CN113773952A - Handheld LAMP detector and system - Google Patents

Handheld LAMP detector and system Download PDF

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Publication number
CN113773952A
CN113773952A CN202111187960.XA CN202111187960A CN113773952A CN 113773952 A CN113773952 A CN 113773952A CN 202111187960 A CN202111187960 A CN 202111187960A CN 113773952 A CN113773952 A CN 113773952A
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chip
lamp
arc
battery
hand
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颜菁
翟锋
石海洋
陆子幸
王佳彬
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Jiangsu Huixian Pharmaceutical Technology Co ltd
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Jiangsu Huixian Pharmaceutical Technology Co ltd
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Priority to CN202111209767.1A priority Critical patent/CN113930322B/en
Priority to CN202111187960.XA priority patent/CN113773952A/en
Publication of CN113773952A publication Critical patent/CN113773952A/en
Priority to PCT/CN2022/084503 priority patent/WO2023060851A1/en
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    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L7/00Heating or cooling apparatus; Heat insulating devices
    • B01L7/52Heating or cooling apparatus; Heat insulating devices with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6844Nucleic acid amplification reactions

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Abstract

The invention discloses a handheld LAMP detector and a handheld LAMP detection system. This hand-held type LAMP detector includes: a shell, which is provided with an inner cavity and a chip port for inserting the LAMP chip; the chip holder is arranged in the inner cavity and used for accommodating the LAMP chip; the heating component is used for heating the LAMP chip at constant temperature and is arranged in the inner cavity; the optical detection device is movably arranged in the inner cavity along the left-right direction and is provided with a plurality of detection positions, and the detection positions are respectively corresponding to the reaction bins on the LAMP chip; the driving mechanism is used for driving the optical detection device to move along the left and right directions and is arranged in the inner cavity; a battery for supplying power; the touch screen is used for displaying the detection result; a printer for printing the detection result; and the code reader is used for reading the bar code information. The invention integrates nucleic acid amplification and detection, automatic code scanning, detection result display and printing, can be detected by hand, and is convenient to use.

Description

Handheld LAMP detector and system
Technical Field
The invention belongs to the technical field of LAMP detection, and relates to a handheld LAMP detector and a system.
Background
LAMP (Loop-mediated isothermal amplification) technology is widely applied to the field of biological diagnosis, such as nucleic acid amplification detection to diagnose whether pathogens exist in samples due to the advantages of mild reaction conditions (lower reaction temperature), short reaction time and the like. The LAMP technology is a process of providing in vitro amplification conditions for nucleic acid fragments, performing exponential amplification on the nucleic acid fragments, adding a fluorescent dye or a fluorescent marker in the nucleic acid amplification process, detecting the intensity of a fluorescent signal by adopting an optical device, and analyzing the fluorescent signal to obtain a nucleic acid amplification result. When the nucleic acid amplification reaction is carried out, the reaction system needs to be heated. The existing LAMP detector can integrate nucleic acid amplification and detection, and after a detection chip (usually a microfluidic chip) is placed in the LAMP detector, a reaction chamber (usually an amplification reaction chamber) of the detection chip can be heated, illuminated, detected and the like. Miniaturization and portability of the LAMP detector are one of the targets of the LAMP detector designers.
Disclosure of Invention
The invention provides a handheld LAMP detector and a handheld LAMP detection system.
According to a first aspect of the invention, a hand-held LAMP detector comprises:
the LAMP holder comprises a shell, a LAMP holder and a LAMP holder, wherein an inner cavity is formed in the shell, and a chip port for inserting an LAMP chip is formed in the shell;
the chip holder is arranged in the inner cavity, and is provided with an accommodating space for accommodating the LAMP chip, and the accommodating space is opposite to the chip port;
the heating component is used for heating the LAMP chip at constant temperature and is arranged in the inner cavity;
an optical detection device which is movably arranged in the inner cavity along the left-right direction, wherein the optical detection device is provided with a plurality of detection positions which are respectively corresponding to a plurality of reaction chambers on the LAMP chip;
the driving mechanism is used for driving the optical detection device to move along the left-right direction and is arranged in the inner cavity;
a battery for powering the heating assembly, the optical detection device, and the drive mechanism, the battery being disposed in the internal cavity;
the touch screen is used for displaying a detection result, and is arranged on the upper side wall of the shell and positioned above the battery;
the printer is used for printing a detection result, is embedded on the upper side wall of the shell and is positioned above the battery;
the code reader is used for reading bar code information, the bar code information comprises sample information and/or user information, and the code reader is embedded in the front side wall of the shell.
In one embodiment, the chip opening is disposed on a front side wall of the casing, the chip holder is located at a front portion of the inner cavity, the battery is located at a rear side of the inner cavity, the heating assembly is disposed on the chip holder, at least a portion of the optical detection device is located above the chip holder, and the driving mechanism is disposed between the chip holder and the battery.
In one embodiment, the chip holder includes a fixing portion and a supporting portion located behind the fixing portion, the accommodating space includes a slot opened in the fixing portion for the LAMP chip to penetrate through, the slot penetrates through the fixing portion in the front-rear direction, the supporting portion has a supporting surface for facing the rear portion of the LAMP chip, and the heating assembly is disposed on the supporting surface. More preferably, the support surface is directed upwards; and/or the slot is opposite to the chip opening.
In one embodiment, the heating assembly comprises a heat conducting plate, a heating film, heat preservation cotton, a temperature sensor and a fuse, wherein the heat preservation cotton is arranged on the chip seat, the heating film is arranged on the heat preservation cotton, the heat conducting plate is arranged on the heating film, and the temperature sensor and the fuse are embedded in the heat preservation cotton.
In one embodiment, the driving mechanism includes a guide rail extending in a left-right direction on an inner wall of the housing, a mounting block movably disposed on the guide rail in the left-right direction, and a motor for driving the mounting block to move in the left-right direction, the motor is disposed on the inner wall of the housing, and the optical detection device is disposed on the mounting block.
In an embodiment, the battery is a rechargeable battery, and a power interface electrically connected to the battery is disposed on the rear side of the housing.
In an embodiment, the hand-held LAMP detector further includes a controller, and the controller is electrically connected to the optical detection device and the printer, respectively.
In an embodiment, the hand-held LAMP detector further includes a controller, and the controller is electrically connected to the heating assembly, the optical detection device, the driving mechanism, and the touch screen, respectively.
In one embodiment, the touch screen has a plurality of display states, and in one of the display states, the touch screen has an instruction input area for a user to input an instruction. The touch screen is used as a human-computer interaction interface.
In one embodiment, the lower portion of the housing is provided with a depression for facilitating gripping by fingers.
According to a second aspect of the invention, the hand-held LAMP detection system comprises a LAMP detector and a LAMP chip, wherein the LAMP detector is the hand-held LAMP detector.
In one embodiment, the LAMP chip includes a chip body, the chip body is provided with a sample addition port, a plurality of reaction chambers and a plurality of exhaust ports, each reaction chamber is communicated with the sample addition port through a first microchannel, each first microchannel has one or more bending portions, and each reaction chamber is further communicated with a corresponding exhaust port through a second microchannel. Reagent backflow in the reaction bin is avoided through the bending part, and the LAMP chip can keep the reagents of all the reaction tanks not to interfere with each other under the condition that a control valve or a piston is not arranged, so that pollution is avoided. In a preferred embodiment, the number of the sample adding ports is only one, and only one sample adding port needs to be added, so that the use is convenient.
In a preferred embodiment, the bending portion includes an arc bending portion having an overall arc shape, and a central angle of the arc shape of the arc bending portion is greater than 90 degrees.
In a more preferred embodiment, the arc-shaped bending portion includes a first arc-shaped bending portion and a second arc-shaped bending portion, the center of the first arc-shaped bending portion is located at the right side of the first arc-shaped bending portion, and the center of the second arc-shaped bending portion is located at the left side of the second arc-shaped bending portion.
Furthermore, first arc kink with second arc kink sets up in the past, and adjacent first arc kink meets with second arc kink directly or meets through sharp form passageway.
In one embodiment, the chip body is further provided with an overflow groove, and the overflow groove is communicated with the sample addition port or surrounds the sample addition port.
In one embodiment, the chip body is provided with a positioning rib on the left side part or the right side part.
In one embodiment, the LAMP chip further includes a cover film that is provided on the surface of the chip body and covers the gas discharge port, and that allows gas to pass therethrough but does not allow liquid to pass therethrough.
In one embodiment, the LAMP chip further comprises a first sealing film for sealing the sample addition port and/or the gas discharge port.
In one embodiment, the sample addition port and the exhaust port are disposed on a first surface of the chip body, the reaction chamber is disposed on a second surface of the chip body, and the LAMP chip further includes a second sealing film for sealing the reaction chamber, the second sealing film being disposed on the second surface.
In a preferred embodiment, the second surface of the chip body is provided with a plurality of grooves. Further, the first microchannel and the second microchannel are also disposed on the second surface of the chip body.
Compared with the prior art, the invention has the following advantages by adopting the scheme:
the LAMP detector and the detection system have compact structure and small volume, the size of the whole LAMP detector can be as small as 250mm multiplied by 120mm multiplied by 80mm, the power is supplied by a battery, and the LAMP detector and the detection system can be held by hand for detection on the premise of integrating nucleic acid amplification and detection, automatic code scanning, detection result display and printing, and are convenient to carry and use; the LAMP chip can be automatically finished by loading the LAMP chip into the kit, and the kit can finish constant-temperature heating amplification, fluorescence detection analysis and detection structure display, so that the detection efficiency is improved.
Drawings
In order to more clearly illustrate the technical solution of the present invention, the drawings needed to be used in the description of the embodiments will be briefly introduced below, and it is obvious that the drawings in the following description are only some embodiments of the present invention, and it is obvious for those skilled in the art to obtain other drawings based on the drawings without creative efforts.
Fig. 1 is a schematic perspective view of a LAMP detection system according to an embodiment of the present invention from a viewing angle.
Fig. 2 is a schematic perspective view of the LAMP detection system according to the embodiment of the present invention from another viewing angle.
Fig. 3 is a schematic view of the internal structure of the LAMP detector according to the embodiment of the present invention at a viewing angle, in which a LAMP chip is inserted.
Fig. 4 is a schematic diagram of the internal structure of the LAMP detector according to the embodiment of the present invention at another viewing angle, in which the LAMP chip has been inserted.
Fig. 5 is an exploded schematic view of the LAMP chip, chip holder and heating assembly.
Fig. 6 is a schematic view of the coating of the first surface of the LAMP chip according to the embodiment of the present invention.
Fig. 7 is a schematic view of the coating film of the second surface of the LAMP chip according to the embodiment of the present invention.
Fig. 8 is a perspective view of the chip body.
Fig. 9 is a schematic view of the first surface of the chip body.
Fig. 10 is a schematic diagram of the second surface of the chip body.
Fig. 11 is a side view of the chip body.
Fig. 12 is a block diagram showing the configuration of a control system of the LAMP detector according to the embodiment of the present invention.
Fig. 13 is a flowchart of the control flow of the LAMP detector according to the embodiment of the present invention.
Wherein the content of the first and second substances,
1. a housing; 10. a chip port; 11. a power interface; 12. a recessed portion;
2. a chip holder; 21. a fixed part; 21a, a slot; 22. a support portion; 22a, a support surface;
3. a heating assembly; 31. a heat conducting plate; 32. heating the film; 33. a temperature sensor; 34. a fuse; 35. pressing the elastic sheet;
4. an optical detection device; 41. a spectral sensor;
5. a drive mechanism; 51. a guide rail; 52. mounting blocks; 53. a motor; 54. a screw rod; 55. an optical coupler;
61. a battery; 610. a battery case; 62. a touch screen; 63. a printer; 64. a code scanner;
7. an LAMP chip; 70. a chip body; 70a, a first surface; 70b, a second surface; 701. a sample addition port; 702. an overflow trough; 703. an exhaust port; 704. a reaction bin; 705. a first microchannel; 705a, a first arc bending part; 705b, a second arc bending part; 706. a second microchannel; 707. a groove; 708. unfilled corners; 71. coating a film; 72. a first sealing film; 73. a second sealing film;
81. a first control chip; 82. and a second control chip.
Detailed Description
Preferred embodiments of the present invention will be described in detail below with reference to the accompanying drawings so that the advantages and features of the invention may be more readily understood by those skilled in the art. It should be noted that the description of the embodiments is provided to help understanding of the present invention, but the present invention is not limited thereto.
In the description of the present application, it is to be understood that the terms "upper", "lower", "left", "right", "front", "rear", "vertical", "horizontal", "inner" and "outer" etc. indicate orientations or positional relationships based on those shown in the drawings, and are only for convenience of description and simplicity of description, and do not indicate or imply that the referred device or element must have a specific orientation, be constructed in a specific orientation, and be operated, and thus, should not be construed as limiting the present application. All directional terms used herein are used with reference to the arrows in FIG. 3.
The embodiment provides a handheld LAMP detector and a handheld LAMP detection system, which are used for nucleic acid detection. Referring to fig. 1 and 2, the hand-held LAMP detection system includes the LAMP detector and the LAMP chip 7 described above. The LAMP detector includes a housing 1, and an inner cavity for mounting internal components is formed in the housing 1. A chip port 10 for inserting the LAMP chip 7 is formed on the front side wall of the shell 1, and the LAMP chip 7 is inserted into the LAMP detector from the chip port 10. The internal structure of the LAMP detector is shown in fig. 3 to 5, in which the case 1 is not shown. As shown in fig. 3 to 5, the LAMP detector further includes a chip holder 2, a heating unit 3, an optical detection device 4, a drive mechanism 5, a battery 61, a touch panel 62, a printer 63, a scanner 64, a control system, and the like. The chip opening 10 is arranged on the front side wall of the shell 1, the chip seat 2 is arranged at the front part of the inner cavity, the battery 61 is arranged at the rear side of the inner cavity, the heating component 3 is arranged on the chip seat 2, at least part of the optical detection device 4 is arranged above the chip seat 2, and the driving mechanism 5 is arranged between the chip seat 2 and the battery 61. Fig. 6 to 11 show the LAMP chip 7 of the hand-held LAMP detection system, and the LAMP chip 7 has a plurality of reaction chambers 704 juxtaposed in the left-right direction.
As shown in fig. 3 to 5, the chip holder 2 is disposed in the inner cavity, the chip holder 2 has an accommodating space for accommodating the LAMP chip 7, the accommodating space is opposite to the chip opening 10, and the LAMP chip 7 is horizontally inserted into the accommodating space from the chip opening 10. Specifically, the chip carrier 2 includes a fixing portion 21 and a supporting portion 22 located at the rear side of the fixing portion 21, and the chip carrier 2 is integrally formed, such as integrally injection-molded plastic. The accommodating space comprises a slot 21a which is arranged on the fixing part 21 and is used for the LAMP chip 7 to penetrate through, and the slot 21a penetrates through the fixing part 21 along the front-back direction; the support portion 22 has a support surface 22a for facing the rear of the LAMP chip 7, and the heating unit 3 is disposed on the support surface 22 a. Further, the slot 21a is substantially horizontal and level with the chip port 10, and the two are opposite; the support surface 22a is specifically located on the upper surface of the support portion 22, the heating component 3 is disposed on the support surface 22a, and after the LAMP chip 7 is inserted, the rear portion of the LAMP chip 7 (i.e., the portion having the reaction chamber 704) is located on the heating component 3 and the two are attached to each other or close to each other, ideally, the two are attached to each other, so as to heat the system in the reaction chamber 704 of the LAMP chip 7 and perform isothermal amplification. The chip holder 2 is fixed to the lower side wall of the front portion of the case 1.
As shown in fig. 3 to 5, the heating unit 3 is used to heat the LAMP chip 7 at a constant temperature, and the heating unit 3 is disposed in the inner cavity of the housing 1 and further disposed on the supporting surface 22a of the chip holder 2. Specifically, as shown in fig. 5, the heating element 3 includes a heat conducting plate 31, a heating film 32, heat insulating cotton, a temperature sensor 33, and a fuse 34, the heat insulating cotton is disposed on the supporting surface 22a of the chip holder 2, the heating film 32 is disposed on the heat insulating cotton, the heat conducting plate 31 is disposed on the heating film 32, and the temperature sensor 33 and the fuse 34 are embedded in the heat insulating cotton. Further, the heat conductive plate 31, the heating film 32, and the heat insulating cotton are laminated on the supporting surface 22a of the chip holder 2 from top to bottom. The fuse 34 is connected in series with the heater film 32 for overcurrent protection. The heating component 3 further comprises a pressing elastic sheet 35 for pressing the LAMP chip 7 on the heat conducting plate 31, and the pressing elastic sheet 35 is fixedly arranged on the mounting seat. The number of the pressing spring pieces 35 is multiple and arranged at intervals along the left-right direction, and the pressing spring pieces 35 can elastically deform. The compressing spring piece 35 is integrally in a U shape with an upward opening, after the LAMP chip 7 is inserted, the compressing spring piece 35 is extruded by the LAMP chip 7 and bends upwards in parallel, and under the action of elastic force, the lower end part of the compressing spring piece 35 abuts against the LAMP chip 7 to compress the LAMP chip 7 on the heat conducting plate 31, so that the LAMP chip and the heat conducting plate are attached to each other, and a better heating effect is achieved.
As shown in fig. 3 and 4, the optical detection device 4 is provided in the cavity so as to be movable in the left-right direction. The optical detection device 4 has a plurality of detection positions for respectively corresponding to the plurality of reaction chambers 704 on the LAMP chip 7. During detection, the optical detection device 4 moves to a detection position to detect a corresponding one of the reaction chambers 704; after the detection is finished, the optical detection device 4 moves to the next detection position to detect another corresponding reaction chamber 704. The optical detection device 4 employs a known optical device capable of emitting a laser beam that irradiates the system in the reaction chamber 704 to excite fluorescence, and also capable of collecting and spectrally analyzing the excited fluorescence. The optical detection device 4 of the present embodiment preferably employs a monochromatic laser light source; the optical detection means 4 further comprise a spectral sensor for spectrally analyzing the excited fluorescence.
As shown in fig. 3 and 4, the driving mechanism 5 is used to drive the optical detection device 4 to move in the left-right direction, and the driving mechanism 5 is disposed in the inner cavity. Specifically, the drive mechanism 5 includes a guide rail 51 provided on an inner wall (specifically, a lower side wall) of the housing 1 and extending in the left-right direction, a mounting block 52 provided on the guide rail 51 so as to be movable in the left-right direction, and a motor 53 for driving the mounting block 52 to move in the left-right direction, the motor 53 is provided on the inner wall of the housing 1, and the optical detection device 4 is provided on the mounting block 52. Further, the motor 53 drives a screw rod 54 extending in the left-right direction to rotate, the screw rod 54 is connected to the mounting block 52 through a nut, and as the screw rod 54 rotates, the mounting block 52 moves in the left-right direction, and the optical detection device 4 is driven to move left and right.
As shown in fig. 3 and 4, a battery 61 is disposed in the inner cavity of the housing 1 for supplying power to the heating assembly 3, the optical detection device 4, the driving mechanism 5, the touch screen 62, the printer 63, the scanner 64, the control system, and the like. Specifically, the battery 61 is disposed in a battery 61 case, and the battery 61 case is disposed on the inner wall of the housing 1. The battery 61 is a rechargeable battery 61, a power interface 11 (shown in fig. 2) electrically connected to the battery 61 is disposed on the rear side of the housing 1, the power interface 11 can be connected to an external power source, and the LAMP detector can be directly powered by the external power source.
As shown in fig. 1 to 4, the printer 63 and the touch screen 62 are embedded in the upper side wall of the housing 1 and located above the battery 61, the touch screen 62 is located in front of the printer 63, the printer 63 can print information such as a detection result, and the touch screen 62 can display information such as a detection result. One of the functions of the touch screen 62 is to display information, and the other function is to serve as a man-machine interface for a user to input instructions. Accordingly, the touch screen 62 has a plurality of display states, and in one display state, the touch screen 62 has an instruction input area for a user to input an instruction, for example, a "start detection" button; in another display state, the touch screen 62 has a detection result display area for displaying a detection result, such as "negative" or "positive".
As shown in fig. 1, 3 and 4, the barcode scanner 64 is embedded in the front side wall of the housing 1 and located at the right side or the left side of the chip holder 2, and can read the barcode on the LAMP chip 7 to obtain barcode scanning information, where the barcode scanning information includes sample information (sample source, etc.).
The lower and/or side portions of the housing 1 are provided with depressions 12 for the user's fingers to grasp, for ergonomics.
Referring to fig. 6 to 11, the LAMP chip 7 includes a chip body 70, and the chip body 70 is provided with a sample addition port 701, a plurality of reaction chambers 704, and a plurality of exhaust ports 703. Each reaction chamber 704 is connected to the sample port 701 through a first micro-channel 705, and each first micro-channel 705 has one or more bending parts. Each reaction chamber 704 is also in communication with a corresponding exhaust port 703 via a second microchannel 706. The LAMP chip 7 is a miniaturized microfluidic chip, does not need any piston or valve for controlling liquid flow, is small in size, and is suitable for being used in a handheld LAMP detector. The first microchannel 705 of each reaction chamber 704 is bent at one or more positions to form one or more bent portions, so that reagents and the like in the reaction chambers 704 can be effectively prevented from flowing back to the first microchannel 705 without arranging a valve or a piston, and pollution to other reaction chambers 704 is avoided. The reaction chambers 704 are provided with amplification reagents such as primers in advance, and the primers in different reaction chambers 704 may be the same or different to detect different pathogens. The thickness of the front portion of the chip body 70, where the sample addition port 701 is opened, is larger than the thickness of the other portions. The chip body 70, or at least the portion corresponding to the reaction chamber 704, is made of a material having a certain transparency (transparent or translucent) to allow laser light to be injected and fluorescence to be emitted.
The bending part comprises an arc bending part which is integrally arc-shaped, and the central angle of the arc bending part is greater than 90 degrees, preferably 170 to 190 degrees. Further, the arc bending portion includes a first arc bending portion 705a and a second arc bending portion 705b, a center of the first arc bending portion 705a is located on a right side thereof, and a center of the second arc bending portion 705b is located on a left side thereof. The first arc bent portion 705a and the second arc bent portion 705b each have a central angle of 180 degrees. As shown in fig. 10, the first curved bending portion 705a and the second curved bending portion 705b are disposed alternately, and the adjacent first curved bending portion 705a and the second curved bending portion 705b are directly connected or connected through a linear channel, that is, each first microchannel 705 has a wavy portion, which effectively prevents the reagents such as primers in the reaction chamber 704 from flowing backwards.
In another embodiment, the bending portion includes a plurality of first bending portions and a plurality of second bending portions, each of the first bending portions integrally forms an acute angle, and each of the second bending portions integrally forms an acute angle. The first and second bent portions are disposed in a staggered manner, and the adjacent first and second bent portions are directly connected or connected through a linear channel, that is, each first microchannel 705 has a zigzag portion.
The chip body 70 is integrally formed in a plate shape, and is formed by integrally molding plastic, such as injection molding. The chip body 70 has a first surface 70a and a second surface 70b opposite to each other, and in the embodiment, the first surface 70a is an upper surface of the chip body 70, and the second surface 70b is a lower surface of the chip body 70. Sample port 701 and vent port 703 are provided on first surface 70a of chip body 70, and reaction chamber 704, first microchannel 705 and second microchannel 706 are provided on second surface 70b of chip body 70.
The LAMP chip 7 further includes a cover film 71 that is provided on the surface of the chip body 70 and covers the gas discharge port 703, allowing gas to pass but not liquid to pass. The LAMP chip 7 further includes a first sealing film 72 for sealing the sample addition port 701 and/or the air vent 703, and after the sample addition is completed, the first sealing film 72 is coated on the first surface 70a of the chip body 70 to isolate the sample addition port 701 and the air vent 703 from the outside, and then, amplification reaction is performed to prevent contamination. The first surface 70a of the chip body 70 is further provided with an overflow groove 702 surrounding the sample loading port 701, so as to prevent the first surface 70a of the chip body 70 from being contaminated during sample loading, and prevent the adhesion between the first sealing film 72 and the first surface 70a from being affected.
The LAMP chip 7 further includes a second sealing film 73 for sealing the reaction chamber 704, the first microchannel 705, and the second microchannel 706, the second sealing film 73 being provided on the second surface 70 b. The second surface 70b of the chip body 70 is provided with a plurality of grooves 707, and the grooves 707 are specifically formed on the region of the second surface 70b not provided with the reaction chamber 704, the first microchannel 705 and the second microchannel 706, and have different shapes, sizes and positions according to the shapes and positions of the reaction chamber, the first microchannel 705 and the second microchannel 706, and avoid the reaction chamber, the first microchannel 705 and the second microchannel 706. These grooves 707 serve to facilitate sealing of the second sealing film 73 and the chip body 70, to prevent generation of bubbles after film attachment, and to prevent the chip body 70 from being bent and deformed.
When the LAMP chip 7 is shipped, the cover film 71 and the second sealing film 73 are previously attached to appropriate positions of the chip body 70, and constant-temperature amplification reagents including primers and the like are previously placed in each reaction tank; after the user adds the nucleic acid sample to be tested, the second sealing film 73 is applied to the sample addition port 701 and the coating film 71 to seal the sample addition port 701 and each exhaust port 703.
The right side of the chip body 70 is provided with a rib or an unfilled corner 708, and correspondingly, the slot 21a of the chip holder 2 is correspondingly provided with a positioning groove matched with the positioning rib or a protrusion matched with the unfilled corner 708, so as to avoid the reverse insertion of the LAMP chip 7 and perform foolproof design.
The hand-held LAMP detector comprises a controller, wherein the controller is electrically connected with the heating component 3, the optical detection device 4, the driving mechanism 5, the battery 61, the touch screen 62, the printer 63, the code scanner 64 and the like respectively, so that the LAMP detector can automatically operate, and the nucleic acid detection, the result display and the like are realized. Fig. 12 shows a control block diagram of the hand-held LAMP detector, wherein the controller specifically includes a first control chip 81 and a second control chip 82 arranged on the PCB, and the first control chip 81 is a main control chip; the second control chip 82 is a control chip of the printer 63 and is used for communicating with the outside, such as via bluetooth, wifi, 4G or 5G.
The power interface 11 is electrically connected to an external power input port of the first control chip 81, and after the power interface 11 is connected to an external power source, the whole LAMP detector can be powered by the external power source and the battery 61 can be charged. The battery 61 is electrically connected with the first control chip 81, and when the external power supply is not connected, the battery 61 supplies power to the whole LAMP detector. The first control chip 81 converts a voltage of 15V from an external power source or a voltage of 12V from the battery 61 and supplies the converted voltage to the second control chip 82, the heating unit 3, the motor 53, the touch panel 62, the scanner 64, the printer 63, and the like. The first control chip 81 is further configured to monitor the power of the battery 61, and send an insufficient power alarm signal through the touch screen 62 when the power is smaller than a set threshold.
The heating film 32 of the heating assembly 3 is electrically connected with the serial port of the first control chip 81 through the fuse 34, and the temperature sensor 33 is electrically connected with the other serial port of the first control chip 81. The first control chip 81 receives the temperature detection data of the temperature sensor 33, compares the temperature detection data with the set temperature, and adjusts the temperature of the heating film 32 in real time by using a PID algorithm to maintain the heating temperature of the heat conducting plate 31 at 65 +/-0.5 ℃.
The serial ports of the motor 53 and the first control chip 81 are electrically connected, the serial ports of the first control chip 81 are also electrically connected with the optical coupler, and whether the motor 53 rotates to a set angle or not is detected through the optical coupler so as to reset and limit the motor 53. The spectrum sensor of the optical detection device 4 is electrically connected to the serial port of the first control chip 81 to receive the detection result. After the motor 53 is at the initial position and the set reaction time passes, the spectrum sensor analyzes and detects the fluorescence of the first reaction chamber 704 and sends the detection result to the first control chip 81; after the first reaction bin 704 finishes detection, the motor 53 rotates to enable the optical coupling sensor to move to the position above the second reaction bin 704, the fluorescence of the second reaction bin 704 is read, and the read result is sent to the second control chip 82; and so on.
The serial port 3 electric connection of touch-sensitive screen 62 and first control chip 81, touch-sensitive screen 62 can receive user's instruction and send it to first control chip 81, and first control chip 81 can send testing result, sweep yard information etc. to touch-sensitive screen 62 and show.
The bar code scanner 64 is electrically connected with the serial port 2 of the first control chip 81, and the bar code scanner 64 can read the bar code information of the sample and obtain information such as the source of the sample and the name of the detected person; the first control chip 81 can accept the read barcode information and associate it with the detection result.
The printer 63 is electrically connected with the serial port 0 of the first control chip 81, the other serial port 0 of the first control chip 81 is electrically connected with the serial port 0 of the second control chip 82, and the first control chip 81 can send the read bar code information and the detection result to the printer 63 for printing.
Referring to fig. 13, the control flow of the hand-held LAMP detector is as follows:
s100, acquiring the electric quantity of the battery 61 by the controller
The first control chip 81 detects the electric quantity of the battery 61, and judges whether the electric quantity is greater than or equal to a set threshold value, if so, the following steps are executed; if not, a low battery alarm signal is sent out through the touch screen 62 and the like.
After receiving the low-power alarm signal, the user accesses an external power supply, and the external power supply supplies power and charges the battery 61.
S101, scanning code
Barcode information is read by the barcode reader 64, and the barcode information includes sample information, user information, and the like, and may be a one-dimensional code or a two-dimensional code provided on the LAMP chip 7.
S102, loading the LAMP chip 7
The LAMP chip 7 is horizontally inserted into the hand-held LAMP detector from the chip port 10, wherein the LAMP chip 7 has been subjected to pretreatment. The pretreatment process is specifically as follows: adding a sample from the sample adding port 701 until the sample flows to the position of the coating film 71 to seal the coating film 71, and even overflowing the added sample to the overflow groove 702; the sample addition port 701 and the cover film 71 are covered with a first sealing film 72, respectively, and the sample addition port 701 and each exhaust port 703 are closed, so that a closed environment isolated from the outside air is formed in the LAMP chip 7, and isothermal amplification and fluorescence detection are performed in the closed environment.
S103, receiving a detection instruction of a user by the touch screen 62
The touch panel 62 is switched to a display state having a "start detection" button, and the user clicks the "start detection" button on the touch panel 62 to start a detection process.
S104, the controller receives the detection instruction, and controls the motor 53 to reset and the heating component 3 to heat
After receiving a start detection instruction from a user, the first control chip 81 sends a control signal to the motor 53, and in response to the control signal, the motor 53 is reset to its initial position; the first control chip 81 specifically determines whether the motor 53 returns to the start position through a signal returned by the optical coupler. Meanwhile, the first control chip 81 controls the heating film 32 to heat, specifically: the first control chip 81 receives the heating temperature value fed back by the temperature sensor 33, compares the heating temperature value with a set temperature value (65 ℃), and controls the heating temperature of the heating film 32 to be maintained at 65 ± 0.5 ℃ by a pid algorithm so as to be capable of heating the reaction system in each reaction chamber 704 of the LAMP chip 7 at a constant temperature.
S105, the controller controls the optical detection device 4 to read the detection result of the first reaction chamber 704
The first control chip 81 sends a control signal to the motor 53, and in response to the control signal, the motor 53 rotates by a certain angle, which is obtained by conversion according to the initial position of the optical detection device 4 and the distance between the first reaction chamber 704, so that the optical detection device 4 can be moved to the first detection position facing the first reaction chamber 704 to perform laser irradiation on the amplification product in the first reaction chamber 704, collect the excited fluorescence, analyze the collected fluorescence through the spectrum sensor, and send the fluorescence analysis value to the first control chip 81.
S106, the controller controls the optical detection device 4 to read the detection result of the next reaction chamber 704
After receiving the fluorescence analysis value of the previous reaction chamber 704, the first control chip 81 sends a control signal to the first control chip 81 to make the motor 53 continue to rotate by another set angle, which is obtained by conversion according to the distance between two adjacent reaction chambers 704, so that the optical detection device 4 can be moved to the next detection position directly facing the next reaction chamber 704 (such as the second, third, and fourth reaction chambers 704) to perform laser irradiation on the amplification product in the next reaction chamber 704, collect the excited fluorescence, analyze the collected fluorescence by the spectral sensor, and send the fluorescence analysis value to the first control chip 81.
S107, the controller judges the fluorescence analysis value sent by the optical detection device 4 to obtain the detection result of the detection item corresponding to each reaction bin 704
After receiving the fluorescence analysis value returned by the optical detection device 4 for the first time, the first control chip 81 determines whether the detection item (e.g., pathogen a) corresponding to the first reaction chamber 704 is positive or negative according to the pre-stored interpretation standard. After receiving the fluorescence analysis value returned by the optical detection device 4 for the second time, the first control chip 81 determines whether the detection item (e.g., pathogen B) corresponding to the second reaction chamber 704 is positive or negative according to the pre-stored interpretation standard. After receiving the fluorescence analysis value returned by the optical detection device 4 for the third time, the first control chip 81 determines whether the detection item (e.g., pathogen C) corresponding to the third reaction chamber 704 is positive or negative according to the pre-stored interpretation standard. After receiving the fluorescence analysis value returned by the optical detection device 4 for the fourth time, the first control chip 81 determines whether the detection item (e.g., pathogen D) corresponding to the fourth reaction chamber 704 is positive or negative according to the pre-stored interpretation standard. And so on.
S108, the controller sends the detection result to the printer 63 for printing and sends the detection result to the touch screen 62 for displaying
The first control chip 81 sends the detection results (negative/positive) of the respective detection items and the information read by scanning the codes to the printer 63, and the second control chip 82 controls the printer 63 to print out a detection report. Meanwhile, the first control chip 81 sends the detection result of each detection item to the touch screen 62, the touch screen 62 is switched to another display state, and the detection result and the information read by the scanning code are displayed.
According to the LAMP detector and the detection system, the layout and the configuration of the internal components are adopted, so that the whole structure is compact, the size is small (the whole size of the LAMP detector can be as small as 250mm multiplied by 120mm multiplied by 80mm), the power is supplied by the battery 61, and the LAMP detector and the detection system can be held by hand for detection on the premise of integrating nucleic acid amplification and detection, automatic code scanning, detection result display and printing, and are convenient to carry and use; the user can automatically complete code scanning, constant-temperature heating amplification, fluorescence detection analysis and detection result display printing by loading the LAMP chip 7 after sample addition, so that the detection efficiency is improved. The LAMP chip 7 can keep the reagents of each reaction tank from interfering with each other under the condition of not configuring a control valve or a piston, thereby avoiding pollution; only one sample port 701 needs to be loaded with sample, so that the use is convenient; because a control valve or a piston is not configured, the whole volume of the LAMP chip 7 is smaller (can be as small as 34mm multiplied by 58mm multiplied by 3mm), so that the whole volume of the LAMP detector matched with the LAMP chip is greatly reduced, and the LAMP detector is suitable for hand-held detection.
As used in this specification and the appended claims, the terms "comprises" and "comprising" are intended to only encompass the explicitly identified steps and elements, which do not constitute an exclusive list, and that a method or apparatus may include other steps or elements. As used herein, the term "and/or" includes any combination of one or more of the associated listed items.
It should be noted that, unless otherwise specified, when a feature is referred to as being "fixed" or "connected" to another feature, it may be directly fixed or connected to the other feature or indirectly fixed or connected to the other feature. Further, the description of the upper, lower, left, right, etc. used in the present invention is only with respect to the positional relationship of the respective components of the present invention with respect to each other in the drawings.
It will be further understood that the terms "first," "second," and the like are used to describe various information and that such information should not be limited by these terms. These terms are only used to distinguish one type of information from another and do not denote a particular order or importance. Indeed, the terms "first," "second," and the like are fully interchangeable. For example, first information may also be referred to as second information, and similarly, second information may also be referred to as first information, without departing from the scope of the present disclosure.
The above embodiments are merely illustrative of the technical ideas and features of the present invention, and are preferred embodiments, which are intended to enable those skilled in the art to understand the contents of the present invention and implement the present invention, and not to limit the scope of the present invention. All equivalent changes or modifications made according to the principles of the present invention should be covered within the protection scope of the present invention.

Claims (10)

1. A hand-held LAMP detector, comprising:
the LAMP holder comprises a shell, a LAMP holder and a LAMP holder, wherein an inner cavity is formed in the shell, and a chip port for inserting an LAMP chip is formed in the shell;
the chip holder is arranged in the inner cavity, and is provided with an accommodating space for accommodating the LAMP chip, and the accommodating space is opposite to the chip port;
the heating component is used for heating the LAMP chip at constant temperature and is arranged in the inner cavity;
an optical detection device which is movably arranged in the inner cavity along the left-right direction, wherein the optical detection device is provided with a plurality of detection positions which are respectively corresponding to a plurality of reaction chambers on the LAMP chip;
the driving mechanism is used for driving the optical detection device to move along the left-right direction and is arranged in the inner cavity;
a battery for powering the heating assembly, the optical detection device, and the drive mechanism, the battery being disposed in the internal cavity;
the touch screen is used for displaying a detection result, and is arranged on the upper side wall of the shell and positioned above the battery;
the printer is used for printing a detection result, is embedded on the upper side wall of the shell and is positioned above the battery;
the code reader is used for reading bar code information, the bar code information comprises sample information and/or user information, and the code reader is embedded in the front side wall of the shell.
2. The hand-held LAMP detector of claim 1, wherein the chip port is located on a front side wall of the housing, the chip holder is located at a front portion of the internal cavity, the battery is located at a rear side of the internal cavity, the heating assembly is disposed on the chip holder, at least a portion of the optical detection device is located above the chip holder, and the driving mechanism is disposed between the chip holder and the battery.
3. The hand-held LAMP detector according to claim 1 or 2, wherein the chip holder includes a fixing portion and a support portion located at a rear side of the fixing portion, the accommodating space includes a slot opened in the fixing portion for the LAMP chip to penetrate therethrough, the slot penetrates through the fixing portion in a front-rear direction, the support portion has a support surface for facing a rear portion of the LAMP chip, and the heating unit is disposed on the support surface.
4. The hand-held LAMP detector according to claim 1, wherein the heating assembly comprises a heat conducting plate, a heating film, heat insulating cotton, a temperature sensor and a fuse, the heat insulating cotton is arranged on the chip holder, the heating film is arranged on the heat insulating cotton, the heat conducting plate is arranged on the heating film, and the temperature sensor and the fuse are embedded in the heat insulating cotton.
5. The hand-held LAMP detector according to claim 1, wherein the driving mechanism includes a guide rail provided on the inner wall of the housing and extending in the left-right direction, a mounting block provided on the guide rail movably in the left-right direction, and a motor for driving the mounting block to move in the left-right direction, the motor being provided on the inner wall of the housing, the optical detection device being provided on the mounting block.
6. The hand-held LAMP detector according to claim 1, wherein the battery is a rechargeable battery, and a power interface electrically connected with the battery is arranged on the rear side of the housing.
7. The hand-held LAMP detector of claim 1 wherein the touch screen has a plurality of display states, and in one of the display states the touch screen has an instruction input area for a user to input instructions.
8. The hand-held LAMP detector of claim 1 wherein the lower portion of the housing is provided with a depression for facilitating finger gripping.
9. A hand-held LAMP detection system, which comprises an LAMP detector and an LAMP chip, and is characterized in that the LAMP detector is the hand-held LAMP detector according to any one of claims 1 to 8.
10. The system of claim 9, wherein the LAMP chip comprises a chip body, the chip body is provided with a sample injection port, a plurality of reaction chambers and a plurality of exhaust ports, each reaction chamber is communicated with the sample injection port through a first microchannel, each first microchannel is provided with one or more bending portions, each reaction chamber is communicated with a corresponding exhaust port through a second microchannel, the bending portions comprise an integrally arc-shaped arc bending portion, the arc-shaped central angle of the arc-shaped bending portion is greater than 90 degrees, the arc-shaped bending portions comprise a first arc-shaped bending portion and a second arc-shaped bending portion, the center of the first arc-shaped bending portion is located on the right side of the first arc-shaped bending portion, and the center of the second arc-shaped bending portion is located on the left side of the first arc-shaped bending portion.
CN202111187960.XA 2021-10-12 2021-10-12 Handheld LAMP detector and system Pending CN113773952A (en)

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