Fluorescence detection device, nucleic acid detection system and full-automatic nucleic acid all-in-one machine

Abstract

The utility model discloses a fluorescence detection device, a nucleic acid detection system and a full-automatic nucleic acid all-in-one machine, the fluorescence detection device comprises an excitation unit and an emission unit, the excitation unit comprises an excitation light source and an incident light path optical fiber, and the incident light path optical fiber is used for guiding incident light generated by the excitation light source to a sample; the emission unit comprises a photoelectric detector and an emission light path optical fiber, and the emission light path optical fiber is used for guiding fluorescence generated by the sample to the photoelectric detector. The nucleic acid detection system comprises a central processing unit and a fluorescence detection device, and the central processing unit is connected with the excitation light source to control the excitation light source to generate incident light; and the central processor is also connected with the photoelectric detector and is used for analyzing and processing data detected by the photoelectric detector. The full-automatic nucleic acid integrated machine comprises the nucleic acid detection system. According to the fluorescence detection device provided by the utility model, a double-path optical fiber design is adopted, so that mutual interference of exciting light and fluorescence signals is avoided, and the overall detection sensitivity and the signal processing precision are improved.

Description

TECHNICAL FIELD

[0001] The utility model relates to nucleic acid detection technical field, concretely relates to a fluorescence detection device, nucleic acid detection system and full -automatic nucleic acid integrated machine. BACKGROUND

[0002] With the rapid development of molecular biology technology, nucleic acid detection has become an important means of disease diagnosis, gene analysis and infection monitoring. Traditional nucleic acid detection method usually needs complex operation steps and long detection time, which limits its application in clinical and on-site detection. In order to improve the detection efficiency, full-automatic nucleic acid integrated machine appears on the market, which integrates sample preparation, nucleic acid amplification and fluorescence detection and multiple modules.

[0003] As a key detection means, fluorescence detection is widely used in quantitative analysis of nucleic acid amplification product. The existing fluorescence detection system has made great progress in sensitivity and specificity, but still faces challenges such as fluorescence signal interference, detection sensitivity and accuracy. Therefore, it has important application value and market potential to develop a kind of efficient and reliable fluorescence detection device to adapt to the automation and rapid detection demand of full-automatic nucleic acid integrated machine. SUMMARY

[0004] The utility model discloses a kind of fluorescence detection devices, nucleic acid detection systems and full-automatic nucleic acid integrated machine, to overcome the above technical deficiencies, solve the technical problem that nucleic acid detection sensitivity and accuracy need to be improved in prior art.

[0005] To achieve the above technical purpose, the utility model takes the following technical scheme:

[0006] Firstly, the utility model provides a kind of fluorescence detection device, comprising:

[0007] Excitation unit, excitation unit includes excitation light source and incident light path optical fiber, incident light path optical fiber one end is towards excitation light source, its other end is used to towards the PCR tube containing sample, incident light path optical fiber is used to guide the incident light generated by excitation light source to sample;

[0008] Emission unit, emission unit includes photodetector and emission light path optical fiber, emission light path optical fiber one end is used to towards the PCR tube containing sample, its other end is towards photodetector, emission light path optical fiber is used to guide the fluorescence generated by sample to photodetector.

[0009] In some embodiments, excitation unit further includes first collimating lens, first optical filter, first lenticular lens and first light uniformity sheet arranged between excitation light source and incident light path optical fiber in turn along incident light transmission direction.

[0010] In some embodiments, the emission unit further comprises, in sequence along the fluorescence transmission direction between the emission light path optical fiber and the photodetector, a second collimating lens, a second filter and a second lenticular lens.

[0011] In some embodiments, the excitation unit comprises a plurality of first lenticular lenses arranged in sequence; and the emission unit comprises a plurality of second lenticular lenses arranged in sequence.

[0012] In a second aspect, the utility model also provides a nucleic acid detection system, including central processing unit and fluorescence detection device, central processing unit is connected with excitation light source to control excitation light source generates incident light, central processing unit is also connected with photodetector to analyze and process the data detected by photodetector.

[0013] In some embodiments, the nucleic acid detection system comprises a plurality of fluorescence detection devices, and the central processing unit is connected with each excitation light source and each photodetector respectively.

[0014] In some embodiments, the nucleic acid detection system further comprises a digital-to-analog converter and a constant current source, and the central processing unit is connected with the digital-to-analog converter, the constant current source and the excitation light source in sequence, the digital-to-analog converter is used to convert the digital signal of the central processing unit into an analog signal so as to control the output current of the constant current source, and the constant current source provides stable current for the excitation light source.

[0015] In some embodiments, the nucleic acid detection system further comprises an IV converter, a filter circuit, a voltage amplifier and an analog-to-digital converter, and the photodetector is connected with the IV converter, the filter circuit, the voltage amplifier, the analog-to-digital converter and the central processing unit in sequence.

[0016] In some embodiments, the nucleic acid detection system further comprises a position sensor, and the position sensor is connected with the central processing unit, and the position sensor is used to detect whether the PCR tube is in place.

[0017] In a third aspect, the utility model also provides a full-automatic nucleic acid integrated machine, which comprises the nucleic acid detection system.

[0018] Compared with the prior art, the fluorescence detection device provided by the utility model adopts a double-path optical fiber design, avoids mutual interference of excitation light and fluorescence signals, optimizes fluorescence excitation and fluorescence signal transmission, and improves overall detection sensitivity and signal processing accuracy; the nucleic acid detection system provided by the utility model integrates various optical elements, guarantees high efficiency, stability and adaptability of the system, and significantly improves speed, sensitivity and accuracy of nucleic acid detection. BRIEF DESCRIPTION OF DRAWINGS

[0019] Figure 1 The utility model provides a fluorescence detection device's structure schematic view for embodiment of the utility model;

[0020] Figure 2 The utility model provides a nucleic acid detection system's structure schematic view for embodiment of the utility model; Figure 1Structure diagram of the excitation unit in the middle;

[0021] Figure 3 For Figure 1 Structure diagram of the emission unit in the middle;

[0022] Figure 4 Structure block diagram of the nucleic acid detection system provided by the embodiment of the utility model;

[0023] Figure 5 Work flow chart of the nucleic acid detection system provided by the embodiment of the utility model. DETAILED DESCRIPTION

[0024] In order to make the purpose, technical scheme and advantages of the utility model more clear, the utility model is further described in detail below in combination with the drawings and embodiments. It should be understood that the specific embodiments described herein are only used to explain the utility model, and are not used to limit the utility model.

[0025] In order to solve the technical problem that the sensitivity and accuracy of nucleic acid detection need to be improved, the utility model provides a fluorescence detection device, nucleic acid detection system and full-automatic nucleic acid integrated machine, which can significantly improve the speed, sensitivity and accuracy of nucleic acid detection.

[0026] It should be noted that the fluorescence detection device, nucleic acid detection system and full-automatic nucleic acid integrated machine are used for but not limited to nucleic acid detection. In order to facilitate the description, in the utility model, only the fluorescence detection device, nucleic acid detection system and full-automatic nucleic acid integrated machine applied to nucleic acid detection are taken as examples for description, and the principle of the fluorescence detection device, nucleic acid detection system and full-automatic nucleic acid integrated machine applied to other substances needing fluorescence detection is substantially the same as that applied to nucleic acid detection, which will not be described one by one.

[0027] Please refer to Figures 1 to 3 , Figure 1 Structure diagram of the fluorescence detection device provided by the embodiment of the utility model; Figure 2 For Figure 1 Structure diagram of the excitation unit in the middle; Figure 3 For Figure 1 Structure diagram of the emission unit in the middle.

[0028] The fluorescence detection device comprises an excitation unit 1 and an emission unit 2.

[0029] The excitation unit 1 comprises an excitation light source 11 and an incident light path optical fiber 12, one end of which is directed towards the excitation light source 11 and the other end of which is used to direct towards the PCR tube 3 containing the sample. The excitation light source 11 is used to provide excitation light in a specific wavelength range for exciting the fluorescent substance in the sample. The incident light path optical fiber 12 is used to guide the incident light generated by the excitation light source 11 to the sample in the PCR tube 3.

[0030] The emission unit 2 comprises a photodetector 21 and an emission light path optical fiber 22, one end of which is used to direct towards the PCR tube 3 containing the sample and the other end of which is directed towards the photodetector 21. The photodetector 21 is used to convert the received fluorescent signal light energy into an electrical signal, and subsequent processing of the electrical signal realizes quantitative analysis of specific fluorescent markers in nucleic acid detection. The emission light path optical fiber 22 is used to guide the fluorescence generated by the sample to the photodetector 21.

[0031] The sample in the PCR tube 3 will generate fluorescence after being irradiated by the incident light, and the emission light path optical fiber 22 transmits the fluorescence to the photodetector 21 for detection and analysis by recognizing the fluorescence signal. The fluorescence detection device adopts a double light fiber design, i.e. the incident light path optical fiber 12 and the emission light path optical fiber 22, which avoids mutual interference of the excitation light and the fluorescence signal, optimizes the transmission of the fluorescence excitation and the fluorescence signal, and improves the overall detection sensitivity and signal processing accuracy.

[0032] In the embodiment, the excitation light source 11 adopts an LED light source (SMT package) with a wavelength of 470 nm, which is equipped with a focusing lens to ensure that the divergence angle of the light source is less than 60 degrees and the power is greater than 1 watt.

[0033] In some embodiments, the excitation unit 1 further comprises a first collimating lens 13, a first filter 14, a first biconvex lens 15 and a first light uniformity sheet 16 arranged in sequence between the excitation light source 11 and the incident light path optical fiber 12 along the incident light transmission direction.

[0034] The first collimating lens 13 is used to collimate the divergent excitation light emitted by the excitation light source 11 to form a parallel light beam, which maximally reduces the divergence of the light beam and ensures that the angle of the light rays entering the first filter 14 is ±5 degrees. In the embodiment, the numerical aperture (NA) of the first collimating lens 13 is in the range of 0.5-1.0, and the optional range of the focal length f is 1 mm, 2 mm, 3 mm, 4 mm, to ensure efficient aggregation and collimation transmission of light energy.

[0035] The first filter 14 is a narrow-band filter, which is used to remove stray light in the excitation light spectrum, transmit light meeting the excitation wavelength requirement of the fluorescent substance in the sample, and ensure selective excitation of the target waveband. In the embodiment, the model of the first filter 14 can be selected as 470 / 11, 470 / 20 or 470 / 25, and the appropriate bandwidth filtering characteristic is selected according to different application scenarios.

[0036] The first lenticular lens 15 further converges the excitation light passing through the first filter 14, so that the focused light spot is smaller than the aperture of the incident optical fiber 12 and is concentrated on the target sample, to improve the excitation efficiency. In the preferred embodiment, at least two first lenticular lenses 15 are arranged in sequence. The two first lenticular lenses 15 can separate the optical power, and the NA of the incident optical fiber is smaller than the maximum light collection NA of the incident optical fiber 12. In the embodiment, the focal length f of the first lenticular lens 15 can be adjusted in the range of 9-12 mm, to ensure that the light beam can be accurately concentrated on the sample area and provide sufficient light energy to excite the fluorescent molecules, so as to obtain stronger fluorescent response.

[0037] The first homogenizing plate 16 is used to homogenize the light spot of the incident optical fiber, to ensure that the light spot irradiating on the PCR tube 3 is relatively uniform (uniformity > 85%), so that a “flat top” appears when the optical fiber is scanned. In the embodiment, the number of grits of the first homogenizing plate 16 is 1200, which is used to homogenize the light spot of the excitation light beam, to make the light spot uniformly distributed and avoid local light spot shadows, to ensure the uniformity of the light irradiation on the sample area, thereby optimizing the excitation effect of the fluorescent light.

[0038] In some embodiments, the photodetector 21 is a photodiode (PD).

[0039] In some embodiments, the emission unit 2 further includes a second collimating lens 23, a second filter 24 and a second lenticular lens 25 arranged in sequence between the emission optical fiber 22 and the photodetector 21 along the fluorescent light transmission direction.

[0040] The second collimating lens 23 is used to collimate the fluorescent signal emitted by the emission optical fiber 22 from a divergent state to parallel light, to ensure that the angle of the light incident on the second filter 24 is ±5 degrees. In the embodiment, the numerical aperture (NA) of the second collimating lens 23 is selected in the range of 0.5-1.0, and the focal length f is selected in the range of 1 mm, 2 mm, 3 mm and 4 mm, to ensure the collimated transmission of the fluorescent signal and improve the light path transmission efficiency.

[0041] The second filter 24 is used to remove redundant background light (mainly excitation light) and stray light signals, and only allow fluorescent signals of a specific waveband to pass through, to improve the signal-to-noise ratio and improve the detection accuracy. In the embodiment, the model of the second filter 24 can be selected as 470 / 11, 470 / 20 or 470 / 25, and the specific selection is based on the target waveband of the monitored sample and the application requirement.

[0042] The second lenticular lens 25 converges the parallel fluorescent light beam passing through the second filter 24, so that the light beam is concentrated on the photodetector 21, improving the detection efficiency and enhancing the capture ability of the weak fluorescent signal. In the preferred embodiment, at least two second lenticular lenses 5 are arranged in sequence. In this embodiment, the focal length f of the second lenticular lens 5 ranges from 9 to 12 mm, so as to ensure that the fluorescent signal can be focused on the predetermined detection area of the light path, ensuring the maximum signal collection efficiency.

[0043] The fluorescence detection device comprises an excitation unit 1 and an emission unit 2. The excitation light of a specific wavelength is provided by an LED, and components such as collimating lenses, filters, lenticular lenses, and homogenizing plates are used to accurately irradiate the sample with the excitation light and improve the excitation efficiency. The fluorescent signal is transmitted to a photodiode (PD) through another independent emission light path optical fiber 22 for efficient collection and conversion into an electrical signal, realizing quantitative analysis of the fluorescent signal. By using a double-path optical fiber design, the mutual interference of the excitation light and the fluorescent signal is avoided. The transmission efficiency of the optical path is optimized, providing a good technical guarantee for the accurate collection and processing of the fluorescent signal in the nucleic acid detection process.

[0044] Please refer to Figure 4 and Figure 5 , Figure 4 the structure block diagram of the nucleic acid detection system provided by the embodiment of the utility model; Figure 5 the working flow chart of the nucleic acid detection system provided by the embodiment of the utility model.

[0045] The nucleic acid detection system comprises a central processing unit 10 and a fluorescence detection device 20. The central processing unit 10 is connected to an excitation light source 11 to control the generation of incident light by the excitation light source 11. The central processing unit 10 is also connected to a photodetector 21 to analyze and process the data detected by the photodetector 21.

[0046] In some embodiments, the central processing unit 10 performs data analysis and is responsible for controlling the operation of the entire system, including adjusting the light intensity of the excitation light source 11, processing user input, and coordinating communication between various components.

[0047] In some embodiments, the nucleic acid detection system comprises multiple fluorescence detection devices 20, and the central processing unit 10 is connected to each excitation light source 11 and each photodetector 21. The arrangement of multiple parallel fluorescence detection devices 20 enables simultaneous detection of multiple samples, enhancing the flexibility and diversity of detection. This makes the system adaptable to various detection needs, thereby widely applicable to fluorescence analysis in different fields and improving detection efficiency. In this embodiment, six fluorescence detection devices 20 are used, which can simultaneously detect six samples.

[0048] In some embodiments, the nucleic acid detection system further comprises a digital-to-analog converter 30 and a constant current source 40, which are sequentially connected to the central processing unit 10, the excitation light source 11.

[0049] The digital-to-analog converter 30 is used to convert the digital signal of the central processing unit 10 into an analog signal, which is used to accurately control the driving current of the excitation light source 11. Through the conversion of the digital-to-analog converter 30, the system can finely adjust the brightness of the excitation light source 11 to meet the detection needs of different samples. A high-precision digital-to-analog converter 30 can provide more detailed current changes, thereby improving the accuracy and stability of the light emitted by the excitation light source 11. This is particularly important in complex fluorescence detection applications, as small changes in light intensity can significantly affect the measurement results.

[0050] The constant current source 40 is responsible for providing stable current in the system, ensuring the uniformity and stability of the light emitted by the excitation light source 11. The light-emitting characteristics of the excitation light source 11, i.e. the LED light source, are very sensitive to current, so the stable output of the constant current source is crucial to maintaining consistent light intensity. Through the action of the constant current source, the system can avoid measurement errors caused by current fluctuations, improving the accuracy and reliability of fluorescence detection.

[0051] In some embodiments, the nucleic acid detection system further comprises an IV converter 50, a filter circuit 60, a voltage amplifier 70, and an analog-to-digital converter 80. The photodetector 21 is sequentially connected to the IV converter 50, the filter circuit 60, the voltage amplifier 70, the analog-to-digital converter 80, and the central processing unit 10.

[0052] The IV converter 50 is used to convert the current signal output by the photodetector 21 into a voltage signal for subsequent signal amplification and processing. The current signal is usually weak and susceptible to interference, and through the conversion of the IV converter 50, the signal is transmitted in the form of more stable voltage. This conversion process is an important link in the signal processing chain, directly affecting the integrity and accuracy of the signal.

[0053] The filter circuit 60 is used to eliminate high and low frequency noise in the collected signal, improving the purity and accuracy of the signal. Fluorescence signals are easily affected by various electromagnetic interferences and thermal noise during transmission and conversion, and the filter circuit can effectively remove these interferences through specific frequency selectivity.

[0054] The voltage amplifier 70 amplifies the voltage signal to a signal amplitude suitable for processing by the analog-to-digital converter 80. Since the fluorescence signal is usually weak, it directly affects the resolution and accuracy of the signal, so the amplifier needs to provide sufficient gain while maintaining low noise and high linearity. The design and selection of the voltage amplifier 70 are directly related to the detection sensitivity and accuracy of the system. Through appropriate amplification, the system can better capture and analyze weak fluorescence signals, improving overall detection performance.

[0055] The analog-to-digital converter 80 is used to convert the amplified analog voltage signal into a digital signal for further analysis and processing by the central processor 10. The resolution and accuracy of the analog-to-digital converter 80 are critical indicators of system performance, directly affecting the accuracy and reliability of the data. High-precision analog-to-digital converter 80 can capture small signal changes, provide more abundant data information, and help achieve more detailed analysis.

[0056] In some embodiments, the nucleic acid detection system further comprises a to-bit sensor 90 connected to the central processor 10, which is used to detect the position and state of the PCR tube and start the detection process after ensuring that the sample is correctly positioned. It provides an initial signal to the central processor 10 to accurately synchronize the operation of the automated equipment, thereby improving the accuracy and efficiency of the detection.

[0057] In some embodiments, the nucleic acid detection system further comprises a terminal 100 connected to the central processor 10. The terminal 100 is the human-computer interaction interface of the system, responsible for displaying the processed data and analysis results to the user intuitively. The terminal 100 can be a liquid crystal display or a computer interface, providing graphical data display and operation options. Users can view real-time data, historical records, and make necessary settings and operations through the terminal 100.

[0058] In order to better understand the present application, the following will be combined Figure 4 and Figure 5 The technical scheme of the present application is described in detail:

[0059] The system realizes the complete process from sample detection to data processing through the cooperation of multiple key components. First, the in-place sensor 90 is responsible for detecting the position and state of the sample, providing an initial signal to the central processor 10, ensuring the accurate start of the detection process. The central processor 10 controls the operation of the entire system and performs data processing. The central processor 10 converts the generated digital signal into an analog signal through the digital-to-analog converter 30, controls the constant current source 40 to provide stable current, and ensures the uniformity and stability of the light emitted by the excitation light source 11. These excitation light sources 11 emit light of a specific wavelength to excite fluorescent substances in the sample. The corresponding photodetector 21 receives the fluorescent signal and converts the optical signal into an electrical signal. Subsequently, the IV converter 50 converts these current signals into voltage signals. The filter circuit 60 eliminates high and low frequency noise in the signal, improving the purity and accuracy of the signal. The voltage amplifier 70 further amplifies the voltage signal to an amplitude suitable for the analog-to-digital converter 80. Finally, the analog-to-digital converter 80 converts the amplified analog voltage signal into a digital signal for the central processor 10 to further analyze and process. The processed data and analysis results are displayed to the user through the terminal 100, realizing the effective transmission and application of detection information.

[0060] The utility model further provides a full -automatic nucleic acid integrated machine, including above -mentioned nucleic acid detection system.

[0061] The above-mentioned specific embodiments of the utility model do not constitute a limitation on the scope of protection of the utility model. Any changes and modifications made in accordance with the technical concept of the utility model shall be included within the scope of protection of the claims of the utility model.

Claims

1. A fluorescence detection device, characterized by, include: An excitation unit is provided, comprising an excitation source and an incident optical fiber. One end of the incident optical fiber faces the excitation source, and the other end faces a PCR tube containing a sample. The incident optical fiber is used to guide the incident light generated by the excitation source to the sample. The emission unit includes a photodetector and an optical fiber for emission. One end of the optical fiber is directed toward a PCR tube containing a sample, and the other end is directed toward the photodetector. The optical fiber is used to guide the fluorescence generated by the sample to the photodetector.

2. The fluorescence detection device of claim 1, wherein, The excitation unit further includes a first collimating lens, a first filter, a first biconvex lens, and a first light homogenizer arranged sequentially between the excitation source and the incident optical fiber along the incident light transmission direction.

3. The fluorescence detection device of claim 2, wherein, The transmitting unit further includes a second collimating lens, a second filter, and a second biconvex lens arranged sequentially between the transmitting optical fiber and the photodetector along the fluorescence transmission direction.

4. The fluorescence detection device of claim 3, wherein, The excitation unit includes a plurality of first biconvex lenses arranged in sequence; the emission unit includes a plurality of second biconvex lenses arranged in sequence.

5. A nucleic acid detection system, characterized by, The device includes a central processing unit and the fluorescence detection device according to any one of claims 1-4, wherein the central processing unit is connected to the excitation light source to control the excitation light source to generate incident light; the central processing unit is also connected to the photodetector to analyze and process the data detected by the photodetector.

6. The nucleic acid detection system of claim 5, wherein, It includes multiple fluorescence detection devices, and the central processing unit is connected to each of the excitation light sources and each of the photodetectors.

7. The nucleic acid detection system of claim 5, wherein, It also includes a digital-to-analog converter and a constant current source. The central processing unit is connected in sequence to the digital-to-analog converter, the constant current source and the excitation light source. The digital-to-analog converter is used to convert the digital signal of the central processing unit into an analog signal, thereby controlling the output current of the constant current source; the constant current source provides a stable current to the excitation light source.

8. The nucleic acid detection system of claim 5, wherein, It also includes an IV converter, a filter circuit, a voltage amplifier, and an analog-to-digital converter, with the photodetector connected in sequence to the IV converter, the filter circuit, the voltage amplifier, the analog-to-digital converter, and the central processing unit.

9. The nucleic acid detection system of claim 5, wherein, It also includes a positioning sensor, which is connected to the central processing unit and is used to detect whether the PCR tube is in place.

10. A fully automatic nucleic acid all-in-one machine, characterized in that, Including the nucleic acid detection system as described in any one of claims 5-9.

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