CN107523494B - Fluid system and nucleic acid sequencing system with same - Google Patents
Fluid system and nucleic acid sequencing system with same Download PDFInfo
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- CN107523494B CN107523494B CN201710879637.6A CN201710879637A CN107523494B CN 107523494 B CN107523494 B CN 107523494B CN 201710879637 A CN201710879637 A CN 201710879637A CN 107523494 B CN107523494 B CN 107523494B
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Abstract
The invention relates to a fluid system and a nucleic acid sequencing system with the fluid system, wherein the fluid system comprises a frame structure, a container support, a reagent container, a pipette, a reagent selection valve manifold, a first sensor, a second sensor, a rotary bracket, a fixed support, a thermoelectric cooling element and a control system; when the reagent container is inserted into the container support, the reagent container collides with the rotating bracket to enable the rotating bracket to rotate, when the container support is lifted to the reagent loading position, the rotating bracket and the fixed bracket respectively trigger the first sensor and the second sensor, and when the control system receives signals of the first sensor and the second sensor to confirm that the reagent container is completely loaded, the reagent in the reagent container can be transferred to other parts through the suction pipe and the reagent selection valve manifold.
Description
Technical Field
The invention relates to a fluid system suitable for a nucleic acid sequencing process and a nucleic acid sequencing system with the fluid system, and relates to the technical field of electronic and optical detection.
Background
In order to better understand human code, a deeper understanding of the human genome is required, and by deciphering the information carried by the genome, it is possible to detect adverse factors that may affect human health and the effects of viral or bacterial specificity and variability on humans, and furthermore, by deciphering the information carried by the genome, genetic diseases can be predicted to some extent. Therefore, the full understanding of the human genome and all its characteristics, linking genes to certain health conditions, can lead to the full treatment of diseases and the improvement of health, lead to the development of therapeutics, and further improve the health conditions of humans, leading to a longer life of humans. The above studies can obviously also be carried out in animals and plants, to allow the development of genetic techniques for improving virus-resistant crops and to avoid the loss of whole crops in certain regions, or to allow the growth of crops in non-traditional environments, such as: planting corn in desert area. At present, knowledge about the human genome or the genome of any other species is far from complete.
As described above, there is a need to develop more techniques for nucleic acid sequencing in order to find commonalities and correlations for sequencing individuals, i.e., animals and plants, to achieve a complete understanding of the genome. Devices for nucleic acid sequencing already exist in the prior art, but they suffer from the disadvantage of being expensive and time consuming, preventing the study of genomes and the common relationship of genomic sequences called genotypes to known physical characteristics, called phenotypes. These studies typically use information from thousands of individuals in order to be statistically valid and relevant, requiring sequencing billions of nucleotides (30 million nucleotides per human genome) and analyzing the common relationship of information each having multiple clinically relevant features, yet existing nucleic acid sequencing devices fail to meet this need.
Disclosure of Invention
In view of the above problems, it is an object of the present invention to provide a fluid system and a nucleic acid sequencing system having the same, which are low in cost and rapid in sequencing.
In order to achieve the purpose, the invention adopts the following technical scheme: a fluidic system comprising a frame structure, a container support, a reagent container, a pipette, a reagent selection valve manifold, a first sensor, a second sensor, a thermoelectric cooling element, and a control system; the frame structure is formed by fixedly connecting a top plate, a bottom plate and a support rod, and a front side plate, a rear side plate, a left side plate and a right side plate are arranged around the frame structure respectively to form a box body structure; the container support is arranged in the box body structure, two ends of the container support are fixedly connected with the left side plate and the right side plate through lifting mechanisms respectively, the front side plate is connected with the lifting mechanisms through connecting rods to form a manual operation door, and the connecting rods push the lifting mechanisms to act to enable the container support to move up and down in the box body structure; the reagent containers are movably inserted in the container support, the suckers are arranged on the top plate at intervals, positions and number of the suckers correspond to those of the suckers, through holes are formed in the top of the container support at intervals, reagent storage grooves are formed in the top of the reagent containers at intervals, reagent selection valve manifolds with the same number as the suckers are fixedly arranged on one side of the top plate, and each reagent selection valve manifold is connected with the corresponding sucker; the rear end part of the top plate is fixedly provided with the first sensor for detecting whether the reagent container is inserted into the container support or not and the second sensor for detecting whether the container support reaches a reagent loading position or not, and the rear side plate is provided with the thermoelectric cooling element; the first sensor, the second sensor and the thermoelectric cooling element are respectively electrically connected with the control system.
Further, corresponding to the positions and the number of the straws, straw brackets for supporting the straws are arranged on the top plate at intervals.
Further, a handle is arranged on the manual operation door, a third sensor and/or an actuator used for detecting whether the manual operation door is in a closed state is correspondingly arranged at the front end parts of the manual operation door and the top plate, and the third sensor and/or the actuator is also electrically connected with the control system.
Further, a rotating bracket and a fixed bracket are arranged at the top of the container bracket corresponding to the first sensor and the second sensor; the reagent container impacts the rotating bracket to rotate the rotating bracket when the reagent container is inserted into the container support, the rotating bracket triggers the first sensor when the container support is lifted to a reagent loading position, and the fixed bracket triggers the second sensor; the rotating bracket remains in a stationary position when the reagent vessel is not inserted into the vessel support, the rotating bracket is disabled from triggering the first sensor when the vessel support is raised to a reagent loading position, and the stationary bracket triggers the second sensor.
Furthermore, two grooves are formed in the front end of the reagent container, more than one aligning guide piece is arranged at the left end, the right end, the upper end and the lower end of the reagent container, the aligning guide pieces matched with the aligning guide pieces are arranged at the left end, the right end, the upper end and the lower end of the container support, a protective adhesive foil for the straw to penetrate through is arranged at the top of the reagent container, and an identification label for identifying the batch number, the manufacturing date or the origin of the reagent in the reagent container is further arranged on the reagent container.
Furthermore, the lifting mechanism comprises two slide block guiding pieces, two slide blocks and two telescopic brackets; each telescopic bracket all adopts parallelogram frame, two slider guide spare longitudinal separation sets up on left side board or the right side board, two the inner of slider guide spare is all through one slider swing joint the container support, two the outer end of slider is connected one telescopic bracket's top removal end is close to the telescopic bracket outside of manually-operated gate removes end fixed connection the one end of connecting rod, the other end fixed connection of connecting rod the manually-operated gate, telescopic bracket's bottom stiff end fixed connection left side board or right side board.
Furthermore, the rear side plate is made of a conductive metal plate, and a heat dissipation device is arranged on the rear side of the thermoelectric cooling element on the rear side plate.
Furthermore, corresponding to the positions and the number of the through holes, sleeves are arranged at the top of the container support, and the straws penetrate through the corresponding sleeves and the through holes and extend into the reagent containers; the upper part of the front side of the frame structure is also provided with a side wall.
Further, the bottom of the top plate is provided with a lighting lamp, and the lighting lamp is also electrically connected with the control system.
A nucleic acid sequencing system is characterized by comprising a fluid system, a flow channel control valve, a flow cell, an excitation system, a detection system, a first peristaltic pump, a second peristaltic pump and a waste liquid box, wherein the flow cell is provided with a first flow channel and a second flow channel; all reagent selection valve manifolds of the fluid system are connected with inlets of the flow channel control valves, two outlets of each flow channel control valve are respectively connected with the first flow channel and the second flow channel, the first flow channel is connected with the waste liquid box through the first peristaltic pump, the second flow channel is connected with the waste liquid box through the second peristaltic pump, and the excitation system and the detection system are arranged in the flow cell and used for providing excitation light sources for exciting nucleic acid sequences marked in the reagents in the flow cell to generate fluorescence and detecting fluorescence signals generated by the marked nucleic acid sequences.
Due to the adoption of the technical scheme, the invention has the following advantages: 1. according to the fluid system, the container support, the lifting mechanism, the connecting rod, the first sensor, the second sensor, the rotating bracket and the fixed support are arranged, when the reagent container is inserted into the container support, the reagent container collides with the rotating bracket to enable the rotating bracket to rotate, the container support is lifted to the reagent loading position after the manual operation door is closed, the rotating bracket and the fixed support respectively trigger the first sensor and the second sensor, and when the control system receives signals of the first sensor and the second sensor to confirm that the reagent container is completely loaded, the reagent in the reagent container can be transferred to other components through the suction pipe and the reagent selection valve manifold. 2. The protective adhesive foil is arranged on the top of the reagent container, so that the freshness of the liquid reagent in the reagent storage groove can be ensured, the liquid reagent is prevented from being polluted and overflowing, and the sensitive reagent can be protected from being irradiated by light. 3. The rear side plate of the invention adopts a metal plate with good electric conductivity, and the thermoelectric cooling element arranged on the metal plate heats or cools the reagent in the reagent container, so that the fluid system of the invention can adapt to different reagent storage conditions and use requirements. 4. The top of the container support is provided with the sleeve, the upper part of the front side of the frame structure is provided with the side wall, and the sleeve and the side wall form a basic protection mechanism for preventing personal injury, so that the personal injury caused by the sharpness of the suction pipe when a user inserts a hand into a reagent container when the reagent container is not in the box body structure can be prevented, and the protection coefficient is increased. 5. The illumination source is arranged in the box body structure, so that a user can easily insert or remove the reagent container under the condition of poor or insufficient external illumination, and the reagent container can be widely applied to the technical field of electronic and optical detection.
Drawings
FIG. 1 is a 3D overview of the fluid system of the present invention in a closed door position;
FIG. 2 is a 3D overview of the fluid system of the present invention in an open door state;
FIG. 3 is a front cross-sectional view of a fluid system of the present invention;
FIG. 4 is a schematic view of the structure of a reagent vessel of the present invention;
FIG. 5 is a schematic cross-sectional view of a reagent vessel of the present invention;
fig. 6 is a schematic view of the structure and the operation state of the lifting mechanism of the present invention, wherein fig. 6(a) is a schematic view of the operation state of the lifting mechanism of the present invention when the fluid system is in the door-open state, and fig. 6(b) is a schematic view of the operation state of the lifting mechanism of the present invention when the fluid system is in the door-close state;
FIG. 7 is a schematic diagram of the structure of a thermoelectric cooling element and corresponding heat sink of the present invention;
FIG. 8 is a central cross-sectional view of the fluid system of the present invention in an open door condition;
FIG. 9 is a central cross-sectional view of the fluid system of the present invention in a closed door condition;
FIG. 10 is a cross-sectional view of a straw and primary protection mechanism for personal injury in a fluid system of the present invention;
FIG. 11 is a cross-sectional view of a pipette fully inserted into a reagent container in a fluidic system of the present invention;
FIG. 12 is a schematic diagram of the structure of the nucleic acid sequencing system of the present invention.
Detailed Description
The present invention is described in detail below with reference to the attached drawings. It is to be understood, however, that the drawings are provided solely for the purposes of promoting an understanding of the invention and that they are not to be construed as limiting the invention. In the description of the present invention, it is to be understood that the terms "first," "second," and the like are used for descriptive purposes only and are not to be construed as indicating or implying relative importance.
As shown in fig. 1-3 and 7-9, the present invention provides a fluidic system comprising a frame structure 1, a container support 2, a lift mechanism 3, a reagent container 4, a pipette 5, a pipette support 6, a reagent selection valve manifold 7, a first sensor 8, a second sensor 9, a third sensor and/or actuator 10, a thermoelectric cooling element 11, and a control system.
The frame structure 1 is formed by fixedly connecting a top plate 1-1, a bottom plate 1-2 and support rods, wherein a front side plate 1-3, a rear side plate 1-4, a left side plate 1-5 and a right side plate 1-6 are respectively arranged on the periphery of the frame structure 1 to form a box body structure, and the rear side plate 1-4 of the box body structure is a metal plate with good electrical conductivity.
A container support 2 is arranged in the box body structure, two ends of the container support 2 are fixedly connected with a left side plate 1-5 and a right side plate 1-6 of the box body structure through a lifting mechanism 3 respectively, a front side plate 1-3 of the box body structure is connected with the lifting mechanism 3 through a connecting rod 1-7 to form a manual operation door, and the lifting mechanism 3 is pushed to act when the connecting rod 1-7 acts, so that the container support 2 can move up and down in the box body structure. Reagent containers 4 are movably inserted in the container support 2, and straw supports 6 for supporting straws 5 are arranged on the top plate 1-1 of the frame structure 1 at intervals. Corresponding to the positions and the number of the straws 5, through holes 2-1 are arranged at intervals on the top of the container support 2, reagent storage grooves 4-1 are arranged at intervals on the top of the reagent containers 4, reagent selection valve manifolds 7 with the same number as the straws 5 are fixedly arranged on one side of the top plate 1-1 of the frame structure 1, and each reagent selection valve manifold 7 is respectively connected with the corresponding straw 5 through a pipeline.
A first sensor 8 and a second sensor 9 are fixedly arranged at the rear end part of a top plate 1-1 of the frame structure 1, and a rotating bracket 2-2 for triggering the first sensor 8 and a fixed bracket 2-3 for triggering the second sensor 9 are arranged at the top part of the container support 2 corresponding to the two sensors. The manual operation door is closed, the lifting mechanism 3 drives the container support 2 to move upwards, the fixed support 2-3 and the rotating bracket 2-2 are both in a lifting state, the second sensor 9 is used for detecting whether the container support 2 reaches a reagent loading position, when the container support 2 is lifted to the reagent loading position, the fixed support 2-3 triggers the second sensor 2-3, the first sensor 8 is used for detecting whether the reagent container 4 is inserted into the container support 2, when the reagent container 4 is inserted into the container support 2, the reagent container 4 collides with the rotating bracket 2-2 to enable the rotating bracket 2-2 to rotate, when the container support 2 is lifted to the reagent loading position, the rotating bracket 2-2 can trigger the first sensor 8, when the reagent container 4 is not inserted into the container support 2, the rotating bracket 2-2 is kept in a static position of about 30 degrees, when the container holder 2 is lifted to the reagent loading position, the rotating bracket 2-2 cannot trigger the first sensor 8. A third sensor and/or actuator 10 is provided in correspondence with the front end of the top plate 1-1 of the frame structure 1 for detecting whether the door is closed.
The rear side plate 1-4 of the box body structure is provided with a plurality of thermoelectric cooling elements 11. The first sensor 8, the second sensor 9, the third sensor and/or actuator 10 and the thermo-electric cooling element 11 are each electrically connected to the control system.
In a preferred embodiment, the manually operated door may be provided with handles 1-8.
In a preferred embodiment, the first sensor 8, the second sensor 9 and the third sensor and/or actuator 10 may each be a magnetic sensor, an optical sensor or a mechanical sensor.
In a preferred embodiment, as shown in fig. 3 to 5, the reagent container 4 may be a rectangular parallelepiped structure, the front end of the reagent container 4 is provided with two grooves 4-2 for facilitating the manual insertion and removal of the reagent container 4 from the container holder 2, the left and/or upper and lower ends of the reagent container 4 are provided with one or more alignment guides 4-3, and the left and/or upper and lower ends of the container holder 2 are provided with alignment guides 2-4 for cooperating with the alignment guides 4-3. The top of the reagent container 4 is provided with a protective adhesive foil 4-4 for the straw 5 to penetrate through, the protective adhesive foil 4-4 can be made of a transparent foil or an aluminum foil made of an adhesive or a non-adhesive, freshness of liquid reagents in the reagent storage groove 4-1 can be guaranteed, the liquid reagents are prevented from being polluted and overflowing, sensitive reagents can be protected from illumination, the shape and the size of the reagent storage groove 4-1 can be set according to actual conditions, and each reagent storage groove 4-1 can also be different in shape and size to meet different reagent volume requirements. In addition, the reagent container 4 is provided with an identification tag 4-5 on the top thereof for identifying the lot number, the date of manufacture, the place of origin, etc. of the reagent in the reagent container 4, and the identification tag 4-5 may be a bar code, a two-dimensional code, an RFID tag, a contact electronic tag or a non-contact electronic tag.
In a preferred embodiment, as shown in fig. 6, the lifting mechanism 3 comprises two slide guides 3-1, two sliding blocks 3-2 and two telescopic supports 3-3, wherein each telescopic support 3-3 adopts a parallelogram frame, two sliding block guiding pieces 3-1 are longitudinally arranged on a left side plate 1-5 or a right side plate 1-6 of the box structure at intervals, the inner ends of the two sliding block guiding pieces 3-1 are movably connected with the container support 2 through one sliding block 3-2, the outer ends of the two sliding blocks 3-2 are connected with the top moving end of one telescopic support 3-3, the outer side moving end of the telescopic support 3-3 close to the manual operation door is fixedly connected with one end of a connecting rod 1-7, the other end of the connecting rod 1-7 is fixedly connected with the manual operation door, and the bottom fixing end of the telescopic support 3-3 is fixedly connected with the left side plate 1-5 or the right side plate 1-6 of the box structure. When the manual operation door is closed, the telescopic support 3-3 is extended through the folding action of the connecting rod 1-7 and the telescopic support 3-3, and the telescopic support 3-3 is extended and drives the sliding block 3-2 to move on the sliding block guide part 3-1, so that the container support 2 moves in the vertical direction.
In a preferred embodiment, as shown in fig. 7, a heat sink 12 is disposed behind each thermoelectric cooling element 11, and the heat sink 12 may be a water-cooled dissipation heat sink or a fan heat sink. The number and size of the thermoelectric cooling elements 11 may vary according to the reagent temperature requirements, which may be of various sizes in different types of embodiments. The number and size of the heat sinks 12 may or may not vary accordingly.
In a preferred embodiment, as shown in fig. 8, the upper front side of the frame structure 1 is provided with side walls 1-9, preventing the entry of hands into the suction pipe 5 from above the container support 2, increasing the protection factor.
In a preferred embodiment, as shown in fig. 8 and 10, in order to pierce the protective adhesive foil 4-4 when the container holder 2 is lifted, the tips of the pipettes 5 are arranged sharp and, if no associated protective measures are taken, the hands may be pricked by the pipettes 5 causing injury, so that, corresponding to the position and number of the through holes 2-1, the container holder 2 is provided with a sleeve 2-5 on top, and the pipettes 5 extend through the corresponding sleeve 2-5 and through hole 2-1 into the reagent container 4.
In a preferred embodiment, as shown in fig. 10, the bottom of the top plate 1-1 of the frame structure 1 is further provided with illuminating lamps 1-10, the illuminating lamps 1-10 can be LED lamps, halogen lamps or other light sources so as to enable the reagent vessel 4 to be conveniently inserted into or removed from the vessel support 2 in the case of poor or insufficient external illumination, and the illuminating lamps 1-10 are also electrically connected with the control system.
In a preferred embodiment, as shown in fig. 10, 11, the pipette 5 may be used in different lengths according to the type of reagent to be used for the reagent container 4, i.e., the pipette 5 may be designed to be both contact type and non-contact type at the bottom of the reagent storage well 4-1.
As shown in fig. 12, the present invention further provides a nucleic acid sequencing system, which includes the above-mentioned fluid system, a flow channel control valve 13, a flow cell 14, an excitation system, a detection system, a first peristaltic pump 15, a second peristaltic pump 16, and a waste liquid box 17, wherein the flow cell 14 is provided with a first flow channel 14-1 and a second flow channel 14-2, and the first peristaltic pump 15 and the second peristaltic pump 16 may be provided with a reversing valve; all reagent selection valve manifolds 7 of the fluid system are connected with inlets of a flow channel control valve 13 through pipelines, two outlets of the flow channel control valve 13 are respectively connected with a first flow channel 14-1 and a second flow channel 14-2 through pipelines, the first flow channel 14-1 is connected with a waste liquid box 17 through a first peristaltic pump 15 through a pipeline, the second flow channel 14-2 is connected with the waste liquid box 17 through a second peristaltic pump 16 through a pipeline, an excitation system and a detection system are arranged in a flow cell 14, the excitation system is used for providing a fluorescence excitation light source for exciting a nucleic acid sequence marked in a reagent in the flow cell 14 to generate fluorescence, and the detection system is used for detecting a fluorescence signal generated by the marked nucleic acid sequence to complete nucleic acid sequencing.
In a preferred embodiment, the detection system may be composed of different optical elements of various properties, including but not limited to filters of different wavelengths, tube lenses, relay lenses, and cameras, which may be CCD or CMOS, and which may perform area, line or TDI scanning. The detection system may include more than one camera, more than one filter, or any combination of all of the above elements. For this process, the flow cell 14 is placed in a sample stage and moved in the X and Y directions while the camera, filters and lenses remain stationary, the motion of the sample stage being synchronized with the camera taking the image to ensure proper image capture. The captured images will then be processed using a particular image to find the location of each nucleic acid cluster, determine the fluorescence received by each filter, and determine the nucleic acid bases synthesized based on the fluorescence received by each filter. Finally, the information of the number of bases and reliability to be determined is recorded in a standard format file.
In a preferred embodiment, the excitation system can adopt lasers or LED light sources, the number is not limited, and the excitation system can be selected for practical use. The excitation system can provide excitation light with different wavelengths according to the requirement of the excitation wavelength of the fluorescent dye.
As will be described further below, in the method of using the nucleic acid sequencing system of the present invention, the flow cell 14 is placed on the sample stage, the nucleotide-based reagents labeled with different dyes are placed in the reagent storage wells 4-1 of the reagent containers 4, the rotary rack 2-2 is rotated on the X-axis by the reagent containers 4, the closed manually-operated door container holder 2 is lifted, the rotary rack 2-2 and the fixed rack 2-3 trigger the first sensor 8 and the second sensor 9, respectively, the control system receives signals from the first sensor 8 and the second sensor 9 to confirm that the reagent containers 4 are fully loaded, and the control system receives signals from the third sensor and/or the actuator 10 to ensure that the manually-operated door is in a fully closed state when the fluidic system is ready for use. The pipettes 5 are completely submerged in the reagent and the reagent may be transferred from the reagent containers 4 to the pipettes 5 and other components of the fluidic system. And adjusting the opening state of the flow channel control valve 13 to select a certain flow channel such as a first flow channel 14-1, opening a first peristaltic pump 15 to enable the reagent to flow into the first flow channel 14-1 from the pipette 5 and a corresponding reagent selection valve manifold 7, emitting excitation light by an excitation system to irradiate the nucleotide base reagent of the first flow channel 14-1, exciting the dye marked by the nucleotide base reagent to emit fluorescence, detecting a fluorescence signal by a detection system after the fluorescence signal is imaged by an imaging system, and processing the detection result by the detection system to complete the sequencing of the nucleotide base reagent.
In a preferred embodiment, nucleic acid sequencing can be performed by sequencing by synthesis or by ligation, incorporating nucleotides into a nucleic acid template, typically arranged in a group of clones called clusters, wherein the clone copies are obtained by amplifying an original template strand using polymerase chain reaction methods. Both of the above nucleic acid sequencing can be detected using fluorescent probes, wherein each different nucleotide base (A, C, T or G) is labeled with a different dye that fluoresces at a different wavelength, and a combination of matched filters can be used to detect the presence of the different nucleotide bases. The different bases containing the fluorescent dye can be imaged simultaneously or independently. If imaged simultaneously, it is desirable to use a filter set to detect the presence of different dyes separately, and if imaged independently, no filter is required, nor is it necessary to have different dyes at different nucleotide bases. Other methods for sequencing may also be used, for example: the coding mechanism can be achieved when different numbers of dyes are attached to the nucleotide bases, when only two dyes are used, two of which receive two different dyes and the third receives a mixture of the two dyes. The fourth nucleotide base does not receive any dye and by using this method only two colors need to be read in the flow cell 14, reducing the complexity for the detection system, which can perform detection of two different colors using a combination of two detection systems, such as a CCD camera, each equipped with a filter matched to the emission wavelength of one dye, or by using one detection system in combination, equipped with a filter selection device, such as a filter wheel, equipped with two filters matched to the emission wavelengths of two dyes. However, this sequencing method requires consideration of: first, the third nucleotide base should receive the balance of the two dyes so as not to be erroneously detected as the other nucleotide base; second, at the start of the sequencing method, a calibration procedure must be performed in order to detect the presence of cluster sites for all clusters, since the fourth nucleotide base will not have an attached dye and therefore will not emit light of any wavelength and will not be detected by the device. Thus, the detection system controller would have to assume that a fourth nucleotide is present when no dye is detected, for which matter the detection system controller would need to take care of all cluster positions on the flow cell 14, and assume that a fourth nucleotide is attached if no dye is detected at a given position where a cluster is known to be present.
The above embodiments are only used for illustrating the present invention, and the structure, connection mode, manufacturing process, etc. of the components may be changed, and all equivalent changes and modifications performed on the basis of the technical solution of the present invention should not be excluded from the protection scope of the present invention.
Claims (9)
1. A fluidic system comprising a frame structure, a container support, a reagent container, a pipette, a reagent selection valve manifold, a first sensor, a second sensor, a thermoelectric cooling element, and a control system;
the frame structure is formed by fixedly connecting a top plate, a bottom plate and a support rod, and a front side plate, a rear side plate, a left side plate and a right side plate are arranged around the frame structure respectively to form a box body structure;
the container support is arranged in the box body structure, two ends of the container support are fixedly connected with the left side plate and the right side plate through lifting mechanisms respectively, the front side plate is connected with the lifting mechanisms through connecting rods to form a manual operation door, and the connecting rods push the lifting mechanisms to act to enable the container support to move up and down in the box body structure; the reagent containers are movably inserted in the container support, the suckers are arranged on the top plate at intervals, positions and number of the suckers correspond to those of the suckers, through holes are formed in the top of the container support at intervals, reagent storage grooves are formed in the top of the reagent containers at intervals, reagent selection valve manifolds with the same number as the suckers are fixedly arranged on one side of the top plate, and each reagent selection valve manifold is connected with the corresponding sucker;
the rear end part of the top plate is fixedly provided with the first sensor for detecting whether the reagent container is inserted into the container support or not and the second sensor for detecting whether the container support reaches a reagent loading position or not, and the rear side plate is provided with the thermoelectric cooling element; a rotating bracket and a fixed bracket are arranged at the top of the container bracket corresponding to the first sensor and the second sensor; the reagent container impacts the rotating bracket to rotate the rotating bracket when the reagent container is inserted into the container support, the rotating bracket triggers the first sensor when the container support is lifted to a reagent loading position, and the fixed bracket triggers the second sensor; the rotating carriage remains in a stationary position when the reagent container is not inserted into the container support, the rotating carriage is disabled from triggering the first sensor when the container support is raised to a reagent loading position, and the stationary carriage triggers the second sensor;
the first sensor, the second sensor and the thermoelectric cooling element are respectively electrically connected with the control system.
2. A fluid system according to claim 1, wherein pipette holders for holding the pipettes are spaced apart on the top plate corresponding to the location and number of the pipettes.
3. The fluid system as claimed in claim 1, wherein the manual door is provided with a handle, the manual door and the front end of the top plate are correspondingly provided with a third sensor and/or actuator for detecting whether the manual door is in a closed state, and the third sensor and/or actuator is electrically connected with the control system.
4. The fluid system according to claim 1, wherein the reagent container has two grooves at the front end thereof, the reagent container has more than one alignment guide at each of the left and right ends and/or the upper and lower ends thereof, the container holder has an alignment guide at each of the left and right ends and/or the upper and lower ends thereof, the reagent container has a protective adhesive foil on the top thereof for the straw to pass through, and the reagent container has an identification tag for identifying a lot number, a manufacturing date, or a place of origin of the reagent in the reagent container.
5. The fluid system of claim 1, wherein the lifting mechanism comprises two slide guides, two slides, and two telescoping legs;
each telescopic bracket all adopts parallelogram frame, two slider guide spare longitudinal separation sets up on left side board or the right side board, two the inner of slider guide spare is all through one slider swing joint the container support, two the outer end of slider is connected one telescopic bracket's top removal end is close to the telescopic bracket outside of manually-operated gate removes end fixed connection the one end of connecting rod, the other end fixed connection of connecting rod the manually-operated gate, telescopic bracket's bottom stiff end fixed connection left side board or right side board.
6. A fluid system according to any one of claims 1 to 5, wherein the rear plate is an electrically conductive metal plate and the thermoelectric cooling elements on the rear plate are provided with heat sinks on their rear sides.
7. A fluid system according to any one of claims 1 to 5, wherein a sleeve is provided at the top of the container holder corresponding to the position and number of the through holes, and the pipette is inserted into the reagent container through the corresponding sleeve and through hole; the upper part of the front side of the frame structure is also provided with a side wall for preventing hands from entering the suction pipe from the upper part of the container bracket.
8. A fluid system according to any one of claims 1 to 5, wherein a light is provided on the bottom of the top plate, the light being further electrically connected to the control system.
9. A nucleic acid sequencing system comprising the fluidic system of any one of claims 1 to 8, a flow channel control valve, a flow cell, an excitation system, a detection system, a first peristaltic pump, a second peristaltic pump, and a waste fluid cassette, wherein the flow cell is provided with a first flow channel and a second flow channel;
all reagent selection valve manifolds of the fluid system are connected with inlets of the flow channel control valves, two outlets of each flow channel control valve are respectively connected with the first flow channel and the second flow channel, the first flow channel is connected with the waste liquid box through the first peristaltic pump, the second flow channel is connected with the waste liquid box through the second peristaltic pump, and the excitation system and the detection system are arranged in the flow cell and used for providing excitation light sources for exciting nucleic acid sequences marked in the reagents in the flow cell to generate fluorescence and detecting fluorescence signals generated by the marked nucleic acid sequences.
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