Gene sequencer and uniform lighting device

Abstract

The utility model discloses a gene sequencer and a dodging lighting device, and the dodging lighting device comprises a double-color laser light source which is used for emitting two kinds of lasers with different wave bands; the rectangular optical fiber is used for transmitting two kinds of lasers with different wave bands emitted by the light source and carrying out light spot homogenization; the shaping mechanism is used for shaping the rectangular optical fiber output light beams; and the objective lens is used for irradiating the light beams output by the shaping mechanism to the surface of the chip. The rectangular optical fiber can disorganize the original wavefront distribution of light beams, so that the light beams in different modes in the optical fiber are mixed with one another, and the effect of homogenizing the light beams is achieved; the double-color laser light source can form uniformly distributed rectangular light beams after being transmitted by the rectangular optical fiber, the rectangular light beams can realize rectangular uniform light illumination on the surface of the biochip after passing through the shaping mechanism and the objective lens, and the illumination area can be limited to be 1-1.2 times of an FOV.

Description

Technical Field

[0001] The utility model relates to the field of gene sequencing, and in particular to a gene sequencer and a uniform light illumination device. Background Art

[0002] In the field of gene sequencing, high-precision optical systems are essential for the detection of fluorescent signals generated during the process. Gene sequencers reveal genetic information by determining the sequence of DNA or RNA in an organism, a process that relies on accurate reading of fluorescent signals. Fluorescent dyes emit light signals when irradiated with excitation light of a specific wavelength, and the intensity and uniformity of these signals are directly related to the accuracy of data reading. Since fluorescent molecules undergo photobleaching under continuous high-intensity laser irradiation, that is, the fluorescent signal gradually weakens over time, the size and uniformity of the illumination must be precisely controlled when performing continuous imaging of multiple adjacent fields of view (FOV). If the illumination area is too large, adjacent FOVs may be affected by the excitation light before being directly imaged, thereby reducing the intensity of the fluorescent signal, which will have an adverse effect on the imaging results of subsequent FOVs.

[0003] In high-throughput sequencing (Next Generation Sequencing, NGS) technology, the design and implementation of uniform light illumination devices are particularly critical. Traditional uniform light illumination systems cannot meet the strict requirements of NGS technology for illumination uniformity and size control. Summary of the invention

[0004] The utility model discloses a gene sequencer and a uniform light illumination device to solve the problem of insufficient uniformity of the illumination device in the prior art.

[0005] In order to solve the above technical problems, the utility model adopts the following technical solutions:

[0006] A light homogenizing illumination device comprises a two-color laser light source for emitting lasers of two different wavelength bands; a rectangular optical fiber for transmitting the lasers of two different wavelength bands emitted by the light source and performing light spot homogenization; a shaping mechanism for shaping the output light beam of the rectangular optical fiber; and an objective lens for irradiating the light beam output by the shaping mechanism onto the surface of a chip.

[0007] Furthermore, the shaping mechanism includes an aspheric lens, a first convex cylindrical mirror, a second convex cylindrical mirror and a filter which are sequentially arranged along the laser light path.

[0008] Furthermore, the aspheric lens is an achromatic lens, and the distance between the aspheric lens and the emitting end face of the rectangular optical fiber is equal to the focal length of the aspheric lens.

[0009] Furthermore, the convex surface of the first convex cylindrical mirror is located on the side facing the aspheric lens; and the convex surface of the second convex cylindrical mirror is located on the side away from the first convex cylindrical mirror.

[0010] Furthermore, the distance between the second convex cylindrical mirror and the first convex cylindrical mirror is equal to the sum of the focal length of the first convex cylindrical mirror and the focal length of the second convex cylindrical mirror.

[0011] Furthermore, the focal length of the second convex cylindrical mirror is smaller than the focal length of the first cylindrical mirror.

[0012] Furthermore, the size of the rectangular spot generated by the objective lens on the chip surface is between 1 and 1.2 times that of a single FOV.

[0013] A gene sequencer comprises the above-mentioned uniform light illumination device.

[0014] The utility model adopts the above technical solution and has the following advantages:

[0015] The rectangular optical fiber of the utility model has the function of disrupting the original wavefront distribution of the light beam, so that light beams of different modes in the optical fiber are mixed with each other, thereby achieving the effect of homogenizing the light beam; the two-color laser light source will form a uniformly distributed rectangular light beam after being transmitted through the rectangular optical fiber, and the rectangular light beam can then pass through a shaping mechanism and an objective lens to achieve rectangular uniform light illumination on the surface of the biochip, and the size of the illumination area can be limited to between 1 and 1.2 times of an FOV. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Figure 1 is a cross-sectional view of the uniform light illumination device on the XZ axis plane;

[0017] Figure 2 is a cross-sectional view of the uniform light illumination device on the YZ axis plane;

[0018] Figure 3 The homogenized spot of a two-color laser light source passing through a rectangular optical fiber.

[0019] Figure numerals: 1 - rectangular optical fiber; 2 - objective lens; 3 - aspherical lens; 4 - first convex cylindrical mirror; 5 - second convex cylindrical mirror; 6 - filter. DETAILED DESCRIPTION

[0020] The technical solutions in the embodiments of the present application are described clearly and completely below. Obviously, the described embodiments are only part of the embodiments of the present application, not all of the embodiments. Based on the embodiments in the present utility model, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present utility model.

[0021] like Figure 1 , Figure 2As shown, a uniform light illumination device is used for a gene sequencer, including a two-color laser light source (not shown) for emitting lasers of two different wavelengths; a rectangular optical fiber 1 for transmitting the lasers of two different wavelengths emitted by the light source and performing light spot uniformity; a shaping mechanism for shaping the output light beam of the rectangular optical fiber 1; and an objective lens 2 for irradiating the light beam output by the shaping mechanism onto the chip surface.

[0022] The rectangular optical fiber 1 of the utility model has the function of disrupting the original wavefront distribution of the light beam, so that light beams of different modes in the optical fiber are mixed with each other, thereby achieving the effect of homogenizing the light beam; the two-color laser light source will form a uniformly distributed rectangular light beam after being transmitted through the rectangular optical fiber 1, and the rectangular light beam can then pass through the shaping mechanism and the objective lens 2 to achieve rectangular uniform light illumination on the surface of the biochip, and the size of the illumination area can be limited to between 1 and 1.2 times of a FOV.

[0023] The rectangular optical fiber 1 of the utility model is used to transmit a two-color laser beam emitted by a light source and limit the cross section of the two-color laser beam to a predetermined shape. The two-color laser beam includes light of two different wavelength bands. The rectangular optical fiber 1 of the utility model also plays a role in homogenizing the light spot.

[0024] Furthermore, the shaping mechanism includes an aspheric lens 3, a first convex cylindrical mirror 4, a second convex cylindrical mirror 5 and a filter 6 which are sequentially arranged along the laser light path.

[0025] The utility model utilizes the characteristic of a cylindrical mirror that it converges or diverges a light beam only in a single axis, and uses two convex cylindrical mirrors to form a beam shaping module. The shaping mechanism of the utility model has a simple structure, is easy to implement, and can help the optical system correct aberrations and improve lighting quality.

[0026] like Figure 1 , Figure 2 As shown, it can be understood that the aspheric lens 3 of the utility model selects an achromatic lens, which is located on the optical path of the first light emitted by the optical fiber, and the distance from the optical fiber emission end face is equal to the focal length f1 of the aspheric lens 3; the two-color laser is collimated into parallel light after passing through the aspheric lens 3 to form a second light. The first convex cylindrical mirror 4 is located on the side of the aspheric lens 3 away from the optical fiber, and the convex surface is located on the side facing the aspheric lens 3, and coincides with the optical axis of the aspheric lens 3, and its focal length is f2; the second light passes through the first convex cylindrical mirror 4 to form a third light, and the third light converges in the XZ axis plane, and still propagates in a parallel direction in the YZ axis plane. The second convex cylindrical mirror 5 is located on the side of the first convex cylindrical mirror 4 away from the aspheric lens 3, with the convex surface located on the side away from the first convex cylindrical mirror 4, coincides with the optical axis of the first convex cylindrical mirror 4 and the distance between the second convex cylindrical mirror 5 and the first convex cylindrical mirror 4 is equal to the sum of the focal length f2 of the first convex cylindrical mirror 4 and the focal length f3 of the second convex cylindrical mirror 5; the third light ray forms the fourth light ray after passing through the second convex cylindrical mirror 5, and the fourth light ray propagates parallel in the XZ axis plane and also propagates parallel in the YZ axis plane.

[0027] Furthermore, the focal length of the second convex cylindrical mirror 5 is smaller than that of the first cylindrical mirror 4, which plays a role in expanding and collimating the light beam in the X direction, so as to achieve the purpose of reducing the spot size in the X direction. The filter 6 is located on the side of the second convex cylindrical mirror 5 away from the first convex cylindrical mirror 4. The fourth light forms the fifth light after passing through the filter 6. The filter 6 does not change the direction of light propagation, and plays a role in purifying the laser spectrum range; the fifth light is focused into a rectangular spot on the chip surface after passing through the objective lens 2. The chip is located at the focal position of the objective lens 2, and the spot size on the chip surface is between 1 and 1.2 times of a FOV.

[0028] The utility model adopts an achromatic aspheric lens 3 to converge the laser beam emitted from the optical fiber, so that the emitted laser beam is collimated light or approximately collimated light. The achromatic aspheric lens 3 adopted by the utility model can calibrate the difference in the size of the irradiated area caused by the chromatic aberration of the lasers of two wavelengths; the first convex cylindrical mirror 4 and the second cylindrical mirror 5 in the beam shaping module of the utility model are used to shrink and shape the light beam in the X direction, and do not produce the effect of converging or diverging the light beam in the Y direction.

[0029] Taking a camera with a Sony IMX253 sensor selected in a gene sequencer image acquisition device as an example, the utility model uniform light illumination device is described. The size of its sensor is 14.13mm×10.35mm. The magnification of the optical system is 10×, and the FOV size of the camera target surface corresponding to the chip surface is 1.13mm×0.828mm. According to the requirements for the uniform light illumination system, the illumination size range of the laser irradiating the chip surface needs to meet the following requirements: 1.13mm~1.256mm in the long direction of the rectangle, and 0.828mm~0.92mm in the wide direction of the rectangle.

[0030] The focal length f1 of the aspheric lens 3 is 3.1 mm, the focal length f4 of the objective lens 2 is 10 mm, the wavelength range of the dual-color laser light source is 525±5 nm, 658±5 nm; the numerical aperture (NA) of the rectangular optical fiber 1 is 0.22, and the core size is 0.385 mm×0.385 mm; after the laser light source is homogenized by the rectangular optical fiber 1, a homogenized light spot with a size almost the same as the end face of the rectangular optical fiber 1 is generated at the exit port of the rectangular optical fiber 1, as shown in FIG. Figure 3 shown.

[0031] Since the first convex cylindrical mirror 4 and the second convex cylindrical mirror 5 do not change the propagation direction of the light beam in the YZ plane, the light beam in the YZ plane is still a parallel light beam after passing through the first convex cylindrical mirror 4 and the second convex cylindrical mirror 5. According to the imaging principle, it can be calculated that the spot size of the YZ plane light beam on the chip surface after being focused by the objective lens 2 is 1.24 mm, which meets the requirements of the size in the long direction of the rectangle.

[0032] Since the first convex cylindrical mirror 4 and the second convex cylindrical mirror 5 play the role of expanding and collimating the light beam in the XZ plane, after the rectangular light spot at the exit port of the rectangular optical fiber 1 passes through the shaping mechanism and the objective lens 2, the size range of the light spot enlarged in the XZ plane needs to meet the length range of the rectangular width direction, that is, the magnification M needs to meet 2.15≤M≤2.38. The magnification M of the XZ plane light beam is related to the focal length ratio, and the magnification M=(f4 / f1)×(f2 / f3). It can be confirmed that the ratio of the focal lengths of the first convex cylindrical mirror 4 and the second convex cylindrical mirror 5 needs to meet 0.67≤f2 / f3≤0.74. According to the focal length requirements of the first convex cylindrical mirror 4 and the second convex cylindrical mirror 5, the focal length f2=7.7mm of the first convex cylindrical mirror 4 and the focal length f3=5.8mm of the second convex cylindrical mirror 5 are selected.

[0033] The light beam emitted by the laser light source is focused on the chip surface into a uniformly illuminated rectangular spot after passing through the shaping mechanism and the objective lens 2, and the spot size just exceeds the size of the FOV but is not greater than 1.2 times.

[0034] The utility model also discloses a gene sequencer, comprising the above-mentioned uniform light illumination device.

[0035] The utility model uniform light illumination device can generate a rectangular uniform light area on the sample surface that is proportional to the sensor, and can ensure that the size of the illumination area is strictly controlled between 1 and 1.2 times of a single FOV, which not only meets the lighting needs, but also avoids adverse effects on adjacent FOVs. The utility model uniform light illumination device can significantly improve the quality of gene sequencing and reduce data reading errors caused by uneven illumination, thereby promoting the development of precision medicine and biological research. The utility model can correct the chromatic aberration of lasers of two different wavelengths and avoid or reduce the difference in the illumination size of lasers of two wavelengths; the utility model has a simple structure, simplifies the complexity of the imaging system, and helps to reduce manufacturing costs and maintenance difficulties.

[0036] The above are merely embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention are included in the scope of the claims of the present invention to be approved.

Claims

1. A uniform light illumination device, characterized in that: It includes a two-color laser light source for emitting lasers of two different wavelengths; a rectangular optical fiber for transmitting the lasers of two different wavelengths emitted by the light source and performing light spot homogenization; a shaping mechanism for shaping the output light beam of the rectangular optical fiber; and an objective lens for irradiating the light beam output by the shaping mechanism onto the chip surface.

2. A uniform light illumination device according to claim 1, characterized in that: The shaping mechanism comprises an aspheric lens, a first convex cylindrical mirror, a second convex cylindrical mirror and a filter which are sequentially arranged along the laser light path.

3. A uniform light illumination device according to claim 2, characterized in that: The aspheric lens is an achromatic lens, and the distance between the aspheric lens and the emitting end face of the rectangular optical fiber is equal to the focal length of the aspheric lens.

4. A uniform light illumination device according to claim 2, characterized in that: The convex surface of the first convex cylindrical mirror is located on the side facing the aspheric lens; the convex surface of the second convex cylindrical mirror is located on the side away from the first convex cylindrical mirror.

5. The uniform light illumination device according to claim 2, characterized in that: The distance between the second convex cylindrical mirror and the first convex cylindrical mirror is equal to the sum of the focal length of the first convex cylindrical mirror and the focal length of the second convex cylindrical mirror.

6. The uniform light illumination device according to claim 2, characterized in that: The focal length of the second convex cylindrical mirror is smaller than the focal length of the first cylindrical mirror.

7. The uniform light illumination device according to claim 1, characterized in that: The size of the rectangular light spot generated by the objective lens on the chip surface is between 1 and 1.2 times of a single FOV.

8. A gene sequencer, characterized in that: The uniform light illumination device comprises the uniform light illumination device as described in any one of claims 1 to 7.

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