Patent Application
20250222461
The present invention relates to a genome amplification module having a branch space adjacent to an inlet through which an extract is introduced.
In modern times, advancements in biotechnology have made it possible to interpret the causes of diseases at the genetic level. Thus, there is an increasing demand for manipulation and biochemical analysis of biological samples for curing or preventing human diseases.
Additionally, technology for extracting and analyzing nucleic acids from biological samples or samples containing cells is required in various fields such as new drug development, pre-test for virus or bacterial infection, and forensics in addition to disease diagnosis.
Meanwhile, Korean Patent Registration No. 10-2362853 discloses an extraction device for preparing an extract containing a genome by pre-treating an injected sample, as a device developed by the present applicant. Extract generated by the extraction device moves to an amplification module connected to the extraction device, and the extract injected into a receptacle of the amplification module is amplified through a nucleic acid amplification reaction. A probe that specifically binds to a target sequence and contains a fluorescent substance is stored in the receptacle, so that, when the target sequence is included in the genome of the extract, fluorescence can be observed through the nucleic acid amplification reaction. In addition, depending on whether fluorescence is observed, whether the individual from which the sample was collected is infected with a disease/virus can be determined.
Meanwhile, in the case of an amplification module having a plurality of receptacles, primers/probes for detecting different targets may be stored in each receptacle. When the extracts injected into the plurality of receptacles are mixed during the injection/amplification process, inaccurate detection results will be obtained. In addition, to ensure relatively uniform results, the same amount of extract needs to be injected into each receptacle to; however, in conventional genome amplification modules, a greater volume of extract tend to be injected into the receptacle that is relatively less affected by gravity.
Thus, the inventors of the present invention devised and completed the present invention to address and resolve the problems of such conventional genome amplification modules. However, technical objectives of the present disclosure are not limited to the foregoing, and other unmentioned objectives or advantages of the present disclosure would be understood from the following description and be more clearly understood from the embodiments of the present disclosure.
According to the present invention, the present invention provides a genome extraction device in which an inner chamber containing reagents required for genome extraction is provided separately from an outer chamber and as upper and lower parts of the inner chamber are sealed, a problem that the reagents accommodated in a single chamber leak out in a genome extraction device according to the related art can be solved.
The present invention also provides a genome extraction device including a safety clip for preventing a sealing member sealing upper and lower openings of an inner chamber from being perforated by protrusion members formed in a cover and the outer chamber by the inner chamber moving up and down due to vibration that occurs during a production and distribution process of a product.
The present invention also provides a genome extraction device that solves the problem of cross-contamination between reagents by a capillary phenomenon occurring through a space between double chambers through a unique inner chamber design (lower inner chamber).
The present invention also provides a genome extraction device that solves the problem of reagents leaking out through a unique inner chamber design (upper inner chamber) in a structure for preventing a capillary phenomenon.
The present invention also provides a genome extraction device in which, due to the configuration of a first protrusion member formed on a bottom surface of an outer chamber, a sealing member can be torn with a small force and a perforated portion is expanded so that a reagent accommodated inside the inner chamber can smoothly flow out to the outside.
The present invention also provides a genome extraction device in which an inclined portion is formed around a discharge hole through which reagents are discharged, so that the reagents can smoothly flow out through the discharge hole.
The present invention also provides a genome extraction device in which a double-structured flow cover-pad is arranged between an outer chamber and a base plate so that the convenience of manufacturing is improved and the problem of a flow path being unintentionally narrowed is solved, compared to a genome extraction device according to the related art in which only one pad is arranged.
The present invention also provides a genome extraction device in which firm coupling between a base plate-flow cover-pad-outer chamber is achieved so that sealed flow paths are formed without a phenomenon of reagents flowing out in the middle during the movement process of the reagents.
The present invention also provides a genome extraction device in which a bead chamber in which beads required for genome extraction and amplification are accommodated, also has a double chamber structure of an outer chamber and a bead chamber so that the performance of beads vulnerable to moisture can be maintained for a long time.
The present invention also provides a genome extraction device in which, even if a bead chamber is opened, the performance of beads is maintained by having a dehumidifying portion located at the upper part of the bead chamber.
The present invention also provides a genome extraction device in which, as a pre-treated extract is injected, air remaining inside a receptacle is easily discharged so that an amplification module into which a sufficient capacity of the extract can be injected, is applied to the genome extraction device.
The present invention also provides a genome extraction device in which an amplification module has a plurality of receptacles and primers and probes for different genome amplifications are stored in each receptacle so that various types of diseases can be diagnosed through one genome extraction.
The present invention also provides a genome amplification module in which a plurality of extract moving passages have the same capacity (volume) so that extracts can be simultaneously injected into all receptacles and the same amount of extract can be injected.
The present invention also provides a genome amplification module in which a branch space is formed in a portion adjacent to an inlet and is wider and deeper than an extract moving passage so that extracts can be simultaneously injected along each extract moving passage after the branch space is filled with the extracts.
The present invention also provides a genome amplification module in which a branch space is formed in a first end adjacent to an inlet and a receptacle is provided in a second end far from the first end so that an amplification product in each receptacle can be prevented from being pushed out to a moving passage by a heating temperature or flowing back to another receptacle during an amplification process.
The present invention also provides a genome amplification module in which a space is formed in a connection point of a receptacle of a gas moving passage and is wider and deeper than other portions so that, even if bubbles are generated, they do not affect the receptacle and thus detection accuracy can be improved.
The present invention also provides a genome amplification module in which the width and depth of a gas moving passage are provided to a minimum so that an extract discharged through the gas moving passage is minimized.
The present invention also provides a genome extraction method using the aforementioned genome extraction device.
According to an aspect of the present invention, there is provided an amplification module including a body, an inlet which is formed in the body and through which an extract is introduced, a plurality of receptacles which are connected to the inlet and in which the introduced extract is accommodated, a first branch space which communicates with the inlet, a plurality of extract moving passages which are branched from the first branch space and connect the inlet and the plurality of receptacles to each other, an outlet which is formed in the body and through which gas is discharged, and a plurality of gas moving passages which connect the outlet and the plurality of receptacles to each other.
The first branch space may include a first penetration portion which penetrates the body while being connected to the inlet, and a first recessed portion which is formed between the first penetration portion and the plurality of extract moving passages and recessed in one surface of the body.
One or more of the inner width and inner depth of the first branch space may be wider or deeper than the inner width and inner depth of the extract moving passages.
Volumes of the plurality of extract moving passages may be all the same.
The first branch space may be formed in a first end of the amplification module in a width direction, and the plurality of receptacles may be formed in a second end opposite to the first end of the amplification module in the width direction, wherein the width direction is defined as a direction from the first branch space toward the plurality of receptacles.
The amplification module may further include a second branch space which is formed between the outlet and the plurality of gas moving passages, wherein the second branch space includes a second penetration portion which penetrates the body while being connected to the outlet, and a second recessed portion which is formed between the second penetration portion and the plurality of gas moving passages and recessed in the other surface of the body.
The first recessed portion and the second recessed portion may have a portion where they overlap partially in the width direction of the body and are recessed in the body.
The amplification module may further include a sealing member including a first surface sealing member which is attached to one surface of the body and a second surface sealing member which is attached to an opposite surface to the one surface, wherein the sealing member is configured to seal the plurality of receptacles, the first branch space, and the second branch space from outside.
The first surface sealing member may seal the plurality of extract moving passages from outside and the second surface sealing member may seal the plurality of gas moving passages from outside.
A space between the plurality of extract moving passages and the first surface sealing member and a space between the plurality of gas moving passages and the second surface sealing member may not communicate with each other.
A space between the first recessed portion and the first surface sealing member and a space between the second surface recessed portion and the second sealing member may not communicate with each other.
The gas moving passage may be connected to an upper part of the receptacle, and the gas moving passage may be provided with a space in a connection point with the receptacle, wherein the space has a larger inner with and a larger inner depth than other portions of the each of the plurality of gas moving passages.
One or more of the inner width and inner depth of the gas moving passage may be narrower or shallower than the inner width and inner depth of the extract moving passage.
The gas moving passage may be formed through a combination of one or more including a first gas moving passage having a first inner width and a first inner depth, a second gas moving passage having a second inner width greater than the first inner width and the first inner depth, and a third gas moving passage having a third inner width greater than the second inner width and a second inner depth deeper than the first inner depth.
A plurality of pillars may protrude from the gas moving passage.
The plurality of gas moving passages may include bended portions and straight portions, and the plurality of pillars may be formed in the straight portions and not in the bended portions.
Gas moving passages connected to the plurality of receptacles may have the same capacity.
Probes and primers for amplifying a first target material may be stored in one of the plurality of receptacles, and probes and primers for amplifying a second target material different from the first target material may be stored in another receptacle.
The plurality of extract passages may be connected to an upper end of the first branch space and connected points where the plurality of extract passages are connected to the first branch space may have all the same height.
Each of the plurality of receptacles may have a generally trapezoidal shape, in which a vertical inner length become gradually smaller in a direction away from the plurality of extract moving passages.
In a genome extraction device according to the present invention, an inner chamber containing reagents required for genome extraction is provided separately from an outer chamber and as upper and lower parts of the inner chamber are sealed, a problem that the reagents accommodated in a single chamber leak out in a genome extraction device according to the related art can be solved.
In addition, the inner chamber moves up and down due to vibration that occurs during a production and distribution process of a product, so that a sealing member sealing upper and lower openings of an inner chamber can be prevented from being perforated by protrusion members formed in a cover and the outer chamber.
In addition, the problem of cross-contamination between reagents can be solved by a capillary phenomenon occurring through a space between double chambers.
In addition, reagents can be prevented from leaking out to the outside in a structure for preventing a capillary phenomenon.
In addition, due to the configuration of a first protrusion member formed on a bottom surface of an outer chamber, a sealing member can be torn with a small force and a perforated portion is expanded so that a reagent accommodated inside the inner chamber can smoothly flow out to the outside.
In addition, an inclined portion is formed around a discharge hole through which the reagents are discharged, so that the reagents can smoothly flow out through the discharge hole.
In addition, a double-structured flow cover-pad is arranged between an outer chamber and a base plate so that in which the convenience of manufacturing is improved and the problem of a flow path being unintentionally narrowed is solved, compared to a genome extraction device according to the related art in which only one pad is arranged.
In addition, firm coupling between a base plate-flow cover-pad-outer chamber is achieved so that sealed flow paths are formed without a phenomenon of reagents flowing out in the middle during the movement process of the reagents.
In addition, a bead chamber in which beads required for genome extraction and amplification are accommodated, also has a double chamber structure of an outer chamber and a bead chamber so that the performance of beads vulnerable to moisture can be maintained for a long time.
Even if the bead chamber is opened, the performance of beads is maintained by having a dehumidifying portion located at the upper part of the bead chamber.
As a pre-treated extract is injected, air remaining inside a receptacle is easily discharged so that a sufficient capacity of the extract can be injected into the amplification module.
In addition, an amplification module has a plurality of receptacles and primers and probes for different genome amplifications are stored in each receptacle so that various types of diseases can be diagnosed through one genome extraction.
In addition, a plurality of extract moving passages have the same capacity (volume) so that extracts can be simultaneously injected into all receptacles and the same amount of extract can be injected.
In addition, a branch space is formed in a portion adjacent to an inlet and is wider and deeper than an extract moving passage so that extracts can be simultaneously injected along each extract moving passage after the branch space is filled with the extracts.
In addition, a branch space is formed in a first end adjacent to an inlet and a receptacle is provided in a second end far from the first end so that an amplification product in each receptacle can be prevented from being pushed out to a moving passage by a heating temperature or flowing back to another receptacle during an amplification process.
In addition, a space is formed in a connection point of a receptacle of a gas moving passage and is wider and deeper than other portions so that, even if bubbles are generated, they do not affect the receptacle and thus detection accuracy can be improved.
In addition, the width and depth of a gas moving passage are provided to a minimum so that an extract discharged through the gas moving passage is minimized.
In some cases, in order to avoid ambiguity in the concept of the present invention, known structures and apparatus may be omitted or illustrated in block diagram form focusing on the core functions of each structure and apparatus.
Throughout the specification, when a part is said to “comprising” a certain component, this does not mean excluding other components unless otherwise specifically stated, but rather includes other components. In addition, terms such as “ . . . part”, “ . . . unit”, and “module” described in the specification mean a unit that processes at least one function or operation, which may be implemented by hardware or software or a combination of hardware and software. In addition, “a or an”, “one”, “the” and similar related words may be used in the context of describing the invention (especially in the context of the claims below) to include both singular and plural meanings, unless otherwise indicated in the present specification or clearly contradicted by the context.
In describing embodiments of the present invention, if it is determined that a specific description of a known function or configuration may unnecessarily obscure the gist of the present invention, the detailed description thereof will be omitted. And the terms described below are terms defined in consideration of functions in the embodiments of the present invention, and may vary depending on the intention or custom of the user or operator. Thus, the definitions should be made based on the contents throughout this specification.
Hereinafter, the present invention will be described in detail with reference to the accompanying drawings.
Referring to
The outer chamber 100 is partitioned into a plurality of first spaces 101, 102, 103, 104, 105, 106, and 107 by an outer chamber partition wall. That is, the plurality of first spaces 101, 102, 103, 104, 105, 106, and 107 may be mutually independent spaces.
The plurality of first spaces 101, 102, 103, 104, 105, 106, and 107 may have an open upper portion and a closed lower portion. On the other hand, first discharge holes 121, 122, 123, 124, and 125 are formed through the bottom surface of the plurality of first spaces 101, 102, 103, 104, and 105 along a circumferential direction while being distanced apart by a first distance from the central portion of the outer chamber 100, and second discharge holes 126 and 127 are formed through the bottom surface of the remaining first spaces 106 and 107 along the circumferential direction while being distanced apart by a second distance from the central portion of the outer chamber 100. In addition, discharge holes 128 and 129 are formed through the bottom surface of a space between the first spaces 106 and 107 and communicate with the amplification module 600. Here, the first distance may be shorter than the second distance, but in another embodiment, the first distance may be longer than the second distance.
Reagents stored in the inner chamber 200 to be described later are placed or introduced into the plurality of first spaces 101, 102, 103, 104, and 105, and beads stored in the bead chamber 900 are placed or introduced into the remaining first spaces 106 and 107.
A piston insertion portion 108 into which the piston 700 is inserted is vertically formed through the center of the plurality of first spaces 101, 102, 103, 104, 105, 106, and 107. The piston 700 is inserted into the piston insertion portion 108, and a driving unit (not shown) of a diagnostic device is coupled to the piston 700 to elevate the piston 700 so that reagents (fluids) in the first spaces 101, 102, 103, 104, 105, 106, and 107 may enter and exit (i.e., flow in and out of) a fluid receptacle 701 inside the piston 700. More specific details will be described later.
Referring to
As the safety clip 500 is coupled to the outer chamber 100, the cover 300 presses the inner chamber 200 coupled to the outer chamber 100 so that upper and lower openings of the inner chamber 200 may be prevented from being opened. It is possible for a user to start an extraction process after removing the safety clip 500 from the outer chamber 100 by gripping the handle 520. In other words, when the safety clip 500 is coupled to the outer chamber 100, the reagents in the inner chamber 200 cannot be introduced into the outer chamber 100. Only when the safety clip 500 is removed from the outer chamber 100, the reagents in the inner chamber 200 can be introduced into the outer chamber 100.
Referring to
The safety clip 500 includes an outer chamber coupling portion 510, the handle 520, an upper extension portion 530, and a side extension portion 540.
The outer chamber coupling portion 510 is coupled to the outer chamber 100 while surrounding at least partially an outer circumference (specifically, the outer surface upper portion 100a) of the outer chamber 100. More specifically, the outer chamber coupling portion 510 is coupled to the outer chamber 100 to surround four outer surfaces of the outer chamber 100, and extension ends of the outer chamber coupling portion 510 may be configured to be spaced apart from each other. As shown in
The handle 520 is a portion that extends outwards from the outer chamber coupling portion 510 and is a portion that is gripped by the user to separate the safety clip 500 from the outer chamber 100.
The upper extension portion 530 extends upwards from one side of the outer chamber coupling portion 510, and the side extension portion 540 extends from the upper extension portion 530 toward the center of the outer chamber 100.
The safety clip 500 according to the embodiment of the present invention is characterized in that a cover support member 541 protrudes upward from the upper surface of the side extension portion 540 and an inner chamber coupling portion 542 protrudes laterally from the extended end of the side extension portion 540. The cover support member 541, when the safety clip 500 is coupled to the outer chamber 100, contacts the bottom surface of the cover 300 and keeps the cover from moving downward. Thereby, the cover support member 541 prevents the protrusion members 311, 312, 313, 314, 315, 316, and 317 formed on the bottom surface of the cover 300 from tearing (perforating) a first sealing member S1, which seals upper openings of a plurality of second spaces 201, 202, 203, 204, and 205 of the inner chamber 200 and a third sealing member S3, which seals an upper opening of the bead chamber 900 when the safety clip 500 is coupled to the outer chamber 100.
As the cover support member 541 protrudes upwards from the upper surface of the side extension member 540, when the safety clip 500 is coupled to the outer chamber 100 and the inner chamber 200, as shown in
The inner chamber coupling portion 542 is a portion that is coupled to the fixing portion 230 of the inner chamber 200 when the safety clip 500 is coupled to the outer chamber 100. When the inner chamber coupling portion 542 is coupled to the fixing portion 230, the bottom surface of the inner chamber 200 is positioned at a position spaced apart from the bottom surface of the outer chamber 100 by a predetermined distance. Therefore, the second sealing member S2, which seals the lower openings of the plurality of second spaces 201, 202, 203, 204, and 205 is prevented from being torn by the protrusion members 111, 112, 113, 114, and 115 formed on the bottom surface of the outer chamber 100 (see
In the attached drawing, the inner chamber coupling portion 542 is illustrated in the form of a coupling projection, and the fixing portion 230 is illustrated in the form of a coupling groove that engages with the coupling projection, but in other embodiments, the inner chamber coupling portion 542 may be provided in the form of a coupling groove, and the fixing portion 230 may be provided in the form of a coupling projection that engages with the coupling groove.
A mounting portion 109, that provides a space in which the fixing portion 230 of the inner chamber 200 is mounted, may be formed by being recessed in the outer chamber 100 (more specifically, in at least one of the outer chamber partition walls). While the inner chamber 200 is fixed at a position spaced apart from the bottom surface of the outer chamber 100 by a coupling structure with the safety clip 500, a fixing force may be further enhanced as the fixing portion 230 of the inner chamber 200 is mounted on and supported by the mounting portion 109.
Referring to
Referring to
The inner chamber 200 is partitioned into a plurality of second spaces 201, 202, 203, 204, and 205 by an inner chamber partition wall. That is, the plurality of second spaces 201, 202, 203, 204, and 205 may be independent spaces.
The upper and lower portions of the plurality of second spaces 201, 202, 203, 204, and 205 are open (that is, the plurality of second spaces have an upper opening and a lower opening), and the upper portion is sealed by a first sealing member S1, and the lower portion is sealed by a second sealing member S2. The first sealing member S1 and the second sealing member S2 may be, for example, a film, but the present invention is not limited thereto. The first sealing member may be made of any material that does not allow fluid to pass through.
Different reagents may be injected into each of the plurality of second spaces 201, 202, 203, 204, and 205. The second sealing member S2 seals the lower portion of the plurality of second spaces, before the reagents are injected. After the reagents are introduced, the first sealing member S1 seals the upper portion of the plurality of second spaces, thereby completing the injection of the reagents into the inner chamber 200.
Referring to
The upper inner chamber 210 is formed integrally and is configured to be in close contact with the inner wall of the outer chamber 100 when the upper inner chamber 210 is inserted into and coupled with the outer chamber 100.
The lower inner chamber 220 is connected to the upper inner chamber 210, and are separated spaced apart from the inner wall of the outer chamber 100 when the lower inner chamber 220 is inserted into and coupled with the outer chamber 100. For such separation and spacing apart from the inner wall of the outer chamber 100, the lower inner chamber 220 may include a curved portion (toward the radial inward direction).
When a dual chamber structure including an inner chamber and an outer chamber is used, there may be a risk of cross-contamination with reagents in the inner chamber 200 during operation. Cross-contamination may occur due to a capillary phenomenon through the microscopic space between the inner chamber and the outer chamber. In order to prevent the cross-contamination problem, the present invention has a configuration in which the inner chamber 200 is sufficiently separated and spaced apart from the inner wall of the outer chamber 100 by way of, for example, adopting a curved structure, thereby preventing the capillary phenomenon.
In addition, in order to prevent reagent leakage through the separated and spaced section between the outer chamber 100 and the inner chamber 200, the upper inner chamber 210 is configured to be in close contact with the inner wall of the outer chamber 100, to leave no space therebetween.
On the other hand, referring to
Each of the first protrusion members 111, 112, 113, 114, and 115 may be arranged to correspond one-to-one with the plurality of first spaces 101, 102, 103, 104, and 105. For example, the first protrusion member corresponding to reference numeral 111 tears the second sealing member S2 which seals the lower opening of the second space corresponding to reference numeral 201, and the first protrusion member corresponding to reference numeral 115 tears the second sealing member S2 which seals the lower opening of the second space corresponding to reference numeral 205.
The first protrusion members 111, 112, 113, 114, and 115 include protrusions 111a, 112a, 113a, 114a, and 115a that protrude upward from the bottom surface of the plurality of first spaces 101, 102, 103, 104, and 105 by a first height h1, and wing portions 111b, 112b, 113b, 114b, and 115b that extend laterally from the protrusions 111a, 112a, 113a, 114a, and 115a and protrude from the bottom surface by a second height h2 that is lower than the first height h1. Here, the wing portions 111b, 112b, 113b, 114b, and 115b may be structures extending in both left and right directions from the protrusions 111a, 112a, 113a, 114a, and 115a. The upward ends of the protrusions 111a, 112a, 113a, 114a, and 115a may have a sharp shape.
The protrusions 111a, 112a, 113a, 114a, and 115a perform the function of perforating the second sealing member S2, and the wing portions perform the function of expanding the perforation portion of the second sealing member S2. In the present invention, since the height of the protrusions 111a, 112a, 113a, 114a, and 115a is higher than that of the wing portions 111b, 112b, 113b, 114b, and 115b, point-contact is made between the second sealing member S2 and the protrusions 111a, 112a, 113a, 114a, and 115a, and the pressure is minimized when the second sealing member S2 is torn through the point-contact. Thus, the second sealing member S2 may be torn with less force.
When the second sealing member S2 is torn by the protrusion members 111, 112, 113, 114, and 115, the reagents stored in the plurality of second spaces 201, 202, 203, 204, and 205 of the inner chamber 200 flow out into the plurality of first spaces 101, 102, 103, 104, and 105 of the outer chamber 100. Then, the flowed out reagents are discharged through the first discharge holes 121, 122, 123, and 124 formed on the bottom surface of the first spaces 101, 102, 103, 104, and 105. In order to facilitate discharge of the reagents into the first discharge holes 121, 122, 123, 124, and 125, the areas around the first discharge holes 121, 122, 123, 124, and 125 are provided with portions inclined downward to (i.e., downward-sloping sections directed toward) the first discharge holes 121, 122, 123, 124, and 125. The inclined portions may have an angle of 3 to 10 degrees, and thus, the reagents that have flowed into the first spaces 101, 102, 103, 104, and 105 can be more easily discharged through the first discharge holes 121, 122, 123, 124, and 125.
The cover 300 is configured to be coupled to the upper portion of the outer chamber 100 and to cover the upper portions of the outer chamber 100 and the inner chamber 200.
Referring to
A first insertion hole 307 aligned with the piston insertion portion 108 and a first specimen injection hole 309 into which a specimen is injected are formed through the cover body 301, and second protrusion members 311, 312, 313, 314, and 315 for tearing the first sealing member S1 and third protrusion members 316 and 317 for tearing the third sealing member S3 protrude from the bottom surface of the cover body 301.
The second protrusion members 311, 312, 313, 314, and 315 may be arranged to correspond one-to-one with the plurality of first spaces 101, 102, 103, 104, and 105, and the third protrusion members 316 and 317 may be arranged to correspond one-to-one with a plurality of third spaces 910 and 920. For example, the second protrusion member corresponding to reference numeral 311 tears the first sealing member S1 for sealing the upper opening of the first space corresponding to reference numeral 101, and the second protrusion member corresponding to reference numeral 315 tears the first sealing member S1 for sealing the upper opening of the first space corresponding to reference numeral 105.
A separation member 320 is formed on the bottom surface of the cover body 301 along the periphery of, or surrounding, the first insertion hole 307. The separation member 320 is a portion that allows the first protrusion member and the first sealing member to be separated from each other when the safety clip 500 is coupled to the outer chamber 100. That is, as the separation member 320 is supported by the cover support member 541, the cover 300 is separated from the inner chamber 100 by a predetermined distance.
The lid 302 is connected to one side of the cover body 301 so as to be hinge-rotatable. A second insertion hole 308 that is aligned with the first insertion hole 307 is formed through the central portion of the lid 302.
When the safety clip 500 is separated from the outer chamber 100 in a state in which the cover 300 is coupled to the outer chamber 100 and then the cover 300 is pressed downwards, the inner chamber 200 coupled to the outer chamber 100 descends along the inner wall of the outer chamber 100. Since first protrusion members 111, 112, 113, 114, and 115 are formed on the bottom surface of the outer chamber 100, and second protrusion members 311, 312, 313, 314, and 315 and third protrusion members 316 and 317 are formed on the bottom surface of the cover 300, the first sealing member S1 and the second sealing member S2 that seal the upper and lower openings of the inner chamber 200 and the third sealing member S3 that seals the upper opening of the bead chamber 900 are torn by the protrusion members. Thus, the reagents accommodated in the inner chamber 200 flow out into the plurality of first spaces 101, 102, 103, 104, and 105 of the outer chamber 100. As the second sealing member S2 for sealing the upper opening of the inner chamber 200 is torn, it functions as an air vent so that the reagents may be sufficiently discharged into the first space.
The base plate 400 is coupled to the lower portion of the outer chamber 100 and includes a plurality of paths that guide a path along which the reagents move between the first spaces 101, 102, 103, 104, 105, 106, and 107 of the outer chamber 100 and the fluid receptacle of the piston 700.
According to an embodiment of the present invention, the base plate 400 may have a liquid flow path through which liquid may move and an air flow path through which air may move. The base plate 400 may further include a flow cover 410 and a pad 420 that is between the outer chamber 100 and the base plate 400 and disposed on the upper surface of the base plate 400 to prevent leakage of liquid when coupled with the outer chamber 100. When the base plate 400—the flow cover 410—the pad 420 are assembled, the liquid flow path and the air flow path of the base plate 400 are sealed on their upside by the flow cover 410 and the pad 420, forming a space and completing a perfect path.
The liquid flow path is fluidly connected to the flow cover 410, the pad 420, and the outer chamber 100 to provide a space through which a specimen and a reagent may move and be mixed.
The air flow path fluidly connects a vacuum control section of the amplification module 600 and the piston 700, thereby controlling the vacuum that may occur when the extracted genome moves to the amplification module 600. Additionally, it prevents contamination of an amplification product that may arise during the amplification of the genome.
A plurality of flow paths 401, 402, 403, 404, 405, 406, 407, 408, and 409 are formed on the upper portion of the base plate 400. Each flow path does not intersect with each other, and is formed to extend from the center to the outer part of the base plate 400. Here, the liquid flow paths correspond to reference numerals 401 to 408, while the air flow path corresponds to reference numeral 409.
Referring to
A piston driving unit insertion hole 400a is formed in the center of the base plate 400 so that the driving unit 800 that rotates the piston 700 may be coupled.
A flow cover 410 is placed in the mounting space on the upper part of the base plate 400. The flow cover 410 may be made of, for example, plastic, and may be formed integrally with the base plate 400 by ultrasonically welding while being mounted on the upper part of the base plate 400.
The flow cover 410 has a first through hole 410a aligned with the piston driving unit insertion hole 400a, and a plurality of first flow cover holes 411a, 412a, 413a, 414a, 415a, 416a, 417a, and 418a are formed in the flow cover 410 on a first circumference at a first distance from the first through hole 410a, and a plurality of second flow cover holes 411b, 412b, 413b, 414b, and 415b are formed in the flow cover 410 on a second circumference at a second distance from the first through hole 410a, and a plurality of third flow cover holes 416b, 417b, and 418b are formed in the flow cover 410 on a third circumference at a third distance from the first through hole 410a. In addition, a fourth flow cover holes 419a and 419b are formed in the flow cover 410. The fourth flow cover holes 419a and 419b communicate with one end and the other end of the air flow path 409, respectively. Here, the first flow cover holes are aligned with the inner ends of the flow paths formed in the base plate 400, the second flow cover holes and the third flow cover holes are aligned with the outer end of the flow path. The fourth flow cover holes communicate with one end and the other end of the air flow path. The second distance may be longer than the first distance and shorter than the third distance.
Referring to
In addition, a molten projection 410c that is coupled along the edges of a plurality of flow paths of the base plate 400 may be formed protruding downward on the bottom surface of the flow cover 410 (see
A pad 420 is placed on the flow cover 410. The pad 420 may be made of, for example, a silicone material, but any material having a predetermined elasticity may be applied without particular limitation.
A plurality of second coupling projections 410d protrude upward from the upper surface of the flow cover 410, and the plurality of second coupling projections 410d are coupled to coupling grooves 420c of the pad 420 so that firm coupling between the flow cover 410 and the pad 420 may be formed. In addition, the first coupling projection 410b of the flow cover 410 is also inserted into the second through hole 420a of the pad 420 so that firm coupling between the two components may be achieved.
The pad 420 has a second through hole 420a aligned with the first through hole 410a, and a plurality of first pad holes 421a, 422a, 423a, 424a, 425a, 426a, 427a, and 428a are formed in the pad 420 on the first circumference at a first distance from the second through hole 420a, and a plurality of second pad holes 421b, 422b, 423b, 424b, and 425b are formed in the pad 420 on the second circumference at a second distance from the second through hole 420a, and a plurality of third pad holes 426b, 427b, and 428b are formed in the pad 420 on the third circumference at a third distance from the second through hole 420a. In addition, fourth pad holes 429a and 429b are formed in the pad 420 and communicate with one end and the other end of the air flow path 409, respectively. Here, the first pad holes are aligned with the first flow cover holes, and the second pad holes are aligned with the second flow cover holes, and the third pad holes are aligned with the third flow cover holes, and the fourth pad holes are aligned with the fourth flow cover holes.
At portions of the upper surface of the pad 420 where a plurality of second pad holes 421b, 422b, 423b, 424b, and 425b, a plurality of third pad holes 426b, 427b, and 428b, and a fourth pad hole 429b are formed, protrusions may be further formed. These protrusions may have a shape that gradually gets smaller as they extend upwards. By having such protrusions, even if the pad 420 is placed in close contact between the outer chamber 100 and the base plate 400, the problem of the diameter of the pad holes decreasing differently from the intended decrease may be solved.
The amplification module 600 is coupled to the outer chamber 100 and is configured to receive a specimen for which pre-treatment has been completed. The completion of the pre-treatment of the specimen means that the genome, such as Deoxyribo nucleic acid (DNA) or Ribo nucleic acid (RNA), contained in the specimen has been dissolved (lysis) into the reagent. When the genome extraction device 1000 according to the present invention is coupled to the diagnostic device (not shown), an amplification process (polymerase chain reaction (PCR), etc.) of the genome accommodated in the amplification module 600 may be performed.
Referring to
Referring to
The body 610 is a portion that constitutes the outer shape of the amplification module 600, and the inlet 621 and the outlet 622 are formed in a first end 613 of the body 610 which is coupled to the discharge holes 128 and 129 of the outer chamber 100.
The inlet 621 is coupled to the discharge hole 129 and serves as an inlet for the extract discharged from the discharge hole 129 to be injected into the receptacle 630, and the outlet 622 is coupled to the discharge hole 128 and serves as an outlet for the air inside the amplification module 600 to be discharged to the air flow path of the extraction device 1000 as the extract is injected into the amplification module 600.
That is, in a state in which the amplification module 600 is coupled to the extraction device 1000, the inlet 621 communicates with the liquid flow path 408, and the outlet 622 communicates with the air flow path 409.
The receptacle 630, which is a space for accommodating the extract introduced through the inlet 621, is formed at a position further away from the extraction device 1000 than a first end 613 of the body 610, the inlet 621, and the outlet 622.
The body 610 of the receptacle 603 may generally have the shape of a panel or a plate having two opposing surfaces.
In an example, the receptacle 630 may be manufactured in a form that penetrates both one side and the opposite side of the body 610. However, in another example, the receptacle 630 may be manufactured in a form that penetrates only one side without passing through the opposite side. In both embodiments, the open sections are sealed by the sealing members S4 and/or S5. Thus, the extract and air are introduced into and discharged from the receptacle 630 only through the gas moving passage 640 and the extract moving passage 650.
One or more receptacles 630 according to an embodiment of the present invention may be provided in one amplification module 600.
The receptacle 630 may have an generally trapezoidal shape, and more specifically, preferably, the receptacle 630 may have a trapezoidal shape with rounded edges.
Here, the trapezoidal shape means a shape whose vertical inner length becomes smaller as it gets farther away from the gas moving passage 640 and the extract moving passage 650. The receptacle 630 has the above shape so that the problem of bubbles being generated even if the extract is injected through the extract moving passage 650 is solved. When bubbles remain in the amplification module 600, especially in the receptacle 630, the problem of low analysis accuracy occurs in a fluorescence detection process after the amplification process, so that the problem may be solved through the shape of the receptacle 630. In the present invention, the amplification process may include an isothermal amplification process (Lamp) and a real-time nucleic acid amplification reaction (Real time Polymerase Chain Reaction), but the present invention is not particularly limited thereto as long as it is a process for a genome.
Primers and probes required for amplifying a genome are stored in the receptacle 630. The amplification module 600 according to the embodiment of the present invention includes one or more receptacles 630, and primers and probes targeting different substances may be provided in each receptacle 630. Thus, detection of various types of viruses/diseases may be performed simultaneously in the genome extracted from one sample. For example, primers and probes for amplifying a coronavirus may be provided in one receptacle 630, and primers and probes for amplifying an influenza virus may be provided in another receptacle 630, and different viruses/diseases with one amplification process in one amplification module 600 can be simultaneously detected.
According to an embodiment, the gas moving passage 640 may be formed on one surface 611 of the body 610 and configured to connect the outlet 622 to the upper part 631 of the receptacle 630. Contrary to this, the extract moving passage 650 may be formed on an opposite surface 612 opposite to the one surface 611 and configured to connect the inlet 621 to the lower part 632 of the receptacle 630.
First, the extract moving passage 650 will be described with reference to
In an embodiment of the present invention, the number of extract moving passages 650 is the same as that of receptacles 630. In other words, in the case of an amplification module 600 including three receptacles 630 as in
Each extract moving passage 650 is configured so that the volumes of the passages is all the same. For example, each extract moving passage 650 may have the same length, width, and depth, and even if at least one of the depth, width, and depth is different, the capacity (volume) of each passage is configured to be the same. Thus, the extract spread along the extract moving passage 650 may reach the receptacles 630 at the same time, so that the extract may be filled in all the receptacles 630.
Meanwhile, in order to minimize the generation of bubbles during the process of the extract being distributed through the extract moving passage 650, the extract moving passage 650 is designed with curved connecting parts of the passage without angled parts to minimize bubble generation.
A first branch space 660 is formed between the extract moving passage 650 and the inlet 621. The first branch space 660 allows the inlet 621 and the extract moving passage 650 to communicate with each other.
Referring to
The first penetration portion 661 is configured to penetrate the body 610 from one surface to the opposite surface while being connected to the inlet 621, and the first recessed portion 662 is formed between the first penetration portion 661 and the extract moving passage 650 without penetrating the body 610, but is configured to be recessed in one surface 611 of the body 610.
As will be described later, a second recessed portion 672 is also formed on the opposite surface 612 of the body 610. Therefore, the first recessed portion 662 and the second recessed portion 672 are formed at positions where they partially overlap along the width direction. (The width direction means a direction from the first end 613 toward the second end 614 of the body 610 or the opposite direction.) However, while the space between the first recessed portion 662 and the sealing member, and the space between the second recessed portion 672 and the sealing member partially overlap along the width direction, the first recessed portion 662 and the second recessed portion 672 are formed in such a way that these spaces (i.e., the space between the first recessed portion 662 and the sealing member and the space between the second recessed portion 672 and the other sealing member) remain independent spaces that do not communicate with each other. If the first recessed portion 662 and the second recessed portion 672 are configured to penetrate the body 610, the extract that is spread into the extract moving passage 650 through the inlet 621 may also be spread into the gas moving passage 640, and conversely, the air that is discharged from the receptacle 630 toward the outlet 622 may also be spread into the extract moving passage 650. Thus, in the present invention, the first recessed portion 662 and the second recessed portion 672 are configured in a recessed configuration on opposite surfaces, not penetrating the body 610 from one surface to the other.
Meanwhile, even if the first penetration portion and the second penetration portion are formed in a penetration configuration, there is no interference problem because they do not overlap each other along the width direction.
Each extract moving passage 650 starts from the first recessed portion 662 and extends to the receptacle 630 while bending at least once. At a first end of each extract moving passage 650 connected to the first recessed portion 662, each extract moving passage 650 may at least initially extend upward. Then, each extract moving passage 605 may bend and extend laterally toward the second end of the amplification module in the width direction. Each extract moving passage 650 then may bend and extend downward. After that, each extract moving passage 650 may bend again and extend toward the second end of the amplification module in the width direction. However, the extract moving passage 650 may not necessarily extend exactly upward or exactly laterally. According to an embodiment, at least at a certain portion of each extract moving passage 650, the extract moving passage 650 may bend and/or extent obliquely, even at the first end of each extract moving passage 650.
The inner width and inner depth of the first penetration portion 661 and the first recessed portion 662 are greater than the inner width and inner depth of the extract moving passage 650.
When a moving passage cross-sectional plane is defined as a virtual plane which is perpendicular to an extension direction of the extract moving passage 650 and a thickness direction is defined as a direction from the one surface 611 toward the opposite surface 612 of the body 610 or the opposite direction thereof, the inner depth of the extract moving passage 650 is measured in the thickness direction in the moving passage cross-sectional plane and the inner width is measured in a direction perpendicular to the thickness direction in the moving passage cross-sectional plane. That is, for example, when the extract moving passage extends upward, the inner width of the extract moving passage 650 is measured in the width direction, and when the extract moving passage extends laterally, the inner width of the extract moving passage 650 is measured in the height direction, which is an upward and/or downward direction.
As for the first penetration portion 661 and the first recessed portion 662, the inner depths of the first penetration portion 661 and the first recessed portion 662 are measured in the thickness direction and the inner widths of the first penetration portion 661 and the first recessed portion 662 are measured in the width direction. (The inner width, the inner depth, and the thickness direction may be defined and understood in an analogous manner for the second branch space 670 and the gas moving passage 640.)
Thus, assuming that the extract moving passage 650 extends in the vertical direction such as at the first end of the extract moving passage 650 and the unit length is defined in the vertical direction, if the volume of the extract moving passage 650 in a unit length is compared with the volumes of the first penetration portion 661 and the first recessed portion 662 in the same unit length, the volume (capacity) of the first penetration portion 661 and the volume (capacity) of the first recessed portion 662 in the unit length are larger than that of the extract moving passage 650 in the unit length.
Therefore, the spreading speed of the extract through the inlet 621 is slower in the first branch space 660 than in the extract moving passage 650, causing a kind of stagnation phenomenon. After the first branch space 660 is completely filled with the extract, the extract may spread into the extract moving passage 650. This configuration has the advantage of allowing the extract to be distributed to each extract moving passage 650 simultaneously, compared to the case where the first branch space 660 is not provided. (In the case of an amplification module without the first branch space, the extract is first injected into the extract moving passage located at the lowest position due to gravity).
Meanwhile, preferably, the first branch space 660 may be formed at the first end 613 of the amplification module 600 in the width direction, and the receptacle 630 may be formed at the second end 614 opposite to the first end 613. In other words, preferably, the receptacle 630 and the first branch space 660 may be far apart in the width direction.
The extract is injected into and accommodated in the receptacle 630, and a heating device/cooling device is brought into close proximity or contact therewith to perform an amplification reaction. In order to prevent the amplification product in each receptacle 630 from being pushed out to the moving passages 640 and 650 by the heating temperature or flowing back to another receptacle 630 in advance during the amplification process, the first branch space 660 and the second branch space 670 described below are positioned at the first end 613 adjacent to the inlet 621 and the outlet 622.
The gas moving passage 640 serves as a passage through which gas (e.g., air) in the receptacle 630 moves. The flow path of the amplification module 600 is connected to the flow path of the genome extraction device 1000, forming an overall closed flow path. Since the receptacle 630 is filled with air before the extract is injected, if the extract is injected, an appropriate amount of air needs to be discharged to the outside. In the present invention, the air inside the amplification module 600 is discharged to the air flow path 409 through the outlet 622 via the gas moving passage 640, thereby preventing excessive pressure increase inside the receptacle 630 that occurs when the extract is injected, and solving the problem of bubbles that occur due to air remaining inside. Also, preferably, the gas moving passage 640 may be provided with smoothly curved connecting portions of the passage without angled portions, like the receptacle 630, to minimize the occurrence of bubbles.
Gas is lighter than a liquid such as an extract, and in the present invention, a plurality of gas moving passages 640 are connected to the upper end 631 of the receptacle 630. At the connection point between the receptacle 630 and the gas moving passage 640, a bubble receptacle 633 is located, which is wider and deeper than other parts of the other gas moving passages. Even if bubbles are generated inside the receptacle 630 as the extract is injected, the bubbles can be accommodated in the wide and deep bubble receptacles 633 and 643, and thus, the effect of the bubbles to the receptacle 630 is minimized.
Both embodiments are characterized by minimizing the inner width and inner depth of the gas moving passage 640, so that liquid inflow into the gas moving passage 640 is minimized and only air can pass through.
The gas moving passage 640 of the amplification module 600 according to the first embodiment is configured as a combination of a first gas moving passage 641, a second gas moving passage 642 and a third gas moving passage 643. The first gas moving passage 641 has a first inner width and a first inner depth. The second gas moving passage 642 has a second inner width greater than the first inner width and a first inner depth, the same inner depth with the first gas moving passage. The third gas moving passage 643 has a third inner width greater than the second inner width and a second inner depth greater than the first inner depth. Specifically, the amplification module 600 according to the first embodiment is configured such that the volumes of each gas moving passage 640 are all the same.
Meanwhile, among the gas moving passages 640 of the amplification module 600 according to the first embodiment, the first gas moving passage 641 having the narrowest inner width and lowest inner depth may have an inner width of 0.135 mm to 0.165 mm, more specifically 0.14 mm to 0.16 mm, even more specifically 0.145 mm to 0.155 mm, and preferably 0.15 mm, and an inner depth of 0.045 mm to 0.055 mm, more specifically 0.0475 mm to 0.0525 mm, and preferably 0.05 mm.
In addition, the gas moving passage 640 of the amplification module 600 according to the second embodiment may have a constant inner width and a constant inner depth along its extension direction, and the inner width may be 0.45 mm to 0.55 mm, more specifically 0.475 mm to 0.525 mm, more specifically 0.49 mm to 0.51 mm, and preferably 0.5 mm, and the inner depth may be 0.045 mm to 0.055 mm, more specifically 0.0475 mm to 0.0575 mm, and more specifically 0.049 mm to 0.051 mm, and preferably 0.05 mm. In addition, on an inner surface of the gas moving passage 640 of the amplification module 600 according to the second embodiment, a plurality of pillars r is provided by protruding from the inner surface, through a laser pattern processing method. Thus, the inner width and inner depth of the gas moving passage 640 are further minimized, so that liquid inflow is minimized and only air can pass through. As with the first embodiment, the amplification module 600 according to the second embodiment is also configured so that the volume of each gas moving passage 640 is the same.
In the embodiment of the present invention, the number of gas moving passages 640 is the same as the number of receptacles 630. In other words, in the case of an amplification module 600 including three receptacles 630 as shown in
The piston 700 is inserted into the piston insertion portion 108 of the outer chamber 100 and is configured to inhale the reagent accommodated in the outer chamber 100 or discharge the reagent inhaled into the outer chamber 100 or the amplification module 600 according to the upward and downward movement.
Referring to
The upper piston 710 has an open top, and a fluid receptacle 701, in which the inhaled fluids are accommodated, is formed inside the upper piston 710. A close-contact portion 711 is installed inside the upper piston 710. The outer surface of the close-contact portion 711 is in close contact with the inner surface of the upper piston 710 leaving no space between the outer surface of the close-contact portion 711 and the inner surface of the upper portion 710, so that the fluid cannot enter or exit through between the outer surface of the close-contact portion 711 and the inner surface of the upper piston 710. A driving unit installation portion 711a, to which a driving unit (not shown) of a diagnostic device is coupled, is recessed in the center of the close-contact portion 711. The driving unit (not shown) of the diagnostic device is coupled to the driving unit installation portion 711a, and ascends and descends the close-contact portion 711 inside the upper piston 710 to inhale the fluid into the fluid receptacle 701 or discharge the fluid accommodated in the fluid receptacle 701 to the outside.
The bottom surface of the upper piston 710 is provided with a coupling structure that engages with the lower piston 720, and a first hole 712 connected to a liquid port 723 of the lower piston 720 and a second hole 713 connected to a filter port 724 of the lower piston 720 are formed in the upper piston 710. The second hole 713 may be formed to have a smaller diameter than a filter mounting space of the filter port 724 so as to prevent detachment of a support structure and a filter.
The lower piston 720 is fixed by engaging with the coupling structure formed on the bottom surface of the upper piston 710.
The lower piston 720 may include a disc-shaped body 721, a shaft 722 formed to protrude downward and outwards from the center of the body 721, and a liquid port 723 and a filter port 724 arranged at an equal distance from the center of the body 721.
The liquid port 723 is used when a specimen and a reagent are inhaled, mixed and discharged into the piston 700, and the filter port 724 may be used when a genome capture filter is washed or a genome is separated from the genome capture filter.
In addition, a groove recessed toward the center may be formed on the outer periphery of the body 721 of the lower piston 720. This groove serves to remove a vacuum that may occur when a liquid moves inside the extraction device.
The liquid port 723 and the filter port 724 are arranged at a certain angle apart from each other on the same circumference. For example, the two ports of the filter port 724 and the liquid port 723 may be arranged at an angle of 18 to 36 degrees, and more specifically, the two ports may be arranged at an angle of 22.5 degrees. When a step motor that performs one rotation by dividing into 16 times is used, the positions of the liquid port 723 and the filter port 724 may be changed by one driving.
The filter port 724 of the lower piston 720 may include a filter mounting space 725, and the filter and the support structure may be arranged in the filter mounting space 725. A glass fiber filter or a mold fixture having various particle sizes may be used as a filter for capturing the genome, and the support structure serves to fix the filter for capturing the genome.
The support structure may be formed of a porous plastic material having a constant particle size so as to prevent the filter from being detached when discharging the fluid and to maintain a constant pressure.
The driving unit 800 is connected to the driving unit (not shown) of the diagnostic device and serves as a medium to rotate the piston 700 at a certain angle.
The driving unit 800 may include a coupling groove formed in the center of one side of the driving unit 800 to engage with the shaft 722 and a driving groove formed in the other side of the driving unit 800 to engage with the driving unit (not shown) of the diagnostic device.
The driving unit 800 is coupled to the piston 700 and allows the liquid port 723 and the filter port 724 to be positioned at positions of the first discharge holes of the appropriate outer chamber 100 so that various chemical reactions required in the genome extraction step may be performed within one device.
The liquid port 723 and the filter port 724 are spaced apart at a certain angle, and the driving unit 800 rotates the ports to positions appropriate for each step during genome extraction.
Referring to
Similar to the inner chamber 200, the upper opening of the bead chamber 900 is also sealed by the third sealing member S3. The third sealing member S3 is perforated by the third protrusion members 316 and 317 formed on the bottom surface of the cover 300 when the cover 300 is coupled to the outer chamber 100. As the upper opening of the bead chamber 900 is opened by the third protrusion members 316 and 317, it becomes possible for a corresponding amount of air to be discharged through the perforated portion when fluid is introduced into the first bead chamber 910 and the second bead chamber 920.
The lower opening of the bead chamber 900 is provided in an open form without being separately sealed by a sealing member. Dry beads (more specifically, freeze-dried beads) are stored in the bead chamber 900, and dry beads have a characteristic of being vulnerable to moisture. In the genome extraction device according to the present invention, the lower opening of the bead chamber 900, the first space of the outer chamber 100, the flow cover 410, the pad 420, the flow path of the base plate 400, and the flow path of the amplification module 600 communicate with one another, but form a closed flow path that is not exposed to the outside air so that the inflow of moisture into the bead chamber 900 may be minimized.
A plurality of dry beads b1 required for genome extraction may be stored in the first bead chamber 910, and a plurality of dry beads b2 required for genome amplification may be stored in the second bead chamber 920.
A first bead holder 911 is installed in the upper opening of the first bead chamber 910 to prevent the dry beads b1 from being discharged while keeping them inside, and a first dehumidifying portion 912 is installed in the dehumidifying chamber 930 for dehumidifying the internal space of the first bead chamber 910. Here, the dry beads for the amplification of the genome material may be provided in the form of a capsule, for example, but the present invention is not particularly limited thereto.
A second bead holder 921 is installed in the upper opening of the second bead chamber 920 to prevent the dry beads b2 from being discharged while keeping them inside, and a second dehumidifying portion 922 is installed above the second bead holder 921 for dehumidifying the inside of the second bead chamber 920.
The third sealing member S3 seals the second bead chamber 920 so that the second bead chamber 920, the dehumidifying chamber 930 and the first bead chamber 910 do not communication with one another, but the first bead chamber 910 and the dehumidifying chamber 930 communicate with each other. This will be specifically described with reference to
The above-described effect is achieved through the height difference configuration between the first bead chamber partition wall 901 and the second bead chamber partition wall 902. Referring to
In other words, the upper part of the second bead chamber partition wall 902 extends to the same height as the upper part of the outer wall that defines the second bead chamber 920, and the upper part of the first bead chamber partition wall 901 extends to a height lower than the upper part of the outer wall that defines the first bead chamber 910.
Thus, even if the upper opening of the bead chamber 900 is sealed by the third sealing member S3, the first bead chamber 910 and the dehumidifying chamber 930 may communicate with each other through the space between the first bead chamber partition wall 901 and the third sealing member S3. Thus, the first bead chamber 910 is dehumidified by the a first dehumidifying portion 912 installed inside the dehumidifying chamber 930.
A lower opening 914 of the first bead chamber 910 (i.e., the outlet of the first bead chamber) and a lower opening 924 of the second bead chamber 920 (i.e., the outlet of the second bead chamber) are formed at the lower ends of discharge passages 913 and 923 that become smaller as they go from the bead chamber 900 toward the base plate 400.
Dry beads may be accommodated inside the discharge passages 913 and 923, and bead holders may be installed on the upper portion of the discharge passages 913 and 923 to prevent external discharge of beads accommodated within them.
The discharge passages 913 and 923 may have a so-called tapered shape that becomes smaller as they go toward the base plate 400. The diameter of the lower openings 914 and 924 located at the lower end of the discharge passages 913 and 923 is provided to be smaller than the diameter of the dry beads so that the beads cannot be discharged to the outside through the lower openings 914 and 924. The fluid flows into the discharge passages 913 and 923 through the lower openings 914 and 942, the introduced fluid melts the dry beads, and may be discharged to the outside (fluid receptacle of the piston or amplification module) through the lower openings 914 and 924 only in the form of the fluid.
Here, the discharge passage 913 of the first bead chamber 910, in which the dry beads required for the genome amplification are stored, has a greater diameter than the discharge passage 923 of the second bead chamber 920 and may become smaller as it goes toward the base plate 400.
Before the pre-treated extract is introduced into the amplification module 600, the final fluid injection takes place in the first bead chamber 910. Since it is essential that the fluid injected into the first bead chamber 910 does not remain inside as much as possible but is instead transferred to the receptacle 630 of the amplification module 600 to obtain accurate detection results, the present invention minimizes fluid retention within the first bead chamber 910 by configuring the discharge passage 913 of the first bead chamber 910 with a larger diameter than the discharge passage 923 of the second bead chamber 920 while gradually narrowing it.
In addition, the bead chamber 900 according to the present invention has first catch protrusions 903 and 904 extending from the bottom surface of the outer walls of the first bead chamber 910 and the second bead chamber 920. As shown in
In the outer chamber 100 coupled to the bead chamber 900, a second catch protrusion 109a is formed on one side of the outer chamber partition wall that partitions a plurality of first spaces, and when force is applied to the bead chamber 900 toward the base plate 400, the first catch protrusions 903 and 904 pass the second catch protrusion 109a and are coupled to each other so that firm coupling between the two components may be achieved. When the first catch protrusions 903 and 904 are coupled to the second catch protrusion 109a, the relative position of the bead chamber 900 with respect to the outer chamber 100 is fixed.
Hereinafter, an extraction method according to an embodiment of the present invention will be specifically described.
First, (a) the inner chamber is coupled to the outer chamber through the upper openings of the plurality of first spaces of the outer chamber. Here, preferably, the fixing portion of the inner chamber may be coupled to the outer chamber while being coupled with the inner chamber coupling portion of the safety clip.
Next, (b) the cover is coupled to the outer chamber, and (c) the safety clip is removed from the outer chamber.
Next, (d) the cover is pressed, and the first sealing member that seals the upper opening of the inner chamber is torn by the first protrusion member formed on the bottom surface of the cover, and the second sealing member that seals the lower opening of the inner chamber is torn by the second protrusion member formed on the bottom surface of the plurality of first spaces of the outer chamber, so that the reagents accommodated in the inner chamber flow out into the plurality of first spaces, and (e) by the driving of the driving unit, the reagents that flow out into the plurality of first spaces are inhaled into and mixed in the fluid receptacle inside the upper piston, and then the mixed reagents are discharged to the amplification module.
The above operation (e) may include a plurality of sub-operations. Hereinafter, the operation (e) will be described in more detail.
First, (e1) a specimen to be analyzed is introduced into one of the plurality of first spaces of the outer chamber through the specimen introduction hole of the cover.
Next, (e2) a piston installed in the piston insertion portion of the outer chamber rotates, so that the liquid port of the piston and the first discharge hole formed in the bottom surface of one of the first spaces into which the specimen to be analyzed is introduced, communicate with each other.
Next, (e3) a close-contact portion installed in the inner space of the piston rises so that the specimen to be analyzed accommodated in one of the first spaces is inhaled into the fluid receptacle inside the upper piston.
Next, (e4) the piston rotates so that the liquid port of the piston and the first discharge hole formed in the bottom surface of another first space communicate with each other.
Next, (e5) the close-contact portion rises so that the first reagent accommodated in the other first space is inhaled into the fluid receptacle inside the upper piston, so that the specimen to be analyzed and the first reagent are mixed in the fluid receptacle.
Next, (e6) the piston rotates so that the liquid port of the piston and the first discharge hole formed in the bottom surface of another first space communicate with each other.
Next, (e7) the close-contact portion rises so that the second reagent accommodated in the other first space is inhaled into the fluid receptacle inside the upper piston so that the specimen to be analyzed, the first reagent, and the second reagent are mixed with one another.
Next, (e8) the piston rotates so that the filter port of the piston and the first discharge hole formed in the bottom surface of another first space communicate with each other.
Next, (e9) the close-contact portion descends so that the mixed solution accommodated in the fluid receptacle passes through the genome capture filter installed in the filter port and is discharged into another first space.
Next, (e10) the piston rotates so that the liquid port of the piston and the first discharge hole formed in the bottom surface of the first space in which the first reagent, the second reagent and other reagents are accommodated, communicate with each other.
Next, (e11) the close-contact portion rises, and other reagents are inhaled into and mixed in the fluid receptacle.
Next, (e12) the piston rotates so that the filter port of the piston and the first discharge hole formed in the bottom surface of the first space in which other reagents are accommodated, communicate with each other.
Next, (e13) the close-contact portion descends so that the mixed solution accommodated in the fluid receptacle passes through the genome capture filter and is discharged into the first space in which other reagents are accommodated.
Next, (e14) the piston rotates so that the liquid port of the piston and the first discharge hole formed in the bottom surface of the first space in which an eluent is accommodated, communicate with each other.
Next, (e15) the close-contact portion rises so that the eluent is inhaled into the fluid receptacle.
Next, (e16) the piston rotates so that the filter port of the piston and the second discharge hole formed in the bottom surface of the first space in which the beads required for genome amplification are accommodated, communicate with each other.
Next, (e17) the close-contact portion descends so that the eluent accommodated in the fluid receptacle passes through the genome capture filter and is discharged into the first space where beads required for genome amplification are accommodated, and the genome captured in the genome capture filter is separated from the genome capture filter and discharged together into the first space.
Next, (e18) the piston rotates so that the liquid port of the piston and the second discharge hole formed in the bottom surface of the first space where the genome is accommodated, communicate with each other.
Next, (e19) the close-contact portion rises so that the extract containing the genome is inhaled into the fluid receptacle.
Next, (e20) the piston rotates so that the liquid port of the piston and the amplification module communicate with each other.
Next, (e21) the close-contact portion descends so that the extract containing the genome accommodated in the fluid receptacle is discharged to the amplification module.
Next, (e22) the extract is introduced into the receptacle of the amplification module through the extract moving passage of the amplification module.
Next, (e23) the remaining air in the receptacle is discharged to the outside of the amplification module through the gas moving passage of the amplification module.
Next, (e24) the amplification device applies heat of a predetermined temperature or higher to the receptacle so that the genome is amplified.
Next, (e25) based on the fluorescence intensity of the amplification product of the genome, whether or not the specimen to be analyzed is infected with a disease is determined.
As described above, although the present specification has been described with reference to the embodiments illustrated in the drawings so that those skilled in the art can easily understand and reproduce the present invention, this is merely exemplary, and it will be understood by those skilled in the art that various modifications and equivalent other embodiments are possible from the embodiments of the present invention. Therefore, the protection scope of the present invention should be determined by the claims.
| Number | Date | Country | Kind |
|---|---|---|---|
| 10-2022-0123435 | Sep 2022 | KR | national |
This application is a by-pass continuation application of International Application No. PCT/KR2023/009297 filed on Jul. 3, 2023, claiming priority based on Korean Patent Application No. 10-2022-0123435 filed on Sep. 28, 2022, the disclosures of which are incorporated herein by reference in their entireties.
| Number | Date | Country | |
|---|---|---|---|
| Parent | PCT/KR2023/009297 | Jul 2023 | WO |
| Child | 19093213 | US |
