A magnetic particle imaging based HPLC tubing blockage detection system and method

Abstract

The application discloses a kind of HPLC pipeline blockage detection system and method based on magnetic particle imaging, solve the problem that traditional indirect measurement mode relies on the experience and ability of instrument user, it is difficult to accurately identify the position and degree of blockage, low efficiency, easy to cause instrument damage.The HPLC pipeline blockage detection system and method based on magnetic particle imaging inject mobile phase containing magnetic nanoparticles into HPLC pipeline, open the flow pressure pump of HPLC to make liquid flow, then excite magnetic nanoparticles in the field-free point (FFP) of gradient field by alternating magnetic field, and use detection coil to induct the signal generated by magnetic nanoparticles, then transmit to data processing system, complete the detection of blockage position information in HPLC pipeline.The detection system and method realize real-time, non-destructive detection of HPLC pipeline blockage by the magnetic response characteristics of magnetic nanoparticles under the action of external magnetic field, can improve the accuracy and stability of analysis result, wide application range.

Description

Technical Field

[0001] The present invention belongs to the technical field of high-performance liquid chromatography pipeline detection technology, and specifically relates to a HPLC pipeline blockage detection system and method based on magnetic particle imaging that can achieve real-time, non-destructive detection of HPLC pipeline blockage through the magnetic response characteristics of magnetic nanoparticles, thereby improving the accuracy and stability of analysis results. Background Art

[0002] High-Performance Liquid Chromatography (HPLC) is an analytical instrument widely used in biology, medicine, chemical engineering, and environmental fields. However, during HPLC operation, internal piping can become clogged due to sample impurities, sediment, and other factors, affecting the instrument's analytical performance and service life. Therefore, to ensure accurate analytical results and proper instrument operation, regular cleaning and maintenance of the HPLC piping is essential.

[0003] Existing technology detects blockages in HPLC pipelines through changes in pressure and flow rate. Specifically, during HPLC system operation, the system's internal pressure is monitored in real time. Any abnormal increase or fluctuation in pressure may indicate a blockage within the pipeline. Simultaneously, the system's flow rate is monitored. Any abnormal change in flow rate may also indicate a blockage. Combining these changes in pressure and flow rate allows for a preliminary assessment and diagnosis of the HPLC's internal pipelines, identifying potential blockages. Based on the diagnostic results, appropriate maintenance measures are implemented, such as cleaning the pipelines and replacing obstructing components, to ensure the proper functioning of the HPLC system. However, this method primarily relies on indirect measurement and is highly dependent on the user's experience and skills. Once an abnormality in instrument use is detected, the pipelines must be individually inspected or dismantled, making it difficult to accurately identify the location and extent of the blockage. This results in inefficiency and can also damage the instrument. Therefore, there is a need to improve existing systems and methods for detecting HPLC pipeline blockages. Summary of the Invention

[0004] The present invention addresses the above-mentioned problems and provides a system and method for detecting HPLC pipeline blockages in real time and non-destructively by exploiting the magnetic response characteristics of magnetic nanoparticles. This can improve the accuracy and stability of analysis results and is widely applicable.

[0005] The technical solution adopted by the present invention is: the HPLC pipeline blockage detection system and method based on magnetic particle imaging includes the following steps:

[0006] Step 1: Prepare the HPLC instrument before testing and clean the internal pipes of the HPLC with ultrapure water;

[0007] Step 2: Adding magnetic nanoparticles of a specific particle size and concentration, which have been tested experimentally, to the mobile phase of HPLC to ensure uniform mixing of the magnetic nanoparticles and the mobile phase. The magnetic nanoparticles have a particle size of less than 10 nm and possess single magnetic domains and superparamagnetism, preventing their internal microscopic magnetic moments from interfering with each other.

[0008] Step 3: Turn on the HPLC instrument and allow the mobile phase containing the magnetic nanoparticles to slowly pass through the internal piping of the HPLC. During this process, the pump of the HPLC system draws the mobile phase from the injector, separates it through the chromatographic column, and then flows into the internal piping;

[0009] Step 4: Based on magnetic nanoparticle imaging technology, a magnetic field generation and detection system is used to capture the magnetic signals generated by the magnetic nanoparticles in the internal pipeline of the HPLC in real time;

[0010] Step 5: Use the system matrix method to convert the imaging problem into the solution of the matrix equation, use the least squares method to obtain the solution of the equation, and convert the detection data into an image;

[0011] Step 6: Determine whether there is blockage in the pipeline, as well as the location and degree of the blockage based on the distribution map of the magnetic nanoparticles in the pipeline;

[0012] Step 7: If there is a pipeline blockage, use a mobile robotic arm to move the magnetic field generation and detection system to the location of the pipeline blockage, and repeat the magnetic nanoparticle imaging and analysis of steps 4 and 5 to determine the specific location and extent of the blockage;

[0013] Step 8. Take appropriate cleaning and repair measures based on the location and degree of pipeline blockage to restore normal flow in the pipeline; after cleaning and repair, repeat steps 1 to 6 to confirm whether the pipeline has returned to normal;

[0014] Step 9: After the test is completed, clean the pipeline to facilitate subsequent use.

[0015] In the second step, in a system where particles do not affect each other, the magnetic moment formula of a single particle under an external magnetic field is:

[0016]

[0017] Where g is the Lande factor, μ B It is the Bohr magneton, is the reduced Planck constant, is the angular momentum of the mechanical motion of a single particle; the related magnetization intensity of the magnetic system can be calculated by the Langevin function:

[0018]

[0019] The excitation relationship formula between particle magnetization intensity M and external magnetic field is:

[0020]

[0021] Where c is the concentration of magnetic nanoparticle solution, m is the magnetic moment of the particle, μ0 is the vacuum permeability, k B is the Boltzmann constant, T P is the particle temperature.

[0022] In step 4, the magnetic field generation and detection system includes an upper cover and a lower cover, and a magnetic field generating coil is arranged between the upper cover and the lower cover; pipeline clamping baffles for fixing the detection pipeline are respectively arranged on both sides of the magnetic field generating coil; the entire magnetic field generation and detection system is connected to the detection body through a mobile robotic arm, and a base is provided at the bottom of the detection body.

[0023] The magnetic field generating coil includes a gradient field coil symmetrically arranged on the upper cover and the lower cover, an excitation coil is arranged between the upper and lower parts of the gradient field coil, and the upper and lower parts of the excitation coil are wound in the same direction; an upper detection coil and a lower detection coil are also arranged in the detection space between the upper and lower parts of the excitation coil, and a detection pipeline is located between the upper detection coil and the lower detection coil; and a Helmholtz offset coil is respectively arranged on the outer sides of the upper and lower parts of the gradient field coil.

[0024] The magnetic field generation and detection system also includes a DC power supply, an AC power supply, a series resonant circuit, a parallel resonant circuit, a bandpass filter, a phase-locked amplifier, an AD acquisition card and a host computer; the output end of the AC power supply is electrically connected to the excitation coil through the series resonant circuit; the DC gradient coil power supply in the DC power supply is electrically connected to the gradient field coil, and the DC offset coil power supply in the DC power supply is electrically connected to the Helmholtz offset coil; the detection coil is electrically connected to the parallel resonant circuit, and the parallel resonant circuit is electrically connected to the input end of the phase-locked amplifier through the bandpass filter, the output end of the phase-locked amplifier is electrically connected to the input end of the AD acquisition card, and the output end of the AD acquisition card is electrically connected to the host computer for image reconstruction.

[0025] The gradient field coil generates a gradient magnetic field, and the offset coil moves the field-free point to locate the pipeline. The excitation coil is responsible for magnetizing the particles to generate signals, and the detection coil converts the generated magnetic field signal into an electrical signal. According to the interaction law, the detection voltage caused by the change in the magnetization intensity of superparamagnetic nanoparticles is:

[0026]

[0027] Where, P R(r) represents the sensitivity of the receiving coil, i.e., all geometric parameters of the coil, such as the inner diameter of the coil and the closed surface S determined by the inner diameter of the ring around which the coil is wound; the coil sensitivity can be calculated from the magnetic field per unit current;

[0028] The voltage signal caused by the external magnetic field is:

[0029]

[0030] The final voltage measured in the receiving coil is u(t), and the signal u caused by the change in the particle magnetic field strength is P , and the excitation signal u caused by the magnetic field change E The superimposed voltage:

[0031] u(t)=u E (t)+u P (t)

[0032] After locking the detection signal of a specific frequency, the signal amplifier amplifies the electrical signal, and the data collector collects the signal and transmits it to the computer; after forming a reconstructed image, real-time imaging is completed, and then the distribution map of the magnetic nanoparticles in the pipeline is obtained.

[0033] The fifth step of determining the particle distribution corresponding to the voltage signal received in the detection coil is an inverse problem. Solving the inverse problem is usually called reconstruction. The relationship between the voltage signal and the distribution of magnetic nanoparticles is linear. After discretization in time and space, a linear equation system can be obtained:

[0034]

[0035] Where S is the system matrix, is the vector of ideal noise-free detection signals, and c is the particle concentration vector;

[0036] In reality, the measurement vector is mixed with noise The measurement vector is thus expressed as follows:

[0037]

[0038] Therefore, the actual measurement vector The relationship between and the particle distribution c can actually be described by an approximation:

[0039]

[0040] The least squares method is used to solve the problem, and the calculation results are visualized to complete the magnetic nanoparticle imaging, which is used to describe the distribution of magnetic nanoparticles in the imaging area.

[0041] The sixth step is to pre-process the magnetic nanoparticle imaging data; the magnetic nanoparticle imaging data is pre-processed, including operations such as denoising and smoothing, to improve the accuracy of subsequent analysis.

[0042] In step six, a threshold method is used to analyze the magnetic nanoparticle distribution image. The threshold method compares the pixel values ​​in the magnetic nanoparticle distribution image with a set threshold, and pixels above the threshold are regarded as the area where the magnetic nanoparticles are located, and pixels below the threshold are regarded as blank areas in the pipeline. By comparing the number of pixels in different areas, it can be determined whether there is blockage in the pipeline, as well as the location and degree of the blockage.

[0043] In step six, an image processing algorithm is used to analyze the magnetic nanoparticle distribution image; the magnetic nanoparticle distribution image is processed using an image processing algorithm, such as edge detection and morphological processing, to extract the magnetic nanoparticle area in the pipeline; by comparing the number and shape of pixels in different areas, it can be determined whether there is blockage in the pipeline, as well as the location and degree of the blockage.

[0044] The beneficial effects of the present invention: Compared with existing technologies, magnetic nanoparticle imaging (MPI) is a non-invasive imaging technology that is mainly used to visualize the distribution of magnetic nanoparticles inside an object in real time and with high resolution. This technology utilizes the magnetic response characteristics of magnetic nanoparticles under the action of an external magnetic field and detects the signals generated by the magnetic nanoparticles to achieve quantification and localization of magnetic nanoparticles.

[0045] The present invention uses magnetic nanoparticle imaging (MPI) technology to perform real-time, non-destructive detection of the internal piping of HPLC (high performance liquid chromatography), which can solve or improve the shortcomings of the existing technology and has the following characteristics:

[0046] 1. Directness: By detecting the nonlinear response characteristics of superparamagnetic nanoparticles and using detection coils to complete data reception and image reconstruction, the distribution information of magnetic nanoparticles inside the pipeline can be directly observed, realizing direct detection of pipeline blockage and avoiding misjudgment. In addition, since various positions inside small pipelines can be imaged, the blockage situation of specific parts can be intuitively observed.

[0047] 2. High precision and high accuracy: Gradient field coils are established that are opposite to each other and carry currents in the same direction, generating a field-free point FFP. The magnetic nanoparticles outside the FFP are in a saturated state. The magnetic signal received by the detection coil is generated by the magnetic nanoparticles at the location of the FFP. The offset field is then added to cause the FFP to move linearly, completing the scanning imaging of the pipeline. This method can accurately identify the location and degree of blockage in the HPLC pipeline, thereby improving detection efficiency.

[0048] 3. Non-destructive: Magnetic nanoparticle imaging technology is a non-destructive detection method that does not require disassembly of HPLC system components, avoiding the destructive problems of other technologies and reducing maintenance costs and risks.

[0049] 4. Real-time detection: The present invention can monitor pipeline blockage in real time, which helps to find and solve problems in time and improve the performance and service life of the instrument.

[0050] 5. No pollution: Magnetic nanoparticles are non-toxic, non-polluting, and highly biocompatible materials. Therefore, adding them to the HPLC system will not affect the sample or cause pollution to the environment.

[0051] 6. Wide applicability: Due to the inherent properties of magnetic nanoparticles, the present invention is applicable to various types of HPLC pipelines and is not restricted by factors such as pipeline materials and sample types. It has strong versatility and practicality. BRIEF DESCRIPTION OF THE DRAWINGS

[0052] Figure 1 It is a principle block diagram of the detection system and method of the present invention.

[0053] Figure 2 It is a structural schematic diagram of the magnetic field generation and detection system of the present invention.

[0054] Figure 3 yes Figure 2 A structural schematic diagram of the detection part of the magnetic field generation and detection system.

[0055] Figure 4 yes Figure 3 A structural diagram of the magnetic field generating coil in FIG.

[0056] Figure 5 This is an imaging result diagram of the detection system and method of the present invention when there is no blockage inside the detection pipeline.

[0057] Figure 6 This is an imaging result diagram of the detection system and method of the present invention after the internal blockage of the detection pipeline.

[0058] Explanation of the serial numbers in the figure: 1 base, 2 detection body, 3 mobile robotic arm, 4 magnetic field generation and detection system, 5 detection pipeline, 6 upper cover, 7 lower cover, 8 magnetic field generating coil, 9 pipeline clamping baffle, 10 gradient field coil, 11 excitation coil, 12 upper detection coil, 13 lower detection coil, 14 Helmholtz offset coil, 15 detection space. DETAILED DESCRIPTION

[0059] The purpose of the present invention is to provide a method for detecting blockage in the internal pipelines of a high performance liquid chromatograph (HPLC) using magnetic nanoparticle imaging technology (MPI). The present invention utilizes the magnetic response characteristics of magnetic nanoparticles to achieve real-time, non-destructive detection of HPLC pipeline blockage, thereby improving the accuracy and stability of the analysis results. This invention is a direct detection method based on magnetic nanoparticle imaging, which is different from the traditional indirect detection method using pressure and flow rate. Figure 1 The system block diagram is shown below. A mobile phase containing magnetic nanoparticles is injected into the HPLC pipeline, and the HPLC flow pump is activated to initiate liquid flow and begin detection. This process typically lasts approximately 5 minutes. The magnetic nanoparticles within the field-free point (FFP) are excited by an alternating magnetic field. This magnetization generates a magnetic field that is sensed by a detection coil and transmitted to the data processing system, enabling the detection of blockage locations within the HPLC pipeline.

[0060] The specific steps of the present invention are described in detail. The HPLC pipeline blockage detection system and method based on magnetic particle imaging include:

[0061] Step 1: If you notice distorted peaks, decreased peak heights, increased column pressure, or unstable pump head pressure in your HPLC results, this is usually caused by a clogged pipeline. Prepare the HPLC for testing by flushing the internal HPLC tubing with ultrapure water.

[0062] Step 2: Add magnetic nanoparticles (MNPs) of a specific particle size and concentration that have been experimentally tested to the mobile phase of HPLC to mix the magnetic nanoparticles and the mobile phase evenly. The magnetic nanoparticles have a particle size of less than 10 nm and have the characteristics of a single magnetic domain and superparamagnetism, so that the internal microscopic magnetic moments do not affect each other. It is understood that, depending on the specific needs of use, the magnetic nanoparticles can be superparamagnetic iron oxide (SPIOs) nanoparticles.

[0063] In a system where particles do not affect each other, the formula for the magnetic moment of a single particle under an external magnetic field is:

[0064]

[0065] Where g is the Lande factor, μ B It is the Bohr magneton, is the reduced Planck constant, is the angular momentum of the mechanical motion of a single particle; the related magnetization intensity of the magnetic system can be calculated by the Langevin function:

[0066]

[0067] The excitation relationship formula between particle magnetization intensity M and external magnetic field is:

[0068]

[0069] Where c is the concentration of magnetic nanoparticle solution, m is the magnetic moment of the particle, μ0 is the vacuum permeability, k B is the Boltzmann constant, T P is the particle temperature.

[0070] These properties of magnetic nanoparticles can produce nonlinear responses through magnetic field excitation. In the HPLC pipeline, if blockage occurs, the concentration c at the blockage point will change, and the magnetization intensity M will also change accordingly. This is the basis for the implementation of the detection system.

[0071] Step three: Turn on the HPLC instrument and allow the mobile phase containing magnetic nanoparticles to slowly pass through the internal pipeline of the HPLC; during this process, the pump of the HPLC system extracts the mobile phase from the injector, separates it through the chromatographic column, and then flows into the internal pipeline.

[0072] Step 4: Based on magnetic nanoparticle imaging technology, a magnetic field generation and detection system is used to capture the magnetic signals generated by the magnetic nanoparticles in the internal pipeline of the HPLC in real time.

[0073] The magnetic field generating and detecting system 4 comprises an upper cover 6 and a lower cover 7, and a magnetic field generating coil 8 is provided between the upper cover 6 and the lower cover 7; a pipeline clamping baffle 9 (such as Figure 3 The entire magnetic field generation and detection system 4 is connected to the detection body 2 through a mobile mechanical arm 3, and a base 1 is provided at the bottom of the detection body 2 (as shown). Figure 2 shown).

[0074] The magnetic field generating coil 8 includes a gradient field coil 10 symmetrically arranged on the upper cover 6 and the lower cover 7. An excitation coil 11 is arranged between the upper and lower parts of the gradient field coil 10. The upper and lower parts of the excitation coil 11 are wound in the same direction. An upper detection coil 12 and a lower detection coil 13 are also arranged in the detection space 15 between the upper and lower parts of the excitation coil 11. The detection pipeline 5 is located between the upper detection coil 12 and the lower detection coil 13. In addition, a Helmholtz offset coil 14 (such as Figure 4 shown).

[0075] The gradient field coils 10 are placed symmetrically up and down, and when a reverse direct current is passed through them, a gradient magnetic field is generated, with a zero magnetic field point (FFP) being generated at the center.

[0076] Excitation coil 11: generates an alternating magnetic field by passing a high-frequency alternating current to excite the magnetic nanoparticles at the center to produce a nonlinear response, and the upper and lower parts are wound in the same direction.

[0077] The upper detection coil 12 can capture the nonlinear response of magnetic nanoparticles caused by excitation and convert the magnetic signal into an electrical signal. The upper and lower parts are wound in opposite directions.

[0078] The lower detection coil 13 has the same function and manufacturing method as the upper detection coil 12, and can detect the HPLC pipeline located below. In this way, the system can detect two pipelines at the same time, greatly increasing the detection efficiency.

[0079] The Helmholtz offset coil 14 acts on the gradient magnetic field generated by the gradient field coil 10 to generate an offset magnetic field to move the zero field point up and down.

[0080] Upper cover 6 and lower cover 7: play a supporting role and protect the internal structure.

[0081] The mobile robot arm 3 causes the magnetic field to generate relative movement with the detection system 4 and the HPLC detection pipeline 5 .

[0082] The magnetic field generation and detection system 4 also includes a DC power supply, an AC power supply, a series resonant circuit, a parallel resonant circuit, a bandpass filter, a phase-locked amplifier, an AD acquisition card, and a host computer. Among them, the output end of the AC power supply is electrically connected to the excitation coil 11 through the series resonant circuit, the DC gradient coil power supply in the DC power supply is electrically connected to the gradient field coil 10, and the DC offset coil power supply in the DC power supply is electrically connected to the Helmholtz offset coil 14; the detection coils (upper detection coil 12 and lower detection coil 13) are electrically connected to the parallel resonant circuit; and the parallel resonant circuit is electrically connected to the input end of the phase-locked amplifier through the bandpass filter, the output end of the phase-locked amplifier is electrically connected to the input end of the AD acquisition card, and the output end of the AD acquisition card is electrically connected to the host computer for image reconstruction (such as Figure 1 shown).

[0083] The gradient field coil 10 generates a gradient magnetic field, and the offset coil moves the field-free point to locate the pipeline. The excitation coil 11 is responsible for magnetizing the particles to generate signals, and the detection coil converts the generated magnetic field signal into an electrical signal. According to the interaction law, the detection voltage caused by the change in the magnetization intensity of superparamagnetic nanoparticles is:

[0084]

[0085] Where, P R (r) represents the sensitivity of the receiving coil, i.e., all geometric parameters of the coil, such as the inner diameter of the coil and the closed surface S determined by the inner diameter of the ring around which the coil is wound; the coil sensitivity can be calculated from the magnetic field per unit current;

[0086] The voltage signal caused by the external magnetic field is:

[0087]

[0088] The final voltage measured in the receiving coil is u(t), and the signal u caused by the change in the particle magnetic field strength is P , and the excitation signal u caused by the magnetic field change E The superimposed voltage:

[0089] u(t)=u E (t)+u P (t)

[0090] After locking the detection signal of a specific frequency, the signal amplifier amplifies the electrical signal, and the data collector collects the signal and transmits it to the computer; after forming a reconstructed image, real-time imaging is completed, and then the distribution map of the magnetic nanoparticles in the pipeline is obtained.

[0091] Step 5: Use the system matrix method to convert the imaging problem into the solution of the matrix equation, use the least squares method to obtain the solution of the equation (there is at least one solution, and there is a unique solution when the matrix s is of full rank), and convert the detection data into an image.

[0092] Determining the particle distribution corresponding to the voltage signal received in the detection coil is an inverse problem. Solving the inverse problem is often called reconstruction. The relationship between the voltage signal and the distribution of magnetic nanoparticles is linear. After discretization in time and space, a linear system of equations can be obtained:

[0093]

[0094] Where S is the system matrix, is the vector of ideal noise-free detection signals, and c is the particle concentration vector;

[0095] In reality, the measurement vector is mixed with noise The measurement vector is thus expressed as follows:

[0096]

[0097] Therefore, the actual measurement vector The relationship between and the particle distribution c can actually be described by an approximation:

[0098]

[0099] The least squares method is used to solve the problem. The resulting concentration data can then be converted into an image using software. For example, a black-white-gray image with large numbers appearing black and small numbers appearing white can be created using Graphr software. Visualization involves creating an image using software. The calculated results are then visualized to create magnetic nanoparticle images, depicting their distribution within the imaged area.

[0100] Step 6: Based on the distribution of magnetic nanoparticles within the pipeline, determine whether there is any blockage within the pipeline, as well as the location and extent of the blockage. Preprocess the magnetic nanoparticle imaging data: The magnetic nanoparticle imaging data is preprocessed, including denoising and smoothing, to improve the accuracy of subsequent analysis.

[0101] Analysis using a threshold method or image processing algorithm: Based on the magnetic nanoparticle distribution image, a threshold method or image processing algorithm is used to analyze the presence, location, and extent of obstruction within the pipeline. Specifically, the threshold method compares the pixel values ​​in the magnetic nanoparticle distribution image with a set threshold. Pixels above the threshold are considered to be areas containing magnetic nanoparticles, while pixels below the threshold are considered to be blank areas within the pipeline. By comparing the number of pixels in different areas, the presence, location, and extent of obstruction within the pipeline can be determined.

[0102] Image processing algorithms: Using image processing algorithms such as edge detection and morphological processing, we process the magnetic nanoparticle distribution image to extract the magnetic nanoparticle regions within the pipeline. By comparing the number and shape of pixels in different regions, we can determine whether there is a blockage in the pipeline, as well as the location and extent of the blockage.

[0103] Step 7: If there is a pipeline blockage, use a mobile robotic arm to move the magnetic field generation and detection system to the pipeline blockage location, and repeat the magnetic nanoparticle imaging and analysis of steps 4 and 5 to determine the specific location and extent of the blockage.

[0104] Step 8: Take appropriate cleaning and repair measures based on the location and degree of the pipeline blockage to restore normal flow. After cleaning and repair, repeat steps 1 to 6 to confirm whether the pipeline has returned to normal.

[0105] Step nine: After the test is completed, clean the pipeline to facilitate subsequent use.

[0106] The magnetic nanoparticle detection tracer used in the present system and method is a new type of nanoparticle material with a particle size of less than tens of nanometers and a single magnetic domain structure, which has the characteristics of superparamagnetism and surface modifiability. Superparamagnetism means that magnetic nanoparticles can quickly produce a hysteresis-free magnetic response under the action of an external magnetic field, ensuring that the magnetic signal generated by the superparamagnetic magnetic nanoparticles is instantly captured by the detection coil. The surface coating of this new type of magnetic nanoparticle material can provide various functional modifications, which is convenient for various types of targeted detection. In addition, the shell of the magnetic nanoparticle material used in the present invention is made of silicon dioxide or PE agent, which is a material with good biocompatibility and high stability. It can ensure the stability and biocompatibility of the magnetic nanoparticles, thereby realizing the detection application in the HPLC pipeline.

[0107] The operating principle of the magnetic field generation and detection system is as follows: First, multiple detection tubes 5 inside an HPLC containing a mobile phase containing magnetic nanoparticles are placed in the detection position. The detection tubes 5 are secured to the plane of the FFP generated by the gradient field coil 10 using tube clamping baffles 9 on both sides. Next, the Helmholtz offset coil 14 is activated, causing the zero magnetic field point to move upward from bottom to top. Simultaneously, a high-frequency alternating current is passed through the excitation coil 11, saturating the magnetic nanoparticles outside the FFP point. At this point, the magnetic signal captured by the detection coil represents the magnetic response signal within the FFP point. Data analysis allows for single-point detection. To achieve detection at multiple points, a robotic arm is used to move the magnetic field generation and detection system or the HPLC detection tubes 5. The above steps are repeated. After completing multiple-point detection, image reconstruction is performed to visualize the internal images of the multiple tubes, thereby determining the blockage status.

[0108] Moreover, during the experiment, a magnetic nanoparticle solution with a concentration of 27.875 mg / mL was first injected into a 2 mm hose. The materials of HPLC pipelines are mostly silicone, polyethersulfone (PES), polytetrafluoroethylene (PTFE), etc., and the common pipe diameters are 1.0 mm, 2.1 mm, and 3.0 mm. Therefore, the experiment uses a pipe made of 2 mm diameter polyvinyl chloride plastic and high-performance polyolefin thermoplastic elastomer (TPE) for simulation. Then use this system to perform the test according to the above nine steps. Before the first imaging, there was no blockage inside the hose, and the imaging results are as follows. Figure 5 Then, a comparative test was conducted, in which a blockage was placed in the middle of the hose. This blockage caused the magnetic nanoparticles to stay in the pipe, thus forming a signal interruption. Subsequently, imaging was performed using this system according to specific steps to obtain the imaging results after the blockage, as shown in the figure below. Figure 6 shown.

[0109] As can be seen from the experimental result graph, before the blockage, the signal inside the hose is continuous without any discontinuity, and the maximum signal value is 29.970 μV; however, after the blockage, due to the fact that the magnetic nanoparticles cannot pass through or only a small amount of magnetic nanoparticles pass through, the signal is much weaker than that in the non-blockage area and is almost 0. Therefore, the signal inside the hose has a clear discontinuity, and the discontinuity is the location of the blockage. In addition, observing the x-axis in the graph, the width of the maximum voltage signal value is about 2 mm, which is close to the diameter of the experimental hose, thereby indicating that the system has a high enough resolution.

[0110] The high-efficiency liquid chromatograph internal pipeline blockage detection system and method based on the magnetic nanoparticle imaging technology can accurately detect the blockage of the pipeline and accurately locate the position of the blockage, thereby helping researchers to timely find problems such as pipeline blockage during the use of the high-efficiency liquid chromatograph, and effectively improving the use efficiency and accuracy of the high-efficiency liquid chromatograph.

Claims

1. A HPLC pipeline obstruction detection system and method based on magnetic particle imaging, characterized in that: The steps include: Step 1: Prepare the HPLC instrument before testing and clean the internal pipes of the HPLC with ultrapure water; Step 2: Adding magnetic nanoparticles of a specific particle size and concentration, which have been tested experimentally, to the mobile phase of HPLC to ensure uniform mixing of the magnetic nanoparticles and the mobile phase. The magnetic nanoparticles have a particle size of less than 10 nm and possess single magnetic domains and superparamagnetism, preventing their internal microscopic magnetic moments from interfering with each other. Step 3: Turn on the HPLC instrument and allow the mobile phase containing the magnetic nanoparticles to slowly pass through the internal piping of the HPLC. During this process, the pump of the HPLC system draws the mobile phase from the injector, separates it through the chromatographic column, and then flows into the internal piping; Step 4: Based on magnetic nanoparticle imaging technology, a magnetic field generation and detection system is used to capture the magnetic signals generated by the magnetic nanoparticles in the internal pipeline of the HPLC in real time; Step 5: Use the system matrix method to convert the imaging problem into the solution of the matrix equation, use the least squares method to obtain the solution of the equation, and convert the detection data into an image; Step 6: Determine whether there is blockage in the pipeline, as well as the location and degree of the blockage based on the distribution map of the magnetic nanoparticles in the pipeline; Step 7: If there is a pipeline blockage, use a mobile robotic arm to move the magnetic field generation and detection system to the location of the pipeline blockage, and repeat the magnetic nanoparticle imaging and analysis of steps 4 and 5 to determine the specific location and extent of the blockage; Step 8. Take appropriate cleaning and repair measures based on the location and degree of pipeline blockage to restore normal flow in the pipeline; after cleaning and repair, repeat steps 1 to 6 to confirm whether the pipeline has returned to normal; Step 9: After the test is completed, clean the pipeline to facilitate subsequent use.

2. The HPLC pipeline obstruction detection system and method based on magnetic particle imaging according to claim 1, characterized in that: In the second step, in a system where particles do not affect each other, the magnetic moment formula of a single particle under an external magnetic field is: Where g is the Lande factor, μ B It is the Bohr magneton, is the reduced Planck constant, is the angular momentum of the mechanical motion of a single particle; the related magnetization intensity of the magnetic system can be calculated by the Langevin function: The excitation relationship formula between particle magnetization intensity M and external magnetic field is: Where c is the concentration of magnetic nanoparticle solution, m is the magnetic moment of the particle, μ0 is the vacuum permeability, k B is the Boltzmann constant, T P is the particle temperature.

3. The HPLC pipeline obstruction detection system and method based on magnetic particle imaging according to claim 1, characterized in that: In step 4, the magnetic field generating and detecting system (4) comprises an upper cover (6) and a lower cover (7), and a magnetic field generating coil (8) is provided between the upper cover (6) and the lower cover (7); pipeline clamping baffles (9) for fixing the detection pipeline (5) are respectively provided on both sides of the magnetic field generating coil (8); the entire magnetic field generating and detecting system (4) is connected to the detection body (2) through a mobile mechanical arm (3), and a base (1) is provided at the bottom of the detection body (2).

4. The HPLC pipeline obstruction detection system and method based on magnetic particle imaging according to claim 3, characterized in that: The magnetic field generating coil (8) comprises a gradient field coil (10) symmetrically arranged on an upper cover (6) and a lower cover (7); an excitation coil (11) is arranged between the upper and lower parts of the gradient field coil (10); the upper and lower parts of the excitation coil (11) are wound in the same direction; an upper detection coil (12) and a lower detection coil (13) are also arranged in a detection space (15) between the upper and lower parts of the excitation coil (11); a detection pipeline (5) is located between the upper detection coil (12) and the lower detection coil (13); and a Helmholtz offset coil (14) is respectively arranged on the outer sides of the upper and lower parts of the gradient field coil (10).

5. The HPLC pipeline obstruction detection system and method based on magnetic particle imaging according to claim 3, characterized in that: The magnetic field generation and detection system (4) also includes a DC power supply, an AC power supply, a series resonant circuit, a parallel resonant circuit, a bandpass filter, a lock-in amplifier, an AD acquisition card and a host computer; the output end of the AC power supply is electrically connected to the excitation coil (11) through the series resonant circuit; the DC gradient coil power supply in the DC power supply is electrically connected to the gradient field coil (10), and the DC offset coil power supply in the DC power supply is electrically connected to the Helmholtz offset coil (14); the detection coil is electrically connected to the parallel resonant circuit, and the parallel resonant circuit is electrically connected to the input end of the lock-in amplifier through the bandpass filter, the output end of the lock-in amplifier is electrically connected to the input end of the AD acquisition card, and the output end of the AD acquisition card is electrically connected to the host computer for image reconstruction.

6. The HPLC pipeline obstruction detection system and method based on magnetic particle imaging according to claim 4, characterized in that: The gradient field coil generates a gradient magnetic field, and the offset coil moves the field-free point to locate the pipeline. The excitation coil is responsible for magnetizing the particles to generate signals, and the detection coil converts the generated magnetic field signal into an electrical signal. According to the interaction law, the detection voltage caused by the change in the magnetization intensity of superparamagnetic nanoparticles is: Where, P R (r) represents the sensitivity of the receiving coil, i.e., all geometric parameters of the coil, such as the inner diameter of the coil and the closed surface S determined by the inner diameter of the ring around which the coil is wound; the coil sensitivity can be calculated from the magnetic field per unit current; The voltage signal caused by the external magnetic field is: The final voltage measured in the receiving coil is u(t), and the signal u caused by the change in the particle magnetic field strength is P , and the excitation signal u caused by the magnetic field change E The superimposed voltage: u(t)=u E (t)+u P (t) After locking the detection signal of a specific frequency, the signal amplifier amplifies the electrical signal, and the data collector collects the signal and transmits it to the computer; after forming a reconstructed image, real-time imaging is completed, and then the distribution map of the magnetic nanoparticles in the pipeline is obtained.

7. The HPLC pipeline obstruction detection system and method based on magnetic particle imaging according to claim 1, characterized in that: The fifth step of determining the particle distribution corresponding to the voltage signal received in the detection coil is an inverse problem. Solving the inverse problem is usually called reconstruction. The relationship between the voltage signal and the distribution of magnetic nanoparticles is linear. After discretization in time and space, a linear equation system can be obtained: Where S is the system matrix, is the vector of ideal noise-free detection signals, and c is the particle concentration vector; In reality, the measurement vector is mixed with noise The measurement vector is thus expressed as follows: Therefore, the actual measurement vector The relationship between and the particle distribution c can actually be described by an approximation: The least squares method is used to solve the problem, and the calculation results are visualized to complete the magnetic nanoparticle imaging, which is used to describe the distribution of magnetic nanoparticles in the imaging area.

8. The HPLC pipeline obstruction detection system and method based on magnetic particle imaging according to claim 1, characterized in that: The sixth step is to pre-process the magnetic nanoparticle imaging data; the magnetic nanoparticle imaging data is pre-processed, including denoising and smoothing operations, to improve the accuracy of subsequent analysis.

9. The HPLC pipeline obstruction detection system and method based on magnetic particle imaging according to claim 1, characterized in that: In step six, a threshold method is used to analyze the magnetic nanoparticle distribution image. The threshold method compares the pixel values ​​in the magnetic nanoparticle distribution image with a set threshold, and pixels above the threshold are regarded as the area where the magnetic nanoparticles are located, and pixels below the threshold are regarded as blank areas in the pipeline. By comparing the number of pixels in different areas, it can be determined whether there is blockage in the pipeline, as well as the location and degree of the blockage.

10. The HPLC pipeline obstruction detection system and method based on magnetic particle imaging according to claim 1, characterized in that: In step six, an image processing algorithm is used to analyze the magnetic nanoparticle distribution image; the image processing algorithm, including edge detection and morphological processing, is used to process the magnetic nanoparticle distribution image to extract the magnetic nanoparticle area in the pipeline; by comparing the number and shape of pixels in different areas, it can be determined whether there is blockage in the pipeline, as well as the location and degree of the blockage.

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