CN113866966B - Imaging lens of gene sequencer, gene sequencer and gene sequencing system - Google Patents
Imaging lens of gene sequencer, gene sequencer and gene sequencing system Download PDFInfo
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- CN113866966B CN113866966B CN202111182388.8A CN202111182388A CN113866966B CN 113866966 B CN113866966 B CN 113866966B CN 202111182388 A CN202111182388 A CN 202111182388A CN 113866966 B CN113866966 B CN 113866966B
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- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
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- C12Q1/6874—Methods for sequencing involving nucleic acid arrays, e.g. sequencing by hybridisation
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Abstract
The invention discloses an imaging lens of a gene sequencer, which comprises an objective lens, a compensation lens group and a barrel lens positioned on the same optical axis with the objective lens, wherein the compensation lens group can enter or move out of the optical axis; when the compensation lens group enters the optical axis, the compensation lens group is positioned between the objective lens and the cylindrical lens. The invention also discloses a gene sequencer and a gene sequencing system. The invention at least solves the technical problems of how to enable the multi-surface imaging image quality of the biochip to reach the diffraction limit and reduce the focusing times of the objective lens on the basis of realizing clear imaging of the multi-surface of the biochip, and can reduce the focusing times of the objective lens to one time.
Description
Technical Field
The invention relates to the technical field of gene detection. More particularly, the present invention relates to an imaging lens of a gene sequencer, a gene sequencer and a gene sequencing system.
Background
In the genetic testing process, a biochip carrying a sample to be tested is usually tested using a genetic sequencer. The biochip typically comprises a plurality of surfaces each carrying a sample to be tested. If it is desired to clearly image all of the samples to be detected on multiple surfaces, multiple focusing of the imaging system of the gene sequencer is required.
For example, in the case where the aforementioned plurality of surfaces includes the first surface and the second surface, when the biochip is detected, the first surface, the second surface, and the objective lens of the gene sequencer are on the same optical axis. Because of the short depth of field of the objective lens, the second surface may be outside the depth of field when the first surface is within the depth of field of the objective lens.
In this case, if focusing is performed only once, only one of the first surface and the second surface can be imaged clearly, and if the other surface is imaged clearly, the objective lens needs to be refocused. Such refocusing process would take a lot of time and effort for the inspector, thereby reducing the inspection efficiency.
Also, the objective lens is designed under the imaging condition of a certain surface (usually the first surface) of the biochip, so that when the surface (the first surface) of the biochip designed by the objective lens is in the depth of field of the objective lens, the image quality can reach the diffraction limit; however, when the surface of the biochip, i.e., other surface of the biochip, such as the second surface, which is not designed by the objective lens, is within the depth of field of the objective lens, the image quality thereof generally cannot reach the diffraction limit.
Disclosure of Invention
It is an object of the present invention to solve at least the above problems and to provide corresponding advantages.
Another object of the present invention is to provide an imaging lens of a gene sequencer, and a gene sequencing system, which at least solve the technical problems of how to enable the multi-surface imaging image quality of a biochip to reach the diffraction limit, and reduce the focusing times of an objective lens based on realizing clear imaging of the multi-surface of the biochip, and can reduce the focusing times of the objective lens to one time. The invention is realized mainly by the following technical proposal:
< first aspect of the invention >
The first aspect of the present invention provides an imaging lens of a gene sequencer, comprising:
an objective lens, a compensating lens group and a barrel lens which is positioned on the same optical axis with the objective lens, wherein,
the compensating lens group can enter or move out of the optical axis;
when the compensation lens group enters the optical axis, the compensation lens group is positioned between the objective lens and the cylindrical lens.
According to the imaging lens of the gene sequencer, provided by the invention, the aberration generated when the imaging lens of the gene sequencer images the surface of the biochip which is not designed by the objective lens is corrected by adding the compensation lens group between the objective lens and the cylindrical lens, so that the imaging lens of the gene sequencer can reach the diffraction limit on the imaging image of the surface. In addition, when the surface of the biochip designed by the objective lens and the surface of the biochip designed by the non-objective lens can reach the diffraction limit, the magnification of the surface of the biochip designed by the objective lens and the surface of the biochip designed by the non-objective lens can be kept the same, so that the later data processing is convenient.
In addition, the focal length of the imaging lens of the gene sequencer is adjusted by adjusting the relative positions of the compensation lens group, the objective lens and the barrel lens, namely, the positions of the objective lens and the barrel lens are not changed after primary focusing in the imaging process of the imaging lens of the gene sequencer, and at the moment, the compensation lens group deviates (namely, moves out of) the optical axes of the objective lens and the barrel lens, so that a first imaging clear region can be obtained; when the compensation lens group enters between the objective lens and the barrel lens and is positioned on the same optical axis with the objective lens and the barrel lens, the focal length of the imaging lens of the gene sequencer can be changed on the premise of not refocusing the objective lens and the barrel lens, and therefore a second imaging clear area can be obtained. Based on the above, the invention can reduce the focusing times of the objective lens on the basis of realizing clear imaging of multiple surfaces of the biochip.
Also, the compensation lens group only needs to be moved to the same optical axis as the objective lens or moved out of the optical axis, and the movement process is simpler and does not consume much time and effort compared with the focusing process of the objective lens.
In some embodiments, the objective lens is configured to be used to design a biochip, and the non-objective lens is configured to be used to design a biochip.
In some aspects, the compensation lens group includes a first doublet lens having negative optical power and a second doublet lens having positive optical power.
Through the technical scheme, the compensation lens group is simple in structure, and the imaging lens added into the gene sequencing instrument is of a simple design and is convenient to realize.
In some embodiments, the first cemented lens is formed by a plano-convex lens cemented with a first biconcave lens.
In some embodiments, the surface of the plano-convex lens near the objective lens is a plane, and the surface near the cylindrical lens is a convex surface.
In some embodiments, the second biconvex lens is formed by bonding a biconvex lens and a second biconcave lens.
In some embodiments, the focal lengths of the plano-convex lens, the first biconcave lens, the biconvex lens, and the second biconcave lens respectively satisfy the following conditions:
-0.062<f 1 /f 0 <-0.051；
0.036<f 2 /f 0 <0.047；
-0.033<f 3 /f 0 <-0.027；
0.047<f 4 /f 0 <0.061；
wherein f 0 F is the combined focal length of the compensating lens group 1 F is the focal length of the plano-convex lens 2 F is the focal length of the first biconcave lens 3 F is the focal length of the lenticular lens 4 Is the focal length of the second biconcave lens.
In some technical solutions, the length of the compensating lens group from the object side to the image side is 20mm.
< second aspect of the invention >
In a second aspect, the present invention provides a gene sequencer comprising:
the imaging lens of the gene sequencer of the first aspect.
< third aspect of the invention >
In a third aspect, the invention provides a gene sequencing system comprising:
a biochip; and
the gene sequencer according to the second aspect, which is used for detecting a sample to be detected placed on the biochip.
The embodiment of the invention has at least the following beneficial effects:
according to the imaging lens of the gene sequencer, provided by the invention, the aberration generated when the imaging lens of the gene sequencer images the surface of the biochip which is not designed by the objective lens is corrected by adding the compensation lens group between the objective lens and the cylindrical lens, so that the imaging lens of the gene sequencer can reach the diffraction limit on the imaging image of the surface. In addition, when the surface of the biochip designed by the objective lens and the surface of the biochip designed by the non-objective lens can reach the diffraction limit, the magnification of the surface of the biochip designed by the objective lens and the surface of the biochip designed by the non-objective lens can be kept the same, so that the later data processing is convenient.
In addition, the focal length of the imaging lens of the gene sequencer is adjusted by adjusting the relative positions of the compensation lens group, the objective lens and the barrel lens, namely, the positions of the objective lens and the barrel lens are not changed after primary focusing in the imaging process of the imaging lens of the gene sequencer, and at the moment, the compensation lens group deviates (namely, moves out of) the optical axes of the objective lens and the barrel lens, so that a first imaging clear region can be obtained; when the compensation lens group enters between the objective lens and the barrel lens and is positioned on the same optical axis with the objective lens and the barrel lens, the focal length of the imaging lens of the gene sequencer can be changed on the premise of not refocusing the objective lens and the barrel lens, and therefore a second imaging clear area can be obtained. Based on the above, the invention can reduce the focusing times of the objective lens on the basis of realizing clear imaging of multiple surfaces of the biochip.
Also, the compensation lens group only needs to be moved to the same optical axis as the objective lens or moved out of the optical axis, and the movement process is simpler and does not consume much time and effort compared with the focusing process of the objective lens.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present application, the drawings that are needed in the description of the embodiments of the present application will be briefly described below, it being obvious that the drawings in the following description are only some embodiments of the present application, and that other drawings may be obtained according to these drawings without inventive effort for a person skilled in the art.
FIG. 1 is a diagram of a compensation lens set, an objective lens and a barrel lens which are not in the same optical axis;
FIG. 2 is a diagram showing the structure of the compensation lens set, the objective lens and the barrel lens in the same optical axis in the present invention;
FIG. 3 is an enlarged view of the compensation lens assembly of the present invention;
fig. 4 is an enlarged view of a portion a of fig. 1;
fig. 5 is an enlarged view of a portion B of fig. 2;
FIG. 6 is a dot pattern of the imaging lens of the gene sequencer of the present invention for clearly imaging the first surface of the biochip;
FIG. 7 is a dot pattern of the imaging lens of the gene sequencer of the present invention for clearly imaging the second surface of the biochip;
reference numerals illustrate:
1. imaging lens of gene sequencer;
10. an objective lens;
20. a compensation lens group; 21. a first doublet lens; 211. a plano-convex lens; 212. a first biconcave lens; 22. a second double cemented lens; 221. a biconvex lens; 222. a second biconcave lens;
30. a cylindrical mirror;
o, optical axis;
u, the first surface;
l, second surface.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the technical solutions in the embodiments of the present application will be clearly and completely described below with reference to the accompanying drawings in the embodiments of the present application, and it is apparent that the described embodiments are some embodiments of the present application, but not all embodiments. All other embodiments, which can be made by one of ordinary skill in the art based on the embodiments herein without making any inventive effort, are intended to be within the scope of the present application.
The terms "first" and "second" and the like in the description of embodiments of the present application are used for distinguishing between different objects and not for describing a particular sequential order of objects. For example, the first doublet and the second doublet are used to distinguish between different doublets, and are not used to describe a particular order of doublets; for another example, the first surface and the second surface are used to distinguish between different surfaces in a biochip, and are not used to describe a particular order of surfaces in a biochip.
In the embodiments of the present application, words such as "exemplary" or "such as" are used to mean serving as examples, illustrations, or descriptions. Any embodiment or design described herein as "exemplary" or "for example" should not be construed as preferred or advantageous over other embodiments or designs. Rather, the use of words such as "exemplary" or "such as" is intended to present related concepts in a concrete fashion.
It should be noted that, in this document, the terms "comprises," "comprising," or any other variation thereof, are intended to cover a non-exclusive inclusion, such that a process, method, system, article, or apparatus that comprises a list of steps or elements is not necessarily limited to those steps or elements that are expressly listed or inherent to such process, method, article, or apparatus.
In addition to the foregoing, it should be emphasized that the references herein to "an embodiment" are intended to mean that a particular feature, structure, or characteristic described in connection with the embodiment can be included in at least one embodiment of the present application. The appearances of such phrases in various places in the specification are not necessarily all referring to the same embodiment, nor are separate or alternative embodiments mutually exclusive of other embodiments. Those skilled in the art will explicitly and implicitly understand that the embodiments described herein may be combined with other embodiments.
For a better understanding of the technical solutions provided by the present invention, the terms presented herein are correspondingly described:
depth of field: it means that there is a certain length of space in the object side (front and rear of the focal point) of the objective lens, the object in this space, which presents image ambiguity in the image side, is within the limit range of the allowable circle of confusion (the limit range of the allowable circle of confusion, i.e. the acceptable clear range), and the length of this space is the depth of field. In other words, the object is in a clear range which is acceptable in the front-back direction along the depth direction from the object side to the optical axis of the image side.
The surface of the biochip designed by the objective lens: the surface of the biochip can reach diffraction limit without other external equipment while being in the depth of field of the objective lens. In this context, the surface of the biochip of the objective lens design referred to herein may be the first surface.
Non-objective designed biochip surface: refers to the surface of the biochip, which can reach diffraction limit only by means of other external equipment while being in the depth of field of the objective lens. In this context, the surface of the biochip of the non-objective design referred to herein may be the second surface, or other surface of the biochip.
The present invention will be described in detail with reference to the accompanying drawings.
< imaging lens of Gene sequencer >
As shown in fig. 1 and 2, the imaging lens 1 of the gene sequencer provided by the invention is in a structure diagram. In fig. 2, the imaging lens 1 of the gene sequencer includes an objective lens 10, a compensation lens group 20, and a barrel lens 30 located on the same optical axis O as the objective lens 10. Wherein the compensation lens group 20 can enter or move out of the optical axis O. When the compensation lens group 20 enters the optical axis O, the compensation lens group 20 is located between the objective lens 10 and the barrel lens 30.
The objective lens 10 may be an objective lens 10 having NA (numerical aperture) of 0.75 and a magnification of 20 times. Which is used to focus the light exiting from the light-exiting surface of the barrel lens 30 onto the corresponding biochip.
The compensation lens group 20 includes a first cemented doublet 21 having negative optical power and a second cemented doublet 22 having positive optical power, as shown in fig. 3. Wherein, the first double cemented lens 21 may be formed by a plano-convex lens 211 and a first biconcave lens 212; the second double cemented lens 22 may be a cemented double convex lens 221 and a second double concave lens 222. The plano-convex lens 211 may be disposed such that the surface on the side close to the objective lens 10 is planar and the surface on the side close to the cylindrical lens 30 is convex.
The barrel lens 30 may be a Thorlabs infinity corrected barrel lens TTL200.
The implementation process of the imaging lens 1 of the gene sequencer provided by the invention for clearly imaging multiple surfaces can be implemented according to the following examples (see fig. 1 to 7):
in the state that the compensating lens group 20 is deviated (i.e. moves out) from the optical axes O of the objective lens 10 and the barrel lens 30, the positions of the objective lens 10 and the barrel lens 30 are not changed after focusing once, at this time, the imaging lens 1 of the gene sequencer can clearly image the first surface U of the biochip, the imaged point diagram is shown in fig. 6, and in fig. 6, the imaging can reach the diffraction limit. The imaging light path diagram with respect to the first surface U can be seen in fig. 1 and 4.
On the basis of the foregoing, the compensation lens group 20 is moved such that the compensation lens group 20 enters the optical axes O of the objective lens 10 and the barrel lens 30. At this time, the imaging lens 1 of the gene sequencer can clearly image the second surface L of the biochip, the point column diagram of the second surface L imaging is shown in fig. 7, and in fig. 7, the imaging can reach the diffraction limit. The imaging light path diagram with respect to the second surface L can be seen in fig. 2 and 5. It should be appreciated that the positions of the objective lens 10 and the barrel lens 30 are unchanged during the movement of the compensation lens group 20.
Fig. 6 and 7 are exemplary dot-column diagrams of Zemax output using optical design and simulation software.
The parameter designs of the biochip, the objective lens 10 and the barrel lens 30 for clearly imaging the first surface U of the biochip can be as shown in table 1.
TABLE 1
| Numbering device | Radius of curvature/mm | Thickness/mm | Focal length/ |
| 1 | Plane surface | 10 | - |
| 2 | - | 180 | 10 |
| 3 | - | 23.755 | - |
| 4 | - | 152.493 | - |
In table 1, parameter information corresponding to the number 1 is parameter information of the first surface U of the biochip; the parameter information corresponding to the number 2 is the parameter information of the objective lens 10; the parameter information corresponding to the number 3 is the parameter information of the mirror surface of the barrel mirror 30 close to the side of the objective lens 10; the parameter information corresponding to the number 4 is the parameter information of the other mirror surface of the cylindrical mirror 30.
The parameter designs of the biochip and the imaging lens 1 of the gene sequencer for clearly imaging the second surface L of the biochip can be shown in table 2.
TABLE 2
In table 2, the parameter information corresponding to the number 1 is the parameter information of the second surface L of the biochip; the parameter information corresponding to the number 2 is the parameter information of the first surface U of the biochip; the parameter information corresponding to the number 3 is the parameter information of the objective lens 10; the parameter information corresponding to the number 4 is the parameter information of the mirror surface of the first cemented lens close to the objective lens 10; the parameter information corresponding to the number 5 is the parameter information of the bonding surface of the first bonding lens; the parameter information corresponding to the number 6 is the parameter information of the mirror surface of the first cemented lens close to the cylindrical mirror 30; the parameter information corresponding to the number 7 is the parameter information of the mirror surface of the second cemented lens close to the objective lens 10; the parameter information corresponding to the number 8 is the parameter information of the bonding surface of the second bonding lens; the parameter information corresponding to the number 9 is the parameter information of the mirror surface of the second cemented lens close to the side of the cylindrical lens 30; the parameter information corresponding to the number 10 is the parameter information of the mirror surface of the barrel mirror 30 close to the side of the objective lens 10; the parameter information corresponding to the number 11 is the parameter information of the other mirror surface of the cylindrical mirror 30. In addition to the above-listed parameter information, it should be understood by those skilled in the art that, in the optical design sense, the parameter information of each optical element of the imaging lens 1 of the gene sequencer may have other matching schemes, and is not limited to the parameter information shown in table 1 and table 2.
Through the above embodiment, the imaging lens 1 of the gene sequencer provided by the invention corrects the aberration generated when the imaging lens 1 of the gene sequencer images the surface of the biochip which is not designed by the objective lens, by adding the compensation lens group 20 (the compensation lens group 20 is made of optical materials with different refractive indexes) between the objective lens 10 and the barrel lens 30, so that the imaging lens 1 of the gene sequencer can reach the diffraction limit on the imaging image of the surface. In addition, when the surface of the biochip designed by the objective lens and the surface of the biochip designed by the non-objective lens can reach the diffraction limit, the magnification of the surface of the biochip designed by the objective lens and the surface of the biochip designed by the non-objective lens can be kept the same, so that the later data processing is convenient.
In addition, the focal length of the imaging lens 1 of the gene sequencer is adjusted by adjusting the relative positions of the compensation lens group 20, the objective lens 10 and the barrel lens 30, namely, the positions of the objective lens 10 and the barrel lens 30 are not changed after focusing once in the imaging process of the imaging lens 1 of the gene sequencer, and at the moment, the compensation lens group 20 deviates (i.e. moves out of) the optical axes O of the objective lens 10 and the barrel lens 30, so that a first imaging clear region can be obtained; when the compensation lens group 20 enters between the objective lens 10 and the barrel lens 30 and is located on the same optical axis O as the objective lens 10 and the barrel lens 30, the focal length of the imaging lens 1 of the gene sequencer can be changed without refocusing the objective lens 10 and the barrel lens 30, and thus, a second clear imaging region can be obtained. Based on this, the present invention can reduce the number of focusing times of the objective lens 10 on the basis of realizing clear imaging of multiple surfaces of the biochip.
Also, the compensation lens group 20 only needs to be moved to the same optical axis O as the objective lens 10 or moved out of the optical axis O, and this movement process is a relatively simple process without taking much time and effort compared to the focusing process of the objective lens 10.
It should be further noted that the biochip according to the present invention may further comprise a third surface and a fourth surface. The specific number of biochip surfaces can be determined by one skilled in the art.
In some embodiments, focal lengths of the plano-convex lens 211, the first biconcave lens 212, the biconvex lens 221, and the second biconcave lens 222 respectively satisfy the following conditions:
-0.062<f 1 /f 0 <-0.051；
0.036<f 2 /f 0 <0.047；
-0.033<f 3 /f 0 <-0.027；
0.047<f 4 /f 0 <0.061；
wherein f 0 For the combined focal length of the compensation lens group 20, f1 is the focal length of the plano-convex lens 211, f2 is the focal length of the first biconcave lens 212, f3 is the focal length of the biconvex lens 221, and f4 is the focal length of the second biconcave lens 222.
In some embodiments, the length of the compensation lens group 20 from the object side to the image side is 20mm. The purpose of this design is to: the volume of the compensation lens group 20 is reduced so that the compensation lens group 20 can be easily moved into or out of the imaging lens 1 of the gene sequencer.
< Gene sequencer >
In a second aspect, the present invention provides a gene sequencer comprising:
the imaging lens of the gene sequencer of the first aspect.
< Gene sequencing System >
In a third aspect, the invention provides a gene sequencing system comprising:
a biochip; and
the gene sequencer according to the second aspect, which is used for detecting a sample to be detected placed on the biochip.
Although embodiments of the present invention have been disclosed above, it is not limited to the details and embodiments shown and described, it is well suited to various fields of use for which the invention would be readily apparent to those skilled in the art, and accordingly, the invention is not limited to the specific details and illustrations shown and described herein, without departing from the general concepts defined in the claims and their equivalents.
Claims (3)
1. Imaging lens of gene sequencing appearance, its characterized in that includes:
an objective lens, a compensating lens group and a barrel lens which is positioned on the same optical axis with the objective lens, wherein,
the compensating lens group can enter or move out of the optical axis;
when the compensation lens group enters the optical axis, the compensation lens group is positioned between the objective lens and the cylindrical lens;
the objective lens is an objective lens with NA of 0.75 and magnification of 20 times, and is used for focusing the light rays emitted from the light emitting surface of the cylindrical lens onto the corresponding biochip;
the compensating lens group comprises a first double-cemented lens with negative focal power and a second double-cemented lens with positive focal power;
the first double-cemented lens is formed by a plano-convex lens and a first biconcave lens;
the second double-cemented lens is formed by a biconvex lens and a second biconcave lens;
the plane convex lens is arranged in such a way that the surface close to one side of the objective lens is a plane, and the surface close to one side of the cylindrical lens is a convex surface;
the focal lengths of the plano-convex lens, the first biconcave lens, the biconvex lens, and the second biconcave lens respectively satisfy the following conditions:
-0.062<f 1 /f 0 <-0.051；
0.036<f 2 /f 0 <0.047；
-0.033<f 3 /f 0 <-0.027；
0.047<f 4 /f 0 <0.061；
wherein f 0 F is the combined focal length of the compensating lens group 1 F is the focal length of the plano-convex lens 2 F is the focal length of the first biconcave lens 3 F is the focal length of the lenticular lens 4 A focal length of the second biconcave lens;
the length of the compensating lens group from the object side to the image side is 20mm.
2. A gene sequencer, comprising:
the imaging lens of the gene sequencer of claim 1.
3. A gene sequencing system, comprising:
a biochip; and
the gene sequencer according to claim 2, which is used for detecting a sample to be detected placed on the biochip.
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| CN115452783B (en) * | 2022-08-22 | 2023-12-22 | 深圳赛陆医疗科技有限公司 | Detection device and gene sequencer |
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| CN1181372C (en) * | 2001-04-23 | 2004-12-22 | 清华大学 | Lens of biochip scanning-detecting system |
| CN1607414A (en) * | 2003-10-15 | 2005-04-20 | 中国科学院光电技术研究所 | Double telecentric imaging objective lens for biochip detection |
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