WO2025206879A1

WO2025206879A1 - A module having a space for sample preparation, amplification, and measurement, and a cartridge comprising the module

Info

Publication number: WO2025206879A1
Application number: PCT/KR2025/095074
Authority: WO
Inventors: Young-Shik Cho; Dong-Hun Kim; In-Ae KIM; Hyo-Lim Park; Sunyoung Lee; Kwanhun Lim
Original assignee: SD Biosensor Inc
Current assignee: SD Biosensor Inc
Priority date: 2024-03-26
Filing date: 2025-03-24
Publication date: 2025-10-02
Anticipated expiration: 2026-09-26

Abstract

A device is provided, in which preparation, amplification, and measurement of a biological sample can all be performed within a module mounted in a cartridge, thereby solving the problem of requiring a complex structure in conventional devices.

Description

A MODULE HAVING A SPACE FOR SAMPLE PREPARATION, AMPLIFICATION, AND MEASUREMENT, AND A CARTRIDGE COMPRISING THE MODULE

The present invention relates to a module that provides a space for sample preparation, amplification, and measurement, and a cartridge comprising the module.

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 the manipulation and biochemical analysis of biological samples to cure or prevent 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-tests for virus or bacterial infection, and forensics in addition to disease diagnosis and other biological applications.

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 a receptacle, so that, when the genome of the extract contains the target sequence, fluorescence can be observed through the nucleic acid amplification reaction. Accordingly, depending on whether fluorescence is observed, it can be determined whether an individual from which the sample was collected is infected with a certain disease/virus, for example.

(Other Prior Art References)

(Patent Documents)

Korean Patent No. 10-2416335 (2022-07-05)

Korean Published Patent No. 10-2021-0065460 (2021-06-04)

In conventional devices, sample preprocessing, particularly the lysis process for genomes, has been performed in a piston and inner and outer chambers rather than in the amplification module. However, this approach requires a complex control process, resulting in a long processing time, and causes issues where genome lysis is not performed efficiently.

The present invention solves these issues and other problems of conventional devices.

According to the present invention, there is a module configured to perform genome lysis, amplification, and measurement, and a cartridge comprising the module, thereby solving the problem of requiring a complex structure in conventional devices for genome analysis.

Furthermore, among two openings formed in the module, one acts as a liquid inlet while the other functions as an air outlet, making it easier for a liquid containing a sample to enter the module.

Additionally, backflow between fluidically connected paths is minimized, and the inflow of liquid into an air discharge path is prevented, making it possible to analyze a genome with high accuracy.

Moreover, a reserve is formed in the air discharge path so that even if a liquid sample mistakenly enters the air discharge path, it does not flow beyond the reserve into other components. This ensures higher accuracy in sample analysis.

One aspect of the present invention provides a module configured with a space for preprocessing, amplification, and measurement of a sample including a genome, for example. The module comprises: a first in/out port through which a sample, including a genome, for example, is introduced, a heating well configured to receive the sample introduced through the first in/out port, a first path formed on one side, allowing fluid communication between the first in/out port and the heating well, a second path formed on an opposite side, connected to the heating well, a second in/out port through which a substance mixed with the lysed sample is introduced, at least one measurement well configured to receive the mixed substance introduced through the second in/out port, a third path formed on the opposite side, allowing fluid communication between the second in/out port and the measurement well, and a fourth path formed on the one side, connected to the measurement well, wherein the first path and the fourth path are connected through a first connecting path, and the second path and the third path are connected through a second connecting path.

The first connecting path may have a smaller width and a smaller depth than the first path.

The second connecting path may have a smaller width and a smaller depth than the third path.

At least one of the second path, the fourth path, the first connecting path, and the second connecting path may include a first partial path portion having a first width, and a second partial path portion connected to the first partial path portion and having a second width larger than the first width.

A depth of a cross-section of the first partial path portion may increase toward an edge, and a depth of a cross-section of the second partial path portion may increase toward a center.

The first partial path portion and the second partial path portion may be repeated in an alternating pattern.

A first partial path portion connected to one end of the second partial path portion and a first partial path portion connected to an opposite end of the second partial path portion may be staggered with each other.

A depth of a longitudinal cross-section of the fourth path may increase toward an edge.

The module may further comprise a third connecting path connecting the heating well and the measurement well.

One or more of edges of the heating well may be rounded.

A first reserve may be provided between the first connecting path and the fourth path, and the first reserve may have a width greater than the first connecting path and the fourth path.

The first reserve may include a repeatedly bent flow path.

The first reserve may have a generally rectangular shape.

The first connecting path may be connected to a bottom side of the first reserve, and the fourth path may be connected to a top side of the first reserve.

At least one second reserve, having a width greater than the first path, may be provided at a point along the second path.

The second reserve may have an "L" shape.

The second reserve may have a generally rectangular shape.

The second path may include a first portion positioned between the heating well and the second reserve, and a second portion positioned between the second reserve and the second connecting path.

The first and second portions of the second path may be connected to the second reserve via a top side of the second reserve.

Additionally, another aspect of the present invention provides a cartridge comprising a module configured with a space for preprocessing, amplification, and measurement of a sample as described above. The cartridge may include, for example, a base plate on which the module is mounted and in which a liquid flow path and an air flow path are formed, aligned with the first in/out port and the second in/out port, a piston including a liquid port aligned with the liquid flow path by rotation and a groove aligned with the air flow path by rotation, and a driving unit connected to the piston to rotate the piston.

The liquid flow path may include a first liquid flow path extending from a point on a first virtual circle centered on a point of the base plate to a connection point with the first in/out port, and a second liquid flow path extending from another point on the first virtual circle to a connection point with the second in/out port.

The air flow path may include a first air flow path extending from a point on the first liquid flow path to a point on a second virtual circle different from the first virtual circle, and a second air flow path extending from a point on the second liquid flow path to another point on the second virtual circle.

In a first position of the piston where the liquid port of the piston is aligned with the first liquid flow path and the groove is aligned with the second air flow path, the sample may be introduced into the heating well.

In a second position of the piston where the liquid port of the piston is aligned with the second liquid flow path and the groove is aligned with the first air flow path, the mixed substance may be introduced into the measurement well.

The first position of the piston may be a position where the first air flow path is not aligned with the groove, and the second position may be a position where the second air flow path is not aligned with the groove.

In the first position of the piston, the sample may be introduced into the heating well through the first liquid flow path, and air inside the module may be discharged through the second air flow path.

In the second position of the piston, the mixed substance may be introduced into the measurement well through the second liquid flow path, and air inside the module may be discharged through the first air flow path.

A module and a cartridge in which the module is mounted according to the present invention enable genome lysis, amplification, and measurement to be performed entirely within the module. As a result, the need for complex structures in conventional devices for genomic analysis is eliminated.

Furthermore, among the two openings formed in the module, one serves as a liquid inlet, while the other functions as an air outlet, making it easier for a liquid containing a sample to enter the module.

Additionally, backflow between fluidically connected paths is minimized, and the inflow of liquid into the air discharge path is prevented, enabling highly accurate genome analysis.

Moreover, a reserve formed in the air discharge path prevents a liquid sample from flowing beyond the reserve into other components even if the liquid sample mistakenly enters the air discharge path. This ensures higher accuracy in sample analysis.

FIG. 1 is a schematic diagram 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 diagram illustrating a base plate of the cartridge in FIG. 1 according to an embodiment of the present invention.

FIGS. 4A, 4B and 5A, 5B are diagrams illustrating a piston of the cartridge in FIG. 1 according to an embodiment of the present invention.

FIGS. 6 and 7 are diagrams illustrating a module of the cartridge in FIG. 1 according to an embodiment of the present invention.

FIGS. 8 and 9 are diagrams illustrating the width and depth of the first and third paths, as well as the first and second connecting paths in the module, according to an embodiment of the present invention.

FIG. 10 is a cross-sectional view illustrating the first and second partial path portions according to an embodiment of the present invention.

FIG. 11 is a cross-sectional view illustrating a portion of the fourth path according to an embodiment of the present invention.

FIGS. 12A and 12B are diagrams illustrating the coupling relationship between the module and the base plate according to an embodiment of the present invention.

FIG. 13A illustrates the flow path connection structure according to an embodiment of the present invention when the piston is in the first position, and FIG. 13B illustrates the flow path connection structure according to an embodiment of the present invention when the piston is in the second position.

FIG. 14 is a diagram illustrating the heating unit used for lysing the sample received in the heating well according to an embodiment of the present invention.

FIGS. 15 and 16 are diagrams illustrating a module according to another embodiment of the present invention.

FIGS. 17 and 18 are diagrams illustrating a module according to yet another embodiment of the present invention.

FIGS. 19 and 20 are diagrams illustrating a module according to another alternative embodiment of the present invention.

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 "comprise" a certain component, this does not mean excluding other components unless otherwise specifically stated, but rather includes other components. 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 understanding 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 understood based on the contents throughout this specification.

In the following, the term "genome" refers to substances that contain genetic information of an organism, such as DNA or RNA.

Hereinafter, the present invention will be described in detail with reference to the accompanying drawings.

Referring to FIG. 1, a cartridge 10 according to an embodiment of the present invention is described.

The cartridge 10 according to an embodiment of the present invention comprises a module 100 that provides a space for sample preprocessing, amplification, and measurement (hereinafter referred to as "module"), a base plate 200, a piston 300, a pad 400, a flow cover 500 (FIG. 2), and a driving unit 600 (FIG. 2).

Additionally, the cartridge may further include an outer chamber, an inner chamber, a cover, a safety clip, and a bead chamber, the details of which are disclosed in Korean Registered Patent Document No. 10-2416335, the entire contents of which are incorporated by reference.

Referring to FIGS. 2 and 3, the base plate 200 is described.

The base plate 200 has a hollow space 201 formed through it. Via the hollow space 201, the piston 300 may be installed in an upper part and the driving unit 600 may be installed in a lower part of the base plate 200. More specifically, the driving unit 600 is coupled to the piston 300 so that the piston 300 rotates together with the driving unit 600.

The upper surface 202 of the base plate 200 is formed with multiple paths 203, 204, 205, 206, 207, 208, 209, 210, 211, and 212 recessed thereon, arranged around the hollow space 201.

Among those paths, fluid paths 203, 204, 205, 206, 207, and 208 are connected to the outer chamber, allowing fluids (e.g., reagents) stored in the outer chamber to be transported into the internal space 301 (FIG. 4A) of the piston 300.

The other flow paths (i.e., first liquid flow path 209, first air flow path 210, second liquid flow path 211, second air flow path 212) are fluidically connected to the module 100, allowing fluids in the internal space 301 of the piston 300 to be transferred into the module 100 or fluids inside the module 100 to be transferred into the piston 300 while air from the module 100, which is necessary during the fluid transfer, may be discharged.

Referring to FIGS. 2, 4A, 4B, 5A, and 5B, the piston 300 comprises: an upper piston 310 with a hollow internal space 301, a sealing part 320 that can move along the internal space 301, and a lower piston 330 coupled to the upper piston 310.

The outer surface of the sealing part 320 is tightly sealed against the inner surface of the upper piston 310, preventing fluid from moving between them. The sealing part 320 has a recessed driving unit installation section 321 at its center, where a driving unit (not shown) of the diagnostic device can be attached. This driving unit moves the sealing part 320 up and down inside the upper piston 310, allowing fluids to be drawn into the internal space 301 or expelled to the outside of the internal space 301.

Meanwhile, the lower surface of the upper piston 310 has a coupling structure that engages with the lower piston 330. A first hole 311 is formed through the lower surface of the upper piston 310, aligning with a liquid port 333 of the lower piston 330.

The lower piston 330 includes: a body 331 shaped like a disk, a shaft 332 protruding outward from the center of the body 331, a liquid port 333 positioned along a virtual circle having its center at the center of the body 331. The liquid port 333 functions to draw, mix, and expel samples and reagents into and out of the piston 300.

Additionally, a groove 335 may be formed along the outer periphery of the body 331 of the lower piston 330. This groove serves to discharge air that may be generated when liquid moves within the module 100.

In another embodiment, the piston 300 may be formed as an integrated structure where the upper piston 310 and lower piston 330 are not separate components to be engaged but a single unit or single structure. In this case, the liquid port 333 allows fluid to move in and out of the internal space 301.

Now, referring to FIG. 3, the flow paths 209, 210, 211, 212 that fluidically connect to the module 100 are described. A first liquid flow path 209 extends from a point on a first virtual circle C1 to a point that aligns with a first in/out port 110 of the module 100 (e.g., FIG. 6). A second liquid flow path 211 extends from another point on the first virtual circle C1 to a position that aligns with a second in/out port 130 (e.g., FIG. 6). A first air flow path 210 extends from a point on the first liquid flow path 209 to a point on the second virtual circle C2. The second air flow path 212 extends from a point on the second liquid flow path 211 to another point on the second virtual circle C2. The first virtual circle C1 and the second virtual circle C2 may be concentric, sharing the same center as the hollow space 201. The second virtual circle C2 may have a larger diameter than C1.

Due to the first and second liquid flow paths 209, 211 and the first and second air flow paths 210, 212, simultaneous liquid inflow and air discharge into and out of the module 100 are possible.

The module (100) is coupled to the cartridge (10), and a sample introduced into the cartridge (10) is pretreated (e.g., lysis), and amplification and measurement of the genome obtained as a result of the sample pretreatment are performed here.

Referring to FIG. 2, the module 100 may be coupled to the cartridge 10 while being oriented vertically, with the first in/out port 110 and the second in/out port 130 facing downward. The module 100 may generally have the shape of a flat panel or a plate having two opposing surfaces - one surface 101 and the opposite surface 102.

Referring to FIGS. 6 and 7, the module 100 includes: a first in/out port 110, a heating well 120, a second in/out port 130, a measurement well 140, a first path 150, a second path 160, a third path 170, a fourth path 180, connecting paths 191, 192, and one or more reserves R₁, R₂.

The first path 150, fourth path 180, first connecting path 191, and first reserve R₁ are formed by being recessed into the one surface 101 of the module 100. The second path 160, third path 170, second connecting path 192, and second reserve R₂ are formed by being recessed into the opposite surface 102 of the module 100. The components on opposite surfaces are structured to avoid interference, as they are recessed into the one surface or the opposite surface such that they do not penetrate the module 100 entirely from the one surface to the other.

Meanwhile, the first path 150 and third path 170, which carry liquid, are connected to the bottom of the heating well 120 and measurement well 140, respectively. The second path 160 and fourth path 180, which carry gas (air), are connected to the top of the heating well 120 and measurement well 140, respectively. This structure reduces air bubble formation and facilitates smooth air discharge during liquid inflow into the module 100.

Additionally, the heating well 120 and measurement well 140 may penetrate through the module 100, and sealing members (not shown) may be attached to the one surface 101 and the opposite surface 102, creating designated spaces to contain fluid.

In operation, a sample introduced into the cartridge 10 follows the paths(include the first liquid path of the base plate) of the cartridge 10, toward the first in/out port 110. The sample entering the first in/out port 110 moves along the first path 150 into the heating well 120. Specifically, the sealing part 320 of the piston 300 descends, pushing the sample through the paths on the cartridge 10 toward the first in/out port 110.

The first, second, third, fourth paths 150, 160, 170, 180 are fluidically connected to the first in/out port 110 and the second in/out port 130, respectively, and extend to the heating well 120 or the measurement well 140, while bending at least once. Throughout the specification, when a flow passage cross-sectional plane is defined as a virtual plane that is perpendicular to an extension direction of the first, second, third, fourth paths 150, 160, 170, 180 and a thickness direction is defined as a direction from the one surface 101 toward the opposite surface 102 of the module 100 or the opposite direction thereof, the depth of the first, second, third, fourth paths 150, 160, 170, 180 is measured in the thickness direction in the moving passage cross-sectional plane and the width is measured in a direction perpendicular to the thickness direction in the moving passage cross-sectional plane. That is, for example, when the first path 150 extends upward (i.e., vertically), the width of the first path 150 is measured in a lateral (i.e., horizontal) direction, and when the first path 150 extends laterally (i.e., horizontally), the width of the first path 150 is measured vertically (i.e., in a vertical direction).

Meanwhile, because the first path 150 is connected to the fourth path 180 via the first connecting path 191, there is a possibility that fluid entering the first in/out port 110 might backflow into the fourth path 180 instead of moving through the first path 150.

To prevent such backflow according to the present invention, the first connecting path 191 is designed to have a narrower width W₂ than the width W₁ of the first path 150 and a shallower depth D₂ than the depth D₁ of the first path 150.

Due to this design, the fluid introduced through the first in/out port 110 is more likely to follow the wider and deeper first path 150 toward the heating well 120 rather than flowing into the first connecting path 191.

To further prevent unintended fluid entry into the first connecting path 191, it is preferable that the front end of the first connecting path 191 (i.e., the area connected to the first path 150) has a narrower width W₂ than the width W₁ of the front end of the first path 150 (i.e., the area connected to the first in/out port 110 and the first connecting path 191), and has a shallower depth D₂ at the front end of the first connecting path 191 than the depth D₁ at the front end of the first path 150 (see FIG. 8).

Additionally, even if liquid enters the first connecting path 191 by mistake, it is prevented from entering the fourth path 180 by the presence of the first reserve R₁, which has a larger width and an expanded internal space, between the first connecting path 191 and the fourth path 180. The first reserve R₁ may be in a generally rectangular shape. The first connecting path 191 may be connected to the bottom side of the reserve R1 and extend laterally toward the first path 150 while the fourth path 180 is connected to the top side of the first reserve R₁.

As the sample enters the heating well 120, the air within the first path 150 and second path 160, which are connected to the heating well 120, must be expelled. In accordance with the present invention, because the second connecting path 192 fluidically connects the second path 160 and the third path 170, and the third path 170 is connected to the second in/out port 130, air from the heating well 120 and its connected first path 150 and second path 160 can be expelled to the outside of the module 100 via the second path 160, second connecting path 192, third path 170, and second in/out port 130.

At this moment, the piston 300 is positioned at the first position, where the groove 335 of the piston 300 aligns with the second air flow path 212 and the liquid port 333 aligns with the first liquid flow path 209 (See FIG. 13A). Thus, the liquid port 333 of the piston 300 allows the sample to be introduced into the first liquid flow path 209 and then into the first in/out port 110, while simultaneously allowing air inside the module 100 to be discharged through the second in/out port 130 via the second air flow path 212. At the first position, the groove 335 of the piston 300 is not aligned with the first air flow path 210.

Additionally, one or more second reserves R₂ may be provided at a specific location in the second path 160. Each second reserve R₂ has a width greater than that of the second path 160 and an expanded internal space. As a result, even if liquid mistakenly enters the second path 160 from the heating well 120, the second reserve R₂ prevents the liquid from reaching the second in/out port 130 and being discharged externally.

The one or more second reserves R₂ may be in a generally rectangular shape. The second path 160 may include a first portion positioned between the heating well 120 and the one or more second reserves R2, and a second portion positioned between the one or more second reserves R2 and the second connecting path 192. The first and second portions of the second path 160 may be connected to the one or more second reserves R₂ via the top side of the one or more second reserves R₂.

Once the sample enters the heating well 120, the heating unit H moves closer to the one surface 101 and opposite surface 102 of the heating well 120 and heats the sample (See FIG. 14). Lysis of the sample's genome occurs due to heating, creating a state in which substances necessary for genome amplification can freely bind to the genome.

Once the heating process(genome lysis process) is completed, the lysed sample is discharged from the module 100 to the internal space 301 of the piston 300, and then mixed with reagent in the inner/outer chamber of the cartridge 10, and then introduced back to the module 100. Hereinafter, the lysed sample mixed with the reagent is referred to as the "mixed substance". The mixed substance is transferred to the measurement well 140 through the second in/out port 130 as the sealing part 320 descends while the piston 300 is in the second position, which will be described later. The measurement well 140 may be provided with one or more wells, and each measurement well 140 contains different oligomers for amplifying different parts of the nucleic acid.

Meanwhile, since the third path 170 is connected to the second path 160 through the second connecting path 192, there is a possibility that the mixed substance introduced through the second in/out port 130 may backflow into the second path 160 instead of the third path 170. In order to prevent such backflow, the width W₄ of the second connecting flow path 192 is narrower than the width W₃ of the third path 170, and the depth D₄ of the second connecting path 192 is shallower than the depth D₃ of the third path 170 (see FIG. 9).

Due to this configuration, the mixed substance introduced through the second in/out port 130 is directed toward the measurement well 140 through the wider and deeper third path 170 rather than the narrow and shallow second connecting path 192. To fundamentally block fluid inflow into the second connecting path 192, it is preferable that the width W₄ of the front end of the second connecting path 192 is narrower than the width W₃ of the front end of the third path 170, and the depth D₄ of the front end of the second connecting path 192 is shallower than the depth D₃ of the front end of the third path 170.

As the mixed substance is introduced into the measurement well 140, the air in the measurement well 140 and the third path 170 connected to the measurement well 140 must be discharged to the outside. In accordance with the present invention, the first path 150 and the fourth path 180 are fluidically connected with each other via the first connecting path 191, and since the first path 150 is connected to the first in/out port 110, the air in the measurement well 140, the third path 170, and the fourth path 180 is discharged to the outside of the module 100 through the fourth path 180, the first connecting path 191, the first path 150, and the first in/out port 110.

At this moment, the piston 300 is in the second position, where the groove 335 of the piston 300 is aligned with the first air flow path 210, and the liquid port 333 of the piston 300 is aligned with the second liquid flow path 211 (see FIG. 13B). Accordingly, the mixed substance can flow through the liquid port 333 of the piston 300, pass through the second liquid flow path 211, and be introduced into the second in/out port 130, while at the same time, the air inside the module 100 can be discharged to the outside through the first in/out port 110 via the first air flow path 210. In the second position, the groove 335 of the piston 300 is not aligned with the second air flow path 212.

Meanwhile, although an example has been provided where the first in/out port 110 is connected to the heating well 120 through the first path 150 and the second in/out port 130 is connected to the measurement well 140 through the third path 170, a configuration where the second in/out port 130 is connected to the heating well 120 and the first in/out port 110 is connected to the measurement well 140 is also within the scope of the invention. In other words, the sample introduced into the heating well 120 through the second in/out port 130 may be lysed through heating by the heating unit H, and the genome amplification process of the mixed substance introduced into the measurement well 140 through the first in/out port 110 may be used to monitor the target, which is also within the scope of the invention. That is, the second in/out port 130 may be connected to the heating well 120 through the first path 150, the heating well 120 may be connected to the second path 160, and air may be discharged to the outside of the module 100 through the second path 160, the second connecting path 192, and the first in/out port 110. Additionally, the first in/out port 110 may be connected to the measurement well 140 through the third path 170, and the measurement well 140 may be connected to the fourth path 180, allowing air to be discharged to the outside of the module 100 through the fourth path 180, the first connecting path 191, and the first in/out port 110.

Furthermore, referring to FIG. 10, according to an embodiment, in order to prevent backflow into the first connecting path 191 and the second connecting path 192 and to prevent the inflow of liquid instead of air, the first and second connecting paths 191, 192 may include a first partial path portion P₁ and a second partial path portion P₂ connected to the first partial path portion P₁. The width of the first partial path portion P₁ may be narrower than that of the second partial path portion P₂, and the first connecting path 191 and the second connecting path 192 can be formed by alternately connecting the first partial path portion P₁ and the second partial path portion P₂.

According to an embodiment, a first partial path portion P₁ connected to one end of a second partial path portion P₂ and a first partial path portion P₁ connected to an opposite end of the second partial path P₂ may be positioned in a staggered zigzag pattern along the extension direction.

Additionally, the cross-section (i.e., a cross-section in the flow passage cross-sectional plane) of the first partial path portion P₁ deepens toward the edges, while the cross-section of the second partial path portion P₂ deepens toward the center. By adopting the aforementioned shape in the first connecting path 191 and the second connecting path 192, the possibility of backflow into the first connecting path 191 when the sample moves from the first path 150 to the heating well 120 is minimized, and the possibility of backflow into the second connecting path 192 when the mixed substance moves from the third path 170 to the measurement well 140 is minimized, thereby preventing the inflow of liquid into each flow path instead of air. The shape of the first partial path portion P₁ and the second partial path portion P₂ may also be applied to the second path 160 and the fourth path 180.

In summary, since the path that is to discharge air rather than liquid includes the first partial path portion P₁ and the second partial path portion P₂, it is possible to prevent the inflow of liquid instead of air into the respective paths for air passage.

Additionally, according to an embodiment, the fourth path 180 may have a portion in which a longitudinal cross-section of the fourth path 180 deepens along the extension direction toward an edge, preventing the inflow of liquid instead of air into the fourth path 180. (See FIG. 11).

Referring to FIGS. 15 and 16, the following section provides an explanation of the module 100 according to another embodiment of the present invention. The module 100 according to another embodiment of the present invention may include a first in/out port 110, a heating well 120, a second in/out port 130, a measurement well 140, a fifth path 151, and a sixth path 161.

The sample introduced into the cartridge 10 may move toward the second in/out port 130 along the flow path of the cartridge 10, and the sample introduced into the second in/out port 130 may be introduced into the measurement well 140 through the fifth flow path 151. Meanwhile, the measurement well 140 is connected to the heating well 120 through the third connecting path 193, and the sample introduced into the measurement well 140 may also be introduced into the heating well 120 through the third connecting path 193.

In this embodiment, for example, the amount of sample introduced may be more than the capacity of the measurement well 140 or correspond to the capacities of the measurement well 140, the third connecting path 193, and the heating well 120. At this moment, the measurement well 140, the third connecting path 193, and the heating well 120 may be filled with the sample. As the sample is introduced, the air inside the module 100 is discharged to the outside through the sixth path 161 connected to the top of the heating well 120 and the first in/out port 110. At this moment, the piston 300 may be positioned in the second position (see FIG. 13B).

When the sample is introduced into the heating well 120 and the measurement well 140, the heating unit H moves closer to the one side 101 and the opposite side 102 of the heating well 120 and the measurement well 140, heating the sample contained in the heating well 120 and the measurement well 140. The heating process facilitates the lysis of the genome from the sample.

Once the heating process is complete, the sealing part 320 of the piston 300 rises, allowing the lysed sample to be transferred into the internal space 301 of the piston 300. The lysed sample then undergoes a mixing process with the reagent contained in the inner and outer chambers.

The mixed substance, which is the lysed sample mixed with the reagent, is transferred to the measurement well 140 through the second in/out port 130 as the sealing part 320 of the piston 300 descends while in the second position. Once the mixed substance is transferred to the measurement well 140, the heating unit H moves again closer to one side 101 and the opposite side 102 of the measurement well 140, enabling the genome amplification process.

With reference to FIGS. 17-20, the following provides an explanation of another embodiment of the module 100 according to the present invention. The overall configuration is the same as the module 100 shown in FIGS. 6 and 7, and the explanation below will focus on the differences in configuration.

In the embodiments of the module 100 shown in FIGS. 17-20, at least the edges (i.e., corners) 121 of the heating well 120 may be rounded. At least one or more of the rounded edges 121 may be the one farthest from the first path 150 (see FIGS. 17 and 18). In another embodiment, at least one or more of the rounded edges 121 may include at least two edges opposite the first path 150 (see FIGS. 19 and 20).

Furthermore, the top of the heating well 120 may be formed to slope downward as it extends further from the first path 150. Also, the bottom of the heating well 120 may be formed to slope upward as it extends further from the first path 150. The heating well 120 may generally have a trapezoidal shape.

In a comparative example where the edges of the heating well 120 are not rounded when a sample is introduced into the heating well 120 through the first path 150, air bubbles may remain trapped at the edges of the heating well 120 and fail to be discharged during the process of introducing the sample into the heating well 120 through the first flow path 150. By contrast, in this embodiment where the edges of the heating well 120 are rounded, the sample is gradually filled from the bottom to the top of the heating well 120, achieving the effect of discharging air along the second path 160 without air bubbles remaining at the edges.

In addition, unlike the first reserve R₁ in the embodiment shown in FIGS. 6 and 7, which has a generally rectangular shape, in the embodiment shown in FIGS. 17-20, the first reserve R₁ may include more than one bent flow path. Because the first reserve R₁ includes more than one bent flow path, even if the sample (in liquid state) introduced through the first in/out port 110 is mistakenly introduced into the first connecting path 191, the mistakenly introduced sample can be more reliably prevented from flowing into the fourth path 180.

According to an embodiment, unlike the second reserve R₂ in the embodiment shown in FIGS. 6 and 7, which has a generally rectangular shape, in the embodiment shown in FIGS. 17-20, the second reserve R₂ may have a hexagonal shape. For example, the second reserve R₂ may have an "L"-shape. Since the second reserve R₂ has a hexagonal shape, compared to the embodiment including a rectangular second reserve R₂, even if the sample in liquid form is mistakenly introduced from the heating well 120 into the second path 160, the presence of the second reserve R₂ more reliably prevents it from being discharged through the second in/out port 130.

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. Also, it is noted that any one feature of an embodiment of the present disclosure described in the specification may be applied to another embodiment of the present disclosure. Similarly, the present invention encompasses any embodiment that combines features of one embodiment and features of another embodiment. 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.

(Explanation of Reference Numerals)

H: Heating unit

P₁: First partial path portion

P₂: Second partial path portion

R₁: First reserve

R₂: Second reserve

100: Module

101: One side surface

102: Opposite side surface

110: First in/out port

120: Heating well

121: Edge

130: Second in/out port

140: Measurement well

150: First path

151: Fifth path

160: Second path

161: Sixth path

170: Third path

180: Fourth path

191: First connecting path

192: Second connecting path

193: Third connecting path

200: Base plate

201: Hollow space

202: Upper surface

203, 204, 205, 206, 207, 208: Fluid paths

209: First liquid flow path

210: First air flow path

211: Second liquid flow path

212: Second air flow path

300: Piston

301: Internal space

310: Upper piston

311: First hole

320: Sealing part

321: Driving unit installation section

330: Lower piston

331: Body

332: Shaft

333: Liquid port

335: Groove

400: Pad

500: Flow cover

600: Driving unit

Claims

A module providing space for preprocessing, amplification, and measurement of a sample including a genome, the module comprising:

a first in/out port through which the sample, including the genome, is introduced;

a heating well configured to receive the sample introduced through the first in/out port;

a first path formed on one surface, allowing fluid communication between the first in/out port and the heating well;

a second path formed on an opposite surface, connected to the heating well;

a second in/out port through which a substance mixed with the lysed sample is introduced;

at least one measurement well configured to receive the mixed substance introduced through the second in/out port;

a third path formed on the opposite surface, allowing fluid communication between the second in/out port and the measurement well; and

a fourth path formed on the one surface, connected to the measurement well,

wherein the first path and the fourth path are connected through a first connecting path,

the second path and the third path are connected through a second connecting path.
The module of claim 1,

wherein the first connecting path has a smaller width and a smaller depth than the first path.
The module of claim 1,

wherein the second connecting path has a smaller width and a smaller depth than the third path.
The module of claim 1,

wherein at least one of the second path, the fourth path, the first connecting path, and the second connecting path includes a first partial path portion having a first width, and a second partial path portion connected to the first partial path portion and having a second width larger than the first width.
The module of claim 4,

wherein a depth of a cross-section of the first partial path portion increases toward an edge, and

a depth of a cross-section of the second partial path portion increases toward a center.
The module of claim 4,

wherein the first partial path portion and the second partial path portion are repeated by alternating, and

the first partial path portion connected to one end of the second partial path portion and the first partial path portion connected to an opposite end of the second partial path portion are positioned to be staggered with each other.
The module of claim 1,

wherein a depth of a longitudinal cross-section of the fourth path increases toward an edge.
The module of claim 1, further comprising a third connecting path connecting the heating well and the measurement well.
The module of claim 1,

wherein at least one of the edges of the heating well is rounded.
The module of claim 1,

wherein a first reserve is provided between the first connecting path and the fourth path, and

the first reserve has a width greater than the first connecting path and the fourth path.
The module of claim 10,

wherein the first reserve includes more than one bent flow path.
The module of claim 10,

wherein the first reserve has a generally rectangular shape, and

the first connecting path is connected to a bottom side of the first reserve, and the fourth path is connected to a top side of the first reserve.
The module of claim 1,

wherein at least one second reserve, having a width greater than the first path, is provided at a point along the second path.
The module of claim 13,

wherein the second reserve has an "L" shape.
The module of claim 13,

wherein the second reserve has a generally rectangular shape,

the second path may include a first portion positioned between the heating well and the second reserve, and a second portion positioned between the second reserve and the second connecting path, and

the first and second portions of the second path are connected to the second reserve via a top side of the second reserve.
A cartridge for the preparation of genome application, the cartridge comprising:

a module providing space for preprocessing, amplification, and measurement of a sample including a genome according to claim 1;

a base plate in which the module is mounted and in which a liquid flow path and an air flow path are formed, aligned with the first in/out port and the second in/out port;

a piston including a liquid port aligned with the liquid flow path by rotation and a groove aligned with the air flow path by rotation; and

a driving unit connected to the piston to rotate the piston.
The cartridge of claim 16,

wherein the liquid flow path includes a first liquid flow path extending from a point on a first virtual circle centered on a point of the base plate to a connection point with the first in/out port, and a second liquid flow path extending from another point on the first virtual circle to a connection point with the second in/out port, and

the air flow path includes a first air flow path extending from a point on the first liquid flow path to a point on a second virtual circle different from the first virtual circle, and a second air flow path extending from a point on the second liquid flow path to another point on the second virtual circle.
The cartridge of claim 17,

wherein, in a first position of the piston where the liquid port of the piston is aligned with the first liquid flow path and the groove is aligned with the second air flow path, the sample is introduced into the heating well, and

in a second position of the piston where the liquid port of the piston is aligned with the second liquid flow path and the groove is aligned with the first air flow path, the mixed substance is introduced into the measurement well.
The cartridge of claim 18,

wherein the first position of the piston is a position where the first air flow path is not aligned with the groove, and

the second position is a position where the second air flow path is not aligned with the groove.
The cartridge of claim 18,

wherein, in the first position of the piston, the sample is introduced into the heating well through the first liquid flow path, and air inside the module is discharged through the second air flow path, and

in the second position of the piston, the mixed substance is introduced into the measurement well through the second liquid flow path, and air inside the module is discharged through the first air flow path.