Stem cell detection system and method based on magnetic particle equilibrium modulation

Abstract

The present invention belongs to the field of magnetic nanoparticle detection, and specifically relates to a stem cell detection system and method based on magnetic particle equilibrium modulation, aiming to solve the problem of insufficient sensitivity in the prior art when using MPI technology for tracing and detecting stem cells. The system proposed by the present invention includes a coil balance assembly and a signal modulation module. The coil balance assembly includes a first receiving coil, a second receiving coil, and a compensation coil. The signal modulation module includes a signal modulation circuit and a gain adjustment resistor. Based on this system, by using the coil balance assembly and the signal modulation module, it is ensured to reduce noise interference from the hardware system. At the same time, in the case of low noise, as much signal from stem cells as possible is extracted, thereby improving the sensitivity of stem cell detection, and stem cells in the order of hundreds can be detected.

Description

Technical Field

[0001] The present invention belongs to the field of magnetic nanoparticle detection, and particularly relates to a stem cell detection system and method based on magnetic particle equilibrium modulation. Background Art

[0002] Cell therapies based on stem cells have great potential in the treatment of various diseases, including tumors, strokes, liver diseases, etc. However, after stem cells are injected into an organism, how to migrate to diseased tissues and achieve in vivo stem cell tracing remains a challenging problem. Currently, a series of stem cell tracing studies have been carried out based on different imaging techniques such as optical imaging, radionuclide imaging, and magnetic resonance imaging. However, the processes of stem cell migration, proliferation, and differentiation have not been fully elucidated, which limits the further clinical translation of stem cell tracing.

[0003] Magnetic Particle Imaging (MPI) technology, as a new type of molecular imaging technology with non-invasive, quantitative detection, radiation-free, nanomolar sensitivity, and no penetration depth limitation, has been preliminarily applied in the field of stem cell tracing and demonstrated great potential.

[0004] Currently, due to the insufficient sensitivity of MPI in the in vivo microenvironment, the application of MPI for highly sensitive stem cell tracing is limited. In the prior art, MPI can minimally detect cell clusters composed of 2,500 in vivo stem cells. During the stem cell tracing process, as stem cells migrate, proliferate, and differentiate, the superparamagnetic iron oxide (SPIO) labeling the stem cells is diluted, and MPI cannot detect a lower number of stem cells, resulting in difficulty in tracking stem cells during the processes of proliferation and differentiation and in judging whether the stem cells still remain in the body or have been excluded. Summary of the Invention

[0005] To solve the above problems in the prior art, that is, the problem of insufficient sensitivity when using MPI to trace and detect stem cells, in a first aspect, the present invention provides a stem cell detection system based on magnetic particle equilibrium modulation, including: a coil balance component and a signal modulation module;

[0006] The coil balance component includes a first receiving coil, a second receiving coil, and a compensation coil. The first receiving coil, the second receiving coil, and the compensation coil are arranged in parallel and coaxially. The coil balance component is configured to collect the magnetic signals of the alternating magnetic field generated by magnetic particles, convert the magnetic signals into electrical signals, and transmit the electrical signals to the signal modulation module;

[0007] The signal modulation module includes a signal modulation circuit and a gain adjustment resistor; one end of the gain adjustment resistor is connected to the input end of the signal modulation circuit, and the other end is connected to the output end of the signal modulation circuit; the compensation coil is connected to the input end of the signal modulation circuit, and the first receiving coil and the second receiving coil are connected in reverse series and connected to the output end of the signal modulation circuit; the signal modulation circuit is used to amplify the voltage signal output by the compensation coil; the gain adjustment resistor is used to control the gain coefficient of the signal modulation circuit by adjusting the resistance value.

[0008] In some preferred embodiments, the first receiving coil and the second receiving coil have the same size and number of turns, and the size and number of turns of the compensation coil are smaller than those of the first receiving coil and the second receiving coil.

[0009] In some preferred embodiments, the spatial positions of the first receiving coil and the second receiving coil are uniformly symmetric, so that the voltage at the output end of the signal modulation circuit reaches a preset minimum value in the case of air measurement. The spatial positions of the first receiving coil and the second receiving coil satisfy:

[0010] ;

[0011] where V is the voltage at the output end of the signal modulation circuit, V1 is the voltage signal of the first receiving coil, V2 is the voltage signal of the second receiving coil, D is the spatial distance between the first receiving coil and the second receiving coil, and min is the preset minimum value of the voltage at the output end of the signal modulation circuit.

[0012] In some preferred embodiments, the compensation coil is arranged inside the alternating magnetic field generated by the magnetic particles, and the parameter settings of the compensation coil satisfy:

[0013] ;

[0014] where V is the voltage at the output end of the signal modulation circuit, Vc is the voltage signal of the compensation coil, N is the number of turns of the compensation coil, P is the spatial position of the compensation coil inside the alternating magnetic field, and min is the preset minimum value of the voltage at the output end of the signal modulation circuit.

[0015] In some preferred embodiments, the parameter settings of the gain adjustment resistor satisfy:

[0016] ;

[0017] where V is the voltage at the output end of the signal modulation circuit, K is the gain of the signal modulation circuit, Rg is the resistance value of the gain adjustment resistor, and min is the preset minimum value of the voltage at the output end of the signal modulation circuit.

[0018] In some preferred embodiments, the voltage at the output terminal of the signal modulation circuit is:

[0019] ;

[0020] where V is the voltage at the output terminal of the signal modulation circuit, V 1 is the voltage signal of the first receiving coil, V 2 is the voltage signal of the second receiving coil, K is the gain coefficient of the signal modulation circuit, V c is the voltage signal of the compensation coil, D is the spatial distance between the first receiving coil and the second receiving coil, N is the number of turns of the compensation coil, P is the spatial position of the compensation coil inside the alternating magnetic field, Rg is the resistance value of the gain adjustment resistor, and min is the preset minimum value of the voltage at the output terminal of the signal modulation circuit.

[0021] In a second aspect of the present invention, a stem cell detection method based on magnetic particle equilibrium modulation is proposed. This method is based on the stem cell detection system based on magnetic particle equilibrium modulation as described in the first aspect. This method includes:

[0022] Using the stem cell detection system, detecting a stem cell sample to be detected, and obtaining the voltage signal output by the signal modulation circuit, where the stem cell sample is a stem cell after magnetic particle incubation;

[0023] Performing a Fourier transform on the voltage signal to obtain the frequency distribution characteristics of the voltage signal;

[0024] Based on the frequency distribution characteristics, screening the voltage signal to obtain a target signal;

[0025] Performing MPI reconstruction based on the target signal to obtain the stem cell detection result.

[0026] In some preferred embodiments, the screening of the voltage signal based on the frequency distribution characteristics includes:

[0027] Performing frequency screening on the voltage signal according to the frequency distribution characteristics to obtain a first signal;

[0028] Performing frequency screening on the first signal according to a preset first signal-to-noise ratio threshold to obtain a second signal;

[0029] Calculating the energy density of each frequency point in the second signal, and performing frequency screening on the second signal according to the energy density and a preset energy density threshold to obtain a third signal;

[0030] Determining the target signal according to the third signal.

[0031] In some preferred embodiments, the first signal is composed of the frequency points where signals exist in the voltage signal, the second signal is composed of the frequency points in the first signal with a signal-to-noise ratio higher than a preset first signal-to-noise ratio threshold, and the third signal is composed of the frequency points in the second signal with an energy density higher than a preset energy density threshold.

[0032] In some preferred embodiments, determining the target signal according to the third signal includes:

[0033] Determining whether the signal-to-noise ratio of the third signal is higher than a preset second signal-to-noise ratio threshold;

[0034] If the signal-to-noise ratio of the third signal is higher than the preset second signal-to-noise ratio threshold, then based on the frequency distribution characteristics, the voltage signal is screened again;

[0035] If the signal-to-noise ratio is not higher than the preset second signal-to-noise ratio threshold, then determine the third signal as the target signal.

[0036] Advantages of the present invention:

[0037] (1) The present invention proposes a high-sensitivity stem cell detection system and method based on magnetic particle balance modulation. By constructing a coil balance component and a signal modulation module, and combining a signal processing method based on the signal characteristics of stem cells, detection of stem cell quantities in the order of dozens to hundreds can be achieved.

[0038] (2) The present invention uses a coil balance component and a signal modulation module to ensure reducing noise interference from the hardware system; at the same time, through the balance modulation of the coil balance component and the further processing method of the output signal, under the condition of low noise, as many signals from stem cells as possible are extracted, thereby realizing the sensitivity of stem cell detection, and stem cell detection in the order of hundreds can be achieved. The present invention is of great significance for predicting the cell therapy effect, evaluating the potential risks of treatment, and optimizing the treatment strategy, and provides new technologies and new methods for the research on the stem cell migration mechanism and new mechanisms of cancer biology. BRIEF DESCRIPTION OF THE DRAWINGS

[0039] By reading the detailed description of the non-limiting embodiments with reference to the following drawings, other features, purposes, and advantages of the present application will become more obvious:

[0040] Figure 1 is a schematic structural diagram of a stem cell detection system based on magnetic particle balance modulation proposed by an embodiment of the present invention;

[0041] Figure 2 is a schematic flowchart of a stem cell detection method based on magnetic particle balance modulation proposed by an embodiment of the present invention;

[0042] Figure 3It is a schematic structural diagram of a computer system proposed in an embodiment of the present invention. Detailed implementation manners

[0043] The present application will be further described in detail below with reference to the accompanying drawings and embodiments. It can be understood that the specific embodiments described herein are only used to explain the related invention, rather than limiting the invention. Additionally, it should be noted that for the sake of description, only the parts related to the relevant invention are shown in the drawings.

[0044] It should be noted that, without conflict, the embodiments in the present application and the features in the embodiments can be combined with each other. The present application will be described in detail below with reference to the drawings and embodiments.

[0045] Refer to Figure 1 , as Figure 1 shown, the present invention provides a stem cell detection system based on magnetic particle balance modulation. The system includes:

[0046] The coil balance component includes a first receiving coil, a second receiving coil, and a compensation coil. The first receiving coil, the second receiving coil, and the compensation coil are arranged in parallel and coaxially. The coil balance component is used to collect the magnetic signal of the alternating magnetic field generated by the magnetic particles, convert the magnetic signal into an electrical signal, and transmit the electrical signal to the signal modulation module;

[0047] The signal modulation module includes a signal modulation circuit and a gain adjustment resistor. One end of the gain adjustment resistor is connected to the input end of the signal modulation circuit, and the other end is connected to the output end of the signal modulation circuit. The compensation coil is connected to the input end of the signal modulation circuit. The first receiving coil and the second receiving coil are connected in reverse series and are connected to the output end of the signal modulation circuit. The signal modulation circuit is used to increase the gain of the voltage signal output by the compensation coil. The gain adjustment resistor is used to control the gain coefficient of the signal modulation circuit by adjusting the resistance value.

[0048] In this embodiment, the role of the compensation coil is to compensate for the interference magnetic field in the whole system or the magnetic field non-uniformity caused by environmental factors, and improve the sensitivity of the whole detection system.

[0049] In this embodiment, for the specific implementation of the signal modulation circuit, a dedicated integrated operational amplifier chip (such as OP07, etc.) can be used to build a basic signal amplification and modulation circuit. Generally speaking, this circuit at least includes a preamplifier, a filter, and a post-amplifier, etc. The preamplifier is used to initially amplify the input weak electrical signal, the filter is used to remove the noise and clutter in the signal, and the post-amplifier further amplifies the signal to meet the requirements of subsequent processing.

[0050] In this embodiment, for the specific implementation of the gain adjustment resistor, a variable resistor (such as a potentiometer, a sliding rheostat, etc.) can be selected, which has a certain resistance range (preferably, 1 kΩ - 10 kΩ) and is connected between the input end and the output end of the signal modulation circuit. Furthermore, the amplification factor of the voltage signal generated by the signal modulation circuit for the compensation coil can be precisely controlled by adjusting its resistance value.

[0051] Based on the system proposed in this embodiment, when magnetic particles generate an alternating magnetic field under the action of an external alternating magnetic field, the first receiving coil and the second receiving coil will simultaneously sense the magnetic signal of this alternating magnetic field and convert the magnetic signal into an electrical signal according to the law of electromagnetic induction. The compensation coil will also sense the alternating magnetic field generated by the magnetic particles and other interference magnetic fields in the environment. The voltage signal generated by it is input to the input end of the signal modulation circuit, and by adjusting the resistance value of the gain adjustment resistor, the amplification factor of the voltage signal of the compensation coil by the signal modulation circuit is further precisely controlled. The amplified compensation signal is then superimposed or subtracted from the signals of the first receiving coil and the second receiving coil (the specific processing method is determined according to the actual signal modulation requirements) to cancel the signal imbalance caused by factors such as environmental interference or coil differences.

[0052] It is easy to understand that the electrical signal processed by the signal modulation module will ultimately be output to a possible signal processing unit (such as a spectrum analyzer, a data acquisition card, a microcontroller, etc., not exemplified in this system) for further analysis, processing, and display, so as to ultimately achieve the accurate detection and analysis of the alternating magnetic field of magnetic particles.

[0053] It should be noted that the system provided in the above embodiment is only illustrated by the division of the above functional modules. In practical applications, the above functions can be allocated to different functional modules as needed, that is, the modules or steps in the embodiments of the present invention can be further decomposed or combined. For example, the modules in the above embodiment can be combined into one module, or further split into multiple sub-modules to complete all or part of the functions described above. For the names of the modules and steps involved in this embodiment and subsequent embodiments, they are only used to distinguish each module or step and are not regarded as an improper limitation of the present invention.

[0054] Furthermore, in this embodiment, the first receiving coil and the second receiving coil have the same size and number of turns, and the size and number of turns of the compensation coil are smaller than those of the first receiving coil and the second receiving coil.

[0055] Among them, the first receiving coil and the second receiving coil have the same size and number of turns, and their specific values can be determined according to the requirements of actual detection sensitivity. For example, the first receiving coil and the second receiving coil can be made of coils wound with 500 turns and a wire diameter of 0.2 mm, which can effectively receive the magnetic signals of the alternating magnetic field generated by magnetic particles. Correspondingly, the size and number of turns of the compensation coil are both smaller than those of the first receiving coil or the second receiving coil. For example, it can be made of a coil wound with 200 turns and a wire diameter of 0.2 mm.

[0056] Further, in this embodiment, the first receiving coil and the second receiving coil are connected in series in reverse and connected to the output end of the signal circuit.

[0057] Further, in this embodiment, the spatial positions of the first receiving coil and the second receiving coil are uniformly symmetric, so that the voltage at the output end of the signal modulation circuit reaches a preset minimum value in the case of air measurement. The spatial positions of the first receiving coil and the second receiving coil satisfy:

[0058] ;

[0059] In the formula, V is the voltage at the output end of the signal modulation circuit, V 1 is the first receiving coil, V 2 is the second receiving coil, and D is the spatial distance between the first receiving coil and the second receiving coil.

[0060] In this embodiment, by adjusting the relative spatial distance D between the receiving coil 1 and the receiving coil 2, it is ensured as much as possible that their positions in the alternating magnetic field space are uniformly symmetric. The voltage signals V1 of the receiving coil 1 and V2 of the receiving coil 2 are connected in series in reverse to the signal modulation circuit. By adjusting the relative spatial positions of the receiving coil 1 and the receiving coil 2, in the case of air measurement (without magnetic particles), the voltage V at the signal output end is made as small as possible, that is, the noise is as small as possible.

[0061] Further, in this embodiment, the compensation coil is arranged inside the alternating magnetic field, and the parameter settings of the compensation coil satisfy:

[0062] ;

[0063] In the formula, V is the voltage at the signal output end, V c is the output voltage of the compensation coil, N is the number of turns of the compensation coil, and P is the spatial position of the compensation coil inside the alternating magnetic field.

[0064] It is easy to understand that in this embodiment, by adjusting the number of turns N and the spatial position P of the compensation coil, the output voltage Vc of the compensation coil is adjusted so that the voltage V at the signal output end is further reduced. Compared with the adjustment of the receiving coil 1 and the receiving coil 2, the ability of the compensation coil to adjust noise is relatively small and belongs to fine-tuning of noise.

[0065] Further, in this embodiment, the parameter setting of the gain adjustment resistor satisfies:

[0066] ;

[0067] where V is the voltage at the signal output end, K is the gain of the signal modulation circuit, and R g is the resistance value of the gain adjustment resistor.

[0068] It is easy to understand that since the compensation coil still reduces the noise at the signal output end by adjusting the magnetic field, the accuracy of its adjustment ability is still limited. Therefore, the cooperation of the gain adjustment resistor is required to further finely adjust the magnitude of the noise at the circuit level.

[0069] Further, in this embodiment, the voltage at the signal output end is:

[0070] ;

[0071] where V is the output voltage of the signal modulation circuit, V1 is the voltage signal of the first receiving coil, V2 is the voltage signal of the second receiving coil, K is the gain of the signal modulation circuit generated by the gain adjustment resistor, Vc is the voltage signal of the compensation coil, D is the spatial distance between the first receiving coil and the second receiving coil, N is the number of turns of the compensation coil, P is the spatial position of the compensation coil inside the alternating magnetic field, and Rg is the resistance value of the gain adjustment resistor. Based on this, through the common limitation and constraint of multiple parameters, when there is no magnetic particle placed (empty measurement), the voltage at the signal output end is as small as possible to meet the requirements of high-sensitivity detection.

[0072] Based on the system proposed in the above embodiment, the method of the present application is further introduced.

[0073] Based on the above system, a second embodiment of the present invention proposes a stem cell detection method based on magnetic particle balance modulation, as Figure 2 shown, the method includes:

[0074] Step S10, using the stem cell detection system to detect the stem cell sample to be detected, and obtaining the voltage signal output by the signal modulation circuit, where the stem cell sample is the stem cell after magnetic particle incubation;

[0075] An object of this embodiment is to screen out the signals generated by magnetic particles in stem cells. In this embodiment, the stem cell sample to be detected is pre-incubated with magnetic particles for a fixed duration (preferably 24 hours), and then washed to remove the magnetic particles that have not entered the stem cells. Then, an extremely high number (in the order of 10 to the sixth to seventh power) of stem cells are measured, and obvious frequency distribution characteristics of the magnetic particles inside the stem cells are detected.

[0076] Step S20: Perform Fourier transform on the voltage signal to obtain frequency distribution characteristics;

[0077] It is easy to understand that performing frequency domain analysis on the signal through Fourier transform and then extracting the corresponding frequency distribution characteristics are common technical means for those skilled in the art. Therefore, this embodiment does not limit this too much.

[0078] Step S30: Based on the frequency distribution characteristics, screen the voltage signal to obtain a target signal;

[0079] Among them, screening the voltage signal based on the frequency distribution characteristics specifically includes:

[0080] Perform frequency screening on the voltage signal according to the frequency distribution characteristics to obtain a first signal, which is composed of the frequency points where there are signals in the voltage signal; perform frequency screening on the first signal according to a preset first signal-to-noise ratio threshold to obtain a second signal, which is composed of the frequency points in the first signal where the signal-to-noise ratio is higher than the preset first signal-to-noise ratio threshold; calculate the energy density of each frequency point in the second signal, and perform frequency screening on the second signal according to the energy density and a preset energy density threshold to obtain a third signal, which is composed of the frequency points in the second signal where the energy density is higher than the preset energy density threshold.

[0081] In this embodiment, first, millions of stem cells incubated with magnetic particles are placed in a magnetic particle spectrometer to test the signal, and then the signal is transformed to the frequency domain through Fourier transform to save the frequency point information of the signals in the stem cells, which is the frequency distribution characteristics.

[0082] Perform frequency screening according to the frequency distribution characteristics, and only retain the frequency points with signals in the stem cells, that is, the first signal is obtained;

[0083] Calculate the signal-to-noise ratio of the frequency points after the first-step screening, set a signal-to-noise ratio threshold (generally, the threshold can be set to 1), retain the frequency points higher than the threshold, and remove the frequency points lower than the threshold, that is, the second signal is obtained;

[0084] Calculate the energy density of the frequency points in the second signal retained in the previous step, that is, calculate the square of the signal amplitude at each frequency point, and also retain the signal frequency points where the energy density is higher than a certain threshold, that is, the third signal is obtained.

[0085] After obtaining the third signal, determine whether the signal-to-noise ratio of the third signal is higher than a preset second signal-to-noise ratio threshold; if the signal-to-noise ratio of the third signal is higher than the preset second signal-to-noise ratio threshold, re-screen the voltage signal based on the frequency distribution characteristic; if the signal-to-noise ratio is not higher than the preset second signal-to-noise ratio threshold, determine that the third signal is the target signal.

[0086] In this embodiment, if it is detected that the signal-to-noise ratio is higher than the second signal-to-noise ratio threshold, the entire process is repeated until the signal-to-noise ratio of the finally obtained third signal is less than the second signal-to-noise ratio threshold, and the final target signal is obtained, which is used for MPI reconstruction.

[0087] Step S40, perform MPI reconstruction based on the target signal to obtain a stem cell detection result.

[0088] Regarding the specific process of MPI reconstruction, it belongs to the common knowledge that can be understood by those skilled in the art. This embodiment does not improve it, and those skilled in the art can implement it according to the existing technology, so it will not be elaborated here in this embodiment.

[0089] Next, refer to Figure 3 , which shows a schematic structural diagram of a computer system of a server suitable for implementing the method embodiments of the present application. Figure 3 The server shown is only an example and should not bring any limitation to the functions and usage scope of the embodiments of the present application.

[0090] As Figure 3 shown, the computer system includes a central processing unit (CPU, Central Processing Unit) 301, which can perform various appropriate actions and processes according to the program stored in the read-only memory (ROM, Read Only Memory) 302 or the program loaded from the storage part 308 into the random access memory (RAM, Random Access Memory) 303. In the RAM 303, various programs and data required for system operation are also stored. The CPU 301, ROM 302, and RAM 303 are connected to each other through a bus 304. The input / output (I / O, Input / Output) interface 305 is also connected to the bus 304.

[0091] The following components are connected to the I / O interface 305: an input section 306 including a keyboard, a mouse, etc.; an output section 307 including a cathode ray tube (CRT), a liquid crystal display (LCD), etc. and a speaker, etc.; a storage section 303 including a hard disk, etc.; and a communication section 309 including a network interface card such as a LAN (Local Area Network) card, a modem, etc. The communication section 309 performs communication processing via a network such as the Internet. A drive 310 is also connected to the I / O interface 305 as needed. A removable medium 311, such as a magnetic disk, an optical disk, a magneto-optical disk, a semiconductor memory, etc., is installed on the drive 310 as needed so that a computer program read from it is installed into the storage section 308 as needed.

[0092] Specifically, according to an embodiment of the present invention, the process described above with reference to the flowchart can be implemented as a computer software program. For example, an embodiment of the present invention includes a computer program product that includes a computer program carried on a computer-readable medium, and the computer program includes program code for performing the method shown in the flowchart. In such an embodiment, the computer program can be downloaded and installed from the network through the communication section 309, and / or installed from the removable medium 311. When the computer program is executed by a central processing unit (CPU) 301, the above functions defined in the method of the present application are executed. It should be noted that the above computer-readable medium in the present application can be a computer-readable signal medium or a computer-readable storage medium or any combination of the two. The computer-readable storage medium can be, for example, but not limited to, an electrical, magnetic, optical, electromagnetic, infrared, or semiconductor system, apparatus, or device, or any combination of the above.

[0093] More specific examples of computer-readable storage media may include, but are not limited to: electrical connections with one or more wires, portable computer disks, hard disks, random access memory (RAM), read-only memory (ROM), erasable programmable read-only memory (EPROM or flash memory), optical fibers, portable compact disk read-only memory (CD-ROM), optical storage devices, magnetic storage devices, or any suitable combination of the foregoing. In this application, a computer-readable storage medium may be any tangible medium that contains or stores a program that can be used by or in conjunction with an instruction execution system, apparatus, or device. And in this application, a computer-readable signal medium may include a data signal propagated in a baseband or as part of a carrier wave, which carries computer-readable program code. Such a propagated data signal may take many forms, including but not limited to electromagnetic signals, optical signals, or any suitable combination of the foregoing. A computer-readable signal medium may also be any computer-readable medium other than a computer-readable storage medium, which can send, propagate, or transmit a program for use by or in conjunction with an instruction execution system, apparatus, or device. The program code contained on a computer-readable medium may be transmitted using any appropriate medium, including but not limited to: wireless, wire, optical fiber, RF, etc., or any suitable combination of the foregoing.

[0094] Computer program code for performing the operations of this application may be written in one or more programming languages or combinations thereof, including object-oriented programming languages such as Java, Smalltalk, C++, and also including conventional procedural programming languages such as the "C" language or similar programming languages. The program code may execute entirely on the user's computer, partly on the user's computer, as a stand-alone software package, partly on the user's computer and partly on a remote computer, or entirely on the remote computer or server. In the case of a remote computer, the remote computer may be connected to the user's computer through any type of network, including a local area network (LAN) or a wide area network (WAN), or may be connected to an external computer (e.g., through the Internet using an Internet service provider).

[0095] The flowcharts and block diagrams in the accompanying drawings illustrate the possible architectures, functions, and operations of systems, methods, and computer program products according to various embodiments of the present application. In this regard, each block in the flowchart or block diagram may represent a module, a segment of a program, or a portion of code that contains one or more executable instructions for implementing a specified logical function. It should also be noted that in some alternative implementations, the functions denoted in the blocks may occur in an order different from that denoted in the accompanying drawings. For example, two consecutive blocks shown may actually be executed substantially in parallel, and they may sometimes be executed in the reverse order, depending on the functions involved. It should also be noted that each block in the block diagram and / or flowchart, and combinations of blocks in the block diagram and / or flowchart, can be implemented by a dedicated hardware-based system that performs the specified functions or operations, or can be implemented by a combination of dedicated hardware and computer instructions.

[0096] The terms "first", "second", etc. are used to distinguish similar objects and not to describe or denote a particular order or sequence.

[0097] The term "comprising" or any other similar term is intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus / device that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements that are inherent to such process, method, article, or apparatus / device.

[0098] So far, the technical solution of the present invention has been described in conjunction with the preferred embodiments shown in the accompanying drawings.

[0099] The above are only embodiments of the present application and are not intended to limit the present application. For those skilled in the art, various changes and modifications can be made to the present application. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present application shall be included within the scope of the claims of the present application.

Claims

1. A stem cell detection system based on magnetic particle equilibrium modulation, characterized in that: include: Coil balancing components, signal modulation modules; The coil balance component comprises a first receiving coil, a second receiving coil and a compensation coil, wherein the first receiving coil, the second receiving coil and the compensation coil are arranged in parallel and coaxially; the coil balance component is used to collect magnetic signals generated by the alternating magnetic field of the magnetic particles, and convert the magnetic signals into electrical signals, and transmit them to the signal modulation module; The signal modulation module comprises a signal modulation circuit and a gain adjustment resistor; one end of the gain adjustment resistor is connected to the input end of the signal modulation circuit, and the other end is connected to the output end of the signal modulation circuit; the compensation coil is connected to the input end of the signal modulation circuit, and the first receiving coil and the second receiving coil are connected in reverse series and connected to the output end of the signal modulation circuit; the signal modulation circuit is used to gain the voltage signal output by the compensation coil; the gain adjustment resistor is used to control the gain coefficient of the signal modulation circuit by adjusting the resistance value; Wherein, the size and number of turns of the first receiving coil are equal to those of the second receiving coil, the size and number of turns of the compensation coil are smaller than those of the first receiving coil and the second receiving coil, and the compensation coil is used to compensate for the magnetic field inhomogeneity of the stem cell detection system; The spatial positions of the first receiving coil and the second receiving coil are uniformly symmetrical, so that the output terminal voltage of the signal modulation circuit reaches a preset minimum value in the case of empty measurement, and the spatial positions of the first receiving coil and the second receiving coil satisfy: ； In the formula, V is the output voltage of the signal modulation circuit, V1 is the voltage signal of the first receiving coil, V2 is the voltage signal of the second receiving coil, D is the spatial distance between the first receiving coil and the second receiving coil, and min is the preset minimum value of the output voltage of the signal modulation circuit.

2. The stem cell detection system based on magnetic particle equilibrium modulation according to claim 1, characterized in that: The compensation coil is disposed inside the alternating magnetic field generated by the magnetic particles, and the parameter setting of the compensation coil satisfies: ； Where V is the voltage at the output of the signal modulation circuit, V c is the voltage signal of the compensation coil, N is the number of turns of the compensation coil, P is the spatial position of the compensation coil inside the alternating magnetic field, and min is the preset minimum value of the output voltage of the signal modulation circuit.

3. The stem cell detection system based on magnetic particle equilibrium modulation according to claim 1, characterized in that: The parameter setting of the gain adjustment resistor satisfies: ； In the formula, V is the voltage at the output of the signal modulation circuit, K is the gain coefficient of the signal modulation circuit, and R g is the resistance value of the gain adjustment resistor, and min is the preset minimum value of the output voltage of the signal modulation circuit.

4. The stem cell detection system based on magnetic particle equilibrium modulation according to claim 1, characterized in that: The voltage at the output end of the signal modulation circuit is: ； Where V is the output voltage of the signal modulation circuit, V1 is the voltage signal of the first receiving coil, V2 is the voltage signal of the second receiving coil, K is the gain coefficient of the signal modulation circuit, V c is the voltage signal of the compensation coil, D is the spatial distance between the first receiving coil and the second receiving coil, N is the number of turns of the compensation coil, P is the spatial position of the compensation coil inside the alternating magnetic field, R g is the resistance value of the gain adjustment resistor, and min is the preset minimum value of the output voltage of the signal modulation circuit.

5. A stem cell detection method based on magnetic particle equilibrium modulation, characterized in that: Based on the stem cell detection system based on magnetic particle balance modulation according to any one of claims 1 to 4, the method comprises: The stem cell detection system based on magnetic particle balance modulation is used to detect the stem cell sample to be detected, and a voltage signal output by the signal modulation circuit is obtained, wherein the stem cell sample is a stem cell incubated with magnetic particles; Performing Fourier transform on the voltage signal to obtain frequency distribution characteristics of the voltage signal; Based on the frequency distribution characteristics, frequency screening is performed on the voltage signal to obtain a target signal; MPI reconstruction is performed based on the target signal to obtain stem cell detection results.

6. The stem cell detection method based on magnetic particle equilibrium modulation according to claim 5, characterized in that: The frequency screening of the voltage signal based on the frequency distribution characteristics includes: Performing frequency screening on the voltage signal according to the frequency distribution characteristics to obtain a first signal; Performing frequency screening on the first signal according to a preset first signal-to-noise ratio threshold to obtain a second signal; Calculating the energy density of each frequency point in the second signal, and performing frequency screening on the second signal according to the energy density and a preset energy density threshold to obtain a third signal; The target signal is determined according to the third signal.

7. The stem cell detection method based on magnetic particle equilibrium modulation according to claim 6, characterized in that: The first signal is composed of frequency points where signals exist in the voltage signal, the second signal is composed of frequency points where the signal-to-noise ratio in the first signal is higher than a preset first signal-to-noise ratio threshold, and the third signal is composed of frequency points where the energy density in the second signal is higher than a preset energy density threshold.

8. The stem cell detection method based on magnetic particle equilibrium modulation according to claim 6, characterized in that: The step of determining the target signal according to the third signal includes: Determining whether the signal-to-noise ratio of the third signal is higher than a preset second signal-to-noise ratio threshold; If the signal-to-noise ratio of the third signal is higher than a preset second signal-to-noise ratio threshold, re-performing frequency screening on the voltage signal; If the signal-to-noise ratio is not higher than a preset second signal-to-noise ratio threshold, the third signal is determined to be the target signal.

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