Analytical device for use in test chips, its operating method, and analytical system

Abstract

An analytical device, analytical system, and method for operating an analytical device for use with a test chip are provided. The analytical device includes a mounting unit, a temperature control unit, and a signal detection unit. The mounting unit is configured to receive and mount the test chip during use and to allow the test chip to be moved. The temperature control unit includes a heater and a cooler. The heater is configured to heat the test chip, and the cooler is configured to cool the test chip. The signal detection unit includes an optical sensor. The optical sensor is configured to receive light from the test chip and perform detection based on the light.

Description

[Technical field]

[0001] An embodiment of the present disclosure relates to an analysis device used in a test chip, an operating method thereof, and an analysis system.

[0002] [CROSS REFERENCE TO RELATED APPLICATIONS] This application claims priority to Chinese patent application having application number 202010367897.7, filed on April 30, 2020, the entire contents of which are hereby incorporated by reference into this application. [Background technology]

[0003] Digital polymerase chain reaction chip technology (dPCR) realizes absolute quantification of single molecule DNA by sufficiently diluting the nucleic acid sample and making the number of sample templates in each reaction chamber no more than 1. Due to its advantages of high sensitivity, high specificity, high test throughput and accurate quantification, it is widely used in clinical diagnosis, gene instability analysis, single cell gene expression, environmental microbial detection and prenatal diagnosis. Summary of the Invention [Means for solving the problem]

[0004] At least one embodiment of the present disclosure provides an analysis device for use with a test chip, the analysis device including a mounting unit, a temperature control unit, and a signal detection unit, wherein the mounting unit is configured to receive and place the test chip during use and to move the test chip; The temperature control unit includes a heater and a cooler, where the heater is configured to heat the test chip and the cooler is configured to cool the test chip; The signal detection portion includes an optical sensor, where the optical sensor is configured to receive light from the test tip and perform detection based on the light.

[0005] For example, in an analysis device according to at least one embodiment of the present disclosure, the mounting unit includes: a transport structure configured to mount the test chip and to be driven at least locally; a driver configured to drive the transport structure to reciprocate the test tip between a first position, a second position, and a third position; wherein the first position allows the test tip to be received in the transport structure; the second position allows the temperature controller to adjust the temperature of the test tip; The third position enables the optical sensor of the signal detection portion to receive the light from a test tip.

[0006] For example, in an analytical device according to at least one embodiment of the present disclosure, the transport structure comprises: a stage configured to mount the test chip during use; a movable platform connected to the driver and configured to move in response to actuation of the driver; a holder configured to connect the stage and the moveable platform such that the stage can be actuated when the moveable platform is actuated.

[0007] For example, in an analysis device according to at least one embodiment of the present disclosure, the holder includes: a first portion configured to receive the stage; a second part configured to be connected to the moveable platform in use; Here, the first portion extends along a first direction, the second portion extends along a second direction, and the first direction is perpendicular to the second direction.

[0008] For example, in an analytical apparatus relating to at least one embodiment of the present disclosure, the stage has a cut-out area so that when the test chip is placed on the stage, the side of the test chip that comes into contact with the stage is at least locally exposed to the cooler.

[0009] For example, in the analysis device according to at least one embodiment of the present disclosure, the test chip includes a heating electrode, the heater includes a contact electrode, the contact electrode being configured to be in electrical contact with the heating electrode of the test tip during use; The heater is further configured to apply an electrical signal to the heating electrode of the test tip through the contact electrode, thereby causing the heating electrode to heat the test tip.

[0010] For example, in the analysis device according to at least one embodiment of the present disclosure, the heater is configured to heat the test chip by providing infrared heating or airflow to the test chip.

[0011] For example, in the analysis device according to at least one embodiment of the present disclosure, the temperature control unit further includes a temperature sensor, and the temperature sensor is configured to detect the temperature of the test chip.

[0012] For example, in an analytical device relating to at least one embodiment of the present disclosure, the temperature sensor and the cooler are configured to be spaced apart from each other, allowing the test chip to be interposed between the temperature sensor and the cooler.

[0013] For example, in the analysis device according to at least one embodiment of the present disclosure, the temperature sensor includes an infrared temperature sensor or a thermocouple temperature sensor.

[0014] For example, in the analysis device according to at least one embodiment of the present disclosure, the cooler includes a fan or a semiconductor cooling sheet.

[0015] For example, in the analysis device according to at least one embodiment of the present disclosure, the signal detection unit includes: a light source configured, in use, to provide light to illuminate the test tip; and a light transmitting portion configured, during use, to transmit the light provided by the light source to the test tip, and to transmit light reflected or transmitted by the test tip to the optical sensor.

[0016] For example, in the analysis device according to at least one embodiment of the present disclosure, the light source includes a fluorescent light source or a laser.

[0017] For example, in the analytical device according to at least one embodiment of the present disclosure, the optical sensor is an image sensor configured to collect optical images of the test chip for analysis.

[0018] For example, in an analysis device according to at least one embodiment of the present disclosure, the analysis device further includes a controller, A signal is connected to the mounting unit to control the mounting unit to move; A signal is connected to the heater to control the heater to heat the test tip; A signal is connected to the cooler to control the cooler to cool the test chip; and analyzing the light from the test tip by being signal-coupled to the optical sensor.

[0019] For example, the analysis device according to at least one embodiment of the present disclosure further includes at least one of the group consisting of a display screen, a touch sensor, a power supply interface, and a data transmission interface.

[0020] At least one embodiment of the present disclosure further provides an analysis system, comprising: An analysis device according to any one of the embodiments of the present disclosure; and the test chip.

[0021] At least one embodiment of the present disclosure further provides a method of operating an analytical device according to any embodiment of the present disclosure, comprising: The mounting unit on which the test chip is placed is moved to the temperature control unit; adjusting the temperature of the test chip by the heater and the cooler; the mounting section on which the test chip is placed is moved to the signal detection section, and the optical sensor acquires the light from the test chip; Analyzing the light from the test tip to obtain an analytical result.

[0022] For example, in the method according to at least one embodiment of the present disclosure, the step of adjusting the temperature of the test chip by the heater and the cooler includes: The heater and the cooler cycle the test chip through at least two temperatures.

[0023] For example, in a method according to at least one embodiment of the present disclosure, the step of acquiring the light from the test tip with the optical sensor includes acquiring an optical image of the test tip with an image sensor; The step of obtaining an analysis result by analyzing the optical information includes: converting the optical image into a grayscale image; identifying reaction chambers of the test chip from the grayscale image; determining a partition line in the grayscale image based on the identified reaction chamber; Dividing the grayscale image based on the partition lines to obtain a plurality of chamber image blocks; The method further comprises determining, as a target image block, a chamber image block having a pixel standard deviation greater than a predetermined threshold value among the plurality of chamber image blocks. [Brief description of the drawings]

[0024] In order to more clearly describe the technical solutions of the embodiments of the present disclosure, the drawings of the embodiments are briefly introduced below. Obviously, the drawings in the following description do not limit the present disclosure, but only relate to some embodiments of the present disclosure.

[0025] [Figure 1] FIG. 1 is a schematic block diagram of an analytical device used in a test chip according to at least one embodiment of the present disclosure. [Diagram 2] FIG. 2 is a schematic block diagram of a mounting portion in accordance with at least one embodiment of the present disclosure. [Diagram 3] FIG. 2 is a structural schematic diagram of a transport structure in an exploded state in accordance with at least one embodiment of the present disclosure. [Figure 4] FIG. 2 is a structural schematic diagram of an assembled transportation structure in accordance with at least one embodiment of the present disclosure. [Diagram 5] FIG. 1 is a schematic block diagram of a test chip according to at least one embodiment of the present disclosure. [Figure 6] FIG. 2 is a structural schematic diagram of a temperature control unit in a disassembled state according to at least one embodiment of the present disclosure. [Figure 7] FIG. 2 is a structural schematic diagram of an assembled state of a temperature control device according to at least one embodiment of the present disclosure. [Figure 8] FIG. 2 is a schematic diagram illustrating a configuration of a signal detection unit according to at least one embodiment of the present disclosure. [Figure 9] FIG. 2 is a schematic diagram showing a specific configuration of a signal detection unit according to at least one embodiment of the present disclosure. [Figure 10] 1 is a structural schematic diagram of a mounting unit, a temperature control unit, and a signal detection unit in an assembled state according to at least one embodiment of the present disclosure. [Figure 11] FIG. 1 is a schematic block diagram of an analysis device in accordance with at least one embodiment of the present disclosure. [Figure 12] FIG. 1 is a front view of an analytical device in accordance with at least one embodiment of the present disclosure. [Figure 13] FIG. 2 is a rear view of an analytical device in accordance with at least one embodiment of the present disclosure. [Figure 14]FIG. 1 is a perspective view of an analytical device in accordance with at least one embodiment of the present disclosure. [Figure 15] FIG. 1 is a schematic block diagram of an analysis system in accordance with at least one embodiment of the present disclosure. [Figure 16] 1 is a flow chart of a method of operating an analytical device in accordance with at least one embodiment of the present disclosure. [Figure 17A] 1 illustrates a process for performing step S320 in accordance with at least one embodiment of the present disclosure. [Figure 17B] 1 illustrates a process for performing step S320 in accordance with at least one embodiment of the present disclosure. [Figure 17C] 1 illustrates a process for performing step S320 in accordance with at least one embodiment of the present disclosure. [Figure 18] FIG. 4 is a temperature change diagram of a temperature control cycle in accordance with at least one embodiment of the present invention. [Figure 19] 1 illustrates a cross-sectional view of an analytical device in accordance with at least one embodiment of the present disclosure upon execution of step S360. [Figure 20] 11 is a flowchart of step S380 in accordance with at least one embodiment of the present disclosure. [Figure 21A] FIG. 13 is a distribution diagram of row pixel value sums of an auxiliary image in accordance with at least one embodiment of the present disclosure. [Figure 21B] FIG. 13 is a distribution diagram of column pixel value sums of an auxiliary image in accordance with at least one embodiment of the present disclosure. [Figure 22A] FIG. 2 is a schematic diagram of row-wise valleys in an auxiliary image in accordance with at least one embodiment of the present disclosure. [Figure 22B] FIG. 13 is a schematic diagram of column-wise valleys in an auxiliary image in accordance with at least one embodiment of the present disclosure. [Figure 23] 1 is an example of an auxiliary image in accordance with at least one embodiment of the present disclosure. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0026] In order to more clearly describe the objectives, technical solutions and advantages of the present disclosure, the technical solutions of the embodiments of the present disclosure will be described below clearly and completely with reference to the drawings of the embodiments of the present disclosure. It is obvious that the described embodiments are only some embodiments of the present disclosure, and not all embodiments. Based on the described embodiments of the present disclosure, any other embodiments that a person skilled in the art can obtain without creative labor are all within the scope of protection of the present disclosure.

[0027] Unless otherwise defined, technical or scientific terms used in this disclosure should have the ordinary meanings understood by those skilled in the art. The terms "first", "second" and similar terms used in this disclosure do not indicate any order, quantity or importance, but are merely used to distinguish different components. Similar terms such as "comprise" and "included" mean that the element or thing appearing before the term includes the element or thing listed after the term and their equivalents, but do not exclude other elements or things. Similar terms such as "connected" and "connected to each other" are not limited to physical or mechanical connections, but may include electrical connections, whether direct or indirect. Terms such as "upper", "lower", "left", "right" and the like are merely used to indicate relative positional relationships, and when the absolute position of the described object is changed, the relative positional relationships may change accordingly.

[0028] To ensure clarity and conciseness in the following description of the embodiments of the present disclosure, the present disclosure omits detailed descriptions of known features and components.

[0029] dPCR products generally require multiple set devices to obtain analysis results, which results in long test times, high test costs, many operation steps, and the risk of reagent contamination.

[0030] At least one embodiment of the present disclosure provides an analytical device, an analytical system, and a method for operating an analytical device used with a test chip, and the analytical device of the embodiment integrates and integrates a mounting unit, a temperature control unit, and a signal detection unit, thereby realizing detection for the test chip in a single device, reducing the number of required set devices, simplifying the operation steps, shortening the detection time, and reducing the risk of reagent contamination.

[0031] 1 is a schematic block diagram of an analysis device used in a test chip according to at least one embodiment of the present disclosure. As shown in FIG. 1, an analysis device 100 used in a test chip according to at least one embodiment of the present disclosure may include at least a mounting unit 110, a temperature control unit 120, and a signal detection unit 130.

[0032] The mounting portion 110 is configured to receive and mount the test chip during use and to allow the test chip to be moved to the temperature control portion and the signal detection portion.

[0033] The temperature control unit 120 includes a heater 121 and a cooler 122. The heater 121 is configured to heat the test chip mounted on the analysis device, and the cooler 122 is configured to cool the test chip mounted on the analysis device, thereby realizing control over the temperature of the test chip.

[0034] The signal detection unit 130 includes an optical sensor 131. The optical sensor 131 is configured to receive light from the test chip and perform detection based on the light from the test chip.

[0035] It should be understood that the test chips described in each embodiment of the present disclosure may be any type of biological or chemical test chip, such as various microfluidic chips, and the embodiments of the present disclosure are not limited thereto.

[0036] 2 is a schematic block diagram of a mounting portion 110 in accordance with at least one embodiment of the present disclosure. The mounting portion 110 can include a transport structure 111 and a driver 112.

[0037] The transport structure 111 is configured to mount the test tip and to be driven at least in part. The driver 112 can drive the transport structure 111, for example, is operably connected to the transport structure 111, and is configured to reciprocate the test tip between a first position, a second position, and a third position. In at least one embodiment, the first position allows the test tip to be accommodated in the transport structure 111, i.e., allows a user to place a test tip loaded with a detection sample in the loading section 110. The second position allows the temperature control section 120 to adjust the temperature of the test tip. The third position allows the optical sensor 131 of the signal detection section 130 to receive light from the test tip. For example, FIG. 17B described below shows an example of the first position P1 in at least one embodiment of the present disclosure. For example, FIG. 17C described below shows an example of the second position P2 in at least one embodiment of the present disclosure. For example, FIG. 19 described below shows an example of the third position P3 in at least one embodiment of the present disclosure.

[0038] However, it should be understood that in some embodiments, the mounting portion 110 may not include the driver 112, thereby allowing the transport structure 111 to be moved (e.g., pushed or pulled) manually, and embodiments of the present disclosure are not limited in this respect.

[0039] 3 is a schematic diagram of a disassembled transport structure in accordance with at least one embodiment of the present disclosure, and FIG. 4 is a schematic diagram of an assembled transport structure in accordance with 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 holder 1113.

[0040] The stage 1111 is configured to place a test chip thereon during use, and in the example shown in the figure, the stage 1111 is a rectangular plate and is movably attached to a holder 1113. The stage 1111 has a first recessed area RA1 for accommodating the test chip, and the contour of the first recessed area RA1 is generally basically the same as the outer shape of the test chip, both being rectangular as shown in the figure, and in order to facilitate the user's insertion and removal of the test chip with their fingers, one side of the first recessed area RA1 has, for example, a semicircular recessed portion protruding outward to accommodate the fingers holding the test chip.

[0041] For example, the stage 1111 is formed of a high temperature resistant material, which may be, for example, metal, plastic, ceramic, rubber, resin, etc. The heat distortion temperature of the high temperature resistant material forming the stage 1111 is, for example, 100° C., 200° C., 300° C., 400° C., 500° C. or higher. The stage 1111 may be formed of a material that is resistant to high temperatures and has poor thermal conductivity. For example, in one specific embodiment, the stage 1111 is formed of ceramic, which is not only light in weight but can also withstand high temperatures.

[0042] In some embodiments, the stage 1111 may further include a level H, which detects whether the stage 1111 is horizontal. For example, if the stage 1111 has a second recessed area RA2, the level H can be accommodated and fixed in the second recessed area RA2. However, it should be understood that the stage 1111 may not have the second recessed area RA2, and the 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 level H may be, for example, a bubble level, an inductance level, a capacitance level, or the like, and the embodiments of the present disclosure are not limited thereto. The level H can hold the test chip placed on the stage 1111 horizontally, which helps the optical sensor 131 receive light from the test chip.

[0043] 3 and 4, the stage 1111 may have a cutout area HA, so that when the test chip is placed on the stage 1111, the side surface of the test chip in contact with the stage 1111 is at least locally exposed, for example, to the cooler 122 of the temperature control unit 120. According to actual requirements, the cutout area HA may have any suitable shape, such as a circle, a triangle, a rectangle, a pentagon, a hexagon, or other irregular shape. Also, for example, the cutout area HA may have one or more openings, and the embodiment of the present disclosure is not limited thereto. The size of the projection of the test chip on the plane where the cutout area HA is located is larger than the size of the cutout area HA, so that the test chip is placed on the stage 1111.

[0044] The movable platform 1112 is operably connected to the driver 112, and is configured to move when driven by the driver 112. The driver 112 may be, for example, a motor, and the movable platform 1112 is, for example, connected to a drive end of the motor. For example, the driver 112 may be a rotary motor, the drive end of which is connected to a lead screw S, thereby rotating the lead screw S, and the movable platform 1112 is connected to the lead screw S by a nut threadedly engaged with the lead screw S, thereby converting the rotation of the lead screw S into a horizontal movement, so that the movable platform 1112 can move when driven by the driver 112. In addition, a guide rod G may be installed parallel to the lead screw S. The movable platform 1112 is movably connected to the guide rod G. The guide rod G serves to restrain the movable platform 1112. It should be understood that the numbers of the guide rods G and the lead screws S shown in FIG. 3 and FIG. 4 are both exemplary, and the embodiments of the present disclosure are not limited thereto. For example, the driver 112 can be a linear motor, and the mover of the linear motor can be connected to the movable platform 1112, thereby driving the movable platform 1112 to move. The embodiments of the present disclosure are not limited to how the driver 112 drives the movable platform 1112, and can further convert rotational motion into horizontal motion through, for example, a rack and pinion combination.

[0045] The movable platform 1112 may be made of any rigid material, such as metal, plastic, ceramic, rubber, resin, etc., and the embodiments of the present disclosure are not limited thereto. It should also be understood that the shapes of the movable platform 1112 shown in Figures 3 and 4 are also exemplary, and the movable platform 1112 may have any suitable shape according to actual requirements.

[0046] The holder 1113 is configured to connect the stage 1111 and the movable platform 1112 such that the stage 1111 can be driven when the movable platform 1112 is driven.

[0047] As shown in the dashed box in FIG. 3, the holder 1113 may include a first portion 1113A and a second portion 1113B. The first portion 1113A is configured to mount the stage 1111 during use. The second portion 1113B is configured to be connected to the movable platform 1112 during use. The first portion 1113A extends along a first direction, and the second portion 1113B extends along a second direction, and the first direction is perpendicular to the second direction. Forming the holder 1113 in an L-shape or T-shape reduces the size in a single direction, which helps reduce the overall volume of the analysis device.

[0048] A first portion 1113A of the holder 1113 is connected to the stage 1111 by, for example, springs or the like, and the horizontal state of the stage 1111 can be adjusted by adjusting the corresponding springs, for example, by using four springs corresponding to the four corners of the stage 1111.

[0049] The second portion 1113B of the holder 1113 may be removably or fixedly connected to the movable platform 1112, for example by screws, thereby enabling the movable platform 1112 to drive the holder 1113 to move therewith. Alternatively, the second portion 1113B may be formed integrally with the movable platform 1112.

[0050] The holder 1113 may be made of any rigid material, such as metal, plastic, ceramic, rubber, resin, etc., and the embodiments of the present disclosure are not limited thereto. It should also be understood that the shape of the holder 1113 shown in Figures 3 and 4 is also merely exemplary, and the holder 1113 may have any suitable shape according to actual requirements.

[0051] 5 is a schematic block diagram of a test chip according to at least one embodiment of the present disclosure. In some embodiments, the test chip C may include a heating electrode CE, and when an electrical signal is received, the heating electrode CE or a resistive wiring electrically connected thereto may generate heat to heat the test chip C. The test chip C may further include electrodes for other purposes, such as electrodes for applying an electrical signal to drive the sample so that the sample moves into the test chip C. As described above, the embodiments of the present disclosure do not limit the type, structure, etc. of the test chip C.

[0052] As shown in FIG. 3 and FIG. 4, in some embodiments, the heater 121 may include a contact electrode 1211. The contact electrode 1211 may be formed of, for example, a high-temperature resistant metal material. The contact electrode 1211 is configured to be in electrical contact with the heating electrode CE of the test chip C during use. The heater 121 is further configured to apply an electrical signal to the heating electrode CE of the test chip C through the contact electrode 1211, thereby causing the heating electrode CE to heat the test chip C. For example, the contact electrode 1211 may be disposed on the stage 1111 and exposed, allowing it to contact the exposed heating electrode CE of the test chip C during use, thereby applying an electrical signal (e.g., a DC voltage or an AC voltage) to the heating electrode CE of the test chip C. After the test chip C is placed on the stage 1111, the contact electrode 1211 may contact the heating electrode CE of the test chip C, thereby transmitting an electrical signal. The contact electrode 1211 may be electrically connected to a power source or a controller by a line passing through the stage 1111 to receive a control signal.

[0053] In addition, the contact electrode 1211 can also serve to fix the test chip C. For example, after the test chip C is placed on the stage 1111, the contact electrode 1211 can be moved, for example, by a spring or the like, so that the contact electrode 1211 comes into contact with the heating electrode CE of the test chip C and applies an acting force to the test chip C, thereby fixing the test chip C by the contact electrode 1211 and the stage 1111.

[0054] In other embodiments, the test tip may not have a heating electrode, and the heater 121 may be configured to heat the test tip by providing infrared heating or airflow to the test tip. For example, the heater 121 may be an infrared heater or a gas heater (e.g., heating air by resistance and driving the heated air to flow by a fan), etc., and the embodiments of the present disclosure are not limited thereto.

[0055] FIG. 6 is a structural schematic diagram of a temperature control unit in a disassembled state according to at least one embodiment of the present disclosure, and FIG. 7 is a structural schematic diagram of a temperature control unit in an assembled state according to at least one embodiment of the present disclosure. As shown in FIG. 6 and FIG. 7, the temperature control unit 120 may include, for example, a temperature sensor 123. The temperature sensor 123 is configured to detect the temperature of the test chip. The temperature sensor 123 may adopt a conventional temperature sensor, and the embodiment of the present disclosure will not describe it. 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 test chip includes a temperature sensor, there is no need to install the temperature sensor 123 in the analysis device.

[0056] As shown in FIG. 7, the temperature sensor 123 and the cooler 122 are spaced apart from each other, allowing the test chip to be interposed between the temperature sensor 123 and the cooler 122. As shown in FIG. 6 and FIG. 7, the temperature control unit 120 may further include a temperature control holder 124, and the temperature sensor 123 and the cooler 122 are spaced apart from each other by being connected to the temperature control holder 124, respectively. It should be understood that the positions of the temperature sensor 123 and the cooler 122 in FIG. 6 and FIG. 7 are merely exemplary, and the embodiments of the present disclosure are not limited thereto. For example, in other embodiments, the temperature sensor 123 may be located above or below the test chip during use, and the cooler 122 may be located on the side of the test chip during use.

[0057] For example, the cooler 122 may include, but is not limited to, a fan or a semiconductor cooling sheet, and the embodiments of the present disclosure do not limit the specific type of the cooler 122. As shown in Figures 6 and 7, the cooler 122 may be, for example, a fan, the outer shape of which is approximately circular, and is fixed to the temperature control holder 124 by four mounting posts installed at the four corners.

[0058] The temperature control holder 124 has an opening so that the temperature sensor 123 and the cooler 122 can be exposed to the test chip during use, thereby allowing the temperature sensor 123 to detect the temperature of the test chip and allowing the cooler 122 to cool the test chip.

[0059] As shown in Figures 6 and 7, the cross section of the temperature control holder 124 may be U-shaped, the cooler 122 may be installed in the opening of the U-shape, and the temperature sensor 123 may be located on the surface of the top of the temperature control holder 124 away from the bottom, and the cooler may be located on the surface of the bottom of the temperature control holder 124 facing the top and may have an opening on the top of the temperature control holder 124, thereby locally exposing the temperature sensor 123 and enabling the temperature sensor 123 to detect the temperature of the test chip when the test chip is located between the top and bottom of the temperature control holder 124.

[0060] The temperature control holder 124 may be made of any rigid material, such as metal, plastic, ceramic, rubber, resin, etc., and the embodiments of the present disclosure are not limited thereto. It should also be understood that the shapes of the temperature control holder 124 shown in Figures 6 and 7 are also exemplary, and the temperature control holder 124 may have any suitable shape according to actual requirements.

[0061] 8 is a schematic diagram of a signal detection unit according to at least one embodiment of the present disclosure. As shown in FIG. 8, in addition to the optical sensor 131, the signal detection unit 130 may further include a light source 132 and a light transmission unit 133 in at least one embodiment of the present disclosure.

[0062] The optical sensor 131 is, for example, an image sensor, and is configured to be used to collect and analyze optical images of the test chip. The optical sensor 131 can include, for example, 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 can also be a photodiode, a photoresistor, an infrared sensor, an ultraviolet sensor, etc., and the embodiments of the present disclosure are not limited thereto.

[0063] The light source 132 is configured to provide light to the test chip to illuminate the test chip during use. The light transmission unit 133 is configured to transmit the light provided by the light source 132 to the test chip during use, and transmit the light reflected or transmitted by the test chip to the optical sensor 131.

[0064] For example, the light source 132 may be of various types and may emit visible light, infrared light, etc., including, for example, a laser or a fluorescent light source, and the wavelengths of the laser and fluorescent light source may be selected according to actual needs, and the embodiments of the present disclosure are not limited thereto.

[0065] FIG. 9 is a specific schematic diagram of a signal detection unit according to at least one embodiment of the present disclosure. As shown in FIG. 9, in some embodiments, the light transmission unit 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 test 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 test chip, and the reflective light path system 1332 further includes a filter, which filters the light transmitted in the optical path from the test chip to the optical sensor 131 so as to transmit only light of a predetermined wavelength. The 90° turning prism system 1331 and the reflective light path system 1332 may both adopt a common design in the present field, and the present disclosure will not describe it.

[0066] 9, in some embodiments, the signal detection unit 130 may further include an objective lens 134. The objective lens 134 is configured to collect light from the test tip. For example, the objective lens 134 may include a lens.

[0067] 9, in some embodiments, the signal detection unit 130 may further include a bracket 135. The bracket 135 is for fixing and mounting at least some components of the signal detection unit 130, such as the light source 132, the light transmission unit 133, etc. In some embodiments, the bracket 135 may be further configured to adjust the distance between the light transmission unit 133 and the test chip so that the test chip is located at the focus of the light transmission unit 133. The bracket 135 may adopt a common design in this field, and the present disclosure will not describe it.

[0068] In some embodiments, the signal detection unit 130 may further include a level H', so as to detect whether the signal detection unit 130 is horizontal. For example, the level H' may be connected to the light transmission unit 133, the optical sensor 131, the light source 132, etc. In FIG. 9, as an example, the level H' is connected to the 90° turning prism system 1331. However, it should be understood that the embodiment of the present disclosure is not limited thereto. The level H' may be connected to other members of the signal detection unit 30 in any suitable manner, such as adhesive, magnetic attraction, screw connection, etc., and the embodiment of the present disclosure is not limited thereto. The level H' may be, for example, a bubble level, an inductance level, a capacitance level, etc., and the embodiment of the present disclosure is not limited thereto. The spirit level H' allows, for example, light transmitted from the optical transmission section 133 to the test chip to be perpendicular to the test chip, or light from the test chip to enter the optical transmission section 133 perpendicularly, thereby facilitating subsequent signal processing and, for example, eliminating the step of performing angle correction on the image of the test chip.

[0069] 10 is a structural schematic diagram of the mounting unit, the temperature control unit, and the signal detection unit 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 mounting unit 110, the temperature control unit 120, and the signal detection unit 130 are all installed on the base 101 and fixed to the base 101 by, for example, screws, jigs, adhesives, etc. The temperature control unit 120 and the signal detection unit 130 are installed along the movement path of the movable platform 1112 on the mounting unit 110, so that the test chip placed on the stage 1111 can be moved to the temperature control unit 120 by the movement of the movable platform 1112 to perform temperature control, and moved to the signal detection unit 130 to collect light from the test chip.

[0070] However, it should be understood that the arrangement shown in FIG. 10 is merely exemplary, and different arrangements may be adopted based on different structures and shapes of the mounting unit 110, the temperature control unit 120 and the signal detection unit 130, and the embodiments of the present disclosure are not limited thereto.

[0071] 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 are configured to perform at least one of the following operations: to control the mounting part 110 so that the mounting part 110 moves by being signal-connected to the mounting part 110; to control the heater 121 to heat the test chip by being signal-connected to the heater 121; to control the cooler 122 to cool the test chip by being signal-connected to the optical sensor 131; and to analyze the light from the test chip by being signal-connected to the optical sensor 131.

[0072] The controller 140 can be implemented, for example, by a central processing unit (CPU), a digital signal processor (DSP), a one-chip microcontroller, a field programmable gate array (FPGA), a complex programmable logic device (CPLD), an application specific integrated circuit (ASIC), etc., and the embodiments of the present disclosure are not limited thereto.

[0073] It should be understood that in some embodiments, the controller 140 can be implemented as multiple sub-controllers, each of which can perform at least one of the above operations, and the multiple sub-controllers can be separably located or integrated into one controller, and the embodiments of the present disclosure are not limited thereto.

[0074] As shown in FIG. 11, in some embodiments, the analysis device 100 may further include a communication unit CP. The communication unit CP is configured to form a signal connection with a mobile terminal, a server, or the like. The signal connection may be a wired connection or a wireless connection, and the embodiments of the present disclosure are not limited thereto. Examples of wireless connections include Wi-Fi (Wireless Fidelity), Bluetooth, Wireless Direct, infrared, and the like. Examples of wired connections include Universal Serial Bus (USB), FireWire, Thunderbolt, or any connection that requires a physical cable.

[0075] 12, 13, and 14 are respectively a front view, a rear view, and a perspective view of an analytical device according to at least one embodiment of the present disclosure. As shown in FIG. 12, the analytical 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 perform display, and may be, for example, a liquid crystal display, an organic light-emitting diode (OLED) display, a quantum dot light-emitting diode (QLED) display screen, a micro light-emitting diode display, an electronic ink display screen, an electronic paper display, etc., and the embodiment of the present disclosure is not limited thereto. For example, the display screen 150 may be a touch screen, thereby receiving user input. However, it should be understood that in some embodiments, the analytical device may not include the display screen 150, but may be connected to a separate display screen or output data such as analysis results in the form of a digital file or a physical file, and the embodiment of the present disclosure is not limited thereto.

[0076] As shown in Fig. 13, the analytical device according to at least one embodiment of the present disclosure may further include a power supply interface 160. The analytical device is connected to a power supply via the power supply interface 160 to obtain power. However, it should be understood that in some embodiments, the analytical device may not have the power supply interface 160, but may have a built-in primary or secondary battery, or a built-in solar cell, and the embodiments of the present disclosure are not limited thereto.

[0077] 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 such as an analysis result to an external device or transmit data from an 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, etc. In at least one embodiment, the data transmission interface and the power interface may be integrated into one interface, for example, a USB interface, which may be used to transmit data and may be used to transmit electrical energy.

[0078] As shown in Fig. 12, the analysis device according to at least one embodiment of the present disclosure may further include a button 180. The button 180 is configured to obtain an input command from a user, and may be, for example, a mechanical button, an optical button, etc., and the embodiment of the present disclosure is not limited thereto. It should be understood that the shape and number of the button 180 in Fig. 12 are merely exemplary, and the embodiment of the present disclosure is not limited thereto.

[0079] 12, the analytical device according to at least one embodiment of the present disclosure may further include a chip mounting port 190. The chip mounting port 190 accommodates a test chip by allowing the stage 1111 to protrude therethrough.

[0080] 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's touch operation, convert the user's touch operation into an electrical signal, and transmit it to a controller or other control device, 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 if the display screen 150 is a touch display or the analysis device includes other types of input devices (e.g., buttons 180, microphones, etc.), the analysis device may not include the touch sensor 192.

[0081] 14, the analysis device according to at least one embodiment of the present disclosure may further include a heat vent 191. The heat vent 191 can be used to release heat from, for example, the controller 140 or the temperature control unit 120. The heat vent 191 can be provided in a dust-free package to prevent dust from entering the inside of the analysis device.

[0082] At least one embodiment of the present disclosure further 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 test chip 220, and can be provided to a user in combination with the analysis device 210 and an unused test chip 220 for use by the user, for example. The analysis device 210 can be any of the analysis devices described above. The test chip 220 can be any of the test chips described above.

[0083] It should be understood that in some embodiments of the present disclosure, the analysis system 200 can further include more components or parts, and the embodiments of the present disclosure are not limited thereto. For detailed descriptions and technical effects of the analysis device 210 and the test chip 220, please refer to the above description of the reaction device, and the description will be omitted here.

[0084] At least one embodiment of the present disclosure further provides a method for operating an analysis device. The method can be applied to the analysis device according to any embodiment of the present disclosure. FIG. 16 is a flowchart 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 step S320, moving a mounting unit on which a test chip is placed to a temperature control unit.

[0085] In step S320, the mounting part on which the test chip is placed can be manually moved to the temperature control part. When the mounting part includes a transport structure on which the test chip is placed and configured to be at least locally operable, and a driver configured to be capable of driving the transport structure, step S320 may include moving the test chip to the temperature control part by driving the transport structure on which the test chip is placed by the driver.

[0086] 17A to 17C show a process of performing step S320 according to at least one embodiment of the present disclosure. In FIG. 17B and FIG. 17C, a test chip C is shown for convenience of explanation. As shown in FIG. 17A, a stage 1111 of an analysis device according to at least one embodiment of the present disclosure accommodates the test chip by extending from a chip mounting port 190 of the analysis device. As shown in FIG. 17B, the test chip C is located at a first position P1, and the test chip C is accommodated and placed on the stage 1111 at the first position P1. As shown in FIG. 17C, the test chip C is located at a second position P2, and the second position P2 allows a temperature controller to adjust the temperature of the test chip C.

[0087] As shown in FIG. 16, the method 300 of operating an analytical device in accordance with at least one embodiment of the present disclosure may further include, step S340, adjusting the temperature of the test tip with a heater and a cooler.

[0088] If the test tip includes a heating electrode and the heater includes a contact electrode, step S340 may include applying an electrical signal to the heating electrode of the test tip via the contact electrode, thereby causing the heating electrode to heat the test tip.

[0089] In some embodiments, step S340 further includes cyclically maintaining the test chip at at least two temperatures by a heater and a cooler. For example, the test chip is heated by a heater and cooled by a cooler, and a plurality of temperature control cycles, for example 30 temperature control cycles, are performed on the test chip, so that the test chip performs PCR thermal cycle amplification. Each temperature control cycle includes maintaining the test chip at 95°C for 10 seconds, maintaining the test chip at 50°C for 10 seconds, and maintaining the test chip at 72°C for 10 seconds. It should be understood that the above temperature control cycles are merely exemplary, and the embodiments of the present disclosure are not limited thereto. FIG. 18 is a temperature change diagram of a temperature control cycle according to at least one embodiment of the present invention. In FIG. 18, the horizontal axis indicates time in minutes, and the vertical axis indicates temperature in degrees Celsius.

[0090] As shown in FIG. 18, a method 300 for operating an analytical device according to at least one embodiment of the present disclosure may further include step 360, moving a mounting portion on which the test chip is placed to a signal detection portion, and acquiring light from the test chip by an optical sensor.

[0091] In step S360, the mounting unit on which the test chip is placed can be manually moved to the signal detection unit. When the mounting unit includes a transport structure on which the test chip is placed and configured to be at least locally operable and a driver configured to be capable of driving the transport structure, step S360 can include moving the test chip to the signal detection unit by driving the transport structure on which the test chip is placed by the driver.

[0092] 19 shows a cross-sectional view of an analysis device according to at least one embodiment of the present disclosure when step S360 is performed. For convenience of explanation, a test chip C is shown in FIG. 19. As shown in FIG. 19, the test chip is located at a third position P3, which allows the optical sensor 131 of the signal detection unit 130 to acquire light from the test chip.

[0093] Step S360 irradiates the test chip with light, and receives the light reflected by or transmitted through the test chip by the optical sensor as light from the test chip.

[0094] If the optical sensor includes an image sensor, step S360 may include acquiring an optical image of the test chip by the image sensor. If the signal detection unit further includes a light source and an optical transmission unit, step S360 may include providing light by the light source, transmitting the light provided by the light source by the optical transmission unit to illuminate the test chip, and transmitting the light reflected or transmitted by the test chip to the optical sensor (or an image sensor included in the optical sensor) by the optical transmission unit as light from the test chip.

[0095] As shown in FIG. 16, the method 300 of operating an assay device in accordance with at least one embodiment of the present disclosure may further include step S380, obtaining an assay result by analyzing the light from the test tip.

[0096] It should be understood that one or more steps and at least some sub-steps in the method 300 can be performed, for example, by software or firmware, such as by a mobile terminal, a server, etc., that is signal-connected to the analysis device, and the embodiments of the present disclosure are not limited thereto.

[0097] In some embodiments, if acquiring light from the test tip with an optical sensor includes acquiring an optical image of the test tip with an image sensor, step S380 may include step S3802, converting the optical image to a grayscale image.

[0098] For example, step S3802 may further include performing a Gaussian smoothing process on the grayscale image to reduce the effects of noise.

[0099] For example, the method 300 may further include step S3804, identifying reaction chambers of the test chip from the grayscale image.

[0100] If the test chip includes a circular reaction chamber, in step S3804, the reaction chamber can be detected from the grayscale image by a Hough circle transform algorithm, but it should be understood that the embodiment of the present disclosure is not limited thereto.

[0101] For example, the method 300 may further include, step S3806, determining a partition line in the grayscale image based on the identified reaction chamber.

[0102] FIG. 20 is a flowchart of step S380 in accordance with at least one embodiment of the present disclosure.

[0103] In some embodiments, step S3806 depicts the reaction chamber in an auxiliary image having the same size as the grayscale image based on the center coordinate and radius of the image area of ​​the identified reaction chamber. It should be understood that the auxiliary image has the same size and number of pixels as the grayscale image, and in the auxiliary image, the pixel values ​​of the circle and its center corresponding to the reaction chamber may be set to any non-zero value, and the pixel values ​​of the area other than the reaction chamber may be set to zero.

[0104] In some embodiments, step S3806 may further include calculating a sum of pixel values ​​of pixels in each row and a sum of pixel values ​​of pixels in each column of the auxiliary image.

[0105] FIG. 21A is a distribution diagram of the sum of row pixel values ​​of an auxiliary image according to at least one embodiment of the present disclosure, and FIG. 21B is a distribution diagram of the sum of column pixel values ​​of an auxiliary image according to at least one embodiment of the present disclosure.

[0106] In some embodiments, before calculating the sum of pixel values ​​of pixels in each row and the sum of pixel values ​​of pixels in each column of the auxiliary image, step S3806 may further include performing processing on the auxiliary image, such as angle correction and noise removal.

[0107] In some embodiments, step S3806 may further include: determining a minimum value of the sum of pixel values ​​in a row direction and a minimum value of the sum of pixel values ​​in a column direction in the auxiliary image; determining the row coordinate corresponding to the minimum value in the row direction as the row coordinate of a partition line extending along the column direction in the grayscale image; and determining the column coordinate corresponding to the minimum value in the column direction as the column coordinate of a partition line extending along the row direction in the grayscale image. For example, in some embodiments, the sum of pixel values ​​of each row of the auxiliary image is differentiated, and the sum of column pixel values ​​of each column of the auxiliary image is differentiated, the differentiation result is quantified with a sign function, the quantification result is differentiated, and noise removal is performed to filter the crests of the waves to obtain a trough. The trough in the row direction (i.e., the minimum value) corresponds to the partition line extending along the column direction, and the trough in the column direction (i.e., the minimum value) corresponds to the partition line extending along the row direction.

[0108] FIG. 22A is a schematic diagram of a valley in the row direction of an auxiliary image according to at least one embodiment of the present disclosure, and FIG. 22B is a schematic diagram of a valley in the column direction of an auxiliary image according to at least one embodiment of the present disclosure.

[0109] For example, the method 300 may further include, step S3808, obtaining a plurality of chamber image blocks by dividing the grayscale image based on the partition lines.

[0110] In some embodiments, step S3808 may include setting the row coordinate of the minimum value of the sum of pixel values ​​in the row direction in the auxiliary image as the row coordinate of a partition line extending along the column direction in the grayscale image, and setting the column coordinate of the minimum value of the sum of pixel values ​​in the column direction in the auxiliary image as the column coordinate of the partition line extending along the row direction in the grayscale image, thereby obtaining the partition line in the grayscale image. Figure 23 is an example of an auxiliary image according to at least one embodiment of the present disclosure. The auxiliary image further shows the positions of valleys (i.e., minimum values) of the sum of pixel values ​​in the row direction and the column direction, which correspond to the partition line in the grayscale image.

[0111] For example, the method 300 may further include step S3810: determining, as the target image block, a chamber image block among the plurality of chamber image blocks having a pixel standard deviation greater than a predetermined threshold.

[0112] In some embodiments, step S3810 may further include: if the reaction chamber identified in step 3804 overlaps with a partition line, designating the reaction chamber as an invalid reaction chamber; otherwise designating the reaction chamber as a valid reaction chamber; calculating a standard deviation of pixels of a chamber image block in which a valid reaction chamber exists; and designating a chamber image block in which the standard deviation of pixels is greater than a predetermined threshold as a target image block.

[0113] In some embodiments, step S380 may further include determining an initial copy number based on the number of target image blocks, the total number of reaction chambers of the test chip, and a sample dilution factor according to the following formula: c=[ln(1-f / n)] / m Here, c denotes the initial copy number, f denotes the number of target image blocks, m denotes the sample dilution factor, and n denotes the total number of reaction chambers in the test chip.

[0114] The following points require further clarification: (1) The drawings of the embodiments of the present disclosure relate only to the structures related to the embodiments of the present disclosure, and for other structures, reference may be made to conventional designs.

[0115] (2) Where there are no conflicts, the embodiments and features of the embodiments of the present disclosure can be combined with each other to obtain new embodiments.

[0116] The above are merely specific embodiments of the present disclosure, and the scope of protection of the present disclosure is not limited thereto, but should be based on the scope of protection of the claims. [Explanation of symbols]

[0117] 100 Analyzer 110 Mounting section 120 Temperature control unit 121 Heater 122 Cooler 130 Signal detection unit 131 Optical Sensor

Claims

1. An analysis device for use with a test chip, comprising a mounting unit, a temperature control unit, and a signal detection unit, the mounting unit is configured to receive and mount a test chip during use and to move the test chip; The temperature control unit includes a heater and a cooler, where the heater is configured to heat the test chip and the cooler is configured to cool the test chip; the signal detection unit includes an optical sensor, wherein the optical sensor is used in a test chip configured to receive light from the test chip and perform detection based on the light; The mounting unit includes: a transport structure configured to mount the test chip and to be at least partially movable; a driver configured to drive the transport structure to reciprocate the test tip between a first position, a second position, and a third position; The transport structure comprises: a stage configured to mount the test chip during use; a movable platform connected to the driver and configured to move in response to actuation of the driver; a holder configured to connect the stage and the movable platform such that the stage can be actuated when the movable platform is actuated; The holder includes: a first portion configured to receive the stage; a second part configured to be connected to the moveable platform in use; Here, the first portion extends along a first direction, the second portion extends along a second direction, and the first direction is perpendicular to the second direction, and the first portion and the second portion are formed into an L-shape or a T-shape.

2. The first position allows the test chip to be accommodated in the transport structure; the second position allows the temperature controller to adjust the temperature of the test tip; The analyzer of claim 1 , wherein the third position enables the optical sensor of the signal detection portion to receive the light from a test tip.

3. The analytical device according to claim 1 , wherein the stage has a cut-out area such that when the test chip is placed on the stage, the side of the test chip that comes into contact with the stage is at least locally exposed to the cooler.

4. The test tip includes a heating electrode; the heater includes a contact electrode, the contact electrode being configured to be in electrical contact with the heating electrode of the test tip during use; The analytical device according to any one of claims 1 to 3, wherein the heater is further configured to apply an electrical signal to the heating electrode of the test chip via the contact electrode, so that the heating electrode heats the test chip.

5. 4. The analysis device according to claim 1, wherein the heater is configured to heat the test chip by providing infrared heating or air current to the test chip.

6. 6. The analysis device according to claim 1, wherein the temperature control unit further includes a temperature sensor, the temperature sensor being configured to detect a temperature of the test chip.

7. 7. The analysis device according to claim 6, wherein the temperature sensor and the cooler are spaced apart from each other, thereby allowing the test chip to be interposed between the temperature sensor and the cooler.

8. The analytical device according to claim 6 or 7, wherein the temperature sensor includes an infrared temperature sensor or a thermocouple temperature sensor.

9. The analytical device according to any one of claims 1 to 8, wherein the cooler includes a fan or a semiconductor cooling sheet.

10. The signal detection unit a light source configured, in use, to provide light to illuminate the test tip; a light transmitting portion configured, in use, to transmit the light provided by the light source to the test tip, and to transmit light reflected or transmitted by the test tip to the optical sensor; The analytical device according to any one of claims 1 to 9, further comprising:

11. The analytical device of claim 10 , wherein the light source comprises a laser or a fluorescent light source.

12. The analytical device according to any one of claims 1 to 11, wherein the optical sensor is an image sensor and is configured to collect optical images of the test chip for analysis.

13. The analytical device further includes a controller, the controller comprising: A signal is connected to the mounting unit to control the mounting unit to move; a signal connection to the heater to control the heater to heat the test tip; a signal connection to the cooler to control the cooler to cool the test tip; 13. The assay device of any one of claims 1 to 12, configured to perform at least one of the following operations: analyzing the light from the test tip by signal connection to the optical sensor.

14. The analytical device according to any one of claims 1 to 13, further comprising at least one of the group consisting of a display screen, a touch sensor, a power supply interface, and a data transmission interface.

15. An analysis device according to any one of claims 1 to 14, The test chip; An analysis system including:

16. The mounting unit on which the test chip is placed is moved to the temperature control unit; adjusting the temperature of the test chip by the heater and the cooler; the mounting section on which the test chip is placed is moved to the signal detection section, and the optical sensor acquires the light from the test chip; A method of operating an assay device according to any one of claims 1 to 14, comprising obtaining an assay result by analysing the light from the test chip.

17. The step of adjusting the temperature of the test chip by the heater and the cooler includes:

17. The method of claim 16, further comprising cycling the test tip through at least two temperatures with the heater and the cooler.

18. The step of acquiring the light from the test tip by the optical sensor comprises: acquiring an optical image of the test tip with an image sensor; The step of obtaining an analysis result by analyzing the light from the test chip includes: converting the optical image into a grayscale image; identifying reaction chambers of the test chip from the grayscale image; determining a partition line in the grayscale image based on the identified reaction chamber; Dividing the grayscale image based on the partition lines to obtain a plurality of chamber image blocks; 18. The method according to claim 16 or 17, further comprising determining, as a target image block, a chamber image block among the plurality of chamber image blocks having a pixel standard deviation greater than a predetermined threshold.

Images