CN111277744B - Focusing method and system, gene sequencer and computer readable storage medium - Google Patents
Focusing method and system, gene sequencer and computer readable storage medium Download PDFInfo
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Abstract
A focusing method is applied to a gene sequencer, the gene sequencer comprises an objective lens, a camera, a chip base, an XY platform and a Z-axis platform which are electrically connected with each other, and the method comprises the following steps: a focusing step of controlling the objective lens to automatically focus based on the currently set Z-axis coordinate value; when the objective lens is successfully focused, controlling the camera to take a picture to obtain graphic data corresponding to an FOV (field of view) which is positioned right below the objective lens on the biochip fixed on the chip base; when the total number of the photographed FOVs on the biochip is smaller than the total number of the FOVs included in the biochip, controlling the XY platform to drive the chip base to move the next FOV of the biochip to be right below the objective lens; and controlling the Z-axis platform to adjust the Z-axis coordinate value of the objective lens and triggering the focusing step. The invention also provides a focusing system, a gene sequencer and a computer readable storage medium. The invention solves the problem that the gene sequencer can not successfully focus when encountering interference.
Description
Technical Field
The invention relates to the field of gene sequencing, in particular to a focusing method and system, a gene sequencer and a computer readable storage medium.
Background
This section is intended to provide a background or context to the implementation of the embodiments of the invention that is recited in the claims and the detailed description. The description herein is not admitted to be prior art by inclusion in this section.
The gene sequencer mainly uses photographing to obtain base signals which are colored by fluorescent substances in pictures to distinguish bases. The quality of the picture is ensured, and the data quantity and the data quality can be effectively improved.
However, when the gene sequencer encounters special conditions such as chip bubbles, impurities, external vibration interference and the like during the focusing process, the problem that the focusing cannot be successful is caused.
Disclosure of Invention
In view of the above, it is necessary to provide a focusing method and system, a gene sequencer, and a computer readable storage medium for solving the technical problem that the gene sequencer cannot successfully focus due to interference, such as chip bubbles, impurities, and external vibration interference, during the focusing process.
The first aspect of the present invention provides a focusing method applied to a gene sequencer, wherein the gene sequencer comprises an objective lens, a camera, a chip base for fixing a biochip, an XY platform and a Z-axis platform which are electrically connected with each other, and the method comprises:
a focusing step of controlling the objective lens to automatically focus based on a currently set Z-axis coordinate value;
a photographing step, when the objective lens is successfully focused, controlling the camera to photograph to obtain graphic data corresponding to an FOV (field of view) which is positioned right below the objective lens on the biochip fixed on the chip base;
a counting step of counting the total number N of the photographed FOVs on the biochip fixed on the chip base;
a first control step, when the total number N is less than the total number S of FOVs included in the biochip fixed on the chip base, controlling the XY platform to drive the chip base to move, and moving the next FOV of the biochip fixed on the chip base to a position right below the objective lens; and
and a second control step of controlling the Z-axis platform to move the objective lens, adjusting a Z-axis coordinate value of the objective lens, and triggering the focusing step.
Preferably, when the XY stage moves the chip base to move the first FOV of the biochip fixed to the chip base to a position directly below the objective lens, the method further includes the steps of:
and controlling the Z-axis platform to move the objective lens to an initial position, wherein a Z-axis coordinate value corresponding to the initial position is an initial value.
Preferably, the initial position is calculated according to the following steps:
controlling the camera to respectively take one picture at different positions based on the objective lens so as to obtain a plurality of pictures, wherein the objective lens at different positions means that the Z-axis coordinate values of the objective lens are different;
respectively calculating the definition of the plurality of photos, and determining the photo with the highest definition;
and when the camera shoots the picture with the highest definition, the position of the objective lens is taken as the initial position.
Preferably, the method for determining that the focusing of the objective lens is successful comprises:
judging whether the objective lens completes focusing within a preset time;
when the objective lens does not finish focusing within the preset time, determining that focusing fails;
when the objective lens completes focusing within the preset time, acquiring a Z-axis coordinate value of the current position of the objective lens;
calculating a difference value between the Z-axis coordinate value of the current position of the objective lens and a preset value; and
and when the difference is larger than or equal to the preset difference, determining that the objective lens fails to be focused.
Preferably, when the objective lens has no record of successful focusing, the preset value is a Z-axis coordinate value corresponding to the initial position; and
and when the objective lens has a record of successful focusing, the preset value is a Z-axis coordinate corresponding to the objective lens which has been successfully focused last time.
Preferably, the controlling the objective lens to automatically focus based on the currently set Z-axis coordinate value includes:
when the objective lens cannot lock a focus based on the currently set Z-axis coordinate value, controlling the Z-axis platform to finely adjust the Z-axis coordinate value of the objective lens, and controlling the objective lens to continuously focus based on the finely adjusted Z-axis coordinate value;
stopping controlling the Z-axis stage to finely adjust the Z-axis coordinate value of the objective lens when the objective lens locks a focus based on the current Z-axis coordinate value.
Preferably, the fine tuning is to control the Z-axis platform to drive the objective lens to move up/down for a preset distance.
A second aspect of the invention provides a gene sequencer comprising a processor for implementing the focusing method when executing a computer program stored in a memory.
A third aspect of the present invention provides a computer-readable storage medium having stored thereon a computer program which, when executed by a processor, implements the focusing method.
The fourth aspect of the present invention provides a focusing system for use in a gene sequencer, the gene sequencer including an objective lens, a camera, a chip base for fixing a biochip, an XY stage, and a Z-axis stage, the system comprising:
the focusing module is used for controlling the objective lens to automatically focus based on the currently set Z-axis coordinate value;
the execution module is used for controlling the camera to take a picture when the objective lens is successfully focused to obtain graphic data corresponding to a FOV (field of view) which is positioned right below the objective lens on the biochip fixed on the chip base;
the execution module is also used for counting the total number N of the photographed FOVs on the biochip fixed on the chip base;
the execution module is further configured to control the XY stage to drive the chip base to move when the total number N is smaller than the total number S of FOVs included in the biochip fixed to the chip base, and move the next FOV of the biochip fixed to the chip base to a position right below the objective lens; and
the focusing module is further used for controlling the Z-axis platform to move the objective lens, adjusting the Z-axis coordinate value of the objective lens, and controlling the objective lens to automatically focus again based on the currently set Z-axis coordinate value.
The focusing method and system, the gene sequencer and the computer readable storage medium in the embodiment of the invention automatically focus by controlling the objective lens based on the currently set Z-axis coordinate value; when the objective lens is successfully focused, controlling the camera to take a picture to obtain graphic data corresponding to a FOV (field of view) which is positioned right below the objective lens on the biochip; counting the total number N of the photographed FOVs on the biochip; when the total number N is smaller than the total number of FOVs included in the biochip, controlling the XY platform to drive the chip base, and moving the next FOV of the biochip fixed on the chip base to a position right below the objective lens; and controlling the Z-axis platform to move the objective lens, adjusting the Z-axis coordinate value of the objective lens, and triggering and controlling the objective lens to automatically focus based on the current set Z-axis coordinate value. The invention can solve the technical problem that the focusing of the gene sequencer can not be successful due to interference such as chip bubbles, impurities, external vibration interference and the like in the focusing process.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, it is obvious that the drawings in the following description are only embodiments of the present invention, and for those skilled in the art, other drawings can be obtained according to the provided drawings without creative efforts.
FIG. 1 is a schematic diagram of the internal structure of a gene sequencer according to a preferred embodiment of the present invention.
FIG. 2 is a schematic diagram of a partial structure of a gene sequencer according to a preferred embodiment of the present invention.
FIG. 3 illustrates the number of FOVs included in the biochip.
FIG. 4 is a functional block diagram of a focusing system according to a preferred embodiment of the present invention.
FIG. 5 is a flowchart of a focusing method according to a preferred embodiment of the present invention.
The following detailed description will further illustrate the invention in conjunction with the above-described figures.
Detailed Description
In order that the above objects, features and advantages of the present invention can be more clearly understood, a detailed description of the present invention will be given below with reference to the accompanying drawings and specific embodiments. It should be noted that the embodiments of the present invention and features of the embodiments may be combined with each other without conflict.
In the following description, numerous specific details are set forth to provide a thorough understanding of the present invention, and the described embodiments are merely a subset of the embodiments of the present invention, rather than a complete embodiment. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The terminology used in the description of the invention herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention.
FIG. 1 is a schematic diagram of the internal structure of a gene sequencer according to an embodiment of the present invention. FIG. 2 is a schematic diagram of a partial structure of a gene sequencer according to an embodiment of the present invention.
Referring to fig. 1 and 2, in the preferred embodiment of the present invention, the gene sequencer 3 includes, but is not limited to, a memory 31, at least one processor 32, at least one communication bus 33, a focusing system 5, an objective lens 35, a camera 36, a chip base 37, a biochip 38, an XY stage 39, and a Z stage 40, which are electrically connected to each other directly.
It will be appreciated by those skilled in the art that the structure of the gene sequencer 3 shown in FIGS. 1 and 2 is not a limitation of the embodiments of the present invention. The structure of the gene sequencer 3 may be either a bus-type structure or a star-shaped structure, and the gene sequencer 3 may further include more or less hardware or software than those shown, or different component arrangements. Although not shown, the gene sequencer 3 may further include a power source (e.g., a battery) for supplying power to the various components, and preferably, the power source may be logically connected to the at least one processor 32 through a power management device, so as to manage the functions of charging, discharging, and power consumption management through the power management device. The power supply may also include one or more dc or ac power sources, recharging devices, power failure detection circuitry, power converters or inverters, power status indicators, and the like. The gene sequencer 3 may also include other elements, such as sensors, Wi-Fi modules, etc., which are not described in detail herein.
It is to be understood that the described embodiments are for purposes of illustration only and that the scope of the appended claims is not limited to such structures.
In this embodiment, the chip mount 37 is used for carrying and fixing the biochip 38. The chip base 37 can control the temperature of the biochip 38 to rise and fall.
In some embodiments, the biochip 38 may be a gene sequencing chip. DNA nanospheres (i.e., DNB, DNA Nanoballs) may be provided on the biochip 38. The DNA Nanospheres (DNBs) may be amplification products comprising DNA fragments. The DNA nanospheres carry fluorescent groups when synthesizing bases, and the fluorescent groups can emit fluorescent signals when being excited.
In this embodiment, the biochip 38 may be any version of the chip. Taking version V1 as an example, the biochip 38 has dimensions of about 75mm 25 mm. The biochip 38 comprises a total number of fields of view (FOV) S, which refers to the range of one performance observation of the objective lens 35. For example, the biochip shown in fig. 3 includes a total number S of FOVs 64 × 9, i.e., 576 FOVs.
Referring to fig. 2 again, in the present embodiment, the chip base 37 is disposed on the XY stage 39, and the XY stage 39 can drive the chip base 37 to move on the XY plane, so that each FOV of the biochip 38 fixed on the chip base 37 can be sequentially moved to a position right below the objective lens 35. The camera 36 is used to photograph the FOV on the biochip 38 currently located directly under the objective lens 35, and record image data corresponding to the FOV. In this embodiment, the Z-axis stage 40 can move the objective lens 35 up and down along the vertical direction (i.e. the direction perpendicular to the XY-plane), so as to adjust the position of the objective lens 35 relative to the surface of the biochip 38.
In some embodiments, the memory 31 is used for storing program codes and various data, such as the focusing system 5 installed in the gene sequencer 3, and realizes high-speed and automatic access to programs or data during the operation of the gene sequencer 3. The Memory 31 includes a Read-Only Memory (ROM), a Random Access Memory (RAM), a Programmable Read-Only Memory (PROM), an Erasable Programmable Read-Only Memory (EPROM), a One-time Programmable Read-Only Memory (OTPROM), an electronically Erasable rewritable Read-Only Memory (EEPROM), a Compact Disc Read-Only Memory (CD-ROM) or other optical Disc Memory, a magnetic disk Memory, a tape Memory, or any other storage medium readable by a computer capable of carrying or storing data.
In some embodiments, the at least one processor 32 may be composed of an integrated circuit, for example, a single packaged integrated circuit, or may be composed of a plurality of integrated circuits packaged with the same or different functions, including one or more Central Processing Units (CPUs), microprocessors, digital Processing chips, graphics processors, and combinations of various control chips. The at least one processor 32 is a Control Unit (Control Unit) of the gene sequencer 3, connects various components of the entire gene sequencer 3 by using various interfaces and lines, and executes various functions of the gene sequencer 3 and processes data, such as the focusing function shown in fig. 5, by running or executing programs or modules stored in the memory 31 and calling data stored in the memory 31.
In some embodiments, the at least one communication bus 33 is configured to enable connection communication between elements of the gene sequencer 3, such as the memory 31, the at least one processor 32, the focusing module 52, the focusing system 5, and the like.
In some embodiments, the focusing system 5 is stored in the memory 31 of the gene sequencer 3 and executed by the at least one processor 32 to implement a focusing function.
Referring to fig. 4, the focusing system 5 may include one or more computer instructions in the form of a program that is stored in the memory 31 and executed by the at least one processor 32. In one embodiment, the focusing system 5 may be integrated into the at least one processor 32. In other embodiments, the focusing system 5 may be independent of the processor 32. Referring to fig. 4, the focusing system 5 may include one or more modules, such as an executing module 51, a focusing module 52, and a determining module 53 shown in fig. 4. The functions of the modules will be described in detail in conjunction with fig. 5.
Reference in this specification to a "module" is to be taken as either hardware or firmware, or to a set of software instructions written in a programming language such as JAVA, C. One or more software instructions in the module may be embedded in firmware, such as in an erasable programmable memory. The modules described in this embodiment may be implemented as software and/or hardware modules and may be stored in any type of non-transitory computer-readable storage medium or other storage medium, such as memory 31.
Fig. 5 is a flowchart of a focusing method according to an embodiment of the present invention.
The focusing method specifically comprises the following steps, and the sequence of the steps in the flowchart can be changed and some steps can be omitted according to different requirements.
Step S1, the execution module 51 controls the XY stage 39 to drive the chip base 37, and the first FOV of the biochip 38 fixed on the chip base 37 is moved to a position right below the objective lens 35. The focusing module 52 controls the Z-axis stage 40 to move the objective lens 35 to an initial position, wherein a Z-axis coordinate value corresponding to the initial position is an initial value. The focusing module 52 also controls the objective lens 35 to automatically focus based on the currently set Z-axis coordinate value.
In one embodiment, the Z-axis coordinate value may refer to an absolute Z-axis coordinate value with respect to a preset one coordinate system xyz.
In one embodiment, the focusing module 52 constructs the preset coordinate system including:
(a1) based on a specified point as an origin O;
(a2) constructing a Z axis based on the direction in which the Z axis platform 40 drives the objective lens 35 to move upwards;
(a3) an X-axis and a Y-axis are constructed based on the origin O and a plane perpendicular to the Z-axis.
It should be noted that the preset coordinate system may also be established in other manners, as long as the objective lens 35 can be distinguished at different positions according to the Z-axis coordinate value during the up-and-down movement of the objective lens 35.
In one embodiment, the method for the focus module 52 to determine the initial position includes:
(b1) controlling the camera 36 to take one picture based on the objective lens 35 at different positions respectively, so as to obtain a plurality of pictures, wherein the different positions of the objective lens 35 mean that the Z-axis coordinate values of the objective lens 35 are different;
(b2) respectively calculating the definition of the plurality of photos, and determining the photo with the highest definition;
(b3) and taking the initial position as the position of the objective lens 35 when the camera 36 takes the picture with the highest definition.
In one embodiment, the focusing module 52 controls the objective lens 35 to perform automatic focusing based on the currently set Z-axis coordinate value, namely, when the objective lens 35 fails to lock the focus based on the currently set Z-axis coordinate value, the Z-axis platform 40 is controlled to finely adjust the Z-axis coordinate value of the objective lens 35, and the objective lens 35 is controlled to continue focusing based on the finely adjusted Z-axis coordinate value. When the objective lens 35 locks the focus based on the current Z-axis coordinate value, the focusing module 52 stops controlling the Z-axis stage 40 to finely adjust the Z-axis coordinate value of the objective lens 35.
In one embodiment, the fine tuning may refer to controlling the Z-axis stage 40 to move the objective lens 35 up/down along the vertical direction by a predetermined distance (e.g., 0.01 μm (micrometer), 0.02 μm, or other values).
Step S2, the determining module 53 determines whether the objective lens 35 completes focusing within a preset time. When the objective lens 35 completes focusing within the preset time, step S3 is performed. When the objective lens 35 does not complete focusing within the preset time, step S13 is performed.
In one embodiment, the preset time may be 15 seconds, 20 seconds, or other time.
Step S3, when the objective lens 35 completes focusing within the preset time, the executing module 51 obtains a Z-axis coordinate value of the current position of the objective lens 35. The executing module 51 further calculates a first difference between the Z-axis coordinate value of the current position of the objective lens 35 and the initial value.
In step S4, the determining module 53 determines whether the first difference is smaller than a predetermined difference. When the first difference is smaller than the preset difference, step S5 is performed, and when the first difference is greater than or equal to the preset difference, step S13 is performed.
In one implementation, the predetermined difference may refer to 49 μm (micrometers), 50 μm, or other values.
In step S5, when the first difference is smaller than the preset difference, the determining module 53 determines that the focusing of the objective lens 35 is successful. The execution module 51 further controls the camera 36 to take a picture, so as to obtain the graphic data corresponding to the FOV on the biochip 38 which is currently located directly below the objective lens 35. It should be understood by those skilled in the art that if the first FOV of the biochip 38 is located directly below the objective lens 35, the camera 36 captures image data corresponding to the first FOV.
In one embodiment, the execution module 51 controls the camera 36 to take at least one (i.e., one or more) picture of the FOV on the biochip 38 that is currently directly below the objective lens 35.
The execution module 51 also adds 1 to the total number N of completed photographed FOVs on the biochip 38 to count the total number N of completed photographed FOVs on the biochip 38.
For example, after the camera 36 photographs the first FOV of the biochip 38, the execution module 51 may statistically determine that the total number N of the photographed FOVs on the biochip 38 is equal to 1.
In step S6, the execution module 51 controls the XY stage 39 to drive the chip base 37 to move, and moves the next FOV of the biochip 38 fixed on the chip base 37 to a position right below the objective lens 35.
For example, if the camera 36 takes a picture to obtain the image data corresponding to the first FOV on the biochip 38 in step S5, in step S6, the XY stage 39 is controlled to drive the chip base 37 to move the second FOV of the biochip 38 fixed on the chip base 37 to the position right below the objective lens 35. The second FOV may be a FOV adjacent to the first FOV. For example, referring to fig. 3, the second FOV may be the FOV to the left of the first FOV in accordance with the right-to-left scan direction.
In step S7, the focusing module 52 controls the Z-axis stage 40 to move the objective lens 35, and adjusts the Z-axis coordinate value of the objective lens 35 to the Z-axis coordinate value corresponding to the latest successful focusing. The focusing module 52 controls the objective lens 35 to automatically focus based on the currently set Z-axis coordinate value.
For example, it is assumed that the focusing module 52 controls the objective lens 35 to successively focus three times. The Z-axis coordinate of the objective lens 35 is Z1 when the first focusing is successful, the Z-axis coordinate of the objective lens 35 is Z2 when the second focusing is successful, and the Z-axis coordinate of the objective lens 35 is Z3 when the third focusing is successful. Then the Z-axis coordinate value corresponding to the latest successful focusing is Z3.
If no record of successful primary focusing is recorded before this step, the Z-axis coordinate value of the objective lens 35 is adjusted to the Z-axis coordinate value corresponding to the initial position in this step. I.e. the objective lens 35 is still moved to the initial position. In other words, when the objective lens 35 has no successfully focused record, the Z-axis coordinate value of the objective lens 35 is adjusted to the Z-axis coordinate value corresponding to the initial position, and when the objective lens 35 has successfully focused record, the Z-axis coordinate value of the objective lens 35 is adjusted to the Z-axis coordinate value corresponding to the last successful focusing of the objective lens 35.
As described above, the controlling of the objective lens 35 to perform the auto-focusing based on the currently set Z-axis coordinate value means controlling the Z-axis stage 40 to finely adjust the Z-axis coordinate value of the objective lens 35 and controlling the objective lens 35 to continue focusing based on the finely adjusted Z-axis coordinate value when the objective lens 35 fails to lock the focus based on the currently set Z-axis coordinate value. When the objective lens 35 locks the focus based on the current Z-axis coordinate value, the focusing module 52 stops controlling the Z-axis stage 40 to finely adjust the Z-axis coordinate value of the objective lens 35.
In step S8, the determining module 53 determines whether the objective lens 35 completes focusing within a preset time. When the objective lens 35 completes focusing within the preset time, step S9 is performed. When the objective lens 35 does not complete focusing within the preset time, step S13 is performed.
In step S9, when the objective lens 35 completes focusing within the preset time, the executing module 51 obtains a Z-axis coordinate value of the current position of the objective lens 35. The executing module 51 further calculates a second difference between the Z-axis coordinate value of the current position of the objective lens 35 and the Z-axis coordinate value corresponding to the latest successful focusing.
In step S10, the determining module 53 determines whether the second difference is smaller than the preset difference. When the second difference is smaller than the preset difference, step S11 is performed, and when the second difference is greater than or equal to the preset difference, step S13 is performed.
In step S11, when the second difference is smaller than the preset difference, the determining module 53 determines that the focusing of the objective lens 35 is successful. The execution module 51 further controls the camera 36 to take a picture, so as to obtain the graphic data corresponding to the FOV on the biochip 38 which is currently located directly below the objective lens 35.
In one embodiment, the execution module 51 controls the camera 36 to take at least one (i.e., one or more) picture of the FOV on the biochip 38 that is currently directly below the objective lens 35.
The execution module 51 also adds 1 to the total number N of completed photographed FOVs on the biochip 38 to count the total number N of completed photographed FOVs on the biochip 38.
For example, after the camera 36 photographs the second FOV of the biochip 38, the execution module 51 may count that the total number N of the photographed FOVs on the biochip 38 is equal to 2.
In step S12, the determining module 53 determines whether the total number N of the FOVs that have been photographed on the biochip 38 is smaller than the total number S of the FOVs included in the biochip 38. If the total number N of the FOVs that have been photographed on the biochip 38 is smaller than the total number S of the FOVs included in the biochip 38, the step S6 is triggered to be executed. If the total number N of the FOV on the biochip 38 that has been photographed is equal to or greater than the total number S of the FOVs included in the biochip 38, the process is ended.
In step S13, the determination module 53 determines that the objective lens 35 fails to focus. The execution module 51 controls the camera 36 to take a picture, so as to obtain the graphic data corresponding to the FOV on the biochip 38 which is currently located right below the objective lens 35.
In one embodiment, the execution module 51 controls the camera 36 to take at least one (i.e., one or more) picture of the FOV on the biochip 38 that is currently directly below the objective lens 35.
The execution module 51 also adds 1 to the total number N of completed photographed FOVs on the biochip 38 to count the total number N of completed photographed FOVs on the biochip 38.
In summary, in the focusing method in the embodiment of the present invention, the objective lens is controlled to automatically focus based on the currently set Z-axis coordinate value; when the objective lens is successfully focused, controlling the camera to take a picture to obtain graphic data corresponding to a FOV (field of view) which is positioned right below the objective lens on the biochip; counting the total number N of the photographed FOVs on the biochip; when the total number N is smaller than the total number of FOVs included in the biochip, controlling the XY platform to drive the chip base, and moving the next FOV of the biochip fixed on the chip base to a position right below the objective lens; and controlling the Z-axis platform to move the objective lens, adjusting the Z-axis coordinate value of the objective lens, and triggering and controlling the objective lens to automatically focus based on the current set Z-axis coordinate value. The invention can solve the technical problem that the focusing of the gene sequencer can not be successful due to interference such as chip bubbles, impurities, external vibration interference and the like in the focusing process.
In this embodiment, the modules described as separate parts may or may not be physically separate, and parts displayed as modules may or may not be physical units, that is, may be located in one place, or may be distributed on multiple network units. Some or all of the modules may be selected according to actual needs to achieve the purpose of the solution of the present embodiment.
In addition, functional modules in the embodiments of the present invention may be integrated into one processing unit, or each unit may exist alone physically, or two or more units are integrated into one unit. The integrated unit can be realized in a form of hardware, or in a form of hardware plus a software functional module.
It will be evident to those skilled in the art that the invention is not limited to the details of the foregoing illustrative embodiments, and that the present invention may be embodied in other specific forms without departing from the spirit or essential attributes thereof. The present embodiments are therefore to be considered in all respects as illustrative and not restrictive, the scope of the invention being indicated by the appended claims rather than by the foregoing description, and all changes which come within the meaning and range of equivalency of the claims are therefore intended to be embraced therein. Any reference sign in a claim should not be construed as limiting the claim concerned. Furthermore, it is obvious that the word "comprising" does not exclude other elements or that the singular does not exclude the plural. A plurality of units or means recited in the apparatus claims may also be implemented by one unit or means in software or hardware. The terms first, second, etc. are used to denote names, but not any particular order.
Finally, it should be noted that the above embodiments are only for illustrating the technical solutions of the present invention and not for limiting, and although the present invention is described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that modifications or equivalent substitutions may be made on the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention.
Claims (8)
1. A focusing method is applied to a gene sequencer, the gene sequencer comprises an objective lens, a camera, a chip base for fixing a biochip, an XY platform and a Z-axis platform which are electrically connected with each other, and the method is characterized by comprising the following steps:
a focusing step of controlling the objective lens to automatically focus based on a currently set Z-axis coordinate value;
a photographing step, when the objective lens is successfully focused, controlling the camera to photograph to obtain graphic data corresponding to an FOV (field of view) which is positioned right below the objective lens on the biochip fixed on the chip base;
a counting step of counting the total number N of the photographed FOVs on the biochip fixed on the chip base;
a first control step, when the total number N is less than the total number S of FOVs included in the biochip fixed on the chip base, controlling the XY platform to drive the chip base to move, and moving the next FOV of the biochip fixed on the chip base to a position right below the objective lens; and
a second control step of controlling the Z-axis platform to move the objective lens, adjusting a Z-axis coordinate value of the objective lens, and triggering the focusing step; wherein the adjusting the Z-axis coordinate value of the objective lens comprises: when the objective lens has no record of successful focusing, the Z-axis coordinate value of the objective lens is adjusted to be the Z-axis coordinate value corresponding to the initial position, and when the objective lens has record of successful focusing, the Z-axis coordinate value of the objective lens is adjusted to be the Z-axis coordinate corresponding to the last successful focusing of the objective lens, wherein the initial position is calculated according to the following steps: controlling the camera to respectively take one picture at different positions based on the objective lens so as to obtain a plurality of pictures, wherein the objective lens at different positions means that the Z-axis coordinate values of the objective lens are different; respectively calculating the definition of the plurality of photos, and determining the photo with the highest definition; and when the camera shoots the picture with the highest definition, the position of the objective lens is taken as the initial position.
2. The focusing method of claim 1, wherein when the XY stage moves the chip holder to move the first FOV of the biochip fixed on the chip holder to a position directly below the objective lens, the method further comprises the steps of:
and controlling the Z-axis platform to move the objective lens to the initial position, wherein the Z-axis coordinate value corresponding to the initial position is an initial value.
3. The focusing method of claim 2, wherein the step of determining that the objective lens is successfully focused comprises:
judging whether the objective lens completes focusing within a preset time;
when the objective lens does not finish focusing within the preset time, determining that focusing fails;
when the objective lens completes focusing within the preset time, acquiring a Z-axis coordinate value of the current position of the objective lens;
calculating a difference value between the Z-axis coordinate value of the current position of the objective lens and a preset value; and
and when the difference is larger than or equal to the preset difference, determining that the objective lens fails to be focused.
4. The focusing method according to claim 1, wherein the controlling the objective lens to automatically focus based on the currently set Z-axis coordinate value includes:
when the objective lens cannot lock a focus based on the currently set Z-axis coordinate value, controlling the Z-axis platform to finely adjust the Z-axis coordinate value of the objective lens, and controlling the objective lens to continuously focus based on the finely adjusted Z-axis coordinate value;
stopping controlling the Z-axis stage to finely adjust the Z-axis coordinate value of the objective lens when the objective lens locks a focus based on the current Z-axis coordinate value.
5. The focusing method of claim 4, wherein the fine tuning is to control the Z-axis stage to move the objective lens up/down by a predetermined distance.
6. A gene sequencer comprising a processor for implementing the focusing method of any one of claims 1 to 5 when executing a computer program stored in a memory.
7. A computer-readable storage medium, on which a computer program is stored, which, when being executed by a processor, carries out a focusing method according to any one of claims 1 to 5.
8. A focusing system operates on a gene sequencer which comprises an objective lens, a camera, a chip base for fixing a biochip, an XY platform and a Z-axis platform which are electrically connected with each other, and is characterized in that the system comprises:
the focusing module is used for controlling the objective lens to automatically focus based on the currently set Z-axis coordinate value;
the execution module is used for controlling the camera to take a picture when the objective lens is successfully focused to obtain graphic data corresponding to a FOV (field of view) which is positioned right below the objective lens on the biochip fixed on the chip base;
the execution module is also used for counting the total number N of the photographed FOVs on the biochip fixed on the chip base;
the execution module is further configured to control the XY stage to drive the chip base to move when the total number N is smaller than the total number S of FOVs included in the biochip fixed to the chip base, and move the next FOV of the biochip fixed to the chip base to a position right below the objective lens; and
the focusing module is further used for controlling the Z-axis platform to move the objective lens, adjusting the Z-axis coordinate value of the objective lens and controlling the objective lens to automatically focus again based on the currently set Z-axis coordinate value; wherein the adjusting the Z-axis coordinate value of the objective lens comprises: when the objective lens has no record of successful focusing, the Z-axis coordinate value of the objective lens is adjusted to be the Z-axis coordinate value corresponding to the initial position, and when the objective lens has record of successful focusing, the Z-axis coordinate value of the objective lens is adjusted to be the Z-axis coordinate corresponding to the last successful focusing of the objective lens, wherein the initial position is calculated according to the following steps: controlling the camera to respectively take one picture at different positions based on the objective lens so as to obtain a plurality of pictures, wherein the objective lens at different positions means that the Z-axis coordinate values of the objective lens are different; respectively calculating the definition of the plurality of photos, and determining the photo with the highest definition; and when the camera shoots the picture with the highest definition, the position of the objective lens is taken as the initial position.
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| WO2024138667A1 (en) * | 2022-12-30 | 2024-07-04 | 深圳华大智造科技股份有限公司 | Leveling control method for chip, and related device |
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