CN113376133A - Nucleic acid detector - Google Patents
Nucleic acid detector Download PDFInfo
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- CN113376133A CN113376133A CN202110633267.4A CN202110633267A CN113376133A CN 113376133 A CN113376133 A CN 113376133A CN 202110633267 A CN202110633267 A CN 202110633267A CN 113376133 A CN113376133 A CN 113376133A
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
- G01N21/64—Fluorescence; Phosphorescence
- G01N21/6428—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING 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
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
- G01N21/64—Fluorescence; Phosphorescence
- G01N21/6428—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"
- G01N2021/6439—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" with indicators, stains, dyes, tags, labels, marks
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Abstract
The invention discloses a nucleic acid detector, which comprises a base, a chip mounting assembly, a heating device, an optical detection device and a mechanical arm assembly, wherein the chip mounting assembly is arranged on the base; the chip mounting assembly is arranged on the left side part of the base and comprises a box body, a chip groove for accommodating the microfluidic chip is formed in the box body, and the chip groove is provided with an upward-facing notch; the heating device is arranged on the front side or the rear side of the chip mounting assembly; the optical detection device is arranged below the chip mounting assembly and is provided with a transmitting light emergent part and an exciting light receiving part which face the lower end part of the microfluidic chip, and the lower end part of the box body is provided with a hollow part which can allow transmitting light to enter the chip groove and allow exciting light to be emitted out of the chip groove; the mechanical arm assembly comprises a mechanical arm capable of moving in the left-right direction, and the mechanical arm is provided with a fork, and the fork is provided with a joint groove for clamping the end part of the piston of the microfluidic chip. The nucleic acid detector of the invention has compact structure and small volume.
Description
Technical Field
The invention belongs to the technical field of nucleic acid detection, and relates to a nucleic acid detector.
Background
The nucleic acid amplification detection technology is a process of providing in vitro amplification conditions for nucleic acid fragments, enabling the nucleic acid fragments to be amplified in an exponential manner in a large quantity, 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 obtaining a nucleic acid amplification result by analyzing the fluorescent signal. When the nucleic acid amplification reaction is carried out, the reaction system needs to be heated. In addition, the nucleic acid detecting instrument can integrate nucleic acid amplification and detection, and can heat, illuminate, detect and the like a reaction cavity (usually, an amplification reaction cavity) of a detection chip (usually, a microfluidic chip) after the detection chip is placed in the nucleic acid detecting instrument. However, most of the existing nucleic acid detectors aim at horizontal microfluidic chips, and are complex in structure, large in size, heavy in weight, high in cost and complex in operation, and occupy more space.
Disclosure of Invention
In view of the above technical problems, the present invention provides a nucleic acid detecting instrument which is compact and small in size.
In order to achieve the purpose, the invention adopts the following technical scheme:
a nucleic acid detector comprises a base, a chip mounting assembly, a heating device, an optical detection device and a mechanical arm assembly,
the chip mounting assembly is arranged on the left side part of the base and comprises a box body, a chip groove for containing the microfluidic chip is formed in the box body, and the chip groove is provided with an upward-facing notch;
the heating device is arranged on the front side or the rear side of the chip mounting assembly and used for heating the microfluidic chip in the chip groove;
the optical detection device is arranged below the chip mounting assembly and is provided with an emitted light emitting part and an excitation light receiving part which face the lower end part of the microfluidic chip, and the lower end part of the box body is provided with a hollow-out part which can allow emitted light to enter the chip groove and allow excitation light to exit the chip groove;
the mechanical arm assembly is arranged on the right side of the chip mounting assembly and comprises a mechanical arm capable of moving in the left-right direction, the mechanical arm is provided with a fork, and the fork is provided with a joint groove for clamping the end part of the piston of the microfluidic chip.
In some preferred embodiments, the cartridge body has a right side wall, the right side wall is provided with a notch extending downward from the upper edge thereof for inserting the right end of the piston on the microfluidic chip and extending the right end out of the cartridge body, and the engaging groove of the fork is aligned with the notch.
More preferably, the notch comprises a first notch and a second notch, the first notch is located at the front side or the rear side of the second notch, and the downward extending depth of the first notch is smaller than the downward extending depth of the second notch.
In some preferred embodiments, the lower end of the box body is hollowed out, and the middle part of the inner wall of the box body is provided with a supporting bump extending inwards.
More preferably, the case has opposite front and rear side walls and opposite left and right side walls, the front, left, rear and right side walls enclosing the chip slot, bottom ends of the left and right side walls being connected to the base, and a bottom of the rear side wall being located at a distance above the base, so that the emission light emitting part and the excitation light receiving part can be located below the chip slot by being located below the rear side wall; and/or a through window which can enable the heating device to pass through and contact with the microfluidic chip is arranged on the rear side wall; and/or the front side wall and the rear side wall are respectively provided with an operation slot convenient for inserting and pulling out the chip, and the operation slots extend downwards from the upper edge of the front side wall or the upper edge of the rear side wall.
In some preferred embodiments, the heating device includes a mounting seat, a heat conduction block and a heater for heating the heat conduction block, the heat conduction block is disposed on the mounting seat, and the heat conduction block has a heating surface disposed corresponding to the reaction chamber of the detection chip.
More preferably, the heat conduction block is movably disposed on the mounting seat, and the heating device further includes an elastic member disposed between the heat conduction block and the mounting seat.
Furthermore, the heat conduction block comprises a body and a connecting pin connected to the body, a connecting hole matched with the connecting pin is formed in the mounting seat, the connecting pin can penetrate through the connecting hole in a sliding mode along the length direction of the connecting pin, threads are arranged on the connecting pin, the connecting pin penetrates through the connecting hole and then is inserted into a nut, and the nut is in threaded connection with the connecting pin.
Further, the heat conduction block has a protrusion, and the heating surface is formed on a front side surface of the protrusion.
Further, the heat conduction block is an aluminum block.
Further, the heater is a heating film attached to the heat conducting block.
In some preferred embodiments, the optical detection device comprises a support, an emission optical path and an excitation optical path, the emission optical path comprises a light source and a first light guide sequentially arranged along a first optical axis, the first light guide has a first end and a second end, the first end is adjacent to the light source, and the emission light exit is formed on the second end; the excitation light path comprises a lens and a fluorescence sensor which are sequentially arranged along a second optical axis, the excitation light path further comprises a second light guide member with a first end part and a second end part, the excitation light receiving part is formed on the first end part of the second light guide member, and the second end part of the second light guide member is adjacent to the lens; an included angle which is larger than 0 and smaller than 180 degrees is formed between the first optical axis and the second optical axis.
More preferably, the included angle is less than 90 degrees.
More preferably, the light source detection device includes a plurality of emission light paths juxtaposed in a left-right direction, and a plurality of excitation light paths juxtaposed in the left-right direction.
Furthermore, the light source is an LED lamp, and the light sources of the plurality of emission light paths form an LED lamp strip extending along the left-right direction.
Further, the first light guide piece comprises a light guide column, a mounting hole is formed in the support, the light guide column is inserted into the mounting hole, and the upper end face of the light guide column is located below the chip groove to form the emitted light emergent portion.
Further, the light guide column is a solid glass column.
Furthermore, the second light guide member is an optical fiber, an upper end surface of the optical fiber is located below the chip groove to form the excitation light receiving portion, and the optical fiber is disposed in the bracket.
Specifically, the support includes a first support and a second support, a lower end of the first support is connected to the base, the emission light path and the second light guide member are disposed on an upper portion of the first support, the lens and the fluorescence sensor are disposed in the second support, and the second support is detachably connected to the first support and located below an upper portion of the first support.
Specifically, the lens is movably disposed in the second holder along the second optical axis.
More preferably, the first optical axis is obliquely added to a horizontal plane, and the second optical axis perpendicularly intersects the horizontal plane.
Specifically, the second light guide member is an optical fiber.
More preferably, the excitation light path further comprises a filter between the lens and the fluorescence sensor.
In some preferred embodiments, the nucleic acid detecting apparatus further includes a cover covering the base, the chip mounting assembly, the heating device, the optical detection device, and the arm assembly are located in the cover, the cover is provided with a slot for inserting the microfluidic device, and the slot is located right above the chip slot.
In some preferred embodiments, the robot arm assembly includes a mounting frame, a robot arm slidably disposed on the mounting frame, and a driving device for driving the robot arm to move, and the robot arm has a fork having an engaging groove for the piston end of the microfluidic chip to be inserted into.
More preferably, the engagement groove has an upwardly facing notch.
More preferably, the robot arm assembly includes a first robot arm and a second robot arm, the first robot arm being higher than the second robot arm, the first robot arm and the second robot arm respectively having the forks, each of the forks respectively having the engagement groove.
Further, the fork of the first robot arm is offset from the fork of the second robot arm by a distance in top view.
Further, the fork of the first mechanical arm and the fork of the second mechanical arm are located on the same side of the microfluidic chip.
Further, the mounting frame is provided with a slide rail extending along the horizontal direction, and the mechanical arm is movably arranged on the slide rail along the horizontal direction.
Furthermore, the mechanical arm is provided with a sliding groove matched with the sliding rail, and the sliding rail is inserted in the sliding groove.
Further, the driving device includes a motor, a lead screw driven by the motor to reciprocate, and the robot arm is connected to the lead screw.
Compared with the prior art, the invention has the following advantages by adopting the scheme:
the nucleic acid detector can insert the vertical micro-fluidic chip into the chip mounting assembly, the mechanical arm assembly drives the micro-fluidic chip piston to move so as to mix a sample and a reagent of the micro-fluidic chip or make the reagent flow into a target chamber, the reaction chamber of the micro-fluidic chip is heated by the heating device to carry out amplification reaction, the reaction chamber is irradiated and received by the optical detection device to excite fluorescence, and qualitative or quantitative detection is carried out according to the color and the intensity of the fluorescence.
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 view showing a structure of a nucleic acid detecting apparatus according to an embodiment of the present invention after insertion into a microfluidic chip, in which a cover is not shown;
FIG. 2 is a schematic view of the nucleic acid detecting apparatus shown in FIG. 1, viewed from another perspective;
FIG. 3 is a schematic view of the nucleic acid detecting apparatus shown in FIG. 1, in a state where the microfluidic chip is not inserted;
FIG. 4 is a schematic structural diagram of a microfluidic chip;
FIG. 5 is a schematic view of a chip mounting assembly from a perspective view;
FIG. 6 is a schematic view of a chip mounting assembly from another perspective;
FIG. 7 is a right side view of the chip mounting assembly;
FIG. 8 is a schematic view of the heating device from a perspective;
FIG. 9 is a schematic view of the heating device from another perspective;
FIG. 10 is a schematic structural view of a heat-conducting block;
FIG. 11 is a schematic structural diagram of an optical inspection apparatus;
FIG. 12 is a cross-sectional view of an optical detection device;
FIG. 13 is a schematic diagram of a first robot;
fig. 14 is a schematic structural view of the second robot arm.
Wherein the content of the first and second substances,
1. a base; 2. a chip mounting assembly; 3. a heating device; 4. a mechanical arm assembly; 5. an optical detection device;
21. a box body; 211. a front side wall; 212. a rear sidewall; 213. a left side wall; 214. a right side wall; 22. a chip slot; 23. a window is penetrated; 24. an operation slot; 24. supporting the projection; 25. a notch;
31. a mounting seat; 311. positioning the projection; 32. a heat conducting block; 321. a body; 322. heating the surface; 323. a connecting pin; 33. heating the film; 34. an elastic member; 35. a nut;
41. mounting; 411. a slide rail; 42a, a first mechanical arm; 42b, a second mechanical arm; 421. a fork-shaped piece; 422. an engaging groove; 423. a chute; 43. a screw rod; 44. a motor;
51. a support; 51a, a first bracket; 51b, a second bracket; 51c, end caps; 52. a light source; 53. a first light guide; 531. a light emission part; 54. a second light guide; 541. exciting a light receiving section; 55. a lens; 56. an optical filter; 57. a fluorescent sensor;
100. a microfluidic chip; 101. a piston; 101a, neck.
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.
According to an embodiment of the present invention, there is provided a nucleic acid detecting apparatus capable of automatically performing nucleic acid extraction, amplification, and detection. Fig. 1 to 3 show the nucleic acid detecting apparatus, and fig. 4 shows a microfluidic chip 100 suitable for the nucleic acid detecting apparatus, and the microfluidic chip 100 is a vertical microfluidic chip, that is, a plate whose height is at least greater than its width and which is vertically placed as a whole. The sample inlet is located at the upper part of the microfluidic chip 100, and the liquid circulates in the microfluidic chip 100 from top to bottom. The microfluidic chip 100 further includes two pistons 101 horizontally movable in the left-right direction, and the right end of the piston 101 is located outside the microfluidic chip 100 and has a neck portion 101a with a smaller outer diameter, through which the neck portion 101a is engaged with the robot arm assembly 4. The movement of the piston 101 may cause mixing of reagents within the microfluidic chip or communication of liquids between chambers. The lower portion of the microfluidic chip 100 is provided with a plurality of reaction chambers in parallel, specifically, in the present embodiment, the number of the reaction chambers is four and the reaction chambers are arranged in parallel along the front-back direction, so as to provide four detection channels.
Referring to FIGS. 1 to 3, the nucleic acid detecting instrument includes a base 1, a chip mounting assembly 2, a heating device 3, a robot arm assembly 4, and an optical detection device 5. Wherein, the chip mounting component 2 is arranged on the left side part of the base 1, the heating device 3 is arranged on the rear side of the chip mounting component 2, the optical detection device 5 is arranged below the chip mounting component 2, and the mechanical arm component 4 is arranged on the right side of the chip mounting component 2. The nucleic acid detecting instrument further comprises a cover body (not shown in the figure) covering the base 1, the chip mounting component 2, the heating device 3, the optical detecting device 5 and the mechanical arm component 4 are positioned in the cover body, and a slot for inserting the microfluidic chip 100 into the chip mounting component 2 is formed in the cover body.
The chip mounting assembly 2 is used to mount and fix the microfluidic chip 100. As shown in fig. 5 to 7, the chip mounting assembly 2 includes a case 21, a chip slot 22 is formed in the case 21 for accommodating the microfluidic chip 100, the chip slot 22 has an upward facing notch, and the socket on the cover is located right above the chip slot 22 and aligned with the notch.
The box body 21 has opposite front and back side walls 211 and 212, and opposite left and right side walls 213 and 214, the front side wall 211, the left side wall 213, the back side wall 212, and the right side wall 214 enclose the chip slot 22, the bottom ends of the left and right side walls 213 and 214 are connected to the base 1, and the bottoms of the front and back side walls 211 and 212 are located at a distance above the base 1, so that the optical detection device 5 can be located below the chip slot 22 through the bottom of the back side wall 212. The right side wall 214 is provided with a notch 25 extending downward from the upper edge thereof for inserting the right end of the piston 101 of the microfluidic chip 100 and extending the right end out of the box body 21. Specifically, the notch 25 includes a first notch and a second notch, the first notch is located at the front side of the second notch, and the depth of the downward extension of the first notch is smaller than the depth of the downward extension of the second notch. In the process of inserting the microfluidic chip 100, the right end of the piston 101 at the upper part of the chip is inserted into the first notch, and the right end of the piston 101 at the lower part of the chip is inserted into the second notch. The rear side wall 212 is provided with a through window 23 allowing the heating device 3 to pass through and be in contact with the reaction chamber of the microfluidic chip 100. The front side wall 211 and the rear side wall 212 are respectively provided with an operation slot 24 for facilitating the insertion and extraction of the chip, and the operation slot 24 extends downwards from the upper edge of the front side wall 211 or the rear side wall 212.
The lower end of the box body 21 is hollowed out, the middle part of the inner wall of the box body 21 is provided with a supporting bump 24 extending inwards, and the supporting bump 24 is flush with the lower edges of the front side wall 211 and the rear side wall 212. When the microfluidic chip 100 is inserted, the lower surface thereof is located above the supporting bumps 24, and the microfluidic chip 100 is supported and positioned by the supporting bumps 24.
The heating device 2 is used for heating the reaction chamber of the microfluidic chip 100. Referring to fig. 8 to 10, the heating device 3 includes a mounting seat 31, a heat conduction block 32, and a heater. The bottom of the mounting seat 31 is connected to the base 1, for example, fixed to the base 1 by screws. The heat-conducting block 32 is disposed on the mounting seat 31, and the heat-conducting block 32 has a heating surface 322 disposed corresponding to the reaction chamber of the microfluidic chip 100. Specifically, the heating surface 322 may be in contact with or disposed near the reaction region of the detection chip 100 so as to transfer heat to the reaction region of the detection chip 100, and in this embodiment, the heating surface 322 is in contact with the reaction region of the detection chip 100. The heater is provided on the heat conductive block 32, and heats the heat conductive block 32.
The heat conduction block 32 is movably provided on the mount 31. The heating device 3 further comprises an elastic member 34, wherein the elastic member 34 is disposed between the heat conducting block 32 and the mounting seat 31, and two ends of the elastic member 34 respectively abut against the heat conducting block 32 and the mounting seat 31. That is, the distance between the heat-conducting block 32 and the mounting seat 31 can be adjusted appropriately, and even in the case where the assembly error is large, the heating surface 322 can be ensured to be always attached to the reaction chamber of the microfluidic chip 100. The heat conducting block 32 comprises a body 321 and a connecting pin 323 connected to the body 321, a connecting hole matched with the connecting pin 323 is arranged on the mounting seat 31, and the connecting pin 323 can penetrate through the connecting hole in a sliding manner along the length direction; the elastic member 34 is a compression spring sleeved on the connection pin 323. The connecting pin 323 is provided with a screw thread (not shown), the connecting pin 323 is inserted into a nut 35 after passing through the connecting hole, and the nut 35 is screwed with the connecting pin 323. Specifically, the connecting pin 323 extends backward from the rear side of the body 321 to pass through the connecting hole in the mount 31, and locks the nut 35; by rotating the nut 35, the elastic deformation amount of the elastic member 34 can be adjusted, thereby achieving the adjustment of the distance between the heat conduction block 32 and the mounting seat 31. The body 321 has a protrusion extending forward on the left side, and the heating surface 322 is the left side of the protrusion, and is integrally strip-shaped and extends in the left-right direction. The heating surface 322 is further a vertically extending vertical plane. The heat-conducting block 32 is an aluminum block integrally formed of aluminum or an aluminum alloy. The protrusion is inserted into a through window 23 on the rear side of the cartridge body 21 of the chip mounting assembly 22, and can be attached to the reaction chamber of the microfluidic chip 100 therein to heat the reaction chamber.
The heater is specifically a heating film 33, which is attached to the lower side of the body 321 of the heat conducting block 32. The heating film 33 is provided with a power supply connection terminal for connecting a power supply. After the power is turned on, the heating film 33 generates heat and transfers the heat to the heat conduction block 32, and the reaction chamber of the microfluidic chip 100 is uniformly heated by the heat conduction block 32. Further, the heating film 33 is attached to the body 321 of the heat conductive block 32.
The upper part of the mounting seat 31 is formed with a positioning protrusion 311, and the heat conduction block 32 abuts on the positioning protrusion 311. Specifically, the positioning protrusion 311 extends leftward, the right side portion of the heat conduction block 32 abuts against the lower side surface of the positioning protrusion 311, and positioning is performed by the positioning protrusion 311, so that assembly can be facilitated.
The mechanical arm assembly 4 is used for driving the piston to move along the left-right direction. Referring to fig. 1 to 4, 13 and 14, the robot arm assembly 4 includes a mounting frame 41, a robot arm slidably disposed on the mounting frame 41, and a driving device for driving the robot arm to move. The mounting bracket 41 is fixedly arranged on the base 1, for example, by screw fastening. The robot arm has a fork 421, and the fork 421 has an engagement groove 422 for an end of the piston 101 of the microfluidic chip 100 (specifically, the neck portion 101a of the piston 101) to be caught, and the engagement groove 422 has a notch facing upward. In this embodiment, as shown in fig. 13 and 14, the robot arm assembly 4 includes a plurality of robot arms, including at least a first robot arm 42a and a second robot arm 42b, the first robot arm 42a is higher than the second robot arm 42b, the first robot arm 42a and the second robot arm 42b respectively have forks 421, and each fork 421 has an engaging groove 422. The fork 421 of the first mechanical arm 42a and the fork 421 of the second mechanical arm 42b are located on the same side, specifically, the right side, of the microfluidic chip 100. In a plan view, the fork 421 of the first robot arm 42a is offset from the fork 421 of the second robot arm 42b by a distance, that is, the first robot arm 42a and the second robot arm 42b are spaced back and forth to be able to simultaneously couple with the two pistons 101. Specifically, the second robot arm 42b is located at the lower rear side of the first robot arm 42a, i.e., the second robot arm 42b is located at a distance from the rear side of the first robot arm 42a so as to match the positions of the two pistons 101 in fig. 4.
The mount 41 has a slide rail 411 extending in the horizontal direction, and the robot arm is provided on the slide rail 411 so as to be movable in the horizontal direction. Wherein, the slide rail 411 has two and sets up from top to bottom. Referring to fig. 13, the upper slide rail 411 corresponds to the first robot arm 42a, a slide slot 423 is disposed on the first robot arm 42a and is engaged with the slide rail 411, and the slide rail 411 is inserted into the slide slot 423 of the first robot arm 42 a. Referring to fig. 14, the slide rail 411 on the lower side corresponds to the second mechanical arm 42b, a slide slot 423 matching with the slide rail 411 is disposed on the second mechanical arm 42b, and the slide rail 411 is inserted into the slide slot 423 of the second mechanical arm 42 b.
The number of the driving devices is two, and corresponds to the first robot arm 42a and the second robot arm 42b, respectively. Each driving device includes a motor 44 and a lead screw 43 driven by the motor 44 to reciprocate in the left-right direction, and a robot arm is connected to an end of the lead screw 43. The motor 44 is fixedly disposed on the mounting bracket 41. When the motor 44 operates, the screw 43 moves left or right along the left-right direction, and the mechanical arm moves left or right along the slide rail 411, so as to drive the piston 101 of the microfluidic chip 100 to move left or right, and further provide positive pressure or negative pressure for the liquid in the microfluidic chip 100, thereby providing power for liquid circulation.
The robot arm assembly 4 has an initial position in which the microfluidic chip 100 is inserted downward into the chip mounting assembly 2, and during the insertion, the neck portion 101a of the front upper side piston 101 is inserted into the engagement groove 422 of the fork 421 of the first robot arm 42a, and the neck portion 101a of the rear lower side piston 101 is inserted into the engagement groove 422 of the fork 421 of the second robot arm 42b while being connected to both pistons 101; after the connection, the mechanical arm moves leftwards or rightwards correspondingly with the operation of the motor 44, so that the piston 101 is pushed in or pulled out, the liquid flow in the microfluidic chip 100 is driven, power is provided for the liquid flow in the microfluidic chip 100 or the reagent is promoted to be uniformly mixed, and the micro-fluidic chip is simple in structure and small in size.
The optical detection device 5 is used for irradiating the reaction chamber at the lower part of the microfluidic chip 100 and receiving fluorescence excited by an amplification product in the reaction chamber, so as to detect according to fluorescence color, intensity and the like. As shown in fig. 11 and 12, the optical detection device 5 includes a light emitting part 531 and a light receiving part 541 facing the lower end of the microfluidic chip 100, and the lower end of the cartridge 21 includes a hollow part capable of allowing the emitted light to enter the chip slot 22 and allowing the excitation light to exit the chip slot 22, specifically, the lower end of the cartridge 21 is open and the emitted light can enter the cartridge 21 and the excited fluorescence can exit the cartridge 21.
The optical detection device 5 comprises a support 51, an emission light path and an excitation light path arranged on the support 51. The emission light path includes a light source 52 and a first light guide 53 sequentially arranged along the first optical axis, the first light guide 53 has a first end portion adjacent to the light source 52 and a second end portion, and the emission light exit portion 531 is formed on the second end portion of the first light guide 53. The excitation light path includes a lens 55 and a fluorescence sensor 57 arranged in this order along the second optical axis, and a second light guide 54 having a first end portion and a second end portion, and the above-mentioned excitation light receiving portion 541 is formed on the first end portion of the second light guide 54, and the second end portion of the second light guide 54 is adjacent to the lens 55. An included angle which is larger than 0 and smaller than 180 degrees is formed between the first optical axis and the second optical axis. Specifically, in this embodiment, the included angle is smaller than 90 degrees, the first optical axis intersects the horizontal plane in an inclined manner, and the second optical axis intersects the horizontal plane in a perpendicular manner. The emission light emitting portion 531 is formed on the upper end surface of the first light guide 53, and the excitation light receiving portion 541 is formed on the upper end surface of the second light guide 54.
Each detection channel corresponds to one emission light path and one excitation light path. Therefore, the light source 52 detection device includes a plurality of emission light paths arranged in parallel in the left-right direction and a plurality of excitation light paths arranged in parallel in the left-right direction. The light sources 52 are LED lamps, and the light sources 52 of the plurality of emission light paths form an LED light bar extending in the left-right direction.
The first light guide 53 includes a light guide pillar, the holder 51 is provided with a mounting hole, the light guide pillar is inserted into the mounting hole, and the upper end surface of the light guide pillar is located below the chip groove 22 to form a light emitting portion 531. The light guide column is a solid organic glass column. The whole light guide column is obliquely arranged in a cylindrical shape, and the central line of the light guide column coincides with the first optical axis. The upper end of the light guide bar is partially cut to form a planar emission light exit 531, and faces the chip grooves 22 on the upper and rear sides thereof.
The second light guide 54 is an optical fiber, the upper end surface of which is located right below the chip groove 22 to form an excitation light receiving portion 541, and which is provided in the holder 51 to guide the fluorescence above the lens 55.
The holder 51 includes a first holder 51a and a second holder 51b, a lower end portion of the first holder 51a is coupled to the base 1, an emission light path and a second light guide 54 are disposed at an upper portion of the first holder 51a, a lens 55 and a fluorescence sensor 57 are disposed in the second holder 51b, and the second holder 51b is detachably coupled to the first holder 51a and positioned below the upper portion of the first holder 51a for easy maintenance. The lens 55 is movably disposed in the second holder 51b along the second optical axis for focusing. Specifically, the lens 55 is screwed into the second holder 51b, and when focusing is performed, the second holder 51b is removed, the lens 55 therein is rotated, and the height of the lens 55 is adjusted, thereby performing focusing.
The excitation light path also includes a filter 56 between the lens 55 and the fluorescence sensor 57 to filter out stray light outside of a particular wavelength range.
The optical detection device further comprises an end cap 51c, and the end cap 51c is arranged below the fluorescent sensor 57 and is hermetically connected with the second bracket 51b to prevent dust and water.
The working process of the nucleic acid detector is as follows:
inserting the microfluidic chip into the chip mounting assembly, and operating a motor to drive a mechanical arm to move so as to drive a piston to move, so that a sample and a reagent of the microfluidic chip are mixed or the reagent flows into a target chamber until the sample and the reagent enter a reaction cavity for amplification reaction; electrifying the heating device to heat the reaction cavity; after the reaction is finished, the heating is stopped, the optical detection device is electrified, the reaction cavity is irradiated and the excited fluorescence is received, and qualitative and quantitative detection is carried out according to the color and the intensity of the fluorescence.
The nucleic acid detection device has the advantages of compact structure, small volume, simple operation and convenient use, and can automatically realize nucleic acid extraction, amplification and 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 (11)
1. The utility model provides a nucleic acid detector, includes base, chip installation subassembly, heating device, optical detection device and arm subassembly, its characterized in that:
the chip mounting assembly is arranged on the left side part of the base and comprises a box body, a chip groove for containing the microfluidic chip is formed in the box body, and the chip groove is provided with an upward-facing notch;
the heating device is arranged on the front side or the rear side of the chip mounting assembly and used for heating the microfluidic chip in the chip groove;
the optical detection device is arranged below the chip mounting assembly and is provided with an emitted light emitting part and an excitation light receiving part which face the lower end part of the microfluidic chip, and the lower end part of the box body is provided with a hollow-out part which can allow emitted light to enter the chip groove and allow excitation light to exit the chip groove;
the mechanical arm assembly is arranged on the right side of the chip mounting assembly and comprises a mechanical arm capable of moving in the left-right direction, the mechanical arm is provided with a fork, and the fork is provided with a joint groove for clamping the end part of the piston of the microfluidic chip.
2. The nucleic acid detecting instrument according to claim 1, wherein: the box body is provided with a right side wall, a notch extending downwards from the upper edge of the right side wall is formed in the right side wall, so that the right end part of the piston on the microfluidic chip can be inserted into the notch and can extend out of the box body, and the joint groove of the fork-shaped piece is aligned with the notch.
3. The nucleic acid detecting instrument according to claim 2, wherein: the notch comprises a first notch and a second notch, the first notch is positioned on the front side or the rear side of the second notch, and the depth of the downward extension of the first notch is smaller than that of the downward extension of the second notch.
4. The nucleic acid detecting instrument according to claim 1, wherein: the lower end part of the box body is hollowed out, and a supporting lug extending inwards is arranged in the middle of the inner wall of the box body; and/or the case has opposite front and back side walls and opposite left and right side walls, the front, left, back and right side walls enclosing the chip slot, the bottom ends of the left and right side walls being connected to the base, the bottom of the back side wall being located at a distance above the base, so that the emission light emitting part and the excitation light receiving part can be located below the chip slot through the bottom of the back side wall; the rear side wall is provided with a through window which can enable the heating device to pass through and be in contact with the microfluidic chip; preceding lateral wall with the back lateral wall is equipped with the operation groove of being convenient for plug chip respectively, the operation groove is from preceding lateral wall or the top edge downwardly extending of back lateral wall.
5. The nucleic acid detecting instrument according to claim 1, wherein: the heating device comprises a mounting seat, a heat conduction block and a heater used for heating the heat conduction block, wherein the heat conduction block is arranged on the mounting seat and is provided with a heating surface which is arranged corresponding to a reaction cavity of the detection chip, the heat conduction block can be movably arranged on the mounting seat, and the heating device further comprises an elastic piece which is arranged between the heat conduction block and the mounting seat.
6. The nucleic acid detecting instrument according to claim 5, wherein: the heat conduction block comprises a body and a connecting pin connected to the body, a connecting hole matched with the connecting pin is formed in the mounting seat, the connecting pin can penetrate through the connecting hole in a sliding mode along the length direction of the connecting pin, threads are formed in the connecting pin, the connecting pin penetrates through the connecting hole and then is inserted into a nut, and the nut is in threaded connection with the connecting pin; and/or the heat conduction block is provided with a bulge, and the heating surface is formed on the front side surface of the bulge; and/or the heat conducting block is an aluminum block; and/or the heater is a heating film which is attached to the heat conducting block.
7. The nucleic acid detecting instrument according to claim 1, wherein: the optical detection device comprises a bracket, an emission light path and an excitation light path, wherein the emission light path and the excitation light path are arranged on the bracket, the emission light path comprises a light source and a first light guide member which are sequentially arranged along a first optical axis, the first light guide member is provided with a first end part and a second end part, the first end part is adjacent to the light source, and an emission light emergent part is formed on the second end part; the excitation light path comprises a lens and a fluorescence sensor which are sequentially arranged along a second optical axis, the excitation light path further comprises a second light guide member with a first end part and a second end part, the excitation light receiving part is formed on the first end part of the second light guide member, and the second end part of the second light guide member is adjacent to the lens; an included angle which is larger than 0 and smaller than 180 degrees is formed between the first optical axis and the second optical axis.
8. The nucleic acid detecting instrument according to claim 7, wherein: the light source detection device comprises a plurality of emission light paths which are arranged in parallel along the left-right direction and a plurality of excitation light paths which are arranged in parallel along the left-right direction.
9. The nucleic acid detecting instrument according to claim 8, wherein: the light sources are LED lamps, and the light sources of the plurality of emission light paths form LED lamp strips extending along the left-right direction; and/or, the first light guide piece comprises a light guide column, the bracket is provided with a mounting hole, the light guide column is inserted into the mounting hole, and the upper end surface of the light guide column is positioned below the chip groove to form the emitted light emergent part; and/or the second light guide part is an optical fiber, the upper end surface of the optical fiber is positioned below the chip groove to form the excitation light receiving part, and the optical fiber is arranged in the bracket.
10. The nucleic acid detecting instrument according to claim 9, wherein: the support includes first support and second support, the lower tip of first support connect in the base, emission light path with the second leaded light spare set up in the upper portion of first support, lens and fluorescence sensor set up in the second support, second support detachably connect in first support and be located the below on the upper portion of first support, lens can follow second optical axis movably set up in the second support.
11. The nucleic acid detecting instrument according to claim 1, wherein: the mechanical arm assembly comprises a mounting frame, a mechanical arm and a driving device, wherein the mechanical arm is slidably arranged on the mounting frame, the driving device is used for driving the mechanical arm to move, the mechanical arm is provided with a fork-shaped part, the fork-shaped part is provided with a joint groove for clamping the end part of a piston of the microfluidic chip,
the engagement groove has a notch facing upward; and/or the presence of a gas in the gas,
the mechanical arm assembly comprises a first mechanical arm and a second mechanical arm, the first mechanical arm is higher than the second mechanical arm, the first mechanical arm and the second mechanical arm are respectively provided with the fork-shaped parts, each fork-shaped part is respectively provided with the joint groove, and the fork-shaped part of the first mechanical arm is offset from the fork-shaped part of the second mechanical arm by a certain distance in a plan view; and/or the presence of a gas in the gas,
the mounting frame is provided with a sliding rail extending along the horizontal direction, the mechanical arm is movably arranged on the sliding rail along the horizontal direction, a sliding groove matched with the sliding rail is formed in the mechanical arm, and the sliding rail is inserted in the sliding groove; and/or the presence of a gas in the gas,
the driving device comprises a motor and a screw rod driven by the motor to reciprocate, and the mechanical arm is connected to the screw rod.
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|---|---|---|---|
| CN202110633267.4A CN113376133A (en) | 2021-06-07 | 2021-06-07 | Nucleic acid detector |
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| CN202110633267.4A CN113376133A (en) | 2021-06-07 | 2021-06-07 | Nucleic acid detector |
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| CN113376133A true CN113376133A (en) | 2021-09-10 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN113945547A (en) * | 2021-09-28 | 2022-01-18 | 江苏汇先医药技术有限公司 | Multi-channel LAMP detector and control method thereof |
| CN114100722A (en) * | 2021-12-27 | 2022-03-01 | 北京梓晶生物科技有限公司 | Portable full-automatic nucleic acid constant temperature amplification device |
| CN114437911A (en) * | 2022-01-13 | 2022-05-06 | 深圳清华大学研究院 | Gene sequencing device |
| WO2023050711A1 (en) * | 2021-09-28 | 2023-04-06 | 江苏汇先医药技术有限公司 | Multi-channel lamp detector |
| WO2023060851A1 (en) * | 2021-10-12 | 2023-04-20 | 江苏汇先医药技术有限公司 | Lamp tester and control method |
| WO2023060850A1 (en) * | 2021-10-12 | 2023-04-20 | 江苏汇先医药技术有限公司 | Handheld lamp detector and system |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113945547A (en) * | 2021-09-28 | 2022-01-18 | 江苏汇先医药技术有限公司 | Multi-channel LAMP detector and control method thereof |
| WO2023050710A1 (en) * | 2021-09-28 | 2023-04-06 | 江苏汇先医药技术有限公司 | Multi-channel lamp detector and control method thereof |
| WO2023050711A1 (en) * | 2021-09-28 | 2023-04-06 | 江苏汇先医药技术有限公司 | Multi-channel lamp detector |
| CN113945547B (en) * | 2021-09-28 | 2023-07-25 | 江苏汇先医药技术有限公司 | Multichannel LAMP detector and control method thereof |
| WO2023060851A1 (en) * | 2021-10-12 | 2023-04-20 | 江苏汇先医药技术有限公司 | Lamp tester and control method |
| WO2023060850A1 (en) * | 2021-10-12 | 2023-04-20 | 江苏汇先医药技术有限公司 | Handheld lamp detector and system |
| CN114100722A (en) * | 2021-12-27 | 2022-03-01 | 北京梓晶生物科技有限公司 | Portable full-automatic nucleic acid constant temperature amplification device |
| CN114100722B (en) * | 2021-12-27 | 2024-06-04 | 北京梓晶生物科技有限公司 | Portable full-automatic nucleic acid isothermal amplification device |
| CN114437911A (en) * | 2022-01-13 | 2022-05-06 | 深圳清华大学研究院 | Gene sequencing device |
| CN114437911B (en) * | 2022-01-13 | 2023-08-01 | 深圳清华大学研究院 | Gene sequencing device |
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