Fluorescence detection device and signal processing system, method and flow cytometer

Abstract

The present application discloses a fluorescence detection device and its signal processing system, method, and flow cytometer. The signal processing system of the fluorescence detection device includes a gain amplifier, an analog-to-digital converter, and a controller electrically connected in sequence, and the gain amplifier is also electrically connected to the controller; the gain amplifier is used to receive analog electrical signals and feedback information. When receiving the feedback information, it can re-determine a new gain based on the input range of the analog-to-digital converter according to the feedback information to perform gain processing on the analog electrical signal, and output the analog electrical signal processed by the gain to the analog-to-digital converter; the analog-to-digital converter is used to receive the analog electrical signal processed by the gain, convert it into a digital signal and output it to the controller; the controller is used to receive the digital signal and process the digital signal in a preset manner. In this way, the range of the signal processed by the signal processing system can be increased, and the accuracy of the processed signal can be improved.

Description

Technical Field

[0001] The present application relates to the field of signal processing technology, and in particular to a fluorescence detection device and a signal processing system, method, and flow cytometer thereof. Background Art

[0002] Instruments that include signal processing systems, such as flow cytometers, are devices that automatically analyze and sort cells. They can quickly measure, store, and display a series of important biophysical and biochemical characteristic parameters of dispersed cells suspended in liquids, and can sort out designated cell subpopulations according to pre-selected parameter ranges.

[0003] During use, the flow cytometer uses fluorescent reagents to mark the detection object, then applies pressure to the marked detection object to make it flow at a certain speed in a preset pipe, and uses laser irradiation to make the marked detection object emit fluorescence, and then converts the fluorescent signal into an analog electrical signal through certain means, and further converts the analog electrical signal into a digital signal, so as to analyze and process the signal according to the different signal intensities to obtain the detection result.

[0004] However, the inventors of the present application discovered during a long period of research and development that in the prior art, when processing analog electrical signals, for example, when the fluorescence detection device of a flow cytometer processes analog electrical signals converted from fluorescence signals, the gain amplifier that amplifies the analog electrical signals can only process them according to the set gain, and it is difficult to achieve automatic adjustment. As a result, when the range of the analog electrical signal after gain processing by the gain amplifier exceeds the input range of the analog-to-digital converter, it cannot be processed normally, thereby limiting the signal processing range of the fluorescence detection device. Summary of the invention

[0005] The main technical problem solved by the present application is to provide a fluorescence detection device and its signal processing system, method, and flow cytometer, which can increase the range of signals processed by the signal processing system and improve the accuracy of processed signals.

[0006] In order to solve the above technical problems, a technical solution adopted in the present application is: to provide a signal processing system for a fluorescence detection device, the signal processing system includes a gain amplifier, an analog-to-digital converter and a controller electrically connected in sequence, wherein the gain amplifier is also electrically connected to the controller; the gain amplifier is used to receive an analog electrical signal and feedback information, and when the feedback information is not received, directly perform gain processing on the analog electrical signal, and when the feedback information is received, re-determine a new gain according to the feedback information to perform gain processing on the analog electrical signal, and output the gain-processed analog electrical signal to the analog-to-digital converter; the analog-to-digital converter is used to receive the gain-processed analog electrical signal, convert the gain-processed analog electrical signal into a digital signal, and output the digital signal to the controller; the controller is used to receive the digital signal and process the digital signal in a preset manner; wherein the feedback information includes a new gain of the analog electrical signal re-determined based on the input range of the analog-to-digital converter.

[0007] In order to solve the above technical problem, another technical solution adopted in the present application is: to provide a fluorescence detection device, wherein the fluorescence detection device includes the above signal processing system.

[0008] In order to solve the above technical problem, another technical solution adopted in the present application is: to provide a flow cytometer, which includes the above fluorescence detection device.

[0009] In order to solve the above technical problems, another technical solution adopted in the present application is: to provide a signal processing method for a fluorescence detection device, the fluorescence detection device includes a signal processing system, the signal processing system includes: a gain amplifier, an analog-to-digital converter and a controller electrically connected in sequence, wherein the gain amplifier is also electrically connected to the controller, and the method includes: when the gain amplifier receives an analog electrical signal, detecting whether the gain amplifier also receives feedback information, wherein the feedback information includes a new gain of the analog electrical signal re-determined based on the input range of the analog-to-digital converter; when the detection result is yes, the gain amplifier re-determines a new gain according to the feedback information to gain process the analog electrical signal, and outputs the gain-processed analog electrical signal to the analog-to-digital converter, so that the analog-to-digital converter converts the gain-processed analog electrical signal into a digital signal, and outputs the digital signal to the controller, and the controller analyzes and processes the digital signal according to the preset method.

[0010] The beneficial effect of the present application is as follows: Different from the prior art, in the signal processing system of the fluorescence detection device of the present application, the gain amplifier is used to receive the analog electrical signal and feedback information, and when the feedback information is not received, the analog electrical signal is directly subjected to gain processing, and when the feedback information is received, the analog electrical signal is subjected to gain processing according to the new gain of the analog electrical signal re-determined based on the input range of the analog-to-digital converter, and the analog electrical signal subjected to gain processing is output to the analog-to-digital converter to convert the analog electrical signal subjected to gain processing into a digital signal, and the digital signal is further processed by the controller in a preset manner. In the above manner, in the process of receiving and processing the analog electrical signal converted from the front-end fluorescence signal, the signal processing system of the fluorescence detection device of the present application can adjust the gain of the analog electrical signal based on the input range of the analog-to-digital converter, thereby reducing the limitation of the input range of the analog-to-digital converter on the range of the received analog electrical signal, so that the signal processing system of the fluorescence detection device can process a larger range of signals, and at the same time can also improve the accuracy of the processed signal to a certain extent. BRIEF DESCRIPTION OF THE DRAWINGS

[0011] In order to more clearly illustrate the technical solutions in the embodiments of the present application, the following briefly introduces the drawings required for use in the description of the embodiments. Obviously, the drawings described below are only some embodiments of the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without creative work. Among them:

[0012] Figure 1 It is a structural schematic diagram of an embodiment of a signal processing system of a fluorescence detection device of the present application;

[0013] Figure 2 It is a structural schematic diagram of another embodiment of the signal processing system of the fluorescence detection device of the present application;

[0014] Figure 3 It is a structural schematic diagram of another embodiment of the signal processing system of the fluorescence detection device of the present application;

[0015] Figure 4 It is a structural schematic diagram of another embodiment of the signal processing system of the fluorescence detection device of the present application;

[0016] Figure 5 It is a structural schematic diagram of another embodiment of the signal processing system of the fluorescence detection device of the present application;

[0017] Figure 6 It is a structural schematic diagram of another embodiment of the signal processing system of the fluorescence detection device of the present application;

[0018] Figure 7It is a structural schematic diagram of an embodiment of the fluorescence detection device of the present application;

[0019] Figure 8 It is a schematic structural diagram of an embodiment of the flow cytometer of the present application;

[0020] Fig. 9 It is a flow chart of an implementation method of a signal processing method of a fluorescence detection device of the present application;

[0021] Fig.10 It is a flow chart of another embodiment of the signal processing method of the fluorescence detection device of the present application;

[0022] Fig.11 It is a flow chart of another embodiment of the signal processing method of the fluorescence detection device of the present application;

[0023] Fig.12 yes Fig.10 Schematic diagram of the process of step S123. DETAILED DESCRIPTION

[0024] The following will be combined with the drawings in the embodiments of the present application to clearly and completely describe the technical solutions in the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, not all of the embodiments. Based on the embodiments in the present application, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of this application.

[0025] See also Figure 1 , Figure 1 1 is a schematic diagram of a structure of a signal processing system of a fluorescence detection device of the present application. The signal processing system of the fluorescence detection device of the present embodiment can be applied to multiple fields involving fluorescence detection, such as aerospace, medical treatment, household appliances, etc.

[0026] Specifically, in this embodiment, a fluorescence signal containing a useful signal is obtained by using fluorescence detection, and the fluorescence signal is further processed by a signal processing system of the fluorescence detection device in this embodiment to obtain a processing result.

[0027] More specifically, the fluorescence detection device in this embodiment can be applied to flow cytometers in the medical field. Flow cytometer is a device for automatically analyzing and sorting cells. It can quickly measure, store, and display a series of important biophysical and biochemical characteristic parameters of dispersed cells suspended in a liquid, and can sort out specified cell subpopulations according to a preselected parameter range. In a flow cytometer, the fluorescence detection device is mainly used to identify and detect viruses, tumors, genes, etc. The products of polymerase chain reactions, etc. are labeled by fluorescent dyes such as phycoerythrin or phycobilichrome protein or fluorescently labeled specific probes. The labeled product can generate a fluorescence signal of a certain wavelength after being excited by a laser of a certain wavelength and a certain light power. Specifically, in a flow cytometer, a motor is controlled to push a syringe to push sample flow particles to be detected into a sheath flow pool. A laser is arranged on one side of the sheath flow pool, and a light spot of a certain size is irradiated on the capillaries of the sheath flow pool through a focusing mirror. After the particles in the sheath flow pool are excited by the laser, a fluorescent signal is scattered. Then, the fluorescent signal of the labeled particles is further collected at a specific angle, and then the fluorescent signal is converted into an analog electrical signal through certain means, and the fluorescent signal is further processed to obtain the detection result.

[0028] In this embodiment, the signal processing system of the fluorescence detection device includes: a gain amplifier 20, an analog-to-digital converter 40 and a controller 60. The gain amplifier 20, the analog-to-digital converter 40 and the controller 60 are electrically connected in sequence, and the gain amplifier 20 is also electrically connected to the controller 60.

[0029] Specifically, the gain amplifier 20 is used to receive an analog electrical signal and feedback information. When no feedback information is received, the analog electrical signal is directly gain processed. When feedback information is received, a new gain is re-determined based on the feedback information to perform gain processing on the analog electrical signal, and the analog electrical signal after gain processing is output to the analog-to-digital converter 40.

[0030] The analog electrical signal received by the gain amplifier 20 is obtained by a certain conversion process of the fluorescent signal generated by the front end of the fluorescent detection device or directly received. The analog electrical signal contains useful information that the fluorescent detection device needs to detect, and needs to be processed by the signal processing system of this embodiment to obtain the information contained therein, which can specifically be a current signal and / or a voltage signal. The analog electrical signal can be an analog electrical signal directly converted from the fluorescent signal, or it can be obtained by a certain preprocessing of the fluorescent signal, which is not specifically limited here.

[0031] Specifically, when the fluorescence detection device in this embodiment is applied to a flow cytometer, the analog electrical signal refers to the fluorescence signal generated by the above-mentioned fluorescent dye labeling and laser irradiation of a certain wavelength, which is converted. It is easy to understand that the signal strength of the analog electrical signal converted from the fluorescence signal is relatively weak, and it needs to be amplified to enhance the signal strength for easy detection. In this embodiment, the gain amplifier 20 is further used for amplification to meet the detection requirements and improve the accuracy of the detection.

[0032] In this embodiment, the analog electrical signal is a voltage signal. The gain amplifier 20 obtains a gain-processed analog electrical signal after gain processing, and outputs the first analog electrical signal to the analog-to-digital converter 40, so that the analog electrical signal after gain processing is analog-to-digital converted by the analog-to-digital converter 40.

[0033] In an application scenario, the signal processing system of the fluorescence detection device in this embodiment may further include a limiting circuit, one end of which is connected to the gain amplifier 20, and the other end is connected to the analog-to-digital converter 40. The limiting circuit is a circuit that can flatten the signal voltage amplitude within a limited range. In this embodiment, the limiting circuit can specifically limit the voltage of the first analog electrical signal output by the gain amplifier 20 according to the input range of the analog-to-digital converter 40, thereby limiting the voltage of the analog electrical signal within the input range of the analog-to-digital converter 40.

[0034] The analog-to-digital converter 40 receives the analog electrical signal obtained by the gain amplifier 20, converts it into a digital signal, and outputs the digital signal to the controller 60. After receiving the digital signal output by the analog-to-digital converter 40, the controller 60 processes the digital signal according to a preset method.

[0035] Specifically, the analog-to-digital converter 40 can be a high-speed analog-to-digital converter according to usage requirements.

[0036] It is easy to understand that the analog-to-digital converter 40 has an input range, such as 0 to 5V. When the voltage of the input signal is greater than 5V, it will not be able to output normally. Specifically, for a 12-bit analog-to-digital converter, when the voltage of the analog electrical signal is greater than 5V, after being limited by the above-mentioned limiting circuit and processed by the analog-to-digital converter 40, it will be output according to the maximum sampling value 4096. At this time, the value received by the controller 60 is obviously not the correct value, which will affect the processing of the controller 60 and further affect the accuracy of the detection result. At the same time, when the voltage of the analog electrical signal received by the analog-to-digital converter 40 is greater than its input range, it means that the gain amplifier 20 needs to reduce the gain multiple so that the voltage of the analog electrical signal output to the analog-to-digital converter 40 meets the input range of the analog-to-digital converter 40.

[0037] In this embodiment, the gain amplifier 20 may further receive feedback information, and the feedback information includes a new gain of the analog electrical signal re-determined based on the input range of the analog-to-digital converter 40. The feedback information may be detected and sent out when the gain amplifier 20 performs gain processing on the received analog electrical signal and is processed by the subsequent limiting circuit, analog-to-digital converter 40 or controller 60. For example, when it is detected that the range of the analog electrical signal processed by the gain amplifier 20 exceeds the preset input range of the analog-to-digital converter 40, feedback information may be sent to the gain amplifier 20 according to the input range. Specifically, the feedback information includes a new gain that the gain amplifier 20 needs to perform on the received analog electrical signal, so that when the gain amplifier 20 performs gain processing on the received analog electrical signal according to the new gain, the range of the analog electrical signal processed by the gain is controlled within the input range of the analog-to-digital converter 40, so that it can be normally received and processed by the analog-to-digital converter 40 and the controller 60.

[0038] Specifically, the controller 60 may be a field programmable gate array FPGA controller 60, and of course may also be other controllers 60 that meet the above requirements, which are not specifically limited here.

[0039] Through the above-mentioned method, when the signal processing system of the fluorescence detection device of the present application receives and processes the analog electrical signal converted from the front-end fluorescence signal, the gain amplifier 20 can adjust the gain of the analog electrical signal based on the input range of the analog-to-digital converter 40, thereby reducing the limitation of the input range of the analog-to-digital converter 40 on the range of the received analog electrical signal, so that the signal processing system of the fluorescence detection device can process a larger range of signals, and at the same time can also improve the accuracy of the processed signal to a certain extent.

[0040] See also Figure 2 , Figure 2 It is a structural schematic diagram of another embodiment of the signal processing system of the fluorescence detection device of the present application.

[0041] In this embodiment, the gain amplifier 20 includes a first gain amplifier 21, and the analog-to-digital converter 40 includes a first analog-to-digital converter 41. The first gain amplifier 21, the first analog-to-digital converter 41 and the controller 60 are electrically connected in sequence, and the first gain amplifier 21 is also electrically connected to the controller 60.

[0042] The first gain amplifier 21 is used to receive an analog electrical signal, perform a first gain processing on the analog electrical signal to obtain a first analog electrical signal, and output the first analog electrical signal to the first analog-to-digital converter 41; receive feedback information from the controller 60, and then perform a second gain processing on the analog electrical signal to obtain a second analog electrical signal, and output the second analog electrical signal to the first analog-to-digital converter 41.

[0043] It should be noted that the analog electrical signal received by the first gain amplifier 21 in this embodiment, and the processing of the analog electrical signal are the same as those of the gain amplifier 20 in the previous embodiment. For relevant details, please refer to the above embodiment and will not be repeated here.

[0044] Among them, the first gain amplifier 21 is a variable gain amplifier, specifically a high-speed variable gain amplifier, and the first gain of the first gain processing of the analog electrical signal can be set according to the actual needs of the first analog-to-digital converter 41, the controller 60, etc. for processing the signal. For example, when the fluorescence detection device in this embodiment is applied to a flow cytometer, it can also be set according to the needs of the items to be detected by the flow cytometer, and different first gains can be set when detecting different items.

[0045] In addition, the first gain of the first gain amplifier 21 may always be the same, or may be automatically and adaptively adjusted according to actual usage requirements during actual use, which is not specifically limited here.

[0046] In this embodiment, the analog electrical signal is a voltage signal. The first gain amplifier 21 obtains a first analog electrical signal after performing a first gain processing on the analog electrical signal, and outputs the first analog electrical signal to the first analog-to-digital converter 41 so as to perform analog-to-digital conversion processing on the first analog electrical signal through the first analog-to-digital converter 41.

[0047] In an application scenario, the signal processing system may further include a first limiting circuit, one end of which is connected to the first gain amplifier 21 , and the other end of which is connected to the first analog-to-digital converter 41 .

[0048] The first limiting circuit has a similar function to the limiting circuit in the above embodiment, and can limit the voltage of the first analog electrical signal to within the input range of the first analog-to-digital converter 41 .

[0049] The first analog-to-digital converter 41 receives the first analog electrical signal obtained by the first gain amplifier 21 after first gain processing, converts the first analog electrical signal into a first digital signal, and outputs the obtained first digital signal to the controller 60 for analysis and processing by the controller 60 .

[0050] Specifically, the first analog-to-digital converter 41 may select a high-speed analog-to-digital converter according to usage requirements.

[0051] Similarly, the first analog-to-digital converter 41 in this embodiment has an input range. When the voltage range of the received first analog electrical signal exceeds the input range, it will not be able to output normally, thereby affecting the accuracy of the detection result.

[0052] In this embodiment, the feedback information received by the first gain amplifier 21 is sent by the controller 60. Specifically, after receiving the first digital signal output by the first analog-to-digital converter 41, the controller 60 determines whether the first analog electrical signal exceeds the input range of the first analog-to-digital converter 41 based on the input range of the first analog-to-digital converter 41, and when it is determined that the first analog electrical signal exceeds the input range of the first analog-to-digital converter 41, it further re-determines that the first gain amplifier 21 needs to perform a second gain processing on the analog electrical signal, and feeds back to the first gain amplifier 21.

[0053] Specifically, the controller 60 can determine the second gain of the first gain amplifier for re-performing the second gain processing on the analog electrical signal according to the input range of the first analog-to-digital converter 41 or the currently detected item. For example, the operator can determine the multiple gains of the first gain amplifier 21 for the analog electrical signal according to the first analog-to-digital converter 41 and the items to be detected in advance. At this time, when the controller 60 detects that the first gain amplifier 21 needs to change the gain to perform the second gain processing on the analog electrical signal, it can further call the pre-set gain to determine.

[0054] It is easy to understand that the first gain amplifier 21 further receives feedback information from the controller 60, obtains the reset second gain contained in the feedback information, performs a second gain processing on the analog electrical signal according to the reset second gain to obtain a second analog electrical signal, and outputs the second analog electrical signal to the first analog-to-digital converter 41. The first analog-to-digital converter 41 receives the second analog electrical signal, converts the second analog electrical signal into a second digital signal, and outputs the second digital signal to the controller 60, and the controller 60 further receives the second digital signal and analyzes and processes the second digital signal.

[0055] It should be noted that after the first gain amplifier 21 performs the second gain processing on the analog electrical signal according to the feedback information of the controller 60, the obtained second analog electrical signal often meets the input range of the first analog-to-digital converter 41, so that it can be normally converted into a second digital signal by the first analog-to-digital converter 41 and output to the controller 60 for signal processing. Of course, in an application scenario, after the first gain amplifier 21 performs the second gain processing on the analog electrical signal according to the feedback information of the controller 60, the obtained second analog signal still exceeds the input range of the first analog-to-digital converter 41. At this time, after the controller 60 receives the second digital signal, it can further detect to re-determine another gain processing that the first gain amplifier 21 needs to perform on the analog electrical signal, until the analog electrical signal after the gain processing by the first gain amplifier 21 can meet the input range of the first analog-to-digital converter 41.

[0056] It should be further pointed out that when applied to the fluorescence detection device of a flow cytometer, the signal processing system in this embodiment can perform signal processing on a single item to further obtain the detection result, and can also perform signal processing on multiple items simultaneously to obtain the detection results of multiple items.

[0057] In the above embodiment, the signal processing system includes a first gain amplifier 21, a first analog-to-digital converter 41 and a controller 60 which are electrically connected in sequence, wherein the first gain amplifier 21 is also electrically connected to the controller 60. The controller 60 can process the first digital signal obtained by the first gain amplifier 21 after the first gain processing and the first analog-to-digital converter 41, and when it is determined that the first analog electrical signal subjected to the first gain processing by the first gain amplifier 21 exceeds the input range of the first analog-to-digital converter 41, the controller 60 re-determines the second gain processing of the analog electrical signal by the first gain amplifier 21 and feeds it back to the first gain amplifier 21, thereby performing the second gain processing on the analog electrical signal, and maintaining the obtained second analog electrical signal within the input range of the first analog-to-digital converter 41, so that the controller 60 can effectively and accurately process the second digital signal obtained by the first analog-to-digital converter 41. In this way, the limitation of the input range of the first analog-to-digital converter 41 on the received signal range can be reduced, so that the signal processing system can process a larger range of signals, and the accuracy of the processed signal can be further improved.

[0058] In one embodiment, after the controller 60 performs the second gain processing on the analog electrical signal based on the first gain amplifier 21, it can further perform restoration processing on the second digital signal.

[0059] It is easy to understand that after the controller 60 determines that the first analog electrical signal exceeds the input range of the first analog-to-digital converter 41 and the first gain amplifier 21 performs a second gain processing on the analog electrical signal, the second analog electrical signal obtained after the second gain processing is converted by the first analog-to-digital converter 41. At this time, if the controller 60 directly analyzes and processes the obtained second digital signal, then the obtained analysis result is obviously not accurate enough, especially when multiple items need to be tested.

[0060] In this embodiment, after the first gain amplifier 21 performs the second gain processing on the analog electrical signal, the second digital signal is further restored. For example, the second gain processing of the analog electrical signal by the first gain amplifier 21 is reduced by 2 times relative to the first gain processing, then the sampling value of the signal collected by the first analog-to-digital converter 41 is further multiplied by 2 to restore the real signal, so that the signal processing system can accurately and effectively detect the received signal.

[0061] In an application scenario, after the first gain amplifier 21 performs a second gain processing on the analog electrical signal, the controller 60 further marks and stores the second digital signal converted by the first analog-to-digital converter 41, so that when the second digital signal is analyzed, the second digital signal can be effectively analyzed and processed according to the mark.

[0062] For example, among the final signals, some are reduced by 2 times after the second gain processing relative to the first gain processing, while some are reduced by 4 times. At this time, the controller 60 may add a first mark to the signal reduced by 2 times during analysis and processing, and add a second mark to the signal reduced by 4 times and store it, so that the controller 60 can further amplify the signal with the first mark by 2 times and the signal with the second mark by 4 times during the final analysis, and then perform analysis and processing.

[0063] In addition, it is easy to understand that from the time the first gain amplifier 21 receives the analog electrical signal and performs the first gain processing to the time it receives the feedback information from the controller 60 and performs the second gain processing on the analog electrical signal, it is obvious that some useful signals will exceed the input range of the first analog-to-digital converter 41 due to the first gain processing and cannot be analyzed and utilized. At this time, the signal that has undergone the second gain processing is marked, so that the controller 60 can further perform a more accurate analysis based on the number of marked first digital signals when performing signal processing, thereby improving the accuracy of the detection results.

[0064] Among them, see Figure 3 , Figure 3 It is a structural diagram of another implementation of the signal processing system of the present application.

[0065] In this embodiment, the signal processing system further includes: a second gain amplifier 22 and a second analog-to-digital converter 42. The second gain amplifier 22, the second analog-to-digital converter 42 and the controller 60 are electrically connected in sequence.

[0066] In this embodiment, the analog electrical signal is processed in two ways, one way through the first gain amplifier 21 and the first analog-to-digital converter 41 , and the other way through the second gain amplifier 22 and the second analog-to-digital converter 42 . Finally, the controller 60 processes the signals.

[0067] The second gain amplifier 22 receives the analog electrical signal, performs a third gain process on the analog electrical signal to obtain a third analog electrical signal, and outputs the third analog electrical signal to the second analog-to-digital converter 42 .

[0068] Among them, the analog electrical signal is the same as that in the above-mentioned embodiment, please refer to the above-mentioned embodiment for details, and no further description is given here. The second gain amplifier 22 can be a fixed gain amplifier, and the third gain of the third gain processing of the analog electrical signal is fixed; in an application scenario, the second gain amplifier 22 can also be a variable gain amplifier, and it can also be a high-speed variable gain amplifier. The operator can set the third gain of the third gain processing of the analog electrical signal by the second gain amplifier 22 to a fixed value according to the input range of the second analog-to-digital converter 42 and the items to be detected, so as to facilitate the operator to debug, and at the same time, different gain multiples can be set for the second gain amplifier 22 according to different projects and other different situations.

[0069] Furthermore, the second analog-to-digital converter 42 receives the third analog electrical signal obtained by the third gain processing performed by the second gain amplifier 22 , converts the third analog electrical signal into a third digital signal, and outputs the third digital signal to the controller 60 .

[0070] In this embodiment, the signal processing system may further include a second limiting circuit, one end of which is connected to the second gain amplifier 22 , and the other end of which is connected to the second analog-to-digital converter 42 .

[0071] Among them, the second limiting circuit can be the same as the limiting circuit in the above-mentioned embodiment, and can flatten the signal voltage amplitude within a limited range. In this embodiment, the second limiting circuit can specifically limit the voltage of the third analog electrical signal output by the second gain amplifier 22 according to the input range of the second analog-to-digital converter 42, thereby limiting the voltage of the third analog electrical signal within the input range of the second analog-to-digital converter 42.

[0072] Among them, the second analog-to-digital converter 42 can be the same as or different from the first analog-to-digital converter 41, and can be set specifically according to actual needs. For example, when the present embodiment is applied to a fluorescence detection device of a flow cytometer, a second analog-to-digital converter 42 with a different input range and a different number of bits can be selected according to the item to be detected and the requirements of the item.

[0073] In this embodiment, the controller 60 further receives a third digital signal and processes the third digital signal.

[0074] Among them, the second gain amplifier 22 can be the same as or different from the first gain amplifier 21. In an application scenario, when the signal processing system is applied to a fluorescence detection device of a flow cytometer, the first gain of the first gain amplifier 21 can be changed, the third gain of the second gain amplifier 22 is fixed, and the first gain is less than the third gain. The first gain amplifier 21 processes the signal with a larger voltage value in the received analog electrical signal, and can detect one item or multiple items with a smaller signal range; while the second gain amplifier 22 processes the analog electrical signal with a smaller voltage value, thereby dividing the analog electrical signal into two paths for simultaneous processing, thereby increasing the signal processing range while improving the processing efficiency of the signal processing system.

[0075] See also Figure 4 , Figure 4 It is a structural diagram of another implementation method of the signal processing system of the present application.

[0076] In this embodiment, the signal processing system also includes a first low-pass filter 31 and a second low-pass filter 32, wherein one end of the first low-pass filter 31 is electrically connected to the first gain amplifier 21, and the other end is electrically connected to the first analog-to-digital converter 41, and one end of the second low-pass filter 32 is electrically connected to the second gain amplifier 22, and the other end is electrically connected to the second analog-to-digital converter 42.

[0077] It is easy to understand that the signal processing system may be interfered by other signals and mixed with other useless signals that need to be removed during the process of processing the received analog electrical signal. In this embodiment, the signal processing system sets a first low-pass filter 31 and a second low-pass filter 32 in the two channels respectively to filter the mixed signals, thereby improving the accuracy of the signal processing system in processing the signal.

[0078] In addition, in the present embodiment, the connection method of the first limiting circuit and the second limiting circuit can also be that one end of the first limiting circuit is electrically connected to the first low-pass filter 31, and the other end is electrically connected to the first analog-to-digital converter 41, and one end of the second limiting circuit is electrically connected to the second low-pass filter 32, and the other end is electrically connected to the second analog-to-digital converter 42, so that the first limiting circuit and the second limiting circuit can respectively perform limiting processing on the analog signal processed by the first low-pass filter 31 and the second low-pass filter 32.

[0079] It should be pointed out that in this embodiment, when the signal processing system is applied to the fluorescence detection device of the flow cytometer, the wavelength of the laser emitted by the laser passing through the fluorescence detection device at the front end is known, and in the determined detection items, the frequency range of the obtained useful signal is also known. Therefore, according to the frequency range, a suitable first low-pass filter 31, second low-pass filter 32, etc. can be selected to remove the mixed signals outside the frequency range of the useful signal, thereby improving the accuracy of signal recognition and improving the accuracy of signal processing by the signal processing system.

[0080] See also Figure 5 , Figure 5 A schematic structural diagram of another implementation manner of the signal processing system of the present application.

[0081] In this embodiment, the signal processing system further includes a preliminary signal preprocessing subsystem 10 .

[0082] It is easy to understand that the analog signal directly obtained may have a signal type that does not meet the processing requirements of the signal processing system, the signal strength is too weak, etc. In this embodiment, the signal processing system further includes an early signal preprocessing subsystem 10. The early signal preprocessing subsystem 10 is electrically connected to the first gain amplifier 21 and the second gain amplifier 22 respectively, so as to preprocess the early signal before the first gain amplifier 21 and the second gain amplifier 22 perform gain processing to obtain an analog electrical signal that meets the post-processing requirements.

[0083] In addition, the signal preprocessing subsystem is further used to divide the preprocessed analog electrical signal into two branches, and transmit them to the first gain amplifier 21 and the second gain amplifier 22 respectively, so as to further process the analog electrical signal according to the above-mentioned embodiment of the present application.

[0084] Specifically, in one application scenario, the signal preprocessing subsystem is used in the fluorescence detection device of a flow cytometer. Figure 6 The early signal preprocessing subsystem 10 includes a photomultiplier tube 11, an amplifier 12 and a signal conditioning circuit 13 which are electrically connected in sequence, wherein the signal conditioning circuit 13 is electrically connected to a first gain amplifier 21 and a second gain amplifier 22 respectively.

[0085] The photomultiplier tube 11 is used to convert the fluorescence signal received from the front end of the fluorescence detection device into an analog current signal.

[0086] However, since the flow cytometer is used for the detection of cells in an organism, the obtained fluorescence signal and the converted analog current signal are very weak, and the signal preprocessing subsystem 10 in this embodiment further includes an amplifier 12 to appropriately amplify the analog current signal. At the same time, since the first analog-to-digital converter 41 and the second analog-to-digital converter 42 can only process voltage signals, the amplifier 12 in this embodiment uses a preamplifier to further convert the analog current signal into an analog voltage signal with a certain voltage amplitude.

[0087] After the amplifier 12 processes the analog current signal to obtain the analog voltage signal, the signal conditioning circuit 13 further performs simple RC regulation and simple filtering on the analog voltage signal to appropriately weaken the mixed signal, thereby enhancing the output of the useful signal.

[0088] In the above manner, the acquired analog signal is processed by the early signal preprocessing subsystem 10 to obtain an analog electrical signal that meets the post-processing requirements of the signal processing system.

[0089] It should be further pointed out that in the prior art, in order to process a wider range of signals, the front-end fluorescence signal is divided into two paths through a spectroscope for collection, one path of fluorescence passes through a low-gain photomultiplier tube, and the other path of fluorescence passes through a high-gain photomultiplier tube. The cost of the photomultiplier tube is relatively high, which will significantly increase the cost of the flow cytometer, and the optical light path will also occupy a relatively large structural area, which is not conducive to people's demand for thinness; in addition, the prior art also uses a logarithmic amplifier to increase the range of processed signals, however, the use of a logarithmic amplifier will cause the output signal waveform to be distorted, thereby affecting the accuracy of signal processing. Compared with the prior art, the signal processing system in this application can significantly reduce the hardware cost, while avoiding signal waveform distortion and improving the accuracy of signal processing.

[0090] See also Figure 7 , Figure 7 It is a structural schematic diagram of an embodiment of a fluorescence detection device of the present application.

[0091] The fluorescence detection device 200 can be applied to instruments that receive or directly generate fluorescence signals and further process the fluorescence signals to obtain detection results, for example, flow cytometers that can be used in the medical field.

[0092] In this embodiment, the fluorescence detection device 200 includes a signal processing system 100 to receive, process and analyze the fluorescence signal. Specifically, the signal processing system 100 is the same as the signal processing system in the above-mentioned signal processing system embodiment of the present application. For relevant details, please refer to the above-mentioned embodiment and will not be repeated here.

[0093] See also Figure 8 , Figure 8 1 is a schematic diagram of the structure of an embodiment of the flow cytometer of the present application. In this embodiment, the flow cytometer 300 includes a fluorescence detection device 200. Specifically, the fluorescence detection device 200 is the same as the fluorescence detection device in the embodiment of the present application described above. For relevant details, please refer to the above embodiment, which will not be repeated here.

[0094] It should be pointed out that in the flow cytometer, the controller identifies and analyzes the front-end fluorescent signal, obtains the test result, and transmits the data with the processor through the data bus, and finally uploads it to the computer, and displays it through the computer display in the form of interface scatter plots and parameters and other indicator parameters. At the same time, in the early debugging process, the operator controls and adjusts the gain of the first gain amplifier and the second gain amplifier through the computer, so as to facilitate the debugging of the operator.

[0095] Please also read Figure 1 and Fig. 9 , Fig. 9 1 is a flow chart of an embodiment of a signal processing method of a fluorescence detection device of the present application. The fluorescence detection device of the present application includes a signal processing system, and the signal processing system includes: a gain amplifier 20, an analog-to-digital converter 40 and a controller 60 electrically connected in sequence, wherein the gain amplifier 20 is also electrically connected to the controller 60. Specifically, the method includes:

[0096] Step S110: when the gain amplifier 20 receives the analog electrical signal, detecting whether the gain amplifier 20 also receives feedback information, wherein the feedback information includes a new gain of the analog electrical signal re-determined based on the input range of the analog-to-digital converter 40;

[0097] Step S120: When the detection result is yes, the gain amplifier 20 re-determines a new gain according to the feedback information to perform gain processing on the analog electrical signal, and outputs the gain-processed analog electrical signal to the analog-to-digital converter 40, so that the analog-to-digital converter 40 converts the gain-processed analog electrical signal into a digital signal, and outputs the digital signal to the controller 60, and the controller 60 processes the digital signal in a preset manner.

[0098] The structure and function of the signal processing system of the fluorescence detection device in this embodiment and the corresponding signal processing method of the fluorescence detection device are as follows: Figure 1 The corresponding signal processing system of the fluorescence detection device of the present application is the same as that in the implementation scheme. For relevant details, please refer to the above implementation scheme and will not be repeated here.

[0099] Please also read Figure 2 and Fig.10 , Fig.10 1 is a flow chart of another embodiment of the signal processing method of the fluorescence detection device of the present application. In this embodiment, the gain amplifier 20 includes a first gain amplifier 21, and the analog-to-digital converter 40 includes a first analog-to-digital converter 41, wherein the first gain amplifier 21, the first analog-to-digital converter 41 and the controller 60 are electrically connected in sequence, and the first gain amplifier 21 is also electrically connected to the controller 60.

[0100] In this implementation manner, before step S110, the following steps are also included:

[0101] Step S101: the first gain amplifier 21 receives an analog electrical signal, performs a first gain process on the analog electrical signal to obtain a first analog electrical signal, and outputs the first analog electrical signal to the first analog-to-digital converter 41;

[0102] Step S102: the first analog-to-digital converter 41 receives the first analog electrical signal, converts the first analog electrical signal into a first digital signal, and outputs the first digital signal to the controller 60;

[0103] Step S103: the controller 60 receives the first digital signal, and determines whether the first analog electrical signal exceeds the input range of the first analog-to-digital converter 41 based on the input range of the first analog-to-digital converter 41;

[0104] Step S104: when the judgment result is yes, it is re-determined that the first gain amplifier 21 needs to perform a new second gain processing on the analog electrical signal, and the second gain processing is fed back to the first gain amplifier 21;

[0105] Step S105: When the judgment result is no, the controller 60 analyzes and processes the second digital signal;

[0106] Furthermore, in this implementation, step S120 includes:

[0107] Step S121: the first gain amplifier 21 receives feedback information from the controller 60, performs a second gain process on the analog electrical signal to obtain a second analog electrical signal, and outputs the second analog electrical signal to the first analog-to-digital converter 41;

[0108] Step S122: the first analog-to-digital converter 41 receives the second analog electrical signal, converts the second analog electrical signal into a second digital signal, and outputs the second digital signal to the controller 60;

[0109] Step S123: the controller 60 receives the second digital signal, and analyzes and processes the second digital signal.

[0110] Similarly, the structure and function of the signal processing system of the fluorescence detection device in this embodiment and the corresponding signal processing method of the fluorescence detection device are similar to those of the present invention. Figure 2The corresponding signal processing system of the fluorescence detection device of the present application is the same as that in the implementation scheme. For relevant details, please refer to the above implementation scheme and will not be repeated here.

[0111] Please also read Figure 3 and Fig.11 , Fig.11 1 is a flow chart of another embodiment of the signal processing method of the fluorescence detection device of the present application. In this embodiment, the gain amplifier 20 also includes a second gain amplifier 22, and the analog-to-digital converter 40 also includes a second analog-to-digital converter 42, wherein the second gain amplifier 22, the second analog-to-digital converter 42 and the controller 60 are electrically connected in sequence. Specifically, in this embodiment, the signal processing method also includes:

[0112] Step S210: the second gain amplifier 22 receives the analog electrical signal, performs a third gain process on the analog electrical signal to obtain a third analog electrical signal, and outputs the third analog electrical signal to the second analog-to-digital converter 42;

[0113] Step S220: the second analog-to-digital converter 42 receives the third analog electrical signal, converts the third analog electrical signal into a third digital signal, and outputs the third digital signal to the controller 60;

[0114] Step S230: the controller 60 receives the third digital signal, and analyzes and processes the third digital signal.

[0115] Similarly, the structure and function of the signal processing system of the fluorescence detection device in this embodiment and the corresponding signal processing method of the fluorescence detection device are similar to those of the present invention. Figure 2 The corresponding signal processing system of the fluorescence detection device of the present application is the same as that in the implementation scheme. For relevant details, please refer to the above implementation scheme and will not be repeated here.

[0116] In one embodiment, step S123 further includes:

[0117] Step S1231: the controller 60 marks and stores the second digital signal, wherein the mark can be distinguished from the first digital signal, and the controller 60 can perform restoration processing on the second digital signal according to the mark;

[0118] Step S1232: The controller 60 receives the second digital signal, and performs restoration processing and analysis processing on the second digital signal.

[0119] Similarly, the structure, function and corresponding signal processing method of the signal processing system of the fluorescence detection device in this embodiment are the same as those in the signal processing system embodiment of the fluorescence detection device of the present application. For relevant details, please refer to the above embodiment and will not be repeated here.

[0120] The above description is only an implementation method of the present application, and does not limit the patent scope of the present application. Any equivalent structure or equivalent process transformation made using the contents of the present application specification and drawings, or directly or indirectly used in other related technical fields, are also included in the patent protection scope of the present application.

Claims

1. A signal processing system for a fluorescence detection device, characterized in that: The signal processing system comprises: a gain amplifier, an analog-to-digital converter and a controller electrically connected in sequence, wherein the gain amplifier is also electrically connected to the controller; The gain amplifier is used to receive an analog electrical signal and feedback information, and directly perform gain processing on the analog electrical signal when the feedback information is not received, and re-determine a new gain according to the feedback information to perform gain processing on the analog electrical signal when the feedback information is received, and output the analog electrical signal after gain processing to the analog-to-digital converter; The analog-to-digital converter is used to receive the analog electrical signal after gain processing, convert the analog electrical signal after gain processing into a digital signal, and output the digital signal to the controller; The controller is used to receive the digital signal and process the digital signal in a preset manner; Wherein, the feedback information includes a new gain of the analog electrical signal re-determined based on the input range of the analog-to-digital converter; The invention also includes: a limiting circuit, one end of which is connected to the gain amplifier, and the other end of which is connected to the analog-to-digital converter; wherein the limiting circuit is used to flatten the signal voltage amplitude within a limited range; the limiting circuit is configured to limit the voltage of the first analog electrical signal output by the gain amplifier according to the input range of the analog-to-digital converter, so as to limit the voltage of the analog electrical signal within the input range of the analog-to-digital converter; The gain amplifier includes a first gain amplifier, and the analog-to-digital converter includes a first analog-to-digital converter, wherein the first gain amplifier, the first analog-to-digital converter and the controller are electrically connected in sequence, and the first gain amplifier is also electrically connected to the controller; The first gain amplifier is used to receive the analog electrical signal, perform a first gain processing on the analog electrical signal to obtain a first analog electrical signal, and output the first analog electrical signal to the first analog-to-digital converter; receive the feedback information of the controller, and then perform a second gain processing on the analog electrical signal to obtain a second analog electrical signal, and output the second analog electrical signal to the first analog-to-digital converter; The first analog-to-digital converter is used to receive the first analog electrical signal, convert the first analog electrical signal into a first digital signal, and output the first digital signal to the controller; receive the second analog electrical signal, convert the second analog electrical signal into a second digital signal, and output the second digital signal to the controller; The controller is used to receive the first digital signal, determine that the first analog electrical signal exceeds the input range of the first analog-to-digital converter based on the input range of the first analog-to-digital converter, and then re-determine that the first gain amplifier needs to perform a second gain processing on the analog electrical signal, and feed back to the first gain amplifier; receive the second digital signal, and analyze and process the second digital signal; The gain amplifier further includes a second gain amplifier, and the analog-to-digital converter further includes a second analog-to-digital converter, wherein the second gain amplifier, the second analog-to-digital converter and the controller are electrically connected in sequence; The second gain amplifier is used to receive the analog electrical signal, perform a third gain process on the analog electrical signal to obtain a third analog electrical signal, and output the third analog electrical signal to the second analog-to-digital converter; The second analog-to-digital converter is used to receive the third analog electrical signal, convert the third analog electrical signal into a third digital signal, and output the third digital signal to the controller; The controller is also used to receive the third digital signal and analyze and process the third digital signal.

2. The signal processing system according to claim 1, characterized in that The system also includes a first low-pass filter and a second low-pass filter, wherein one end of the first low-pass filter is electrically connected to the first gain amplifier and the other end is electrically connected to the first analog-to-digital converter, and one end of the second low-pass filter is electrically connected to the second gain amplifier and the other end is electrically connected to the second analog-to-digital converter.

3. The signal processing system according to claim 1, characterized in that The system also includes an early signal preprocessing subsystem, which is electrically connected to the first gain amplifier and the second gain amplifier respectively. The signal preprocessing subsystem is used to preprocess the early signal to obtain an analog electrical signal, divide the analog electrical signal into two branches, and transmit them to the first gain amplifier and the second gain amplifier respectively.

4. The signal processing system according to claim 3, characterized in that: The early signal preprocessing subsystem includes a photomultiplier tube, an amplifier, and a signal conditioning circuit which are electrically connected in sequence, wherein the signal conditioning circuit is electrically connected to the first gain amplifier and the second gain amplifier respectively.

5. The signal processing system according to claim 1, characterized in that: The first gain of the first gain amplifier is changeable, the third gain of the second gain amplifier is fixed, and the first gain is smaller than the second gain.

6. The signal processing system according to claim 1, characterized in that: The controller is a field programmable gate array (FPGA) controller.

7. The signal processing system according to claim 1, characterized in that The controller is further configured to perform restoration processing on the second digital signal after the first gain amplifier performs the second gain processing on the analog electrical signal.

8. The signal processing system according to claim 7, characterized in that: The controller is further configured to mark and store the second digital signal, wherein the mark can be distinguished from the first digital signal, and the controller can perform restoration processing on the second digital signal according to the mark.

9. A fluorescence detection device, characterized in that: The fluorescence detection device comprises the signal processing system according to any one of claims 1-8.

10. A flow cytometer, characterized in that: The flow cytometer comprises the fluorescence detection device as claimed in claim 9.

11. A signal processing method for a fluorescence detection device, characterized in that: The fluorescence detection device includes a signal processing system, the signal processing system includes: a gain amplifier, an analog-to-digital converter and a controller electrically connected in sequence, wherein the gain amplifier is also electrically connected to the controller, and the method includes: When the gain amplifier receives the analog electrical signal, detecting whether the gain amplifier also receives feedback information, wherein the feedback information includes a new gain of the analog electrical signal re-determined based on the input range of the analog-to-digital converter; When the detection result is yes, the gain amplifier re-determines a new gain according to the feedback information to perform gain processing on the analog electrical signal, and outputs the analog electrical signal after the gain processing to the analog-to-digital converter, so that the analog-to-digital converter converts the analog electrical signal after the gain processing into a digital signal, and outputs the digital signal to the controller, so that the controller processes the digital signal in a preset manner; The signal processing system further comprises: a limiting circuit, one end of which is connected to the gain amplifier, and the other end of which is connected to the analog-to-digital converter; wherein the limiting circuit is used to flatten the signal voltage amplitude within a limited range; the limiting circuit limits the voltage of the first analog electrical signal output by the gain amplifier according to the input range of the analog-to-digital converter, so as to limit the voltage of the analog electrical signal to within the input range of the analog-to-digital converter; The gain amplifier includes a first gain amplifier, and the analog-to-digital converter includes a first analog-to-digital converter, wherein the first gain amplifier, the first analog-to-digital converter and the controller are electrically connected in sequence, and the first gain amplifier is also electrically connected to the controller; Before the step of detecting whether the gain amplifier has also received feedback information when the gain amplifier receives the analog electrical signal, the method further includes: The first gain amplifier receives an analog electrical signal, performs a first gain process on the analog electrical signal to obtain a first analog electrical signal, and outputs the first analog electrical signal to the first analog-to-digital converter; The first analog-to-digital converter receives the first analog electrical signal, converts the first analog electrical signal into a first digital signal, and outputs the first digital signal to the controller; The controller receives the first digital signal and determines whether the first analog electrical signal exceeds the input range of the first analog-to-digital converter based on the input range of the first analog-to-digital converter; When the judgment result is yes, re-determining that the first gain amplifier needs to perform a new second gain processing on the analog electrical signal, and feeding back the second gain processing to the first gain amplifier; When the judgment result is no, the controller analyzes and processes the second digital signal; When the detection result is yes, the gain amplifier performs gain processing on the analog electrical signal according to the feedback information and the new gain, and outputs the gain-processed analog electrical signal to the analog-to-digital converter, so that the analog-to-digital converter converts the gain-processed analog electrical signal into a digital signal, and outputs the digital signal to the controller, and the controller processes the digital signal according to the preset method, further comprising: The first gain amplifier receives feedback information from the controller, performs a second gain process on the analog electrical signal to obtain a second analog electrical signal, and outputs the second analog electrical signal to the first analog-to-digital converter; The first analog-to-digital converter receives the second analog electrical signal, converts the second analog electrical signal into a second digital signal, and outputs the second digital signal to the controller; The controller receives the second digital signal and analyzes and processes the second digital signal; The gain amplifier further includes a second gain amplifier, and the analog-to-digital converter further includes a second analog-to-digital converter, wherein the second gain amplifier, the second analog-to-digital converter, and the controller are electrically connected in sequence, and the method further includes: The second gain amplifier receives the analog electrical signal, performs a third gain process on the analog electrical signal to obtain a third analog electrical signal, and outputs the third analog electrical signal to the second analog-to-digital converter; The second analog-to-digital converter receives the third analog electrical signal, converts the third analog electrical signal into a third digital signal, and outputs the third digital signal to the controller; The controller receives the third digital signal, and analyzes and processes the third digital signal.

12. The signal processing method according to claim 11, characterized in that: The controller receives the second digital signal and performs analysis and processing on the second digital signal, further comprising: The controller receives the second digital signal, and performs restoration processing and analysis processing on the second digital signal.

13. The signal processing method according to claim 12, characterized in that: Before the controller receives the second digital signal and performs restoration processing and analysis processing on the second digital signal, the method further includes: The controller marks and stores the second digital signal, wherein the mark can be distinguished from the first digital signal, and enables the controller to perform restoration processing on the second digital signal according to the mark.

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