Optical signal processing circuit for hematology analyzer

Abstract

The invention relates to the technical field of external diagnosis equipment, in particular to an optical signal processing circuit for a hematology analyzer. Comprising a light source driving monitoring module, a sheath flow control circuit module, a photoelectric detector, a transconductance amplifier, a low-noise amplifier, a buffer, a high-gain amplifier, a low-gain amplifier, a first gain adjusting unit, a first filter, a first analog-to-digital converter, a second gain adjusting unit and a second filter. A second analog-to-digital converter and a programmable gate array / digital processing unit; a high-low gain dual-channel multi-stage amplification and signal processing technology is adopted, so that weak optical platelet signals can be effectively captured, amplified and processed; and correct counting of medium and large volume cells such as red blood cells and white blood cells can be ensured. The circuit can automatically adjust the gain multiple value of the amplifier in a test, identifies various cell signals between two channels through a digital algorithm, and has good accuracy and precision in a whole blood cell test.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of external diagnostic equipment, and particularly relates to an optical signal processing circuit for a blood cell analyzer. BACKGROUND

[0002] The blood cell analyzer is an instrument for automatically analyzing various cells and their constituent components in blood. In the existing blood cell analyzer technology, a sheath flow optical method is usually adopted to detect the blood sample, and the main principle is to use the hydrodynamic liquid flow focusing technology to gather the cell suspension in the sheath flow (sample flow) formed in the sheath flow device, and the cells pass through the sheath flow device one by one in order, and a laser beam is irradiated on the cells, different cells will reflect light signals at different angles, and through data processing and analysis of the detection results of the light signals, the number, size, shape and other information of various blood cells can be obtained.

[0003] However, in the existing blood cell analyzer, when the optical method is used to detect the whole blood cells, there are not only small platelets but also large white blood cells in the sample. Because of the characteristics of platelets, there are some challenges in the design of the signal processing circuit, especially the forward channel, one of which is that due to the characteristics of platelets themselves, the volume of platelets is quite different from that of normal red blood cells and white blood cells. After chemical reagent treatment, the diameter of small platelets can be as low as 1 um, and the diameter of large white blood cells can be more than 20 um. According to the Mie scattering theory of optics, the intensity of forward scattering of cells under laser irradiation is proportional to the volume of the cells. This means that the difference in scattering light intensity after the laser beam acts on the cells is up to thousands of times. Since the movement of the liquid flow in the flow channel determines that the signal-to-noise ratio cannot be too high, the design of the conventional circuit cannot meet the dynamic range requirement of whole blood cell counting by improving the signal-to-noise ratio, resulting in problems such as large noise interference of small cells, low resolution, inaccurate analysis results, and the like, which affect the stability of the final results.

[0004] Therefore, it is of great significance to develop a new type of processing circuit for processing the optical platelet signal of the blood cell analyzer for the clinical detection of blood cells. SUMMARY

[0005] The present application aims to provide an optical signal processing circuit for a blood cell analyzer, which aims to solve the problem of insufficient dynamic range of the conventional linear amplification circuit design in whole blood cell counting, low signal-to-noise ratio of small signals, and low accuracy of optical platelet recognition and counting.

[0006] In order to achieve the above object, the application provides an optical signal processing circuit for a blood cell analyzer, comprising a light source driving monitoring module, a sheath flow control circuit module, a photoelectric detector, a transconductance amplifier, a low noise amplifier, a buffer, a high gain amplifier, a low gain amplifier, a first gain adjusting unit, a first filter, a first analog-digital converter, a second gain adjusting unit, a second filter, a second analog-digital converter and a programmable gate array / digital processing unit.

[0007] The light source driving monitoring module is connected with the sheath flow control circuit module, the photoelectric detector is connected with the sheath flow control circuit module, the transconductance amplifier is connected with the low noise amplifier and the transconductance amplifier respectively, the buffer is connected with the low noise amplifier, the high gain amplifier and the low gain amplifier respectively, the first gain adjusting unit, the first filter and the first analog-digital converter are connected in sequence, the second gain adjusting unit, the second filter and the second analog-digital converter are connected in sequence, the first gain adjusting unit is connected with the high gain amplifier, the second gain adjusting unit is connected with the low gain amplifier, and the programmable gate array / digital processing unit is connected with the first analog-digital converter and the second analog-digital converter respectively.

[0008] The light source driving monitoring module is composed of a light source driving circuit, a light source detection circuit and a laser light source.

[0009] The sheath flow control circuit module is composed of a sheath flow control circuit and a sheath flow chamber.

[0010] The photoelectric detector is a PIN PD silicon photocell with a spectral response range of 400-1100nm of Hamamatsu, and similar PIN PDs of Osram and Rom can also be used in actual implementation, and high sensitivity light detection devices such as APD and SiPM can also be used if the cell scattering light intensity is extremely weak.

[0011] The digital processing unit in the programmable gate array / digital processing unit can use other signal processing technologies such as digital filtering, signal transformation and feature extraction to further improve the quality and accuracy of the signal.

[0012] The optical signal processing circuit for a blood cell analyzer of the present application, the main function of the light source driving monitoring module is to generate a stable laser signal, which irradiates the cell particles in the flow cell and produces different scattered light, thereby distinguishing different cell types such as platelet cells, the sheath flow control circuit module is used to control the stability and uniformity of the cell flow, which is realized by air pressure pump / valve. The photodetector is used to receive the weak optical signal scattered or excited by platelets and other cells in the sample test, and convert it into a corresponding current signal of different sizes according to the size of the received light intensity, the transimpedance amplifier (TIA) converts the weak current signal converted by the photodetector into a voltage signal, and improves the signal amplitude and quality. Due to its high input impedance and low output impedance characteristics, it is very suitable for sensor signal amplification, the low noise amplifier is used to amplify the weak voltage signal after TIA, and can further reduce the noise interference in the photodetector output signal to improve the signal clarity, the buffer is used to stabilize the steady-state level of the channel signal, prevent mutual interference between different gain channels, and enhance the driving ability of the output signal to ensure signal quality, the high gain amplifier and the low gain amplifier are used to adjust the gain of the signal according to the needs of the measured sample, so that the amplitude of the signal is more suitable for subsequent processing and analysis. This gain adjustment process needs to be realized by cooperating with the first gain adjusting unit and the second gain adjusting unit to adapt to different sample test items and requirements and correct the inter-machine difference between different instruments, the first filter and the second filter are used to filter the noise and ripple interference in the signal in the above-mentioned channel, which can improve the quality and accuracy of the signal, so that the subsequent processing and analysis are more accurate. The signals filtered by the first filter and the second filter are respectively converted into digital signals by the first analog-to-digital converter and the second analog-to-digital converter (ADC) for subsequent digital calculation processing and analysis, and the data of the high gain and low gain channels are combined by the programmable gate array / digital processing unit through program code processing, which can effectively identify the optical platelet signal and distinguish it from other cell signals. The high gain channel can provide stronger signal strength, and the low gain channel can provide better noise suppression effect. By combining the data of the two channels, the different signal characteristics can be fully utilized to realize the identification and distinction of the optical platelet signal. In addition, the digital processing unit can also use other signal processing techniques, such as digital filtering, signal transformation, feature extraction, etc., to further improve the quality and accuracy of the signal, as well as the identification and distinction ability of the optical platelet signal, providing more accurate basis for subsequent data analysis and diagnosis.Adopt high and low gain dual-channel multi-stage amplification and signal processing technology, the high gain channel can effectively capture weak optical platelet signal and amplify and process it; the low gain channel can ensure the correct counting of medium and large volume cells such as red blood cells and white blood cells. At the same time, the circuit also adopts automatic gain control technology, which can automatically adjust the gain multiple value of the amplifier during testing according to different test items, and identify various cell signals between the two channels through the back-end digital algorithm, so that the technical scheme has good accuracy and precision in whole blood cell testing, thereby solving the problems of insufficient dynamic range, low signal-to-noise ratio of small signal, and low accuracy and precision of optical platelet recognition and counting in the design of conventional linear amplification circuit in whole blood cell counting.

[0013] The circuit combines the advantages of linear and nonlinear circuits, adopts dual-channel gain control technology, one channel is a high gain channel for ensuring sufficient signal strength during platelet counting, thereby accurate recognition and counting. One channel is a low gain channel for ensuring the correct counting of large cells such as red blood cells and white blood cells, avoiding signal out-of-range caused by too high gain. In order to further improve the accuracy and precision of platelet recognition, both channels of the circuit adopt programmed gain regulation, which can adjust appropriate gain according to different scenes, combined with multi-stage amplification and signal processing technology, so that platelet signal is easier to be detected and recognized, and the precision and accuracy are higher.

[0014] Compared with existing technical means, this newly proposed circuit not only has higher signal-to-noise ratio and accuracy of platelet recognition and counting, but also can effectively obtain accurate cell volume information by maintaining the linear relationship of different cell amplification effects, providing strong support for cell biology research. At the same time, this design also effectively avoids the complexity of system design, reduces the difficulty and cost of circuit design. Therefore, the circuit has a relatively wide application prospect in optical platelet detection and counting based on fluorescence methodology, and can play a greater role in PLT-O (optical platelet) clinical detection of blood cell analyzers.

[0015] Advantages

[0016] I. The scheme can solve the problems of insufficient detection dynamic range, low signal-to-noise ratio of small cells such as platelet cells, and low accuracy and precision of platelet recognition and counting in blood analyzers during single whole blood cell counting by combining dual channels.

[0017] II. The scheme can avoid the problem that the scattering information of the platelet and the red blood cell is not in linear relationship with the volume of the platelet and the red blood cell, which is caused by the design of the nonlinear amplification circuit to improve the amplification ratio of the small signal such as the platelet and the small red blood cell, so as to expand the detection application range.

[0018] III. The scheme can reduce the complexity and difficulty of the circuit system design caused by the identification and detection of the platelet signal, and can realize higher performance at a lower cost. BRIEF DESCRIPTION OF DRAWINGS

[0019] In order to more clearly illustrate the technical solutions in the embodiments of the present application or the prior art, the drawings needed to be used in the embodiments or the prior art description will be briefly introduced below. Obviously, the drawings in the following description are only some embodiments of the present application, and other drawings can also be obtained by those skilled in the art without creative labor.

[0020] Figure 1 It is a connection diagram of an optical signal processing circuit for a blood cell analyzer provided by the present application.

[0021] Figure 2 It is an example schematic diagram of a blood cell volume pulse signal.

[0022] Figure 3 It is a screening logic and flowchart of a pulse signal.

[0023] Figure 4 It is a partial schematic diagram of a circuit of a certain type of blood cell analyzer of the URIT company.

[0024] Figure 5 It is an ADC acquisition value summary curve schematic diagram of a high-gain channel and a low-gain channel.

[0025] Figure 6 It is a schematic diagram of the result of digital merging processing of the high-gain and low-gain two-way sampling data through program design.

[0026] In the figure: 1- light source driving monitoring module, 2- sheath flow control circuit module, 3- photodetector, 4- transconductance amplifier, 5- low noise amplifier, 6- buffer, 7- high gain amplifier, 8- low gain amplifier, 9- first gain adjusting unit, 10- first filter, 11- first analog-to-digital converter, 12- second gain adjusting unit, 13- second filter, 14- second analog-to-digital converter, 15- programmable gate array / digital processing unit. DETAILED DESCRIPTION

[0027] Embodiments of the present application are described below in the context of a method of manufacturing a semiconductor device. Those of ordinary skill in the art will realize that the embodiments of the present application apply to other types of devices and methods and can be implemented in a wide variety of contexts. Although embodiments of the present application are described with reference to the accompanying drawings, it is to be understood that the application is not limited to the specific devices or methods disclosed. One skilled in the relevant art will recognize that the application can be practiced with a variety of other systems. The word "comprising" is used herein to mean including possibly one or more elements or ingredients. It is to be understood that such words are not to be interpreted in an exclusive or exhaustive sense. Functionality described can be provided by one or more components and / or devices, and in some embodiments can be distributed over various components and / or devices. Likewise, functionality described as being performed by one or more components and / or devices can be performed by a single component and / or device, or by multiple components and / or devices operating in coordination. Unless otherwise specified, terms of approximation, such as "substantially", "approximately", "generally", or the like, refer to values that are within ten percent of the value being discussed. Other definitions, context-specific definitions, and preferred ranges can be found elsewhere in the specification.

[0028] Referring to Figures 1 to 6 The present application provides an optical signal processing circuit for a blood cell analyzer, comprising a light source driving monitoring module 1, a sheath flow control circuit module 2, a photodetector 3, a transimpedance amplifier 4, a low noise amplifier 5, a buffer 6, a high gain amplifier 7, a low gain amplifier 8, a first gain adjusting unit 9, a first filter 10, a first analog-to-digital converter 11, a second gain adjusting unit 12, a second filter 13, a second analog-to-digital converter 14 and a programmable gate array / digital processing unit 15.

[0029] The light source driving monitoring module 1 is connected with the sheath flow control circuit module 2, the photodetector 3 is connected with the sheath flow control circuit module 2, the transimpedance amplifier 4 is connected with the low noise amplifier 5 and the transimpedance amplifier 4 respectively, the buffer 6 is connected with the low noise amplifier 5, the high gain amplifier 7 and the low gain amplifier 8 respectively, the first gain adjusting unit 9, the first filter 10 and the first analog-to-digital converter 11 are connected in sequence, the second gain adjusting unit 12, the second filter 13 and the second analog-to-digital converter 14 are connected in sequence, the first gain adjusting unit 9 is connected with the high gain amplifier 7, the second gain adjusting unit 12 is connected with the low gain amplifier 8, and the programmable gate array / digital processing unit 15 is connected with the first analog-to-digital converter 11 and the second analog-to-digital converter 14 respectively.

[0030] In the embodiment of the present application, the main function of the light source driving and monitoring module 1 is to generate a stable laser signal, which is used to irradiate the cell particles in the flow cell and generate different scattered light, thereby distinguishing different cell types such as platelet cells. The sheath flow control circuit module 2 is used to control the stability and uniformity of the cell flow, which is realized by a gas pressure pump / valve. The photodetector is used to receive the weak optical signal scattered or excited by platelets and other cells in the sample test, and convert it into a corresponding current signal of different sizes according to the intensity of the received light. The trans-impedance amplifier 4 (TIA) converts the weak current signal obtained by the photodetector 3 into a voltage signal and improves the signal amplitude and quality. Due to its high input impedance and low output impedance characteristics, it is very suitable for sensor signal amplification. The low noise amplifier 5 is used to amplify the weak voltage signal after TIA and further reduce the noise interference in the output signal of the photodetector 3 to improve the clarity of the signal. The buffer 6 is used to stabilize the steady-state level of the channel signal, prevent mutual interference between different gain channels, and enhance the driving ability of the output signal to ensure signal quality. The high gain amplifier 7 and the low gain amplifier 8 are used to adjust the gain of the signal according to the needs of the measured sample, so that the amplitude of the signal is more suitable for subsequent processing and analysis. This gain adjustment process needs to be realized by the first gain adjustment unit 9 and the second gain adjustment unit 12 to adapt to different sample test items and requirements and correct the inter-lab difference between different instruments. The first filter 10 and the second filter 13 are used to filter the noise and ripple interference in the signal in the channel after the above processing, which can improve the quality and accuracy of the signal and make the subsequent processing and analysis more accurate. The signals filtered by the first filter 10 and the second filter 13 are respectively digitized by the first analog-to-digital converter 11 and the second analog-to-digital converter 14 (ADC) for subsequent digital calculation processing and analysis. By processing the data of the high gain and low gain channels through the programmable gate array / digital processing unit 15, the optical platelet signal can be effectively recognized and distinguished from other cell signals. The high gain channel can provide stronger signal strength, and the low gain channel can provide better noise suppression effect. By combining the data of the two channels, the different signal characteristics can be fully utilized to realize the recognition and distinction of the optical platelet signal. In addition, the digital processing unit can also use other signal processing techniques such as digital filtering, signal transformation, feature extraction, etc. to further improve the quality and accuracy of the signal and the recognition and distinction ability of the optical platelet signal, providing more accurate basis for subsequent data analysis and diagnosis.The high-gain channel can effectively capture weak optical platelet signals and amplify and process them, and the low-gain channel can ensure correct counting of medium and large volume cells such as red blood cells and white blood cells. At the same time, the circuit also adopts an automatic gain control technology, which can automatically adjust the gain multiple value of the amplifier during testing according to different test items, and identify various cell signals between the two channels through the back-end digital algorithm, so that the technical scheme has good accuracy and precision in whole blood cell testing, thereby solving the problems of insufficient dynamic range, low signal-to-noise ratio of small signals, and low accuracy and precision of optical platelet recognition and counting in the conventional linear amplification circuit design when counting whole blood cells.

[0031] The circuit combines the advantages of linear and nonlinear circuits and adopts a dual-channel gain control technology, one channel being a high-gain channel for ensuring sufficient signal strength when counting platelets and thus accurate recognition and counting, and the other channel being a low-gain channel for ensuring correct counting of large cells such as red blood cells and white blood cells and avoiding signal out-of-range caused by excessively high gain. To further improve the accuracy and precision of platelet recognition, both channels of the circuit adopt a programmed gain adjustment method, which can adjust appropriate gain according to different scenarios, combined with multi-stage amplification and signal processing technology, so that platelet signals are more easily detected and recognized, and the precision and accuracy are higher.

[0032] Compared with existing technical means, the newly proposed circuit not only has higher signal-to-noise ratio and accuracy of platelet recognition and counting, but also effectively obtains accurate cell volume information by maintaining a linear relationship between the amplification effects of different cells, providing strong support for cell biology research. At the same time, this design effectively avoids the complexity of system design and reduces the difficulty and cost of circuit design. Therefore, the circuit has a relatively wide application prospect in optical platelet detection and counting based on fluorescence methodology, and can play a greater role in PLT-O (optical platelet) clinical detection of blood cell analyzers.

[0033] Advantages

[0034] I. The scheme can solve the problems of insufficient detection dynamic range, low signal-to-noise ratio of small cells such as platelet cells, and low accuracy and precision of platelet recognition and counting when a blood analyzer performs single whole blood cell counting through dual-channel combination.

[0035] II. The scheme can circumvent the problem that the use of a nonlinear amplification circuit design to improve the amplification of small signals such as platelets and small red blood cells results in a nonlinear relationship between the scattering information of the platelet and red blood cell, white blood cell characteristic volume, which cannot effectively obtain accurate cell volume information in some specific cell biology research projects, thereby expanding the detection application range.

[0036] III. The scheme can reduce the complexity and difficulty of the circuit system design caused by the identification and detection of platelet signals, and can achieve higher performance at a lower cost.

[0037] To better understand the technical scheme, the following embodiments are provided for further explanation:

[0038] The following will be combined Figure 2 Further explanation of the specific implementation of optical platelet signal processing.

[0039] Figure 2 is an example of a characteristic blood cell volume pulse signal, and the deep black L_Gain represents the signal of the low gain channel, and the light gray H_Gain represents the signal of the high gain channel.

[0040] For small cells in the blood sample, mainly small platelet cells, since the scattered light intensity is very weak, in order to improve the signal-to-noise ratio of the platelet cell signal, a high gain channel needs to be used for amplification processing, which can increase the accuracy of the platelet signal, and the back end can more accurately detect and identify the platelet cell signal. Conversely, for larger cells, mainly red blood cells and white blood cells, since the scattered light intensity is relatively strong, a low gain channel can be used for amplification processing, and the use of a high gain channel will exceed the voltage rail and cause saturation.

[0041] Further explanation can be made according to Figure 2

[0042] For example, the figure intercepts 5 cell pulse signals, for the 2nd cell pulse signal, if a low gain amplification method is used, the signal amplitude is less than 10mV, as can be seen from the figure, the signal is almost submerged in the noise, the result is that the signal cannot be effectively identified, or the amplitude accuracy of the identified signal is very poor, and it is impossible to know whether it belongs to a normal platelet cell or not. At this time, if a high gain amplification method is used, the cell characteristics appear obviously, and the identification is very easy and accurate. For large cell signals, such as the first and last two cell signals in the example, when a high gain amplification method is used, the signal is saturated and produces a pin top phenomenon, and it is impossible to obtain accurate size information, at this time, if a low gain amplification method is used, it can be better identified.

[0043] ​Through the foregoing manner, the signals processed by the high-gain and low-gain have been obtained, and then the signals need to be screened and combined to increase the detection dynamic range. The screening and combination of the signals can be realized through the following flow:

[0044] I. According to the fact that the pulse rising edge of the high-gain channel is earlier than that of the low-gain channel, the first rising edge of the waveform, i.e., the rising edge of the high-gain channel pulse signal, is determined as the detection starting point, and the high-gain pulse signal of the cell is found in combination with the cell pulse characteristics.

[0045] II. By analyzing the high-level characteristics of the signal or the threshold value set in the circuit, it can be judged whether the found high-gain pulse signal has reached a saturation state or entered a nonlinear region.

[0046] III. If it is determined that the signal has not reached the saturation state or the preset threshold value, the Peak value of the peak point is divided by the difference between the amplification multiples of the high-gain channel and the low-gain channel, and the obtained value is recorded as the signal amplitude value. That is, AM_n=High_Peak*GAIN_Low / GAIN_High.

[0047] IV. If it is determined that the signal has reached the preset threshold value or the saturation nonlinear state, the rising edge of the next pulse (i.e., the low-gain channel) is taken as the detection starting point, and the Peak value of the pulse is recorded. That is, AM_n=Low_Peak.

[0048] V. In this way, the effective Peak values of all pulses passing through the sheath flow cell are recorded until the counting period ends, and the recorded data is plotted and the cell pulse count is performed.

[0049] Referring to Figure 4 , Part 1 is the photodetector 3. The detector used in the present example is a PIN PD silicon photocell with a spectral response range of 400-1100 nm from Hamamatsu. In actual implementation, similar PIN PDs from companies such as Osram and Rohm can also be used. If the intensity of the cell scattered light is extremely weak, high-sensitivity light detection devices such as APD and SiPM can also be used. In the corresponding laser wavelength range, the size of the dark current should be controlled, and the current Is-min obtained by multiplying the lowest expected scattered light of the system by the responsivity of the PD should be greater than the dark current, which can ensure that a signal higher than the noise floor is generated. In the present example, the dark current of the PD is less than 50 nA. The PD can work in photovoltaic mode or photoconductive mode.

[0050] The second part of the schematic diagram is a TIA amplification conversion circuit, which is used to extract the small signal generated by the sensor in a high background noise environment. Due to the weakness of the signal, the amplifier should minimize the error introduced by it, which mainly consists of the offset current error and the voltage error. The TIA amplification conversion circuit unit in the present example is composed of an operational amplifier U2 (in the present example, AD549 is used, and the current offset is only 60 fA), a resistor R201, a resistor R7, and a capacitor C201. The ideal relationship between the output voltage and the input current of the conversion circuit can be expressed as: Vout = -(Is x Rf), where Rf is R201 in the diagram. The resistor R7 serves as an isolation function to suppress the potential resonance risk caused by the packaging small inductance and the internal capacitance of the amplifier. The value of this resistor is generally selected to be less than 50 ohms. Because the presence of the PD junction capacitance can easily lead to unstable circuit state, a capacitor C201 is needed for phase lead compensation. The size of the compensation capacitor is determined in combination with the system design index and the formula:

[0051]

[0052] where: R f is the resistance value of the gain resistor R201. f p is the 3dB bandwidth, which is determined by the signal characteristics of the cell pulse.

[0053] The third part of the schematic diagram is a low-noise amplification conversion circuit, which is mainly composed of U3, i.e., the peripheral resistors R202, R203, R204, and the capacitor C202. The purpose is to further amplify the cell pulse signal on the basis of the first stage, further reduce the noise interference in the output signal of the photodetector 3, and improve the signal clarity. Therefore, the operational amplifier should be selected to have a low voltage noise index. In the present example, ADI's AD8034 is selected. The circuit is a reverse amplifier, and the gain is Vout ≈ -Vin x (R204 / R202). The function of C202 is a frequency compensation capacitor, and R203 is a balancing resistor used to reduce the voltage offset error.

[0054] The fourth part of the schematic diagram is the buffer 6, which is a voltage follower composed of an operational amplifier. Before the signal enters the buffer 6, it passes through a first-order low-pass filter composed of R8 and C8. This filter also has the function of adjusting the delay amount of the pulse signal to correct the pulse time offset between different channels.

[0055] The 5th part and the 6th part of the schematic diagram are the start of the high and low gain channels of the same pulse signal source, the pulse signal is divided into two branches from here, the 5th part is the high gain amplifier branch, and the 6th part is the low gain amplifier branch, the signal amplitude of the input high and low gain channels is about 0 (submerged in the background PLT signal) ~ 0.5V (large white blood cell signal), the width of the pulse is calculated according to the bottom of the pulse, in most sheath flow systems, the pulse width is distributed in 0.5uS ~ 2uS (the half-height width is about 0.4 ~ 1.8uS), the single signal pulse pattern is similar to the clock type distribution of the Gaussian pulse, which is approximately described as:

[0056] f(x) = A*e -(x-b)2 / (2σ2)

[0057] In the formula, A is the amplitude, b is the peak center, and sigma is the standard deviation. According to the variance conversion relationship between the time domain and the frequency domain of the one-dimensional Gaussian function, the signal frequency to be processed is distributed in the range of about 800KHz ~ 3.6MHz. For large signals, the slew rate is usually used instead of the bandwidth to evaluate the performance of the amplifier, and the operational amplifier used in this example is TPH2502, which forms a reverse amplifier with R316, R317 and C475. The gain of the two circuit branches is set to differ by a fixed multiple, and this data is determined according to the background noise and the saturation amplitude of the amplifier as well as the dynamic range of the signal chain. In specific applications, this number is usually distributed between 16 ~ 64 times, that is, R316 is equal to R228, R317 is 16 ~ 64 times of R289, and C455 is also about 16 ~ 64 times of C475.

[0058] The 7th and 8th parts of the schematic diagram, i.e. the program-controlled gain adjusting circuits of the high and low gain two branches, are mainly used for adapting to the requirements of different sample test items and correcting the bench-to-bench difference between different instruments. In the present example, the digital potentiometer is used to realize the dynamic gain adjusting function. For the convenience of description, the forward amplification is used in the present example, and in the actual application, the reverse amplification or other mixed amplification forms can be used. Taking the high gain channel as an example, the signal output by the front-stage circuit is taken as the input of the present circuit, and the signal output of the present circuit is Uo = Ui * (1 + (Rf + R319) / R311). Wherein, Rf is the resistance value of the feedback channel, and the size of the value is determined by the program control to adjust the tap position of the digital potentiometer, and the DAC can also be used to replace the digital potentiometer to realize the same function. C483 and R320 constitute a high-pass filter, which is used to adjust the baseline to the vicinity of 0 level, R326 is used to isolate the influence of the capacitor, and C469 is used to avoid the change of the baseline in the gain adjusting process. The digital gain adjusting unit is used to adjust the gain amplification, which can be adjusted in a dynamic way or in a static way. The unit is connected to the feedback channel of the amplifier as part of the feedback channel of the amplifier, so as to achieve the purpose of gain control. In the present example, the gain adjustment adopts the 8-bit digital potentiometer AD5144TRUZ10, and the gain configuration instructions of each analog channel are sequentially issued by the FPGA or other digital control circuit through the SPI interface. The interface on the circuit is L_B1, L_W1, L_B3 and L_W3 in the figure, which represents the B and W taps in the three-tap potentiometer. The A tap in the other section is not shown in the figure, and it is short-circuited with the B or W tap.

[0059] The 9th and 10th parts of the schematic diagram are the signal filtering parts of the high and low gain two branches, especially the high gain channel of the front-stage. The saturation of the operational amplifier leads to the rich frequency components of the signal edge, and the signal edge may produce certain distortion, so it is necessary to filter and smooth the signal. The signal edge trimming filter module is mainly composed of U52, U5 and peripheral resistance and capacitance devices, and its essence is a two-order active low-pass Sallen-Key filter with gain coefficient composed of operational amplifier.

[0060] The 11th and 12th parts of the schematic diagram are the ADC buffer driving circuits of the high and low gain two branches. In the present example, the ADA4940 operational amplifier is used as the driving, and the single-ended signal is converted into differential signal at the same time. The resistance values of the gain adjusting resistors R17-R20 and R24-R27 are equal, R21 and R22 are output impedance, generally less than 33 ohm, R23 is matching resistance, generally selected in the range of 50-100 ohm, and C540 is matching capacitor, generally selected in the range of 20-80 pF according to the signal characteristics generated by the sample.

[0061] The 13th part of the schematic diagram is an ADC and a digital processing unit (usually a DSP or an FPGA), which combines the data of the high-gain and low-gain channels into one signal through program code processing according to the flow and logic described above, and identifies the optical platelet signal. Thus, the effect of digitally expanding the dynamic range of the signal is achieved. Figure 3

[0062] The following are test results of standard particles of different sizes after the scheme is used on a certain type of blood cell analyzer of the URIT company, Figure 5 are ADC acquisition value summary curves of the high-gain channel and the low-gain channel. In this example, 12-bit ADCs are used to acquire analog signals. From the ADC acquisition results, it can be seen that for the high-gain channel, the ADC sampling values of the 3rd to 7th standard particles are already saturated, and the acquisition value reaches 4095. For the low-gain channel, the ADC sampling values of the 1st to 3rd standard particles are relatively low, and the difference with the background noise is not obvious, and the signal-to-noise ratio is insufficient. Figure 6 is the result of digital merging and processing of the high-gain and low-gain two-channel sampling data through program design. The final digital value has a good linear relationship with the size of the particle, and the stability of the value is good, effectively expanding the dynamic range of cell measurement, and greatly improving the recognition rate of optical platelets.

[0063] The above only discloses a preferred embodiment of an optical signal processing circuit for a blood cell analyzer of the present application, and of course cannot limit the scope of the rights of the present application. Those skilled in the art can understand that all or part of the above-mentioned embodiments are implemented, and equivalent changes made according to the claims of the present application still belong to the scope covered by the present application.​

Claims

1. An optical signal processing circuit for a hematology analyzer, Characterized in that; The optical signal processing circuit for the blood cell analyzer comprises a light source driving monitoring module, a sheath flow control circuit module, a photodetector, a transconductance amplifier, a low-noise amplifier, a buffer, a high-gain amplifier, a low-gain amplifier, a first gain adjusting unit, a first filter, a first analog-to-digital converter, a second gain adjusting unit, a second filter, a second analog-to-digital converter, and a programmable gate array / digital processing unit. The light source driving monitoring module is connected with the sheath flow control circuit module, the photodetector is connected with the sheath flow control circuit module, the transconductance amplifier is connected with the low-noise amplifier and the transconductance amplifier respectively, the buffer is connected with the low-noise amplifier, the high-gain amplifier, and the low-gain amplifier respectively, the first gain adjusting unit, the first filter, and the first analog-to-digital converter are connected in sequence, the second gain adjusting unit, the second filter, and the second analog-to-digital converter are connected in sequence, the first gain adjusting unit is connected with the high-gain amplifier, the second gain adjusting unit is connected with the low-gain amplifier, and the programmable gate array / digital processing unit is connected with the first analog-to-digital converter and the second analog-to-digital converter respectively.

2. The optical signal processing circuit for a hematology analyzer as claimed in claim 1, characterized in that ； The light source driving monitoring module is composed of a light source driving circuit, a light source detection circuit, and a laser light source.

3. The optical signal processing circuit for the blood cell analyzer according to claim 1, characterized in that; The sheath flow control circuit module is composed of a sheath flow control circuit and a sheath flow chamber.

4. The optical signal processing circuit for a hematology analyzer as claimed in claim 1, characterized in that ； The photodetector is a PIN PD silicon photocell with a spectral response range of 400-1100 nm from Hamamatsu, and similar PIN PDs from Osram and Rohm can also be used in actual implementation. If the intensity of the cell scattered light is extremely weak, high-sensitivity light detection devices such as APD and SiPM can also be used.

5. The optical signal processing circuit for a blood cell analyzer as described in claim 1, Characterized in that; The digital processing unit in the programmable gate array / digital processing unit can use other signal processing techniques such as digital filtering, signal transformation, and feature extraction to further improve the quality and accuracy of the signal.

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