Gene sequencer and lighting device

Abstract

The utility model discloses a gene sequencer and a lighting device. The lighting device comprises a first light source, a second light source and a third light source, the beam combining device is used for combining the light beams generated by the first light source, the second light source and the third light source and then emitting the light beams on the same light path; the first light source and the second light source are red light sources; the third light source is a green light source. According to the utility model, the light beams of the two red light sources are combined through a spatial beam combination method, so that the light power of the red light sources is simply and effectively improved, and the cost is low; and the light beams of the red and green light sources are combined through a wavelength beam combining method, so that the working bandwidth of the light sources is increased.

Description

Technical Field

[0001] The utility model relates to the field of gene sequencing, and particularly to a gene sequencer and an illumination device. Background Art

[0002] Gene sequencing is a key technology in biological research and medical diagnosis, which involves determining the nucleotide sequence in the DNA or RNA of an organism. With the development of personalized and precision medicine, the demand for high-throughput, high-precision and cost-effective gene sequencing technologies is increasing continuously. A gene sequencer is a key device to achieve these goals, and its performance depends to a large extent on the quality and accuracy of the optical system.

[0003] In the process of gene sequencing technology of Next Generation Sequencing (NGS), nucleotides are labeled with specific fluorescent dyes when they are synthesized. Each fluorescently labeled nucleotide (A, T, C, G) has its unique fluorescent color, that is, they can emit light of a specific wavelength. During the sequencing process, when these labeled nucleotides are added to the growing DNA strand one by one, the excitation light is used to excite the corresponding fluorescent dyes. The energy of the excitation light is absorbed by the fluorescent molecules, making them enter the excited state. When these excited-state molecules return to the ground state, they emit light of a specific wavelength, and this process is called fluorescence emission. The process of illuminating the fluorescent dyes by the excitation light source to generate fluorescent signals and collecting the emitted fluorescent signals is the basic signal collection process for completing gene sequencing.

[0004] Due to the requirements of gene sequencing for the optical system, the illumination device must be able to provide multi-bandwidth, uniform, stable and precisely controlled illumination to ensure high-quality imaging and sequencing accuracy; however, the existing illumination device has a complex structure and high cost, and cannot meet the bandwidth requirements. Summary of the Invention

[0005] The utility model discloses a gene sequencer and an illumination device to solve the problems of complex structure and high cost in the prior art.

[0006] To solve the above technical problems, the utility model adopts the following technical solutions:

[0007] An illumination device, comprising:

[0008] A first light source, a second light source and a third light source;

[0009] A beam combining device for combining the beams generated by the first light source, the second light source and the third light source and emitting them in a common optical path;

[0010] The first light source and the second light source are red light sources; the third light source is a green light source.

[0011] Furthermore, the beam combining device includes:

[0012] A collimating aspheric lens, a first reflector, a filter, a beam splitter, a dichroic mirror, and a focusing aspheric lens arranged in sequence along the optical path of the first light source;

[0013] A collimating aspheric lens and a second reflector arranged in sequence along the optical path of the second light source;

[0014] A collimating aspheric lens, a filter, a beam splitter, and a third reflector arranged in sequence along the optical path of the third light source;

[0015] The beam of the second light source is reflected by the second reflector to the first reflector, and is combined to the optical path of the first light source through the first reflector;

[0016] The beam of the third light source is reflected by the third reflector to the dichroic mirror, and is combined to the optical path of the first light source by the dichroic mirror.

[0017] Furthermore, the size of the first reflector is half of that of the second reflector, which is used to realize the spatial beam combining of the beams emitted by the first light source and the second light source.

[0018] Furthermore, the first reflector, the second reflector, and the third reflector are all inclined at an angle of 45° to the beam propagation direction.

[0019] Furthermore, the dichroic mirror is inclined at an angle of 45° to the propagation direction of the beam of the third light source.

[0020] Furthermore, the beam splitter is inclined at an angle of 45° to the beam propagation direction.

[0021] Furthermore, it further includes an optical power detector, which is located on the optical path of the beam reflected by the beam splitter and is used to monitor the light source power in real time.

[0022] Furthermore, it further includes a rectangular optical fiber, and the incident end of the rectangular optical fiber is located at the focal position of the focusing aspheric lens.

[0023] Furthermore, the first light source and the second light source are both red laser diodes; the third light source is a green laser diode.

[0024] A gene sequencer includes the illumination device described above.

[0025] The present utility model adopts the above technical solutions and has the following advantages:

[0026] The present utility model combines the beams of two red light sources through a spatial beam combining method, simply and effectively improves the optical power of the red light source, and has low cost; then combines the beams of the red and green light sources through a wavelength beam combining method to increase the working bandwidth of the light source. Description of the Drawings

[0027] Figure 1 Schematic diagram of the lighting device of the present utility model;

[0028] Figure 2 Cross-sectional view of the lighting device of the present utility model;

[0029] Figure 3 Transmission spectrum of the dichroic mirror of the present utility model;

[0030] Figure 4 Schematic diagram of spatial beam combining of the present utility model, where d is the diameter of a single beam, L is the diameter of the combined beam, and HR is a mirror;

[0031] Figure 5 Beam spot after spatial beam combining of the present utility model;

[0032] Figure 6 Schematic diagram of wavelength beam combining of the present utility model;

[0033] Figure 7 Spot shapes of red and green laser beams at the incident and exit ends of a rectangular optical fiber, where (a) is the spot shape of the red laser at the incident end of the optical fiber; (b) is the spot shape of the red laser at the exit end of the optical fiber; (c) is the spot shape of the green laser at the incident end of the optical fiber; (d) is the spot shape of the green laser at the exit end of the optical fiber.

[0034] Reference numerals: 1 - first light source; 2 - second light source; 3 - third light source; 4 - collimating aspherical lens; 5 - first mirror; 6 - filter; 7 - beam splitter; 8 - dichroic mirror; 9 - focusing aspherical lens; 10 - second mirror; 11 - third mirror; 12 - optical power detector; 13 - rectangular optical fiber. Detailed Embodiment

[0035] The technical solutions in the embodiments of the present application will be clearly and completely described below. Obviously, the described embodiments are only a part of the embodiments of the present application, rather than all of the embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present utility model without creative efforts shall fall within the protection scope of the present utility model.

[0036] As Figure 1 、 Figure 2 shown, a lighting device includes a first light source 1, a second light source 2, and a third light source 3; a beam combining device for combining the beams generated by the first light source 1, the second light source 2, and the third light source 3 and emitting them in a common optical path; the first light source 1 and the second light source 2 are red light sources; the third light source 3 is a green light source.

[0037] The utility model combines the beams of two red light sources through a spatial beam combination method, which simply and effectively improves the optical power of the red light source and has a low cost; then combines the beams of the red and green light sources through a wavelength beam combination method to increase the working bandwidth of the light source.

[0038] The beam combination device includes a collimating aspheric lens 4, a first reflector 5, a filter 6, a beam splitter 7, a dichroic mirror 8 and a focusing aspheric lens 9 arranged in sequence along the optical path of the first light source; a collimating aspheric lens 4 and a second reflector 10 arranged in sequence along the optical path of the second light source; a collimating aspheric lens 4, a filter 6, a beam splitter 7 and a third reflector 11 arranged in sequence along the optical path of the third light source; the beam of the second light source 2 is reflected by the second reflector 10 to the first reflector 5 and combined to the optical path of the first light source through the first reflector 5; the beam of the third light source 3 is reflected by the third reflector 11 to the dichroic mirror 8 and combined to the optical path of the first light source by the dichroic mirror 8.

[0039] Through precise optical path design, the utility model ensures that the combined red and green light can be coupled into the optical fiber to the greatest extent, and then the optical fiber transmits the beam into the optical mechanical system to meet the requirements of the gene sequencer for the illumination system.

[0040] Further, both the first light source 1 and the second light source 2 are red laser diodes of the same model; the third light source 3 is a green laser diode; wherein, the central wavelength of the laser beam generated by the green laser diode is 658 nm; the central wavelength of the laser beam generated by the red laser diode is 525 nm.

[0041] The utility model uses a green laser diode with a central wavelength of 658 nm to generate a laser beam; this green laser beam first passes through a collimating aspheric lens 4 and is shaped into a parallel beam, and then the beam passes through a green laser filter to refine its wavelength band.

[0042] Further, the distance between the collimating aspheric lens 4 and the light source is equal to the focal length f1 of the collimating aspheric lens 4, and the light source beam is collimated into a parallel beam after passing through the aspheric lens; the reflectors are all located on the optical path after the light source beam is collimated by the aspheric lens and are inclined at an angle of 45° to the beam propagation direction to play a role in turning the optical path; wherein, the size of the first reflector 5 is half of that of the second reflector 10, which is used to realize the spatial beam combination of the beams emitted by the first light source 1 and the second light source 2.

[0043] Further, the utility model also includes an optical power detector 12, which is located on the optical path of the laser beam reflected by the beam splitter 7 and is used to monitor the laser power in real time.

[0044] In the present utility model, the beam splitter 7 is located on the optical path of the parallel beam behind the filter 6 and is inclined at an angle of 45° to the beam propagation direction; most of the beam (high energy) will transmit through the beam splitter 7 and then be coupled into the optical fiber; a small part of the beam (low energy) will be reflected and thus enter the optical power detector 12 for real-time monitoring of the laser power.

[0045] Furthermore, the dichroic mirror 8 is located at the overlapping position of the red parallel beam and the green parallel beam after spatial beam combining and is inclined at an angle of 45° to the propagation direction of the green parallel beam, playing the role of wavelength beam combining.

[0046] In the present utility model, the focusing aspherical lens 9 is located on the optical path of the dual-color parallel laser beam after wavelength beam combining. The beam is focused into an extremely small spot after passing through the focusing aspherical lens 9 and thus coupled into the rectangular optical fiber 13; the incident end face of the rectangular optical fiber 13 in the present utility model is located near the focal point of the focusing aspherical lens 9 for receiving the laser and coupling the laser into the optomechanical system.

[0047] In the present utility model, the green light source beam is split by a beam splitter 7 with a splitting ratio of 1:99 into two paths. Among them, 1% of the green light source beam is reflected to the optical power detector 12 to monitor the power output of the green laser; the remaining 99% continues to transmit through the beam splitter 7, propagates along the original path, and then passes through the third mirror 11 inclined at 45°, causing its propagation direction to turn by 90°. Then it passes through a dichroic mirror 8 inclined at 45°. This dichroic mirror 8 is specially designed to reflect the green beam in the 658 nm band and transmit the red beam in the 525 nm band at the same time; the reflected green laser has the same beam path as the red laser beam.

[0048] The two beams of the second light source 2 of the present utility model pass through the first mirror 5 whose size is half of that of the second mirror 10. The first mirror 5 precisely covers only the path of the second light source beam without interfering with the first light source beam, enabling the two red laser beams to be spatially combined into a single beam, whose size meets the requirements of fiber coupling. The combined red laser then passes through a red laser filter to further purify the working wavelength band. Subsequently, similar to the green laser, the red laser beam also passes through a beam splitter 7 with a splitting ratio of 1:99, where 1% of the beam is used for power monitoring, and 99% of the beam continues to propagate. Finally, it passes through a dichroic mirror 8 and continues to move forward in the original direction without being affected. The red and green laser beams are finally combined into a dual-color laser with a wider working wavelength band. Ultimately, this dual-color laser passes through a focusing aspheric lens 9 and is precisely coupled into a rectangular optical fiber 13. The role of the rectangular optical fiber 13 is to disrupt the original laser mode distribution to achieve the homogenization of the laser spot. The homogenized laser beam is coupled into the optical system of the gene sequencer through the fiber port, providing it with illumination conditions with stable power, appropriate size, wavelength matching, and uniform distribution.

[0049] The transmission spectrum of the dichroic mirror 8 of the present utility model is as Figure 3 shown. The present utility model uses a spatial beam combination method to combine the lasers emitted by two red laser diodes to increase the red laser power. The specific implementation principle is as Figure 4 , 5 shown. Two parallel red light beams are spatially combined into a single parallel red light beam with the same propagation direction through a first mirror whose size is only half of that of other mirrors, and the spot size after the combination of the two beams can meet the fiber coupling conditions. The present utility model uses a wavelength beam combination method to combine the two-color laser beams to increase the working bandwidth of the laser beam. The specific implementation principle is as Figure 6 shown.

[0050] In order to ensure a relatively high level of efficiency when the laser beam is coupled into the optical fiber, the spot after the beam is focused needs to meet the following conditions:

[0051] (1) The divergence angle of the coupled beam needs to meet the total reflection condition, that is, the parameter of the fiber core diameter must be greater than the maximum diameter of the spot after coupling;

[0052] (2) The size of the spot after coupling needs to be smaller than the size of the fiber core diameter;

[0053] (3) The beam parameter product BPP of the spot after coupling needs to be smaller than the beam parameter product of the optical fiber. The expression of the specific constraint conditions is as follows:

[0054] ;

[0055] ;

[0056] 。

[0057] Among them, is the far-field divergence angle of the laser, is the maximum acceptable incident angle of the fiber core diameter, is the incident beam diameter, is the fiber core diameter size, is the beam parameter product of the laser, and NA is the numerical aperture of the fiber.

[0058] Such as Figure 7 shows the spot shapes of red and green laser beams at the incident end and the output end of the rectangular fiber. Among them, (a) is the spot shape of the red laser at the incident end of the fiber; (b) is the spot shape of the red laser at the output end of the fiber; (c) is the spot shape of the green laser at the incident end of the fiber; (d) is the spot shape of the green laser at the output end of the fiber.

[0059] The present utility model also discloses a gene sequencer, which includes the illumination device described above.

[0060] The present utility model uses light sources of two different wavelength bands to meet the fluorescence excitation requirements of using two-color or four-color fluorescent dyes in the gene sequencer; the present utility model combines wavelength beam combining and spatial beam combining to combine the beams emitted by three laser diodes, including two red laser diodes and one green laser diode. After beam combining, the working bandwidth and working power of the laser both increase, meeting the requirements of the gene sequencer for the illumination light source; the present utility model uses a rectangular fiber to collect the beams emitted by the laser diodes and propagates the beams into the opto-mechanical system of the gene sequencer through the fiber. The rectangular fiber has the function of homogenizing the beam; the present utility model can detect the laser power in real time, ensuring that the excitation light source always excites the fluorescent dye at an appropriate power, avoiding phenomena such as low laser power resulting in low fluorescence excitation efficiency and high laser power resulting in bleaching of the fluorescent dye.

[0061] The above are only the embodiments of the present utility model and are not used to limit the present utility model. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principle of the present utility model are included in the scope of the claims of the present utility model pending approval.

Claims

1. A lighting device, characterized in that: include: a first light source, a second light source, and a third light source; A beam combining device, used for combining the light beams generated by the first light source, the second light source and the third light source and emitting them along a common light path; The first light source and the second light source are red light sources; the third light source is a green light source.

2. A lighting device according to claim 1, characterized in that: The beam combining device comprises: A collimating aspheric lens, a first reflector, a filter, a beam splitter, a dichroic mirror and a focusing aspheric lens are sequentially arranged along the optical path of the first light source; A collimating aspheric lens and a second reflecting mirror are sequentially arranged along the optical path of the second light source; A collimating aspheric lens, a filter, a beam splitter and a third reflector are sequentially arranged along the optical path of the third light source; The light beam of the second light source is reflected by the second reflector to the first reflector, and combined by the first reflector to the light path of the first light source; The light beam of the third light source is reflected by the third reflector to the dichroic mirror, and is combined by the dichroic mirror to the light path of the first light source.

3. A lighting device according to claim 2, characterized in that: The size of the first reflector is half of that of the second reflector, and is used to achieve spatial beam combining of the light beams emitted by the first light source and the second light source.

4. The lighting device according to claim 2, characterized in that: The first reflector, the second reflector and the third reflector are all inclined at an angle of 45° to the light beam propagation direction.

5. The lighting device according to claim 2, characterized in that: The dichroic mirror is inclined at an angle of 45° to the propagation direction of the light beam from the third light source.

6. The lighting device according to claim 2, characterized in that: The beam splitter is inclined at an angle of 45° to the propagation direction of the light beam.

7. The lighting device according to claim 2, characterized in that: It also includes an optical power detector, which is located on the optical path of the light beam reflected by the beam splitter and is used for real-time monitoring of the light source power.

8. The lighting device according to claim 2, characterized in that: It also includes a rectangular optical fiber, the incident end of which is located at the focal position of the focusing aspheric lens.

9. The lighting device according to claim 1, characterized in that: The first light source and the second light source are both red laser diodes; the third light source is a green laser diode.

10. A gene sequencer, characterized in that: A lighting device comprising any one of claims 1 to 9.

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