CN115637209B - Sample extraction cartridge, sample extraction method, and nucleic acid detection apparatus - Google Patents

Abstract

The invention discloses a sample extraction card box, a sample extraction method and nucleic acid detection equipment, wherein the sample extraction card box comprises a card box base and a plurality of chamber combinations, each chamber combination comprises a first chamber, a second chamber, a first mixing chamber, a second mixing chamber, a third chamber and a fourth chamber, a preservative solution is stored in the first chamber, a washing solution is stored in the second chamber, a cracking solution is stored in the second mixing chamber, the third chamber is used for communicating with an air source, and an eluent is stored in the fourth chamber; the cartridge base is provided with a plurality of fluid path assemblies. Each chamber of the chamber combination is correspondingly switched on and off with each liquid path of the liquid path combination, so that sample liquid mixing, washing, residual liquid cleaning, elution and liquid discharging are realized, the extraction efficiency and the detection efficiency are improved, and the waste liquid is stored in the first chamber, so that the structure utilization rate is improved. The amplification card box is designed to be provided with a plurality of chamber combinations and a plurality of liquid path combinations, so that a multi-channel parallel card box structure is obtained, and sample liquid can be synchronously processed. The invention can be widely applied to the technical field of biomedical instruments.

Description

Sample extraction cartridge, sample extraction method, and nucleic acid detection apparatus

Technical Field

The invention relates to the technical field of biomedical instruments, in particular to a sample extraction card box, a sample extraction method and nucleic acid detection equipment.

Background

In the biomolecule detection, the transfer and specific operation between liquids are involved, and in the transfer process, most of the methods adopt open suction, transfer or pouring between reagent tubes, which easily causes volatile toxic reagents to volatilize and diffuse to the outside of the container, pollutes the external environment, and endangers the personal safety of operators.

In recent years, rapid and high-throughput detection becomes a new requirement for pathogen detection, the detection must be safe and rapid, and both traditional manual detection and existing automatic detection equipment inevitably cause external pollution to a use scene, so that specialized planning operation needs to be performed.

In addition, although the current commercialized nucleic acid detection equipment also has full-automatic detection equipment integrating extraction, sample extraction and detection, most of the equipment adopts a single-channel card box or completes high flux in a mode of overlapping the single-channel card boxes, so that the requirement of the nucleic acid detection equipment on high flux is difficult to meet, and the detection efficiency is not high.

Disclosure of Invention

In order to solve at least one of the above problems, the present invention provides a sample extraction cartridge, a sample extraction method, and a nucleic acid detection apparatus, using the following technical solutions.

The sample extraction cartridge nucleic acid detection device provided by the invention comprises a sample extraction cartridge.

The sample extraction card box provided by the invention comprises a card box base and a plurality of chamber combinations, wherein the chamber combinations are connected with the card box base, each chamber combination comprises a first chamber, a second chamber, a first mixing chamber, a second mixing chamber, a third chamber and a fourth chamber, a preserving fluid can be stored in the first chamber, and the first chamber is connected with the card box base; the second chamber is connected with the cartridge base, washing liquid can be stored in the second chamber, and the second chamber is provided with a second plunger; the first mixing chamber is connected with the cartridge base, the first mixing chamber being provided with a first mixing plunger; the second mixing chamber is connected with the card box base, a lysate can be stored in the second mixing chamber, and a second mixing plunger is arranged in the second mixing chamber; the third chamber is connected with the card box base and is used for being communicated with a gas source; the fourth chamber is connected with the cassette base, eluent can be stored in the fourth chamber, and a fourth plunger is arranged in the fourth chamber; the card box base is provided with a plurality of liquid path combinations in parallel, each liquid path combination comprises a first liquid path, a second liquid path, a third liquid path and a fourth liquid path, the first liquid paths are respectively used for connecting the first cavity, the second cavity and the first mixing cavity, the second liquid paths are respectively used for connecting the first mixing cavity and the second mixing cavity, the third liquid paths are respectively used for connecting the second mixing cavity, the third cavity and the fourth cavity, the fourth liquid paths are used for discharging processed sample liquid, and each liquid path in the liquid path combinations can be respectively switched on and off.

In some embodiments of the present invention, a magnetic element receiving region is disposed between the first mixing chamber and the second mixing chamber.

In some embodiments of the invention, the sample extraction cartridge comprises a magnetic element that is movable in a direction perpendicular to the surface of the cartridge base towards or away from a magnetic attraction chamber of the cartridge base in the magnetic element receiving area.

In some embodiments of the present invention, the chamber combination includes a fifth chamber, the fifth chamber is connected to the cartridge base, the fifth chamber is used for storing mineral oil or gas, the fifth chamber is provided with a fifth plunger, the fifth chamber is communicated with the third fluid path, and the connection between the fifth chamber and the third fluid path can be switched on and off.

In some embodiments of the invention, the sample extraction cartridge comprises a plurality of on-off valves, each on-off valve being slidably connected to the cartridge base; and the switch valve is used for synchronously controlling the on-off of the liquid paths in each liquid path combination.

In some embodiments of the present invention, the two opposite sides of the cartridge base are respectively provided with the liquid path assembly, and the first liquid path, the second liquid path and the third liquid path are respectively symmetrically arranged at two opposite sides of the cartridge base.

In some embodiments of the present invention, the open/close valve is provided with a plurality of flow paths, the flow paths forming first communication ports and second communication ports on side surfaces of the open/close valve, the first communication ports being arranged in one or two rows on an upper side surface of the open/close valve, and the second communication ports being located on opposite side surfaces of the open/close valve, respectively.

In some embodiments of the invention, the sample extraction cartridge comprises a plurality of covers, the covers being connected to the first chamber in a split or integral manner.

In some embodiments of the present invention, a filter element is disposed in the cover.

In certain embodiments of the invention, the third chamber is provided with a filter element.

In certain embodiments of the invention, the second mixing plunger is provided with a travel control element that controls the distance of travel of the second mixing plunger.

In some embodiments of the invention, the sample extraction cartridge comprises four of the chamber combinations and four of the fluid path combinations.

The sample extraction method provided by the invention uses the sample extraction card box, the extraction process of the sample extraction method comprises magnetic bead activation, sample addition, cracking reaction, washing and elution, and the on-off of the liquid paths in the liquid path combination in parallel connection is synchronously controlled through the switch valve in sliding connection, so that the transfer of fluid is completed.

The invention can be widely applied to the technical field of biomedical instruments, and the embodiment of the invention at least has the following beneficial effects:

each chamber in the chamber combination of the sample extraction card box is correspondingly switched on and off with each liquid path in the liquid path combination, mixing, washing, residual liquid cleaning, elution and liquid discharging of sample liquid are continuously realized in a closed environment, extraction and detection efficiency is improved, and generated waste liquid can be stored in the first chamber, so that the structure utilization rate is improved.

The design sample draws card box has a plurality of cavity combinations and a plurality of liquid way combinations, and parallelly connected between each liquid way combination to obtain the parallelly connected card box structure of multichannel, prevent the series flow, can handle many copies appearance liquid in step, further raise the efficiency.

The switch valve is designed in the card box base and can slide to change positions, so that the on-off of each liquid path in the liquid path combination is controlled, the liquid paths in the liquid path combinations can be controlled simultaneously by the switch valve, and the operation is more convenient.

The liquid path combinations are symmetrically arranged on two opposite sides of the card box base and are mutually independent, so that liquid mixing is prevented, the mixing or flowing time of sample liquid in each liquid path combination is consistent, and the detection accuracy is ensured.

Drawings

The described and/or additional aspects and advantages of embodiments of the present invention will become apparent and readily appreciated from the following description of the embodiments, taken in conjunction with the accompanying drawings. It should be noted that the embodiments presented in the following figures are exemplary only and are not to be construed as limiting the invention.

FIG. 1 is a diagram of one embodiment of a sample extraction cartridge.

Figure 2 is a block diagram of the sample extraction cartridge of figure 1 showing the on-off valves exploded from the cartridge base and the chambers grouped into four.

Fig. 3 shows 12 sample extraction cartridges arranged in a 4 x 12 layout.

Fig. 4 shows 24 sample extraction cartridges arranged symmetrically in two rows, shown as horizontal 4 and vertical 24, according to a 4 x 12 x 2 layout.

Fig. 5 shows 24 sample extraction cartridges arranged symmetrically in two rows, shown as horizontal 8 and vertical 12, in a 4 x 12 x 2 layout.

Reference numerals:

1000. a cassette base;

1101. a first fluid path; 1102. a second fluid path; 1103. a third fluid path; 1104. a fourth fluid path;

1201. a first on-off valve; 1202. a second on-off valve; 1203. a third on/off valve; 1204. a fourth switching valve; 1205. a fifth on-off valve;

1301. a first mixing switching valve; 1302. a second mixing switching valve;

2101. a first chamber; 2102. a second chamber; 2103. a third chamber; 2104. a fourth chamber; 2105. a fifth chamber;

2201. a first mixing chamber; 2202. a second mixing chamber;

2300. a cover body;

3000. and a sample extraction tube.

Detailed Description

Embodiments of the invention, examples of which are illustrated in the accompanying drawings, are described in detail below with reference to fig. 1-5, wherein like or similar reference numerals refer to like or similar elements or elements with like or similar functionality throughout. The embodiments described below with reference to the accompanying drawings are illustrative only for the purpose of explaining the present invention, and are not to be construed as limiting the present invention.

In the description of the present invention, it is to be understood that if the terms "center", "middle", "longitudinal", "lateral", "length", "width", "thickness", "upper", "lower", "front", "rear", "left", "right", "vertical", "horizontal", "top", "bottom", "inner", "outer", "axial", "radial", "circumferential", etc., are used in an orientation or positional relationship indicated based on the drawings, it is merely for convenience of description and simplicity of description, and it is not intended to indicate or imply that the referenced device or element must have a particular orientation, be constructed and operated in a particular orientation, and therefore, is not to be considered as limiting the present invention. Furthermore, a feature defined as "first" or "second" may explicitly or implicitly include one or more of that feature. In the description of the present invention, "a plurality" means two or more unless otherwise specified.

In the description of the present invention, it should be noted that, unless otherwise explicitly specified or limited, the terms "mounted," "connected," and "connected" are to be construed broadly, e.g., as meaning either a fixed connection, a removable connection, or an integral connection; can be mechanically or electrically connected; they may be connected directly or indirectly through intervening media, or they may be interconnected between two elements. The specific meanings of the above terms in the present invention can be understood in a specific case to those of ordinary skill in the art.

The invention relates to a nucleic acid detection device, which comprises a sample extraction card box, wherein sample liquid of nucleic acid is discharged for detection after being cracked, washed and eluted in the sample extraction card box.

Other configurations and operations of the nucleic acid detecting apparatus are well known to those skilled in the art and will not be described in detail herein, and the structure of the sample extraction cartridge will be described below.

The invention relates to a sample extraction cartridge comprising a cartridge base 1000 and a plurality of chamber combinations, wherein each chamber combination comprises a first chamber 2101, a second chamber 2102, a first mixing chamber 2201, a second mixing chamber 2202, a third chamber 2103 and a fourth chamber 2104, and specifically, the first chamber 2101, the second chamber 2102, the first mixing chamber 2201, the second mixing chamber 2202, the third chamber 2103 and the fourth chamber 2104 are respectively connected with the cartridge base 1000. Further, a preservation solution can be stored in the first chamber 2101, a throat swab stuck with a sample solution is placed in the first chamber 2101 and mixed with the preservation solution, a washing solution can be stored in the second chamber 2102, a lysate can be stored in the second mixing chamber 2202, magnetic beads are mixed in the lysate, the third chamber 2103 is used for communicating with an air source, and an eluent can be stored in the fourth chamber 2104.

The cartridge base 1000 is provided with a plurality of liquid path combinations, and the liquid path combination is arranged in realizing the intercommunication between each cavity in the cavity combination, and specifically, the liquid path combination includes first liquid path 1101, second liquid path 1102, third liquid path 1103 and fourth liquid path 1104, and each liquid path is formed through receiving processing a little, is the liquid path of micron level, and each liquid path in the liquid path combination can break-make respectively to realize the intercommunication between the different cavities. Furthermore, all the liquid path combinations are connected in parallel, and all the chamber combinations form a parallel and mutually independent card box structure through the corresponding liquid path combinations, so that the structure is compact, liquid mixing is avoided, a plurality of sample liquids of nucleic acid can be processed simultaneously, and the efficiency is improved.

The first liquid path 1101 is used for connecting the first chamber 2101, the second chamber 2102 and the first mixing chamber 2201, specifically, the first chamber 2101 and the second chamber 2102 can be connected with the first liquid path 1101 in a on-off mode, the second liquid path 1102 is used for connecting the first mixing chamber 2201 and the second mixing chamber 2202, and the first mixing chamber 2201 can be switched to communicate with the first liquid path 1101 or the second liquid path 1102. It is understood that if the first mixing chamber 2201 is switched to communicate with the second liquid passage 1102, the first mixing chamber 2201 is disconnected from the first liquid passage 1101.

Of course, in the case where the first mixing chamber 2201 is switched to communicate with the first liquid passage 1101, then the first mixing chamber 2201 is disconnected from the second liquid passage 1102, at which time: if the first chamber 2101 is in communication with the first fluid path 1101 and the second chamber 2102 is disconnected from the first fluid path 1101, the first chamber 2101 is in communication with the first mixing chamber 2201 and fluid can flow between the first chamber 2101 and the first mixing chamber 2201; if the second chamber 2102 is in communication with the first fluid path 1101 and the first chamber 2101 is in communication with the first fluid path 1101, the second chamber 2102 is in communication with the first mixing chamber 2201 and fluid may flow between the second chamber 2102 and the first mixing chamber 2201.

The third liquid path 1103 is used for connecting the second mixing chamber 2202, the third chamber 2103, the fourth chamber 2104 and the fourth liquid path 1104, specifically, the second mixing chamber 2202 is in switchable communication with the second liquid path 1102 or the third liquid path 1103, the third chamber 2103 is in switchable communication with the third liquid path 1103, the third liquid path 1103 is in switchable communication with the fourth chamber 2104 or the fourth liquid path 1104, and the fourth liquid path 1104 is used for discharging processed sample liquid.

It is understood that in the case where the second mixing chamber 2202 is switched to communicate with the second liquid passage 1102, the second mixing chamber 2202 is disconnected from the third liquid passage 1103, and at this time, if the first mixing chamber 2201 is switched to communicate with the second liquid passage 1102, the second mixing chamber 2202 communicates with the first mixing chamber 2201.

Of course, if the second mixing chamber 2202 is switched to be communicated with the third liquid path 1103 and the third liquid path 1103 is set to be communicated with the third chamber 2103, the fourth chamber 2104 or the fourth liquid path 1104, the second mixing chamber 2202 is correspondingly communicated with the third chamber 2103, the fourth chamber 2104 or the fourth liquid path 1104.

Further, the first mixing chamber 2201 is provided with a first mixing plunger, the second mixing chamber 2202 is provided with a second mixing plunger, the first mixing plunger and the second mixing plunger are push-and-pull, the second chamber 2102 is provided with a second plunger which can push the washing solution out of the second chamber 2102, the fourth chamber 2104 is provided with a fourth plunger which can push the washing solution out of the fourth chamber 2104.

In some examples, the second plunger, the first mixing plunger, the second mixing plunger, and the fourth plunger move in an automated manner. Specifically, the second plunger, the first mixed plunger, the second mixed plunger and the fourth plunger are driven to move through the plurality of electric telescopic structures respectively, and the upper computer is used for controlling the work of each electric telescopic structure respectively. Of course, it is also possible to replace: driven hydraulically or pneumatically.

It will be appreciated that, corresponding to the chamber combination and the fluid path combination, the sample extraction cartridge includes a plurality of sample extraction tubes 3000, with reagents for detecting a sample fluid in the sample extraction tubes 3000, the sample extraction tubes 3000 being connected with the cartridge base 1000, in particular, the sample extraction tubes 3000 being connected with the underside of the cartridge base 1000, the underside of the cartridge base 1000 being provided with an interface for mounting the sample extraction tubes 3000.

Further, the sample extraction tube 3000 is communicated with a fourth liquid path 1104, and the processed sample liquid is discharged to the sample extraction tube 3000 through the fourth liquid path 1104. Specifically, the processed sample liquid remains in the second mixing chamber, and the sample liquid is discharged to the sample extraction tube 3000 through the third liquid path 1103 and the fourth liquid path 1104 by pushing the second mixing plunger. It will be appreciated that the sample liquid is discharged in fixed amounts by controlling the stroke of the second mixing plunger. In some examples, the second mixing plunger is configured with a stroke control element that can control the distance of movement of the second mixing plunger.

As an embodiment, a magnetic element receiving area is disposed between the first mixing chamber 2201 and the second mixing chamber 2202. Further, the sample extraction cartridge includes magnetic elements that are adjacent to the magnetic chambers of the cartridge base 1000 and can attract and immobilize magnetic beads in the liquid. Specifically, the magnetic element may be close to or far from the magnetic attraction chamber of the cartridge base 1000 in a direction perpendicular to the surface of the cartridge base 1000 in the magnetic element accommodation region.

Of course, as an alternative, it is also possible to provide: the sample extraction cartridge does not have magnetic elements, but the user purchases magnetic elements in addition, reducing the production cost of the sample extraction cartridge.

As an embodiment, the sample extraction cartridge comprises a plurality of switch valves, the cartridge base 1000 is provided with a plurality of recessed installation areas, the switch valves are arranged in the installation areas, each switch valve is used for connecting or disconnecting each connection between the liquid path combination and the chamber combination, and the connection and disconnection at the corresponding position can be switched by switching the positions of the switch valves. Specifically, the open/close valve is provided with a flow path that forms a first communication port and a second communication port on a side surface of the open/close valve.

It will be appreciated that each of the on-off valves is movably coupled to the cartridge base 1000, and in particular, each of the on-off valves is slidably coupled to the cartridge base 1000. Further, each of the switching valves slides in the cartridge base 1000 in an automatic manner. In some examples, the switch valves are driven to move by a plurality of electric telescopic structures, and the upper computer is used for controlling the work of each electric telescopic structure. Of course, it is also possible to replace: driven hydraulically or pneumatically.

The first chamber 2101 is switched to be connected with or disconnected from the first liquid path 1101 by a corresponding switching valve, the switching valve corresponding to the first chamber 2101 is set as a first switching valve 1201, and a first communication port in the first switching valve 1201 is used for communicating the first chamber 2101 and a second communication port is used for communicating the first liquid path 1101. It is understood that, by changing the position of the first open/close valve 1201, the first communication port and the second communication port can be shifted or positioned from the communication point between the first chamber 2101 and the first fluid path 1101, respectively. With reference to the drawings, when the first switching valve 1201 moves to the left, the first chamber 2101 is communicated with the first fluid path 1101; when the first switching valve 1201 moves rightward, the first chamber 2101 is disconnected from the first fluid path 1101.

The second chamber 2102 is switched to be communicated with or disconnected from the first liquid path 1101 by a corresponding switching valve, the switching valve corresponding to the second chamber 2102 is set as a second switching valve 1202, and a first communication port in the second switching valve 1202 is used for communicating the second chamber 2102 and the second communication port for communicating the first liquid path 1101. It is understood that, by changing the position of the second open/close valve 1202, the first and second communication ports can be displaced from or aligned with the communication positions of the second chamber 2102 and the first liquid passage 1101, respectively. With reference to the drawings, when the second on-off valve 1202 moves to the left, the second chamber 2102 communicates with the first liquid path 1101; when the second switching valve 1202 moves rightward, the second chamber 2102 is disconnected from the first channel 1101.

The first mixing chamber 2201 is switched to communicate with the first liquid path 1101 or the second liquid path 1102 by a corresponding on-off valve, the on-off valve corresponding to the first mixing chamber 2201 is set as a first mixing on-off valve 1301, and a first communication port in the first mixing on-off valve 1301 is used for communicating the first mixing chamber 2201 and a second communication port is used for communicating the first liquid path 1101 or the second liquid path 1102. It is understood that, by changing the position of the first mixing switch valve 1301, the second communication port can be switched to communicate with the first liquid passage 1101 or the second liquid passage 1102, and the first communication port is kept in communication with the first mixing chamber 2201. With reference to the drawings, when the first mixing switching valve 1301 is moved to the left, the first mixing chamber 2201 is communicated with the first liquid path 1101; when the first mixing switch valve 1301 moves to the right, the first mixing chamber 2201 communicates with the second liquid passage 1102.

The second mixing chamber 2202 is switched to communicate with the second liquid passage 1102 or the third liquid passage 1103 by a corresponding on-off valve, the on-off valve corresponding to the second mixing chamber 2202 is provided as a second mixing on-off valve 1302, and the first communication port of the second mixing on-off valve 1302 is used for communicating with the second mixing chamber 2202 and the second communication port is used for communicating with the second liquid passage 1102 or the third liquid passage 1103. It is understood that, by changing the position of the second mixing switch valve 1302, the second communication port can be switched to communicate with the second liquid passage 1102 or the third liquid passage 1103, and the first communication port can be kept in communication with the second mixing chamber 2202. With reference to the figure, when the second mixing switching valve 1302 moves to the left, the second mixing chamber 2202 communicates with the second liquid path 1102; when the second mixing switching valve 1302 moves rightward, the second mixing chamber 2202 communicates with the third liquid passage 1103.

The third chamber 2103 is switched to be communicated with or disconnected from the third liquid path 1103 through a corresponding switch valve, the switch valve corresponding to the third chamber 2103 is set as a third switch valve 1203, and a first communication port in the third switch valve 1203 is used for communicating the third chamber 2103 and a second communication port is used for communicating the third liquid path 1103. It is understood that, by changing the position of the third switching valve 1203, the first communication port and the second communication port can be displaced from or aligned with the communication positions of the third chamber 2103 and the third liquid passage 1103, respectively. With reference to the drawing, when the third switching valve 1203 moves to the left, the third chamber 2103 communicates with the third liquid path 1103; when the third switching valve 1203 moves rightward, the third chamber 2103 is disconnected from the third liquid path 1103.

The fourth chamber 2104 can switch the third liquid path 1103 to communicate with the fourth chamber 2104 or the third liquid path 1103 communicates with the fourth liquid path 1104 through a corresponding switch valve, the switch valve corresponding to the fourth chamber 2104 is set as the fourth switch valve 1204, a second communication port in the fourth switch valve 1204 is communicated with the third liquid path 1103, and the first communication port is used for communicating with the fourth chamber 2104. It is understood that, when the position of the fourth switching valve 1204 is changed and the first communication port and the fourth chamber 2104 are communicated with each other in a position, the second communication port and the fourth liquid path 1104 are disconnected from each other, and the third liquid path 1103 and the fourth chamber 2104 are communicated with each other; when the first communication port and the fourth chamber 2104 are displaced and disconnected from each other, the second communication port communicates with the third liquid passage 1103 and the fourth liquid passage 1104, respectively. With reference to the drawings, when the fourth switching valve 1204 moves to the left, the third fluid path 1103 communicates with the fourth chamber 2104; when the fourth switching valve 1204 moves rightward, the third liquid path 1103 communicates with the fourth liquid path 1104.

As an embodiment, the chamber combination comprises a fifth chamber 2105, the fifth chamber 2105 is connected with the cartridge base 1000, the fifth chamber 2105 is communicated with the third liquid path 1103, and the connection between the fifth chamber 2105 and the third liquid path 1103 can be opened or closed. The fifth chamber 2105 is used for storing mineral oil or gas, and after the processed sample liquid is discharged from the sample extraction cartridge to the sample extraction tube 3000, in order to improve the accuracy of quantitative extraction and prevent the sample liquid from remaining in the liquid path, the sample liquid remaining in the liquid path is pushed out to the sample extraction tube 3000 by using mineral oil or gas.

Further, the fifth chamber 2105 is provided with a fifth plunger for pushing out the mineral oil or gas in the fifth chamber 2105. In some examples, the fifth plunger moves in the fifth chamber 2105 in an automated manner. Specifically, the fifth plunger is driven to move through the electric telescopic structure, and the upper computer is used for controlling the work of the electric telescopic structure. Of course, it is also possible to replace: driven hydraulically or pneumatically.

The fifth chamber 2105 is switched to be connected to or disconnected from the third liquid path 1103 by a corresponding on-off valve, and specifically, the on-off valve corresponding to the fifth chamber 2105 is set as a fifth on-off valve 1205. It will be appreciated that the fifth on/off valve 1205 is movably connected to the cartridge base 1000. Specifically, the fifth switching valve 1205 is slidably connected to the cartridge base 1000. Further, the fifth switching valve 1205 slides in the cartridge base 1000 in an automatic manner. In some examples, the fifth switch valve 1205 is driven by the electric telescopic structure to move, and the upper computer is used to control the operation of the electric telescopic structure. Of course, it is also possible to replace: driven hydraulically or pneumatically.

The fifth opening/closing valve 1205 is provided with a flow path that forms a first communication port for communicating with the fifth chamber 2105 and a second communication port for communicating with the third liquid path 1103, on a side surface of the fifth opening/closing valve 1205. It is understood that, by changing the position of the fifth on-off valve 1205, the first communication port and the second communication port can be displaced from or aligned with the communication positions of the fifth chamber 2105 and the third liquid passage 1103, respectively.

It can be understood that, under the condition that the chamber combination and the liquid path combination are respectively provided with a plurality of chambers, the switch valve is used for synchronously controlling the on-off of the liquid paths in the liquid path combinations, and the same switch valve can simultaneously control the on-off of the same liquid path in different liquid path combinations. Specifically, each ooff valve is provided with a plurality of flow paths respectively, utilizes one set of ooff valve combination can a plurality of independent card box structures of simultaneous control, realizes independent multichannel sample and draws, satisfies the demand that each card box structure independently handled appearance liquid.

In some examples, two opposite side surfaces of the cartridge base 1000 are respectively provided with a liquid path combination, and the first liquid path 1101, the second liquid path 1102 and the third liquid path 1103 are respectively symmetrically arranged on two opposite sides of the cartridge base 1000, so that on one hand, the on-off valve can conveniently control the on-off of a plurality of liquid path combinations at the same time, and on the other hand, the time for mixing or flowing samples in each liquid path combination is consistent, so that the transfer amount and the mixing degree of each sample can be ensured to be consistent, and the detection accuracy can be ensured. It is understood that the second communication ports are located on the open/close valve on opposite sides of the open/close valve, and the first communication ports are arranged in a row on the upper side of the open/close valve. In this case, the chambers corresponding to the respective on-off valves are arranged in a row on the cartridge base 1000. Specifically, the first chambers 2101, the first mixing chambers 2201, and the second mixing chambers 2202 are arranged in a line on the cartridge base 1000, and the flow paths on the first switching valve 1201, the first mixing switching valve 1301, and the second mixing switching valve 1302 are arranged in a line.

Of course, as an alternative, it is also possible to provide: on the upper side of the switch valves, the first communication ports are arranged in two rows, in which case the chambers corresponding to the switch valves are arranged in two rows on the cartridge base 1000. Specifically, the second chambers 2102, the third chambers 2103, the fourth chambers 2104 and the fifth chambers 2105 are arranged in two rows on the cartridge base 1000, and the flow paths on the second switch valve 1202, the third switch valve 1203, the fourth switch valve 1204 and the fifth switch valve 1205 are arranged in two rows.

It will be appreciated that the number of sample extraction tubes 3000 corresponds to the number of chamber combinations and fluid path combinations. Further, the sample collection tubes 3000 are sequentially spaced apart from each other in the axial direction of the cartridge base 1000, and the sample collection tubes 3000 are arranged in a row. In this case, the length of the fourth liquid path 1104 connected to the sample collection tube 3000 is not uniform, and the sample liquid in the liquid path can be discharged by the mineral oil or gas in the fifth chamber 2105 in order to eliminate the quantitative variation of the liquid collection.

With reference to the drawings, the number of the chamber combination and the number of the liquid path combination are four, respectively, to form a quadruplet cartridge, and accordingly, the number of the sample extraction tubes 3000 is four. Further, two liquid path combinations are respectively arranged on two opposite side surfaces of the cartridge base 1000. Specifically, four first chambers 2101, four first mixing chambers 2201, and four second mixing chambers 2202 are arranged in a line on the cartridge base 1000, respectively, and accordingly, the first communication ports of the first on-off valve 1201, the first mixing on-off valve 1301, and the second mixing on-off valve 1302 are arranged in a line on the upper side surface, respectively. The four second chambers 2102, the four third chambers 2103, the four fourth express chambers, and the four fifth chambers 2105 are arranged in two rows on the cartridge base 1000, and the first communication ports of the second switch valve 1202, the third switch valve 1203, the fourth switch valve 1204, and the fifth switch valve 1205 are arranged in two rows on the upper side surface.

It can be understood that a single sample extraction cartridge can process four nucleic acid samples, and in the nucleic acid detection device, a plurality of quadruplet cartridges are combined, so that automatic detection under the closed condition of high-throughput cartridges can be conveniently realized, the detection quantity and the detection speed are improved, and high-throughput detection is realized.

As an embodiment, the sample extraction cartridge includes a cover 2300, the cover 2300 being connected to the first chamber 2101, and the connection being detachable. It will be appreciated that to maintain the air pressure in the first chamber 2101 in equilibrium, the first cover 2300 is in communication with a gas source, which may be provided as an atmosphere or a gas cylinder, and the cover 2300 is provided. Further, a filter element is disposed in the cover 2300 to filter the gas and improve the gas purity.

It is to be understood that, in the case where the first chamber 2101 is provided in plurality, accordingly, the cover 2300 is provided in plurality. Further, the covers 2300 are integrally joined to open and close the covers 2300 at the same time. With reference to the drawings, the covers 2300 are integrally connected to the sample extraction cartridge. As an alternative, it is of course also possible to provide: each cover 2300 is separately connected to each first chamber 2101.

As an embodiment, the third chamber 2103 is provided with a filter element, the air source connected to the third chamber 2103 is an atmosphere or a gas bottle, and the filter element is arranged at the opening of the third chamber 2103 to filter the gas, so that the gas purity is improved.

The following will supplement the description of the nucleic acid detecting apparatus with respect to the structure of the above-described sample extraction cartridge.

In one embodiment, the number of the sample extraction cartridges is 12, the sample extraction cartridge has four chamber combinations and four liquid path combinations, the sample extraction tubes 3000 are arranged in a 4 × 12 array, and the sample extraction cartridges are arranged in a row in the nucleic acid detecting apparatus. In this case, the cartridge has reasonable layout, is butted with a sample plate of the PCR instrument, and can realize the detection of 48 independent samples.

In one embodiment, the number of the sample extraction cartridges is 24, the sample extraction cartridges have four chamber assemblies and four fluid path assemblies, the sample extraction tubes 3000 are distributed in a 4 × 12 × 2 array, and the sample extraction cartridges are symmetrically arranged in two rows in the nucleic acid detecting apparatus. In this case, detection of 98 independent samples can be achieved.

The symmetrical arrangement mode has two types: the integral layout is that 3000 sample extraction tubes are 8 in the transverse direction and 12 in the longitudinal direction; another overall arrangement is 4 sample extraction tubes 3000 in the transverse direction and 24 in the longitudinal direction.

Furthermore, if 24 sample extraction cartridges are added in any of the above symmetrical manners, 192 independent samples can be detected.

With the above detailed description of the construction of the sample extraction cartridge in mind, and the following discussion of a sample extraction method for processing a sample fluid using the sample extraction cartridge, it is noted that the following description is illustrative and not intended to be a specific limitation of the invention.

The invention relates to a sample extraction method, which adopts an automatic mode to control the on-off of liquid paths and chambers in a sample extraction card box, the extraction process of the sample extraction method comprises magnetic bead activation, sample addition, cracking reaction, washing and elution, and the on-off of the liquid paths in a plurality of parallel liquid path combinations is synchronously controlled through a switch valve in sliding connection to complete the transfer of fluid.

The sample extraction method comprises the following steps: s1, adding a sample solution; s2, cracking and mixing, magnetically attracting, and discharging waste liquid; s3, removing liquid path residues; s4, washing, magnetically attracting and discharging waste liquid; s5, eluting and magnetically attracting; and S6, quantitatively discharging.

In step S1, the sample solution to be processed is put into the first chamber 2101 and premixed in the first mixing chamber 2201.

The throat swab is inserted into the first cavity 2101, the sample liquid adhered to the throat swab is mixed with the preservation liquid, and the cover 2300 is closed with the first cavity 2101.

The first switching valve 1201 moves to the left to communicate the first chamber 2101 with the first liquid path 1101; the first mixing switching valve 1301 is shifted left to communicate the first mixing chamber 2201 with the first liquid path 1101; the sample fluid is transferred to the first mixing chamber 2201 by pushing or pulling the first mixing plunger, which can facilitate mixing of the sample fluid and the preservation fluid.

In step S2, the lysis solution is mixed with the sample solution, the nucleic acid molecules in the sample solution are magnetically adsorbed, and the waste solution after lysis is transferred to the first chamber 2101.

The first mixing switching valve 1301 moves to the right, and the first mixing chamber 2201 is switched to be communicated with the second liquid path 1102; the second mixing switching valve 1302 moves left, and the second mixing chamber 2202 communicates with the second liquid passage 1102; the sample solution and the lysate are mixed by pushing and pulling the first mixing plunger and the second mixing plunger, and the sample solution mixed lysate flows back and forth between the first mixing chamber 2201 and the second mixing chamber 2202, thereby sufficiently performing lysis mixing.

The magnetic element is close to the magnetic suction chamber of the cartridge base 1000, and the magnetic element moves downwards in the magnetic element accommodating area to be close to the magnetic suction chamber of the cartridge base 1000; the second mixing plunger is pushed, the liquid is transferred from the second mixing chamber 2202 to the first mixing chamber 2201, and the magnetic element adsorbs magnetic beads and the magnetic beads are fixed in the flowing process of the sample liquid. It can be understood that the mixing speed is reduced during the process of adsorbing the fixed magnetic beads by the magnetic element.

The first mixing switch valve 1301 moves to the left, and the first mixing chamber 2201 is switched to be communicated with the first liquid path 1101; the first switching valve 1201 moves to the left, and the first chamber 2101 is communicated with the first liquid path 1101; the lysed waste is transferred to the first chamber 2101 by pushing the first mixing plunger.

In step S3, the gas in the third chamber 2103 is used to clean the residual liquid in the first liquid path 1101 and the second liquid path 1102, and the residual liquid is transferred to the first chamber 2101.

The third switching valve 1203 moves left, and the third chamber 2103 is communicated with the third liquid path 1103; the second mixing switching valve 1302 moves to the right, and the second mixing chamber 2202 is switched to communicate with the third liquid path 1103; drawing gas from the third chamber 2103 to the second mixing chamber 2202 through the second mixing plunger; the third switching valve 1203 moves rightward, and the third chamber 2103 is disconnected from the third liquid path 1103.

The second mixing switching valve 1302 moves to the left, and the second mixing chamber 2202 is switched to communicate with the second liquid passage 1102; the first mixing switching valve 1301 moves to the right, and the first mixing chamber 2201 is switched to communicate with the second liquid passage 1102; by pushing the second mixing plunger, gas is transferred from the second mixing chamber 2202 to the first mixing chamber 2201, which can clean up the residual liquid in the second liquid path 1102.

The first mixing switch valve 1301 moves to the left, and the first mixing chamber 2201 is switched to be communicated with the first liquid path 1101; the first switching valve 1201 moves to the left, and the first chamber 2101 is communicated with the first liquid path 1101; by pushing the first mixing plunger, gas is admitted from the first mixing chamber 2201 into the first chamber 2101, the gas is able to clean up the raffinate in the first liquid path 1101.

In step S4, the nucleic acid molecules adsorbed by the magnetic beads are washed, and the waste solution after washing is transferred to the first chamber 2101.

The second switching valve 1202 moves to the left, and the second chamber 2102 communicates with the first liquid path 1101; the first mixing switch valve 1301 moves to the left, and the first mixing chamber 2201 is switched to be communicated with the first liquid path 1101; the first plunger is pushed and the wash solution is transferred from the second chamber 2102 to the first mixing chamber 2201 by pulling the first mixing plunger.

The first mixing switching valve 1301 moves to the right, and the first mixing chamber 2201 is switched to communicate with the second liquid passage 1102; the second mixing switching valve 1302 moves to the left, and the second mixing chamber 2202 is switched to communicate with the second liquid passage 1102; the wash liquid is caused to flow between the first mixing chamber 2201 and the second mixing chamber 2202 by pushing and pulling the first mixing plunger and the second mixing plunger. It will be appreciated that in this process, the magnetic elements are remote from the magnetically attracted chamber of the cartridge base 1000 and the magnetic beads are suspended in the wash solution to facilitate processing of the nucleic acid molecules by the wash solution.

The magnetic element is close to the magnetic suction chamber of the cassette base 1000, and the magnetic element moves downwards in the magnetic element accommodating area to be close to the magnetic suction chamber of the cassette base 1000; the second mixing plunger is pushed, the first mixing plunger is pulled, the washing solution is transferred from the second mixing chamber 2202 to the first mixing chamber 2201, and in the flowing process of the liquid, the magnetic elements adsorb and fix the magnetic beads. It can be understood that the mixing speed is reduced during the process of adsorbing the fixed magnetic beads by the magnetic element.

The first mixing switch valve 1301 moves to the left, and the first mixing chamber 2201 is switched to be communicated with the first liquid path 1101; the first switching valve 1201 moves leftwards, and the first chamber 2101 is communicated with the first liquid path 1101; the washed waste liquid is transferred to the first chamber 2101 by pushing the first mixing plunger.

In step S5, the nucleic acid molecules adsorbed by the magnetic beads are eluted, and a sample solution obtained by the elution is stored in the second mixing chamber 2202.

The second mixing switching valve 1302 moves to the right, and the second mixing chamber 2202 is switched to communicate with the third liquid path 1103; the fourth switching valve 1204 moves left, and the fourth chamber 2104 is switched to communicate with the third liquid path 1103; pushing the fourth plunger and pulling the second mixing plunger, eluent is transferred from the fourth chamber 2104 to the second mixing chamber 2202.

The second mixing switching valve 1302 moves to the left, and the second mixing chamber 2202 is switched to communicate with the second liquid passage 1102; the first mixing switching valve 1301 moves to the right, and the first mixing chamber 2201 is switched to be communicated with the second liquid path 1102; eluent is flowed between the first mixing chamber 2201 and the second mixing chamber 2202 by pushing and pulling the first mixing plunger and the second mixing plunger.

During elution, the magnetic element is far away from the magnetic suction chamber of the cartridge base 1000, and the magnetic beads are suspended in the sample liquid; after the elution is completed, the magnetic element is close to the magnetic attraction chamber of the cartridge base 1000, the magnetic beads are adsorbed and fixed in the magnetic attraction chamber, and the sample solution after the eluent treatment is transferred to the second mixing chamber 2202.

In step S6, the sample solution obtained after elution is quantitatively discharged to the sample extraction tube 3000, and the sample solution remaining in the third liquid path 1103 and the fourth liquid path 1104 is cleaned up to the sample extraction tube 3000.

The second mixing switching valve 1302 moves to the right, and the second mixing chamber 2202 is switched to communicate with the third liquid path 1103; the fourth switching valve 1204 is moved leftwards, and the fourth chamber 2104 is switched to be communicated with the third liquid path 1103; the gas remaining in the third liquid path 1103 is transferred to the fourth chamber 2104 by pushing the second mixing plunger to fill the third liquid path 1103 with the sample liquid.

The fourth switching valve 1204 is shifted to the right, the fourth liquid path 1104 is switched to communicate with the third liquid path 1103, a fixed amount of sample liquid is extracted by pushing the second mixing plunger, and the sample liquid is discharged to the sample extraction tube 3000 through the third liquid path 1103 and the fourth liquid path 1104. It will be appreciated that by setting the distance of travel of the second mixing plunger, a quantitative discharge can be achieved.

The second mixing switching valve 1302 moves leftward, and the second mixing chamber 2202 is switched to communicate with the second liquid passage 1102, so that the second mixing chamber 2202 is disconnected from the third liquid passage 1103; the fifth switching valve 1205 is moved to the left, and the fifth chamber 2105 is communicated with the third liquid path 1103; the fifth plunger is pushed, mineral oil or gas in the fifth chamber 2105 fills the third liquid path 1103 and the fourth liquid path 1104, and sample liquid in the third liquid path 1103 and the fourth liquid path 1104 is discharged, so that accurate quantitative liquid taking is realized.

It is understood that, during the washing in step S4, it may alternatively be designed to: the magnetic element is close to the magnetic attraction chamber of the cartridge base 1000 and remains attracted to the magnetic beads during the washing process.

In the description herein, references to the terms "one embodiment," "some examples," "some embodiments," "illustrative embodiments," "examples," "specific examples," or "some examples" or the like, if any, mean that a particular feature, structure, material, or characteristic described in connection with the embodiment or example is included in at least one embodiment or example of the invention. In this specification, the schematic representations of the terms used above do not necessarily refer to the same embodiment or example. Furthermore, the particular features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples.

While the embodiments of the present invention have been described in detail with reference to the drawings, the present invention is not limited to the above embodiments, and various changes can be made without departing from the spirit of the present invention within the knowledge of those skilled in the art.

In the description of the present invention, the appearances of the patent names "and" in the patent specification are the same as each other, but the patent names "and" are not necessarily the same as each other. For example, the patent names "a and B" illustrate that the claimed invention is: the technical scheme with the subject name of A and the technical scheme with the subject name of B.

Claims (14)

1. A sample extraction cartridge, characterized by: comprises a cartridge base (1000) and a plurality of chamber combinations, the chamber combinations are connected with the cartridge base (1000), and the chamber combinations comprise

A first chamber (2101) in which a preservation solution can be stored, the first chamber (2101) being connected to the cartridge base (1000);

a second chamber (2102), the second chamber (2102) being connected to the cartridge base (1000), a washing liquid being storable in the second chamber (2102), the second chamber (2102) being provided with a second plunger;

a first mixing chamber (2201), the first mixing chamber (2201) being connected with the cartridge base (1000), the first mixing chamber (2201) being provided with a first mixing plunger;

a second mixing chamber (2202), the second mixing chamber (2202) being connected to the cartridge base (1000), lysate being storable in the second mixing chamber (2202), the second mixing chamber (2202) being provided with a second mixing plunger;

a third chamber (2103), wherein the third chamber (2103) is connected with the cartridge base (1000), and the third chamber (2103) is used for being communicated with a gas source;

a fourth chamber (2104) connected to the cartridge base (1000), an eluent being storable in the fourth chamber (2104), the fourth chamber (2104) being provided with a fourth plunger;

the cartridge base (1000) is provided with a plurality of liquid path combinations connected in parallel, each liquid path combination comprises a first liquid path (1101), a second liquid path (1102), a third liquid path (1103) and a fourth liquid path (1104), the first liquid path (1101) is used for connecting the first chamber (2101), the second chamber (2102) and the first mixing chamber (2201), the second liquid path (1102) is used for connecting the first mixing chamber (2201) and the second mixing chamber (2202), the third liquid path (1103) is used for connecting the second mixing chamber (2202), the third chamber (1104) and the fourth chamber (2104), the fourth liquid path (2103) is used for discharging processed sample liquid, and each liquid path in the liquid path combinations can be respectively switched on and off.

2. The sample extraction cartridge of claim 1, wherein: a magnetic element accommodating area is arranged between the first mixing chamber (2201) and the second mixing chamber (2202).

3. The sample extraction cartridge of claim 2, wherein: the sample extraction cartridge comprises a magnetic element that is movable in a direction perpendicular to the surface of the cartridge base (1000) in the magnetic element receiving area towards or away from a magnetic attraction chamber of the cartridge base (1000).

4. The sample extraction cartridge of claim 3, wherein: the chamber combination comprises a fifth chamber (2105), the fifth chamber (2105) is connected with the cartridge base (1000), the fifth chamber (2105) is used for storing mineral oil or gas, a fifth plunger is arranged in the fifth chamber (2105), the fifth chamber (2105) is communicated with the third liquid path (1103), and the connection between the fifth chamber (2105) and the third liquid path (1103) can be switched on and off.

5. The sample extraction cartridge of claim 4, wherein: the sample extraction cartridge comprises a plurality of switch valves, each switch valve being slidably connected to the cartridge base (1000); and the switch valve is used for synchronously controlling the on-off of the liquid paths in each liquid path combination.

6. The sample extraction cartridge of claim 5, wherein: the two opposite side surfaces of the card box base (1000) are respectively provided with the liquid path combination, and the first liquid path (1101), the second liquid path (1102) and the third liquid path (1103) are respectively symmetrically arranged at two opposite sides of the card box base (1000).

7. The sample extraction cartridge of claim 6, wherein: the opening and closing valve is provided with a plurality of flow paths, the flow paths form first communication ports and second communication ports on the side surface of the opening and closing valve, the first communication ports are arranged in one row or two rows on the upper side surface of the opening and closing valve, and the second communication ports are respectively positioned on two opposite side surfaces of the opening and closing valve.

8. The sample extraction cartridge of claim 1, wherein: the sample extraction cartridge comprises a plurality of covers (2300), the covers (2300) being connected to the first chamber (2101) in a split or integrated manner.

9. The sample extraction cartridge of claim 8, wherein: a filter element is arranged in the cover body (2300).

10. The sample extraction cartridge of any one of claims 1 to 9, wherein: the third chamber (2103) is provided with a filter element.

11. The sample extraction cartridge of any one of claims 1 to 7, wherein: the second mixing plunger is provided with a stroke control element that controls the distance of movement of the second mixing plunger.

12. The sample extraction cartridge of any one of claims 4 to 7, wherein: the sample extraction cartridge includes four of the chamber combinations and four of the fluid path combinations.

13. A method for extracting a sample, comprising: the sample extraction method uses the sample extraction cartridge of any one of claims 5 to 7, the extraction process of the sample extraction method comprises magnetic bead activation, sample addition, lysis reaction, washing and elution, and the switching valve in sliding connection synchronously controls the on-off of the liquid paths in the plurality of parallel liquid path combinations to complete the transfer of fluid.

14. A nucleic acid detecting apparatus characterized in that: comprising a sample extraction cartridge according to any of claims 1 to 12.

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