Figure 14 for Figure 11 FF cross-section.

[0045] Figure 15 This is a side view and cross-sectional view of the magnetic core coil of Embodiment 1 of the present invention.

[0046] Figure 16 This is a three-dimensional structural diagram of the magnetocaloric array microfluidic chip of Embodiment 2 of the present invention.

[0047] Figure 17 This is a top view of the magnetocaloric array microfluidic chip of Embodiment 2 of the present invention.

[0048] Figure 18 This is a front view of the magnetocaloric array microfluidic chip of Embodiment 2 of the present invention.

[0049] Figure 19 This is a side view of the magnetocaloric array microfluidic chip of Embodiment 2 of the present invention.

[0050] Figure 20 This is a schematic diagram illustrating the principle of thermophoretic enrichment of particles using a magnetothermal array microfluidic chip according to Embodiment 2 of the present invention.

[0051] Figure 21 This is a three-dimensional structural diagram of the circulating heating microfluidic chip of Embodiment 3 of the present invention.

[0052] Figure 22 This is a top view of the circulating heating microfluidic chip of Embodiment 3 of the present invention.

[0053] Figure 23 This is a front view of the circulating heating microfluidic chip of Embodiment 3 of the present invention.

[0054] Figure 24 This is a side view of the circulating heating microfluidic chip according to Embodiment 3 of the present invention.

[0055] Figure 25 This is a three-dimensional structural diagram of the high-throughput metal detection microfluidic chip of Embodiment 4 of the present invention.

[0056] Figure 26 This is a top view of the high-throughput metal detection microfluidic chip in Embodiment 4 of the present invention.

[0057] Figure 27 This is a front view of the high-throughput metal detection microfluidic chip in Embodiment 4 of the present invention.

[0058] Figure 28 This is a side view of the high-throughput metal detection microfluidic chip in Embodiment 4 of the present invention.

[0059] Among them, 1-electromagnetic coil, 2-magnetic core, 3-first support, 4-second support, 5-coolant channel, 6-support connection port, 7-circulating cooling pump, 8-circulating cooling pipe, 9-AC resonant power supply, 10-circuit control module, 11-circuit connection line, 12-microfluidic chip, 13-liquid circuit control module, 14-connection pipe, 15-thermal infrared detection module, 16-data acquisition module, 17-data connection line, 18-fluorescence detection module, 19-magnetothermal microchamber, 20-magnetothermal array chip layer, 21-magnetothermal array chip upper substrate, 22-magnetothermal array chip lower substrate, 23-capture micropore, 24-magnetic medium, 25-circulating heating chip layer, 26-circulating heating chip substrate, 27-first circulating heating chip inlet, 28-first circulating heating chip inlet microchannel, 29-first circulating heating and detection chamber, 30-first circulating heating chip outlet microchannel, 31-first circulating heating core 32 - Second cycle heating chip inlet; 33 - Second cycle heating chip inlet microchannel; 34 - Second cycle heating and detection chamber; 35 - Second cycle heating chip outlet microchannel; 36 - Second cycle heating chip outlet; 37 - Third cycle heating chip inlet; 38 - Third cycle heating chip inlet microchannel; 39 - Third cycle heating and detection chamber; 40 - Third cycle heating chip outlet microchannel; 41 - Third cycle heating chip outlet; 42 - Metal detection chip layer; 43 - Metal detection chip substrate; 44 - First metal detection chip inlet; 45 - First metal detection chip inlet microchannel; 46 - Second metal detection chip inlet; 47 - Second metal detection chip inlet microchannel; 48 - Metal detection chip sample mixing chamber; 49 - Metal detection chip chamber connection channel; 50 - Metal detection chip detection chamber; 51 - Metal detection chip outlet microchannel; 52 - Metal detection chip outlet. Detailed Implementation

[0060] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are some embodiments of the present invention, but not all embodiments. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are within the scope of protection of the present invention.

[0061] Example 1:

[0062] like Figure 1 As shown, this embodiment provides a magnetothermal microfluidic system, which includes a magnetothermal unit, a microfluidic chip unit, and a detection unit. The magnetothermal unit provides an alternating strong magnetic field to a specific area of ​​the microfluidic chip unit, thereby heating the metallic or magnetic medium within that area. The microfluidic chip unit serves as a carrier for sample reaction, control, and detection. Based on efficient heating of trace samples, it achieves functions such as enrichment, detection, and reaction of various biochemical samples through specific microchannel structures. For example, it can use magnetic beads to achieve the function of enriching and sorting biochemical samples through magnetothermal-thermophoretic coupling effect, pre-aggregating metals or magnetic media to be detected, and performing functions such as thermal stress reaction and PCR amplification reaction of biological samples. The detection unit performs thermal infrared detection and / or fluorescence detection on the samples in the microfluidic chip, thereby achieving quantitative or qualitative detection of metallic, magnetic, or biological samples.

[0063] like Figures 1-3 As shown, the magnetothermal unit includes an electromagnetic coil 1, a magnetic core 2, an AC resonant power supply 9, and a circuit control module 10. There are two electromagnetic coils 1 and two magnetic cores 2. Each magnetic core 2 is embedded in an electromagnetic coil 1, forming two magnetic core coils arranged opposite each other. The two electromagnetic coils 1 are connected by a circuit connection line 11, and the current directions are the same. The AC resonant power supply 9 provides excitation current to the two electromagnetic coils 1 and is connected to the circuit control module 10.

[0064] Furthermore, each electromagnetic coil 1 is wound on a first support 3. The electromagnetic coil 1 is made of conductive metals such as copper and aluminum, with a wire diameter ranging from 0.3 to 10 mm. Each coil has 1 to 3000 turns. The electromagnetic coil 1 is wound along the length of the magnetic core 2. The distance from the innermost coil of the electromagnetic coil 1 to the surface of the magnetic core 2 is 1 to 50 mm. Two electromagnetic coils 1 are connected in series or in parallel in the same direction through a circuit connection line 11. In this embodiment, series connection is used, meaning the current direction is the same. The magnetic core 2 is fixed on a second support 4. The magnetic core 2 can be a columnar body with any cross-sectional shape (e.g., rectangular, circular, triangular, etc.), with a length of 10 to 200 mm and a cross-sectional area of ​​1 to 10000 mm². 2The magnetic core 2 is made of a high-permeability material, such as permalloy, silicon steel, ferrite, etc. The magnetic core 2 can be a one-piece structure or a stack of sheet structures. The distance between the two magnetic cores 2 is 1-300mm. When the electromagnetic coil 1 is supplied with alternating current, it will generate an alternating magnetic field. At this time, the magnetic core 2 will be magnetized, thereby amplifying the magnetic field of the coil and focusing it on the area between the two magnetic cores, that is, the area where the microfluidic chip 12 is located.

[0065] Furthermore, the AC resonant power supply 9 can provide an adjustable AC power supply to the electromagnetic coil 1 to drive the electromagnetic coil 1 to generate a high-intensity alternating magnetic field. This alternating magnetic field is further amplified by the magnetic core 2 and focused onto a specific area where the microfluidic chip 12 is located. This alternating magnetic field can generate a magnetocaloric effect on the metallic and magnetic media within the microfluidic chip 12. The circuit control module 10 can control the output frequency, current magnitude, and energizing time of the AC resonant power supply 9, thereby controlling the temperature rise and fall and temperature gradient within the microfluidic chip 12. The output frequency adjustment range is 20-1000kHz, the output current adjustment range is 1-100A, and the energizing time can be any time. Through the cooperation of the AC resonant power supply 9, the electromagnetic coil 1, and the magnetic core 2, a strong alternating magnetic field can be generated in a specific area of ​​the microfluidic chip 12. The maximum magnetic field strength can reach 200mT at a frequency of 400kHz, providing a magnetic field basis for heating trace samples within the microfluidic chip 12.

[0066] Furthermore, the magnetothermal unit also includes a circulating cooling module, which can cool the magnetic core 2 and power electronic components, enabling the power supply to operate for extended periods. The circulating cooling module includes a circulating cooling pump 7 and a circulating cooling pipe 8. The first bracket and the second bracket are sealed together through the bracket connection port 6, forming a coolant channel 5 inside the two brackets. The two coolant channels 5 are connected through the circulating cooling pipe 8, and the circulating cooling pump 7 is connected to the circulating cooling pipe 8. Under the action of the circulating cooling pump 7, the coolant is circulated into the two coolant channels 5, thereby cooling the magnetic core 2.

[0067] Furthermore, the microfluidic chip unit includes a microfluidic chip 12 and a liquid path control module 13. The liquid path control module 13 drives the sample into the microfluidic chip 12 through a connecting pipe 14. The microfluidic chip 12 can be composed of different microchambers and microchannels according to specific application scenarios, such as: 1) arrayed magnetothermal-thermophoretic microchambers for high-throughput enrichment and sorting of biochemical samples, or for thermal stress studies of biological samples; 2) cyclic heating microchambers for PCR nucleic acid amplification; 3) high-throughput microchambers for the detection of metal or magnetic media content. All of the above chip structures can be controlled by the liquid path control module 13. The sample position is controlled, thereby controlling the sample's temperature rise and fall. The sample in the microchamber is controlled by the liquid path control module 13 and the connecting pipe 14, which can drive the sample into the corresponding functional microchamber according to the specific application. Through the magnetocaloric effect, the temperature can be raised in a specific area within the microchamber of the microfluidic chip 12, forming a certain temperature gradient. Combined with the microchamber with a specific structure and the liquid path control module, local temperature rise and fall and on-chip thermophoresis can be achieved, which can be used to achieve functions such as sorting and enrichment of micro and nanoscale biochemical samples, on-chip PCR, and thermal stress research on biological samples with the help of functional magnetic beads.

[0068] Furthermore, the temperature rise and fall and aggregation state of the sample in the microfluidic chip can be detected by the detection unit. In this embodiment, the detection unit has two detection methods: thermal infrared detection and fluorescence detection. Therefore, the detection unit may include a thermal infrared detection module 15, a data acquisition module 16, and a fluorescence detection module 18. The probes of the thermal infrared detection module 15 and the fluorescence detection module 18 are aligned with the sample within the microfluidic chip unit. In this embodiment, the thermal infrared detection module 15 and the fluorescence detection module 18 are arranged facing each other. The data acquisition module 16 is connected to the thermal infrared detection module 15 and the fluorescence detection module 18 respectively via data connection lines 17. In this embodiment, the thermal infrared detection module 15 is positioned above the microfluidic chip 12, and the fluorescence detection module 18 is positioned below the microfluidic chip 12. However, those skilled in the art will readily understand that the thermal infrared detection module 15 can also be positioned below the microfluidic chip 12, and the fluorescence detection module 18 can be positioned above the microfluidic chip 12. The thermal infrared detection module 15 and the fluorescence detection module 18 are connected to the same data acquisition module 16. The data acquisition module 16 can acquire and display fluorescence and thermal infrared signals in real time, and can convert fluorescence or thermal infrared signals into electrical signals. This data acquisition module can acquire both detection signals simultaneously or acquire only one signal, meeting the needs of different application scenarios. Thermal infrared detection can directly monitor temperature changes on the surface of the solution in the microcavity, thereby detecting the content of metals or magnetic media. Fluorescence detection requires the use of appropriate fluorescent dyes, including thermosensitive fluorescent dyes and conventional fluorescent dyes. Thermosensitive fluorescent dyes can sense temperature changes and emit fluorescence of different intensities, converting the temperature signal into a fluorescence signal. The fluorescence detection system can then detect temperature changes and distribution within the microcavity, thus enabling the detection of the content of metals or magnetic media within the microfluidic chip. Furthermore, after labeling biochemical samples with conventional fluorescent dyes, the aggregation state of the samples can be determined by fluorescence signal detection. For example, after enriching or sorting samples through on-chip thermophoresis, changes in fluorescence signals can be used to detect the enriched samples.

[0069] Figure 4 and Figure 5 A schematic diagram showing the relative positions of the magnetic core coil and the microfluidic chip is shown, in which the microfluidic chip 12 is located in the region between the two magnetic cores 2. This region can generate an alternating strong magnetic field through the magnetic cores 2. When the magnetic field strength reaches a certain level, the magnetic core will heat up, so it needs to be cooled during operation. The coolant enters from the coolant channel 5 on one side of the second support 4, and then flows through the magnetic core 2 region inside the first support 3 to cool the magnetic core 2. Finally, it flows out from the coolant channel 5 on the other side. The coolant can cool both magnetic cores 2 simultaneously through the cooling circulation pipe 8.

[0070] Figures 6a-6dThe diagram shows the assembly of the magnetic core coil. The electromagnetic coil 1 is wound on the first bracket 3. The size of the first bracket 3 can be adjusted according to the size of the coil. The second bracket 4 can fix the magnetic core 2 and embed it in the first bracket 3, so that the magnetic core 2 is placed inside the electromagnetic coil 1 and can be better magnetized by the magnetic field of the coil. The first bracket 3 and the second bracket 4 are sealed together through the bracket connection port 6 to form a coolant channel 5. This bracket split design can flexibly adapt to magnetic cores 2 of various shapes and electromagnetic coils 1 of various specifications.

[0071] Figures 7-10 , Figures 11-14 , Figure 15 The diagram shows perspective views and cross-sectional views from three angles (front view, top view, and side view) of the assembled electromagnetic coil 1, magnetic core 2, first bracket 3, and second bracket 4. The first bracket 3 and second bracket 4 are made of materials such as plastic, nylon, and resin, and can be manufactured using processes such as 3D printing and injection molding. The part of the first bracket 4 that fixes the magnetic core 2 can be adapted to fit the shape of the magnetic core 2. Figures 7-10 , Figures 11-14 , Figure 15 The magnetic core has a cuboid structure, which forms a coolant channel 5 between the magnetic core 2 and the first support 3, so that the magnetic core 2 can be cooled and cooled in all directions during operation.

[0072] Example 2:

[0073] The magnetocaloric microfluidic system in this embodiment also includes a magnetocaloric unit, a microfluidic chip unit, and a detection unit. The difference is that the microfluidic chip in this embodiment is a magnetocaloric array microfluidic chip, such as... Figures 16-19 As shown, this magnetocaloric array microfluidic chip is mainly used for high-throughput enrichment and sorting of biochemical samples coupled with magnetocaloric-thermophoresis. It includes an upper substrate 19 of the magnetocaloric array chip, a magnetocaloric array chip layer 20, and a lower substrate 21 of the magnetocaloric array chip. The lower substrate 21 of the magnetocaloric array chip has multiple capture micropores 23, which are used to capture magnetic media 24. The magnetocaloric array chip layer 20 is disposed above the lower substrate 21 of the magnetocaloric array chip. The magnetocaloric array chip layer 20 includes multiple magnetocaloric microcavities 19. The number of magnetocaloric microcavities 19 is the same as the number of capture micropores 23. Each capture micropore 23 is located at the lower center of the corresponding magnetocaloric microcavity 19. The upper substrate 19 of the magnetocaloric array chip is disposed above the magnetocaloric array chip layer 20.

[0074] Furthermore, the substrate 22 under the magnetocaloric array chip is made of glass with high thermal conductivity, such as sapphire glass. The trapping micropores 23 on its surface are fabricated through processes such as laser engraving and etching. The trapping micropores 23 are circular or square in shape, with a cross-sectional area of ​​0.5-10000μm. 2The depth is 1-100μm and the number ranges from 1 to 1000. In this embodiment, there is a 4×6 microcavity array. Similarly, the substrate 21 on the magnetocaloric array chip is also made of glass with high thermal conductivity.

[0075] Furthermore, the magnetic medium 24 is made of micro- or nano-materials that can generate a magnetocaloric effect, such as metal microparticles, magnetic oxides, magnetic nanowires, carbon nanotubes, and graphene. The magnetic medium 24 can be a single particle or a cluster of smaller micro- or nano-particles. In this embodiment, it is a spherical particle with a cross-sectional area that is 1.1 to 3 times the cross-sectional area of ​​its corresponding trapping micropore 23. This ensures that the magnetic medium is above the trapping micropore 23 and does not sink into it completely.

[0076] Furthermore, the magnetothermal array chip layer 20 is made of materials such as polydimethylsiloxane (PDMS), acrylic sheet (PMMA), glass, plastic, and transparent resin, with a thickness of 100-2000μm. The magnetothermal microcavity 19 is a through hole processed by PDMS mold, laser cutting, wire cutting, etc., and its shape is circular or square, with a cross-sectional area 50-2000 times that of the capture microhole 23.

[0077] During the assembly of the magnetocaloric array microfluidic chip, a solution containing magnetic medium 24 is first allowed to flow over the surface of the lower substrate 22 of the magnetocaloric array chip (the side with the capture micropores). At the same time, a permanent magnet is placed below the lower substrate 22 of the magnetocaloric array chip. When the magnetic medium 24 flows over the capture micropores 23, it will be embedded in the capture micropores 23 due to the magnetic force. Since the magnetic medium 24 is slightly larger than the capture micropores 23, only a portion of the magnetic medium 24 will be embedded in the capture micropores 23, while the other portion will be exposed in the magnetocaloric microcavity 19. When most or all of the capture micropores 23 are filled with magnetic medium 24, the uncaptured magnetic medium 24 is then rinsed off with pure water to remove it from the surface of the lower substrate 22 of the magnetocaloric array chip. Then, the magnetocaloric array chip layer 20 is aligned and placed above the lower substrate 22 of the magnetocaloric array chip, so that the magnetic medium 24 is located at the lower center of the magnetocaloric microcavity 19, and the sample solution to be enriched and sorted is dropped into the magnetocaloric microcavity 19; finally, the upper substrate 21 of the magnetocaloric array chip is attached above the magnetocaloric array chip layer 20 to seal the magnetocaloric microcavity 19; wherein the magnetocaloric array chip layer 20 and the upper and lower substrates are tightly attached together by bonding, gluing or clamping to form a complete magnetocaloric array microfluidic chip.

[0078] Figure 20The diagram illustrates the principle of thermophoretic enrichment of particulate samples using a magnetocaloric array chip. Two methods are employed: thermophoresis towards a heat source and thermophoresis towards a cold source. These directions can be flexibly controlled by adjusting the thermophoretic temperature difference or the sample solute concentration. The temperature difference and duration are adjusted via the circuit control module 10. The heating range of the magnetic medium is 0-15℃, meaning the temperature difference is adjustable within this range. In the case of thermophoresis towards the heat source, on one hand, the particles in the sample are driven towards the magnetic medium 24 (heat source) by thermophoretic force; on the other hand, the heat source also induces convective motion in the sample, causing it to circulate within the magnetocaloric microchamber 19. Under the combined effect of thermophoresis and convection, the particulate sample is enriched around the magnetic medium 24, forming a ring-shaped enrichment region. Figure 20 (The black area in the image). In the case of thermophoresis towards a cold source, the particles in the sample will be moved away from the magnetic medium 24 (heat source) by the thermophoretic force. Under the combined action of thermophoresis and convection, the sample particles will be enriched near the outer periphery of the bottom chamber, forming a ring-shaped enrichment area. Figure 20 (The black area in the image). Both of these methods can achieve enrichment and sorting of micro- and nano-scale particle samples.

[0079] Example 3:

[0080] The magnetocaloric microfluidic system in this embodiment also includes a magnetocaloric unit, a microfluidic chip unit, and a detection unit. The difference is that the microfluidic chip in this embodiment is a cyclically heated microfluidic chip, such as... Figures 21-24 As shown, the circulating heating microfluidic chip includes a circulating heating chip layer 25, a circulating heating chip substrate 26, and a circulating heating microfluidic module. The circulating heating chip layer 25 is disposed above the circulating heating chip substrate 26, and the circulating heating microfluidic module is disposed in the circulating heating chip layer 25.

[0081] Furthermore, the circulating heating microfluidic module includes a circulating heating chip inlet, a circulating heating chip inlet microchannel, a circulating heating and detection chamber, a circulating heating chip outlet microchannel, and a circulating heating chip outlet connected in sequence.

[0082] Furthermore, there are three circulating heating chip inlets, three circulating heating chip inlet microchannels, three circulating heating and detection chambers, three circulating heating chip outlet microchannels, and three circulating heating chip outlets. The three circulating heating chip inlets are the first circulating heating chip inlet 27, the second circulating heating chip inlet 32, and the third circulating heating chip inlet 37. The three circulating heating chip inlet microchannels are the first circulating heating chip inlet microchannel 28, the second circulating heating chip inlet microchannel 33, and the third circulating heating chip inlet microchannel 39. The three circulating heating and detection chambers are the first circulating heating and detection chamber 29, the second circulating heating and detection chamber 34, and the third circulating heating and detection chamber 39. The three circulating heating chip outlet microchannels are the first circulating heating chip outlet microchannel 30, the second circulating heating chip outlet microchannel 35, and the third circulating heating chip outlet microchannel 40. The three circulating heating chip outlets are the first circulating heating chip outlet 31, the second circulating heating chip outlet 36, and the third circulating heating chip outlet 41.

[0083] Furthermore, the first circulating heating chip inlet 27, the first circulating heating chip inlet microchannel 28, the first circulating heating and detection chamber 29, the first circulating heating chip outlet microchannel 30, and the first circulating heating chip outlet 31 are used for heating and detecting nucleic acid sample A; the second circulating heating chip inlet 32, the second circulating heating chip inlet microchannel 33, the second circulating heating and detection chamber 34, the second circulating heating chip outlet microchannel 35, and the second circulating heating chip outlet 36 are used for heating and detecting nucleic acid sample B; and the third circulating heating chip inlet 37, the third circulating heating chip inlet microchannel 38, the third circulating heating and detection chamber 39, the third circulating heating chip outlet microchannel 40, and the third circulating heating chip outlet 36 are used for heating and detecting nucleic acid sample C.

[0084] Taking nucleic acid sample A as an example, after nucleic acid sample A and magnetic beads (magnetic medium) are uniformly mixed, they enter the first circulating heating and detection chamber 29 through the first circulating heating chip inlet 27 and the first circulating heating chip inlet microchannel 28. In the first circulating heating and detection chamber 29, nucleic acid sample A can be heated and amplified. The heating temperature and time can be controlled by the circuit control module 10, and the heating range is adjustable from 0 to 70°C. The fluorescence signal generated after sample amplification is detected by the fluorescence detection module 18 and the data acquisition module 16. After detection, the sample enters the first circulating heating chip outlet 31 through the first circulating heating chip outlet microchannel 30.

[0085] Furthermore, the cyclic heating microfluidic chip of this embodiment can also conduct thermal stress studies on magnetic bead-labeled single-cell samples (which have been fluorescently stained). The sample is passed into the cyclic heating and detection chamber. Under different controlled heating times and temperatures, the cells will generate different thermal stresses, causing changes in the fluorescence signals of the proteins on their surface. The thermal stress results can then be characterized by fluorescence detection. Theoretically, this cyclic heating microfluidic chip can simultaneously heat and detect several samples. The samples are controlled by the liquid path control module 13.

[0086] Furthermore, the material of the circulating heating chip substrate 26 is glass, plastic, or transparent resin, and the material of the circulating heating chip layer 25 is polydimethylsiloxane (PDMS), acrylic sheet (PMMA), glass, plastic, transparent resin, etc. The microchannel and microcavity structures are fabricated using MEMS technology, soft lithography, or 3D printing. The circulating heating chip layer 25 and the circulating heating chip substrate 26 are tightly attached together by bonding, adhesive, or clipping. The volumetric capacity of the first circulating heating and detection chamber 29, the second circulating heating and detection chamber, and the third circulating heating and detection chamber 39 is 0.001-2000 μL, and the number of circulating heating and detection chambers ranges from 1 to 100,000. If there are more circulating heating and detection chambers, their volume range and... Figures 21-24 The consistency of these three chambers.

[0087] Example 4:

[0088] The magnetocaloric microfluidic system in this embodiment also includes a magnetocaloric unit, a microfluidic chip unit, and a detection unit. The difference is that the microfluidic chip in this embodiment is a high-throughput metal detection microfluidic chip, such as... Figures 25-28 As shown, the high-throughput metal detection microfluidic chip includes a metal detection chip layer 42, a metal detection chip substrate 43, and a metal detection microfluidic module. The metal detection chip layer 42 is disposed above the metal detection chip substrate 43, and the metal detection microfluidic module is disposed in the metal detection chip layer 42.

[0089] Furthermore, the metal detection microfluidic module includes a first metal detection chip inlet 44, a second metal detection chip inlet 46, a first metal detection chip inlet microchannel 45, a second metal detection chip inlet microchannel 47, a metal detection chip sample mixing chamber 48, a metal detection chip chamber connection channel 49, a metal detection chip detection chamber 50, a metal detection chip outlet microchannel 51, and a metal detection chip outlet 52.

[0090] The first metal detection chip inlet 44 is connected to the first metal detection chip inlet microchannel 45, the second metal detection chip inlet 46 is connected to the second metal detection chip inlet microchannel 47, the first metal detection chip inlet microchannel 45 and the second metal detection chip inlet microchannel 47 are respectively connected to the metal detection chip sample mixing chamber 48, the metal detection chip sample mixing chamber 48, the metal detection chip chamber connecting channel 49, the metal detection chip detection chamber 50, the metal detection chip outlet microchannel 51 and the metal detection chip outlet 52 are connected in sequence.

[0091] This embodiment of the high-throughput metal detection microfluidic chip has two detection methods: thermal infrared detection and fluorescence detection. When using thermal infrared detection, a liquid sample containing metal is injected into the chip through the first metal detection chip inlet 44 and the second metal detection chip inlet 46. After passing through the first metal detection chip inlet microchannel 45 and the second metal detection chip inlet microchannel 47, it enters the metal detection chip sample mixing chamber 48. In this chamber, the metal particles in the sample can be uniformly dispersed through fluid mixing. Then, the uniformly dispersed sample enters the metal detection chip detection chamber 50 through the metal detection chip chamber connecting channel 49. This metal detection chip detection chamber 50 is an open chamber, meaning the metal detection chip layer 42 is penetrated through this chamber and directly contacts the outside air. This is to allow the thermal infrared detection module 15 to directly detect the thermal infrared signal on the sample surface. Changes in the thermal infrared signal can reflect the metal content in the sample. After final detection, the sample enters the metal detection chip outlet 52 through the metal detection chip outlet microchannel 51. When using fluorescence detection, the liquid sample containing metal is injected into the chip from the first metal detection chip inlet 44 and enters the metal detection chip sample mixing chamber 48 through the first metal detection chip inlet microchannel 45. At the same time, the thermosensitive fluorescent indicator is injected into the chip through the first metal detection chip inlet 46 and enters the metal detection chip sample mixing chamber 48 through the first metal detection chip inlet microchannel 45. In the metal detection chip sample mixing chamber 48, the metal sample and the thermosensitive fluorescent indicator will be thoroughly mixed and then enter the metal detection chip detection chamber 50 through the metal detection chip chamber connection channel 49. In the metal detection chip detection chamber 50, the metal in the sample will be heated. At this time, the thermosensitive fluorescent indicator will sense the temperature change of the sample and generate a fluorescence signal, which will be detected by the fluorescence detection module 18. The metal content in the sample can be reflected by the change of thermal infrared signal. After final testing, the sample enters the metal detection core outlet 52 through the metal detection chip outlet microchannel 51. After cleaning, the chip can be reused. In addition to detecting metal content, the chip can also detect the magnetic medium content in the sample using the same method.

[0092] Furthermore, the metal detection chip substrate 43 is made of glass, plastic, or transparent resin. The metal detection chip layer 42 is made of polydimethylsiloxane (PDMS), acrylic sheet (PMMA), glass, plastic, transparent resin, etc., and the microchannel and microcavity structures therein are fabricated using MEMS technology, soft lithography, or 3D printing. The metal detection chip substrate 43 and the metal detection chip layer 42 are tightly attached together by bonding, adhesive, or clipping. The capacity of the metal detection chip detection chamber 50 is 0.001-5000 μL.

[0093] In summary, the magnetothermal microfluidic system of the present invention has the following advantages:

[0094] 1) The principle of confined field enhancement is used to greatly improve the alternating magnetic field strength of magnetothermal therapy. The maximum magnetic field strength can reach 200mT at a frequency of 400kHz. In current magnetothermal therapy or induction heating equipment, the maximum magnetic field strength is less than 50mT.

[0095] 2) For the first time, magnetothermal and microfluidic systems are combined to achieve efficient magnetothermal processing of trace samples within the microfluidic system. It has wide applicability in fluid control systems and can achieve different functions in the biochemical field when combined with microfluidic chips of different structures and various functional magnetic beads.

[0096] 3) It can achieve high-throughput sorting and detection of biological and chemical samples coupled with magnetothermal-thermophoresis, including micron- and nano-sized samples.

[0097] 4) It can detect the metal content at the micro-nano scale in liquids and is used for the calibration and measurement of metal contaminants in oil or water.

[0098] 5) It can perform heat stress studies on single biological samples (e.g., single cells) and polymerase chain reaction (PCR) studies.

[0099] The above description is only a preferred embodiment of the present invention, but the implementation of the present invention is not limited to the above embodiments. Any changes, modifications, substitutions, combinations, or simplifications made without departing from the spirit and principle of the present invention shall be considered equivalent substitutions and shall be included within the protection scope of the present invention.

Claims

1. A magnetothermal microfluidic system, characterized in that, The device includes a magnetocaloric unit, a microfluidic chip unit, and a detection unit. The magnetocaloric unit comprises an electromagnetic coil, a magnetic core, an AC resonant power supply, a circuit control module, and a circulating cooling module. There are two electromagnetic coils and two magnetic cores, with each magnetic core embedded within an electromagnetic coil, forming two magnetic core coils arranged opposite each other. The two electromagnetic coils are connected by a circuit connection line, and the current flows in the same direction. The AC resonant power supply provides excitation current to the two electromagnetic coils and is connected to the circuit control module. The microfluidic chip unit is positioned between the two magnetic cores, and the detection unit is used to detect samples within the microfluidic chip unit. The circulating cooling module includes a circulating cooling pump and a circulating cooling pipe; each electromagnetic coil is wound on a first bracket, each magnetic core is fixed on a second bracket, the interior of the first bracket and the interior of the second bracket form a coolant channel, the two coolant channels are connected by the circulating cooling pipe, and the circulating cooling pump is connected to the circulating cooling pipe. The microfluidic chip unit includes a microfluidic chip and a liquid path control module. The liquid path control module drives the sample into the microfluidic chip through a connecting pipeline. Through the cooperation of an AC resonant power supply, an electromagnetic coil and a magnetic core, an alternating strong magnetic field is generated in a specific area of ​​the microfluidic chip, wherein the maximum magnetic field strength reaches 200mT at a frequency of 400kHz.

2. The magnetocaloric microfluidic system according to claim 1, characterized in that, The microfluidic chip is a magnetocaloric array microfluidic chip, which includes an upper substrate, a layer, and a lower substrate. The lower substrate has multiple capture micropores for capturing magnetic media. The layer is disposed above the lower substrate and includes multiple magnetocaloric microcavities, the number of which is the same as the number of capture micropores. Each capture micropore is located at the lower center of its corresponding magnetocaloric microcavity. The upper substrate is disposed above the layer.

3. The magnetocaloric microfluidic system according to claim 1, characterized in that, The microfluidic chip is a circulating heating microfluidic chip, which includes a circulating heating chip layer, a circulating heating chip substrate, and a circulating heating microfluidic module. The circulating heating chip layer is disposed above the circulating heating chip substrate, and the circulating heating microfluidic module is disposed in the circulating heating chip layer.

4. The magnetocaloric microfluidic system according to claim 3, characterized in that, The circulating heating microfluidic module includes a circulating heating chip inlet, a circulating heating chip inlet microchannel, a circulating heating and detection chamber, a circulating heating chip outlet microchannel, and a circulating heating chip outlet, which are connected in sequence.

5. The magnetocaloric microfluidic system according to claim 1, characterized in that, The microfluidic chip is a high-throughput metal detection microfluidic chip, which includes a metal detection chip layer, a metal detection chip substrate, and a metal detection microfluidic module. The metal detection chip layer is disposed above the metal detection chip substrate, and the metal detection microfluidic module is disposed in the metal detection chip layer.

6. The magnetocaloric microfluidic system according to claim 5, characterized in that, The metal detection microfluidic module includes a first metal detection chip inlet, a second metal detection chip inlet, a first metal detection chip inlet microchannel, a second metal detection chip inlet microchannel, a metal detection chip sample mixing chamber, a metal detection chip chamber connection channel, a metal detection chip detection chamber, a metal detection chip outlet microchannel, and a metal detection chip outlet; The first metal detection chip inlet is connected to the first metal detection chip inlet microchannel, the second metal detection chip inlet is connected to the second metal detection chip inlet microchannel, the first metal detection chip inlet microchannel and the second metal detection chip inlet microchannel are respectively connected to the metal detection chip sample mixing chamber, the metal detection chip sample mixing chamber, the metal detection chip chamber connecting channel, the metal detection chip detection chamber, the metal detection chip outlet microchannel and the metal detection chip outlet are connected in sequence.

7. The magnetocaloric microfluidic system according to any one of claims 1-6, characterized in that, The detection unit includes a thermal infrared detection module, a data acquisition module, and a fluorescence detection module. The probes of the thermal infrared detection module and the fluorescence detection module are aligned with the sample in the microfluidic chip unit. The data acquisition module is connected to the thermal infrared detection module and the fluorescence detection module respectively via data connection lines.

8. A microfluidic method, implemented based on the magnetocaloric microfluidic system according to any one of claims 1-7, characterized in that, The method includes: The output frequency, current magnitude, and energizing time of the AC resonant power supply are controlled by the circuit control module. By combining an AC resonant power supply, an electromagnetic coil, and a magnetic core, an alternating strong magnetic field is generated in a specific region of the microfluidic chip unit. The microfluidic chip unit detects samples, enabling quantitative or qualitative detection of metallic, magnetic, or biological samples.

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