Optical detection system of flow type fluorescence instrument and flow type instrument

Abstract

The utility model relates to the field of biological detection, in particular to an optical detection system of a flow type fluorescence instrument and the flow type instrument, which comprises an optical substrate, the optical substrate is respectively provided with a laser light source, a laser light path adjusting device, a laser shaping and focusing device, a forward scattered light receiving device, a fluorescence receiving device and a flow chamber, the laser light path adjusting device is arranged at a light outlet of a laser light source, a laser shaping and focusing device is arranged on one side of the laser light path adjusting device, and a forward scattered light receiving device, a fluorescent light receiving device and a flowing chamber are arranged beside the laser shaping and focusing device. Laser beam shaping is not carried out in the laser, and the multiple laser beams are shaped and focused at the same position in front of incidence of the flow chamber. And the use number of the shaping prisms and the debugging flexibility are reduced. Meanwhile, the receiving channels of the fluorescence receiving device are mutually independent and adjustable, and different optical filters can be replaced according to different dyes for more detection and analysis.

Description

Technical Field

[0001] The utility model relates to the field of biological detection, in particular to an optical detection system of a flow fluorescence instrument and a flow instrument. Background Art

[0002] The colorimetric analysis method that relies on manual operation has made great contributions to my country's testing industry. After more than decades of development, my country has successfully achieved the historical transformation from medical testing to laboratory medicine. At this stage, laboratory medicine has formed an unprecedented new pattern.

[0003] Flow fluorescence, also known as suspension array, liquid phase chip, etc., is a multi-index joint diagnostic technology that has gradually developed in the past 20 years. This technology is based on fluorescent coded microspheres, integrating the principles of flow cytometry, laser analysis, high-speed digital signal processing, computer operation rules and other technologies. It can analyze multiple indicators in parallel and accurately and quantitatively detect hundreds of different biological molecules in one tube at the same time; it has the characteristics of high throughput, fast speed, high accuracy, good repeatability, high sensitivity, wide linear range, parallel detection, etc.; it can be used for immunoassay, nucleic acid research, enzymatic analysis, receptor, ligand recognition analysis and other aspects and fields of research. It represents the development direction of basic research in life sciences and medical diagnostic technology, and is one of the trending technologies for clinical diagnosis.

[0004] The technical principle of coded microspheres is to dye microspheres of different diameters into different fluorescent colors with a variety of classified fluorescent dyes in different ratios, thereby obtaining up to thousands of coded microspheres. Antibody molecules or antigen molecules for different analytes are covalently cross-linked to specific coded microspheres, and each coded microsphere corresponds to a corresponding test item. First, the fluorescent coded microspheres for different analytes are mixed, and then the analyte is added, and the formed complex reacts with the labeled fluorescent element. Driven by the flowing sheath fluid, the microspheres pass through the red and blue lasers in a single row. The red laser is used to determine the fluorescent coding of the microspheres, and the blue laser is used to measure the fluorescence intensity of the reporter molecules on the microspheres. Thereby achieving the purpose of rapid and accurate quantitative detection of multiple items.

[0005] Liquid chip technology has been developed to this day, but it is not widely used in clinical applications. The main reasons are: 1. Foreign products are mainly positioned in the field of scientific research and are not clinically friendly. All pre-processing processes need to be done manually. The degree of automation is too low and clinical applications are too cumbersome. 2. Instruments and coded microspheres are too expensive, which is fatal to large-scale clinical applications. Summary of the invention

[0006] The utility model aims to solve the technical problem that quantitative analysis cannot be performed due to low detection accuracy of fluorescence collection devices in the clinical application field, and provides an optical detection system of a flow fluorescence instrument and a flow instrument.

[0007] In order to achieve the above technical effects, the utility model is implemented through the following technical solutions:

[0008] An optical detection system for a flow fluorescence instrument comprises an optical path substrate, on which a laser light source, a laser optical path adjustment device, a laser shaping and focusing device, a forward scattered light receiving device, a fluorescence receiving device and a flow chamber are respectively mounted, the laser optical path adjustment device is arranged at the light outlet of the laser light source, a laser shaping and focusing device is arranged on one side of the laser optical path adjustment device, and a forward scattered light receiving device, a fluorescence receiving device and a flow chamber are respectively arranged next to the laser shaping and focusing device.

[0009] Furthermore, there are two laser light sources, namely a blue laser light source and a red laser light source.

[0010] Furthermore, an adjustable laser component is arranged inside the laser light source, and the adjustable laser component is adjusted forward and backward by a fine-tuning precision thread pair, and is fixed in the hole of the open fixing block by screws after the light beam emitted by the laser LED lamp is collimated.

[0011] Furthermore, there are two laser light path adjustment devices, and the blue laser light source and the red laser light source correspond to the first laser light path adjustment device and the second laser light path adjustment device respectively.

[0012] Furthermore, the laser shaping and focusing device comprises a rotating adjustment frame, a double-cemented lens and a shaping prism. The double-cemented lens and the shaping prism are mounted on the rotating adjustment frame, and the shaping prism is located in front of the double-cemented lens.

[0013] Furthermore, the forward scattered light receiving device includes a forward base, in which an aperture, a front collimating lens, a rear focusing lens, a filter structure, and a receiver are installed. The front collimating lens is located between the aperture and the filter structure, and the rear focusing lens is installed between the filter structure and the receiver.

[0014] Furthermore, the fluorescence receiving device comprises a fourth channel receiving device, a third channel receiving device, a second channel receiving device, a first dichroic mirror structure, a second dichroic mirror structure and a focusing lens installed on a fluorescence optical path base, and a flow chamber is arranged in front of the focusing lens.

[0015] Furthermore, the exterior of the optical path substrate is covered with an optical path light shielding device.

[0016] Furthermore, an optical path temperature control device is provided at the bottom of the optical path substrate.

[0017] A flow instrument includes an optical detection system, a liquid circuit system, a pre-treatment system and an electrical control system. The liquid circuit system is used to provide a sample flow to be tested, a sheath liquid flow and collect waste liquid of the sample flow after detection. The pre-treatment system is used for the reaction process between the sample and the reagent. The electrical control system is used for the motion control and information processing of the entire instrument.

[0018] The advantages of the utility model are:

[0019] 1. The prior art does not have a forward scattered light collection device. The laser of the present application does not perform laser beam shaping inside. Instead, multiple laser beams are shaped and focused at the same position in front of the flow chamber. This reduces the number of shaping prisms used and the flexibility of debugging. At the same time, the receiving channels of the fluorescence receiving device are independently adjustable and different filters can be replaced according to different dyes for more detection and analysis.

[0020] 2. The prior art uses a 525nm laser, while the present application uses a 488nm laser, which is compatible with more fluorescent dyes and has a different optical path design method.

[0021] 3. The existing technology uses prisms to shape the beam inside each laser. We use multiple groups of lasers to shape the beam at the same position outside, making the laser more compact and saving multiple groups of shaping prisms. The fluorescent receiving device is processed by structural segmentation, so that each debugging position can be adjusted independently, which greatly reduces the difficulty of installation and debugging, not only optimizes the overall performance, but also improves the practicality and efficiency of the solution.

[0022] 4. The core coded microspheres, flow liquid system, optical system, detection system, and software system involved in the utility model are all completely independently developed, with controllable costs and a localization rate of more than 95%. It has broken through many bottleneck technologies and achieved the goal of single-person, fully automatic, and multiple inspections with extremely high cost-effectiveness. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 It is a structural diagram of the optical detection system in the utility model.

[0024] Figure 2 It is a schematic diagram of the structure of the laser shaping and focusing device in the utility model.

[0025] Figure 3 It is a schematic diagram of the external structure of the forward scattered light receiving device in the utility model.

[0026] Figure 4 It is a schematic diagram of the internal structure of the forward scattered light receiving device in the utility model.

[0027] Figure 5 It is a schematic diagram of the structure of the fluorescence receiving device in the utility model.

[0028] Figure 6 This is a schematic diagram of the structure of the adjustable laser component in the utility model.

[0029] Figure 7 It is a structural schematic diagram of the light path light shielding device in the utility model.

[0030] Figure 8 This is a schematic diagram of the structure of the optical path temperature control device in the utility model.

[0031] In the attached figure:

[0032] 1-optical path substrate, 2-blue laser light source, 3-red laser light source, 4-fourth channel receiving device, 5-third channel receiving device, 6-second channel receiving device, 7-second dichroic mirror structure, 8-first dichroic mirror structure, 9-fluorescent light path base, 10-focusing lens, 11-forward scattered light receiving device, 12-flow chamber, 13-rotating adjustment frame, 14-double glued lens, 15-shaping prism, 16-first laser light path adjusting device, 17-second laser light path adjusting device, 18-adjustable laser assembly, 19-optical path light shielding device, 20-optical path temperature control device, 110-forward base, 111-aperture, 112-front collimating lens, 113-filter structure, 114-rear focusing lens, 115-receiver. DETAILED DESCRIPTION

[0033] The following is a detailed description of an embodiment of the present invention. This embodiment is implemented on the premise of the technical solution of the present invention, and a detailed implementation method and a specific operation process are given, but the protection scope of the present invention is not limited to the following embodiment.

[0034] It should be pointed out that all directional indications in the embodiments of the present invention (such as both sides, edges, up, down, left, right, front, back, middle, top, bottom, tail, axial, radial...) are only used to explain the relative position relationship, movement state, etc. between the components in a certain specific posture (as shown in the accompanying drawings). If the specific posture changes, the directional indication will also change accordingly.

[0035] Example 1

[0036] like Figure 1As shown, an optical detection system of a flow fluorescence instrument includes an optical path substrate 1, on which a laser light source, a laser light path adjustment device, a laser shaping and focusing device, a forward scattered light receiving device 11, a fluorescence receiving device and a flow chamber 12 are respectively installed, the laser light path adjustment device is arranged at the light outlet of the laser light source, a laser shaping and focusing device is arranged on one side of the laser light path adjustment device, and the forward scattered light receiving device 11, the fluorescence receiving device and the flow chamber 12 are respectively arranged next to the laser shaping and focusing device.

[0037] The laser light source is not limited to blue light and red laser light source 3, but blue light 488nm can be used to excite 585nm fluorescence detection, and red light 638nm can be used to excite 660nm and 780nm fluorescence signals. The fluorescence wavelengths excited by these two lasers are far apart, and there is little interference between them, which can improve the signal-to-noise ratio.

[0038] The optical path substrate 1 is used to fix various components of the optical system. The optical path substrate 1 is required to have good rigidity and high thermal conductivity to facilitate temperature control of the entire optical path system.

[0039] Example 2

[0040] like Figure 1 As shown, an optical detection system of a flow fluorescence instrument includes an optical path substrate 1, on which a laser light source, a laser light path adjustment device, a laser shaping and focusing device, a forward scattered light receiving device 11, a fluorescence receiving device and a flow chamber 12 are respectively installed, the laser light path adjustment device is arranged at the light outlet of the laser light source, a laser shaping and focusing device is arranged on one side of the laser light path adjustment device, and the forward scattered light receiving device 11, the fluorescence receiving device and the flow chamber 12 are respectively arranged next to the laser shaping and focusing device.

[0041] The laser light source is not limited to blue light and red laser light source 3, but blue light 488nm can be used to excite 585nm fluorescence detection, and red light 638nm can be used to excite 660nm and 780nm fluorescence signals. The fluorescence wavelengths excited by these two lasers are far apart, and there is little interference between them, which can improve the signal-to-noise ratio.

[0042] The optical path substrate 1 is used to fix various components of the optical system. The optical path substrate 1 is required to have good rigidity and high thermal conductivity to facilitate temperature control of the entire optical path system.

[0043] There are two laser light sources, namely a blue laser light source 2 and a red laser light source 3. The laser light sources are used to illuminate and excite the coded microspheres to emit fluorescence.

[0044] An adjustable laser component 18 is arranged inside the laser gas light source. The adjustable laser component 18 is adjusted forward and backward by a fine-tuning precision thread pair. After the light beam emitted by the laser LED lamp is collimated, it is fixed in the hole of the open fixing block by screws.

[0045] There are two laser light path adjustment devices, the blue laser light source 2 and the red laser light source 3 correspond to the first laser light path adjustment device 16 and the second laser light path adjustment device 17 respectively, which are used to adjust the tilt and pitch angle of the laser light source. The two laser light path adjustment devices are respectively used to independently adjust the two groups of laser light sources so that the two groups of lasers can reach the required accurate position in the flow chamber 12. The laser light path adjustment device adopts a flat spring structure and is driven by a fine screw, which has high precision, good stability and is more convenient to install.

[0046] The laser shaping and focusing device includes a rotating adjustment frame 13, a double glued lens 14 and a shaping prism 15, wherein the double glued lens 14 and the shaping prism 15 are mounted on the rotating adjustment frame 13, and the shaping prism 15 is located in front of the double glued lens 14. The laser shaping and focusing device is used to adjust the spot size of two different lasers and to adjust the focus at the same position. The light beam is focused at the center of the flow chamber 12 by adjusting the handle of the rotating adjustment frame 13. The shaping prism 15 can be glued to the prism seat, which is located on the surface of the rotating adjustment frame 13. The shaping prism 15 compresses the elliptical spot into a more elongated spot at a compression ratio of 2:1.

[0047] The forward scattered light receiving device 11 comprises a forward base 110, in which an aperture 111, a front collimating lens 112, a rear focusing lens 114, a filter structure 113, and a receiver 115 are installed. The front collimating lens 112 is located between the aperture 111 and the filter structure 113, and the rear focusing lens 114 is installed between the filter structure 113 and the receiver 115. The forward scattered light receiving device 11 is used for counting the number of encoded microspheres.

[0048] The fluorescence receiving device comprises a fourth channel receiving device 4, a third channel receiving device 5, a second channel receiving device 6, a first dichroic mirror structure 8, a second dichroic mirror structure 7 and a focusing lens 10 mounted on a fluorescence optical path base 9, wherein a flow chamber 12 is arranged in front of the focusing lens 10. The fluorescence receiving device is used to collect and collimate fluorescence, and output signals of each channel through a photoelectric conversion device.

[0049] Each channel is determined by the transmittance of the filter wavelength. The first two-way mirror structure 8 is a 700nm reflector, which passes wavelengths above 700nm and reflects wavelengths below 700nm. Wavelengths above 700nm pass through the corresponding filter and are received by the fourth channel receiving device 4, and wavelengths below 700nm are reflected by the second two-way mirror structure 7660nm reflector. Wavelengths above 660nm pass through the corresponding filter and are received by the third channel receiving device 5, and wavelengths below 660nm pass through the corresponding filter and are received by the second channel receiving device 6. Channels are named according to the order on the circuit board. The forward scattered light receiving device 11 can be considered as the first channel receiving device.

[0050] The fourth channel receiving device 4 of the 660nm fluorescence filter, the third channel receiving device 5 of the 585nm fluorescence filter, and the second channel receiving device 6 of the 725nm filter. The first dichroic mirror structure 8 includes a first dichroic mirror of 660nm glued on a dichroic mirror mounting seat. The second dichroic mirror structure 7 includes a dichroic mirror of 700nm glued on a dichroic mirror mounting seat. A waist-shaped through hole is opened on the fluorescent light path mounting base to facilitate the focal length adjustment of the focusing lens of the fluorescent receiving device. The flow chamber 12 provides a detection position for the sample. The sample passes through the small hole in the center of the flow chamber 12 under the wrapping of the sheath flow, and the laser excites the sample to emit fluorescence.

[0051] The outside of the optical path substrate 1 is covered with an optical path light shielding device 19, which is used to shield the interference of other natural light on the optical path system. The light shielding is achieved by covering the entire optical path structure with black plastic spraying.

[0052] An optical path temperature control device 20 is provided at the bottom of the optical path substrate 1. The optical path temperature control device 20 is used for constant temperature control of the fluorescence receiving device to ensure the stability of the output of the photoelectric conversion device. The optical path temperature control device 20 keeps the entire fluorescence receiving device in a constant temperature state through the cooling plate and the heat dissipation structure. Specifically, the cooling plate is placed at the bottom of the fluorescence receiving device through a heat dissipation silicone plate, and the other side of the cooling plate is connected to the heat dissipation structure. The heat dissipation structure is tightly attached to the optical path substrate 1, and finally the heat is taken away and dissipated through the optical path substrate 1.

[0053] Example 3

[0054] Figure 1 It is a schematic diagram of the structure of an embodiment of the utility model. As shown in the figure, the blue laser light source 2 and the red laser light source 3 are arranged on the optical path substrate 1, and the adjustable laser component 18 inside the laser light source is adjusted so that the light beams of the red and blue laser light sources 2 are in a collimated state.

[0055] The first laser light path adjusting device 16 , the second laser light path adjusting device 17 , and the laser shaping and focusing device are respectively arranged on the light path substrate 1 , and the adjusting frames are independently adjusted to make the light beam irradiate the center position of the flow chamber 12 .

[0056] The rotating adjustment frame 13 moves in the X direction, and the focusing position of the light beam is exactly at the center of the flow chamber 12 through the double cemented lens 14.

[0057] The forward scattered light receiving device 11 is arranged on the optical path substrate 1. An aperture 111 is installed in front of the forward scattered light receiving device 11 to block the axial light spot passing through the flow chamber 12. The front and rear lenses focus the scattered light onto the photoelectric conversion device, and a filter is arranged between the front and rear lenses.

[0058] The fluorescence receiving device is arranged on the optical path substrate 1. After the laser excites the fluorescence of the microsphere, the excited fluorescence is collimated by the focusing lens 10 arranged on the fluorescence optical path base 9 and reaches the first dichroic mirror structure 8 arranged on the fluorescence optical path base 9. The fluorescence to be received is separated by the first dichroic mirror structure 8 and reaches the second channel receiving device 6 and then outputs the corresponding electrical signal. The other fluorescence reaches the second dichroic mirror structure 7 arranged on the fluorescence optical path base 9. The fluorescence to be received outputs the corresponding electrical signal through the third channel receiving device 5 arranged on the fluorescence optical path base 9. The other fluorescence reaches the fourth channel receiving device 4 arranged on the fluorescence optical path base 9 and then outputs the corresponding electrical signal.

[0059] The red laser light source 3 is arranged on the optical path substrate 1, and the adjustable laser component 18 inside the red laser light source 3 is adjusted so that the light beam of the red laser light source 3 is in a collimated state.

[0060] The second laser optical path adjusting device 17 and the laser shaping and focusing device are respectively arranged on the optical path substrate 1. The second laser optical path adjusting device 17 is rotated so that the red laser beam is irradiated to the center position of the flow chamber 12 and the blue laser beam is irradiated to the upper position.

[0061] The adjustable laser assembly 18 inside the red laser light source 3 is fine-tuned so that the light beam of the red laser light source 3 is in a focused state at the center of the flow chamber 12 .

[0062] The fluorescence receiving device, after the red laser excites the fluorescence of the microsphere, the excited fluorescence is collimated by the focusing lens 10 arranged on the fluorescence light path base 9, and reaches the first dichroic mirror structure 8 arranged on the fluorescence light path base 9. The fluorescence passing through the first dichroic mirror structure 8 reaches the second channel receiving device 6 and outputs a corresponding electrical signal; the reflected fluorescence reaches the second dichroic mirror structure 7 arranged on the fluorescence light path base 9, and the APC signal passing through the second dichroic mirror structure 7 is output by the fourth channel receiving device 4 arranged on the fluorescence light path base 9 as a corresponding electrical signal.

[0063] Example 4

[0064] A flow instrument includes an optical detection system, a liquid circuit system, a pretreatment system and an electrical control system as described in Examples 1-3, wherein the liquid circuit system is used to provide a sample flow to be tested, a sheath liquid flow and to collect waste liquid of the sample flow after detection, the pretreatment system is used for the reaction process between the sample and the reagent, and the electrical control system is used for motion control and information processing of the entire instrument.

[0065] The liquid path system is used to provide a sample flow to be tested, a sheath flow and collect waste liquid of the sample flow after detection. The optical detection system is used to provide a light beam to illuminate the sample flow and obtain information of the sample flow after being illuminated by the light beam. The optical detection system includes a plurality of fluorescence receiving devices. The method includes:

[0066] The control-coded microspheres are arranged in a single row under the wrapping of the sheath liquid, pass through the flow chamber 12 at a uniform speed, and are irradiated by two beams of red and blue laser light sources. The red laser is used to excite the fluorescence coding of the microspheres, and the blue laser is used to excite the fluorescence of the reporter molecules on the microspheres. The fluorescence signal is converted into a photoelectric signal through a silicon photomultiplier tube, and enters a high-speed ADC after passing through an amplification circuit. The ADC result is read by the FPGA, and finally the data is sent to the software for analysis to complete the data acquisition. The microspheres of different projects can be identified separately, so that the detection of multiple reactions can be carried out simultaneously in a mixed reaction system.

Claims

1. An optical detection system for a flow fluorescence instrument, comprising an optical path substrate (1), characterized in that: A laser light source, a laser light path adjustment device, a laser shaping and focusing device, a forward scattered light receiving device (11), a fluorescence receiving device and a flow chamber (12) are respectively mounted on the optical path substrate (1); the laser light path adjustment device is arranged at the light outlet of the laser light source; a laser shaping and focusing device is arranged on one side of the laser light path adjustment device; and the forward scattered light receiving device (11), the fluorescence receiving device and the flow chamber (12) are respectively arranged next to the laser shaping and focusing device.

2. The optical detection system of a flow fluorescence instrument according to claim 1, characterized in that: The laser light sources are two, namely a blue laser light source (2) and a red laser light source (3).

3. The optical detection system of a flow fluorescence instrument according to claim 1, characterized in that: An adjustable laser component (18) is arranged inside the laser light source. The adjustable laser component (18) is adjusted forward and backward by a fine-tuning precision thread pair, and is fixed in a hole of an open fixing block by screws after collimating the light beam emitted by the laser LED lamp.

4. The optical detection system of a flow fluorescence instrument according to claim 2, characterized in that: There are two laser light path adjustment devices, and the blue laser light source (2) and the red laser light source (3) correspond to the first laser light path adjustment device (16) and the second laser light path adjustment device (17).

5. The optical detection system of a flow fluorescence instrument according to claim 1, characterized in that: The laser shaping and focusing device comprises a rotating adjustment frame (13), a double-cemented lens (14) and a shaping prism (15); the double-cemented lens (14) and the shaping prism (15) are mounted on the rotating adjustment frame (13), and the shaping prism (15) is located in front of the double-cemented lens (14).

6. The optical detection system of a flow fluorescence instrument according to claim 1, characterized in that: The forward scattered light receiving device (11) comprises a forward base (110), wherein an aperture (111), a front collimating lens (112), a rear focusing lens (114), a filter structure (113), and a receiver (115) are installed in the forward base (110), wherein the front collimating lens (112) is located between the aperture (111) and the filter structure (113), and the rear focusing lens (114) is installed between the filter structure (113) and the receiver (115).

7. The optical detection system of a flow fluorescence instrument according to claim 1, characterized in that: The fluorescence receiving device comprises a fourth channel receiving device (4), a third channel receiving device (5), a second channel receiving device (6), a first dichroic mirror structure (8), a second dichroic mirror structure (7) and a focusing lens (10) mounted on a fluorescence light path base (9); a flow chamber (12) is arranged in front of the focusing lens (10).

8. The optical detection system of a flow fluorescence instrument according to claim 1, characterized in that: The exterior of the optical path substrate (1) is covered with an optical path light shielding device (19).

9. The optical detection system of a flow fluorescence instrument according to claim 1, characterized in that: An optical path temperature control device (20) is provided at the bottom of the optical path substrate (1).

10. A flow instrument, characterized in that: The invention comprises an optical detection system, a liquid circuit system, a pre-treatment system and an electrical control system of a flow fluorescence instrument as described in any one of claims 1 to 9, wherein the liquid circuit system is used for providing a sample flow to be tested, a sheath liquid flow and collecting waste liquid of the sample flow after detection, the pre-treatment system is used for the reaction process between the sample and the reagent, and the electrical control system is used for the motion control and information processing of the entire instrument.

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