A microfluidic device comprising at least one microfluidic structure and an analytical method for supplying samples thereto.
The automated pretreatment, separation, and detection of samples are achieved through a microfluidic device driven by a rotating body, which solves the problem of low efficiency of manual operation in existing technologies and enables rapid and accurate analysis of multiple target substances.
Patent Information
- Application Number
- CN202180046786.9
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2021-06-16
- Publication Date
- 2025-10-31
- Estimated Expiration
- 2041-06-16
AI Technical Summary
Existing microfluidic devices require manual assembly and processing of multiple samples during on-site diagnostics, resulting in low efficiency and an inability to quickly and effectively analyze a variety of samples.
Design a microfluidic device based on a rotating body, comprising a pretreatment section, a storage section, and a detection section, which automatically processes samples and solutions through rotational force to achieve sample pretreatment, separation, storage, and detection of target substances.
It enables rapid and accurate analysis of multiple target substances in a microfluidic device, and is suitable for the rapid detection of large numbers of samples in on-site diagnostics.
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Figure CN115867387B_ABST
Abstract
Description
Technical Field
[0001] This disclosure relates to a microfluidic device comprising at least one microfluidic structure and a sample analysis apparatus using the microfluidic device. More specifically, it relates to a microfluidic device for extracting and diagnosing genomic DNA, target antigens, or target substances from a sample, and a sample analysis apparatus for performing a method of analyzing a sample supplied thereto. Background Technology
[0002] To diagnose viral diseases such as influenza, avian influenza, and coronaviruses, technologies are being developed to analyze proteins or genomes in samples. In particular, there is a need to develop technologies that can rapidly and quickly diagnose bacterial or viral diseases with a wide social impact on the field.
[0003] To enable rapid on-site diagnosis of these pathogens, microfluidic devices capable of inducing biological or chemical reactions by manipulating small amounts of fluid are currently used. Microfluidic devices can include microfluidic structures of various shapes placed within the body, such as chips and disks. By using microfluidic devices for on-site diagnosis of various pathogens, pathogens can be rapidly blocked, thus reducing personal injury and economic losses.
[0004] However, due to space constraints, conventional microfluidic devices have limitations in processing multiple samples simultaneously on a single chip. Furthermore, in field diagnostics, a significant amount of time is required to assemble and operate the sampling tubes and microfluidic devices used for sample injection.
[0005] Therefore, there is a need to develop a microfluidic device that can effectively analyze various samples without separate manual operation, as well as a sample analysis device that uses the microfluidic device. Summary of the Invention
[0006] The problem that the invention aims to solve
[0007] According to the disclosed embodiments, a microfluidic device is provided that can move a sample based on the rotation of a rotating body.
[0008] Furthermore, according to one embodiment, a sample analysis apparatus using the above-described microfluidic device is provided.
[0009] Solution for solving the problem
[0010] According to one embodiment, a microfluidic device is provided, comprising: a rotating body; and at least one microfluidic structure disposed at a predetermined distance inside the rotating body, the microfluidic structure comprising: a pretreatment section that shares a solution injected through a solution injection port with other adjacent microfluidic structures via a shared channel, and performs a pretreatment process on a sample injected through a sample injection port and the solution; a storage section located radially outward from the pretreatment section inside the rotating body, separating and storing the sample and solution pretreated by the pretreatment section along the rotation direction of the rotating body; and a detection section that detects a target substance in the pretreated sample dispensed from the storage section.
[0011] According to one embodiment, the pretreatment unit may include: a sample chamber for containing a sample injected through the sample injection port; a solution chamber for containing a solution injected through the solution injection port; and a capture filter for capturing target substances from the injected sample.
[0012] According to one embodiment, the pretreatment unit may further include: a first manual valve, which provides the sample contained in the sample chamber to the capture filter based on a first rotational force generated by the rotating body; and a second manual valve, which provides the solution contained in the solution chamber to the capture filter based on a second rotational force generated by the rotating body.
[0013] According to one embodiment, the shared channel is formed in a zigzag shape along the circumferential direction inside the rotating body. The rotating body can be stationary or rotated so that the solution in the solution chamber cannot move to the capture filter until the solution in the solution chamber is shared with other solution chambers in other microfluidic structures.
[0014] According to one embodiment, the storage unit may include: a collection chamber for storing an elution solution containing target material in the sample and target material captured by the capture filter in the solution; and a first waste chamber for storing a cleaning solution for cleaning remaining material other than the sample that has passed through the capture filter and the target material captured by the capture filter in the solution.
[0015] According to one embodiment, the storage unit may further include: a transfer chamber for obtaining an elution solution containing the target substance or a sample passing through the capture filter and the washing solution from the capture filter, and selectively transferring the elution solution containing the target substance to the collection chamber along the rotation direction of the rotating body, or transferring the sample passing through the capture filter and the washing solution to the first waste chamber, wherein a reaction solution for detecting the target substance is freeze-dried in the collection chamber.
[0016] According to one embodiment, the detection unit may include: a siphon channel, one end of which is connected to the collection chamber; a distribution unit, which is connected to the other end of the siphon channel and includes a plurality of distribution chambers, such that a predetermined amount of elution solution containing the target substance from the collection chamber is distributed to the plurality of distribution chambers; and a reaction unit, which includes a reaction chamber for obtaining the elution solution containing the target substance provided by the distribution chamber and freeze-drying primers and reaction solution for detecting the target substance.
[0017] According to one embodiment, the detection unit may further include a second waste chamber for storing the remaining elution solution after it has been allocated to the allocation chamber from the elution solution containing the target substance obtained from the siphon channel.
[0018] According to one embodiment, the detection unit may further include a wax storage unit for storing wax, wherein the wax generates oil at a preset temperature for use in the dispensing chamber, so that after the elution solution containing the target substance is dispensed into the dispensing chamber, the elution solution is prevented from evaporating.
[0019] According to one embodiment, the rotating body can remain stationary for a preset time, so that the rotational force generated by the rotating body acting on at least a portion of the channels in the siphon channel is less than the capillary force generated in at least a portion of the channels, thereby causing the target material in the collection chamber to begin moving toward the siphon channel.
[0020] According to one embodiment, the rotating body can rotate such that the rotational force applied to the elution solution containing the target substance in the dispensing chamber is greater than the air pressure stored in the reaction chamber.
[0021] According to one embodiment, a sample analysis apparatus may be provided, comprising: the aforementioned microfluidic device; a first drive unit for rotating the microfluidic device along the aforementioned rotation axis; a second drive unit for moving an injection mechanism, wherein the injection mechanism injects the sample and the solution into the microfluidic device along a preset drive axis; a supply unit for storing the sample and solution to be supplied to the injection mechanism, and selectively supplying the stored sample and solution to the injection mechanism; and a control unit for controlling the first drive unit, the second drive unit, and the supply unit, such that the sample and the solution in the microfluidic structure move along a preset path.
[0022] According to one embodiment, the first drive unit may include: a rotating component, which is configured to be fastened to the microfluidic device and is capable of rotating together with the microfluidic device along the rotation axis of the microfluidic device; and a spindle motor, which rotates the rotating component in a predetermined rotation direction and rotation speed based on a first control signal obtained by the control unit.
[0023] According to one embodiment, the second driving unit may include: at least one guide shaft, which is arranged at preset intervals; a first driving component, which is connected to one end of the driving shaft and fastens the injection mechanism; a second driving component, which is connected to the other end of the driving shaft and transmits driving force to the driving shaft so that the driving shaft rotates at a predetermined angular interval; and a stepper motor for rotating the second driving component.
[0024] According to one embodiment, the second driving component may further include: a through hole for allowing the at least one guide shaft to pass through; and a ball screw component that contacts the surface formed in the through hole, and the second driving component moves along the at least one guide shaft when the ball screw component and the thread formed on the at least one guide shaft are in a tight fit.
[0025] According to one embodiment, the above-described sample analysis device may further include: a heating element formed at the bottom of the microfluidic device and cylindrically surrounding at least a portion of the first driving element in the direction outside the first driving element; and a linear guide for aligning the position of the heating element in the direction outside the first driving element.
[0026] According to one embodiment, the sample may include a target substance as the object of analysis, and the solution may include: a cleaning solution for washing away remaining substances other than the target substance, an elution solution for separating the target substance, and a reaction solution for amplifying the target substance in the sample.
[0027] According to one embodiment, the supply unit may include: a storage unit that separately stores the sample, the cleaning solution, and the elution solution; a supply channel connected to the storage unit and separately obtaining the sample, the cleaning solution, the elution solution, and the reaction solution from the storage unit; a port valve that, under the control of the control unit, selects a channel from the supply channel to be connected to the injection mechanism; and an injection pump for moving the sample, the cleaning solution, the elution solution, and the reaction solution from the storage unit to the injection mechanism.
[0028] According to one embodiment, the storage unit may include: a sample storage unit for storing the sample; a cleaning solution storage unit for storing the cleaning solution; an elution solution storage unit for storing the elution solution; and a reaction solution storage unit for storing the reaction solution. Furthermore, the sample storage unit, the cleaning solution storage unit, and the elution solution storage unit also include a connection hole for communicating with the supply channel.
[0029] According to one embodiment, the above-described sample analysis apparatus may further include: a first housing, configured to house the first drive unit, the second drive unit, and the control unit inside the first housing; and a second housing, connected to the first housing in an openable and closable manner, thereby enabling selective exposure of the microfluidic device.
[0030] According to another embodiment for solving the above-mentioned technical problems, a microfluidic device is provided, comprising: at least one microfluidic structure disposed at a predetermined distance inside the rotating body; and a waste chamber located radially outward inside the rotating body compared to the at least one microfluidic structure, and connected to the at least one microfluidic structure respectively. The microfluidic structure includes: a solution chamber for containing a solution injected through a solution injection port, and sharing the contained solution with other adjacent microfluidic structures via a first shared channel; a sample chamber located radially outward inside the rotating body compared to the solution chamber, and containing a solution injected through an externally open vent; and a siphon channel, one end of which is connected to the sample chamber and the other end to the waste chamber, thereby transferring the sample and the solution to the waste chamber.
[0031] According to one embodiment, the microfluidic structure may further include a manual valve, one end of which is connected to the solution chamber and provides the solution contained in the solution chamber to the sample chamber based on the rotational force generated by the rotating body.
[0032] According to one embodiment, the waste chamber may further include a superabsorbent polymer, which absorbs the sample and solution into the interior of the waste chamber.
[0033] According to one embodiment, the first shared channel is formed in a zigzag shape along the circumferential direction inside the rotating body. The rotating body, by being stationary or rotating, prevents the solution in the solution chamber from moving to the sample chamber until the solution in the solution chamber is shared with the solution chambers in other microfluidic structures.
[0034] According to one embodiment, the sample chamber can be configured to be connected to a second shared channel, which shares the sample injected through the vent with other adjacent microfluidic structures.
[0035] According to one embodiment, the rotating body can remain stationary for a preset time, so that the rotational force generated by the rotating body acting on at least a portion of the channels in the siphon channel is less than the capillary force generated in at least a portion of the channels, thereby causing the sample and solution in the collection chamber to begin moving toward the siphon channel.
[0036] According to one embodiment, the inner surface of the sample chamber is pre-coated with a first antibody that can bind to the target substance in the sample. The solution chamber can obtain the following solutions through the solution injection port: a solution containing a second antibody with a chromogenic enzyme for enzyme-linked immunosorbent assay (ELISA), a solution containing a chromogenic substrate, and a solution for washing the target substance in the sample that has not bound to the first antibody.
[0037] According to one embodiment, the at least one microfluidic structure can be disposed inside the rotating body in a circumferential direction with the rotation axis of the rotating body as the center. The rotating body can rotate a preset number of revolutions with the at least one rotation axis as the center. The sample and the solution can move within the microfluidic structure based on the rotational force generated by the rotation of the rotating body.
[0038] According to one embodiment, a sample analysis apparatus may be provided, comprising: the aforementioned microfluidic device; a first drive unit for rotating the microfluidic device along the aforementioned rotation axis; a second drive unit for moving an injection mechanism, wherein the injection mechanism injects the sample and the solution into the microfluidic device along a preset drive axis; a supply unit for storing the sample and solution to be supplied to the injection mechanism, and selectively supplying the stored sample and solution to the injection mechanism; and a control unit for controlling the first drive unit, the second drive unit, and the supply unit, such that the sample and the solution in the microfluidic structure move along a preset path.
[0039] According to one embodiment, the first drive unit may include: a rotating component, which is configured to be fastened to the microfluidic device and is capable of rotating together with the microfluidic device along the rotation axis of the microfluidic device; and a spindle motor, which rotates the rotating component in a predetermined rotation direction and rotation speed based on a first control signal obtained by the control unit.
[0040] According to one embodiment, the second driving unit may include: at least one guide shaft, which is arranged at preset intervals; a first driving component, which is connected to one end of the driving shaft and fastened to the injection mechanism; a second driving component, which is connected to the other end of the driving shaft and transmits driving force to the driving shaft so that the driving shaft rotates at a predetermined angular interval; and a stepper motor for rotating the second driving component.
[0041] According to one embodiment, the second driving component may further include: a through hole for allowing the at least one guide shaft to pass through; and a ball screw component that contacts the surface formed in the through hole, and the second driving component moves along the at least one guide shaft when the ball screw component and the thread formed on the at least one guide shaft are in a tight fit.
[0042] According to one embodiment, the above-described sample analysis device may further include: a heating element formed at the bottom of the microfluidic device and cylindrically surrounding at least a portion of the first driving element in the direction outside the first driving element; and a linear guide for aligning the position of the heating element in the direction outside the first driving element.
[0043] According to one embodiment, the sample may include a target substance as the object of analysis, and the solution may include a cleaning solution for washing away any remaining substances other than the target substance, and a reaction solution for enzyme-linked immunosorbent assay (ELISA).
[0044] According to one embodiment, the supply unit may include: a storage unit that separately stores the sample, the cleaning solution, and the reaction solution; a supply channel connected to the storage unit and separately obtaining the sample, the cleaning solution, and the reaction solution from the storage unit; a port valve that, under the control of the control unit, selects a channel from the supply channel to be connected to the injection mechanism; and an injection pump for moving the sample, the cleaning solution, and the reaction solution from the storage unit to the injection mechanism.
[0045] According to one embodiment, the storage unit may include: a sample storage unit for storing the sample; a cleaning solution storage unit for storing the cleaning solution; and a reaction solution storage unit for storing the reaction solution. Furthermore, the sample storage unit, the cleaning solution storage unit, and the reaction solution storage unit may also include a connection hole for communicating with the supply channel.
[0046] According to one embodiment, the above-described sample analysis device may further include: a first housing, configured to house the first drive unit, the second drive unit, and the control unit inside the first housing; and a second housing, connected to the first housing in an openable and closable manner, thereby selectively exposing the microfluidic device.
[0047] According to one embodiment, the above-mentioned sample analysis device may further include: a camera that acquires images of the microfluidic device at preset time intervals; and a network interface that transmits information about the images acquired from the camera to an external device connected to the sample analysis device.
[0048] According to another embodiment for achieving the above-mentioned objective, a microfluidic device can be provided, comprising: a rotating body; and at least one microfluidic structure disposed at a predetermined distance inside the rotating body, the microfluidic structure comprising: a pretreatment section that shares a solution injected through a solution injection port with other adjacent microfluidic structures via a shared channel, and performs a pretreatment process on a sample and solution injected through a sample injection port; and a dispensing section that is radially located outside the pretreatment section inside the rotating body, dispensing a target substance from the sample pretreated by the pretreatment section, and detecting the dispensed target substance.
[0049] According to one embodiment, the pretreatment unit may include: a sample chamber for containing a sample injected through the sample injection port; a solution chamber for containing a solution injected through the solution injection port; and a capture filter for capturing target substances from the injected solution.
[0050] According to one embodiment, the pretreatment unit may further include: a first manual valve, which provides the sample contained in the sample chamber to the capture filter based on a first rotational force generated by the rotating body; and a second manual valve, which provides the solution contained in the solution chamber to the capture filter based on a second rotational force generated by the rotating body.
[0051] According to one embodiment, the shared channel is formed in a zigzag shape along the circumferential direction inside the rotating body. The rotating body, by being stationary or rotating, prevents the solution in the solution chamber from moving to the capture filter until the solution in the solution chamber is shared with the solution chambers in other microfluidic structures.
[0052] According to one embodiment, the above-mentioned dispensing unit may include: a collection chamber for storing an elution solution containing target material captured by the capture filter; and a waste chamber for storing a cleaning solution for cleaning remaining material other than the sample that has passed through the capture filter and the target material captured by the capture filter in the solution.
[0053] According to one embodiment, the above-mentioned dispensing unit may further include: a transfer chamber for obtaining an elution solution containing the target substance or a sample passing through the capture filter and the washing solution from the capture filter, and selectively transferring the elution solution containing the target substance to the collection chamber along the rotation direction of the rotating body, or transferring the sample passing through the capture filter and the washing solution to the waste chamber.
[0054] According to one embodiment, the channels in the first manual valve and the second manual valve are formed such that the area of some channels is wider than the area of the inlet of the first manual valve and the second manual valve, and the surfaces of the channels in the first manual valve and the second manual valve can be hydrophobically treated.
[0055] According to one embodiment, the above-mentioned capture filter may include a filter formed of glass fiber of a predetermined thickness, or a matrix containing a plurality of silica beads, and is configured to capture target substances in a sample using the matrix.
[0056] According to one embodiment, the rotating body rotates around at least one rotation axis and in a preset number of revolutions and rotation direction. The sample and the solution move in the microfluidic structure based on the rotational force generated by the rotation of the rotating body, and move in different directions in the microfluidic structure along the rotation direction of the rotating body.
[0057] According to one embodiment, the at least one microfluidic structure set at a preset distance can be arranged inside the rotating body in a circumferential direction with the rotation axis as the center.
[0058] According to one embodiment, a sample analysis apparatus may be provided, comprising: the aforementioned microfluidic device; a first drive unit for rotating the microfluidic device along the aforementioned rotation axis; a second drive unit for moving an injection mechanism, wherein the injection mechanism injects the sample and the solution into the microfluidic device along a preset drive axis; a supply unit for storing the sample and solution to be supplied to the injection mechanism, and selectively supplying the stored sample and solution to the injection mechanism; and a control unit for controlling the first drive unit, the second drive unit, and the supply unit, such that the sample and the solution in the microfluidic structure move along a preset path.
[0059] According to one embodiment, the first drive unit may include: a rotating component, which is configured to be fastened to the microfluidic device and is capable of rotating together with the microfluidic device along the rotation axis of the microfluidic device; and a spindle motor, which rotates the rotating component in a predetermined rotation direction and rotation speed based on a first control signal obtained by the control unit.
[0060] According to one embodiment, the second driving unit may include: at least one guide shaft, which is arranged at preset intervals; a first driving component, which is connected to one end of the driving shaft and fastened to the injection mechanism; a second driving component, which is connected to the other end of the driving shaft and transmits driving force to the driving shaft so that the driving shaft rotates at a predetermined angular interval; and a stepper motor for rotating the second driving component.
[0061] According to one embodiment, the second driving component may further include: a through hole for allowing the at least one guide shaft to pass through; and a ball screw component that contacts the surface formed in the through hole; and the second driving component moves along the at least one guide shaft when the ball screw component and the thread formed on the at least one guide shaft are in a tight fit.
[0062] According to one embodiment, the above-described sample analysis device may further include: a heating element formed at the bottom of the microfluidic device and cylindrically surrounding at least a portion of the first driving element in the direction outside the first driving element; and a linear guide for aligning the position of the heating element in the direction outside the first driving element.
[0063] According to one embodiment, the sample may include a target substance as the object of analysis, and the solution includes a cleaning solution for washing away residual substances other than the target substance, and an elution solution for separating the target substance.
[0064] According to one embodiment, the supply unit may include: a storage unit that separately stores the sample, the cleaning solution, and the elution solution; a supply channel connected to the storage unit and separately obtaining the sample, the cleaning solution, and the elution solution from the storage unit; a port valve that, under the control of the control unit, selects a channel from the supply channel to be connected to the injection mechanism; and an injection pump for moving the sample, the cleaning solution, and the elution solution from the storage unit to the injection mechanism.
[0065] According to one embodiment, the storage unit may include: a sample storage unit for storing the sample; a cleaning solution storage unit for storing the cleaning solution; and an elution solution storage unit for storing the elution solution. Furthermore, the sample storage unit, the cleaning solution storage unit, and the elution solution storage unit may also include a connection hole for communicating with the supply channel.
[0066] According to one embodiment, the above-described sample analysis apparatus may further include: a first housing, configured to house the first drive unit, the second drive unit, and the control unit inside the first housing; and a second housing, connected to the first housing in an openable and closable manner, thereby enabling selective exposure of the microfluidic device.
[0067] According to one embodiment, the above-mentioned sample analysis device may further include: a camera that acquires images of the microfluidic device at preset time intervals; and a network interface that transmits information about the images acquired from the camera to an external device connected to the sample analysis device.
[0068] Invention Effects
[0069] According to one embodiment of the present disclosure, multiple target substances can be effectively analyzed in a microfluidic device.
[0070] According to one embodiment, target substances in a large number of samples can be rapidly and accurately diagnosed in on-site diagnostics. Attached Figure Description
[0071] Figure 1a This is a diagram illustrating, schematically, the process of analyzing a sample using a microfluidic device according to an embodiment and a sample analysis apparatus using the microfluidic device described above.
[0072] Figure 1bThis is a diagram illustrating the structure of a microfluidic device having multiple microfluidic structures according to an embodiment.
[0073] Figure 1c This is a diagram illustrating the structure of a microfluidic structure according to an embodiment.
[0074] Figure 1d This is a diagram illustrating the movement of fluid in a microfluidic structure according to one embodiment.
[0075] Figure 2a This is a diagram illustrating, schematically, the process of analyzing a sample using a microfluidic device according to another embodiment and a sample analysis apparatus using the microfluidic device described above.
[0076] Figure 2b This is a diagram illustrating the structure of a microfluidic device having multiple microfluidic structures according to another embodiment.
[0077] Figure 2c This is a diagram illustrating the structure of a microfluidic structure according to another embodiment.
[0078] Figure 3a This is a diagram illustrating, schematically, the process of analyzing a sample using a microfluidic device according to another embodiment and a sample analysis apparatus using the microfluidic device described above.
[0079] Figure 3b This is a diagram illustrating the structure of a microfluidic device having multiple microfluidic structures according to another embodiment.
[0080] Figure 3c This is a diagram illustrating the structure of a microfluidic structure according to another embodiment.
[0081] Figure 3d This is a diagram illustrating the operation of a manual valve in a microfluidic structure according to one embodiment.
[0082] Figure 4 This is a diagram illustrating the structure of a sample analysis apparatus according to one embodiment.
[0083] Figure 5 This is a diagram illustrating the operation and structure of a sample analysis apparatus according to one embodiment.
[0084] Figure 6 This is a diagram illustrating the operation and structure of a sample analysis apparatus according to one embodiment.
[0085] Figure 7 This is a diagram illustrating the specifications of the components of a sample analysis apparatus in one embodiment.
[0086] Figure 8 It shows the basis Figures 1a to 1d The figure shows a microfluidic device and a sample analysis device using the microfluidic device to analyze a sample.
[0087] Figure 9 It shows the basis Figures 2a to 2c The figure shows a microfluidic device and a sample analysis device using the microfluidic device to analyze a sample.
[0088] Figure 10 It shows the basis Figures 3a to 3c The figure shows a microfluidic device and a sample analysis device using the microfluidic device to analyze a sample.
[0089] Figure 11 This is a block diagram illustrating a sample analysis apparatus according to one embodiment.
[0090] Figure 12 This is a block diagram illustrating a sample analysis apparatus according to another embodiment.
[0091] Figure 13 This is a block diagram showing a server connected to a sample analysis apparatus according to an embodiment.
[0092] Best Implementation of the Invention
[0093] According to one embodiment, a microfluidic device includes: a rotating body; and at least one microfluidic structure disposed at a predetermined distance inside the rotating body, the microfluidic structure including: a pretreatment section configured to share a solution injected through a solution injection port with other adjacent microfluidic structures via a shared channel, and to perform a pretreatment process on a sample injected through a sample injection port and the solution; a storage section located radially outward from the pretreatment section inside the rotating body, separating and storing the sample and solution pretreated by the pretreatment section along the rotation direction of the rotating body; and a detection section configured to detect a target substance in the pretreated sample dispensed from the storage section.
[0094] According to one embodiment, a sample analysis apparatus is provided, comprising: the aforementioned microfluidic device; a first drive unit for rotating the microfluidic device along the rotation axis; a second drive unit for moving an injection mechanism, wherein the injection mechanism injects the sample and the solution into the microfluidic device along a preset drive axis; a supply unit for storing the sample and solution to be supplied to the injection mechanism and selectively supplying the stored sample and solution to the injection mechanism; and a control unit for controlling the first drive unit, the second drive unit, and the supply unit, such that the sample and the solution in the microfluidic structure move along a preset path. Detailed Implementation
[0095] The following provides a brief explanation of the terminology used in this specification and a detailed description of this disclosure.
[0096] The terms used in this disclosure are selected as far as possible from commonly used terms that are widely used today, while taking into account the function of this disclosure. However, they may vary depending on the intent or precedent of those skilled in the art, the emergence of new technologies, etc. In addition, in certain cases, there are terms arbitrarily chosen by the applicant, in which case their meanings will be described in detail in the summary of the invention. Therefore, the terms used in this disclosure should be defined based on the meaning of the terms and the overall content of this disclosure, and not merely on the names of the terms.
[0097] Throughout this specification, when a component is referred to as "including" another component, unless otherwise stated, it means that other components may be further included, rather than excluding other components. Additionally, terms such as "section" and "module" used in this specification refer to a unit that performs at least one function or operation, which may be implemented as hardware or software, or a combination of hardware and software.
[0098] Hereinafter, embodiments of the present disclosure will be described in detail with reference to the accompanying drawings, so that those skilled in the art can readily implement the embodiments of the present invention. However, the present disclosure can be implemented in various different forms and is not limited to the embodiments described herein. Furthermore, for the sake of clear description of the present disclosure in the drawings, parts unrelated to the description have been omitted, and similar reference numerals have been used for similar parts throughout the specification.
[0099] Figure 1a This is a diagram illustrating, schematically, the process of analyzing a sample using a microfluidic device according to an embodiment and a sample analysis apparatus using the microfluidic device described above.
[0100] According to one embodiment, a microfluidic device 1000 may include: a rotatable rotating body 122a, a chamber within the rotating body capable of containing a sample and a solution, and microfluidic structures 102a and 104a providing multiple channels for movement of the sample and solution. For example, the microfluidic device 1000 may include multiple microfluidic structures 102a and 104a arranged at predetermined intervals within the rotating body 122a. The microfluidic structures may be arranged circumferentially within the rotating body 122a with at least one rotation axis 113a as a center, and the sample and solution within the microfluidic structures can be moved based on the rotational force generated by the rotation of the rotating body and the rotation direction of the rotating body.
[0101] According to one embodiment, the microfluidic structures 102a and 104a may include: a pretreatment unit 112a, which shares a solution injected through a solution injection port with other adjacent microfluidic structures via a shared channel, and performs a pretreatment process on the sample injected through a sample injection port and the solution; a storage unit 114a, located radially outward from the pretreatment unit inside the rotating body 122a, separating and storing the sample and solution pretreated by the pretreatment unit along the rotation direction of the rotating body 122a; and a detection unit 116a, which detects target substances in the pretreated sample dispensed from the storage unit.
[0102] See below Figures 1b to 1c A more detailed description of the structure of microfluidic structures will be provided.
[0103] The microfluidic device 1000 includes at least one of the aforementioned microfluidic structures and can rotate with a predetermined rotation axis 113a to move the sample and solution within the microfluidic structure. The microfluidic device 1000 according to this disclosure can be mounted on a sample analysis device 2000 and, under the control of the sample analysis device 2000, can be used in an automated sample analysis process.
[0104] According to one embodiment, the sample analysis device 2000 can extract samples and solutions from a storage section 134 pre-stored with samples and solutions. The sample analysis device 2000 can inject the samples and solutions extracted from the storage section 134 into the microfluidic device 1000 by controlling the injection port 132 for supplying samples and solutions to the microfluidic device 1000. The sample analysis device 2000 can rotate the microfluidic device 1000 containing the injected samples or solutions at a preset number of rotations and rotation direction to move the samples or solutions within the microfluidic device. That is, the sample analysis device 2000 can detect target substances contained in various samples by moving the samples within the microfluidic device 1000, which contains at least one microfluidic structure. According to one embodiment, the target substance can be a genome containing genetic information. Furthermore, unlike conventional sample analysis devices, the sample analysis device 2000 automatically supplies pre-stored samples and solutions to the microfluidic device, thereby enabling rapid and accurate analysis of samples injected into the microfluidic device.
[0105] Furthermore, according to one embodiment of this disclosure, the microfluidic device and the sample analysis apparatus controlling the microfluidic device can move within the microfluidic device an elution solution for separating a sample and a target substance in the sample, and a washing solution for washing substances other than the target substance captured by the capture filter. Furthermore, according to one embodiment, a reaction solution for inducing an amplification reaction of the target substance in the sample can be pre-freeze-dried in the collection chamber or reaction chamber of the microfluidic device. According to one embodiment, the reaction solution may include a reaction solution for loop-mediated isothermal amplification (LAMP) or polymerase chain reaction (PCR) amplification of the target substance.
[0106] Figure 1b This is a diagram illustrating the structure of a microfluidic device having multiple microfluidic structures according to an embodiment.
[0107] According to one embodiment, the microfluidic device 1000 may include a plurality of microfluidic structures arranged circumferentially around a rotation axis. According to one embodiment, the microfluidic structures 210a may be arranged inside the rotating body 218a at a predetermined interval.
[0108] According to one embodiment, microfluidic structures can share samples or solutions stored in chambers within adjacent microfluidic structures via at least one shared channel. For example, microfluidic structure 210a can share samples or solutions stored in chambers within microfluidic structures adjacent to it on both sides. Microfluidic structures adjacent to microfluidic structure 210a can be connected to other microfluidic structures in the same manner. According to one embodiment, all microfluidic structures within rotating body 218a can be connected to each other via at least one shared channel.
[0109] The microfluidic structure 210a may include: a pretreatment section 212a; a storage section 214a located radially outward from the pretreatment section within the rotating body 128a; and a detection section 216a located radially outward from the pretreatment section within the rotating body 218a. The microfluidic structure 210a can dispense samples or solutions injected through an injection port, detect target substances in the dispensed samples, and store substances other than the target substances in the samples, as well as the solution.
[0110] According to one embodiment, the microfluidic structure may include 10 microfluidic structures 210a. However, it can be varied, and is not limited to, depending on the type of sample and solution to be analyzed, the analytical method, the size of the rotating body, the size of the microfluidic structure, etc.
[0111] Figure 1cThis is a diagram illustrating the structure of a microfluidic structure according to an embodiment.
[0112] According to one embodiment, the microfluidic structure 310a may include: a pretreatment section 320a; a storage section 340a, located radially outward from the pretreatment section within the rotating body, which separates and stores the sample and solution pretreated by the pretreatment section along the rotation direction of the rotating body; and a detection section 360a, which detects target substances in the pretreated sample dispensed from the storage section. The microfluidic structure 310a can move the sample injected through the sample injection port and the solution injected through the solution injection port to the storage section, and move a portion of the sample and solution moved to the storage section to the detection section.
[0113] According to one embodiment, the pretreatment unit 320a may include: a sample chamber 324a for containing a sample injected through a sample injection port; a solution chamber 326a for containing a solution injected through a solution injection port; and a capture filter 328a for capturing target substances from the injected sample. According to another embodiment, the pretreatment unit 320a may further include: a first manual valve 331a for connecting the sample chamber 324a and the capture filter 328a; and a second manual valve 334a for connecting the solution chamber 326a and the capture filter 328a.
[0114] According to one embodiment, the pretreatment unit 320a can contain samples and solutions, and at least one of the contained samples or solutions can be shared with other adjacent microfluidic structures via a shared channel. Figure 1c As shown, the shared channel 321a can be formed in a portion of the solution chamber 326a, but when a solution injection port is formed in the solution chamber 326a, the shared channel 321a can also be connected to one end of the solution injection port. According to another embodiment, a shared channel different from the shared channel connected to the solution chamber described above can also be formed at one end of the sample chamber 324a or at one end of the sample injection port. According to one embodiment, the shared channel can be formed only on the solution chamber, or it can be formed on at least one of the solution chamber or the sample chamber.
[0115] For samples and solutions contained in the pretreatment section 320a of the microfluidic structure 310a, manual valves connected to one end of the sample chamber 324a and the solution chamber 326a can prevent them from moving to the capture filter until the samples and solutions are shared with the individual sample chambers and solution chambers in other microfluidic structures.
[0116] The sample chamber 324a can contain a solution injected through the first sample injection port 323a. According to one embodiment, the first sample injection port 323a, formed at one end of the sample chamber, can be connected to a second sample injection port 319a via an injection port channel 322a, and the sample chamber 324a can also receive a solution injected through the second sample injection port. Furthermore, according to one embodiment, when a shared channel is formed on the sample chamber 324a, the shared channel formed on the sample chamber can also be connected to at least one of the first sample injection port 323a, the injection port channel 322a, or the second sample injection port 319a.
[0117] According to one embodiment, when the solution chamber 326a receives a solution through the solution injection port, the solution injection port may not be exposed to the surface of the rotating body on which the microfluidic structure 310a is formed. For example, the solution injection port connecting to the solution chamber 326a may be connected to the solution chamber at a predetermined depth from the surface of the rotating body. The solution injection port may be formed at one end of the solution chamber or at least a portion of a shared channel connected to the solution chamber. As described above, a shared channel 321a may be connected to one side of the solution chamber 326a.
[0118] Solution chamber 326a can be connected to capture filter 328a via a second manual valve. For a sample contained in solution chamber 326a, the second manual valve can prevent it from moving to the capture filter until the solution fills the solution chamber within the other microfluidic structures.
[0119] According to one embodiment, the shared channel 321a connected to at least one of the sample chamber 324a or solution chamber 326a may be formed in a zigzag shape, but is not limited thereto, and may also be formed in other shapes that allow the sample and solution to be shared to the respective sample chambers and solution chambers in other microfluidic structures.
[0120] The first manual valve 331a may include: a first channel 332a having the same area as the area passing through the first manual valve inlet; and at least one second channel 333a having a wider area than the area passing through the first manual valve inlet and formed between the first channels. According to one embodiment, the surface within the first manual valve 331a may be hydrophobically treated.
[0121] More specifically, due to the area difference between the first channel 332a and the second channel 333a within the manual valve, the first manual valve 331a allows the interfaces of the fluids passing through the first channel 332a and the second channel 333a to have different radii. The capillary force generated by the difference in radii between the two interfaces can control the sample in the sample chamber, preventing it from moving to the capture filter. Furthermore, in addition to utilizing the area difference between the first and second channels within the first manual valve, the first manual valve 331a can also ensure greater resistance by making at least a portion of its area hydrophobic, thus preventing the sample in the sample chamber from moving to the capture filter.
[0122] At least a portion of the channel within the first manual valve 331a is characterized by a larger area than the inlet through the first manual valve, and the resistance generated by the hydrophobic material treated on the internal surface can be configured such that the sample in the sample chamber 324a can be moved to the capture filter 28a by a first rotational force generated by the rotation of the rotating body.
[0123] The second manual valve 334a may include: a third channel 335a having the same area as the area through which the second manual valve inlet passes; and at least one fourth channel 336a having a wider area than the area through which the second manual valve inlet passes and formed between the third channels. According to one embodiment, the surface within the second manual valve 334a may be hydrophobically treated.
[0124] More specifically, due to the area difference between the third channel 335a and the fourth channel 336a within the manual valve, the second manual valve 334a allows the interfaces between the fluids passing through the third and fourth channels to have different radii. The capillary force generated by the difference in radii between the two interfaces can control the solution contained in the solution chamber, preventing it from moving to the capture filter. Furthermore, in addition to utilizing the area difference between the third channel 335a and the fourth channel 336a within the second manual valve, the second manual valve 334a can also ensure greater resistance by making at least a portion of its area hydrophobic, thus preventing the solution in the solution chamber from moving to the capture filter.
[0125] At least a portion of the passage within the second manual valve 334a is characterized by having a larger area than the inlet through the second manual valve, and the resistance generated by the hydrophobic material treated on the internal surface can be configured such that the solution in the solution chamber 326a can be moved to the capture filter 328a by the second rotational force generated by the rotation of the rotating body.
[0126] The capture filter 328a can capture target substances from the injected solution. For example, the capture filter 328a can be formed as glass fiber with a predetermined thickness. Furthermore, according to one embodiment, the capture filter 328a can be a glass fiber filter with a predetermined thickness or a matrix of silica beads containing multiple silica beads. The capture filter 328a can capture target substances in a sample using the silica bead matrix.
[0127] The storage unit 340a may include a collection chamber 344a and a first waste chamber 342a. According to another embodiment, the collection chamber 344a may further include a transfer chamber 346a. For example, the storage unit 340a is located radially outward from the pretreatment unit 320a within the rotating body, and along the rotation direction of the rotating body, it separates and stores samples and solutions pretreated by the aforementioned pretreatment unit.
[0128] For example, the storage unit 340a can selectively store samples and solutions into the collection chamber 344a or the first waste chamber 342a based on the rotational force and rotational direction of the rotating body containing the microfluidic structure 310a.
[0129] The collection chamber 344a can store the eluent containing the target substance captured by the capture filter. For example, the collection chamber 344a can be based on a first rotational direction of the rotating body where the microfluidic structure 310a is located (e.g., when...). Figure 1a (The rotating body shown rotates clockwise with its rotation axis as the center) to obtain an eluent containing the target substance captured by the capture filter. More specifically, as the rotating body rotates along the first rotation direction, the eluent containing the target substance captured in the capture filter can move towards... Figure 1c The transfer chamber 346a shown is tilted and moved to the right to store the target material in the collection chamber 344a. According to another embodiment, in addition to the elution solution containing the target material, the collection chamber 344a may also include a pore for passing a reaction solution pre-freeze-dried for the amplification reaction of the target material through a solution chamber. According to one embodiment, the reaction solution may include a LAMP cocktail solution for reacting with the target material in the sample or a reaction solution for PCR amplification.
[0130] According to one embodiment, one end of the collection chamber 344a can be connected to the transfer chamber 346a, and the other end of the collection chamber 344a can be connected to the siphon channel 362a. The elution solution containing the target substance in the collection chamber 344a can fill a portion of the channel of the siphon channel 362a. More specifically, the elution solution containing the target substance stored in the collection chamber 344a can fill a portion of the channel 361a located within the siphon channel corresponding to the height of the solution filled in the collection chamber 344a. As the rotating body comes to a stop after a predetermined time, the elution solution containing the target substance filled into the portion of the channel 361a within the siphon channel can move to the distribution chamber 364a based on the capillary force acting on the portion of the channel 361a.
[0131] Furthermore, according to one embodiment, when a predetermined solution is injected into the collection chamber 344a, and the injected predetermined solution fills at least a portion of the channel portion 361a in the siphon channel, the rotating body provided with the microfluidic structure 310a can, after a preset resting time, perform an action of alternating rotation and shaking of the collection chamber along a first direction or a second direction. By shaking the collection chamber 344a according to this disclosure, a reaction (e.g., PCR or LAMP amplification reaction) can be induced between the elution solution containing the target substance stored in the collection chamber and the reaction solution pre-freeze-dried in the collection chamber.
[0132] Once the elution solution containing the target substance in collection chamber 344a begins to move into distribution chamber 364a, the rotating body can rotate at high speed again. (See reference...) Figure 1d A more detailed explanation of the motion of the rotating bodies associated with the siphon channel is provided.
[0133] The first waste chamber 342a may be located adjacent to the collection chamber 344a and contain a cleaning solution for rinsing substances other than the target material captured by the capture filter in the sample and solution, excluding the target material captured by the capture filter 328a. For example, the first waste chamber 342a may contain residual material from the capture filter that was not captured by the capture filter, as well as the cleaning solution contained in the solution chamber, based on the second rotation direction of the rotating body of the fixed microfluidic structure 310a. More specifically, as the rotating body rotates along the second rotation direction, residual material from the sample that was not captured by the capture filter, and a portion of the solution contained in the solution chamber, may move towards... Figure 1c The transfer chamber 346a shown is tilted and moved to the left and stored in the first waste chamber 342a.
[0134] The transfer chamber 346a can be configured such that one upper end is connected to the capture filter 328a, one lower end is connected to the collection chamber 344a, and the other lower end is connected to the waste chamber 342a. The transfer chamber 346a can connect the capture filter 328a to the collection chamber 344a and the first waste chamber 342a respectively, and selectively transfer a portion of the sample or solution contained in the transfer chamber to the collection chamber 344a or the first waste chamber 342a along the rotation direction of the rotating body.
[0135] According to one embodiment, the transfer chamber 346a can obtain an elution solution containing the target substance or a sample passing through the capture filter and the washing solution from the capture filter, and selectively transfer the elution solution containing the target substance to the collection chamber 344a along the rotation direction of the rotating body, or transfer the sample passing through the capture filter and the washing solution to the first waste chamber 342a.
[0136] The detection unit 360a may include: a siphon channel 362a, one end of which is connected to a collection chamber 344a; a distribution unit 363a, which is connected to the other end of the siphon channel 362a and includes a plurality of distribution chambers 364a and 365a, such that a predetermined amount of elution solution containing the target substance from the collection chamber 344a is distributed to the plurality of distribution chambers 364a and 365a; and a reaction unit 366a, including a reaction chamber 367a, which is used to obtain the elution solution containing the target substance provided by the distribution chamber and to provide primers and reaction solutions for detecting the target substance.
[0137] According to another embodiment, in addition to the siphon channel 362a, the distribution section 363a, and the reaction section 366a, the detection section 360a may also include a second waste chamber 368a. According to another embodiment, in addition to the siphon channel 362a, the distribution section 363a, the reaction section 366a, and the second waste chamber 368a, the detection section 360a may also include a wax storage section 370a.
[0138] The detection unit 360a can obtain an elution solution containing the target substance from the collection chamber 344a of the storage unit 340a through the siphon channel 362a, and distribute the elution solution containing the obtained target substance into the distribution chamber in a certain preset amount. Based on the rotational force of the rotating body, the elution solution containing the target substance distributed in the distribution chamber is injected into the reaction chamber 367a, thereby inducing a biological or chemical reaction for the target substance.
[0139] The siphon channel 362a can move the elution solution or cocktail mixture containing the target substance in the collection chamber to the distribution chamber 365a of the distribution section 363a based on the capillary force provided by the siphon channel and the rotational force generated by the rotating body in which the microfluidic structure 310a is located. For example, as described above, the solution stored in the collection chamber 344a can fill at least a portion of the channel portion 361a in the siphon channel. As the rotating body comes to rest after a predetermined time, the solution filled into at least a portion of the channel portion 361a in the siphon channel can move to the distribution chamber 364a based on the capillary force of the siphon channel acting in the aforementioned portion of the channel portion 361a toward the distribution chamber 364a. Once the solution stored in the collection chamber 344a begins to move toward the distribution chambers 364a and 365a, the rotation number of the rotating body can be increased again.
[0140] The dispensing unit 363a can dispense the elution solution containing the target substance obtained from the collection chamber 344a through the path siphon channel 362a into a solution dispensing chamber capable of accommodating a predetermined volume. According to one embodiment, after the rotating body remains stationary for a predetermined time, the solution filling at least a portion of the channel portion 361a within the siphon channel 362a begins to move towards the dispensing chambers 364a and 365a. The rotating body can then rotate at high speed along a first direction, thereby sequentially dispensing the elution solution containing the target substance through the path siphon channel into the dispensing chambers adjacent to the siphon channel.
[0141] According to one embodiment, the dispensing unit 363a may further include a waste liquid chamber 364a for storing the remaining solution after it has been dispensed to the dispensing chamber 365a. More specifically, based on the rotation of a rotating body rotating along a first rotation direction, the elution solution containing the target substance in the siphon channel can be sequentially moved from the dispensing chamber adjacent to the siphon channel to the waste liquid chamber 364a.
[0142] When the elution solution containing the target substance is dispensed into the dispensing chamber 365a, oil generated from the wax storage section 370a can be injected into the upper part of the dispensing chamber to prevent the evaporation of the elution solution or mixture. According to one embodiment, after the elution solution containing the target substance is dispensed into the dispensing chamber, heat above a preset temperature can be provided to the wax storage section 370a, and the oil generated by the liquefaction of the wax in the wax storage section 370a by the provided heat can be injected into the dispensing chambers 364a and 365a. Since the dispensing chamber is currently filled with the elution solution containing the target substance, the oil injected into the dispensing chamber can cover the upper part of the elution solution that has pre-filled the dispensing chamber.
[0143] According to the sample analysis apparatus 2000 of this disclosure, an elution solution containing a quantitative amount of target substance can be injected into the reaction chamber 367a using a wax storage section 370a, thereby inducing an accurate biological or chemical amplification reaction for the target substance.
[0144] The reaction section 366a is located radially further outward on the rotating body than the dispensing chambers 364a and 365a, thereby allowing the elution solution or mixture containing the target substance to be obtained from the dispensing chamber. According to one embodiment, the reaction section 366a may include at least one reaction chamber, inside which primers and reaction solutions (e.g., reaction solutions required for PCR or LAMP amplification) for detecting the target substance may be pre-freeze-dried. More specifically, in the reaction chamber 367a, primers for detecting the target substance may be located on the surface of the reaction chamber in a freeze-dried (e.g., freezing-dry) state. Furthermore, as a mixture for the amplification reaction, a reaction solution containing a LAMP cocktail mixture or a reaction solution for PCR amplification may be freeze-dried on the inner surface of the reaction chamber. The reaction section 366a can induce an amplification reaction for the target substance by reacting the pre-freeze-dried primers and reaction solutions in the reaction chamber with the elution solution containing the target substance stored in the dispensing chamber.
[0145] The second waste chamber 368a can obtain the elution solution containing the target substance from the waste liquid chamber 364a, which is used to store the remaining elution solution containing the target substance after it has been allocated to the allocation chamber. According to another embodiment, when the elution solution containing the target substance begins to move from the collection chamber, the second waste chamber 368a can also obtain the remaining elution solution after it has been allocated to the allocation chamber 365a.
[0146] As described above, the microfluidic structure 310a can induce an amplification reaction for the target substance by moving a sample containing the target substance and an elution solution for separating the target substance within the sample inside the microfluidic structure 310a. In the reaction chamber or collection chamber within the microfluidic structure 310a according to one embodiment, a reaction solution for LAMP amplification or PCR amplification of the target substance can be pre-freeze-dried. In this case, the microfluidic structure can be used to induce LAMP amplification, PCR amplification, etc., for the amplification reaction of the target substance, but is not limited thereto. That is, the sample analysis device 2000 can effectively perform the extraction and amplification reactions of various samples by using the microfluidic device 1000 with the microfluidic structure 310a arranged at a preset interval.
[0147] Figure 1d This is a diagram illustrating the movement of fluid in a microfluidic structure according to one embodiment.
[0148] The microfluidic structure 410a may include: a first manual valve 409a for connecting the sample chamber 424a and the capture filter 428a; and a second manual valve 420a for connecting the solution chamber 426a and the capture filter 428a. For example, the first manual valve 409a may include: a first channel 412a having the same area as the area through the inlet of the first manual valve; and a second channel 414a having a wider area than the area through the inlet of the first manual valve and formed between the first channels 412a.
[0149] Furthermore, the second manual valve 420a may include: a third channel 421a having the same area as the area through the inlet of the second manual valve; and at least one fourth channel 422a having a wider area than the area through the inlet of the second manual valve and formed at a predetermined interval between the third channels. Figure 1d The operation of the second manual valve is explained with the fourth channel in the second manual valve 420a closest to the solution chamber 426a as the center.
[0150] Despite Figure 1d Not shown in the image, such as Figure 1b As shown, the solution chamber 426a within the microfluidic structure 410a can be located close to the rotation axis of the rotating body on which the microfluidic structure 410a is mounted. Therefore, when the rotating body rotates about the rotation axis, the rotational force generated by the rotation can be generated along the direction from the solution chamber to the second manual valve.
[0151] Furthermore, since the inlet area of the second manual valve 420a is narrower than that of the solution chamber 426a, the solution in the solution chamber 426a can move to the inlet of the second manual valve 420a due to the capillary pressure difference. The solution that has moved to the inlet of the second manual valve 420a can then pass through a portion of the third channel 421a, which has the same area as the inlet of the second manual valve 420a, and reach the inlet of the fourth channel 422a, which has a wider area than the third channel. At this time, because the fourth channel is wider than the third channel, a difference will occur between the capillary force 402a corresponding to the interface of the solution formed along the direction of the third channel and the capillary force 404a corresponding to the interface of the solution formed along the direction of the fourth channel.
[0152] Because the fourth channel 422a has a larger radius interface than the third channel 421a, the capillary force 404a corresponding to the interface of the fourth channel can be formed to be greater than the capillary force 402a corresponding to the interface of the third channel. Therefore, the substantial capillary force generated by the fact that a portion of the channel within the second manual valve is wider than the inlet area of the second manual valve can create resistance, preventing the solution in the solution chamber 426a from moving into the capture filter 428a.
[0153] Therefore, the solution stored in the solution chamber 426a can be moved to the capture filter 428a based on the rotational force generated by the rotation of the rotating body and the resistance provided by the second manual valve 420a. According to one embodiment, the second manual valve 420a can move the solution injected from the solution chamber 426a to the capture filter 428a based on a second rotational force generated by the rotating body. According to one embodiment, the second rotational force can be configured to be smaller or the same as the resistance provided by the second manual valve.
[0154] Similar to the operation of the second manual valve described above, the first manual valve 409a can also utilize the difference in capillary pressure generated by the area difference between the first and second channels within the first manual valve to restrict the movement of the sample stored in the sample chamber 424a to the capture filter 428a. According to one embodiment, the first manual valve 409a can move the sample injected from the sample chamber 424a to the capture filter 428a based on a first rotational force generated by the rotating body. Furthermore, as described above, since at least a portion of the internal surfaces of the first and second manual valves are hydrophobically treated, additional resistance to the sample or solution is provided.
[0155] Samples and solutions provided from sample chamber 424a and solution chamber 426a, respectively, can be stored in collection chamber 444a and first waste chamber 442a after path transfer chamber 429a. As described above, collection chamber 444a can store an elution solution containing target material captured by a capture filter based on the rotation direction of the rotating body where the microfluidic structure 410a is located. According to another embodiment, a reaction solution (e.g., a LAMP cocktail mixture) for the amplification reaction of the target material can be freeze-dried in collection chamber 424a.
[0156] A siphon channel 462a connected to one end of the collection chamber 444a can move the solution or mixture stored in the collection chamber 444a (located radially inward on the rotating body) to the distribution chambers 464a and 465a (located radially outward) in the distribution section 463a. The siphon channel 462a can move the solution based on the capillary force provided by the siphon channel and the rotational force generated by the rotating body where the aforementioned microfluidic structure 410a is located.
[0157] According to one embodiment, when an elution solution containing the target substance is injected into a collection chamber 444a, the elution solution injected into the collection chamber 444a can move to at least a portion of the channel portion 461a in the siphon channel. According to one embodiment, the elution solution containing the target substance can fill a portion of the channel portion 461a located in the siphon channel 462a corresponding to the height to which the solution is filled in the collection chamber 444a.
[0158] As the rotating body comes to a standstill after a preset time, the solution filling a portion of the channel section 461a within the siphon channel can begin to move towards the distribution chambers 464a and 465a through the outlet within the siphon channel. For example, when the rotating body has been stationary for the preset time, the capillary force acting on at least a portion of the channel section 461a within the siphon channel is greater than the rotational force acting on the solution located in the aforementioned portion of the channel section 461a, thereby allowing the solution in the siphon channel 461a to begin moving towards the distribution chamber. Once the solution in the siphon channel 461a begins to move towards the distribution chamber, the rotating body can rotate at a fifth rotational speed (e.g., 5000 rpm).
[0159] The elution solution containing the target substance, dispensed into at least one dispensing chamber 464a, 465a within the dispensing unit 463a, can be moved to the reaction chamber 467a within the reaction unit 466a via channels connected to the respective dispensing chambers. More specifically, the reaction chamber 467a may contain pre-freeze-dried primers and reaction solutions for amplifying the target substance. Furthermore, the reaction chamber 467a may have resistance 434a generated by the air pressure of the reaction chamber itself, excluding the primers or pre-stored reaction solutions. Therefore, in order to move the elution solution containing the target substance stored in the dispensing chambers 464a, 465a to the reaction chamber 467a, the rotational force needs to be greater than the resistance 434a generated by the air pressure of the reaction chamber itself. According to one embodiment, the elution solution containing the target substance dispensed into the dispensing chambers 464a and 465a can be moved into the reaction chamber 467a within the reaction section 466a based on the rotational force generated by the rotation of the rotating body at a sixth rotational speed (e.g., 5000 rpm or more).
[0160] Figure 2aThis is a diagram illustrating, schematically, the process of analyzing a sample using a microfluidic device according to another embodiment and a sample analysis apparatus using the microfluidic device described above.
[0161] According to one embodiment, the microfluidic device 1000 may include: a rotatable rotating body 152b; at least one microfluidic structure 102b, 104b disposed at a predetermined distance within the rotating body 152b; and a waste chamber 124b located radially outward within the rotating body compared to the at least one microfluidic structure, and connected to the at least one microfluidic structure. More specifically, the rotating body 152b may include a region for forming the microfluidic structure, which is distinct from the space within the rotating body 152b where the waste chamber 124b is formed.
[0162] According to one embodiment, the microfluidic device 1000 may include microfluidic structures arranged at predetermined intervals radially inside the region where the waste chamber 124b is formed. These microfluidic structures may be arranged circumferentially within the rotating body 152b, centered on at least one rotation axis 113b. Furthermore, the microfluidic structures can move samples and solutions within them based on the rotational force and direction of the rotating body 152b.
[0163] According to one embodiment, microfluidic structures 102b and 104b may include: a solution chamber 123b for containing a solution injected through a solution injection port (not shown) and sharing the contained solution with other adjacent microfluidic structures via a first shared channel 130b; a sample chamber 128b, formed to be located radially outward from the solution chamber within the interior 152b of the rotating body and containing a solution injected through an externally open vent 129b; and a siphon channel 131b, formed to be connected at one end to the sample chamber and at the other end to the waste chamber, thereby transferring the sample and the solution to the waste chamber 124b.
[0164] According to one embodiment, the microfluidic structures 102b and 104b may further include a manual valve 125b, one end of which is connected to the solution chamber 123b and provides the solution contained in the solution chamber 123b to the sample chamber 128b based on the rotational force generated by the rotating body.
[0165] See below Figures 2b to 2c right Figure 2a The structure of the microfluidic structure disclosed herein will be described in more detail.
[0166] The microfluidic device 1000 includes at least one of the aforementioned microfluidic structures and can rotate and move samples and solutions within the microfluidic structure along a predetermined rotation axis 113b. The microfluidic device 1000 according to this disclosure can be mounted on a sample analysis device 2000 and used for automated sample analysis processes under the control of the sample analysis device 2000.
[0167] According to one embodiment, the sample analysis device 2000 can pre-store a sample containing a target substance corresponding to the antigen to be detected, a washing solution, an elution solution, and a reaction solution for detecting the target antigen in a storage unit 134. The sample analysis device 2000 can extract the sample, washing solution, elution solution, and reaction solution stored in the storage unit 134 from the storage unit 134, and inject the extracted sample, washing solution, elution solution, and reaction solution into a chamber within the microfluidic device 1000 through the injection port 137.
[0168] The sample analysis device 2000 can rotate the microfluidic device 1000, which is filled with a sample or solution, at a preset number of revolutions and in a preset direction, thereby controlling the movement of the sample or solution in the microfluidic device.
[0169] That is, the sample analysis device 2000 can detect target substances contained in various samples by moving samples and solutions in a microfluidic device 1000 containing at least one microfluidic structure.
[0170] According to one embodiment, the target substance may correspond to a target nucleic acid, target antigen, target RNA, or target DNA that carries genetic information. Unlike conventional sample analysis devices, the sample analysis device 2000 rapidly and accurately detects the target substance in the solution injected into the microfluidic device by automatically supplying pre-stored samples and solutions to the microfluidic device.
[0171] Furthermore, according to one embodiment of this disclosure, the microfluidic device and the sample analysis apparatus for controlling the microfluidic device can also move a sample containing a target antigen, or a solution containing an antibody or enzyme, into the interior of the microfluidic device for use in an enzyme-linked immunosorbent assay (ELISa). However, it is not limited to this; it can also be used for other chemical or biological tests by moving a sample or solution into the interior of the microfluidic device to detect target substances in the sample and cause them to react.
[0172] Figure 2b This is a diagram illustrating the structure of a microfluidic device having multiple microfluidic structures according to another embodiment.
[0173] According to one embodiment, the microfluidic device 1000 may include a plurality of microfluidic structures 210b arranged circumferentially with a rotation axis as the center. According to one embodiment, the microfluidic structures 210b may be arranged inside the rotating body 220b at a predetermined interval.
[0174] According to one embodiment, microfluidic structures can share samples or solutions stored in chambers within adjacent microfluidic structures via at least one shared channel 218b. For example, microfluidic structure 210b can share samples or solutions stored in chambers within microfluidic structures adjacent to it on both sides. Microfluidic structures adjacent to microfluidic structure 210b can be connected to other microfluidic structures in the same manner. According to one embodiment, all microfluidic structures within the rotating body 220b can also be connected to each other via at least one shared channel 218b.
[0175] According to one embodiment, the solution chamber within the microfluidic structure 210b can be connected to solution chambers within other microfluidic structures via a shared channel 218b. A passive valve can be connected to one end of the solution chamber within each microfluidic structure 210b. Therefore, the solution stored in the solution chamber 212b of this disclosure can be restricted from moving to the sample chamber connected to the other end of the aforementioned passive valve until the solution chambers within other microfluidic structures are filled with solution.
[0176] The microfluidic structure 210b may be located radially more inward than the waste chamber 222b formed by separating it from the edge portion of the rotating body 220b at a predetermined interval. As described above, the microfluidic structure 210b may include: a solution chamber 212b that contains a reaction solution for detecting a washing solution or a target substance (e.g., a solution containing a second antibody with an attached chromogenic enzyme, a solution containing a chromogenic substrate, a washing solution, etc.) through a solution injection port; a sample chamber 214b located radially more outward than the solution chamber; and a siphon channel 216b connecting the sample chamber 214b and the waste chamber 222b.
[0177] According to one embodiment, the microfluidic device 1000 may include 30 microfluidic structures. However, it is not limited to this and can be varied depending on the type of sample and solution to be analyzed, the analytical method, the size of the rotating body, the size of the microfluidic structures, etc.
[0178] Figure 2c This is a diagram illustrating the structure of a microfluidic structure according to another embodiment.
[0179] According to one embodiment, the microfluidic structure 310b may include: a solution chamber 332b for containing a solution injected through a solution injection port, and sharing the contained solution with solution chambers in adjacent microfluidic structures via a first shared channel 338b; a sample chamber 334b formed radially outward of the solution chamber 332b within the rotating body, and containing a solution injected through an externally open vent 346b; a manual valve 341b, one end of which is connected to the solution chamber 332b and the other end of which is connected to the sample chamber 334b; and a siphon channel 336b for transferring a sample or solution in the sample chamber 334b to a waste chamber 348b.
[0180] like Figure 2a As shown, microfluidic structures 310b can be disposed on the rotating body at predetermined intervals, and each siphon channel 336b of the microfluidic structures disposed on the rotating body can be connected to a waste chamber 348b located on the rotating body. Furthermore, the waste chamber 348b can be formed from the edge of the rotating body 352b constituting the microfluidic device at predetermined intervals. According to one embodiment, the rotating body 352b can be formed as a disc shape using PMMA material.
[0181] One end of the solution chamber 332b can be connected to a shared channel, and the other end of the solution chamber can be connected to a manual valve 341b. According to one embodiment, the solution chamber 332b can contain a washing solution for washing antigens not captured by antibodies pre-coated in the sample chamber, a solution containing antibodies attached with a chromogenic enzyme for an enzyme-linked immunosorbent assay (ELISA), and a solution containing a chromogenic substrate.
[0182] The manual valve 341b may include: a first channel 342b having an area similar to that of the inlet of the manual valve 341b; and a second channel 343b having a wider area than the area of the inlet of the manual valve and formed on a portion of the first channel. According to another embodiment, in addition to the second channel 343b formed on a portion of the first channel with an area wider than the area of the inlet of the manual valve, the manual valve 341b may also include: a third channel 344b formed on a portion of the first channel with an area wider than the area of the inlet of the manual valve and smaller than the area of the second channel. However, according to one embodiment, the third channel may also be formed with an area similar to that of the first channel. According to one embodiment, the surface within the manual valve 341b may be hydrophobically treated.
[0183] For example, the manual valve 341b can make the interface radius of the fluid passing through the first channel 342b and the second channel 343b different by the area difference between the first channel 342b and the second channel 343b. The capillary force generated by the difference in the radii of the two interfaces can restrict the solution in the solution chamber 332b from moving to the sample chamber 334b.
[0184] Furthermore, in addition to utilizing the area difference between the first channel 342b and the second channel 343b within the manual valve 341b, the manual valve 341b can also ensure greater resistance by hydrophobically treating at least a portion of its area, preventing the solution in the solution chamber 332b from moving to the sample chamber 334b. The feature that at least a portion of the channels within the manual valve 341b are formed to have a larger area than the inlet of the manual valve, and the resistance generated by the hydrophobic material treated on the internal surface, can be configured such that the solution in the solution chamber 332b can move to the sample chamber by a predetermined rotational force generated by the rotation of the rotating body.
[0185] More specifically, the solution chamber 332b within the microfluidic structure 310b can be located near the rotation axis of the rotating body on which the microfluidic structure 310b is mounted. Therefore, when the rotating body rotates around the rotation axis, the rotational force generated by the rotation can be generated along the direction from the solution chamber 332b to the manual valve 341b. Since the inlet area of the manual valve 341b is narrower than the area of the solution chamber 332b, the solution within the solution chamber 332b can move to the inlet of the manual valve 341b due to the capillary pressure difference.
[0186] Solution moving to the inlet of manual valve 341b can, after passing through a portion of a first channel 342b having a similar area to the inlet of manual valve 341b, reach the inlet of a second channel having a wider area than the first channel 342b. At this point, because the second channel is wider than the first channel, a difference arises between the capillary force at the interface corresponding to the solution formed along the direction of the first channel and the capillary force at the interface corresponding to the solution formed along the direction of the second channel.
[0187] Since the second channel can have an interface with a larger radius than the first channel, the capillary force corresponding to the interface of the second channel can be larger. Therefore, the substantial capillary force generated by the sum of the capillary force generated at the interface of the second channel and the capillary force corresponding to the interface of the first channel can create resistance, preventing the solution in the solution chamber 332b from moving to the sample chamber 334b.
[0188] Therefore, the solution stored in solution chamber 332b can be moved to sample chamber 334b based on the rotational force generated by the rotation of the rotating body and the resistance provided by manual valve 341b. According to one embodiment, manual valve 341b can move the solution injected into solution chamber 332b to sample chamber 334b based on a second rotational force generated by the rotating body. According to one embodiment, the second rotational force can be configured to be greater than or equal to the resistance provided by manual valve 341b.
[0189] Furthermore, as described above, due to the manual valve 341b connected to one end of the solution chamber 332b and the first shared channel 338b formed at the other end of the solution chamber and connected to the solution chambers in other microfluidic structures, the solution stored in the solution chamber 332b cannot be moved to the sample chamber 334b by the manual valve 341b until the solution in the solution chambers in other microfluidic structures is filled.
[0190] Furthermore, according to one embodiment, a first shared channel 338b, connected to one end of the solution chamber 332b to share the solution in other microfluidic structures, can be formed in a zigzag shape along the circumferential direction inside the rotating body containing the microfluidic structures. However, it is not limited to this; the first shared channel 338b can also be formed in other shapes to share the solution between the microfluidic structures.
[0191] The sample chamber 334b can contain a sample containing at least one target substance. According to one embodiment, the sample chamber 334b can be connected to a vent 346b, thereby connecting to the external space of the sample chamber. The sample chamber 334b can be injected from the outside through the vent 346b. As described later, when the sample chamber 334b is secured to the sample analysis device 2000, the sample chamber 334b can obtain a sample from the injection port of the sample analysis device through the vent 346b.
[0192] According to another embodiment, sample chamber 334b can be connected to a second shared channel, which is used to share the solution injected through vent 346b with sample chambers 334b in adjacent microfluidic structures. Furthermore, according to one embodiment, the second shared channel can also be formed in a zigzag shape similar to the first shared channel described above. However, according to one embodiment, unlike the solution chambers, each sample chamber 334b can also be connected to sample chambers in other microfluidic structures without a shared channel.
[0193] According to one embodiment, an antibody complementary to a target substance (e.g., target antigen, genome) in the sample chamber 334b may be pre-coated in the sample chamber. According to another embodiment, the inner surface of the sample chamber 334b may further include defined well regions for immobilizing the antibody. When a sample is obtained from the sample chamber 334b through a vent, the antigen, which is complementary to the antibody in the sample, can bind to the pre-coated antibody.
[0194] Furthermore, sample chamber 334b can obtain a cleaning solution from the solution chamber for cleaning substances other than antigens bound to antibodies immobilized on the internal surface, and transfer target substances (e.g., antigens) and impurities not captured with the cleaning solution to waste chamber 348b via siphon channel 336b. According to one embodiment, sample chamber 334b can also obtain a solution containing antibodies with attached chromogenic enzymes and a solution containing chromogenic substrates via solution chamber 332b. In sample chamber 334b, antigens bound to pre-immobilized antibodies can form conjugates with antibodies with attached chromogenic enzymes, and the chromogenic substrates act on the chromogenic enzymes linked to these conjugates, thereby inducing a chromogenic reaction.
[0195] In sample chamber 334b, antigens, impurities, washing solutions, and other reaction solutions used for enzyme-linked immunosorbent assays that are not captured by antibodies can begin to flow into siphon channel 336b as the rotating body equipped with microfluidic structure 310b rotates.
[0196] A siphon channel 336b, connected to one end of the sample chamber 334b, is located radially outward on the rotating body compared to the sample chamber 334b, and is connected to a waste chamber located outward compared to the siphon channel 336b. The siphon channel 336b can move the solution based on the capillary force provided by the siphon channel and the rotational force generated by the rotating body in which the aforementioned microfluidic structure 310b is located.
[0197] More specifically, the sample obtained from the sample chamber 334b through the vent 346b can be filled into the outlet portion 339b of the siphon channel 336b connected to the waste chamber 348b. For example, a sample discharged through the injection port of the sample analysis device 2000 can be filled into the outlet portion 339b, which is the other end of the siphon channel 336b and is discharged into the waste chamber 348b, by the injection pressure generated by the injection pump of the sample analysis device 2000. When the rotation of the rotating body is activated, the sample filling the siphon channel 336b can be moved into the waste chamber 348b by the rotational force.
[0198] For example, a sample can be injected into sample chamber 334b while the rotating body is stationary. In the injected sample, antigens other than those binding to the pre-coated antibody in sample chamber 334b (e.g., target material), along with any impurities contained in the sample, can fill the outlet portion 339b of the siphon channel. After a predetermined time has elapsed to allow the antigens in the sample to react with the pre-coated antibody in the sample chamber, as the rotating body rotates, antigens and impurities not bound to the pre-coated antibody in sample chamber 334b will be moved to waste chamber 348b.
[0199] Furthermore, as described above, with the second rotational force generated by the rotation of the rotating body at a second rotational speed, the solution moved from the solution chamber 332b to the sample chamber 334b via the manual valve 341b can be moved to a portion of the siphon channel. According to one embodiment, the solution moved to the sample chamber 334b via the manual valve 341b can be moved by the second rotational force to at least a portion of the siphon channel 337b. According to one embodiment, the solution injected into the sample chamber 334b via the manual valve 341b can fill a portion of the siphon channel 337b located within the siphon channel corresponding to the height of the solution-filled sample chamber 334b.
[0200] As the rotating body comes to a standstill after a preset time, the solution in the channel portion 337b that fills the siphon channel can move to the outlet portion 339b in the siphon channel, and when the solution begins to flow into the waste chamber 348b, the rotating body where the microfluidic structure 310 is located can rotate at high speed again.
[0201] According to one embodiment, a reaction solution, such as a first cleaning solution for washing target substances, a second cleaning solution, a solution containing an antibody with an attached chromogenic enzyme, and a solution containing a chromogenic substrate, etc., for enzyme-linked immunosorbent assay (ELISA), is moved to the sample chamber 334b via a manual valve 341b. This reaction solution is then moved to a portion 337b within a siphon channel that corresponds to the height to which the solution is filled in the sample chamber 334b. Subsequently, as the rotating body comes to rest and as the capillary force on the portion 337b of the siphon channel exceeds the rotational force of the rotating body, the reaction solution can be moved to the waste chamber 348b.
[0202] Waste chambers 348b are formed at predetermined intervals from the edge portion of the disk-shaped substrate 352b and are respectively connected to at least one microfluidic structure, thereby storing samples or solutions moving along the respective siphon channels of the at least one microfluidic structure. Furthermore, according to one embodiment, waste chamber 124b may also include a superabsorbent polymer (SAP) capable of absorbing samples and solutions inside the waste chamber, thereby effectively absorbing samples and solutions.
[0203] Figure 3a This is a diagram illustrating, schematically, the process of analyzing a sample using a microfluidic device according to another embodiment and a sample analysis apparatus using the microfluidic device described above.
[0204] According to one embodiment, a microfluidic device 1000 may include: a rotatable rotating body 122c, a chamber within the rotating body capable of containing a sample and a solution, and microfluidic structures 102c and 104c providing multiple channels for moving the sample. For example, the microfluidic device 1000 may include multiple microfluidic structures 102c and 104c arranged at predetermined intervals within the rotating body 122c. The microfluidic structures may be arranged circumferentially within the rotating body 122c, centered on a rotation axis 111c, and the sample and solution within the microfluidic structures may move based on the rotational force generated by the rotation of the rotating body and the rotation direction of the rotating body.
[0205] According to one embodiment, the microfluidic structures 102c and 104c may include: a pretreatment unit 112c, which shares a solution injected through a solution injection port with other adjacent microfluidic structures via a shared channel, and performs a pretreatment process on the sample injected through a sample injection port and the solution; and a dispensing unit 114c, which is located radially outward from the pretreatment unit within the rotating body, and detects target substances in the sample pretreated by the pretreatment unit.
[0206] According to another embodiment, the pretreatment unit 112c, within the microfluidic structures 102c and 104c, can share a shared channel with adjacent microfluidic structures the sample injected through the sample injection port and the solution injected through the solution injection port, and can also perform a pretreatment process on the injected sample and solution. (Refer to the following description.) Figures 3b to 3c A more detailed description of the structure of microfluidic structures will be provided.
[0207] The microfluidic device 1000 includes at least one of the aforementioned microfluidic structures and is rotatable along a predetermined rotation axis 111c, allowing movement of samples and solutions within the microfluidic structure. The microfluidic device 1000 according to this disclosure can be mounted on a sample analysis device 2000 and used for automated sample analysis processes under the control of the sample analysis device 2000.
[0208] According to one embodiment, the sample analysis device 2000 can extract samples and solutions from a storage section 134 pre-stored with samples and solutions. The sample analysis device 2000 can inject the samples and solutions extracted from the storage section 134 into the microfluidic device 1000 by controlling an injection port 132 for supplying samples and solutions to the microfluidic device 1000. The sample analysis device 2000 can rotate the microfluidic device 1000 containing the injected samples or solutions at a preset number of revolutions and rotation direction to move the samples or solutions within the microfluidic device.
[0209] That is, the sample analysis device 2000 can extract target substances from multiple samples simultaneously by moving samples within a microfluidic device 1000 containing at least one microfluidic structure. Furthermore, unlike conventional sample analysis devices, the sample analysis device 2000 can rapidly and accurately analyze samples injected into the microfluidic device by automatically supplying pre-stored samples and solutions to the microfluidic device. According to one embodiment of this disclosure, the target substance contained in the sample may include, but is not limited to, genetic material, genome, nucleic acid, RNA, or DNA.
[0210] Figure 3b This is a diagram illustrating the structure of a microfluidic device having multiple microfluidic structures according to another embodiment.
[0211] According to one embodiment, the microfluidic device 1000 may include a plurality of microfluidic structures arranged circumferentially around a rotation axis. According to one embodiment, the microfluidic structures 210c may be arranged at predetermined intervals inside the rotating body 216c.
[0212] According to one embodiment, microfluidic structures can share samples or solutions stored in chambers within adjacent microfluidic structures via at least one shared channel. For example, microfluidic structure 210c can share samples or solutions stored in chambers within microfluidic structures adjacent to it on both sides. According to another embodiment, microfluidic structure 210c can also share solutions stored only in chambers within microfluidic structures adjacent to it on both sides. Microfluidic structures adjacent to microfluidic structure 210c can be connected to other microfluidic structures in the same manner. According to one embodiment, at least one microfluidic structure within rotating body 216c can also be connected to each other via at least one shared channel.
[0213] The microfluidic structure 210c may include a pretreatment section 212c and a dispensing section 214c located radially outward from the interior of the rotating body 216c compared to the pretreatment section 212c. The rotating body 216c and the dispensing section 214c may be connected via at least one channel. The microfluidic structure 210c may dispense samples or solutions injected through an injection port, detect target substances in the dispensed samples, and store substances other than the target substances in the samples, as well as the solutions.
[0214] According to one embodiment, the microfluidic structure 210c may include 30 microfluidic structures. However, it is not limited to this and can be varied depending on the type of sample and solution to be analyzed, the analytical method, the size of the rotating body, the size of the microfluidic structures, etc.
[0215] Figure 3c This is a diagram illustrating the structure of a microfluidic structure according to another embodiment.
[0216] According to one embodiment, the microfluidic structure may include a pretreatment section 320c and a dispensing section 340c. For example, the microfluidic structure can move at least one of a sample injected through a sample injection port and a sample or solution injected through a solution injection port into a predetermined chamber within the dispensing section.
[0217] According to one embodiment, the pretreatment unit 320c may include: a sample chamber 324c for containing a sample injected through a sample injection port; a solution chamber 326c for containing a solution injected through a solution injection port; and a capture filter 328c for capturing target substances from the injected sample. According to another embodiment, the pretreatment unit 320c may further include: a first manual valve for connecting the sample chamber 324c and the capture filter 328c; and a second manual valve for connecting the solution chamber 326c and the capture filter 328c.
[0218] According to one embodiment, the pretreatment unit 320c can contain samples and solutions, and at least one of the contained samples or solutions can be shared with other adjacent microfluidic structures via a shared channel. Figure 3c As shown, the shared channel 321c can be formed in a part of the solution chamber 326c, but when a solution injection port is formed in the solution chamber 326c, the shared channel 321c can also be connected to one end of the solution injection port. According to another embodiment, the shared channel can be formed only at one end of the solution chamber or at one end of the solution injection port, or it can also be formed at one end of the sample chamber or at one end of the sample injection port. According to another embodiment, the shared channel can be formed in both the solution chamber and the sample chamber, or it can be formed at both the solution injection port and the sample injection port.
[0219] The sample and solution contained in the pretreatment section 320c of the microfluidic structure 310c can be prevented from moving to the capture filter by a manual valve connected to one end of the sample chamber 324c and the solution chamber 326c, until the sample and solution are shared with the individual sample chambers and solution chambers in other microfluidic structures.
[0220] The sample chamber 324c can contain a solution injected through the first sample injection port 323c. The first sample injection port 323c can be formed at one end of the sample chamber 324c. According to one embodiment, the first sample injection port 323c formed at one end of the sample chamber can be connected to a second sample injection port 319c via an injection port channel 322c, and the sample chamber 323c can also receive a solution injected through the second sample injection port. According to one embodiment, when the sample chamber 324c receives a sample through the first sample injection port 323c, the second sample injection port 319c, and the injection port channel 322c, the injection port channel 322c can be formed at a depth having a predetermined distance from the surface of the rotating body (PMMA substrate). For example, the second sample injection port 319c can be formed on the surface of the rotating body, and one end of the second sample injection port 319c is connected to the surface of the rotating body, while the other end is connected to the injection port channel 322c. The injection port channel 322c can be connected to the first sample injection port 323c at a predetermined depth within the rotating body. At this time, the first sample injection port 323c may not be exposed to the external space. The first sample injection port 323c is connected to the injection port channel 322c at a predetermined depth from the surface of the rotating body to prevent exposure to the external space. Similarly, the sample chamber 324c may be connected to the first sample injection port 323c at a predetermined depth with the surface of the rotating body as a reference. Furthermore, according to one embodiment, the shared channel of the sample chamber 324c for sharing samples with other microfluidic structures may also be connected to at least one of the first sample injection port 323c, the injection port channel 322c, or the second sample injection port 319c.
[0221] Solution chamber 326c can contain solution injected through a solution inlet (not shown). According to one embodiment, the solution inlet can be formed at one end of the solution chamber or at least a portion of a shared channel connected to the solution chamber. As described above, a shared channel 321c can be connected to one side of the solution chamber 326c. Solution chamber 326c can be connected to a capture filter 328c via a second manual valve. A sample contained in solution chamber 326c can be prevented from moving to the capture filter by the second manual valve until the solution fills the solution chamber within other microfluidic structures.
[0222] According to one embodiment, the shared channel connected to at least one of the sample chamber 324c or solution chamber 326c can be formed in a zigzag shape, but is not limited thereto; it can also be formed in other shapes that allow the sample and solution to be shared to the respective sample chambers and solution chambers in other microfluidic structures. However, as described above, the shared channel can be formed only in solution chamber 326c, and the microfluidic structures formed on the rotating body can also share only solution through the shared channel.
[0223] The first manual valve 331c may include: a first channel having the same area as the area through which the first manual valve inlet passes; and at least one second channel having a wider area than the area through which the first manual valve inlet passes and formed between the first channels. According to one embodiment, the surface within the first manual valve 331c may be hydrophobically treated.
[0224] More specifically, due to the area difference between the first channel 332c and the second channel 333c within the manual valve, the first manual valve 331c allows the radii of the interfaces between the fluids passing through the first and second channels to be different. This capillary force generated by the difference in radii between the two interfaces can restrict the sample in the sample chamber from moving to the capture filter. Furthermore, in addition to utilizing the area difference between the first and second channels within the first manual valve, the first manual valve 331c can also ensure greater resistance by making at least a portion of its area hydrophobic, thus preventing the sample in the sample chamber from moving to the capture filter.
[0225] At least a portion of the channel within the first manual valve 331c is characterized by a larger area than the inlet through the first manual valve, and the resistance generated by the hydrophobic material treated on the internal surface can be configured such that the sample in the sample chamber 324c can be moved to the capture filter 328c by a first rotational force generated by the rotation of the rotating body.
[0226] The second manual valve 334c may include: a third channel having the same area as the area through the second manual valve inlet; and at least one fourth channel having a wider area than the area through the second manual valve inlet and formed between the third channels. According to one embodiment, the surface within the second manual valve 334c may be hydrophobically treated.
[0227] More specifically, due to the area difference between the third channel 335c and the fourth channel 336c within the manual valve, the second manual valve 334c allows the interfaces between the fluids passing through the third and fourth channels to have different radii. This capillary force generated by the difference in radii between the two interfaces restricts the solution contained in the solution chamber, preventing it from moving to the capture filter. Furthermore, in addition to utilizing the area difference between the third and fourth channels within the second manual valve, the second manual valve 334c can also ensure greater resistance by making at least a portion of its area hydrophobic, thus preventing the solution in the solution chamber from moving to the capture filter.
[0228] At least a portion of the passage within the second manual valve 334c is characterized by having a larger area than the inlet of the second manual valve, and the resistance generated by the hydrophobic material treated on the internal surface can be configured such that the solution in the solution chamber 326c can be moved to the capture filter 328c by the second rotational force generated by the rotation of the rotating body.
[0229] The capture filter 328c can capture target substances from an injected solution. For example, the capture filter 328c may include a filter formed of glass fiber of a predetermined thickness, or a matrix containing multiple silica beads. The capture filter 328c can use the aforementioned matrix to capture target substances in a sample. According to one embodiment, the capture filter 333c may be a glass microfiber filter with a predetermined particle retention capacity, but is not limited thereto, and may include other matrices for capturing target substances in a sample.
[0230] The dispensing unit 340c may include a collection chamber 342c and a waste chamber 344c. According to another embodiment, in addition to the collection chamber 342c and waste chamber 344c, the dispensing unit 340c may further include a transfer chamber 346c. For example, the dispensing unit 340c may be located radially outward from the pretreatment unit 320c within the rotating body, dispensing the target substance from the sample pretreated by the pretreatment unit and detecting the dispensed target substance. According to one embodiment, the dispensing unit 340c may selectively store samples and solutions into the collection chamber or the waste chamber based on the rotational force and direction of rotation of the rotating body on which the microfluidic structure 310c is mounted.
[0231] Collection chamber 342c can store an elution solution containing the target material captured by the capture filter. For example, collection chamber 342c can obtain an elution solution containing the target material captured by the capture filter based on a second rotational direction of the rotating body where the microfluidic structure 310c is located. More specifically, as the rotating body rotates along the second rotational direction, the elution solution containing the target material captured in the capture filter can be directed towards… Figure 3c The transfer chamber 346c shown is tilted and moved to the left, thereby storing the contents in the collection chamber 342c.
[0232] Waste chamber 344c may be located adjacent to the collection chamber and may store a cleaning solution for rinsing substances other than the target material captured by the capture filter in the sample and solution. For example, the first waste chamber 344c may contain residual material from the capture filter that was not captured by the capture filter, as well as the cleaning solution contained in the solution chamber, based on a first rotation direction of the rotating body of the fastened microfluidic structure 310c. More specifically, as the rotating body rotates along the first rotation direction, residual material from the sample that was not captured by the capture filter, as well as a portion of the solution contained in the solution chamber, may move towards... Figure 3c The transfer chamber 346c shown is tilted and moved to the right and stored in the waste chamber 344c.
[0233] The transfer chamber 346c can be configured such that one upper end is connected to the capture filter 328c, one lower end is connected to the collection chamber 342c, and the other lower end is connected to the waste chamber 344c. The transfer chamber 346c can connect the capture filter to the collection chamber and the waste chamber respectively, and selectively transfer a portion of the sample or solution contained in the transfer chamber to the collection chamber 342c or the waste chamber 344c along the rotation direction of the rotating body.
[0234] According to one embodiment, the transfer chamber 346c can obtain an elution solution containing the target substance or a sample passing through the capture filter and the washing solution from the capture filter, and selectively transfer the elution solution containing the target substance to the collection chamber 342c along the rotation direction of the rotating body, or transfer the sample passing through the capture filter and the washing solution to the waste chamber 344c.
[0235] According to one embodiment, when the sample injected into the microfluidic structure 310c is a sample containing a genome such as RNA or DNA, the target genome captured by the capture filter can be stored as a target material together with the elution solution in the collection chamber 342c.
[0236] Figure 3dThis is a diagram illustrating the operation of a manual valve in a microfluidic structure according to one embodiment.
[0237] The microfluidic structure 410c may include: a first manual valve 409c for connecting the sample chamber 424c and the capture filter 428c; and a second manual valve 420c for connecting the solution chamber 426c and the capture filter 428c. For example, the first manual valve 331c may include: a first channel having the same area as the area through the inlet of the first manual valve; and a second channel having a wider area than the area through the inlet of the first manual valve.
[0238] Furthermore, the second manual valve 420c may include: a third channel having the same area as the area through the inlet of the second manual valve; and at least one fourth channel having a wider area than the area through the inlet of the second manual valve and formed at a predetermined interval between the third channels. Figure 3d The operation of the second manual valve is explained with the fourth channel in the second manual valve 420c closest to the solution chamber 426c as the center.
[0239] Despite Figure 3d Not shown in the image, such as Figure 3b As shown, the solution chamber 426c within the microfluidic structure 410c can be located near the rotation axis of the rotating body on which the microfluidic structure 410c is mounted. Therefore, when the rotating body rotates about the rotation axis, the rotational force 412c generated by the rotation can be generated along the direction from the solution chamber to the second manual valve.
[0240] Furthermore, since the inlet area of the second manual valve 420c is narrower than that of the solution chamber 426c, the solution in the solution chamber 426c can move to the inlet of the second manual valve 420c due to the capillary pressure difference. The solution moving to the inlet of the second manual valve 420c can then pass through a portion of a third channel having the same area as the inlet of the second manual valve 420c, and reach the inlet of a fourth channel that has a wider area than the third channel. At this time, because the fourth channel is wider than the third channel, a difference will occur between the capillary force 402c corresponding to the interface of the solution formed along the direction of the third channel and the capillary force 404c corresponding to the interface of the solution formed along the direction of the fourth channel.
[0241] Since the fourth channel can have an interface with a larger radius than the third channel, the capillary force 404c corresponding to the interface of the fourth channel can be made larger. Similarly, among the multiple fourth channels within the second manual valve 420c, the capillary force 406c generated by the fourth channel adjacent to the capture filter 428c can also be made larger than the capillary force 406c corresponding to the interface of the third channel. Therefore, the substantial capillary forces 414c and 416c generated because a portion of the channel within the second manual valve is wider than the inlet area of the second manual valve can create resistance, preventing the solution in the solution chamber 426c from moving into the capture filter 428c.
[0242] Therefore, the solution stored in solution chamber 426c can be moved to capture filter 428c based on the rotational force generated by the rotation of the rotating body and the resistance provided by the second manual valve 420c. According to one embodiment, the second manual valve 420c can move the solution injected from solution chamber 426c to capture filter 428c based on a second rotational force generated by the rotating body. According to one embodiment, the second rotational force can be configured to be smaller or the same as the resistance provided by the second manual valve.
[0243] Similar to the operation of the second manual valve described above, the first manual valve 409c can also utilize the difference in capillary pressure generated by the area difference between the first and second channels within the first manual valve to restrict the movement of the sample stored in the sample chamber 424c to the capture filter 428c. According to one embodiment, the first manual valve 409c can move the sample injected from the sample chamber 424c to the capture filter 428c based on a first rotational force generated by the rotating body. Furthermore, as described above, since at least a portion of the internal surfaces of the first and second manual valves are hydrophobically treated, additional resistance to the sample or solution can be provided.
[0244] Figure 4 This is a diagram illustrating the structure of a sample analysis apparatus according to one embodiment.
[0245] According to one embodiment, a sample analysis apparatus 2000 equipped with a microfluidic device 1000 may include: a first drive unit 520 for rotating the microfluidic device 1000 along a predetermined rotation axis; a second drive unit 540 for moving an injection mechanism for injecting samples and solutions along a preset drive axis; a supply unit 560 for storing samples and solutions to be supplied to the injection mechanism and selectively supplying the stored samples and solutions to the injection mechanism; and a control unit (not shown) for controlling the first drive unit, the second drive unit, and the supply unit.
[0246] However, not all of the illustrated components are necessary. The sample analysis device 2000 can be implemented with more or fewer components than those illustrated. According to one embodiment, the sample analysis device 2000 may further include: a first housing 572, configured to house the first drive unit 520, the second drive unit 540, and the control unit (not shown) of the sample analysis device 2000; and a second housing 574, connected to the first housing 572 in an openable / closable manner, thereby enabling selective exposure of the microfluidic device. Furthermore, according to one embodiment, the sample analysis device 2000 may further include: a network interface (not shown) for communicating with other electronic devices; and a camera (not shown) for acquiring images of the microfluidic device.
[0247] Figure 5 This is a diagram illustrating the operation and structure of a sample analysis apparatus according to one embodiment.
[0248] like Figure 4 As shown, the sample analysis device 2000 may include: a first drive unit 520 for rotating the microfluidic device 1000 along a predetermined rotation axis; a second drive unit 540 for moving an injection mechanism for injecting samples and solutions along a preset drive axis; and a supply unit 560 for storing samples and solutions to be supplied to the injection mechanism and selectively supplying the stored samples and solutions to the injection mechanism.
[0249] The following is for reference Figure 5 The characteristics of the components within each sample analysis device are described in detail.
[0250] The first drive unit 520 may include: a rotating component (not shown) fastened to the microfluidic device 1000 and configured to rotate along the rotation axis of the microfluidic device with the microfluidic device; and a spindle motor 632, which rotates the rotating component at a predetermined rotation direction and speed based on a first control signal obtained from the control unit. Under the control of the control unit, the spindle motor 632 can rotate at a preset speed and direction to rotate the microfluidic device 1000. The first drive unit 520 may set different rotation speeds and directions to rotate the rotating body depending on the type of solution injected from the injection mechanism or the progress of the reaction process using the solution and sample.
[0251] The second drive unit 540 may include: at least one guide shaft 620; a first drive component 622 connected to one end of the drive shaft and securing the injection mechanism 621; a second drive component 624 connected to the other end of the drive shaft and transmitting driving force to the drive shaft, causing the drive shaft to rotate at predetermined angular intervals; and a stepper motor 626 that rotates the second drive component 624 at predetermined angles. Under the control of the control unit, the second drive unit 540 can inject samples or solutions into predetermined chambers within the microfluidic device.
[0252] The first drive component 622 is connected to one end of the drive shaft 623 and can secure the injection mechanism 621. According to one embodiment, the first drive component 622 can be integrally formed with the drive shaft 623 or detachably formed. The drive shaft 623 can obtain rotational force generated by the stepper motor by connecting to the second drive component 624.
[0253] At least one guide shaft 620 may be located at the upper end of the stepper motor 626 and provide a guide path so that the first drive component 622, drive shaft 623, injection mechanism 621, and second drive component 624 within the second drive unit 540 can move in a vertical direction. According to one embodiment, the guide shafts 620 may be spaced apart at a predetermined interval, and at least one of the guide shafts may have threads formed on it for engaging with a ball screw component. Furthermore, at least one guide shaft 620 may be formed in three forms, but is not limited thereto.
[0254] The second drive component 624 may include: a through hole penetrating at least one guide shaft 620; and a ball screw component in contact with a surface formed within the through hole. With the ball screw component and the thread formed on the at least one guide shaft in close contact, the second drive component can move along the at least one guide shaft. Furthermore, the second drive component 624 can transmit the driving force generated by the stepper motor 626 to the injection mechanism 621 via the drive shaft 623. For example, the second drive component 624 can rotate the drive shaft 623, which is connected to one end of the second drive component 624, at predetermined angular intervals, so that the injection mechanism moves at predetermined angular intervals.
[0255] The supply unit 560 may include: a storage unit 642 for separating and storing samples and solutions; a supply channel 646 for obtaining samples and solutions from the storage unit; a port valve 649 for selecting a supply channel from the supply channels to be connected to an injection channel 619 or an injection mechanism 621; and an injection pump 644 for pumping the samples and solutions stored in the storage unit 642.
[0256] The storage unit 642 may include various storage units for separately storing samples and solutions. For example, the storage unit 642 may include a sample storage unit for storing samples, a washing solution storage unit for storing washing solutions, and an elution solution storage unit for storing elution solutions. However, it is not limited to this; the storage unit 642 may also include multiple storage chambers for storing other types of samples and solutions. Furthermore, according to one embodiment, each sample storage unit, washing solution storage unit, and elution solution storage unit within the storage unit 642 may also include a connection hole communicating with a supply channel.
[0257] The supply channel 646 can be connected to the connection port of the storage chamber in the storage unit 642 where various samples and solutions are stored. The supply channel 646 can separate and obtain the samples and solutions stored in the storage unit 642. One end of the supply channel 646 can be connected to the storage unit 642, and the other end of the supply channel 646 can be connected to the port valve 649.
[0258] Port valve 649 can select one of the supply channels for moving samples and solutions stored in storage unit 642 and connect the selected supply channel to injection mechanism 621. According to another embodiment, port valve 649 can also select one of multiple supply channels and connect the selected supply channel to the injection channel connected to injection mechanism 621. According to one embodiment, port valve 649 can be configured with eight ports that can be connected to eight supply channels, but is not limited thereto; it can have different numbers of ports depending on the number of samples and solutions required for sample analysis.
[0259] The syringe pump 644 can pump samples and solutions stored in the storage compartment, thereby discharging them through an injection mechanism. For example, the syringe pump may include a stepper motor inside the pump, which can convert the rotational motion of the stepper motor into the linear motion of the syringe pump by connecting to a frame on which a pneumatic pump is mounted. According to one embodiment, the syringe pump 644 can discharge samples, washing solutions, and elution solutions stored in the storage compartment 642 based on the control of the control unit via the injection mechanism.
[0260] According to one embodiment, the sample analysis device 2000 may further include: heating elements 632 and 634 formed at the bottom of the microfluidic device and cylindrically surrounding at least a portion of the first driving element in the direction outside the first driving element; and linear guides 636 and 638 for aligning the position of the heating elements in the direction outside the first driving element.
[0261] For example, the sample analysis device 2000 can control the first drive unit, the second drive unit, and the microfluidic device so that when a specified sample and solution are injected into the microfluidic device, the heating elements 632 and 634 located at the bottom of the microfluidic device can be controlled to maintain a certain temperature for the sample and solution within the microfluidic device 1000. Furthermore, the sample analysis device 2000 can align the position of the heating element below the first drive unit using a linear guide, thereby maintaining a constant temperature in the chamber containing the sample and solution within the microfluidic device 1000. Therefore, the sample analysis device 2000 can provide the appropriate temperature required for the extraction and reaction of the target substance.
[0262] Figure 6 This is a diagram illustrating the operation and structure of a sample analysis apparatus according to one embodiment.
[0263] Reference Figure 6 The composition of the sample analysis device related to the second drive unit is described in detail.
[0264] The second drive unit 540 may include a stepper motor 722, which transmits driving force to the drive shaft 704 via the second drive member 702. According to one embodiment, the drive shaft 704 can be driven along a predetermined axial direction (e.g., the z-axis direction) based on the driving force transmitted from the second drive member 702. A first drive member 706, 726 for fixing the injection mechanism 728 may be formed at one end of the drive shaft 704. The second drive unit can inject samples and solutions into the microfluidic device 1000 by controlling the movement of the second drive member 702, drive shaft 704, first drive member 706, 726, and injection mechanism 728 along the predetermined axial direction.
[0265] According to one embodiment, the second drive unit can stably move the first drive components 706 and 726, the drive shaft 704, the injection mechanism 728, and the second drive component in a vertical direction via at least one guide shaft 724 arranged at a preset interval. According to one embodiment, the second drive unit can drive the injection mechanism 728 in the region corresponding to the microfluidic device located above the first drive unit.
[0266] Furthermore, according to one embodiment, the first drive unit may include a spindle motor as described above and a rotating component 712, which may be located between the first heating unit 708 and the second heating unit 710, which are in the shape of a fan or cylinder. The rotating component may rotate at a predetermined speed under the control of the spindle motor.
[0267] Figure 7 This is a diagram illustrating the specifications of the components of a sample analysis apparatus in one embodiment.
[0268] According to one embodiment, the total length 802 of the second drive unit 540 in the sample analysis device in the height direction can be 27 cm, the lateral width 804 of the housing where the stepper motor is located can be 7 cm, the height length 806 of at least one guide shaft can be 15 cm, the length 808 of the drive shaft can be 14 cm, the width 809 of the supply unit for supplying samples and solutions can be 10 cm, and the diameter 810 of the heating unit located at the lower part of the microfluidic device can be 13 cm. Furthermore, according to another embodiment, the height length 814 of the first drive unit of the sample analysis device can be 10 cm, the diameter 812 can be 5.5 cm, the total length 816 of at least one guide shaft set at a preset interval can be 7 cm, the lateral length 818 of the supply unit for supplying samples and solutions can be 5 cm, and the height length 820 can be 26 cm.
[0269] However, the specifications of the sample analysis device 2000 and the microfluidic device 1000 according to this disclosure are not limited thereto, and may vary depending on conditions such as the amount of sample and solution to be analyzed, the analysis speed, the analysis accuracy, and the location where the analysis is performed.
[0270] Figure 8 It shows the basis Figures 1a to 1d The figure shows a microfluidic device and a sample analysis device using the microfluidic device to analyze a sample.
[0271] The process of sample analysis by the sample analysis device 2000 using the microfluidic device 1000 will be described in detail according to one embodiment. According to one embodiment, the sample analysis device 2000 can induce an amplification reaction of a target substance (e.g., a specific genome) in the sample using the microfluidic device 1000. Furthermore, the sample analysis device 2000 can amplify the target substance in the sample using the microfluidic device 1000 and detect the amplified target substance for diagnostic purposes.
[0272] The sample analysis device 2000 can rotate a rotating body of a microfluidic device integrated with the sample analysis device about at least one rotation axis and at a preset number of revolutions and rotation direction. The sample analysis device 2000 can move samples and solutions injected into the microfluidic device 1000 to the interior of at least one microfluidic structure within the microfluidic device based on the rotational force generated by the rotation of the rotating body. The sample analysis device 2000 can control the movement of the sample or solution along different directions by controlling at least one of the rotation direction and rotation speed of the rotating body.
[0273] According to one embodiment, the sample injected into the microfluidic device 1000 via the sample analysis device 2000 may include a target substance as the object of analysis and impurities other than the target substance. Furthermore, the solution injected into the microfluidic device 1000 via the sample analysis device 2000 may include a cleaning solution for washing away substances other than the target substance, and an elution solution (e.g., water) for separating the target substance from the capture filter.
[0274] In step S902a, the sample analysis device 2000 may inject a sample into the sample chamber 902a of the microfluidic device 1000, which is fastened to a rotating component of the sample analysis device. For example, the sample analysis device 2000 may inject a pre-stored sample into a storage unit by connecting an injection mechanism to a sample injection port connected to the sample chamber 902a. According to one embodiment, the sample chamber 902a of the microfluidic device 1000 may be connected to a first manual valve for controlling the movement of the sample in the sample chamber into a capture filter based on a predetermined rotational force.
[0275] Therefore, the sample in the sample chamber cannot move to the capture filter until the sample analysis device 2000 injects the sample into all the sample chambers in the microfluidic device 1000.
[0276] In step S904a, the sample analysis device 2000 can control the rotating component to rotate in a second rotation direction (e.g., counterclockwise) and a first rotational speed. Based on the first rotational force generated by the rotating body rotating in the second rotation direction 904a and the first rotational speed, the sample stored in the sample chamber 902a of each microfluidic structure can be moved to the first waste chamber 904a. According to one embodiment, the first rotational force may be greater than or equal to the resistance provided by a first manual valve connected to the sample chamber 902a.
[0277] In step S904a, the sample analysis device 2000 generates a first rotational force by controlling the rotating body, so that the sample in the sample chamber stored in each fluid structure can pass through the capture filter, and the capture filter 903a may contain substances other than the target substances captured by the silica bead matrix and the target substances in the sample.
[0278] In step S906a, the sample analysis device 2000 may inject a solution into the solution chamber 906a of the microfluidic device 1000. More specifically, the sample analysis device 2000 may inject a cleaning solution for cleaning substances other than the target substance in the sample into the solution chamber 906a. For example, the sample analysis device 2000 may inject pre-stored cleaning solution into a storage section by connecting an injection mechanism to a sample injection port connected to the solution chamber 906a. According to one embodiment, the solution chamber of the microfluidic device 1000 may be connected to a second manual valve for controlling the movement of the solution in the solution chamber to a capture filter based on a predetermined rotational force, and a shared channel for sharing the solution to solution chambers in other microfluidic structures. Therefore, the cleaning solution in the solution chamber 906a may not be able to move to the capture filter until all solution chambers within the microfluidic device 1000 have been injected with cleaning solution.
[0279] In step S908a, the sample analysis device 2000 can control the rotating component to rotate in a second rotation direction 905a and a second rotation speed. Based on the second rotational force generated by the rotating body rotating in the second rotation direction 905a and the second rotation speed, the solution (e.g., a first cleaning solution) stored in the solution chamber 706a of each microfluidic structure can be moved to the first waste chamber 908a. According to one embodiment, the second rotational force can be greater than or equal to the resistance provided by a second manual valve connected to the solution chamber 906a.
[0280] According to one embodiment, the sample analysis apparatus 2000 can generate a second rotational force by controlling a rotating body, so that the solution stored in the solution chambers within each fluid structure passes through a capture filter. The capture filter 903a may contain residual substances and impurities other than the captured target substance, and these residual substances and impurities can be moved to the first waste chamber 908a along with the injected first cleaning solution.
[0281] According to one embodiment, the first manual valve for controlling the movement of a sample within the sample analysis device 2000 and the second manual valve for controlling the movement of a solution can provide the same resistance. However, according to another embodiment, the first and second manual valves can provide different resistances, and the sample analysis device 2000 can control the movement of the sample and solution based on different rotational forces by rotating the rotating body at different speeds.
[0282] In step S910a, the sample analysis device 2000 may inject a second cleaning solution into the solution chamber 910a of the microfluidic device 1000. For example, although a cleaning process was performed by the sample analysis device 2000 in step S908a, impurities and uncaptured target substances may still be present in the capture filter. Therefore, the sample analysis device 2000 may prepare for a second cleaning process by injecting the second cleaning solution into the solution chamber 910a of the microfluidic device 1000.
[0283] In step S912a, the sample analysis device 2000 can control the rotating component to rotate in a second rotation direction 905a and a second rotation speed. Based on the second rotational force generated by the rotating body rotating in the second rotation direction 905a and the second rotation speed, the solution stored in the solution chamber 910a of each microfluidic structure (e.g., the second-injected cleaning solution) can be moved to the first waste chamber 912a. In step S912a, during the process of the sample analysis device 2000 moving the cleaning solution in the solution chamber to the first waste chamber 912a, residual substances other than the target material captured by the capture filter can be cleaned. Therefore, the purified target material will ultimately be located in the capture filter.
[0284] In step S914a, the sample analysis device 2000 may inject elution solution into the solution chamber 914a of the fluid device 1000. More specifically, the sample analysis device 2000 may inject elution solution (elution) for separating target substances captured by the capture filter into the solution chamber 914a through a solution injection port. The sample analysis device 2000 may inject pre-stored elution solution into a storage unit by connecting an injection mechanism to the solution injection port connected to the solution chamber 914a.
[0285] According to one embodiment, the solution chamber 914a of the microfluidic device 1000 may be connected to a second manual valve for controlling the movement of the solution in the solution chamber to the capture filter based on a predetermined rotational force. Therefore, the washing solution in the solution chamber 914a may not be able to move to the capture filter until all solution chambers within the microfluidic device 1000 have been injected with elution solution.
[0286] In step S916a, the sample analysis device 2000 can control the rotating component to rotate in a first rotation direction 915a and a third rotational speed. Based on the third rotational force generated by the rotating body rotating in the first rotation direction 904a and the third rotational speed, the elution solution stored in the solution chambers 914a of the various microfluidic structures can be moved to the collection chamber 916a. That is, during the movement of the elution solution injected into the microfluidic device 1000, the sample analysis device 2000 can rotate the rotating component along other rotational directions used for moving the sample and the washing solution. According to one embodiment, the third rotational force can be greater than or equal to the resistance provided by a second manual valve connected to the solution chamber 914a.
[0287] More specifically, as described above, the elution solution collected in the collection chamber 916a can be filled into at least a portion of the channel within the siphon channel 918a connected to one end of the collection chamber 916a. According to one embodiment, the elution solution can be filled into a portion of the siphon channel corresponding to the height to which the elution solution fills the collection chamber 916a. According to one embodiment, when the elution solution has filled at least a portion of the siphon channel, the sample analysis device 2000 can station the rotating body for a preset time, and then rotate the rotating body alternately along a first direction and a second direction. For example, the sample analysis device 2000 can shake the collection chamber 916a by alternately rotating the rotating body along the first and second directions.
[0288] According to one embodiment, it is assumed that the reaction solution used to amplify the target substance in the collection chamber 918a is freeze-dried. When the elution solution fills at least a portion of the siphon channel connected to one end of the collection chamber 916a, the sample analysis device 2000 can briefly suspend the rotating body for a period of time and rotate the rotating body alternately in two directions so that the reaction solution in the collection chamber can react with the target substance contained in the elution solution.
[0289] In step S918a, after a predetermined time, the sample analysis device 2000 can bring the rotating body to a standstill for a preset time. According to one embodiment, the sample analysis device 2000 can bring the rotating body to a standstill for a longer time than the standstill time before shaking the collection chamber 916a. As the rotating body comes to a standstill, the capillary force acting on the elution solution filling at least a portion of the channels in the siphon channel 918a connected to one end of the collection chamber 918a will be greater than the rotational force acting on the elution solution in the aforementioned portion of the channels, thereby allowing the elution solution in the siphon channel 918a to begin moving to the dispensing chamber 920a.
[0290] That is, by keeping the rotating component stationary for a predetermined time, the sample analysis device 2000 can move the elution solution stored in a portion of the siphon channel and the collection chamber to the dispensing chamber under the action of capillary force within the siphon channel 918a. According to one embodiment, the sample analysis device 2000 can move the elution solution containing the target substance stored in the collection chamber to the dispensing chamber by rotating the rotating component at a fourth rotational speed (e.g., RPM 0). According to one embodiment, the action of rotating the rotating component at the fourth rotational speed by the sample analysis device 2000 can correspond to the action of keeping the rotating component stationary. In step S918a, once the elution solution stored in at least a portion of the collection chamber 916a and the siphon channel begins to move towards the reaction chamber, the sample analysis device 2000 can rotate the rotating component at a fifth rotational speed (e.g., 5000 RPM).
[0291] In step S920a, the sample analysis device 2000 can dispense the elution solution containing the target substance, which has been moved to the dispensing chamber through the siphon channel 918a, into the dispensing chamber. According to one embodiment, the sample analysis device 2000 can dispense the elution solution containing the target substance, which has been moved to the dispensing chamber through the siphon channel, into the dispensing chamber by rotating the rotating member in a first rotation direction and a fifth rotation speed.
[0292] In step S922a, when the elution solution containing the target substance is dispensed into the dispensing chamber, the sample analysis device 2000 can generate oil by applying a predetermined heat to the wax storage section, thereby dispensing the generated oil into the dispensing chamber. In step S924a, the sample analysis device 1000 can inject the solution containing the target substance dispensed into the dispensing chamber into the reaction chamber 924a by rotating the rotating component in a first rotation direction and a sixth rotation speed.
[0293] In step S926a, the sample analysis device 2000 can maintain the microfluidic device 1000 at a preset temperature, thereby maintaining the interior of the reaction chamber 926a at a predetermined temperature for the amplification reaction of the target substance. As described above, the reaction chamber 926a may contain a pre-freeze-dried reaction solution for the amplification reaction of the target substance. According to one embodiment, the sample analysis device 2000 can induce an amplification reaction for the target substance in the reaction chamber by maintaining the microfluidic device 1000 at 65 degrees.
[0294] The sample analysis device 2000 can induce an amplification reaction of the target substance in the reaction chamber according to the above-described series of sample analysis methods, and during the amplification reaction, capture images of the microfluidic device at predetermined time intervals. The sample analysis device 2000 can also obtain a first image by capturing images of a preset microfluidic device at preset time intervals, and extract an image of the reaction chamber region within the first image. The sample analysis device 2000 can also quantify the amplification reaction process and the concentration of the target substance in the sample based on the change in color values in the image of the reaction chamber region.
[0295] According to another embodiment, the sample analysis device 2000 may also transmit the first or second image obtained above to a server connected to the sample analysis device 2000, and receive information about the sample analysis results from the server.
[0296] Figure 9 It shows the basis Figures 2a to 2c The figure shows a microfluidic device and a sample analysis device using the microfluidic device to analyze a sample.
[0297] The process of sample analysis by the sample analysis device 2000 using the microfluidic device 1000 will be described in detail according to one embodiment. According to one embodiment, the sample analysis device 2000 can quantitatively measure the amount and presence of target substances (e.g., target antigens) in a sample using the microfluidic device 1000.
[0298] The sample analysis device 2000 can rotate a rotating body of a microfluidic device integrated with the sample analysis device around at least one rotation axis and at a preset number of rotations and rotation direction. The sample analysis device 2000 can move samples and solutions injected into the microfluidic device 1000 to the interior of at least one microfluidic structure within the microfluidic device based on the rotational force generated by the rotation of the rotating body. The sample analysis device 2000 can control the movement of the sample or solution along different directions by controlling at least one of the rotation direction and rotation speed of the rotating body.
[0299] According to one embodiment, the sample injected into the microfluidic device 1000 via the sample analysis device 2000 may include a target substance (e.g., target antigen) as the object of analysis, as well as impurities other than the target substance. Furthermore, the solution injected into the microfluidic device 1000 via the sample analysis device 2000 may include: a washing solution for washing away remaining substances other than the target substance (e.g., target antigen); a solution containing an antibody with an attached chromogenic enzyme as a reaction solution for an enzyme-linked immunosorbent assay (ELISA); and a solution containing a chromogenic substrate.
[0300] In step S902b, a microfluidic device 1000, comprising at least one microfluidic structure for moving samples and solutions, can be securely attached to the sample analysis device 2000. In step S904a, the sample analysis device 2000 can inject a sample into the sample chamber 904b of the microfluidic device 1000, which is secured to a rotating component of the sample analysis device. For example, the sample analysis device 2000 can inject a pre-stored sample into a storage compartment by connecting an injection mechanism to a vent connected to the sample chamber 904b. According to one embodiment, as... Figure 2c As shown, the sample injected into the sample chamber 904b can be filled to the outlet portion of the siphon channel 906b connected to the waste chamber. According to one embodiment, the sample injected through the sample analysis device 2000 may contain the target antigen to be detected.
[0301] According to one embodiment, the interior of sample chamber 904b may be pre-coated with antibodies capable of complementary binding to target antigens. For example, when the rotating body is stationary, after a sample containing target antigens injected into sample chamber 904b is injected into the distal portion of the siphon channel (e.g., the portion of the siphon channel closest to the waste chamber where the sample is injected), a predetermined incubation time (e.g., approximately 30 minutes) can be provided. After incubation, the target antigens in the sample can bind to the antibodies pre-coated in sample chamber 904b. Furthermore, substances other than the target antigens bound to the antibodies, such as unbound target antigens and other impurities, may be present in sample chamber 904b.
[0302] In step S906b, the sample analysis device 2000 injects a sample into the sample chamber, filling the end of the siphon channel connecting one end of the sample chamber and the waste chamber. According to one embodiment, with the rotating body stationary, the sample analysis device 2000 injects the sample into the sample chamber and the aforementioned siphon channel. In step S906b, after injecting the sample into the sample chamber and the siphon channel, the sample analysis device 2000 waits for a predetermined incubation time. During incubation, the target substance in the sample injected by the sample analysis device 2000 can bind to the antibody pre-stored in the sample chamber.
[0303] In step S908b, the sample analysis device 2000 can move a sample containing target antigens not captured by pre-coated antibodies and impurities stored in the sample chamber 904b and the siphon channel to the waste chamber by rotating the rotating component at a first rotation speed.
[0304] In step S910b, the sample analysis device 2000 may inject a solution into the solution chamber 910b of the microfluidic device 1000. For example, the sample analysis device 2000 may inject a cleaning solution used to clean target antigens and other impurities that have not bound to antibodies in the sample chamber 904b into the solution chamber 910b. As described above, a manual valve may be attached to one end of the solution chamber 910b to prevent the solution in the solution chamber from moving into the sample chamber until all solution chambers in other microfluidic structures are filled with solution.
[0305] In step S912b, the sample analysis apparatus 2000 moves the washing solution stored in the solution chamber to the sample chamber via a manual valve by rotating the rotating component at a second rotational speed. During the rotation of the rotating component at the second rotational speed, the solution moved to the sample chamber 904b via the manual valve can move to a portion of the siphon channel. According to one embodiment, under the action of a second rotational force, the solution moved to the sample chamber via the manual valve can move to a portion of the siphon channel located at a height corresponding to the solution-filled height in the sample chamber.
[0306] When the solution fills a portion of the siphon channel, the sample analysis device 2000 can stop the rotation of the rotating component for a preset time, and then rotate the rotating component alternately in two directions. For example, if the solution moves into a portion of the siphon channel while the sample analysis device 2000 is rotating the rotating component at a second rotation speed, the sample analysis device 2000 can stop the rotating component for a short period of time and then shake the microfluidic device 1000.
[0307] The sample analysis device 2000 can shake the microfluidic device by alternately rotating the rotating component in two directions, so that the washing solution in the sample chamber separates the target antigens that are not bound to the antibody and other impurities in the sample chamber.
[0308] In step S914b, the sample analysis device 2000 can reduce the rotational speed of the rotating component or temporarily stop the rotating component to allow a washing solution containing unbound target antigens and impurities from the sample chamber 904b to be injected into the siphon channel 914b. As the capillary force provided by the siphon channel 914b exceeds the rotational force of the rotating component, the washing solution containing unbound target antigens and impurities from the sample chamber 904b can begin to be injected into the siphon channel.
[0309] In step S916b, the sample analysis device 2000 may allow the rotating component to remain stationary for a preset time to allow the washing solution containing unbound target antigens and impurities in the sample chamber 904b to move to the waste chamber 916b, after which the rotating component is rotated again at a third rotation speed. In step S916b, purified antibody-antigen conjugates may be present in the sample chamber 904b.
[0310] More specifically, with the washing solution injected into the sample chamber 904b filling a portion of the siphon channel, the sample analyzer, by shaking, cannot move to the end of the siphon channel but remains within at least a portion of the siphon channel and inside the sample chamber 904b, separating unbound antigens and impurities from the sample chamber. The sample analyzer 2000 can rotate the rotating component alternately in two directions for a predetermined time period and then bring it to a standstill for a preset time. According to one embodiment, the sample analyzer 2000 can allow the rotating component to remain stationary for a longer period than the time it remained stationary before the shaking action.
[0311] When the sample analysis device 2000's rotating component is stationary, the cleaning solution filling at least a portion of the siphon channel, impurities contained in the cleaning solution, and antigens not bound to antibodies can move to the outlet portion of the siphon channel under the capillary force of the siphon channel. When the cleaning solution in the siphon channel, along with the impurities and antigens not bound to antibodies contained in the cleaning solution, begins to move towards the waste chamber, the sample analysis device 2000 can again move the rotating component at a third rotational speed.
[0312] According to one embodiment, the sample analysis device 2000 can use different cleaning solutions (e.g., a second cleaning solution, a third cleaning solution, and a fourth cleaning solution) to repeat the cleaning process of steps S910b to S916b a predetermined number of times. For example, the sample analysis device 2000 can also use the first cleaning solution, the second cleaning solution, the third cleaning solution, and the fourth cleaning solution to repeat the cleaning process four times. However, it is not limited to this.
[0313] In step S918b, the sample analysis device 2000 may inject a solution containing an antibody coated with a chromogenic enzyme for an enzyme-linked immunosorbent assay (ELISA) into the solution chamber 918b of the microfluidic device 1000. For example, the sample analysis device 2000 may conjugate a second antibody and a solution containing a chromogenic enzyme conjugated to the second antibody into the solution chamber 918b. The second antibody is capable of binding to a target antigen that has bound to a first antibody pre-coated on the sample chamber 904b. According to one embodiment, the first and second antibodies provided may be the same antibody.
[0314] In step S920b, the sample analysis device 2000 can move a solution containing a second antibody coated with a chromogenic enzyme, stored in the solution chamber, to the sample chamber 920b via a manual valve by rotating the rotating component of the microfluidic device 1000 at a second rotational speed. During the rotation of the rotating component at the second rotational speed, the solution containing the second antibody coated with the chromogenic enzyme, moved to the sample chamber 920 via the manual valve, can move to a portion of the siphon channel. According to one embodiment, under the action of a second rotational force, the solution moved to the sample chamber via the manual valve can move to a portion of the siphon channel located at a height corresponding to the solution-filled height in the sample chamber.
[0315] When the solution fills a portion of the siphon channel, the sample analysis device 2000 can allow the rotating component to remain stationary for a preset time before rotating it alternately in two directions. For example, if the solution moves into a portion of the siphon channel while the sample analysis device 2000 is rotating the rotating component at a second rotation speed, the sample analysis device 2000 can allow the rotating component to remain stationary for a short period of time before shaking the microfluidic device 1000.
[0316] The sample analysis device 2000 can agitate the microfluidic device by alternately rotating the rotating component in two directions, thereby allowing a second antibody, which is attached to a chromogenic enzyme inside the sample chamber, to be attached to a conjugate of purified antigen and first antibody immobilized in the sample chamber.
[0317] In step S922b, the sample analysis device 2000 may allow the rotating component to remain stationary for a preset time before rotating it at a third rotation speed. This allows the second antibody, which is not connected to the antigen-first antibody conjugate fixed in the sample chamber 920b and is connected to a chromogenic enzyme, and the solution containing the second antibody, injected in step S918, to move through the siphon channel 922b to the waste chamber 924b. According to one embodiment, the sample analysis device 2000 may allow the stationary time of the rotating component to be longer than the stationary time before shaking the rotating component.
[0318] As the rotating component comes to a standstill, the capillary force acting on the solution filling a portion of the siphon channel increases, allowing the second antibody, which is not bound to the antigen and the first antibody but is bound to the chromogenic enzyme, and the solution containing the second antibody to move to the outlet portion of the siphon channel. When the solution begins to move into the waste chamber 924b, the sample analysis device 2000 can rotate again at a third rotation speed.
[0319] According to one embodiment, although in Figure 9As not shown, after performing steps S918b to S924b, the sample analysis device 2000 may further perform a cleaning process to clean the second antibody, which is not linked to the antigen and the first antibody conjugate and is linked to the chromogenic enzyme. According to one embodiment, after step S924b, the sample analysis device 2000 may again perform the actions of steps S910b to S916b.
[0320] In step S926b, the sample analysis device 2000 may inject a solution containing a chromogenic substrate into the solution chamber 926b. For example, the sample analysis device 2000 may inject a solution containing a chromogenic substrate that can react with a secondary conjugate linked to a chromogenic enzyme.
[0321] In step S928b, the sample analysis device 2000 can move the solution containing the chromogenic substrate stored in the solution chamber 926b to the sample chamber 982b via a manual valve by rotating the rotating component of the microfluidic device 1000 at a second rotational speed. As described later in step S932b, the chromogenic substrate moved to the sample chamber 928b can react with a secondary conjugate to which the chromogenic enzyme is attached to produce a chromogenic reaction 932b.
[0322] According to one embodiment, during the rotation of the rotating body at a second rotational speed, the solution containing the chromogenic substrate, which has been moved to the sample chamber 928b via a manual valve, can move to a portion of the siphon channel. According to another embodiment, under the action of a second rotational force generated by the rotating component, the solution containing the chromogenic substrate, which has been moved to the sample chamber via a manual valve, can move to a portion of the siphon channel located at a height corresponding to the height to which the solution fills the sample chamber. When the solution containing the chromogenic substrate has filled a portion of the siphon channel, the sample analysis device 2000 can, after a preset time of rest from rotation of the rotating component, alternately rotate the rotating component in two directions.
[0323] For example, while the sample analysis device 2000 is rotating the rotating component at a second rotational speed, if a solution containing the aforementioned chromogenic substrate moves into a portion of the siphon channel, the sample analysis device 2000 can allow the rotating component to remain stationary for a short period before shaking the microfluidic device 1000. The sample analysis device 2000 can induce a chromogenic reaction by causing the chromogenic substrate to react with the chromogenic enzyme through the shaking of the sample chamber.
[0324] In step S930b, after a predetermined time, the sample analysis device 2000 may allow the rotating component to remain stationary for a preset time before rotating it at a third rotational speed, so that the solution containing the chromogenic substrate in the sample chamber 928b moves through the siphon channel 930b to the waste chamber 932b. According to one embodiment, the sample analysis device 2000 may allow the stationary time of the rotating component to be longer than the stationary time before shaking the rotating component, thereby causing the solution containing the chromogenic substrate stored in a portion of the siphon channel and in the sample chamber to begin moving towards the waste chamber. When the solution containing the chromogenic substrate begins to move towards the waste chamber, the sample analysis device 2000 may again rotate the rotating component at the third rotational speed.
[0325] In step S932b, the sample analysis device 2000 may wait for the time required for the reaction between the chromogenic substrate and the chromogenic enzyme in the sample chamber 928b. According to one embodiment, in order to purify the chromogenic reaction through the reaction between the chromogenic substrate and the chromogenic enzyme, the sample analysis device 2000 may capture images of the microfluidic device at preset time intervals to obtain a first image. The sample analysis device 2000 may extract a second image related to the sample chamber from the first image and analyze the color information within the extracted second image to quantify the reaction process.
[0326] As described above, the sample analysis device 2000 can inject a sample containing the target antigen, a cleaning solution for cleaning antigens and impurities that are not bound to antibodies in the sample chamber, and other reaction solutions for enzyme-linked immunosorbent assay (ELISa) into the microfluidic device 1000, and rotate the microfluidic device 100 at a specified speed and direction of rotation to effectively induce reactions occurring inside multiple microfluidic structures in the microfluidic device.
[0327] Furthermore, as mentioned above, although Figure 9 As not shown in the diagram, the sample analysis device 2000 can also obtain a first image by taking pictures of the microfluidic device at preset time intervals, extract a second image related to the sample chamber region in the obtained first image, and automatically analyze the reaction process based on the changes in the color values of the extracted second image.
[0328] Figure 10 It shows the basis Figures 3a to 3c The figure shows a microfluidic device and a sample analysis device using the microfluidic device to analyze a sample.
[0329] The process of sample analysis by sample analysis device 2000 via microfluidic device 1000 will be described in detail according to one embodiment. According to one embodiment, sample analysis device 2000 can extract target substances (e.g., specific genomes) from samples via microfluidic device 1000.
[0330] The sample analysis device 2000 can rotate a rotating body of a microfluidic device integrated with the sample analysis device around at least one rotation axis and at a preset number of revolutions and rotation direction. The sample analysis device 2000 can move samples and solutions injected into the microfluidic device 1000 to the interior of at least one microfluidic structure within the microfluidic device based on the rotational force generated by the rotation of the rotating body. The sample analysis device 1000 can control the movement of the sample or solution along different directions by controlling the rotation direction and rotation speed of the rotating body.
[0331] According to one embodiment, the sample injected into the microfluidic device 1000 via the sample analysis device 2000 may include a target substance as the object of analysis and impurities other than the target substance. Furthermore, the solution injected into the microfluidic device 1000 via the sample analysis device 2000 may include a cleaning solution for rinsing away any remaining substances other than the target substance, and an elution solution, such as water, for separating the target substance from the capture filter.
[0332] In step S902c, the sample analysis device 2000 may fasten the microfluidic device 1000 to the rotating component. In step S904c, the sample analysis device 2000 may inject a sample into the sample chamber 902c of the microfluidic device 1000. For example, the sample analysis device 2000 may inject a pre-stored sample into a storage unit by connecting an injection mechanism to a sample injection port connected to the sample chamber. According to one embodiment, the sample chamber of the microfluidic device 1000 may be connected to a first manual valve for controlling the movement of the sample in the sample chamber to the capture filter based on a predetermined rotational force. Therefore, the sample in the sample chamber may not be able to move to the capture filter until the sample analysis device 2000 injects the sample into all sample chambers within the microfluidic device 1000.
[0333] In step S906a, the sample analysis device 2000 can control the rotating component to rotate in a first rotation direction 904c and a first rotational speed. Based on the first rotational force generated by the rotating body rotating in the first rotation direction 904c and the first rotational speed, the sample stored in the sample chamber 902c of each microfluidic structure can be moved to the waste chamber 906c. According to one embodiment, the first rotational force may be greater than or equal to the resistance provided by a first manual valve connected to the solution chamber 902c.
[0334] According to one embodiment, the sample analysis apparatus 2000 can generate a first rotational force by controlling a rotating body, thereby causing a sample stored in sample chambers within various fluid structures to pass through a capture filter. The capture filter 905c may include: glass fibers of a predetermined thickness, a plurality of silica beads, or a silica bead matrix, and the glass fibers of the predetermined thickness, the silica beads, or the silica bead matrix can be used to capture target substances within the sample. Substances other than the captured target substances and the target substances in the sample may be present in the capture filter.
[0335] In step S908c, the sample analysis device 2000 may inject a solution into the solution chamber 908c of the microfluidic device 1000. More specifically, the sample analysis device 2000 may inject a cleaning solution for cleaning substances other than the target substance in the sample into the solution chamber 908c. For example, the sample analysis device 2000 may inject pre-stored cleaning solution into a storage compartment by connecting an injection mechanism to a sample injection port connected to the solution chamber 908c. According to one embodiment, the solution chamber of the microfluidic device 1000 may be connected to a second manual valve for controlling the movement of the solution in the solution chamber to the capture filter based on a predetermined rotational force. Therefore, the cleaning solution in the solution chamber 908c may not be able to move to the capture filter until all solution chambers within the microfluidic device 1000 have been injected with cleaning solution.
[0336] In step S910c, the sample analysis device 2000 can control the rotating component to rotate in a first rotation direction 904c and a second rotation speed. Based on the second rotational force generated by the rotating body rotating in the first rotation direction 904c and the second rotation speed, the solution (e.g., a cleaning solution) stored in the solution chamber 908c of each microfluidic structure can be moved to the waste chamber 912c. The second rotational force can be greater than or equal to the resistance provided by a second manual valve connected to the solution chamber 908c.
[0337] According to one embodiment, the sample analysis apparatus 2000 can generate a second rotational force by controlling a rotating body, which can cause the solution stored in the solution chambers within each fluid structure to pass through a capture filter. The capture filter 905c may contain residual substances and impurities other than the captured target substance, and these residual substances and impurities can be moved to the waste chamber 912c along with the injected cleaning solution.
[0338] According to one embodiment, in the sample analysis apparatus 2000, the first manual valve for controlling the movement of the sample and the second manual valve for controlling the movement of the solution can provide the same resistance. Alternatively, according to another embodiment, the first and second manual valves can provide different resistances, and the sample analysis apparatus 2000 can rotate the rotating body at different speeds, thereby controlling the movement of the sample and solution based on different rotational forces.
[0339] In step S912c, the sample analysis device 2000 may inject a cleaning solution into the solution chamber 914c of the microfluidic device 1000. For example, although a cleaning process was performed by the sample analysis device 2000 in step S910c, impurities and uncaptured target substances may still be present in the capture filter. Therefore, the sample analysis device 2000 may prepare for a second cleaning process by injecting a cleaning solution into the solution chamber 914c of the microfluidic device 1000. According to one embodiment, after injecting a first cleaning solution into the microfluidic device in step S908c, the sample analysis device 2000 may inject a second cleaning solution different from the first cleaning solution in step S912c. According to one embodiment, the first cleaning solution and the second cleaning solution may also be the same cleaning solution.
[0340] In step S914c, the sample analysis device 2000 can control the rotating component to rotate in a first rotation direction 904c and a second rotation speed. Based on the second rotational force generated by the rotating body rotating in the first rotation direction 904c and the second rotation speed, the solution stored in the solution chamber 914c of each microfluidic structure (e.g., the cleaning solution injected for the second time) can be moved to the waste chamber 914c.
[0341] In step S916c, the sample analysis device 2000 may inject the elution solution into the solution chamber 918c of the microfluidic device 1000. More specifically, the sample analysis device 2000 may inject the elution solution (Elusion) used to separate the target substance captured by the capture filter into the solution chamber 918c through the solution injection port. The sample analysis device 2000 may inject pre-stored elution solution into the storage section by connecting the injection mechanism to the solution injection port connected to the solution chamber 918c.
[0342] According to one embodiment, the solution chamber 918c of the microfluidic device 1000 may be connected to a second manual valve for controlling the movement of the solution in the solution chamber to the capture filter based on a predetermined rotational force. Therefore, the washing solution in the solution chamber 908c may not be able to move to the capture filter until all solution chambers within the microfluidic device 1000 have been injected with elution solution.
[0343] In step S918c, the sample analysis device 2000 can control the rotating component to rotate in a second rotation direction 904c and a third rotational speed. Based on the third rotational force generated by the rotating body rotating in the second rotation direction 920c and the third rotational speed, the elution solution stored in the solution chamber 918c of each microfluidic structure can be moved to the collection chamber 922c. That is, during the movement of the elution solution injected into the microfluidic device 1000, the sample analysis device 2000 can cause the rotating component to rotate along other rotational directions used for moving the sample and the washing solution. According to one embodiment, the third rotational force can be greater than or equal to the resistance provided by a second manual valve connected to the solution chamber 918c.
[0344] More specifically, based on the third rotational force generated by the rotation of the rotating body, the eluent stored in the solution chamber 918c can move to the capture filter despite the resistance provided by the second manual valve. The eluent moving to the capture filter can separate the purified target material captured by the capture filter from the capture filter. In step S918c, since the rotating part is in a state of rotating in the second rotation direction 920c, the eluent containing the captured target material can be moved through the transfer chamber to the collection chamber 922c instead of the waste chamber.
[0345] According to an embodiment of the present disclosure, the sample analysis apparatus 2000 executes the sample analysis method in the above-described sequence, thereby enabling rapid processing of a large number of samples and automatic extraction of target substances from pre-processed samples.
[0346] According to one embodiment, the sample analysis device 2000 can obtain a first image of the microfluidic device 1000 for each of the above steps. According to another embodiment, after step S918c, the sample analysis device 2000 can obtain a first image of the microfluidic device 1000 at predetermined time intervals. The sample analysis device 2000 can obtain a second image of the collection chamber by preprocessing the first image.
[0347] The sample analysis device 2000 can identify pixel values of a second image relating to a collection chamber and determine the amount of color change in the collection chamber within the second image based on the identified pixel values. The sample analysis device 2000 can also identify the concentration of a target substance stored in the collection chamber within the microfluidic device based on the amount of color change in the collection chamber. According to another embodiment, the sample analysis device 2000 can also transmit information regarding the identification results of the first image, the second image, or the concentration of the target substance to other external devices or servers connected to the sample analysis device 2000.
[0348] Figure 11 This is a block diagram illustrating a sample analysis apparatus according to one embodiment.
[0349] Figure 12 This is a block diagram illustrating a sample analysis apparatus according to another embodiment.
[0350] like Figure 11 As shown, the sample analysis apparatus 2000 may include a processor 1300, a memory 1700, a first drive unit 1810, a second drive unit 1820, and a supply unit 1920. However, not all of the components shown are necessary. The sample analysis apparatus 2000 can be implemented with more components than shown, or it can be implemented with fewer components.
[0351] For example, Figure 12 As shown, a sample analysis apparatus 2000 according to one embodiment includes: a drive unit 1800 including a processor 1300, a first drive unit 1810 and a second drive unit 1820; a memory 1700; and a supply unit 1920. In addition, it may also include: a user input interface 1100, an output unit 1200, a sensing unit 1400, a network interface 1500, an A / V input unit 1600, a heating unit 1940 and a linear guide 1960.
[0352] User input interface 1100 refers to a unit for user input to control the sequence of the sample analysis device 2000. For example, user input interface 1100 may include a keypad, dome switch, touchpad (using methods such as contact capacitance, pressure impedance film, infrared sensing, surface ultrasonic conduction, integral tension measurement, and piezoelectric effect), rotary wheel, rotary switch, etc., but is not limited to these. User input interface 1100 can receive user input sequence for the images output by the sample analysis device 2000 to the display. Furthermore, user input interface 1100 can also receive touch input from the user touching the display or key input via the graphical user interface of the display.
[0353] The output unit 1200 can output audio signals, image signals, or vibration signals, and the output unit 1200 may include: a display unit 1210, a sound output unit 1220, and a vibration motor 1230.
[0354] The display unit 1210 may include a screen for displaying and outputting information processed by the sample analysis device 2000. Furthermore, the screen refers to an image captured within the collection chamber or reaction chamber connected to the dispensing chamber of the microfluidic device, which can be used to analyze the results of biological or chemical reactions occurring inside the reaction chamber or collection chamber.
[0355] The sound output unit 1220 can output audio data received by the network interface 1500 or stored in the memory 1700. Furthermore, the sound output unit 1220 can output sound signals related to the functions performed in the sample analysis device 2000. The vibration motor 1230 can output vibration signals. For example, the vibration motor 1230 can output vibration signals corresponding to the output of functions performed in the electronic device 1000.
[0356] The processor 1300 is generally used to control the overall operation of the sample analysis device 2000. For example, the processor 1300 can execute a program stored in the memory 1700 to perform overall control of the user input unit 1100, output unit 1200, sensor unit 1400, network interface 1500, A / V input unit 1600, etc. Furthermore, the processor 1300 can execute a program stored in the memory 1700 to perform... Figures 1a to 10 The functions of the sample analysis device 2000 described in the document.
[0357] Specifically, the processor 1300 can obtain user input by controlling the user input unit to touch the screen of the sample analysis device 2000. According to one embodiment, the processor 1300 can also control a microphone to obtain the user's voice. The processor 1300 can execute applications for moving samples and solutions within the microfluidic device based on user input, and can also execute applications for measuring the reaction results with target substances in the collection chamber. Furthermore, other user input can be obtained through the applications executed by the processor 1300.
[0358] According to one embodiment, the processor 1300 can automatically execute a sample analysis process in a microfluidic device combined with the sample analysis device 2000 by executing at least one instruction related to a sample analysis method stored in the memory 1700.
[0359] According to one embodiment, the processor 1300 can control a first drive unit to rotate the microfluidic device along the aforementioned rotation axis. Furthermore, according to another embodiment, the processor 1300 can also control a second drive unit that can move an injection mechanism for injecting the sample and solution along a preset drive axis to the microfluidic device.
[0360] Furthermore, according to one embodiment, the processor 1300 can control the supply unit for storing samples and solutions to be provided to the injection unit, so that the stored samples and solutions (washing solutions and elution solutions, washing solutions and reaction solutions for ELISA reactions) are selectively provided to the injection unit.
[0361] According to one embodiment, the processor 1300 can generate a first rotational force by controlling the rotating component to rotate in a first rotational direction and a first rotational speed. According to another embodiment, the processor 1300 can also generate a second rotational force along the first rotational direction by controlling the rotating component to rotate in a first rotational direction and a second rotational speed.
[0362] According to another embodiment, the processor 1300 can also control the rotating component to rotate in a second rotation direction and a first rotational speed, causing the rotating component to generate a first rotational force along the second rotation direction. Additionally, according to another embodiment, the processor 1300 can also control the rotating component to rotate in a second rotation direction and a second rotational speed, causing the rotating component to generate a second rotational force along the second rotation direction.
[0363] According to one embodiment, the processor 1300 can control a second drive component within the second drive unit to move up and down along at least one guide shaft. Additionally, the processor 1300 can control a stepper motor to rotate the second drive component within the second drive unit at predetermined angular intervals, thereby controlling the injection mechanism connected to one end of the drive shaft to be positioned on a predetermined fluid structure within the microfluidic device.
[0364] According to one embodiment, the processor 1300 can maintain the temperature required for sample reaction by controlling a heating element located at the lower part of the sample analysis device compactly integrated into the microfluidic device 1000. Furthermore, the processor 1300 can also control the heating element to provide uniform thermal energy to the microfluidic device by controlling a linear guide for aligning the position of the heating element in the direction outside the first drive unit.
[0365] According to one embodiment, the processor 1300 can control a port valve within the supply section to connect one of the supply channels connected to the storage section to the injection channel of the injection mechanism. Furthermore, the processor 1300 can control an injection pump so that after the supply channel connected to the storage section is connected to the injection channel, the solution or sample stored in the storage section is discharged into the injection mechanism through both the supply channel and the injection channel.
[0366] According to one embodiment, the processor 1300 can acquire images of the microfluidic device at preset time intervals by controlling a camera within the sample analysis apparatus. Furthermore, the processor 1300 can also transmit information about the images acquired from the camera to other external devices connected to the sample analysis apparatus.
[0367] According to one embodiment, the processor 1300 can also identify reaction chamber regions within an image of the microfluidic device obtained by a camera, and quantify the course of a chemical or biological reaction occurring in the reaction chamber region based on the color values of the image of the identified reaction chamber region.
[0368] For example, when the reaction chamber contains target material, primers, and LAMP solution, the processor 1300 can also obtain images of the reaction chamber region by taking pictures of the reaction chamber at preset time intervals, and analyze the amplification reaction of the target material based on the amount of change in color values within the obtained images.
[0369] According to another embodiment, when the sample chamber contains an antibody that binds to a target substance (e.g., a target antigen), an antibody that binds to a chromogenic enzyme, and a solution containing a chromogenic substrate capable of reacting with the aforementioned chromogenic enzyme, the processor 1300 obtains an image of the sample chamber region by taking pictures of the sample chamber at preset time intervals, and analyzes the process of the ELISA reaction based on the amount of change in color values within the obtained image.
[0370] According to another embodiment, the processor 1300 can also identify a collection chamber region within an image of the microfluidic device obtained by a camera, and quantify the course of a chemical or biological reaction occurring in the chamber region based on the color values of the image of the identified collection chamber region.
[0371] According to another embodiment, the processor 1300 can also control the network interface to transmit images of the reaction chamber obtained at preset time intervals to an external device, and receive the results of image analysis received by the external device.
[0372] According to another embodiment, the processor 1300 can also control the network interface to transmit images of the sample chamber obtained at preset time intervals to an external device, and receive the results of image analysis received by the external device.
[0373] According to another embodiment, the processor 1300 can also control the network interface to transmit images of the collection chamber obtained at preset time intervals to an external device, and receive the results of image analysis received by the external device.
[0374] The sensing unit 1400 enables the sample analysis device 2000 to detect the surrounding conditions and transmit the detected information to the processor 1300. The sensing unit 1400 may include, but is not limited to, at least one of the following: an acceleration sensor 1420, a temperature / humidity sensor 1430, an infrared sensor 1440, a gyroscope sensor 1450, a barometric pressure sensor 1470, a proximity sensor 1480, and an illuminance sensor 1490. Since those skilled in the art can intuitively infer the function of each sensor from its name, a detailed description of it will be omitted.
[0375] The network interface 1500 may include one or more components for enabling the sample analysis device 2000 to communicate with other devices (not shown) and the server 4000. Other devices (not shown) may be devices similar to the sample analysis device, or computing devices capable of acquiring images and analyzing the color values of the acquired images, or sensor devices, but are not limited thereto. For example, the network interface 1500 may include: a wireless communication interface 1510, a wired communication interface 1520, and a mobile communication unit 1530.
[0376] The wireless communication interface 1510 may include, but is not limited to, a short-range wireless communication unit, a Bluetooth communication unit, a near-field communication unit, a wireless local area network (WLAN) communication unit, a Zigbee communication unit, an infrared data association (IrDA) communication unit, or a Wi-Fi Direct (WFD) communication unit. The wired communication interface 1520 can be connected to the server 2000 or the sample analysis device 2000 via a wired connection.
[0377] Mobile communication unit 1530 can transmit / receive wireless signals via a mobile communication network to at least one of a base station, an external terminal, or a server. The wireless signals may include voice signals, video call signals, or various types of data transmitted / received based on text / multimedia messages.
[0378] According to one embodiment, the network interface 1500 can transmit images of the microfluidic device to a server under the control of a processor. Furthermore, the network interface 1500 can also receive analysis results from the server regarding the extent of the reaction within the reaction chamber.
[0379] The A / V (Audio / Video) input unit 1600 can be used to input audio or image signals, and may include a camera module 1610 and a microphone 1620, etc. The camera module 1610 can acquire image frames such as still images or moving images via an image sensor in video call mode or shooting mode. Images captured by the image sensor can be processed by a processor 1300 or a separate image processing unit (not shown). For example, the camera module 1610 can acquire images of the reaction chamber according to a predetermined shooting cycle.
[0380] Microphone 1620 can receive external sound signal input and process it into electronic voice data. For example, microphone 1620 can receive sound signals from external devices or users. Microphone 1620 can receive user voice input. Microphone 1620 can use various noise cancellation algorithms to remove noise generated during the reception of external sound signals.
[0381] The memory 1700 can store programs for processing and control by the processor 1300, and can also store data input or output from the sample analysis device 2000. Furthermore, the memory 1700 can store various drive instructions required by the sample analysis device 2000 to control the first drive unit and the second drive unit. Additionally, the memory 1700 may include various instructions required by the sample analysis device 2000 for extracting samples or solutions from the supply unit, injecting the extracted samples or solutions into the microfluidic device, and automatically executing the sample analysis process by rotating the microfluidic device in a predetermined direction and speed.
[0382] The memory 1700 may include at least one of the following types of storage media: flash memory, hard disk, multimedia card micro, card type memory (e.g., SD or XD memory), random access memory (RAM), network static random access memory (SRAM), read-only memory (ROM), electrically erasable programmable read-only memory (EEPROM), programmable read-only memory (PROM), magnetic storage, magnetic disk, optical disk.
[0383] The programs stored in memory 1700 can be classified into multiple modules according to their functions, such as UI module 1710, touch screen module 1720, notification module 1730, etc.
[0384] UI module 1710 can provide each application with a dedicated UI, GUI, etc., that interacts with sample analysis device 2000. Touchscreen module 1720 can detect user touch gestures on the touchscreen and send information about the touch gestures to processor 1300. According to some embodiments, touchscreen module 1720 can recognize and analyze touch codes. Touchscreen module 1720 can also be configured as a separate hardware component including a controller.
[0385] The notification module 1730 can generate a signal to notify the sample analysis device 2000 of an event that has occurred. Examples of events occurring in the sample analysis device 2000 include: receiving a call signal, receiving a message, inputting a key signal, and notification of a schedule. The notification module 1730 can output the notification signal as an image signal via the display unit 1210; it can also output the notification signal as an audio signal via the sound output unit 1220; or it can output the notification signal as a vibration signal via the vibration motor 1230.
[0386] The drive unit 1800 may include a first drive unit 1810 and a second drive unit 1820. Each component of the drive unit 1800 may correspond to... Figures 4 to 7 The first drive unit 520 and the second drive unit 540 described herein will therefore be omitted in their detailed description.
[0387] The supply unit 1920 can store samples and solutions to be supplied to the injection mechanism, and supply the stored samples and solutions to the injection mechanism through specific supply channels. Each component of the supply unit 1920 can correspond to... Figures 4 to 7 The port valve 649, supply channel 646 and storage unit 642 described herein will therefore be omitted in their detailed description.
[0388] The heating element 1940 can generate heat at the bottom of the microfluidic device, thereby providing a suitable temperature for the reaction of the sample and solution within the microfluidic device. When the specified sample and solution are injected into the microfluidic device, the linear guide 1960 can align with the heating element located at the bottom of the microfluidic device, thereby providing a constant heat to the microfluidic device 1000. The heating element 1940 and the linear guide 1960 can respectively target the reaction of the sample and solution within the microfluidic device. Figure 5 The heating elements 632 and 634 and the linear guides 636 and 638 described herein will therefore be omitted in their detailed description.
[0389] Figure 13 This is a block diagram showing a server connected to a sample analysis apparatus according to an embodiment.
[0390] Server 4000 may include: network interface 4100, database 4200, and processor 4300. Network interface 4100 may correspond to... Figures 11 to 12The network interface 1500 of the sample analysis device 1000 shown is illustrated. For example, the network interface 4100 can receive images of the collection chamber within the microfluidic device from the sample analysis device 2000, and can also transmit information about the image analysis results of the collection chamber determined in the server 4000 to the sample analysis device 2000.
[0391] According to another embodiment, the network interface 4100 can receive images of the sample chamber within the microfluidic device from the sample analysis device 2000, and can also transmit information about the image analysis results of the sample chamber determined in the server 4000 to the sample analysis device 2000.
[0392] Database 4200 can correspond to Figure 11 The sample analysis device 2000 shown has a memory 1700. For example, the database 4200 may store information about: a first image of the microfluidic device received from the sample analysis device 2000, a second image of the collection chamber generated by preprocessing the first image, and a reaction result determined by analyzing the color information in the first and second images.
[0393] Furthermore, according to one embodiment, the database 4200 may also store information about the following: the color value of the collection chamber obtained from the image of the collection chamber, the amount of change in the reaction time of the color value, and the concentration of the target substance determined based on the amount of change in the color value of each collection chamber.
[0394] According to another embodiment, the database 4200 may store information about: a first image of the microfluidic device received from the sample analysis device 2000, a second image of the sample chamber generated by preprocessing the first image, and an immunodiagnostic result determined by analyzing the color information in the first image and the second image.
[0395] According to another embodiment, the database 4200 may also store information about the color values of the sample chambers obtained from images of the sample chambers, the amount of change in the reaction time of the color values, and the concentration of the target substance determined based on the amount of change in the color values of each sample chamber.
[0396] According to another embodiment, the database 4200 may store information about the following: a first image of the microfluidic device received from the sample analysis device 2000, a second image of the collection chamber generated by preprocessing the first image, and a reaction result determined by analyzing the color information in the first image and the second image.
[0397] Processor 4300 is generally used to control the overall operation of server 4000. For example, processor 4300 can control database 4200 and network interface 4100 as a whole by executing programs stored in database 4200 on server 4000. Furthermore, processor 4300 can execute programs stored in database 4100 to perform... Figures 1a to 10 The operation of part of the sample analysis device 2000 described in the document.
[0398] For example, during the extraction of target material from the collection chamber in the sample analysis device 2000, the processor 4300 may also acquire a first image of the microfluidic device, acquire a second image of the reaction chamber from the acquired first image, and identify color information of the reaction chamber from the second image.
[0399] According to another embodiment, during an immune response to a target substance in a collection chamber in the sample analysis device 2000, the processor 4300 may also acquire a first image of the microfluidic device, acquire a second image of the reaction chamber from the acquired first image, and identify color information of the sample chamber from the second image.
[0400] In addition, the processor 4300 can also identify the amplification reaction process of the target substance extracted in the reaction chamber based on the obtained color information, quantify the change in concentration or color of the target substance, and transmit the quantification result information of the target substance to the sample analysis device 2000.
[0401] According to another embodiment, the processor 4300 can also identify the concentration of the target substance extracted in the sample chamber based on the acquired color information, and transmit the identified concentration information of the target substance to the sample analysis device 2000.
[0402] The method according to one embodiment can be implemented in the form of program instructions executable by various computer devices and recorded on a computer-readable medium. The computer-readable medium may individually include program instructions, data files, data structures, etc., or may include combinations thereof. The program instructions recorded on the medium are specifically designed and configured for this disclosure, but may also be known and available to those skilled in the art of computer software.
[0403] Furthermore, a computer program apparatus including a recording medium storing a program for performing other methods according to one of the above embodiments can be provided. Examples of computer-readable recording media include: magnetic media such as hard disks, floppy disks, and magnetic tapes; optical media such as CD-ROMs and DVDs; magneto-optical media such as floppy disks; and hardware devices specifically configured to store and execute program instructions, such as read-only memory (ROM), random access memory (RAM), and flash memory. Examples of program instructions include not only machine language code generated by a compiler but also high-level language code that can be executed by a computer using an interpreter.
[0404] The embodiments of this disclosure have been described in detail above, but the scope of protection of this invention is not limited thereto. Various modifications and improvements made by those skilled in the art based on the basic concept of this disclosure as defined in the following claims are all within the scope of this invention.
Claims
1. A microfluidic device, characterized in that, include: Solid of revolution; At least two microfluidic structures are arranged at a predetermined distance inside the rotating body; Solution injection port; as well as A shared channel connects all microfluidic structures by connecting the solution injection port to any one of the at least two microfluidic structures; for the remaining microfluidic structures, they are connected by linking one microfluidic structure to an adjacent microfluidic structure. Each of the aforementioned microfluidic structures includes: The pretreatment unit shares the solution injected through the solution injection port with other adjacent microfluidic structures via the shared channel, and performs a pretreatment process on the sample injected through the sample injection port and the solution. A storage unit, located radially outward from the pretreatment unit within the rotating body, separates and stores the sample and solution pretreated by the pretreatment unit along the rotation direction of the rotating body; and The detection unit detects the target substance in the pre-treated sample dispensed from the storage unit. The preprocessing unit includes: A sample chamber for containing a sample injected through the sample injection port; A solution chamber for receiving a solution injected through the solution inlet via the shared channel; A capture filter for capturing target substances from the injected sample; A first manual valve, connected between the sample chamber and the capture filter, controls the flow from the sample chamber to the capture filter such that the sample in the sample chamber cannot move to the capture filter until the sample is injected into all sample chambers of each microfluidic structure; and A second manual valve is connected between the solution chamber and the capture filter and controls the flow from the solution chamber to the capture filter so that the solution in the solution chamber cannot move to the capture filter until the solution is shared to all solution chambers of each of the microfluidic structures.
2. The microfluidic device according to claim 1, characterized in that, The shared channel is formed in a zigzag shape along the circumference inside the rotating body. The rotating body, by being stationary or rotating, prevents the solution in the solution chamber from moving to the capture filter until the solution in the solution chamber is shared with the various solution chambers in other microfluidic structures.
3. The microfluidic device according to claim 1, characterized in that, The storage unit includes: A collection chamber for storing an elution solution containing the target substance in the sample and the target substance captured by the capture filter in the solution; and A first waste chamber is used to store a cleaning solution for cleaning remaining substances other than the sample that has passed through the capture filter and the target material captured by the capture filter in the solution.
4. The microfluidic device according to claim 3, characterized in that, The storage unit further includes a transfer chamber for obtaining an elution solution containing the target substance or a sample passing through the capture filter and the washing solution from the capture filter, and selectively transferring the elution solution containing the target substance to the collection chamber along the rotation direction of the rotating body, or transferring the sample passing through the capture filter and the washing solution to the first waste chamber. The reaction solution used to detect the target substance in the collection chamber is freeze-dried.
5. The microfluidic device according to claim 3, characterized in that, The detection unit includes: A siphon channel, one end of which is connected to the collection chamber; A dispensing unit, connected to the other end of the siphon channel, includes multiple dispensing chambers such that a predetermined amount of elution solution containing the target substance from the collection chamber is dispensed into the multiple dispensing chambers; and The reaction section includes a reaction chamber for obtaining an elution solution containing the target substance provided by the dispensing chamber, and freeze-drying primers and reaction solution for detecting the target substance.
6. The microfluidic device according to claim 5, characterized in that, The detection unit further includes a second waste chamber for storing the remaining elution solution after it has been allocated to the allocation chamber from the elution solution containing the target substance obtained from the siphon channel.
7. The microfluidic device according to claim 5, characterized in that, The detection unit further includes a wax storage unit for storing wax, which generates oil at a preset temperature for use in the dispensing chamber, so as to prevent the evaporation of the elution solution containing the target substance after it is dispensed into the dispensing chamber.
8. The microfluidic device according to claim 5, characterized in that, The rotating body remains stationary for a preset time, causing the rotational force generated by the rotating body acting on at least a portion of the siphon channel to be less than the capillary force generated in the at least a portion of the channel, thereby causing the target substance in the collection chamber to begin moving towards the siphon channel.
9. The microfluidic device according to claim 5, characterized in that, The rotating body rotates such that the rotational force applied to the elution solution containing the target substance in the dispensing chamber is greater than the air pressure stored in the reaction chamber.
10. A sample analysis device, characterized in that, include: The microfluidic device as described in claim 1; A first drive unit is used to rotate the microfluidic device along a rotation axis; The second drive unit is used to move the injection mechanism, which injects the sample and the solution into the microfluidic device along a preset drive axis. A supply unit is used to store samples and solutions to be supplied to the injection mechanism, and to selectively supply the stored samples and solutions to the injection mechanism; as well as The control unit controls the first drive unit, the second drive unit, and the supply unit to make the sample and the solution in the microfluidic structure move along a preset path.
11. The sample analysis apparatus according to claim 10, characterized in that, The first driving unit includes: A rotating component, configured to be fastened to the microfluidic device and capable of rotating with the microfluidic device along its axis of rotation; and The spindle motor rotates the rotating component in a predetermined direction and speed based on a first control signal obtained from the control unit.
12. The sample analysis apparatus according to claim 10, characterized in that, The second drive unit includes: At least one guide shaft is provided at preset intervals; A first driving component is connected to one end of the driving shaft and fastens the injection mechanism; A second driving component is connected to the other end of the drive shaft and transmits driving force to the drive shaft so that the drive shaft rotates at predetermined angular intervals; and A stepper motor is used to rotate the second drive component.
13. The sample analysis apparatus according to claim 12, characterized in that, The second driving component further includes: Through hole, for allowing the at least one guide shaft to pass through; and The ball screw component is in contact with the surface formed in the through hole. Furthermore, with the ball screw component and the thread formed on the at least one guide shaft in a tight fit, the second drive component moves along the at least one guide shaft.
14. The sample analysis apparatus according to claim 10, characterized in that, The sample analysis device further includes: A heating element is formed at the bottom of the microfluidic device and surrounds at least a portion of the first driving element in a cylindrical shape in the direction outside the first driving element; and A linear guide is used to align the position of the heating element in the outer direction of the first driving part.
15. The sample analysis apparatus according to claim 10, characterized in that, The sample includes target substances that are the subjects of analysis. The solution comprises: a cleaning solution for washing away any remaining substances other than the target substance, an elution solution for separating the target substance, and a reaction solution for amplifying the target substance in the sample.
16. The sample analysis apparatus according to claim 15, characterized in that, The supply department includes: A storage unit that separately stores the sample, the washing solution, and the elution solution; A supply channel, which is connected to the storage unit, and separately obtains the sample, the washing solution, the elution solution, and the reaction solution from the storage unit; A port valve, under the control of the control unit, selects from the supply channels the channel to be connected to the injection mechanism; and An injection pump is used to move the sample, the washing solution, the elution solution, and the reaction solution from the storage unit to the injection mechanism.
17. The sample analysis apparatus according to claim 16, characterized in that, The storage unit includes: A sample storage unit is used to store the samples; A cleaning solution storage section for storing the cleaning solution; Elution solution storage section for storing the elution solution; and A reaction solution storage section is used to store the reaction solution. Furthermore, the sample storage unit, the cleaning solution storage unit, and the elution solution storage unit also include a connection hole for communicating with the supply channel.
18. The sample analysis apparatus according to claim 10, characterized in that, The sample analysis device further includes: A first housing is configured to house the first drive unit, the second drive unit, and the control unit within the first housing; and A second housing is connected to the first housing in an openable and closable manner, thereby selectively exposing the microfluidic device.
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