WO2021133071A1

WO2021133071A1 - Cartridge for sample processing comprising movable solution shuttle

Info

Publication number: WO2021133071A1
Application number: PCT/KR2020/019028
Authority: WO
Inventors: Jae Young Kim
Original assignee: Seegene, Inc.
Priority date: 2019-12-27
Filing date: 2020-12-23
Publication date: 2021-07-01
Also published as: KR20220114061A

Abstract

The present invention relates to a cartridge for processing a sample, including a movable solution shuttle and, more specifically, to a cartridge comprising a body including a plurality of extraction chambers linearly disposed in a lengthwise direction and at least one solution shuttle configured to be movable between the plurality of extraction chambers and a sample processing device including a station for receiving the cartridge and a moving module for moving the cartridge. Since the cartridge and device of the present invention may contain all reagents required for sample processing in the cartridge, it has a simple structure and may automatically perform sample processing required for an assay in a single cartridge.

Description

CARTRIDGE FOR SAMPLE PROCESSING COMPRISING MOVABLE SOLUTION SHUTTLE

The present invention relates to a sample processing cartridge comprising a movable solution shuttle.

As modern people's interest in health increases and life expectancy is prolonged, nucleic acid-based in vitro molecular diagnosis, such as accurate analysis of pathogens and gene analysis of patients becomes more significant and its demand is on the rise.

Nucleic acid-based molecular diagnosis is performed by extracting nucleic acids from a sample and then checking the presence or absence of a target nucleic acid among the extracted nucleic acids. The sample processing of extracting nucleic acid from a sample includes sequentially mixing the sample and various reagents and removing residues other than the nucleic acid. Such sample processing requires an elaborate processing of a small amount of solution and, thus, is mostly performed manually by an experimenter or using a piece of liquid handling equipment that may be precisely controlled. Conventional liquid handling equipment is costly and needs professional manpower. Further, since it is a system that simultaneously processes a large number of samples, it takes a long time from sample collection to confirming the test result when the number of samples generated per hour is small, so it is not suitable for use in local hospitals and clinics where a small number of samples are to be processed.

The POC system is designed to be able to proceed with sample processing as soon as the sample is collected, so it has strengths in the local medical site. A conventional type of sample processing POC system for molecular diagnosis comprises a flow path between chambers and controls the flow path to thereby process samples. Compared to the traditional pipette method, such a method suffers from inaccuracy in the volume of the solution to be processed and lack of cartridge versatility for various sample processing schemes. Another type of conventional POC system configures a cartridge with sample processing chambers and allows a pipet module in the device operating the cartridge to perform liquid movement between the chambers. In this method, consumables such as tips used for the pipette module in the device need to be separately provided, and the up-down or left-right movement of the pipette module is required to be performed accurately with respect to the cartridge. Thus, this method requires use of expensive parts such as a conventional mass sample processing device. Further, the cartridge needs a top opening to allow for liquid movement during the sample processing reaction.

Therefore, a need arises for developing a POC system that may be operated by non-professionals by minimizing separate device operation except for mounting a cartridge and may process the solution in a pipette manner.

In view of the background, the inventors have tried to develop a POCT(point of care test) system in which solution treatment is performed in a pipette manner, and no other additional consumables than a cartridge are installed in the device. Further, efforts were made to design a cartridge that renders it possible to secure the positional accuracy of the cartridge of the moving module in such a system by the physical structure of the cartridge as much as possible. As a result, the inventors have developed a cartridge that has a plurality of extraction chambers in a housing including a flat base surface and includes a solution shuttle configured to be movable between the plurality of extraction chambers and a sample processing device capable of operating the cartridge.

Thus, an object of the present invention is to provide a cartridge for sample processing, comprising a body including a plurality of extraction chambers linearly disposed in a lengthwise direction and a solution shuttle configured to be movable between the plurality of extraction chambers.

Another object of the present invention is to provide a sample processing device comprising a station for accommodating the cartridge and a moving module capable of moving the solution shuttle in the cartridge.

The other objectives and advantages of the present invention will be apparent to the embodiments and claims described below in detail with reference to the accompanying drawings.

To achieve the foregoing objects, there is provided a cartridge for sample processing, according to the present invention.

The cartridge comprises a body including a plurality of extraction chambers linearly disposed in a lengthwise direction and at least one solution shuttle configured to be movable between the plurality of extraction chambers.

According to other objects of the present invention, there is provided a sample processing device comprising a station for accommodating the cartridge and a moving module capable of moving the solution shuttle in the cartridge.

Since the cartridge of the present invention may contain all reagents required for sample processing in the cartridge, it has a simple structure and may automatically perform sample processing required for an assay in a single cartridge.

It may be prepared by previously injecting a predetermined volume of solution into each extraction chamber of the cartridge. Since the position control, in the upper and lower directions, of the moving shuttle in the cartridge may be physically performed, it is possible to eliminate the need for use of an expensive liquid handling part in the sample processing device operating the cartridge. Therefore, it is possible to develop low-cost sample processing devices.

Since the cartridge of the present invention has a built-in solution shuttle, there is no need to mount additional consumables such as pipette tips in the sample processing device, so that the sample processing device for operating the cartridge may be miniaturized.

Use of the cartridge and sample processing device of the present invention allows even a person, who lacks specialized techniques for nucleic acid extraction, purification, and detection, to perform an assay with simple manipulation as most of the sample processing and nucleic acid detection processes are performed automatically.

When the extraction chambers of the cartridge are arranged in a linear shape according to an embodiment of the present invention, it is possible to minimize the unnecessary space in the cartridge, thereby making the cartridge more compact.

According to an embodiment of the present invention, the cover may prevent contamination of the device due to fugitive emissions, such as aerosols, generated during the course of processing the sample in the cartridge.

Fig. 1 is a view illustrating a cartridge according to an embodiment of the present invention;

Fig. 2 is an exploded perspective view illustrating a cartridge according to an embodiment of the present invention;

Fig. 3 is a reference view illustrating operations of a solution shuttle according to an embodiment of the present invention;

Fig. 4 is a view illustrating a cartridge and a sample processing device according to an embodiment of the present invention;

Fig. 5 is a view illustrating a cartridge and a sample processing device according to an embodiment of the present invention; and

Fig. 6 is a view illustrating a cartridge including a detachable cover having an opening disposed in a loop and having a port for a capturing module.

The configuration and effects of the present invention are now described in further detail in connection with embodiments thereof. The embodiments are provided merely to specifically describe the present invention, and it is obvious to one of ordinary skill in the art that the scope of the present invention is not limited to the embodiments.

The same or substantially the same reference denotations are used to refer to the same or substantially the same elements throughout the specification and the drawings. When determined to make the subject matter of the present invention unclear, the detailed description of the known configurations or functions may be skipped.

Such denotations as "first," "second," "A," "B," "(a)," and "(b)," may be used in describing the components of the present invention. These denotations are provided merely to distinguish a component from another, and the essence of the components is not limited by the denotations in light of order or sequence. When a component is described as "connected," "coupled," or "linked" to another component, the component may be directly connected or linked to the other component, but it should also be appreciated that other components may be "connected," "coupled," or "linked" between the components.

I. Sample processing cartridge

According to an aspect of the present invention, there is provided a sample processing cartridge, comprising:

a body including a plurality of extraction chambers linearly disposed in a lengthwise direction and at least one solution shuttle configured to be movable between the plurality of extraction chambers.

Fig. 1 illustrates a sample processing cartridge according to an embodiment.

As used herein, the term "sample" may encompass biological samples (e.g., cells, tissues, or fluids from biological sources) and non-biological samples (e.g., foods, water, and soil). The biological samples include virus, germs, tissues, cells, blood (e.g., whole blood, plasma, and serum), lymph, bone marrow fluid, saliva, sputum, swab, aspiration, milk, urine, stool, ocular humor, semen, brain extracts, spinal fluid, joint fluid, thymus fluid, bronchoalveolar lavage fluid, ascites, and amniotic fluid.

Sample processing refers to a series of processes to primarily separate an analyte from the sample to thereby obtain a material in the state capable of detection reaction. The term 'sample processing' may be used as further meaning the process of detecting a target analyte from the substance in the detection reaction-capable state. The analyte may be, e.g., a nucleic acid. According to an embodiment, the sample processing may include the process of extracting a nucleic acid.

Referring to FIG. 1, the sample processing cartridge according to the present invention includes a body including a plurality of extraction chambers linearly arranged in a lengthwise direction.

Referring to FIG. 1, a sample processing cartridge 100 of the present invention includes a body 110 including a plurality of extraction chambers 130. The extraction chamber is a space in which a material necessary for the process of extracting a detection target material from a sample is stored, and a physical and chemical process for extraction is performed. The detection target material may be, e.g., a nucleic acid.

According to an embodiment of the present invention, the plurality of extraction chambers may be arranged in a straight line in the lengthwise direction. As shown in Figure 1, the plurality of extraction chambers 130 of the present invention are arranged in a straight line in a lengthwise direction 139. When the plurality of extraction chambers are arranged in a straight line, a device for controlling the movement of a solution shuttle for moving a solution between the plurality of extraction chambers may be simply configured.

According to an embodiment of the present invention, the extraction chamber is configured to accommodate a solution. Specifically, the extraction chamber includes an opening 131 at the top thereof, through which the solution may enter and exit, and a solution receiving portion 135 extending downward from the opening 131.

The plurality of extraction chambers may have a cylindrical shape or a polygonal column shape tapered downward and, without limitations thereto, may have other shapes. Each extraction chamber may be configured to accommodate 3000 microliters or less, 2000 microliters or less, 1000 microliters or less, 800 microliters or less, 700 microliters or less, 500 microliters or less, 400 microliters or less, 300 microliters or less, 200 microliters or less, or 100 microliters or less of solution. The plurality of extraction chambers may be formed of PC (polycarbonate), ABS (acrylonitrile-butadiene-styrene copolymer), nylon, or a synthetic material of two or more thereof.

According to an embodiment of the present invention, a fixed suction auxiliary means may be fixed inside at least one of the plurality of extraction chambers. As shown in FIG. 1C, the suction auxiliary means 134 may be configured so that the solution shuttle 140 may come in tight contact and suck the solution on the lower surface of the extraction chamber 130. The suction auxiliary means 134 is a means for allowing the solution shuttle 140 to suck the solution on the lower surface of the extraction chamber. The suction auxiliary means 134 may have a top opening and a bottom opening, and an upper portion of the suction auxiliary means 134 may have a structure capable of tightly contacting the solution nozzle 142 of the solution shuttle 140. The lower surface of the suction auxiliary means 134 may be fixed close to the bottom of the extraction chamber 130. When the suction auxiliary means 134 is implemented in the extraction chamber 130, the solution nozzle 142 of the solution shuttle 140 does not need to be long and, thus, the vertical movement range of the solution shuttle 140 may decrease.

According to an embodiment of the present invention, at least one of the plurality of extraction chambers may include a means for imposing a lower limit on a vertical movement of the solution shuttle. Specifically, at least one of the plurality of extraction chambers may include a means for restricting the lower limit of the vertical movement of the solution shuttle to a second height. For example, the edge of the open top of the extraction chamber may contact a specific portion of the solution shuttle, limiting vertical downward movement of the solution shuttle. In another embodiment, a structure that guides the position of the solution nozzle of the solution shuttle and limits downward movement distance may be configured inside the extraction chamber.

According to an embodiment of the present invention, the plurality of extraction chambers 130 may include a sample chamber 135 and a holding chamber 133. The holding chamber 133 is a chamber for storing materials necessary for a sample processing reaction, such as magnetic particles, lysis solution, washing solution, and elution solution. The sample chamber 135 is a chamber containing a sample. Referring to FIG. 2, a sample injection port 126 configured in the cover 120 may be preferably disposed adjacent to the sample chamber 135.

The number of extraction chambers 130 included in the sample processing cartridge 100 may differ depending on sample processing methods. The number of extraction chambers is not particularly limited, but may be, e.g., 5, 6, 7 or 8 or more, or may be, e.g., 20, 15, 14, 13, 12 or less.

Referring to FIG. 1, the cartridge 100 of the present invention includes a body 110 including the plurality of extraction chambers 130. The body 110 is a structure including the plurality of extraction chambers 130 and other components. The body 110 fixes the plurality of extraction chambers to maintain a constant relative position between the chambers.

According to an embodiment of the present invention, the body 110 includes a first plane 111 including a longitudinal direction and a transverse direction and configured horizontally, and the openings 131 of the plurality of extraction chambers may be configured in the first plane 111. The cartridge 100 of the present invention may include the extraction chambers 130 under the first plane 111 and a cover 120 over the first plane 111. The solution shuttle 140 of the present invention may be positioned in an inner area defined by the cover 120 and the first plane 111 of the body 110.

According to an embodiment of the present invention, the cartridge may include a nucleic acid reaction chamber 150. The nucleic acid reaction chamber 150 refers to a chamber for receiving the nucleic acid extracted from the extraction chamber 130 and proceeding with a reaction.

The nucleic acid reaction chamber 150 may be a thin film-shaped chamber having a nucleic acid injection hole configured in one side thereof and including a flow path connected to the nucleic acid injection hole. Alternatively, the nucleic acid reaction chamber 150 may be a cylindrical tube-shaped or polygonal column-shaped chamber having a nucleic acid injection hole at the top.

According to an embodiment of the present invention, the cartridge may comprise a chamber coupling portion (not shown) for coupling an additional chamber. The chamber coupling portion enables a reagent-containing external chamber to be coupled to the cartridge. A reagent that needs to be stored separately or be used selectively depending on the sample may be stored in a separate external chamber and, if necessary, may be selectively mounted on the cartridge and used for sample processing reaction. The chamber coupling portion may be configured in the body. The chamber coupling portion, along with the existing extraction chambers, may be arranged linearly in the longitudinal direction. The chamber coupling portion may include a hole for coupling an external chamber. The chamber coupling portion may include a fixing member capable of fixing the coupled external chamber.

According to an embodiment of the present invention, the cartridge may include the body 110 and the cover 120 for covering the solution shuttle 140. The cover 120 may be configured to cover the upper surface of the body 110 and to provide a space in which the solution shuttle 140 may move between the upper surface of the body 110 and the cover 120. The upper surface refers to the upper surface of the first plane of the body 110. The space in which the solution shuttle 140 may move may be a space sized and shaped to enable the solution shuttle 140 to move between the plurality of extraction chambers. Specifically, the space in which the solution shuttle 140 may move has a height, at which the lower end of the solution shuttle 140 may be positioned higher than the upper surface of the first plane of the body 110, and a length, at which the solution shuttle 140 may move between all the chambers.

Fig. 2 is an exploded perspective view illustrating a cartridge according to an embodiment of the present invention. Referring to FIG. 2, the cover 120 may include a plurality of

side walls

121, 122, 123, and 124 covering both end edges, in the longitudinal direction, of the body 110 and both side edges, in the longitudinal direction, of the body 110 and a roof 125 connecting the side walls. According to an embodiment of the present invention, the cover 120 may be configured to shield the body 110 from the top, front, rear, and left and right sides.

The cover 120 provides a space in which the solution shuttle 140 moves, and prevents the solution from flowing out of the plurality of extraction chambers 130 disposed in the body 110. To that end, the cover 120 includes the

side walls

121, 122, 123, and 124 configured upward from the entire edge (or periphery) of the first plane 111 included in the body 110 and the roof 125 covering the top of the side walls. Referring to FIG. 2, the plurality of

side walls

121, 122, 123, and 124 include a front wall 121 and rear wall 122 covering both end edges, in the longitudinal direction 139, of the first plane 111 of the body 110, and a left side wall 123 and right side wall 124 covering both side edges, in the longitudinal direction 139, of the first plane 111 of the body, that is, both end edges, in the transverse direction, of the first plane 111. The height of the side walls may be determined so that the solution shuttle inside the cartridge may horizontally move over the first plane 111.

According to an embodiment of the present invention, the cartridge 100 may include a guide surface for guiding the solution shuttle 140. The guide surface may be an inner surface of the left side wall 123 and the right side wall 124 of the cover. Alternatively, the guide surface may be configured separately from the

side walls

121, 122, 123, and 124 of the cover 120. For example, the guide surface may be configured inside the cover 120 separately from the side walls. Alternatively, the side end of the upper surface of the cartridge body may extend upward, configuring the guide surface.

According to an embodiment of the present invention, the

side walls

123 and 124, which cover both side edges, in the longitudinal direction, among the plurality of side walls, may guide the movement of the solution shuttle 140.

The left wall 123 and the right wall 124 may guide the movement of the solution shuttle 140 between the plurality of extraction chambers along the moving path, preventing the solution shuttle from deviating from a desired path. Where the solution shuttle 140 couples to, in a rotatable coupling manner, or decouples from the moving means, the left and

right side walls

123 and 124 serves to hold the solution shuttle not to rotate with the solution shuttle when the moving means rotates. Thus, according to an embodiment of the present invention, the left side wall 123 and the right side wall 124 covering both side edges, in the longitudinal direction, among the plurality of side walls may be positioned opposite and parallel to each other. The distance between the left side wall 123 and the right side wall 124 may be equal to the horizontal size of the solution shuttle 140 without leaving a gap or tolerance, or may be 0.1mm to 2mm greater than the horizontal size of the solution shuttle 140.

According to an embodiment of the present invention, the guide surface may be formed to guide both a vertical movement and horizontal movement of the solution shuttle. A vertical movement range and a horizontal movement range may be preset or predetermined for the vertical movement and horizontal movement, respectively, guided by the guide surface. The vertical movement range refers to a range between the highest position of the solution shuttle for movement between the chambers to the lowest position of the solution shuttle for sucking the solution from the chamber. The horizontal movement range refers to a range between the position where the solution shuttle may exchange the solution with the foremost chamber in the longitudinal direction of the cartridge and the position where the solution may exchange the solution with the rearmost chamber.

As shown in FIG. 2A, according to an embodiment of the present invention, a sample injection port 126 through which a sample may be injected into at least one of the plurality of extraction chambers is configured in the cover 120. A sample is injected into one of the extraction chambers through the sample injection port. The cover may include a lid 128 for opening and closing the opening of the sample injection port 126.

As shown in Figure 2A, according to an embodiment of the present invention, the cover 120 may include an opening 127 in one of the plurality of

side walls

121, 122, 123, and 124 to allow the solution shuttle 140 to interact with the outside. In other words, the cover 120 may include the opening 127 to allow the solution shuttle 140 to be coupled to the moving module of the sample processing device.

A coupling element, such as a shaft 221 of the device operating the cartridge, may be coupled to the solution shuttle 140 through the opening 127. According to an embodiment of the present invention, the opening 127 may be configured in the rear wall 122 or the front wall 121 of the cover 120. Alternatively, the opening 127 may be configured in the left side wall 123, the right side wall 124 or the roof 125 of the cover 120.

While the sample solution is processed in the cartridge, aerosols may be generated during the course of mixing, heating, or dispensing the solution. Repetitive occurrence of these fugitive emissions may contaminate the sample processing device. In particular, when the sample processing device repeatedly processes cartridges that detect a specific pathogen, its contamination may affect the test result. Referring to FIG. 6, the cover 120 of the cartridge of the present invention may be configured to prevent contamination of the sample processing device by such fugitive emissions.

According to an embodiment of the present invention, a shielding means 129 may be configured on the opening 127. The shielding means 129 may block the diffusion of fugitive emissions to the outside of the cartridge through the opening 127 while allowing the moving module of the sample processing device to move the solution shuttle through the opening 127. The shielding is to suppress the flow of air through the opening. The shaft 221 of the moving module required for movement of the solution shuttle needs to enter or exit or move through the opening 127. Therefore, the shielding means 129 does not completely seal the opening to completely block the flow of air. The shielding means 129 may be, e.g., a cut-out film. Through the cut portion, the shaft may enter and exit the cartridge to couple with the solution shuttle and move. Another embodiment of the shielding means 129 may be a plate of an elastic material (e.g., rubber or silicone) which has a slit or cut.

According to an embodiment of the present invention, the cover may have a port 128 for a capturing module. The capturing module is a module included in the sample processing device to prevent scattering, and this is described below in detail. The cover of the cartridge of the present invention may be comprise a port 128 through which the capturing module may be connected to the cartridge. The air inside the cartridge is moved to the capturing module through the port 128, and the fugitive emissions are captured in the capturing module. Further, the negative pressure inside the cartridge is maintained to prevent the diffusion of fugitive emissions generated inside the cartridge to the outside. The port 128 may be an opening that is coupled to a connection member of the capturing module. The port 128 may include an air filter.

According to an embodiment of the present invention, the cover may be configured to be detachable from the upper surface of the body or a lower surface of the body. According to an embodiment of the present invention, the cover 120 may be configured to be detachably coupled to the upper surface of the body 110. According to an embodiment of the present invention, the cover 120 may be configured to be detachably coupled to the lower surface of the body 110 and detachably coupled to the upper surface of the body 110. According to an embodiment of the present invention, the cover 120 may include a coupling part to allow the cover 120 to be attached to or detached from the upper surface and lower surface of the body 110. The coupling part is not particularly limited, but may include, e.g., a coupling hole or a coupling groove configured in the cover 120 and a coupling protrusion configured in the body 110 and to be inserted into the coupling hole or coupling groove. The coupling protrusion may be configured to be disposed both in a position where the cover 120 is coupled to the upper surface of the body 110 and a position where the cover 120 is coupled to the lower surface of the body 110. In an embodiment, the coupling part configured on the upper surface of the body 110 may be a coupling part that cannot or may hardly be removed once it is coupled with the cover 120, and the coupling part configured on the lower surface of the body 110 may be a coupling part that is easier to detach from the cover 120 than the coupling part on the upper surface. According to an embodiment of the present invention, the coupling part may be located only in the position where the cover 120 is coupled to the upper surface of the body 110. In the cartridge of the present invention, the cover 120 may relatively easily be removed from the lower surface, increasing the user's operation convenience. After the cover 120 is coupled to the upper surface, the cover 120 is not removed even with a strong force, so that it may operate stably within the sample processing device.

Fig. 6 illustrates a cartridge including a detachable cover 120 according to an embodiment of the present invention. Referring to Fig. 6C, the cover 120 may be coupled to the lower surface of the body 110 before using the cartridge. The cover 120 coupled to the lower surface of the body 110 allows the cartridge to be placed on the floor more stably. Therefore, it is possible to more safely perform the operation of loading the sample taken from the patient into the cartridge. Further, when the cover 120 is coupled to the lower surface of the body 110, the volume of the entire cartridge is reduced by half, so that packaging and distribution of the cartridge may be carried out much more efficiently. In particular, the nucleic acid reaction chamber 150 is made of a thin and less durable material for the purpose of heat transfer efficiency and optical detection and the nucleic acid reaction chamber 150 has to be in close contact with the various modules of the sample processing device for nucleic acid reaction and optical detection. Thus, although the nucleic acid reaction chamber 150 has a structure that is weak against impact, it is difficult to form a structure for protecting the nucleic acid reaction chamber 150 during distribution in the body 110. When the cover 120 remains coupled to the lower surface of the body 110 during distribution, it is possible to effectively prevent damage to the nucleic acid reaction chamber 150.

After inserting the sample into the cartridge, the cover 120 coupled to the lower surface of the body 110 is removed and coupled to the upper surface of the body as shown in FIG. 6B, and then the cartridge may be loaded into the sample processing device. When the cover 120 is coupled to the upper surface as shown in FIG. 6B, the cover 120 provides a moving space for the solution shuttle 140, guides the movement of the solution shuttle 140, and suppresses the spread of fugitive emissions inside the cartridge.

Referring to Fig. 1, the sample processing cartridge of the present invention includes a solution shuttle.

The solution shuttle 140 moves a material between the plurality of extraction chambers and proceeds with a series of extraction reactions.

To that end, the solution shuttle 140 is configures to be movable between the plurality of extraction chambers 130. The solution shuttle 140 may include a flat portion that faces each of the left side wall 123 and the right side wall 124 of the cover 120. When a guide surface is configured on the cover 120 separately from both the side walls, the solution shuttle 140 may include at least one portion in contact with the guide surface. The portion in contact with the guide surface may be configured to contact the guide surface while the solution shuttle 140 moves horizontally and vertically. According to an embodiment of the present invention, the solution shuttle 140 may comprise irregularities on a surface of the solution furface facing the guide surface. The irregularities may reduce friction by reducing the contact area between the guide surface and the solution shuttle 140. The solution shuttle 140 has a hole that is an internal empty space for accommodating a solution. The solution shuttle 140 may have a polygonal column shape tapered downward but, without limitations thereto, may have other shapes. The inner hole of the solution shuttle may have a volume capable of accommodating 3000 microliters or less, 2000 microliters or less, 1500 microliters or less, 1000 microliters or less, 800 microliters or less, 700 microliters or less, 500 microliters or less, 400 microliters or less, 300 microliters or less, 200 microliters or less or 100 microliters or less of solution.

According to an embodiment of the present invention, the solution shuttle 140 includes an air port 141 and a solution nozzle 142. The solution shuttle 140 may have a closed structure without openings other than the air port 141 and the solution nozzle 142.

The solution nozzle 142 is an opening through which the solution shuttle 140 sucks or discharges the substance in the extraction chamber. The solution nozzle 142 is disposed on the lower surface of the solution shuttle 140, and preferably in the center of the lower surface. In the solution shuttle 140, an upper portion of the solution nozzle 142 is a part containing a solution. A lower portion of the solution shuttle 140 may be configured in a funnel shape around the solution nozzle 142 so that the solution contained in the solution shuttle 140 may be smoothly discharged through the solution nozzle 142.

The air port 141 configured in the solution shuttle 140 is a structure for coupling with a connection component of the sample processing device, such as a shaft, for moving the solution shuttle 140 and for adjusting the pressure in the solution shuttle so as to suck and discharge the solution into/from the solution shuttle 140. An opening through which air may enter and exit is configured in the air port 141, and a fastening means capable of being coupled to, e.g., a shaft, is configured. The position where the air port 141 is disposed is not particularly limited, but may vary depending on the direction in which the shaft is connected to the cartridge, and may be, e.g., an upper surface, a rear surface, or a side surface of the solution shuttle 140.

FIG. 2 illustrates an embodiment in which the air port 141 is disposed on the rear surface of the solution shuttle 140. According to an embodiment of the present invention, the air port 141 of the solution shuttle 140 may be configured in the longitudinal direction 139 in which the plurality of extraction chambers are arranged. In this case, the size of the opening 127 configured in the cover 120 may be minimized.

According to an embodiment of the present invention, the air port 141 of the solution shuttle 140 may be configured in a direction perpendicular to the longitudinal direction 139 in which the plurality of extraction chambers are arranged. In this case, since the opening 127 is configured in the left side wall 123 or the right side wall 124 of the cover 120, the size of the opening 127 is increased, but the length of the shaft connected to the solution shuttle 140 to move the solution shuttle 140 need not be formed as long as the length, in the lengthwise, of the cartridge.

According to an embodiment of the present invention, the air port 141 of the solution shuttle 140 may be configured in an upward direction of the solution shuttle that is opposite to the solution nozzle 142. In this case, there is no need to increase the length of the shaft connected to the solution shuttle 140, and vertical movement of the shaft enables both the operation of coupling the shaft and the solution shuttle and the operation of placing the solution shuttle at an appropriate depth in the extraction chamber. Therefore, the mechanical configuration of the moving module of the sample processing device may be simplified.

According to an embodiment of the present invention, the air port may be configured in an upper portion of the solution shuttle. According to an embodiment of the present invention, the opening of the air port may be configured to face upward of the solution shuttle.

Fig. 3 is a view illustrating the movement of the solution shuttle 140 in the cartridge of the present invention. The solution shuttle is configured to be movable within the cartridge. Referring to FIG. 3, the solution shuttle may move horizontally and vertically within the cartridge.

The horizontal movement is a movement for the solution shuttle to move between the plurality of extraction chambers within the cartridge. Referring to FIG. 3A, the horizontal movement means a movement of the solution shuttle indicated by 140c to a position indicated by 140a, for example. The horizontal movement of the solution shuttle may be performed at a height where the horizontal movement is not disturbed by the plurality of extraction chambers, and the 'height at which the plurality of extraction chambers may be moved' is referred to as a first height for convenience. Referring to FIG. 3A, the first height means the height at which the solution shuttle denoted by 140a or 140c is positioned. The first height may be a height at which the lower end of the solution nozzle of the solution shuttle 140 may be positioned higher than the upper opening of the plurality of extraction chambers 130.

The vertical movement of the solution shuttle refers to a movement of the solution shuttle between the 'height at which the solution contained in the plurality of extraction chambers may be sucked' (a second height) and the first height. For example, referring to FIG. 3B, the height of the solution shuttle indicated by 140b may be the second height. The second height may be a height at which the lower end of the solution nozzle of the solution shuttle may be positioned lower than the upper openings of the plurality of extraction chambers 130.

According to an embodiment of the present invention, the solution shuttle may be configured to be vertically movable to the height at which the solution shuttle 140 may move between the plurality of extraction chambers and the height at which the solution shuttle may suck the solution contained in the plurality of extraction chambers. Referring to FIG. 3B, the vertical movement refers to a movement between the height of the solution shuttle, indicated by 140a, and the height of the solution shuttle, indicated by 140b.

According to an embodiment of the present invention, all of the extraction chambers of the cartridge of the present invention may be configured to allow the solution shuttle to suck the solution in each extraction chamber when the solution shuttle reaches the second height above each extraction chamber. For example, the plurality of extraction chambers may be configured such that the lower ends of the extraction chambers have the same height. Alternatively, when a suction auxiliary means is provided in each extraction chambers to come in tight contact with the solution nozzle of the solution shuttle and allow the solution in the extraction chamber to be sucked into the solution shuttle, the extraction chambers may be configured such that the suction auxiliary means of the extraction chambers come in tight contact with the solution nozzle in the same position. As such, where the cartridge is configured so that all functions are possible even when the vertical movement of the solution shuttle is possible only between the first height and the second height, precise control of the vertical movement of the solution shuttle is not required, thus eliminating the need for high-cost parts. Further, even with a simple physical configuration, such as a stopper or a position guide, the vertical movement of the solution shuttle may be controlled very accurately.

According to an embodiment of the present invention, there may be provided a plurality of solution shuttles. In other words, the cartridge of the present invention may include a plurality of solution shuttles. When the cartridge includes a plurality of solution shuttles, a sample processing operation may be performed by alternately using the plurality of solution shuttles, so that the possibility of contamination is decreased as compared with when a single solution shuttle is used.

The number of the plurality of solution shuttles may be 2 to 5, 2 to 4, or 2 to 3.

According to an embodiment of the present invention, the cartridge of the present invention may include a space in which the plurality of solution shuttles may be positioned.

II. Sample processing device

According to an aspect of the present invention, there is provided a sample processing device including a station for accommodating the cartridge and a moving module capable of moving the solution shuttle in the cartridge. The sample processing device operates the cartridge of the present invention, allowing the desired reaction to proceed.

Figs. 4 and 5 illustrate a sample processing device according to an embodiment of the present invention. Figs. 4A and 4B are a side view and a plan view of a sample processing device 200 with a cartridge mounted thereon, according to an embodiment of the present invention. Fig. 5 is a perspective view illustrating a sample processing device 200 with a cartridge mounted thereon, according to an embodiment of the present invention. Hereinafter, the device of the present invention will be described with reference to FIGS. 4 and 5.

The sample processing device 200 of the present invention includes a station 210 capable of accommodating a cartridge 100. The station 210 fixes the cartridge 100 in a proper position so that the cartridge 100 received therein may normally interact with various parts, such as a moving module and a heat transfer module included in the sample processing device. To that end, the station may include a position guide member 210a and a support 210b for the cartridge 100. According to an embodiment of the present invention, the station may include a cartridge moving member for moving the cartridge. The cartridge moving member moves the cartridge inserted into the device to an operable position.

The sample processing device 200 of the present invention also includes a moving means 220 capable of moving the solution shuttle.

According to an embodiment of the present invention, the moving means 220 may include a shaft 221.

The shaft 221 has a hollow tubular shape with a shaft wall having a predetermined thickness, and the shaft 221 includes a first end and a second end. The inner diameter may be 2mm to 20mm, 2mm to 15mm, or 2mm to 10mm, for example. The length of the shaft may vary depending on the length of the cartridge and may be, e.g., 30mm to 200mm, 30mm to 150mm, 30mm to 120mm, 40mm to 100mm, or 50mm to 100mm.

The first end may be provided with a fastening means capable of coupling with the air port 141 of the solution shuttle 140 of the cartridge. The second end may be coupled to a

rotation fastening module

222 and 223. According to an embodiment of the present invention, the shaft 221 may include an air filter member. The air filter member may be, e.g., a cotton ball, and filters air supplied into the cartridge to prevent contamination.

The

rotation fastening module

222 and 223 rotate the shaft 221 so that the shaft 221 is coupled with the solution shuttle 140. Further, the

rotation fastening module

222 and 223 rotates the shaft 221 in the opposite direction so that the shaft 221 is separated from the solution shuttle 140. The

rotation fastening module

222 and 223 includes a rotation motor 222 and a first support 223. The rotation shaft of the rotation motor 222 is coupled to the second end, and the rotation motor 222 is fixed to the first support 223. According to an embodiment of the present invention, a bushing member 224 may be configured to be fixed to the first support 223 in front of the rotation shaft of the rotation motor 222 and surrounds the shaft 221. The bushing member 224 holds the shaft 221 so that the shaft 221 may stably rotate about the rotation shaft.

According to an embodiment of the present invention, the moving means may include a vertical driving module and a horizontal driving module.

The first support is coupled to the

vertical driving module

225 and 226. The vertical driving module is intended for vertically driving the solution shuttle 140 of the cartridge 100 and, to that end, the vertical driving module vertically moves the first support 223. The vertical driving module includes a second support 226 and a first linear actuator 225. The second support 226 supports the first linear actuator 225. The first linear actuator 225 is fixed to the second support 226 so that the moving axis of the moving body 225a is in a vertical direction. The moving body 225a of the first linear actuator 225 is coupled with the first support 223, moving the first support 223 in a vertical direction.

According to an embodiment of the present invention, the vertical driving module may further include one or more LM guides. The LM guide may be configured such that the moving axis of the moving block is parallel to the moving axis of the moving body of the first linear actuator. In the LM guide, the rail may be fixed to the second support, and the moving block may be fixed to the first support. The LM guide allows the first support to move stably.

The second support 226 is coupled to the

horizontal driving module

227 and 228. The horizontal driving module horizontally drives the solution shuttle of the cartridge. Specifically, the horizontal driving module horizontally moves the second support 226. The horizontal driving module includes a third support 228 and a second linear actuator 227. The third support 228 supports the second linear actuator 227. The second linear actuator 227 is fixed to the third support so that the moving axis of the moving body 227a is in a horizontal direction. The moving body 227a of the second linear actuator 227 is coupled with the second support 226, moving the second support 226 in the horizontal direction. The first and second linear actuators may include, e.g., a pneumatic, hydraulic cylinder, or a motor and a ball screw.

According to an embodiment of the present invention, the device may include a pressure control module 241. The pressure control module enables the solution shuttle to suck or discharge the solution through the shaft 221. The pressure control module includes an air pump 241. According to an embodiment of the present invention, the air pump 241 may be fixed to the first support 223 or the second support 226. The air pump 241 may be connected to the shaft 221 using an air tube. To that end, a nozzle 221a may be configured on one side of the shaft to be connected to one end of the air tube, and the other end of the air tube may be connected to the nozzle 214a of the air pump 241.

According to an embodiment of the present invention, the device of the present invention may include a heat transfer module for controlling the temperature of the nucleic acid reaction chamber of the cartridge. The heat transfer module for controlling the temperature of the nucleic acid reaction chamber is referred to as a first heat transfer module 250. The first heat transfer module 250 converts the nucleic acid reaction chamber 150 of the cartridge 100 into two or more temperatures. The first heat transfer module 250 may be a module capable of both heating and cooling. According to an embodiment of the present invention, the first heat transfer module may include a Peltier element capable of both supplying and absorbing heat to/from the nucleic acid reaction chamber.

According to an embodiment of the present invention, the device of the present invention may include a heat transfer module for controlling the temperature of at least one of the plurality of extraction chambers of the cartridge. The heat transfer module for controlling the temperature of the extraction chamber is referred to as a second heat transfer module 260. The second heat transfer module 260 may include a heater and a thermally conductive member. The heater may include a resistance heating element supplying heat to the extraction chamber. Alternatively, the second heat transfer module 260 may be a module capable of both heating and cooling. According to an embodiment of the present invention, the second heat transfer module 260 may include a Peltier element capable of both supplying and absorbing heat to/from the nucleic acid reaction chamber. The second heat transfer module 260 includes a thermally conductive member. The thermally conductive member transfers the heat generated from the resistance heating element or the Peltier element to the extraction chamber to be heated. The thermally conductive member may be configured to come in tight contact with at least one surface of the extraction chamber to be heated.

According to an embodiment of the present invention, the device of the present invention may include a magnetic module 270 configured to control magnetic particles in the extraction chamber. The magnetic module 270 captures the magnetic particles in the extraction chamber so that only the solution may be selectively removed. The magnetic module 270 may be configured to allow a device capable of turning on/off magnetism to be positioned close to a lower surface of the extraction chamber. Alternatively, the magnetic module 270 may include a permanent magnet and a moving member 270a capable of moving the permanent magnet, and may be configured to bring the permanent magnet close to the lower surface of the extraction chamber when necessary.

According to an embodiment of the present invention, the device of the present invention may include a capturing module. The capturing module maintains a negative pressure in the cartridge to prevent contamination of the sample processing device due to, e.g., aerosols generated inside the cartridge and captures fugitive emissions, such as aerosols generated in the cartridge. The capturing module may include an air pump for sucking air in the cartridge, a connection member coupled to the port of the cartridge, and a filter for capturing fugitive emissions.

According to an embodiment of the present invention, the device of the present invention may include an optical module. The optical module detects an optical signal generated in the nucleic acid reaction chamber of the cartridge. The optical module may include a detector.

According to an embodiment of the present invention, the device of the present invention may include a controller. The controller controls parts, such as the moving means, the optical module, the heat transfer module, and the magnetic module of the sample processing device, to perform sample processing in the cartridge.

[CROSS-REFERENCE TO RELATED APPLICATIONS]

This application claims priority from Korean Patent Application No. 10-2019-0177105, filed on December 27, 2019, in the Korean Intellectual Property Office, the disclosure of which is incorporated herein by reference in its entirety.

Claims

A cartridge for processing a sample, the cartridge comprising:

a body including a plurality of extraction chambers linearly disposed in a lengthwise direction; and

at least one solution shuttle configured to be movable between the plurality of extraction chambers and including an air port and a solution nozzle.
The cartridge of claim 1, wherein the air port of the solution shuttle is disposed at an upper portion of the solution shuttle.
The cartridge of claim 1, further comprising a nucleic acid reaction chamber.
The cartridge of claim 1, further comprising a chamber coupling portion for coupling an additional chamber.
The cartridge of claim 1, wherein the at least one solution shuttle is a plurality of solution shuttle.
The cartridge of claim 1, further comprising a guide surface for guiding a movement of the solution shuttle.
The cartridge of claim 6, wherein the guide surface is configured to guide both a vertical movement and horizontal movement of the solution shuttle.
The cartridge of claim 6, wherein the solution shuttle includes a portion in contact with the guide surface.
The cartridge of claim 1, further comprising a cover covering an upper surface of the body, wherein the cover is configured to provide a space in which the solution shuttle moves.
The cartridge of claim 9, wherein the cover includes a sample injection port through which the sample is injected into at least one of the plurality of extraction chambers.
The cartridge of claim 9, wherein the cover is configured to be detachable from the upper surface of the body or a lower surface of the body.
The cartridge of claim 9, wherein the cover includes an opening to allow the solution shuttle to be coupled with a moving module of a sample processing device.
The cartridge of claim 12, further comprising a shielding means in the opening.
The cartridge of claim 9, wherein the cover includes a port for a capturing module.
The cartridge of claim 1, wherein a suction auxiliary means is fixed inside at least one of the plurality of extraction chambers, and wherein the suction auxiliary means is configured to suck in a solution positioned on a bottom of the extraction chamber, with the solution shuttle in tight contact therewith.
The cartridge of claim 1, wherein at least one of the plurality of extraction chambers includes a means for imposing a lower limit on a vertical movement of the solution shuttle.
A device for processing a sample, the device comprising:

(i) a station for receiving a cartridge, wherein

the cartridge including a body including a plurality of extraction chambers linearly disposed in a lengthwise direction and at least one solution shuttle configured to be movable between the plurality of extraction chambers; and

(ii) a moving module for moving the solution shuttle in the cartridge.
The device of claim 17, further comprising a pressure control module for sucking or discharging a solution into/from the solution shuttle.
The device of claim 17, wherein the moving module includes a vertical driving module and a horizontal driving module.
The device of claim 17, further comprising a first heat transfer module for controlling a temperature of a nucleic acid reaction chamber.
The device of claim 17, further comprising a second heat transfer module for controlling a temperature of at least one of the plurality of extraction chambers.
The device of claim 17, further comprising an optical module for measuring an optical signal generated from a nucleic acid reaction chamber.
The device of claim 17, further comprising a magnetic module configured to control magnetic particles in the extraction chamber.
The device of claim 17, further comprising a capturing module.