KR20210126445A - Diagnostic chip and diagnostic cartridge having the same - Google Patents

Abstract

The present invention relates to an in vitro diagnostic chip which can interrupt adsorption of DNA in a sample introduction path by introducing a sample directly to a well array through a pipette and can reduce sample loss, and an in vitro diagnostic cartridge including the same. The in vitro diagnostic chip includes a base member, tape, well array, well cover, guide member and a guide cap. The tape is attached to the top surface of the base member. The well array is disposed on the tape and has a plurality of wells therein. The well cover includes a cover groove formed to cover the well array, a sample inlet formed to link the outside with one side of the cover groove, and an air outlet formed to link the outside with the other side of the cover groove, and is attached to the top surface of the tape, while covering the well array. The guide member covers the well cover and allows the well cover to be exposed partially through a hollow hole. The guide cap is disposed on the lateral side of the guide member and seals the sample inlet and air outlet of the well cover.

Description

In vitro diagnostic chip and in vitro diagnostic cartridge having the same

The present invention relates to an in vitro diagnostic chip and an in vitro diagnostic cartridge having the same, and more particularly, by directly injecting a sample sample into a well array through a pipette, it is possible to block DNA adsorption in the sample sample inflow path and reduce sample loss. The present invention relates to an in vitro diagnostic chip and an in vitro diagnostic cartridge having the same.

Gene amplification technology is an essential process in molecular diagnosis, and is a technology that repeatedly replicates and amplifies a specific nucleotide sequence of a trace amount of deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) in a sample. Among them, the polymerase chain reaction (PCR) is a representative gene amplification technology and consists of three steps: DNA denaturation, primer annealing, and DNA extension. Since the step depends on the temperature of the sample, DNA can be amplified by repeatedly changing the temperature of the sample.

Previously, PCR was typically performed in 96 or 384-well micro well plates. When higher throughput is required, the conventional PCR method on microplatelets is not cost effective or efficient because it requires a large amount of reagents. On the other hand, reducing the PCR reaction volume may reduce the consumption of reagents and shorten the amplification time at a reduced heat mass of the reaction volume. This strategy can also be implemented in an array format (m x n), resulting in many smaller reaction volumes. The use of any array also allows for scalable and high-throughput assays with increased quantitative sensitivity, dynamic range and specificity.

Using very many arrays of very small reaction volumes, digital polymerase chain reaction (dPCR) can be performed. Results from dPCR can be used to detect and quantify concentrations of rare alleles, provide absolute quantification of nucleic acid samples, and also sensitively measure low nucleic acid concentrations.

The array format of most quantitative polymerase chain reaction (qPCR) platforms is designed for assay experiments on a sample-by-sample basis, where PCR results must be addressable for post-mortem analysis. However, dPCR does not analyze each PCR result to a specific location, but only the number of positive and negative target copies per sample.

0001) Korean Patent Publication No. 2017-0024827 (2017.03.08.) 0002) Korean Patent Laid-Open Patent No. 2016-0086937 (2016. 07. 20.)

Accordingly, the technical problem of the present invention is based on this point, and an object of the present invention is to directly inject a sample sample into a well array through a pipette to block DNA adsorption in the sample sample inflow path and to reduce sample loss. To provide an in vitro diagnostic chip.

Another object of the present invention is to provide an in vitro diagnostic cartridge having the above in vitro diagnostic chip.

In order to achieve the above object of the present invention, an in vitro diagnostic chip according to an embodiment includes a base member, a well array, a well cover, a guide member, a stopper, and a guide cap. The well array is disposed on the base member, and a plurality of wells are formed. The well cover includes a cover groove formed to cover the well array, a sample reservoir formed to connect one side of the cover groove, and a sample inlet formed to connect the sample reservoir and the outside, having a shape that is extended toward the outside. and disposed to cover the well array. The guide member covers the well cover and exposes a portion of the well cover through the hollow hole formed therein. The stopper seals the sample inlet of the well cover. The guide cap accommodates a portion of the stopper, and is fastened to a side surface of the guide member in a hook manner.

In order to achieve the above object of the present invention, an in vitro diagnostic chip according to another embodiment includes a base member, a tape, a well array, a well cover, a guide member, and a guide cap. The tape is attached to the upper surface of the base member. The well array is disposed over the tape, and a plurality of wells are formed. The well cover includes a cover groove formed to cover the well array, a sample inlet formed to connect the outside and one side of the cover groove, and an air outlet formed to connect the outside and the other side of the cover groove, It is attached to the top surface of the tape while covering it. The guide member covers the well cover and exposes a portion of the well cover through the hollow hole formed therein. The guide cap is disposed on a side surface of the guide member, and seals the sample inlet and the air outlet of the well cover.

In order to realize another object of the present invention, an in vitro diagnostic cartridge according to an embodiment includes an in vitro diagnostic chip, a CMOS image sensor, a PCB, a middle body, and an upper cover. The lower body is disposed under the in vitro diagnostic chip and accommodates the in vitro diagnostic chip. The CMOS image sensor is disposed between the lower body and the in vitro diagnostic chip, and the in vitro diagnostic chip captures a PCR reaction product. The PCB houses the CMOS image sensor. The middle body is disposed on the PCB to expose the CMOS image sensor through a hollow hole, and supports the in vitro diagnostic chip. The upper cover is disposed on the in vitro diagnostic chip, and is fastened to the lower body while pressing the in vitro diagnostic chip according to a user's push operation.

In order to realize another object of the present invention, an in vitro diagnostic cartridge according to another embodiment includes an in vitro diagnostic chip, a lower body, a CMOS image sensor, a PCB, an upper cover, a hinge member, and a push lever. The lower body is disposed under the in vitro diagnostic chip and accommodates the in vitro diagnostic chip. The CMOS image sensor is disposed between the lower body and the in vitro diagnostic chip, and the in vitro diagnostic chip captures a PCR reaction product. The PCB houses the CMOS image sensor. The upper cover is disposed on the in vitro diagnostic chip, and is fastened to the lower body while pressing the in vitro diagnostic chip according to a user's push operation. The hinge member is disposed on side surfaces of the lower body and the upper cover to couple the lower body and the upper cover. The push lever is disposed on a side surface of the lower body, engages the lower body and the upper cover according to a user's upper surface pressing operation, and separates the upper cover from the lower body according to the user's side pressing operation.

According to such an in vitro diagnostic chip and an in vitro diagnostic cartridge having the same, by directly injecting a sample sample into the well array through a pipette, it is possible to block DNA adsorption at the sample inlet or in the flow path from the sample inlet to the well array, and loss can be reduced. In addition, by sequentially sealing the sample inlet and air outlet of the well cover using a guide cap after the sample is injected, air present in the well array can be discharged through the air outlet. In addition, it is possible to block the inflow of foreign substances from the outside, increasing the reliability of the inspection.

1 is a perspective view illustrating an in vitro diagnostic chip according to an embodiment of the present invention.
FIG. 2 is an exploded perspective view illustrating the in vitro diagnostic chip shown in FIG. 1 .
FIG. 3 is a rear perspective view for explaining the fastening of the in vitro diagnostic chip shown in FIG. 1 .
4 is a view for explaining a process of injecting a sample sample into the in vitro diagnostic chip shown in FIGS. 1 to 3 .
5A is a perspective view for explaining a state before assembly of the in vitro diagnostic cartridge according to an embodiment of the present invention, and FIG. 5B is a perspective view for explaining a state after assembly of the in vitro diagnostic cartridge according to an embodiment of the present invention.
6 is an exploded perspective view illustrating the in vitro diagnostic cartridge shown in FIGS. 5A and 5B.
7 is a cross-sectional view for explaining the in vitro diagnostic cartridge shown in FIG.
8 is a perspective view for explaining an assembly process of the in vitro diagnostic cartridge shown in FIG.
9 is a perspective view illustrating a state before and after assembly of an in vitro diagnostic chip according to another embodiment of the present invention.
FIG. 10 is an exploded perspective view illustrating the in vitro diagnostic chip shown in FIG. 9 .
11 is a view for explaining a process of injecting a sample sample into the in vitro diagnostic chip shown in FIGS. 9 and 10 .
12 is an exploded perspective view illustrating an in vitro diagnostic cartridge according to another embodiment of the present invention.
13 is a perspective view for explaining a process of fastening the in vitro diagnostic chip shown in FIGS. 9 and 10 to the in vitro diagnostic cartridge shown in FIG. 12 .
14 are images in which some components are processed to be transparent in order to explain the process of fastening the in vitro diagnostic chip shown in FIGS. 9 and 10 to the in vitro diagnostic cartridge shown in FIG. 12 .
15 is a perspective view for explaining a process of separating the in vitro diagnostic chip shown in FIGS. 9 and 10 from the in vitro diagnostic cartridge shown in FIG. 12 .

Hereinafter, an in vitro diagnostic chip and an in vitro diagnostic cartridge having the same according to the present invention will be described in more detail with reference to the accompanying drawings. Since the present invention can have various changes and can have various forms, specific embodiments are illustrated in the drawings and described in detail in the text. However, this is not intended to limit the present invention to the specific disclosed form, it should be understood to include all modifications, equivalents and substitutes included in the spirit and scope of the present invention.

In describing each figure, like reference numerals have been used for like elements. In the accompanying drawings, the dimensions of the structures are enlarged than the actual size for clarity of the present invention.

Terms such as first, second, etc. may be used to describe various elements, but the elements should not be limited by the terms. The above terms are used only for the purpose of distinguishing one component from another. For example, without departing from the scope of the present invention, a first component may be referred to as a second component, and similarly, a second component may also be referred to as a first component. The singular expression includes the plural expression unless the context clearly dictates otherwise.

In the present application, terms such as “comprise” or “have” are intended to designate that a feature, number, step, operation, component, part, or combination thereof described in the specification exists, but one or more other features It is to be understood that it does not preclude the possibility of the presence or addition of numbers, steps, operations, components, parts, or combinations thereof.

In addition, unless otherwise defined, all terms used herein, including technical or scientific terms, have the same meaning as commonly understood by one of ordinary skill in the art to which the present invention belongs. Terms such as those defined in commonly used dictionaries should be interpreted as having a meaning consistent with the meaning in the context of the related art, and should not be interpreted in an ideal or excessively formal meaning unless explicitly defined in the present application. does not

Hereinafter, preferred embodiments of the present invention will be further described with reference to the accompanying drawings. The same reference numerals are used for the same components in the drawings, and repeated descriptions of the same components are omitted.

The present invention relates to a structure for mounting samples, sample volumes or reaction volumes in a predetermined arrangement on a substrate, and more particularly, to mounting the samples in a predetermined arrangement of respective reaction positions in a substrate.

In various embodiments, apparatus, apparatus, systems, and methods for mounting samples in an article used to detect targets in small volume samples of an array type are provided. Such targets may be any suitable biological target, but include DNA sequences, RNA sequences, genes, oligonucleotides, molecules, proteins, biomarkers, cells (eg, circulating tumor cells), or other suitable target organisms. Those that include, but are not limited to, molecules. In various embodiments, these biological components include fetal diagnosis, multiplex diagnosis of disease, pathogen detection, and quantitation standardization, genotyping identification, nucleotide sequence validation, mutation detection, rare allele detection, and gene copy number change ( It may also be used in conjunction with a variety of general PCR, quantitative PCR (qPCR), and/or digital PCR (dPCR) methods and systems in applications such as copy number variation detection.

In general, although it is also applicable to quantitative polymerase chain reaction (qPCR) in which large amounts of samples are processed, it should be appreciated that any suitable PCR method may be used in accordance with the various embodiments described herein. Suitable PCR methods include, for example, digital PCR, isothermal PCR, allele specific PCR, asymmetric PCR, ligation mediated PCR, multiplex PCR, nested PCR, qPCR, casting PCR, genome walking (genome walking), including but not limited to bridge PCR.

As described below in accordance with various embodiments described herein, reaction locations include, but are not limited to, for example, through holes, sample holding areas, wells, indentations, spots, cavities, and reaction chambers. doesn't happen

1 is a perspective view illustrating an in vitro diagnostic chip according to an embodiment of the present invention. FIG. 2 is an exploded perspective view illustrating the in vitro diagnostic chip shown in FIG. 1 . FIG. 3 is a rear perspective view for explaining the fastening of the in vitro diagnostic chip shown in FIG. 1 .

1 to 3 , the in vitro diagnostic chip 100 according to an embodiment of the present invention includes a base member 110 , a tape 120 , a well array 130 , a well cover 140 , and a guide member ( 150 ) and a guide cap 160 .

The base member 110 has a D-shape and is disposed under the tape 120 . In this embodiment, the base member 110 may include a silicone material.

The tape 120 has a D-shape and is attached to the upper surface of the base member 110 . An opening is formed in the tape 120 to correspond to a region corresponding to the well array 130 . In addition, openings are formed in the tape 120 to correspond to a region in contact with a sample inlet and a region in contact with an air outlet, which will be described later. In this embodiment, the tape 120 may be a double-sided tape.

The well array 130 is disposed on the tape 120 , and a plurality of wells are formed. In this embodiment, the number of wells is illustrated, but not limited thereto. The well array 130 has an overall rectangular shape, and a diagonal line of the well array 130 is parallel to the insertion direction of the guide cap 160 .

The well cover 140 includes a body 141 having a D-shape, a protrusion 142 protruding upward from the body 141 and exposed through a hollow hole of the guide member 150 , and a protrusion 142 . ) includes a retracted valley 143 corresponding to the edge of the. In the present embodiment, the well cover 140 may include a thermoplastic elastomer (TPE) material. In this embodiment, the valley 143 may serve to reduce the force generated when the protrusion 142 is pressed. In addition, the valley 143 also serves to reduce stress applied to a component disposed under the well cover 140 .

In addition, the well cover 140 includes a cover groove 146 formed to cover the well array 130 , a sample inlet 147 formed to connect the outside and one side of the cover groove 146 , and the outside and the cover groove 146 . It includes an air outlet 148 formed to connect the other side, and is attached to the top surface of the tape 120 while covering the well array 130 . Accordingly, the sample injected through the sample inlet 147 is injected into the well array 130 disposed in the cover groove 146 . As the sample is injected into the well array 130 , air may be discharged through the air outlet 148 . In the present embodiment, the cover groove 146 is formed in an island shape retracted from the bottom surface of the well cover 140 , and the sample inlet 147 is formed in the bottom surface of the well cover 140 with the cover groove 146 and the outer surface. It is formed in a line shape connecting the side surfaces, and the air outlet 148 is formed in a line shape connecting the cover groove 146 and the outer surface on the bottom surface of the well cover 140 .

The guide member 150 covers the well cover 140 and exposes a portion of the well cover 140 through the hollow hole formed. In this embodiment, the guide member 150 may include a plastic material such as polycarbonate (PC).

The guide cap 160 includes a cap body 162 having a D-shape, a first protrusion 164 protruding from the cap body 162, and a second protrusion 166 protruding from the cap body 162, , is disposed on the side of the guide member 150 , and seals the sample inlet 147 and the air outlet 148 of the well cover 140 . In this embodiment, the guide cap 160 may include a plastic material such as polycarbonate (PC). The first protrusion 164 protrudes from the cap body 162 to be inserted into the sample inlet 147 . The second protrusion 166 protrudes from the cap body 162 to be inserted into the air outlet 148 .

The length of the first protrusion 164 is longer than the length of the second protrusion 166 . Also, the thickness of the first protrusion 164 is greater than the thickness of the second protrusion 166 . Accordingly, the sample inlet 147 is first sealed by the first protrusion 164 and then the air outlet 148 is sealed by the second protrusion 166 . Accordingly, when the first protrusion 164 is inserted into the sample inlet 147 , a portion of the remaining air may be discharged through the air outlet 148 . Then, the air outlet 148 is sealed by the second protrusion 166 .

The length of the sample inlet 147 and the length of the air outlet 148 may be substantially the same.

The in vitro diagnostic chip 100 may further include a filter 170 disposed in the air outlet 148 . The filter 170 may serve to discharge air and block the sample from being discharged. In this embodiment, the filter 170 may have hydrophobic properties by including molecules having a hydrophobic radical.

4 is a view for explaining a process of injecting a sample sample into the in vitro diagnostic chip shown in FIGS. 1 to 3 .

1 to 4 , first, in the in vitro diagnostic chip 100 to which the guide member 150 and the guide cap 160 are coupled, the guide cap 160 is separated from the guide member 150 . Accordingly, the sample inlet 147 and the air outlet 148 are exposed to the outside.

Then, the sample sample is directly filled into the well array 130 via the sample inlet 147 through a pipette (not provided). Here, the reason for directly filling the sample sample into the well array 130 through the pipette is that DNA is adsorbed or the sample is lost in the space of the sample inlet 147 or in the inflow path between the sample inlet 147 and the well array 130 . in order to reduce

Next, the in vitro diagnostic chip 100 is closed by inserting the guide cap 160 having the first protrusion 164 and the second protrusion 166 of different lengths into the guide member 150 .

Then, the in vitro diagnostic chip 100 is put into the centrifugal injection device and rotated. When the in vitro diagnostic chip 100 is disposed in the centrifugal injection device, the well array 130 of the in vitro diagnostic chip 100 is disposed to be inclined with respect to the ground. That is, a diagonal line of the well array 130 having a rectangular shape is disposed vertically or horizontally with respect to the ground. Accordingly, even if air pockets exist in the well array 130 , the air pockets may be concentrated at the apex of the well array. In addition, since the liquid sample is evenly distributed in the corners or edge regions of the well array 130, which is the reaction space, by centrifugal force, it is possible to prevent air pockets from being generated in the reaction space. Accordingly, it is possible to prevent an error caused by the air pocket in the PCR test result.

As described above, according to the present embodiment, by directly injecting a sample sample into the well array 130 through a pipette, DNA adsorption in the inlet path to the sample inlet 147 or the well array 130 is prevented. It can block and reduce sample loss.

In addition, after the sample is injected, the sample inlet 147 and the air outlet 148 of the well cover 140 using the guide cap 160 having the first protrusion 164 and the second protrusion 166 of different lengths. By sequentially sealing the cells, air present in the well array 130 may be discharged through the air outlet 148 . Accordingly, since the air pocket is removed from the well array, the reliability of the test may be increased. In addition, since it is sealed by the guide cap, it is possible to block the inflow of foreign substances from the outside.

5A is a perspective view illustrating a state before assembly of the in vitro diagnostic cartridge according to an embodiment of the present invention, and FIG. 5B is a perspective view illustrating a state after assembly of the in vitro diagnostic cartridge according to an embodiment of the present invention. 6 is an exploded perspective view illustrating the in vitro diagnostic cartridge shown in FIGS. 5A and 5B. 7 is a cross-sectional view for explaining the in vitro diagnostic cartridge shown in FIG.

5A to 7 , an in vitro diagnostic cartridge 200 according to an embodiment of the present invention includes an in vitro diagnostic chip 100 , a lower body 210 , a CMOS image sensor 220 , a PCB 230 , and a middle It includes a body 240 , an upper cover 250 , a hinge member 260 , a push lever 270 , and a push button 280 . Each of the lower body 210 and the upper cover 250 has a flat cylindrical shape, and accommodates the CMOS image sensor 220 , the PCB 230 , the middle body 240 , the push lever 270 and the push button 280 . do.

The in vitro diagnostic chip 100 is disposed between the middle body 240 and the upper cover 250 . Since the in vitro diagnostic chip 100 has been described with reference to FIGS. 1 to 3 , a detailed description thereof will be omitted.

The lower body 210 is disposed below the in vitro diagnostic chip 100 and accommodates the in vitro diagnostic chip 100 .

The CMOS image sensor 220 is disposed between the lower body 210 and the in vitro diagnostic chip 100 , and the in vitro diagnostic chip 100 captures a PCR reaction product. In the present embodiment, the CMOS image sensor 220 is disposed under the well array 130 of the in vitro diagnostic chip 100 , and captures PCR reaction products in the wells of the well array 130 . Specifically, the CMOS image sensor 220 is disposed to correspond to the substrate hole formed in the PCB 230 and receives light emitted from the well array 130 to measure a PCR reaction product performed in the PCR device.

The detection of the target according to various embodiments is, for example, detection through PCR method, detection through immunochemistry, fluorescence or chemiluminescence or cell imaging through chromogenic reaction or staining, alone or in combination thereof. detectable, but not limited to

In the present embodiment, an anti-scratch film (reference numeral not assigned) may be further formed on the upper surface of the CMOS image sensor 220 . The scratch-resistant film can protect the upper surface of the CMOS image sensor 220 even when the in vitro diagnostic chip 100 is repeatedly attached and detached to the in vitro diagnostic cartridge 200, so the in vitro diagnostic cartridge 200 can be recycled.

The PCB 230 is disposed between the lower body 210 and the middle body 240 to accommodate the CMOS image sensor 220 .

The middle body 240 is disposed on the PCB 230 and supports the in vitro diagnostic chip 100 . A groove portion 242 having a predetermined width and extending in the Y-axis direction is formed in the middle body 240 , and a square-shaped opening 244 is formed in the center of the groove portion 242 , and CMOS mounted on the PCB 230 . The image sensor 220 is exposed. A receiving protrusion is formed on the middle body 240 to correspond to the receiving bone formed in the in vitro diagnostic chip 100 . In this embodiment, a first receiving protrusion 246 is formed on one side of the groove portion 242 , and a second receiving projection 248 is formed on the other side of the groove portion 242 .

The upper cover 250 is disposed on the in vitro diagnostic chip 100 and is fastened to the lower body 210 while pressing the in vitro diagnostic chip 100 according to a user's push operation.

The hinge member 260 is disposed on side surfaces of the lower body 210 and the upper cover 250 to couple the lower body 210 and the upper cover 250 . Based on the hinge member 260 , the in vitro diagnostic cartridge 200 may be opened and closed.

The push lever 270 is disposed on the side of the lower body 210 to fasten the lower body 210 and the upper cover 250 according to the user's upper surface pressing operation, and the upper cover 250 according to the user's side pressing operation. ) is separated from the lower body 210 . A plurality of grooves formed in the vertical direction are formed on the side of the push lever 270 , and a fastening groove 271 corresponding to the fastening protrusion 251 of the upper cover 250 is formed on the upper portion of the push lever 270 . The fastening protrusion 251 of the upper cover 250 is inserted into the fastening groove 271 of the push lever 270 according to the user's upper surface pressing operation, and the push lever 270 is fastened according to the user's side pressing operation. The groove 271 is moved in the pressing direction so that the fastening protrusion 251 of the upper cover 250 is separated.

The push lever 270 is connected to the lower body 210 by a buffer member such as a spiral spring 272 or a plate spring. For example, one side of the spiral spring 272 may be connected to the push lever 270 , and the other side of the spiral spring 272 may be connected to the side surface of the middle body 240 . On the other hand, both ends of the plate-shaped spring may be connected to the push lever 270 , and the block portion of the plate-shaped spring may be disposed toward the side surface of the middle body 240 .

The push button 280 is disposed between the in vitro diagnostic chip 100 and the upper cover 250 , and is exposed to the outside through a hollow hole formed in the center of the upper cover 250 . The user presses the in vitro diagnostic chip 100 as the user presses the push button 280 .

In this embodiment, the in vitro diagnostic cartridge 200 may further include a heater (not shown) for thermal circulation. As used herein, thermal cycling uses a thermal cycler, isothermal amplification, thermal convection, infrared mediated thermal cycling, or helicase dependent amplification. It may include the step of In some embodiments, a chip may be integrated with an embedded heating element. In various embodiments, the chip may be integrated with semiconductors. Detection of the target according to various embodiments may, for example, but not limited to, fluorescence detection, positive or negative ion detection, pH (pH) detection, voltage detection, or current detection alone or in combination.

8 is a perspective view for explaining an assembly process of the in vitro diagnostic cartridge shown in FIG.

5A to 8 , the upper cover 250 is opened in the lower body 210 based on the hinge member 260 . Accordingly, the middle body 240 disposed on the lower body 210 and the CMOS image sensor 220 exposed by the groove portion 242 of the middle body 240 are exposed.

Next, the in vitro diagnostic chip 100 is disposed in the groove portion 242 of the middle body 240 .

Then, the upper cover 250 is pressed toward the lower body 210 to fasten the upper cover 250 and the lower body 210 in a hook manner.

Meanwhile, as shown in FIG. 4 , the centrifugal injection operation may be performed after the in vitro diagnostic cartridge 200 is disposed in the centrifugal injection device. The centrifugal injection operation may be performed after injecting the sample into the in vitro diagnostic chip 100 , or may be performed after the in vitro diagnostic chip 100 is placed inside the in vitro diagnostic cartridge 200 .

According to this centrifugal injection operation, the in vitro diagnostic cartridge 200 is rotated so that the plane of the in vitro diagnostic cartridge 200 on which the in vitro diagnostic chip 100 into which the liquid sample is injected is mounted is vertically rotated, thereby transferring the liquid sample into the reaction space by centrifugal force. can be evenly distributed. That is, by configuring the centrifugal injection device so that the liquid sample is also distributed in the corner or edge region of the well array 130, which is the reaction space, by centrifugal force, it is possible to block the creation of air pockets in the reaction space. Accordingly, it is possible to prevent an error caused by the air pocket in the PCR test result.

As described above, according to the present invention, by directly injecting a sample sample into the well array through a pipette, it is possible to block DNA adsorption at the sample inlet or in the flow path from the sample inlet to the well array. and sample loss can be reduced. In addition, by sequentially sealing the sample inlet and air outlet of the well cover using a guide cap after the sample is injected, air present in the well array can be discharged through the air outlet. Accordingly, since the air pocket is removed from the well array, the reliability of the test may be increased. In addition, since it is sealed by the guide cap, it is possible to block the inflow of foreign substances from the outside.

9 is a perspective view illustrating a state before and after assembly of an in vitro diagnostic chip according to another embodiment of the present invention. FIG. 10 is an exploded perspective view illustrating the in vitro diagnostic chip shown in FIG. 9 .

9 and 10, the in vitro diagnostic chip 300 according to another embodiment of the present invention includes a base member 310, a well array 320, a well cover 330, a guide member 340, and a stopper ( 350 ) and a guide cap 360 .

The base member 310 has a rectangular shape and is disposed under the well array 320 . In this embodiment, the base member 310 may include a silicon material.

The well array 320 is disposed on the base member 310 , and a plurality of wells are formed. In this embodiment, the number of wells is illustrated, but not limited thereto. For example, 20,000 wells may be formed in the well array 320 . However, it is not limited to 20,000 pieces. The well array 320 has an overall rectangular shape, and a diagonal of the well array 320 is parallel to the insertion direction of the guide cap 360 .

The well cover 330 includes a body 331, a protrusion 332 protruding upward from the body 331 and exposed through a hollow hole of the guide member 340, and the edge of the protrusion 332. and a retracted bone 333 . In this embodiment, the well cover 330 may include a thermoplastic elastomer (TPE) material. In this embodiment, the valley 333 may serve to reduce the force generated when the protrusion 332 is pressed. In addition, the valley 333 also serves to reduce stress applied to a component disposed under the well cover 330 .

In addition, the well cover 330 includes a cover groove (reference numeral not assigned) formed to cover the well array 320, a sample reservoir 335 formed to connect one side of the cover groove (shown in FIG. 11 to be described later), and a sample inlet 336 (shown in FIG. 11 to be described later) formed to connect the sample reservoir 335 and the outside, and is attached to the upper surface of the base member 310 while covering the well array 320 . In this embodiment, the sample inlet 336 has a shape that is extended from the center side of the well cover 330 toward the outside. In the sample inlet 336 having an expanded shape, a pipette may be more easily positioned for injection. The sample injected into the sample reservoir 335 through the sample injection hole 336 may be distributed in the wells of the well array 320 disposed in the cover groove. For example, if the in vitro diagnostic chip 300 is placed in a centrifuge and centrifuged, the sample injected into the sample reservoir 335 may be evenly distributed in each of the wells of the well array 320 .

The guide member 340 covers the well cover 330 and exposes a portion of the well cover 330 through the hollow hole formed therein. An injection hole is formed in the side surface of the guide member 340 to correspond to the sample injection hole 336 of the well cover 330 . In addition, a first fastening groove and a second fastening groove are formed on the side surface of the guide member 340 for fastening the guide cap 360 . In this embodiment, the guide member 340 may include a plastic material such as polycarbonate (PC).

The stopper 350 seals the sample injection hole 336 of the well cover 330 via the injection hole of the guide member 340 . The stopper 350 may include a silicon material.

The guide cap 360 includes a cap body 361, a first fastening protrusion 362 protruding from the cap body 361, and a second fastening protrusion 363 protruding from the cap body 361, and a guide member ( It is disposed on the side of the 340 and is fastened to the guide member 340 . A groove for accommodating a portion of the stopper 350 may be formed in the guide cap 360 . The groove may be formed between the first fastening protrusion 362 and the second fastening protrusion 363 . In this embodiment, the guide cap 360 may include a plastic material such as polycarbonate (PC). The first fastening protrusion 362 protrudes from the cap body 361 to be inserted into the first fastening groove 341 formed on the side surface of the guide member 340 , and the second fastening protrusion 363 is the guide member 340 . It protrudes from the cap body 361 to be inserted into the second fastening groove 342 formed on the side surface.

11 is a view for explaining a process of injecting a sample sample into the in vitro diagnostic chip shown in FIGS. 9 and 10 .

9 to 11 , first, in the in vitro diagnostic chip 300 to which the guide member 340 and the guide cap 360 are coupled, the guide cap 360 is separated from the guide member 340 . Accordingly, the sample inlet 336 is exposed to the outside.

Then, the sample sample is directly injected into the well array 320 through the sample inlet 336 through a pipette (reference numeral not assigned). A sample sample that has not yet been injected into the well array 320 may be filled in the sample reservoir 335 . However, the sample sample filled in the sample reservoir 335 may be completely filled in the well array 320 through a centrifugal injection process to be described later.

Next, the in vitro diagnostic chip 300 is closed by inserting the guide cap 360 into the guide member 340 .

Then, the in vitro diagnostic chip 300 is put into the centrifugal injection device and rotated. When the in vitro diagnostic chip 300 is disposed in the centrifugal injection device, the well array 320 of the in vitro diagnostic chip 300 is disposed to be inclined with respect to the ground. That is, a diagonal line of the well array 320 having a rectangular shape is disposed vertically or horizontally with respect to the ground. Accordingly, even if air pockets exist in the well array 320 , the air pockets may be concentrated at the apex of the well array 320 . In addition, since the liquid sample is evenly distributed in the corners or edge regions of the well array 320 as the reaction space by centrifugal force, it is possible to prevent air pockets from being generated in the reaction space. Accordingly, it is possible to prevent an error caused by the air pocket in the PCR test result.

As described above, according to the present embodiment, since the sample inlet 336 is expanded, it is possible to more easily position the pipette to inject the sample sample, thereby increasing the sample sample injection efficiency and shortening the injection time. can

12 is an exploded perspective view illustrating an in vitro diagnostic cartridge according to another embodiment of the present invention.

12, the in vitro diagnostic cartridge 400 according to another embodiment of the present invention includes a lower body 410, a bottom plate 412, a CMOS image sensor 414, a printed circuit board (PCB) 416, It includes a middle body 418 , an upper ring 420 , a push button 422 , and an upper cover 424 , and accommodates the in vitro diagnostic chip 300 . Each of the lower body 410 and the upper cover 424 has a flat cylindrical shape, and accommodates the CMOS image sensor 414 , the PCB 416 , and the middle body 418 .

The in vitro diagnostic chip 300 is disposed between the middle body 418 and the upper cover 424 . Since the in vitro diagnostic chip 300 has been described with reference to FIGS. 9 and 10 , a detailed description thereof will be omitted.

The lower body 410 is disposed below the in vitro diagnostic chip 300 and accommodates the in vitro diagnostic chip 300 . A rectangular hole is formed in the lower body 410 to correspond to the CMOS image sensor 414 .

The bottom plate 412 has a rectangular shape and is disposed on the bottom surface of the lower body 410 . A rectangular hole is formed in the bottom plate 412 to correspond to the CMOS image sensor 414 .

The PCB 416 is disposed between the bottom plate 412 and the middle body 418 to accommodate the CMOS image sensor 414 .

The CMOS image sensor 414 is mounted on the PCB 416 to photograph the PCR reaction product in the in vitro diagnostic chip 300 . In the present embodiment, the CMOS image sensor 414 is disposed under the well array of the in vitro diagnostic chip 300 and captures PCR reaction products in the wells of the well array. Specifically, the CMOS image sensor 414 is disposed to correspond to the substrate hole formed in the PCB 416 and receives light emitted from the well array to measure the PCR reaction product performed in the PCR device.

In the present embodiment, an anti-scratch film (reference numeral not assigned) may be further formed on the upper surface of the CMOS image sensor 414 . The scratch-resistant film can protect the upper surface of the CMOS image sensor 414 even if the in vitro diagnostic chip 300 is repeatedly attached and detached to the in vitro diagnostic cartridge 400, so the in vitro diagnostic cartridge 400 can be recycled.

The middle body 418 is disposed on the PCB 416 and supports the in vitro diagnostic chip 300 . A groove portion extending in the Y-axis direction is formed in the middle body 418 , and a square-shaped opening 244 is formed in the center of the groove portion to accommodate the CMOS image sensor 414 mounted on the PCB 416 . expose A receiving protrusion is formed on the middle body 418 to correspond to the receiving bone formed in the in vitro diagnostic chip 300 . In this embodiment, a first receiving protrusion is formed on one side of the groove, and a second receiving protrusion is formed on the other side of the groove.

The first toggle 430 is disposed under the middle body 418 and is connected to the other end of the first spring 432 having one end connected to a sidewall adjacent to the groove portion of the middle body 418 . The second toggle 440 is disposed below the middle body 418 , and the second toggle 440 is connected to the other end of the second spring 442 having one end connected to a sidewall adjacent to the groove portion of the middle body 418 . . The first toggle 430 and the second toggle 440 are disposed to face each other based on the groove portion of the middle body 418 .

The lower magnet stream 450 includes a first magnet 452 , a second magnet 454 , a third magnet 456 , and a fourth magnet 458 , and is disposed under the middle body 418 to be hidden. A separate receiving groove for accommodating the lower magnets 450 may be formed in the middle body 418 . In this embodiment, the polarities of the first magnet 452 and the second magnet 454 are the same as each other, the polarities of the third magnet 456 and the fourth magnet 458 are the same as each other, and the first magnet 452 ) and the polarity of the third magnet 456 are preferably different from each other. In the present embodiment, the polarity of the lower magnet stream 450 may mean a polarity toward the upper side, that is, the upper magnet stream 460 .

12, the first toggle 430, the second toggle 440, the first spring 432, the second spring 442 and the lower magnets 450 are disposed on the middle body 418, This is only shown for convenience of description and is actually a first toggle 430, a second toggle 440, a first spring 432, a second spring 442 and a lower magnet under the middle body 418 ( 450) is placed and hidden.

The upper ring 420 is disposed to correspond to the periphery of the lower periphery of the upper cover 424 , and is fastened to the upper cover 424 through the first binding sphere 462 and the second binding sphere 464 . Receiving holes are formed in the upper ring 420 for accommodating the upper magnets 460 . In this embodiment, the upper ring 420 is fastened to the upper cover 424 by each of the first binding sphere 462 and the second binding sphere 464 to be spaced apart. For example, the upper ring 420 and the upper cover 424 are fastened to each other by the first binding sphere 462 and the second binding sphere 464 so as to be vertically spaced apart by an interval of 1 mm. The vertical separation of the upper ring 420 may correspond to the vertical operation of the upper magnets 460 accommodated in the upper ring 420 .

The upper magnets 460 include a fifth magnet 462 , a sixth magnet 464 , a seventh magnet 466 , and an eighth magnet 468 , and are accommodated in the receiving holes formed in the upper ring 420 . do. The upper magnet flow 460 and the lower magnet flow 450 have different polarities. In this embodiment, the polarities of the fifth magnet 462 and the sixth magnet 464 are the same as each other, the polarities of the seventh magnet 466 and the eighth magnet 468 are the same, and the fifth magnet 462 ) and the polarity of the seventh magnet 466 are preferably different from each other. In this embodiment, the polarity of the upper magnet stream 460 may mean a polarity toward the lower side, that is, the lower magnet stream 450 .

The upper magnet flow 460 may be disposed to correspond to the lower magnet flow 450 . That is, the first magnet 452 corresponds to the fifth magnet 462 , the second magnet 454 corresponds to the sixth magnet 464 , and the third magnet 456 corresponds to the seventh magnet 466 . Correspondingly, the fourth magnet 458 may be disposed to correspond to the eighth magnet 468 . That is, if the first magnet 452 and the second magnet 454 have an S polarity, the third magnet 456 and the fourth magnet 458 disposed on the same plane have an N polarity, and the fifth magnet 462 has an N polarity. and the sixth magnet 464 has an N polarity, and the seventh magnet 466 and the eighth magnet 468 have an S polarity. On the other hand, if the first magnet 452 and the second magnet 454 have an N polarity, the third magnet 456 and the fourth magnet 458 disposed on the same plane have an S polarity, and the fifth magnet 462 has an S polarity. and the sixth magnet 464 has an S polarity, and the seventh magnet 466 and the eighth magnet 468 have an N polarity.

As such, since magnets of different polarities and magnets of the same polarity are arranged on the same plane, and magnets of different polarities and magnets of the same polarity are arranged on a plane facing each other, the upper corresponding to the upper plane The cover 424 and the lower body 410 corresponding to the lower plane may be automatically aligned by magnets.

The push button 422 is disposed to correspond to the in vitro diagnostic chip 300 .

The upper cover 424 is disposed on the in vitro diagnostic chip 300 , exposes the push button 422 through the hollow hole, and presses the in vitro diagnostic chip 300 as the user pushes the push button 422 .

In this embodiment, the in vitro diagnostic cartridge 400 may further include a heater (not shown) for thermal circulation. As used herein, thermal cycling uses a thermal cycler, isothermal amplification, thermal convection, infrared mediated thermal cycling, or helicase dependent amplification. It may include the step of In some embodiments, a chip may be integrated with an embedded heating element. In various embodiments, the chip may be integrated with semiconductors. Detection of the target according to various embodiments may, for example, but not limited to, fluorescence detection, positive or negative ion detection, pH (pH) detection, voltage detection, or current detection alone or in combination.

13 is a perspective view for explaining a process of fastening the in vitro diagnostic chip shown in FIGS. 9 and 10 to the in vitro diagnostic cartridge 400 shown in FIG. 12 . 14 are images in which some components are processed to be transparent in order to explain the process of fastening the in vitro diagnostic chip shown in FIGS. 9 and 10 to the in vitro diagnostic cartridge shown in FIG. 12 .

9 to 14 , the upper cover 424 is removed from the in vitro diagnostic cartridge 400 to expose the middle body 418 coupled to the lower body 410 and the CMOS image sensor 414 .

Next, the in vitro diagnostic chip 300 is seated in the groove formed in the middle body 418 of the in vitro diagnostic cartridge 400 , and the separated upper cover 424 is disposed on the middle body 418 for fastening.

Then, as the upper cover 424 is disposed on the middle body 418 , the upper magnets 460 and the lower magnets 450 are automatically aligned by magnetism.

Then, as the user pushes the upper cover 424 , each of the first toggle 430 and the second toggle 440 is pushed back and returned to lock the upper cover 424 to the lower body 410 . do. Specifically, as the user pushes the upper cover 424 , each of the first fastening hooks 424a and the second fastening hooks 424b formed on the upper cover 424 is a first disposed under the middle body 418 . Push the toggle 430 and the second toggle 440 . Each of the first toggle 430 and the second toggle 440 is shifted to the outer surface of the lower body 410 as it is pushed by the first fastening hook 424a and the second fastening hook 424b. At this time, the first fastening hook 424a and the second fastening hook 424b are descended and restored to their original positions by the first spring 432 and the second spring 442 . As such, when the first fastening hook 424a and the second fastening hook 424b are engaged with the first toggle 430 and the second toggle 440, respectively, the upper cover 424 is the lower body to which the middle body 418 is fastened. It is fastened to (410).

Meanwhile, as shown in FIG. 11 , the centrifugal injection operation may be performed after the in vitro diagnostic cartridge 400 is disposed in the centrifugal injection device. The centrifugal injection operation may be performed after injecting the sample into the in vitro diagnostic chip 300 , or may be performed after the in vitro diagnostic chip 300 is placed inside the in vitro diagnostic cartridge 400 .

According to this centrifugal injection operation, the in vitro diagnostic cartridge 400 is rotated so that the plane of the in vitro diagnostic cartridge 400 on which the in vitro diagnostic chip 300 into which the liquid sample is injected is mounted is vertically rotated, thereby transferring the liquid sample into the reaction space by centrifugal force. can be evenly distributed. That is, by configuring the centrifugal injection device so that the liquid sample is distributed even in the corners or edge regions of the well array, which is the reaction space, by centrifugal force, it is possible to prevent air pockets from being generated in the reaction space. Accordingly, it is possible to prevent an error caused by an air pocket in the PCR test result.

15 is a perspective view for explaining a process of separating the in vitro diagnostic chip 300 shown in FIGS. 9 and 10 from the in vitro diagnostic cartridge 400 shown in FIG. 12 .

Referring to FIG. 15 , the upper cover 424 coupled to the lower body 410 is rotated clockwise by about 10 degrees. As the upper cover 424 is rotated, it is out of the toggle position.

Then, it returns to the step before push.

Next, the upper cover 424 is removed from the lower body 410 to separate the in vitro diagnostic chip 300 from the in vitro diagnostic cartridge 400 .

Although not shown, the process of discarding the in vitro diagnostic chip 300 separated from the in vitro diagnostic cartridge 400 and re-arranging a new in vitro diagnostic chip 300 may be performed. Accordingly, since the in vitro diagnostic cartridge 400 can be used multiple times, it can be recycled.

Although the above has been described with reference to the embodiments, those skilled in the art can variously modify and change the present invention within the scope without departing from the spirit and scope of the present invention described in the claims below You will understand.

The present invention has industrial applicability that can be used for research, medical use, disaster prevention, livestock breeding, pet treatment, etc. as a device for testing biochemical substances, blood testing device, disease testing device, and the like.

100, 300: in vitro diagnostic chip 110, 310: base member
120: tape 130, 320: well array
140, 320 well cover 147 sample inlet
148: air outlet 150, 340: guide member
160, 360: guide cap 162: cap body
164: first projection 166: second projection
170: filter 200, 400: in vitro diagnostic cartridge
210, 410: lower body 220, 414: CMOS image sensor
230, 416: PCB 240: middle body
250, 424: upper cover 260: hinge member
270: push lever 280, 422: push button
350: stopper 412: bottom plate
418: middle body 420: upper ring
430: first toggle 432: first spring
440: second toggle 442: second spring
450: lower magnets 460: upper magnets

Claims (20)

base member;
a well array disposed on the base member and including a plurality of wells;
a cover groove formed to cover the well array; a sample reservoir formed to connect one side of the cover groove; a well cover disposed to cover the well array;
a guide member covering the well cover and exposing a portion of the well cover through a hollow hole formed therein;
a stopper sealing the sample inlet of the well cover; and
and a guide cap accommodating a portion of the stopper and fastened to a side surface of the guide member in a hook manner. The in vitro diagnostic chip according to claim 1, wherein a longitudinal direction of the guide member and a diagonal direction of the well array are parallel to each other. The in vitro diagnostic chip according to claim 1, wherein the stopper comprises a silicone rubber material. in vitro diagnostic chip;
a lower body disposed under the in vitro diagnostic chip and accommodating the in vitro diagnostic chip;
a CMOS image sensor disposed between the lower body and the in vitro diagnostic chip and configured to photograph a PCR reaction product in the in vitro diagnostic chip;
a PCB accommodating the CMOS image sensor;
a middle body disposed on the PCB, exposing the CMOS image sensor through a hollow hole, and supporting the in vitro diagnostic chip; and
and an upper cover disposed on the in vitro diagnostic chip and coupled to the lower body while pressing the in vitro diagnostic chip according to a user's push operation. [Claim 5] The external body of claim 4, further comprising an upper ring disposed to correspond to the periphery of the lower periphery of the upper cover and fastened to the upper cover so as to be spaced apart from the upper cover through a first binding sphere and a second binding sphere. diagnostic cartridge. The apparatus of claim 5, further comprising: lower magnets disposed under the middle body and hidden; and
The in vitro diagnostic cartridge according to claim 1, further comprising upper magnets accommodated in a receiving hole formed in the upper ring corresponding to the lower magnets. 7. The method of claim 6, wherein the lower magnets include a first magnet, a second magnet, a third magnet, and a fourth magnet,
The first magnet and the second magnet have the same polarity, the third magnet and the fourth magnet have the same polarity, and the first magnet and the third magnet have different polarities. In vitro diagnostic cartridge. The method according to claim 7, wherein the upper magnets include a fifth magnet, a sixth magnet, a seventh magnet, and an eighth magnet,
The fifth magnet and the sixth magnet have the same polarity, the seventh magnet and the eighth magnet have the same polarity, and the fifth magnet and the seventh magnet have different polarities. In vitro diagnostic cartridge. 5. The method of claim 4,
a first toggle disposed under the middle body and connected to the other end of a first spring having one end connected to a sidewall adjacent to the groove portion of the middle body; and
The in vitro diagnostic cartridge according to claim 1, wherein the second toggle further comprises a second toggle connected to the other end of a second spring disposed under the middle body, the second toggle having one end connected to a sidewall adjacent to the groove portion of the middle body. The method of claim 9, wherein the upper cover further comprises a first fastening hook and a second fastening hook protruding toward the middle body,
The upper cover is locked to the lower body by engaging the first and second fastening hooks while the first and second toggles are respectively pushed back and returned as the upper cover is pressed by the user. In vitro diagnostic cartridge. base member;
a well array disposed on the base member and including a plurality of wells;
and a cover groove formed to cover the well array, a sample inlet formed to connect the outside to one side of the cover groove, and an air outlet formed to connect the outside to the other side of the cover groove, and arranged to cover the well array well cover;
a guide member covering the well cover and exposing a portion of the well cover through a hollow hole formed therein; and
and a guide cap disposed on a side surface of the guide member and sealing the sample inlet and air outlet of the well cover. The method of claim 11, wherein the guide cap,
cap body;
a first protrusion protruding from the cap body to be inserted into the sample inlet; and
and a second protrusion protruding from the cap body to be inserted into the air outlet. The in vitro diagnostic chip according to claim 12, wherein a length of the first protrusion is longer than a length of the second protrusion. The in vitro diagnostic chip according to claim 12, wherein a thickness of the first protrusion is greater than a thickness of the second protrusion. The in vitro diagnostic chip according to claim 1, wherein the well array has an overall rectangular shape, and a diagonal of the well array is parallel to an insertion direction of the guide cap. The in vitro diagnostic chip according to claim 11, wherein the well cover includes a protrusion that protrudes upward and is exposed through a hollow hole of the guide member, and a bone retracted to correspond to an edge of the protrusion. in vitro diagnostic chip;
a lower body disposed under the in vitro diagnostic chip and accommodating the in vitro diagnostic chip;
a CMOS image sensor disposed between the lower body and the in vitro diagnostic chip and configured to photograph a PCR reaction product in the in vitro diagnostic chip;
a PCB accommodating the CMOS image sensor;
an upper cover disposed on the in vitro diagnostic chip and coupled to the lower body while pressing the in vitro diagnostic chip according to a user's push operation;
a hinge member disposed on side surfaces of the lower body and the upper cover to fasten the lower body and the upper cover; and
A push lever disposed on the side of the lower body to fasten the lower body and the upper cover according to the user's upper surface pressing operation, and to separate the upper cover from the lower body according to the user's side pressing operation. diagnostic cartridge. 18. The method of claim 17, wherein the in vitro diagnostic chip comprises:
base member;
a well array disposed on the base member and including a plurality of wells;
and a cover groove formed to cover the well array, a sample inlet formed to connect the outside to one side of the cover groove, and an air outlet formed to connect the outside to the other side of the cover groove, and arranged to cover the well array well cover;
a guide member covering the well cover and exposing a portion of the well cover through a hollow hole formed therein; and
and a guide cap disposed on a side surface of the guide member and sealing the sample inlet and the air outlet of the well cover. 18. The method of claim 17, further comprising a middle body supporting the in vitro diagnostic chip,
The in vitro diagnostic cartridge, characterized in that the middle body has a receiving protrusion corresponding to the receiving bone formed in the in vitro diagnostic chip. 18. The in vitro diagnostic cartridge according to claim 17, further comprising an anti-scratch film formed on an upper surface of the CMOS image sensor.

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