Patent Publication Number: US-2023160823-A1

Title: Analysis device for detection chip and method of operating thereof, and analysis system

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
     The present application claims the priority of Chinese patent application No. 202010367897.7, filed on Apr. 30, 2020, and the entire content of the Chinese patent application is incorporated herein by reference as a part of the present application. 
     TECHNICAL FIELD 
     Embodiments of the present disclosure relate to an analysis device for a detection chip and a method of operating the analysis device, and an analysis system. 
     BACKGROUND 
     Digital polymerase chain reaction chip technology (dPCR) is to fully dilute nucleic acid samples so that the number of sample templates in each reaction chamber is less than or equal to 1, so as to achieve absolute quantification of single-molecule DNA. Due to the dPCR has the advantages of high sensitivity, strong specificity, high detection throughput, accurate quantification and the like, it is widely used in clinical diagnosis, gene instability analysis, single-cell gene expression, environmental microbial detection and prenatal diagnosis and the like. 
     SUMMARY 
     At least one embodiment of the present disclosure provides an analysis device for a detection chip, the analysis device for the detection chip comprises a loading part, a temperature control part and a signal detection part, 
     the loading part is configured to receive and hold the detection chip in use, and the loading part is capable of moving the detection chip; 
     the temperature control part comprises a heater and a cooler, the heater is configured to heat the detection chip and the cooler is configured to cool the detection chip; and 
     the signal detection part comprises an optical sensor, and the optical sensor is configured to receive light from the detection chip and perform detection according to the light. 
     For example, in the analysis device according to at least one embodiment of the present disclosure, the loading part comprises: 
     a transport structure, configured to hold the detection chip and at least partially drivable; and
 
a driver, configured to be capable of driving the transport structure, to move the detection chip back and forth among a first position, a second position and a third position, the first position allows the detection chip to be received in the transport structure; the second position allows the temperature control part to adjust a temperature of the detection chip; and
 
the third position allows the optical sensor of the signal detection part to receive the light from the detection chip.
 
     For example, in the analysis device according to at least one embodiment of the present disclosure, the transport structure comprises: 
     a stage, configured to hold the detection chip in use;
 
a movable platform, configured to be connected to the driver, so as to move under a driving of the driver; and
 
a bracket, configured to connect the stage and the movable platform, thereby the stage is driven under a condition that the movable platform is driven.
 
     For example, in the analysis device according to at least one embodiment of the present disclosure, the bracket comprises: 
     a first portion, configured to hold the stage; and
 
a second portion, configured to be connected to the movable platform in use, the first portion extends in a first direction, the second portion extends in a second direction, and the first direction is perpendicular to the second direction.
 
     For example, in the analysis device according to at least one embodiment of the present disclosure, the stage has a hollow region, so that a side surface of the detection chip in contact with the stage is at least partially exposed to the cooler under a condition that the detection chip is placed on the stage. 
     For example, in the analysis device according to at least one embodiment of the present disclosure, the detection chip comprises a heating electrode, 
     the heater comprises a contact electrode, the contact electrode is configured to be in electrical contact with the heating electrode of the detection chip in use, and
 
the heater is further configured to apply an electrical signal to the heating electrode of the detection chip by the contact electrode, so that the heating electrode heats the detection chip.
 
     For example, in the analysis device according to at least one embodiment of the present disclosure, the heater is configured to provide an infrared ray or airflow for heating to the detection chip, to heat the detection chip. 
     For example, in the analysis device according to at least one embodiment of the present disclosure, the temperature control part further comprises a temperature sensor, and the temperature sensor is configured to detect a temperature of the detection chip. 
     For example, in the analysis device according to at least one embodiment of the present disclosure, the temperature sensor and the cooler are configured to be spaced apart from each other, to allow the detection chip to be sandwiched between the temperature sensor and the cooler. 
     For example, in the analysis device according to at least one embodiment of the present disclosure, the temperature sensor comprises an infrared temperature sensor or a thermocouple temperature sensor. 
     For example, in the analysis device according to at least one embodiment of the present disclosure, the cooler comprises a fan or a semiconductor refrigeration sheet. 
     For example, in the analysis device according to at least one embodiment of the present disclosure, the signal detection part further comprises: 
     a light source, configured to provide light in use, to illuminate the detection chip; and
 
a light transmission part, configured to transmit the light provided by the light source to the detection chip and transmit light reflected or transmitted by the detection chip to the optical sensor in use.
 
     For example, in the analysis device according to at least one embodiment of the present disclosure, the light source comprises a laser or a fluorescent light source. 
     For example, in the analysis device according to at least one embodiment of the present disclosure, the optical sensor comprises an image sensor, so as to be configured to acquire an optical image of the detection chip for analysis. 
     For example, in the analysis device according to at least one embodiment of the present disclosure, the analysis device further comprises a controller, and the controller is configured to perform at least one of following operations: 
     connecting to the loading part in a signal connection manner, to control the loading part to move;
 
connecting to the heater in a signal connection manner, to control the heater to heat the detection chip;
 
connecting to the cooler in a signal connection manner, to control the cooler to cool the detection chip; and
 
connecting to the optical sensor in a signal connection manner, to analyze the light from the detection chip.
 
     For example, the analysis device according to at least one embodiment of the present disclosure further comprises at least one of a group consisting of a display screen, a touch sensor, a power interface, and a data transmission interface. 
     At least one embodiment of the present disclosure provides an analysis system, the analysis system comprises: 
     an analysis device as described in any embodiment of the present disclosure; and the detection chip. 
     At least one embodiment of the present disclosure further provides a method of operating an analysis device as described in any embodiment of the present disclosure, the method comprises: 
     moving the loading part holding the detection chip to the temperature control part;
 
adjusting a temperature of the detection chip by the heater and the cooler;
 
moving the loading part holding the detection chip to the signal detection part, and acquiring light from the detection chip by the optical sensor; and
 
analyzing the light from the detection chip, to obtain analysis result.
 
     For example, in the method according to at least one embodiment of the present disclosure, the adjusting the temperature of the detection chip by the heater and the cooler comprises: cyclically maintaining the detection chip at at least two temperatures by the heater and the cooler. 
     For example, in the method according to at least one embodiment of the present disclosure, the acquiring the light from the detection chip by the optical sensor comprises: acquiring an optical image of the detection chip by an image sensor; and the analyzing the light from the detection chip, to obtain the analysis result comprises: 
     converting the optical image to a grayscale image;
 
identifying a reaction chamber of the detection chip in the grayscale image;
 
determining a spaced line in the grayscale image according to the identified reaction chamber;
 
dividing the grayscale image, to obtain a plurality of chamber image blocks, according to the spaced line; and
 
determining a chamber image block with a pixel mean square error being greater than a preset threshold in the plurality of chamber image blocks as a target image block.
 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       In order to explain the technical solutions of the embodiments of the present disclosure more clearly, the drawings of the embodiments will be briefly introduced below. It is obvious that the described drawings are only related to some embodiments of the present disclosure and thus are not limitative to the present disclosure. 
         FIG.  1    is a schematic block diagram of an analysis device for a detection chip according to at least one embodiment of the present disclosure; 
         FIG.  2    is a schematic block diagram of a loading part according to at least one embodiment of the present disclosure; 
         FIG.  3    is a schematic structural diagram of a transport structure in an exploded state according to at least one embodiment of the present disclosure; 
         FIG.  4    is a schematic structural diagram of a transport structure in an assemble state according to at least one embodiment of the present disclosure; 
         FIG.  5    is a schematic block diagram of a detection chip according to at least one embodiment of the present disclosure; 
         FIG.  6    is a schematic structural diagram of a temperature control part in an exploded state according to at least one embodiment of the present disclosure; 
         FIG.  7    is a schematic structural diagram of a temperature control part in an assemble state according to at least one embodiment of the present disclosure; 
         FIG.  8    is a schematic structural diagram of a signal detection part according to at least one embodiment of the present disclosure; 
         FIG.  9    is a schematic structural diagram of a specific example of a signal detection part according to at least one embodiment of the present disclosure; 
         FIG.  10    is a schematic structural diagram of a loading part, a temperature control part and a signal detection part in an assembled state according to at least one embodiment of the present disclosure; 
         FIG.  11    is a schematic block diagram of an analysis device according to at least one embodiment of the present disclosure; 
         FIG.  12    is a front view of an analysis device according to at least one embodiment of the present disclosure; 
         FIG.  13    is a rear view of an analysis device according to at least one embodiment of the present disclosure; 
         FIG.  14    is a perspective view of an analysis device according to at least one embodiment of the present disclosure; 
         FIG.  15    is a schematic block diagram of an analysis system according to at least one embodiment of the present disclosure; 
         FIG.  16    is a flow diagram of a method for operating an analysis device according to at least one embodiment of the present disclosure; 
         FIG.  17 A ,  FIG.  17 B  and  FIG.  17 C  show a process of implementing step S 320  according to at least one embodiment of the present disclosure; 
         FIG.  18    is a temperature change diagram of a temperature control cycle according to at least one embodiment of the present disclosure; 
         FIG.  19    shows a cross-sectional view of an analysis device according to at least one embodiment of the present disclosure when step S 360  is performed; 
         FIG.  20    is a flow diagram of step S 380  according to at least one embodiment of the present disclosure; 
         FIG.  21 A  is a distribution diagram of sums of row pixel values of an auxiliary image according to at least one embodiment of the present disclosure; 
         FIG.  21 B  is a distribution diagram of sums of column pixel values of an auxiliary image according to at least one embodiment of the present disclosure; 
         FIG.  22 A  is a schematic diagram of troughs in the row direction of an auxiliary image according to at least one embodiment of the present disclosure; 
         FIG.  22 B  is a schematic diagram of troughs in the column direction of an auxiliary image according to at least one embodiment of the present disclosure; and 
         FIG.  23    is an example of an auxiliary image according to at least one embodiment of the present disclosure. 
     
    
    
     DETAILED DESCRIPTION 
     In order to make objects, technical details and advantages of the embodiments of the present disclosure apparent, the technical solutions of the embodiments of the present disclosure will be described in a clearly and fully understandable way in connection with the drawings related to the embodiments of the present disclosure. It is obvious that the described embodiments are just a part but not all of the embodiments of the present disclosure. Based on the described embodiments herein, those skilled in the art can obtain other embodiment(s), without any inventive work, which should be within the scope of the invention. 
     Unless otherwise defined, all the technical and scientific terms used herein have the same meanings as commonly understood by one of ordinary skill in the art to which the present disclosure belongs. The terms, such as “first,” “second,” or the like, which are used in the description and the claims of the present disclosure, are not intended to indicate any sequence, amount or importance, but for distinguishing various components. The terms, such as “comprise/comprising,” “include/including,” or the like are intended to specify that the elements or the objects stated before these terms encompass the elements or the objects and equivalents thereof listed after these terms, but not preclude other elements or objects. The terms, such as “connect/connecting/connected,” “couple/coupling/coupled” or the like, are not limited to a physical connection or mechanical connection, but may include an electrical connection/coupling, directly or indirectly. The terms, “on,” “under,” “left,” “right,” or the like are only used to indicate relative position relationship, and when the position of the object which is described is changed, the relative position relationship may be changed accordingly. 
     In order to keep the following description of the embodiments of the present disclosure clear and concise, the present disclosure omits detailed descriptions of known functions and known components. 
     Some dPCR products usually require a plurality of ancillary apparatuses to obtain an analysis result, which leads to long detecting time, high detecting cost, multiple operation steps, and the risk of reagent contamination. 
     At least one embodiment of the present disclosure provides an analysis device for a detection chip, an analysis system, and a method for operating the analysis device. The analysis device of the embodiment integrates a loading part, a temperature control part, and a signal detection part, so that the detection of a detection chip can be realized with a single device, thereby reducing the number of required ancillary apparatus, simplifying the operation steps, shortening detection time, and reducing the risk of reagent contamination. 
       FIG.  1    is a schematic block diagram of an analysis device for a detection chip according to at least one embodiment of the present disclosure. As shown in  FIG.  1   , an analysis device  100  for a detection chip according to at least one example of the present disclosure may at least include a loading part  110 , a temperature control part  120  and a signal detection part  130 . 
     The loading part  110  is configured to receive and hold the detection chip in use and allow the detection chip to be moved to the temperature control part and the signal detection part. 
     The temperature control part  120  includes a heater  121  and a cooler  122 . The heater  121  is configured to heat the detection chip loaded in the analysis device, and the cooler  122  is configured to cool the detection chip loaded in the analysis device, thereby realizing control of the temperature of the detection chip. 
     The signal detection part  130  includes an optical sensor  131 . The optical sensor  131  is configured to receive light from the detection chip and perform detection according to the light of the detection chip. 
     It should be understood that the detection chip described in the various embodiments of the present disclosure may be any type of biological detection chip or chemical detection chip, such as various microfluidic chips, and the embodiments of the present disclosure are not limited thereto. 
       FIG.  2    is a schematic block diagram of the loading part according to at least one embodiment of the present disclosure. The loading part  110  may include a transport structure  111  and a driver  112 . 
     The transport structure  111  is configured to hold the detection chip and may be at least partially driven. The driver  112  is configured to be capable of driving the transport structure  111 . For example, the driver  112  may be operatively connected to the transport structure  111 , so that the detection chip is moved back and forth among a first position, a second position and a third position. In at least one embodiment, the first position allows the detection chip to be received in the transport structure  111 , that is, the first position allows the user to put the detection chip loaded with the detection sample into the loading part  110 . The second position allows the temperature control part  120  to adjust the temperature of the detection chip. The third position allows the optical sensor  131  of the signal detection part  130  to receive the light from the detection chip. For example,  FIG.  17 B , which will be described below, shows an example of the first position P 1  in at least one embodiment of the present disclosure. For example,  FIG.  17 C , which will be described below, shows an example of the second position P 2  in at least one embodiment of the present disclosure. For example,  FIG.  19   , which will be described below, shows an example of the third position P 3  in at least one embodiment of the present disclosure. 
     However, it should be understood that, in some embodiments, the loading part  110  may not include the driver  112 , so that the transport structure  111  may be manually moved (for example, pushed or pulled), which is not limited in the embodiments of the present disclosure. 
       FIG.  3    is a schematic structural diagram of an exploded state of a transport structure according to at least one embodiment of the present disclosure, and  FIG.  4    is a schematic structural diagram of an assemble state of a transport structure according to at least one embodiment of the present disclosure. As shown in  FIG.  3    and  FIG.  4   , the transport structure  111  may include a stage  1111 , a movable platform  1112  and a bracket  1113 . 
     The stage  1111  is configured to hold the detection chip in use. In the example in the figure, the stage  1111  is of a rectangular plate shape and is capable of being movably arranged on the bracket  1113 . The stage  1111  has a first recessed region RA 1  for accommodating the detection chip. The outline of the first recessed region RA 1  is usually basically the same as the shape of the detection chip, as shown in the figure, both are rectangular. In order to facilitate the user to put in and take out the detection chip by fingers, for example, a semi-circular recessed part protrudes from a side of the first recessed region RA 1 , so as to accommodate the fingers holding the detection chip. 
     For example, the stage  1111  may be formed of a high temperature resistant material, and the high temperature resistant material may be, for example, metal, plastic, ceramic, rubber, resin, and the like. The heat distortion temperature of the high temperature resistant material forming the stage  1111  may be, for example, above 100° C., 200° C., 300° C., 400° C. and 500° C. The stage  1111  may also be formed of a material with a high temperature resistance and poor thermal conductivity. For example, in a specific embodiment, the stage  1111  may be formed of ceramic, so that the stage  1111  has a lighter weight and can withstand high temperature. 
     In some embodiments, the stage  1111  may further include a spirit level H, so as to detect whether the stage  1111  is level. For example, in a case where the stage  1111  has a second recessed region RA 2 , the spirit level H may be accommodated and fixed in the second recessed region RA 2 . However, it should be understood that the stage  1111  may not have the second recessed region RA 2 , the spirit level H is attached to the stage  1111  by an adhesive or the like, and the embodiments of the present disclosure are not limited thereto. The spirit level H may be, for example, a bubble spirit level, an inductive spirit level and a capacitive spirit level, etc., and the embodiments of the present disclosure are not limited thereto. The detection chip carried on the stage  1111  can be kept level by the spirit level H, thereby helping the optical sensor  131  to receive the light from the detection chip. 
     As shown in  FIG.  3    and  FIG.  4   , the stage  1111  may have a hollow region HA, so that a side surface of the detection chip in contact with the stage  1111  is at least partially exposed, for example, exposed to the cooler  122  of the temperature control part  120 , while the detection chip is placed on the stage  1111 . According to actual requirements, the hollow region HA may have any suitable shape, such as a circle, a triangle, a rectangle, a pentagon, a hexagon or other irregular shapes, etc. For another example, the hollow region HA may have one or more openings, and the embodiments of the present disclosure are not limited thereto. A size of a projection of the detection chip on a plane where the hollow region HA is located is larger than a size of the hollow region HA, so that the detection chip is carried on the stage  1111 . 
     The movable platform  1112  is configured to be operatively connected to the driver  112 , so as to move under the drive of the driver  112 . The driver  112  may be a motor, for example, and the movable platform  1112  is connected to a driving end of the motor, for example. For example, the driver  112  may be a rotating motor, a driving end of the rotating motor is connected to a lead screw S so that the lead screw S can be rotated, and the movable platform  1112  is connected to the lead screw S through a nut threaded with the lead screw S, so that the rotation of the lead screw S is converted into horizontal movement, so as to move the movable platform  1112  by the drive of the driver  112 . In addition, a guide rod G parallel to the lead screw S may also be provided. The movable platform  1112  is movably connected to the guide rod G. The guide rod G plays a role of restraining the movable platform  1112 . It should be understood that the number of the guide rods G and the number of the lead screws S shown in  FIG.  3    and  FIG.  4    are all exemplary, and the embodiments of the present disclosure are not limited thereto. For example, the driver  112  may be a linear motor, and a mover of the linear electric machine may be connected to the movable platform  1112 , so as to drive the movable platform  1112  to move. The embodiment of the present disclosure does not limit how the driver  112  drives the movable platform  1112 , and for example, a gear and rack combination may also be used to convert a rotational movement into a horizontal movement. 
     The movable platform  1112  may be formed of any rigid material, for example, metal, plastic, ceramic, rubber, resin, etc., which is not limited in the embodiments of the present disclosure. In addition, it should be understood that the shape of the movable platform  1112  shown in  FIG.  3    and  FIG.  4    is only exemplary, and the movable platform  1112  may have any suitable shape according to actual requirements. 
     The bracket  1113  is configured to connect the stage  1111  to the movable platform  1112 , thereby enabling the stage  1111  to be driven when the movable platform  1112  is driven. 
     As shown by a dashed box in  FIG.  3   , the bracket  1113  may include a first portion  1113 A and a second portion  1113 B. The first portion  1113 A is configured to hold the stage  1111  in use. The second portion  1113 B is configured to connect to the movable platform  1112  in use. The first portion  1113 A extends in a first direction, the second portion  1113 B extends in a second direction, and the first direction is perpendicular to the second direction. The bracket  1113  is formed into an L shape or a T shape, thereby reducing a size in a single direction, which helps to reduce the overall volume of the analysis device. 
     The first portion  1113 A of the bracket  1113 , for example, may be connected to the stage  1111  through a spring or the like. For example, the first portion  1113 A may be connected to the stage  1111  through four springs corresponding to four corners of the stage  1111 , so that a level state of the stage  1111  can be adjusted by adjusting the corresponding spring. 
     The second portion  1113 B of the bracket  1113 , for example, may be detachably connected or fixedly connected to the movable platform  1112  by screws or the like, so as to allow the movable platform  1112  to drive the bracket  1113  to move together. Alternatively, the second portion  1113 B may be integrally formed with the movable platform  1112 . 
     The bracket  1113  may be formed of any rigid material, for example, metal, plastic, ceramic, rubber, resin, etc., which is not limited in the embodiments of the present disclosure. In addition, it should be understood that a shape of the bracket  1113  shown in  FIG.  3    and  FIG.  4    is only exemplary, and the bracket  1113  may have any suitable shape according to actual requirements. 
       FIG.  5    is a schematic block diagram of a detection chip according to at least one embodiment of the present disclosure. In some embodiments, the detection chip C may include a heating electrode CE, and in a case where an electrical signal is received, the heating electrode CE or a resistance wiring electrically connected to the heating electrode CE can generate heat to heat the detection chip C. The detection chip C may further include an electrode for other purposes, such as an electrode used to apply an electrical signal to drive the sample to move in the detection chip C. As described above, the embodiments of the present disclosure do not limit the type and structure of the detection chip C. 
     As shown in  FIG.  3    and  FIG.  4   , in some embodiments, the heater  121  may include a contact electrode  1211 . The contact electrode  1211 , for example, may be formed of a high temperature resistant metal material. The contact electrode  1211  is configured to be in electrical contact with the heating electrode CE of the detection chip C in use. The heater  121  is further configured to apply an electrical signal to the heating electrode CE of the detection chip C by the contact electrode  1211 , so that the heating electrode CE heats the detection chip C. For example, the contact electrode  1211  may be arranged on the stage  1111  and exposed, so as to allow the contact electrode  1211  to contact with the exposed heating electrode CE of the detection chip C in use, thereby applying an electrical signal (for example, a direct current voltage or the alternating current voltage) to the heating electrode CE of the detection chip C. After the detection chip C is arranged on the stage  1111 , the contact electrode  1211  contacts with the heating electrode CE of the detection chip C, so that the electrical signal can be transmitted. The contact electrode  1211  may be electrically connected to a power source or a controller through a line passing through the stage  1111  to receive a control signal. 
     In addition, the contact electrode  1211  may further play a role in fixing the detection chip C. For example, after the detection chip C is arranged on the stage  1111 , the contact electrode  1211  may be moved by a way of spring or the like, so that the contact electrode  1211  contacts the heating electrode CE of the detection chip C and exerts a force on the detection chip C, thereby fixing the detection chip C by the contact electrode  1211  and the stage  1111 . 
     In other embodiments, the detection chip may not have a heating electrode, and the heater  121  may be configured to provide an infrared ray or airflow for heating to the detection chip, so as to heat the detection chip. For example, the heater  121  may be an infrared heater or a gas heater (for example, heating the air by a resistance and driving the heated air to flow by a fan) and the like, and the embodiments of the present disclosure are not limited thereto. 
       FIG.  6    is a schematic structural diagram of an exploded state of a temperature control part according to at least one embodiment of the present disclosure, and  FIG.  7    is a schematic structural diagram of an assemble state of a temperature control part according to at least one embodiment of the present disclosure. As shown in  FIG.  6    and  FIG.  7   , the temperature control part  120 , for example, may include a temperature sensor  123 . The temperature sensor  123  is configured to detect the temperature of the detection chip. The temperature sensor  123  may be a conventional temperature sensor, which will not be repeated in the embodiments of the present disclosure. For example, the temperature sensor  123  may include an infrared temperature sensor or a thermocouple temperature sensor. It should be understood that, in some embodiments of the present disclosure, if the detection chip includes a temperature sensor, there is no need to provide the temperature sensor  123  in the analysis device. 
     As shown in  FIG.  7   , the temperature sensor  123  and the cooler  122  are configured to be spaced apart from each other to allow the detection chip to be sandwiched between the temperature sensor  123  and the cooler  122 . As shown in  FIG.  6    and  FIG.  7   , the temperature control part  120  may further include a temperature control bracket  124 , and the temperature sensor  123  and the cooler  122  are connected to the temperature control bracket  124  so as to be spaced apart from each other. It should be understood that positions of the temperature sensor  123  and the cooler  122  in  FIG.  6    and  FIG.  7    are only exemplary, and the embodiments of the present disclosure are not limited thereto. For example, in other embodiments, the temperature sensor  123  may be above or below the detection chip in use, and the cooler  122  may be on a side of the detection chip in use. 
     For example, the cooler  122  may include but is not limited to a fan or a semiconductor refrigeration sheet, and the specific type of the cooler  122  is not limited in the embodiment of the present disclosure. As shown in  FIG.  6    and  FIG.  7   , the cooler  122  may be, for example, a fan which has a roughly circular shape and is fixed in the temperature control bracket  124  by four mounting posts arranged at four corners. 
     The temperature control bracket  124  may have an opening to expose the temperature sensor  123  and the cooler  122  to the detection chip in use, thereby allowing the temperature sensor  123  to detect the temperature of the detection chip and the cooler  122  to cool the detection chip. 
     As shown in  FIG.  6    and  FIG.  7   , a cross section of the temperature control bracket  124  may be in a shape of “⊏”, the cooler  122  is arranged in an opening of the “⊏” shape, the temperature sensor  123  may be on a surface of the top of the temperature control bracket  124  away from the bottom, the cooler may be on a surface of the bottom of the temperature control bracket  124  facing the top, and the top of the temperature control bracket  124  may have an opening to partially expose the temperature sensor  123 , thereby allowing the temperature sensor  123  to detect the temperature of the detection chip when the detection chip is between the top and bottom of the temperature control bracket  124 . 
     The temperature control bracket  124  may be formed of any rigid material, for example, metal, plastic, ceramic, rubber, resin, etc., which is not limited in the embodiments of the present disclosure. In addition, it should be understood that the shape of the temperature control bracket  124  shown in  FIG.  6    and  FIG.  7    is only exemplary, and the temperature control bracket  124  may have any suitable shape according to actual requirements. 
       FIG.  8    is a schematic structural diagram of a signal detection part according to at least one embodiment of the present disclosure. As shown in  FIG.  8   , in at least one embodiment of the present disclosure, in addition to the optical sensor  131 , the signal detection part  130  may further include a light source  132  and a light transmission portion  133 . 
     The optical sensor  131  may be, for example, an image sensor, so as to be configured to acquire an optical image of the detection chip for analysis. For example, the optical sensor  131  may include a charge coupled device (CCD) or a complementary metal oxide semiconductor (CMOS). However, it should be understood that in other embodiments, the optical sensor  131  may also be a photodiode, a photo resistor, an infrared sensor, an ultraviolet sensor, etc., and the embodiments of the present disclosure are not limited thereto. 
     The light source  132  may be configured to provide light in use to illuminate the detection chip. The light transmission portion  133  may be configured to transmit the light provided by the light source  132  to the detection chip and transmit the light reflected or transmitted by the detection chip to the optical sensor  131  in use. 
     For example, the light source  132  may be of various types that may emit visible light, infrared light, etc., for example, including a laser or a fluorescent light source. The wavelengths of the laser and the fluorescent light source may be selected according to actual needs, which is not limited in the embodiments of the present disclosure. 
       FIG.  9    is a schematic structural diagram of a specific example of a signal detection part according to at least one embodiment of the present disclosure. As shown in  FIG.  9   , in some embodiments, the light transmission portion  133  may include a 90° turning prism system  1331  and a reflective light path system  1332 . The 90° turning prism system  1331  may be configured to transmit light from the detection chip to the optical sensor  131 . The reflective light path system  1332  may be configured to transmit light from the light source  132  to illuminate the detection chip, and the reflective light path system  1332  may further include an optical filter. The optical filter is on a light path from the detection chip to the optical sensor  131  to filter the light transmitted on the light path, thereby only allowing the light with a set wavelength to pass through. Both the 90° turning prism system  1331  and the reflective light path system  1332  may adopt conventional designs in the art, which will not be repeated in the present disclosure. 
     As shown in  FIG.  9   , in some embodiments, the signal detection part  130  may further include an objective lens  134 . The objective lens  134  is configured to acquire light from the detection chip. For example, the objective lens  134  may include a lens. 
     As shown in  FIG.  9   , in some embodiments, the signal detection part  130  may further include a holder  135 . The holder  135  is used for fixing and carrying at least portion of components in the signal detection part  130 , such as the light source  132  and the light transmission portion  133 . In some embodiments, the holder  135  may also be configured to adjust a distance between the light transmission portion  133  and the detection chip, so that the detection chip is at the focal point of the light transmission portion  133 . The holder  135  may adopt a conventional design in the field, which will not be repeated in the present disclosure. 
     In some embodiments, the signal detection part  130  may further include a spirit level H′, to detect whether the signal detection part  130  is level. For example, the spirit level H′ may be connected to the light transmission portion  133 , the optical sensor  131 , the light source  132 , and the like. In  FIG.  9   , as an example, the spirit level H′ is connect to the 90° turning prism system  1331 . However, it should be understood that the embodiments of the present disclosure are not limited thereto. The spirit level H′ may be connected to other components of the signal detection part  130  by any suitable means, such as adhesing, magnetic adsorption, threaded connection, etc., which are not limited in the embodiment of the present disclosure. The spirit level H′, for example, may be a bubble level, an inductive level, a capacitive level, etc., which is not limited in the embodiments of the present disclosure. For example, the spirit level H′ can make the light transmitted from the light transmission portion  133  to the detection chip perpendicular to the detection chip or the light from the detection chip enter the optical transmission portion  133  vertically, thereby facilitating subsequent signal processing. For example, a step of performing angle correction on the image of the detection chip may be omitted. 
       FIG.  10    is a schematic structural diagram of a loading part, a temperature control part and a signal detection part in an assembled state according to at least one embodiment of the present disclosure. As shown in  FIG.  10   , the analysis device may include a base  101 , and the loading part  110 , the temperature control part  120  and the signal detection part  130  are all arranged on the base  101 . For example, the loading part  110 , the temperature control part  120  and the signal detection part  130  are fixed on the base  101  by using a screw, a clamp, adhesive, and the like. The temperature control part  120  and the signal detection part  130  may be arranged along a moving path of the movable platform  1112  in the loading part  110 , so that the detection chip holding on the stage  1111  may be moved to the temperature control part  120  by the movement of the movable platform  1112  to perform temperature control and may be moved to the signal detection part  130  to acquire the light from the detection chip. 
     However, it should be understood that the arrangement shown in  FIG.  10    is exemplary, and different arrangements may be used according to the different structures and shapes of the loading part  110 , the temperature control part  120 , and the signal detection part  130 , which are not limited in the embodiments of the present disclosure. 
       FIG.  11    is a schematic block diagram of an analysis device according to at least one embodiment of the present disclosure. As shown in  FIG.  11   , the analysis device  100  further includes one or more controllers  140 . The one or more controllers  140  may be configured to perform at least one of the flowing operations: 
     connecting to the loading part  110  in a signal connection manner, to control the loading part  110  to move;
 
connecting to the heater  121  in a signal connection manner, to control the heater  121  to heat the detection chip;
 
connecting to the cooler  122  in a signal connection manner, to control the cooler  122  to cool the detection chip; and
 
connecting to the optical sensor  131  in a signal connection manner, to analyze the light from the detection chip.
 
     The controller  140  may be implemented, for example, by a central processing unit (CPU), a digital signal processor (DSP), a single-chip microcomputer, a field programmable gate array (FPGA), a complex programmable logic device (CPLD), or an application specific integrated circuit (ASIC) and the like, and the embodiments of the present disclosure are not limited thereto. 
     It should be understood that, in some embodiments, the controller  140  may be implemented as a plurality of sub-controllers, and the plurality of sub-controllers may respectively perform at least one of the foregoing operations. The plurality of sub-controllers may be separately provided or integrated in one controller, and the embodiments of the present disclosure are not limited thereto. 
     As shown in  FIG.  11   , in some embodiments, the analysis device  100  may further include a communication part CP. The communication part CP is configured to form a signal connection with a mobile terminal, a server, and the like. The signal connection may be a wired connection or a wireless connection, which is not limited in the embodiments of the present disclosure. Exemplary, the wireless connection includes Wi-Fi, Bluetooth, Wireless Direct, and infrared ray. Exemplary, the wired connection includes Universal Serial Bus (USB), FireWire, Thunderbolt, or any connection that requires a physical cable. 
       FIG.  12   ,  FIG.  13    and  FIG.  14    are respectively a front view, a rear view and a perspective view of an analysis device according to at least one embodiment of the present disclosure. As shown in  FIG.  12   , the analysis device according to at least one embodiment of the present disclosure may further include a display screen  150 . The display screen  150  is configured to display. For example, the display screen  150  may be a liquid crystal display screen, an organic light emitting diode (OLED) display screen, a quantum dot light emitting diode (QLED) display screen, a micro light emitting diode display screen, an electronic ink screen, and an electronic paper display screen, etc., and the embodiments of the present disclosure are not limited thereto. For example, the display screen  150  may be a touch display screen to receive inputting of a user. However, it should be understood that, in some embodiments, the analysis device may not include the display screen  150 , but may be connected to a separately provided display screen or output data, such as analysis result, in the form of digital file or physical file, and the embodiments of the present disclosure are not limited thereto. 
     As shown in  FIG.  13   , the analysis device according to at least one embodiment of the present disclosure may further include a power interface  160 . The analysis device is connected to a power source by the power interface  160  to acquire electrical energy. However, it should be understood that, in some embodiments, the analysis device may not have the power interface  160 , but has a built-in primary battery or a built-in secondary battery, or a built-in solar battery, and the embodiments of the present disclosure are not limited thereto. 
     As shown in  FIG.  13   , the analysis device according to at least one embodiment of the present disclosure may further include a data transmission interface  170 . The data transmission interface  170  is configured to output data of the analysis device, such as analysis result, to an external device, or transmit data from the external device to the analysis device. The data transmission interface  170  may be, for example, a universal serial bus (USB) interface, a serial advanced technology attachment (SATA) interface, or the like. In at least one embodiment, the data transmission interface and the power interface may be combined into one interface, such as a USB interface, which can be used to transmit data as well as power. 
     As shown in  FIG.  12   , the analysis device according to at least one embodiment of the present disclosure may further include a key  180 . The key  180  is configured to acquire a user&#39;s input instruction and may be a mechanical key, an optical key, etc., and the embodiments of the present disclosure are not limited thereto. It should be understood that the shape and number of the keys  180  in  FIG.  12    are only exemplary, and the embodiment of the present disclosure does not limit this. 
     As shown in  FIG.  12   , the analysis device according to at least one embodiment of the present disclosure may further include a chip loading port  190 . The chip loading port  190  allows the stage  1111  to be protruded from the chip loading port, to receive the detection chip. 
     As shown in  FIG.  12   , the analysis device according to at least one embodiment of the present disclosure may further include a touch sensor  192 . The touch sensor  192  is configured to receive and detect a user&#39;s touch operation, and convert the user&#39;s touch operation into an electrical signal for transmission to a controller or other control devices, such as the controller  140  or an external server. The touch sensor  192  may be, for example, a capacitive touch sensor, a resistive touch sensor, etc., and the embodiments of the present disclosure are not limited thereto. It should be understood that when the display screen  150  is a touch screen or the analysis device includes other forms of input devices (for example, a key  180 , a microphone, etc.), the analysis device may not include the touch sensor  192 . 
     As shown in  FIG.  14   , the analysis device according to at least one embodiment of the present disclosure may further include a heat dissipation port  191 . For example, the heat dissipation port  191  may be used for releasing heat of the controller  140  or the temperature control part  120 . The heat dissipation port  191  may be packaged in a dust-free package to prevent dust from entering the inside of the analysis device. 
     At least one embodiment of the present disclosure also provides an analysis system.  FIG.  15    is a schematic block diagram of an analysis system according to at least one embodiment of the present disclosure. As shown in  FIG.  15   , the analysis system  200  includes an analysis device  210  and a detection chip  220 . For example, the combination of the analysis device  210  and the unused detection chip  220  may be provided to a user for use by the user. The analysis device  210  may be any analysis device described above. The detection chip  220  may be any detection chip described above. 
     It should be understood that in some embodiments of the present disclosure, the analysis system  200  may further include more components or parts, and the embodiments of the present disclosure are not limited thereto. The detailed description and technical effect of the analysis device  210  and the detection chip  220  may refer to the above description of the reaction device, which will not be repeated here. 
     At least one embodiment of the present disclosure also provides a method for operating an analysis device. The method is applicable to the analysis device according to any embodiment of the present disclosure.  FIG.  16    is a flow schematic diagram of a method for operating an analysis device according to at least one embodiment of the present disclosure. As shown in  FIG.  16   , the method  300  for operating an analysis device according to at least one embodiment of the present disclosure may include the flowing steps: 
     step S 320 , moving the loading part carrying the detection chip to the temperature control part. 
     In step S 320 , the loading part carrying the detection chip may be manually moved to the temperature control part. In the case where the loading part includes a transport structure configured to carry the detection chip and at least partially be driven and a driver configured to be capable of driving the transport structure, the step S 320  may include driving the transport structure carrying the detection chip by the driver, so as to move the detection chip to the temperature control part. 
       FIG.  17 A ,  FIG.  17 B  and  FIG.  17 C  show a process of implementing the step S 320  according to at least one embodiment of the present disclosure. In  FIG.  17 B  and  FIG.  17 C , the detection chip C is shown for convenience of description. As shown in  FIG.  17 A , the stage  1111  of the analysis device according to at least one embodiment of the present disclosure is protruded from the chip loading port  190  of the analysis device, to receive the detection chip. As shown in  FIG.  17 B , the detection chip C is at the first position P 1 , and the detection chip C is received and held on the stage  1111  at the first position P 1 . As shown in  FIG.  17 C , the detection chip C is at a second position P 2 , and the second position P 2  allows the temperature control part to adjust the temperature of the detection chip C. 
     As shown in  FIG.  16   , the method  300  for operating an analysis device according to at least one embodiment of the present disclosure may further include: 
     step S 340 , adjusting a temperature of the detection chip by the heater and the cooler. 
     In a case where the detection chip includes a heating electrode and the heater includes a contact electrode, the step S 340  may include applying an electrical signal to the heating electrode of the detection chip by the contact electrode, to heat the detection chip by the heating electrode. 
     In some embodiments, the step S 340  further includes: cyclically maintaining the detection chip at at least two temperatures by the heater and the cooler. For example, the detection chip is heated by the heater and is cooled by the cooler, so as to implement a plurality of temperature control cycles to the detection chip, such as thirty temperature control cycles, so that the detection chip performs PCR thermal cycle amplification. Each of a plurality of temperature control cycles includes: maintaining the detection chip at 95° C. for 10 seconds; maintaining the detection chip at 50° C. for 10 seconds; and maintaining the detection chip at 72° C. for 10 seconds. It should be understood that the temperature control cycle described above is only exemplary, and the embodiments of the present disclosure do not limit this.  FIG.  18    is a temperature change diagram of a temperature control cycle according to at least one embodiment of the present disclosure. In  FIG.  18   , the horizontal axis represents time, the unit is minute, and the vertical axis represents temperature, the unit is degrees Celsius. 
     As shown in  FIG.  16   , the method  300  for operating an analysis device according to at least one embodiment of the present disclosure may further include: 
     step S 360 , moving the loading part holding the detection chip to the signal detection part, and acquiring light from the detection chip by the optical sensor. 
     In the step S 360 , the loading part holding the detection chip may be manually moved to the signal detection part. In a case where the loading part includes a transport structure configured to carry the detection chip and at least partially be driven and a driver configured to be capable of driving the transport structure, the step S 360  may include driving the transport structure holding the detection chip by the driver, to move the detection chip to the signal detection part. 
       FIG.  19    shows a cross-sectional view of an analysis device according to at least one embodiment of the present disclosure when the step S 360  is performed. In  FIG.  19   , the detection chip C is shown for convenience of description. As shown in  FIG.  19   , the detection chip C is at the third position P 3 , and the third position P 3  allows the optical sensor  131  of the signal detection part  130  to acquire the light from the detection chip. 
     The step S 360  may further include: 
     illuminating the detection chip by light, and acquiring the light reflected or transmitted by the detection chip as the light from the detection light by the optical sensor. 
     In a case where the optical sensor includes an image sensor, the step S 360  may include acquiring an optical image of the detection chip by the image sensor. In addition, in a case where the signal detection part further includes a light source and a light transmission part, the step S 360  may include: providing light by the light source; transmitting the light provided by the light source by the light transmission part, to illuminate the detection chip; and transmitting the light reflected or transmitted by the detection chip as the light from the detect chip to the optical sensor (or the image sensor included by the optical sensor) by the light transmission part. 
     As shown in  FIG.  16   , the method  300  for operating an analysis device according to at least one embodiment of the present disclosure may further include: 
     step S 380 , analyzing the light from the detection chip to obtain the analysis result. 
     It should be understood that one or more steps and at least portion of the sub-steps in the above-mentioned method  300  may be executed by software or firmware, for example, executed by a mobile terminal, a server, etc. being in signal connection with the analysis device, and the embodiments of the present disclosure are not limited thereto. 
     In some embodiments, in a case where the acquiring the light from the detection chip by the optical sensor includes acquiring an optical image of the detection chip by the image sensor, the step S 380  may include: 
     step S 3802 , converting the optical image to a grayscale image. 
     For example, step S 3802  may further include performing Gaussian smoothing processing on the grayscale image, to reduce the influence of noise. 
     For example, the method  300  may further include: 
     step S 3804 , identifying a reaction chamber of the detection chip in the grayscale image. 
     In a case where the detection chip includes a circular reaction chamber, in the step S 3804 , the reaction chamber may be detected out in the grayscale image by a Hough circle transformation algorithm, but it should be understood that the embodiment of the present disclosure is not limited to this. 
     For example, the method  300  may further include: 
     step S 3806 , determining a spaced line in the grayscale image according to an identified reaction chamber. 
       FIG.  20    is a flow schematic diagram of the step S 380  according to at least one embodiment of the present disclosure. 
     In some embodiments, the step S 3806  may include: drawing a reaction chamber on an auxiliary image that is as large as the grayscale image according to coordinates of a center and a radius of an image zone of the identified reaction chamber. It should be understood that the auxiliary image and the grayscale image have the same size and the number of pixels, and in the auxiliary image, a pixel value of a circle corresponding to the reaction chamber and a pixel value of a center of the circle may be set to any non-zero value, and pixel values of a region outside the reaction chamber may be set to zero. 
     In some embodiments, the step S 3806  may further include: calculating a sum of pixel values of each row of pixels and a sum of the pixel values of each column of pixels in the auxiliary image. 
       FIG.  21 A  is a distribution diagram of sums of row pixel values of an auxiliary image according to at least one embodiment of the present disclosure, and  FIG.  21 B  is a distribution diagram of sums of column pixel values of an auxiliary image according to at least one embodiment of the present disclosure. 
     In some embodiments, before calculating the sum of pixel values of each row of pixels and the sum of pixel values of each column of pixels in the auxiliary image, the step S 3806  may further include performing processing such as angle correction and denoising on the auxiliary image. 
     In some embodiments, the step S 3806  may further include: determining a minimum value of sums of pixel values in a row direction and a minimum value of the sums of pixel values in a column direction in the auxiliary image; taking a row coordinate corresponding to the minimum value in the row direction as a row coordinate of the spaced line extending along the column direction in the grayscale image, and taking a column coordinate corresponding to the minimum value in the column direction as a column coordinate of the spaced line extending along the row direction in the grayscale image. For example, in some embodiments, performing derivation on the sum of pixel values of each row of the auxiliary image and the sum of pixel values of each column of the auxiliary image, performing sign function quantization on derivation results, and performing derivation on results of the quantization, and performing denoising, so as to filter out a wave peak and obtain a trough. The trough in the row direction (that is, the minimum value) corresponds to the spaced line extending in the column direction, and the trough in the column direction (that is, the minimum value) corresponds to the spaced line extending in the row direction. 
       FIG.  22 A  is a schematic diagram of troughs in the row direction of an auxiliary image according to at least one embodiment of the present disclosure, and  FIG.  22 B  is a schematic diagram of troughs in the column direction of an auxiliary image according to at least one embodiment of the present disclosure. 
     For example, the method  300  may further include: 
     step S 3808 , Dividing the grayscale image, to obtain a plurality of chamber image blocks according to the spaced line. 
     In some embodiments, the step S 3803  may include: taking the row coordinate of the minimum value of the sums of the pixel values in the row direction of the auxiliary image as the row coordinate of the spaced line extending along the column direction, and taking the column coordinate of the minimum value of the sums of the pixel values in the column direction of the auxiliary image as the column coordinate of the spaced line extending along the row direction, thereby obtaining the spaced line in the grayscale image.  FIG.  23    is an example of an auxiliary image according to at least one embodiment of the present disclosure. The auxiliary image also schematically shows positions of the troughs (that is, the minimum value) of the sums of pixel values in the row direction and the position of the troughs (that is, the minimum value) of the sums of pixel values in the column direction, which correspond to the spaced lines in the grayscale image. 
     For example, the method  300  may further include: 
     step S 3810 , determining a chamber image block with a pixel mean square error greater than a preset threshold in the plurality of chamber image blocks as a target image block. 
     In some embodiments, the step S 3810  may further include: 
     if the reaction chamber identified in the step S 3804  overlaps with the spaced line, determining the reaction chamber as an invalid reaction chamber, otherwise determining the reaction chamber as an effective reaction chamber; calculating the pixel mean square error of the chamber image blocks in which the effective reaction chamber is located, and determining a chamber image block with a pixel mean square error greater than a preset threshold as a target image block. 
     In some embodiments, the step S 380  may further include: determining an initial copy number by the following formula according to the number of target image blocks, the total number of reaction chambers of the detection chip and the sample dilution factor: 
         c =[1 n (1− f/n )]/ m  
 
     In the above formula, the c represents the initial copy number, the f represents the number of target image blocks, the m represents the sample dilution factor, and the n represents the total number of reaction chambers of the detection chip. 
     The following statements should be noted: 
     (1) The accompanying drawings involve only the structure(s) in connection with the embodiment(s) of the present disclosure, and other structure(s) can be referred to common design(s).
 
(2) In case of no conflict, features in one embodiment or in different embodiments can be combined to obtain a new embodiment.
 
     What are described above is related to the specific embodiments of the disclosure only and not limitative to the scope of the present disclosure. The protection scope of the present disclosure shall be based on the protection scope of the claims.