Microfluidic chip, cartridge, and genetic analysis device including same
Patent Information
- Application Number
- PCT/KR2024/010868
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2023-08-09
- Filing Date
- 2024-07-25
- Publication Date
- 2025-02-13
Smart Images

Figure KR2024010868_13022025_PF_FP_ABST
Abstract
Description
Microfluidic chip, cartridge and genetic analysis device including the same
[0001] The present invention relates to a microfluidic chip, a cartridge, and a genetic analysis device including the same, and more particularly, to a device that has a compact analytical tool capable of accommodating a genetic amplification reaction and a solution therefor, capable of obtaining rapid analysis results on site, and capable of automatically performing a genetic analysis process.
[0002] As of January 2023, confirmed cases of COVID-19 worldwide have exceeded 765 million, and seasonal influenza remains a significant respiratory pathogen, circulating globally in various types and subtypes.
[0003] Consequently, rapid and reliable methods for detecting viral pathogens are essential to ensure timely treatment and mitigate the spread of disease.
[0004] Currently available rapid test kits are crucial for SARS-CoV-2 screening, as identified by the Centers for Disease Control and Prevention, but their accuracy is limited, especially in the early stages of infection.
[0005] The most reliable technique for virus detection is reverse transcription-polymerase chain reaction (RT-PCR), which amplifies and identifies target viral RNA / DNA through fluorescent signals. However, it has the disadvantage of requiring long operating times (3-4 hours), bulky equipment, and skilled analysts.
[0006] These shortcomings limit on-site diagnostics in high-risk locations such as airports, universities, bus stops, and community health clinics.
[0007] The purpose of the present invention is to provide a compact analytical tool capable of accommodating a genetic amplification reaction and a solution therefor, capable of obtaining rapid analysis results on site, and capable of automatically performing the genetic analysis process.
[0008] In one embodiment, a cartridge may include a chamber block that is arranged on the upper side of a microfluidic chip and has a chamber in which a solution is positioned, wherein each chamber formed on the microfluidic chip is connected vertically through a channel having a set diameter and rotated in a set direction so that the solution is moved by centrifugal force and supplied to the chamber of the microfluidic chip.
[0009] The chamber block may be characterized in that a plurality of washing and elution cartridge chambers are arranged to be spaced apart from each other, and the washing and elution cartridge chambers are connected to each other through an amplification fractionation channel having a set diameter, so that when a solution is injected into one of the washing and elution cartridge chambers, it is moved to the plurality of washing and elution cartridge chambers.
[0010] The chamber block may be characterized in that a plurality of chambers are formed, an injection port is formed that is connected to the chambers and is connected downwardly to the outside of the chambers, and the injection port and the chamber are connected by a flow path having a set diameter, so that when the chamber block is rotated in a set direction, a solution positioned within the chamber is supplied to the chamber of the microfluidic chip through the injection port.
[0011] The chamber block may be characterized in that a plurality of amplification cartridge chambers are formed spaced apart from the washing and elution cartridge chambers, and the amplification cartridge chambers are communicated through an amplification fractionation channel that connects the amplification cartridge chambers to at least the inside of the chamber block, not the surface.
[0012] A microfluidic chip positioned at the lower side of the cartridge is rotatable with the chamber block, and a plurality of chambers are formed, and are communicated with the chambers of the cartridge through an injection port, and each chamber of the microfluidic chip is characterized in that a plurality of chambers are arranged from the center to the outside, and each chamber is communicated with a channel of a set diameter and rotates in a set direction so that the solution of the cartridge can move.
[0013] The above microfluidic chip may be characterized in that it includes a sample chamber, a membrane column communicating with the outside of the sample chamber and capturing viruses, and a transfer chamber communicating with the membrane column from the outside of the membrane column, and when rotated in a set direction, a solution passing through the sample chamber passes through the membrane column and is transferred to the transfer chamber.
[0014] The above-mentioned transfer chamber may be arranged along the shape of an arc, one side connected to a reaction chamber, and the other side connected to a waste chamber located outside the transfer chamber, so as to transfer the solution to the reaction chamber or the waste chamber depending on the direction of rotation.
[0015] The above reaction chamber and the transfer chamber may include a flow path having a set diameter, and the solution positioned in the transfer chamber may not be moved to the reaction chamber unless the microfluidic chip is rotated in a set direction at a set speed or more.
[0016] The above reaction chamber is connected to the transfer chamber through a euro channel formed in the shape of an arc, and the above reaction chamber may be characterized in that it is composed of a plurality of reaction chambers and is formed to the outside spaced apart along the euro channel.
[0017] It may further include a wax chamber in which wax is placed on the inside along the shape of the above euro channel.
[0018] A genetic analysis device according to one embodiment may include a microfluidic chip, a cartridge coupled with the microfluidic chip, a solution loading unit that injects a solution into the cartridge, and a genetic analysis unit that measures a fluorescent signal generated from the microfluidic chip by placing the microfluidic chip thereon.
[0019] The genetic analysis unit may include a rotation motor that rotates the microfluidic chip by placing the microfluidic chip thereon, a reaction heater that is positioned to face the reaction chamber of the microfluidic chip and applies heat to the reaction chamber, and a fluorescence detector that scans the reaction chamber to measure a fluorescence signal in real time.
[0020] The microfluidic chip may further include a wax heater that is positioned so as to face the wax chamber and applies heat to the wax chamber, and a cooling fan that cools the reaction heater and the wax heater.
[0021] The above solution loading unit may include a robot arm, an elevation unit installed on the robot arm, and a support unit installed on the elevation unit on which a syringe or pipette is placed.
[0022] The above-mentioned lifting unit may include a first lifting unit coupled to the robot arm, and a second lifting unit installed on the first lifting unit and raised and lowered by the first lifting unit, and having the support unit installed thereon to raise and lower the support unit.
[0023] The support member may be installed on the elevating member. In addition, the support member may include a support coupling rod through which the finger rest of the syringe is slidably connected or separated. In addition, the support member may be installed on the elevating member and positioned above the support coupling rod, and may include a button coupling rod through which the push button of the syringe is slidably connected or separated.
[0024] The above support member may be installed on the lifting member. In addition, the support member may include a pipette fixing rod that penetrates the outer tube of the pipette and is fixed to the upper end of the outer tube, a pipette tip removal rod that is installed on the lifting member and separates the pipette tip from the pipette, and a button lifting rod that is installed on the lifting member and to which the push button of the pipette is fixed.
[0025] The microfluidic chip, cartridge and genetic analysis device including the same according to the present invention can accommodate a solution for genetic analysis in the cartridge and microfluidic chip, and can perform all genetic analysis processes such as injection of the solution, sample pretreatment, genetic amplification and fluorescent signal measurement in an automated manner.
[0026] Additionally, the overall size is compact, making it easy to carry, transport, and deploy on site.
[0027] In addition, the present invention can perform multiple genetic tests using a single microfluidic chip, thereby enabling rapid genetic analysis.
[0028] Figure 1 is a front view of a genetic analysis device according to one embodiment of the present invention.
[0029] Figure 2 is a perspective view of the genetic analysis unit illustrated in Figure 1.
[0030] Figure 3 is a bottom view of the wax heater and reaction heater arranged inside the housing illustrated in Figure 2.
[0031] Figure 4 is a perspective view of a cooling fan and a fluorescent detector placed inside the housing illustrated in Figure 2.
[0032] Figure 5 is a perspective view of the tip rack and syringe rack shown in Figure 1.
[0033] Fig. 6 is a perspective view of the elevator shown in Fig. 1.
[0034] Fig. 7 (a) is a side view showing a state in which a syringe is coupled to the syringe support shown in Fig. 6.
[0035] Figure 7 (b) is a side view showing a state in which a pipette tip is coupled to the pipette illustrated in Figure 6.
[0036] Figure 8 (a) is an enlarged view showing the state before the syringe is coupled to the syringe support shown in Figure 6.
[0037] Figure 8 (b) is an enlarged view showing a state in which a syringe is coupled to the syringe support shown in Figure 6.
[0038] Figure 9 (a) is an enlarged view showing the state before the pipette tip is attached to the pipette illustrated in Figure 6.
[0039] Figure 9 (b) is an enlarged view showing a state in which a pipette tip is coupled to the pipette illustrated in Figure 6.
[0040] Figure 10 is an exploded view of the cartridge and microfluidic chip illustrated in Figure 1.
[0041] Fig. 11 (a) is a plan view of the cartridge illustrated in Fig. 10.
[0042] Figure 11 (b) is a bottom view of the cartridge illustrated in Figure 10.
[0043] Figure 12 (a) is a perspective view showing a state in which a swab sample containing a virus is inserted into the cartridge illustrated in Figure 10.
[0044] Figure 12 (b) is a perspective view showing a state in which the cartridge illustrated in Figure 10 is combined with a microfluidic chip.
[0045] Fig. 13 is a bottom view of the microfluidic chip illustrated in Fig. 10, showing an actually manufactured microfluidic chip.
[0046] Figure 14 is a bottom view of the microfluidic chip illustrated in Figure 10.
[0047] Figure 15 is a partially enlarged view of the microfluidic chip illustrated in Figure 14.
[0048] Fig. 16 is a plan view showing the flow state of the solution in the cartridge and microfluidic chip illustrated in Fig. 10.
[0049] Figure 17 is a diagram showing the results of a clinical sample test for detection of four respiratory viruses using the genetic analysis device illustrated in Figure 1.
[0050] Figure 18 is a diagram showing the LOD test results for influenza A H1N1, influenza A H3N2, and influenza B using the genetic analysis device illustrated in Figure 1.
[0051] Figure 19 is a diagram showing the LOD test results for the SARS-CoV-2 orf1ab and S genes using the genetic analysis device illustrated in Figure 1.
[0052] In order to explain in detail the technical idea of the present invention to a degree that a person having ordinary skill in the art to which the present invention pertains can easily practice the present invention, the most preferred embodiment of the present invention will be described with reference to the attached drawings.
[0053] First, when adding reference signs to the components of each drawing, it should be noted that identical components are given the same signs whenever possible, even if they are shown on different drawings.
[0054] In addition, when describing the present invention, if it is determined that a detailed description of a related known configuration or function may obscure the gist of the present invention, the detailed description is omitted.
[0055] Hereinafter, a genetic analysis device according to an embodiment of the present invention will be described with reference to FIGS. 1 to 19.
[0056] Figure 1 is a front view of a genetic analysis device according to one embodiment of the present invention.
[0057] Referring to FIG. 1, a genetic analysis device (10) may include a microfluidic chip (100), a cartridge (200), a solution loading unit (300), and a genetic analysis unit (400).
[0058] The solution loading unit (300) injects a solution into the cartridge (200), and the cartridge (200) is coupled with the microfluidic chip (100) so that the solution injected into the cartridge (200) can flow into the microfluidic chip (100).
[0059] A microfluidic chip (100) containing a solution is placed in a genetic analysis unit (400), and the genetic analysis unit (400) can measure a fluorescent signal generated from the microfluidic chip (100).
[0060] Fig. 2 is a perspective view of the genetic analysis unit illustrated in Fig. 1, Fig. 3 is a bottom view of the wax heater and reaction heater arranged inside the housing illustrated in Fig. 2, and Fig. 4 is a perspective view of the cooling fan and fluorescence detector arranged inside the housing illustrated in Fig. 2.
[0061] Referring to FIGS. 2 to 4, the genetic analysis unit (400) may include a housing (410), a rotation motor (420), a reaction heater (440), and a fluorescence detector (460).
[0062] The rotary motor (420) is a known motor such as a spindle motor, a step motor, or a servo motor, and is placed inside the housing (410) and is mounted on the upper surface of the stand (480), and the stand (480) can slide and be inserted into or extracted from the housing (410).
[0063] The stand (480) may be in the shape of an 'L' and may include a mounting plate (481) on which a rotary motor (420) is installed, and a finishing plate (482) that extends from the end of the mounting plate (481) and is formed by bending upward.
[0064] A holder insertion hole (411) is formed on the side of the housing (410), and a mounting plate (481) is inserted into the holder insertion hole (411) so that the closing plate (482) comes into contact with the side of the housing (410) and the holder insertion hole (411) can be closed.
[0065] The size of the housing (410) is 290x250x270mm, and the vertical length of the housing (410) is 400mm when the stand (480) is pulled out, making it compact and easy to carry, transport, and deploy on site.
[0066] In addition, the layout space of the genetic analysis device (10, shown in FIG. 1) can be made smaller than that of a conventional PCR workstation, at 400 mm, x550 mm x 300 mm.
[0067] The microfluidic chip (100) is placed on top of the rotary motor (420) with the cartridge (200) coupled thereto, and the bolt (B, shown in FIG. 2) sequentially passes through the bolt fastening holes (111, 230, shown in FIG. 10, FIG. 14) formed in the cartridge (200) and the microfluidic chip (100) to be coupled to the rotary motor (420) and firmly fixed thereto.
[0068] The rotation motor (420) can control the flow of the solution flowing into the microfluidic chip (100) by rotating the microfluidic chip (100) at a preset rotation speed and rotation direction.
[0069] The reaction heater (440) uses a Peltier heater and is placed on the upper part of the microfluidic chip (100) so as to face the reaction chamber (129) of the microfluidic chip (100), and can apply heat to the reaction chamber (129) to proceed with a gene amplification reaction.
[0070] The fluorescence detector (460) is placed at the bottom of the microfluidic chip (100) so as to face the reaction chamber (129) of the microfluidic chip (100), and can sequentially scan a plurality of reaction chambers (129) to measure fluorescence signals in real time.
[0071] The genetic analysis unit (400) may further include a wax heater (430), a cooling fan (450), a display (470, shown in FIG. 2), and a control unit.
[0072] The wax heater (430) uses a Peltier heater and can be placed on the upper part of the microfluidic chip (100) so as to face the wax chamber (128) of the microfluidic chip (100).
[0073] The wax heater (430) can apply heat to the wax chamber (128) of the microfluidic chip (100) to melt the paraffin wax contained inside the wax chamber (128), and the melted paraffin wax can seal the reaction chamber (129) of the microfluidic chip (100) to prevent the solution contained in the reaction chamber (129) from leaking out or being cross-contaminated.
[0074] The cooling fan (450) is placed above the reaction heater (440) and the wax heater (430) to cool the reaction heater (440) and the wax heater (430) and quickly control the temperature of the reaction heater (440) and the wax heater (430).
[0075] The display (470) is a touch screen and is installed on the upper surface of the housing (410) so that real-time fluorescence signals and analysis values of the fluorescence signals can be displayed.
[0076] The control unit is mounted on a printed circuit board and placed inside the housing (410), and can selectively control the operation of the configuration comprising the genetic analysis unit (400) and the solution loading unit (300) based on preset values input to the display (470).
[0077] The control unit automatically measures, analyzes, and processes the fluorescence signal generated from the microfluidic chip (100), and in addition to the display (470), the analysis results can be transmitted in real time to the smartphone of the patient or analysis personnel via a wireless network such as the Internet or Wi-Fi, thereby enabling accurate diagnosis and rapid on-site diagnosis to be implemented simultaneously.
[0078] Figure 5 is a perspective view of the tip rack and syringe rack shown in Figure 1.
[0079] Referring to FIG. 1 and FIG. 5, the solution loading unit (300) may include a robot arm (310), an elevating unit (320), a support unit (330), a syringe rack (350), a tip rack (360), and a waste container (370).
[0080] The robot arm (310) is a multi-joint arm that can move up and down, forward and backward, and rotate left and right via a turntable.
[0081] The syringe rack (350) and tip rack (360) are holders for syringes (20) and pipette tips (30), and syringes (20) and pipette tips (30) that have a predetermined solution in advance can be held thereon.
[0082] Fig. 6 is a perspective view of the lifting unit illustrated in Fig. 1, (a) of Fig. 7 is a side view showing a state in which a syringe is coupled to the syringe support illustrated in Fig. 6, and (b) of Fig. 7 is a side view showing a state in which a pipette tip is coupled to the pipette illustrated in Fig. 6.
[0083] And, (a) of Fig. 8 is an enlarged view showing a state before the syringe is coupled to the syringe support shown in Fig. 6, and (b) of Fig. 8 is an enlarged view showing a state in which the syringe is coupled to the syringe support shown in Fig. 6.
[0084] And, (a) of Fig. 9 is an enlarged view showing a state before the pipette tip is combined with the pipette shown in Fig. 6, and (b) of Fig. 9 is an enlarged view showing a state when the pipette tip is combined with the pipette shown in Fig. 6.
[0085] Referring to FIG. 1, FIG. 6 to FIG. 9 (b), the lifting unit (320) is installed on the robot arm (310, shown in FIG. 1), and the support unit (330) is installed on the lifting unit (320) so that a syringe (20) or a pipette (340) can be placed thereon.
[0086] That is, the lifting unit (320) moves to a certain position of the syringe rack (350), tip rack (360), and genetic analysis unit (400, shown in FIG. 1) by the operation of the robot arm, and the lifting unit (320) raises and lowers the support unit (330) to enable fine adjustment of the syringe (20) or pipette (340).
[0087] A waste container (370, shown in FIG. 1) can be used to store the syringe (20) and pipette tip (30) from which the solution has been withdrawn, separated from the support (330) for later processing.
[0088] The elevator unit (320) includes a first elevator unit (321) and a second elevator unit (322), and the remaining components except for the motor can be manufactured using a 3D printer.
[0089] The first lifting unit (321) is coupled with the robot arm (310) and moves in synchronization with the movement of the robot arm (310), the second lifting unit (322) is installed in the first lifting unit (321) and is raised and lowered by the first lifting unit (321), and the support unit (330) is installed so as to raise and lower the support unit (330).
[0090] The first lifting unit (321) may include a first fixing unit (321d), a first lifting motor (321a), a first pinion gear (321b), and a first rack bar (321c).
[0091] The first fixing member (321d) is a stand for the first lifting motor (321a), and can be fixed by being connected to the robot arm (310) using a known fixing member such as a bolt, screw, piece, or clamp.
[0092] Hereinafter, fixation between the components of the solution loading section (300) is achieved through a fixing member, and a detailed description thereof will be omitted.
[0093] The first lifting motor (321a) uses a known motor such as a spindle motor, a step motor, or a servo motor, and the motor shaft is fixed by penetrating the first pinion gear (321b), and the first rack bar (321c) can be engaged with the first pinion gear (321b) in the vertical direction.
[0094] The second lifting unit (322) may include a second settling unit (322d), a second lifting motor (322a), a second pinion gear (322b), and a second rack bar (322c).
[0095] The second fixing portion (322d) may be fixedly connected to the upper end of the first rack bar (321c) or may be formed as an integral extension, and the second lifting motor (322a) may be placed on the second fixing portion (322d).
[0096] The second lifting motor (322a) is identical to the first lifting motor (321a), and the motor shaft is fixed by penetrating the second pinion gear (322b), and the second rack bar (322c) can be engaged with the second pinion gear (322b) in the vertical direction.
[0097] The support (330) may include a syringe support (331) and a pipette support (332).
[0098] The syringe support (331) is a structure in which a syringe (20) placed on a syringe rack (350) is moved and placed, and may include a pedestal coupling rod (331a) and a button coupling rod (331b).
[0099] The pedestal coupling rod (331a) is formed to extend to the side of the second mounting portion (322d), and a pedestal insertion groove (331aa) is formed at an end along the length of the pedestal coupling rod (331a), so that the finger rest (22) of the syringe (20) can be slidably coupled to or separated from the pedestal insertion groove (331aa).
[0100] The button coupling rod (331b) is formed to extend from the upper end of the second rack bar (322c) and is placed on the upper end of the support coupling rod (331a), and a button insertion groove (331ba) is formed at the end of the button coupling rod (331b) along the length of the button coupling rod (331b), so that the push button (23) of the syringe (20) can be slidably coupled to or separated from the button insertion groove (331ba).
[0101] The pipette support (332) is a structure in which a pipette (340) is placed and fixed, and may include a pipette fixing rod (332a), a pipette tip removal rod (332b), and a button lifting rod (332c).
[0102] One end of the pipette fixing rod (332a) is formed to extend to the second fixing portion (322d), and the other end penetrates the outer tube (341) of the pipette (340) so that it can be integrally fixed to the upper end of the outer tube (341).
[0103] One end of the pipette tip removal rod (332b) is formed to extend to the lower end of the second rack bar (322c), the other end penetrates the outer tube (341), and can move linearly along the second rack bar (322c) to separate the pipette tip (30) from the pipette (340).
[0104] One end of the button lifting rod (332c) is formed to extend to the top of the second rack bar (322c), and the other end can be fixed by being combined with the push button (342) of the pipette (340).
[0105] That is, the syringe (20) can be coupled or separated from the support (330) or the pipette tip (30) can be coupled or separated from the pipette (340) by the operation of the robot arm (310) and the lifting unit (320).
[0106] Looking at the process of combining and separating the pipette tip (30), first, the lifting unit (320) is placed near the tip rack (360) by the robot arm (310), and the second lifting unit (322) is lowered by the driving of the first lifting motor (321a), so that the outer tube (341) of the pipette (340) and the pipette tip (30) placed on the tip rack (360) are combined, and the second lifting unit (322) is raised by the driving of the first lifting motor (321a), so that the pipette tip (30) can be separated from the tip rack (360).
[0107] Afterwards, the pipette tip (30) is placed on top of the cartridge (200) mounted on the genetic analysis unit (400) by the robot arm (310), and the second rack bar (322c) is lowered by the driving of the second lifting motor (322a), so that the button lifting rod (332c) presses the push button (342) of the pipette (340) to inject the solution contained in the pipette (340) into the cartridge (200).
[0108] Afterwards, the pipette tip (30) is placed on the upper part of the waste container (370) by the robot arm (310), and the second rack bar (322c) is lowered by the second lifting motor (322a) more than when the solution is injected, so that the pipette tip removal rod (332b) presses the pipette tip (30), so that the pipette tip (30) can be separated from the outer tube (341) of the pipette (340) and fall into the waste container (370).
[0109] Looking at the process of combining and disassembling the syringe (20), first, the lifting unit (320) is placed near the syringe rack (350) by the robot arm (310), and the first rack bar (321c) and the second rack bar (322c) are raised and lowered by the driving of the first lifting motor (321a) and the second lifting motor (322a), so that the positions of the support combining rod (331a) and the button combining rod (331b) can be adjusted to correspond to the finger rest (22) and the push button (23) of the syringe (20) placed on the syringe rack (350).
[0110] Afterwards, the upper part of the finger rest (22) and the push button (23) are slidably connected to the rest insertion groove (331aa) and the button insertion groove (331ba) by the robot arm (310), and the first rack bar (321c) and the second rack bar (322c) are raised by the driving of the first lifting motor (321a) and the second lifting motor (322a), so that the syringe (20) can be separated from the syringe rack (350).
[0111] Afterwards, the syringe (20) is placed on the upper part of the cartridge (200) by the robot arm (310), and the second rack bar (322c) is lowered by the driving of the second lifting motor (322a), so that the button coupling rod (331b) presses the push button (23) of the syringe (20), thereby injecting the solution contained in the syringe (20) into the cartridge (200).
[0112] Afterwards, since the syringe (20) is placed on top of the waste container (370) by the robot arm (310), and the waste container (370) is placed in contact with the syringe rack (350), when the syringe (20) collides with the syringe rack (350) by the rotation of the robot arm (310), the finger rest (22) and push button (23) of the syringe (20) slide due to the impact and are separated from the rest insertion groove (331aa) and the button insertion groove (331ba), so that the syringe (20) can fall into the waste container (370).
[0113] Fig. 10 is an exploded perspective view of the cartridge and microfluidic chip illustrated in Fig. 1, (a) of Fig. 11 is a plan view of the cartridge illustrated in Fig. 10, and (b) of Fig. 11 is a bottom view of the cartridge illustrated in Fig. 10.
[0114] And, (a) of Fig. 12 is a perspective view showing a state in which a swab sample containing a virus is inserted into the cartridge shown in Fig. 10, and (b) of Fig. 12 is a perspective view showing a state in which the cartridge shown in Fig. 10 is coupled with a microfluidic chip.
[0115] Referring to (b) of FIGS. 10 to 12, the cartridge (200) may include a chamber block (210) and a cartridge lead (220).
[0116] The chamber block (210) is cylindrical in shape and is made of a 7 mm thick PMMA sheet. A plurality of chambers and channel patterns are formed, and a pressure-sensitive adhesive (PSA) film can be attached to each side of the cartridge (200) for sealing.
[0117] The cartridge lid (220) is made of a 2 mm thick PMMA sheet, is combined with the upper part of the chamber block (210), and has an injection hole (221) formed in communication with the chamber formed in the chamber block (210), so that a solution withdrawn from a syringe (20) or pipette (340) through the injection hole (221) can be introduced into the chamber.
[0118] The chamber block (210) may include an amplification cartridge chamber (213), a sample cartridge chamber (211), and a wash and elution cartridge chamber (212).
[0119] The amplification cartridge chamber (213) can be injected with an amplification mixture solution, the sample cartridge chamber (211) can be injected with a virus sample or a dissolution solution, and the washing and elution cartridge chamber (212) can be injected with a washing solution or an elution solution.
[0120] The sample cartridge chamber (211) is formed with a capacity of 300 μL and is formed in a long length so that a swab sample from which a virus has been collected is inserted and a dissolving solution is injected to dissolve the virus.
[0121] In this embodiment, the cartridge (200) is composed of one set of an amplification cartridge chamber (213), a sample cartridge chamber (211), and a washing and elution cartridge chamber (212), and a total of four sets are arranged spaced apart from each other along the circumference of the chamber block (210) so that four genetic analysis processes can be performed simultaneously.
[0122] Here, the number of sets of the amplification cartridge chamber (213), the sample cartridge chamber (211), and the washing and elution cartridge chamber (212) is not limited to four sets, and the number can be adjusted according to the size of the chamber block (210) or the genetic analysis apparatus.
[0123] The chamber block (210) may further include an injection port (214), an amplification flow channel (217), and a washing and elution flow channel (216).
[0124] The injection port (214) is a vertical port, and is formed in multiple pieces to protrude from the lower surface of the chamber block (210) and is inserted into a port insertion hole (112, shown in FIG. 14) formed in the chamber of the microfluidic chip (100), so that the chamber of the cartridge (200) and the chamber of the microfluidic chip (100) can be mutually communicated.
[0125] The amplification flow channel (217) connects the injection port (214) communicating with the amplification chamber (123, shown in FIG. 15) of the microfluidic chip (100) and the amplification cartridge chamber (213), and the washing and elution flow channel (216) can connect the injection port (214) communicating with the washing and elution chamber (122, shown in FIG. 15) of the microfluidic chip (100) and the washing and elution cartridge chamber (212).
[0126] The amplification cartridge chamber (213) and the washing and elution cartridge chamber (212) are connected to the injection port (214) via a channel, but the injection port (214) is formed inside the sample cartridge chamber (211) so that it can be communicated with the sample chamber (121, shown in FIG. 15) of the microfluidic chip (100).
[0127] The chamber block (210) may further include a washing and elution fractionation channel (218) and an amplification fractionation channel (215).
[0128] As described above, the washing and elution cartridge chamber (212) and the amplification cartridge chamber (213) are formed in multiple numbers, and the washing and elution collection channel (218) is formed on the upper side of the chamber block (210) to connect the multiple washing and elution cartridge chambers (212), and the amplification collection channel (215) is formed on the lower side of the chamber block (210) to connect the multiple amplification cartridge chambers (213).
[0129] That is, when a solution is injected into one of the plurality of washing and elution cartridge chambers (212) and amplification cartridge chambers (213), the solution can be divided along the washing and elution fractionation channel (218) and amplification fractionation channel (215) and then introduced into the remaining washing and elution cartridge chambers (212) and amplification cartridge chambers (213).
[0130] Here, the amplification fractionation channel (215) and the washing and elution fractionation channel (218) are formed in a zigzag shape and treated with a hydrophobic coating, thereby reducing the hydrodynamic resistance and allowing the solution to flow and divide quickly.
[0131] The sample cartridge chambers (211) each contain a virus sample and are not connected to each other to prevent contamination.
[0132] The width of the amplification fractionation channel (215) and the washing and elution fractionation channel (218) may be formed to be 1 mm, and the width of the amplification flow channel (217) and the washing and elution flow channel (216) may be formed to be 0.2 mm.
[0133] That is, the fluid dynamic resistance is increased through the microstructure of the amplification flow channel (217) and the washing and elution flow channel (216), thereby reducing the flow rate of the solution, so that the solution can be stably introduced from the cartridge (200) into the microfluidic chip (100).
[0134] Fig. 13 is a bottom view of the microfluidic chip illustrated in Fig. 10, showing an actually manufactured microfluidic chip, Fig. 14 is a bottom view of the microfluidic chip illustrated in Fig. 10, and Fig. 15 is a partial enlarged view of the microfluidic chip illustrated in Fig. 14.
[0135] Referring to FIGS. 13 to 15, the microfluidic chip (100) is in the form of a disk (110) having a thickness of 3 mm and a diameter of 130 mm, and is formed of a polymethyl methacrylate (PMMA) layer in which a plurality of chambers and channel patterns are formed, and a pressure-sensitive adhesive (PSA) film can be attached to each of both sides of the microfluidic chip (100) for sealing.
[0136] The microfluidic chip (100) may include an amplification chamber (123), a sample chamber (121), a washing and elution chamber (122), a membrane column (124), a transfer chamber (125), a waste chamber (127), a collection chamber (126), a reaction chamber (129), and a wax chamber (128).
[0137] The amplification chamber (123) can receive an amplification mixed solution from the cartridge (200), the sample chamber (121) can receive a dissolution solution from the cartridge (200), and the washing and elution chamber (122) can receive a washing solution or an elution solution from the cartridge (200).
[0138] The membrane column (124) communicates with the sample chamber (121) and the washing and elution chamber (122), and a filtering member can be accommodated inside for RNA purification.
[0139] The filter element uses GF / F glass filter papers with a diameter of 4 mm, and three sheets of glass filter papers are overlapped and inserted into and attached to a membrane column (124), so that the dissolution solution can pass through the membrane column (124) to capture RNA in the filter element.
[0140] The transfer chamber (125) communicates with the amplification chamber (123) and the membrane column (124), the waste chamber (127) communicates with one side of the transfer chamber (125), and the collection chamber (126) can communicate with the other side of the transfer chamber (125).
[0141] The waste chamber (127) can absorb the solution accommodated in the waste chamber (127) by containing a superabsorbent polymer (SAP), thereby preventing backflow.
[0142] The reaction chamber (129) is connected to the collection chamber (126), and is composed of a plurality of chambers, spaced apart from each other along the circumference of the microfluidic chip (100), and the inner surface can be coated with a primer solution capable of reacting with target RNA.
[0143] The wax chamber (128) is connected to the reaction chamber (129) and paraffin wax can be accommodated inside.
[0144] The wax is melted by the wax heater (430) to seal the reaction chamber (129), thereby preventing the solution contained in the reaction chamber (129) from leaking or being contaminated by cross-contamination during the gene amplification reaction.
[0145] In this embodiment, seven reaction chambers (129) are formed, and target RNA can be analyzed according to each reaction chamber (129).
[0146] The microfluidic chip (100) may further include a first flow channel (131) to a seventh flow channel (137).
[0147] One end of the first flow channel (131) is branched and communicates with the sample chamber (121) and the washing and elution chamber (122), respectively, and the other end can communicate with one side of the transfer chamber (125) by passing through the membrane column (124).
[0148] The second flow channel (132) can connect one side of the transfer chamber (125) and the waste chamber (127), the third flow channel (133) can connect the amplification chamber (123) and the other side of the transfer chamber (125), and the fourth flow channel (134) can connect the other side of the transfer chamber (125) and the collection chamber (126).
[0149] One end of the fifth flow channel (135) communicates with the collection chamber (126), the other end branches off and communicates with the reaction chamber (129), and the sixth flow channel (136) can connect the wax chamber (128) and the other end of the fifth flow channel (135).
[0150] A siphon valve (S) is formed at one end of the fifth flow channel (135), and the siphon valve (S) is an on-off valve that slows down the flow rate of the liquid, and can temporarily suppress the solution from flowing from the collection chamber (126) to the reaction chamber (129).
[0151] The seventh flow channel (137) is connected to the fifth flow channel (135) so that air can move.
[0152] Additionally, a waste chamber (137a) is formed between the seventh flow channel (137) and the fifth flow channel (135) so that excess solution that is not introduced into the reaction chamber (129) can be accommodated.
[0153] The solution introduced into the microfluidic chip (100) flows by centrifugal force generated by the rotation motor (420) of the genetic analysis unit (400). When the centrifugal force is large, the solution remains contained inside the chamber, and when the centrifugal force is small, the solution can flow along the channel.
[0154] To utilize this centrifugal force, the chambers of the microfluidic chip (100) can be sequentially arranged along the diameter direction of the microfluidic chip (100).
[0155] More specifically, the amplification chamber (123), the sample chamber (121), and the washing and elution chamber (122) can be placed on the inner side near the center of the microfluidic chip (100).
[0156] The membrane column (124) is positioned outside the sample chamber (121) and the washing and elution chamber (122) based on the diameter of the microfluidic chip (100), so that the solution accommodated in the sample chamber (121) and the washing and elution chamber (122) can be introduced by centrifugal force.
[0157] The transfer chamber (125) is positioned outside the membrane column (124) and the amplification chamber (123) based on the diameter of the microfluidic chip (100), so that a solution passing through the membrane column (124) or a solution accommodated in the amplification chamber (123) can be introduced by centrifugal force.
[0158] The collection chamber (126) and the waste chamber (127) are positioned outside the transfer chamber (125) based on the diameter of the microfluidic chip (100), so that the solution passing through the transfer chamber (125) can be introduced by centrifugal force.
[0159] The reaction chamber (129) is positioned outside the collection chamber (126) and the wax chamber (128) based on the diameter of the microfluidic chip (100), so that the solution contained in the collection chamber (126) or the wax contained in the wax chamber (128) can be introduced by centrifugal force.
[0160] Fig. 16 is a plan view showing the flow state of the solution in the cartridge and microfluidic chip illustrated in Fig. 10.
[0161] The genetic analysis process is as follows with reference to Figures 1 to 16.
[0162] First, a swab sample from which a virus has been collected is inserted into a sample cartridge chamber (211) of a cartridge (200), and an injection port (214, shown in FIG. 11) of a chamber block (210) is inserted into a port insertion hole (112, shown in FIG. 14) of a microfluidic chip (100), so that the chamber block (210) is coupled with the microfluidic chip (100), and then a cartridge lead (220) is coupled with the chamber block (210).
[0163] Thereafter, the microfluidic chip (100) is placed on top of the rotary motor (420, shown in FIG. 2), and the bolts sequentially pass through the cartridge (200) and the bolt fastening holes (111, 230, shown in FIG. 10, FIG. 14) formed in the microfluidic chip (100) to be fastened to the rotary motor (420) and fixed.
[0164] A tip rack (360, shown in FIG. 5) may be prepared by pre-positioning a pipette tip (30) containing 180 μL of a dissolution solution, and a syringe rack (350) may be prepared by pre-positioning a syringe (20) containing 200 μL, 200 μL, and 140 μL of a dissolution solution, a syringe (20) containing a washing solution containing 70% ethanol, and a syringe (20) containing an amplification kit for a gene amplification reaction.
[0165] A hole is formed in advance in the film attached to the upper surface of the chamber block (210) for inserting a cotton swab into the sample cartridge chamber (211), so that a dissolution solution can be injected using a pipette (340).
[0166] Afterwards, a pipette tip (30) containing a dissolved solution is connected to a pipette (340) by a solution loading section (300, shown in FIG. 1) and placed on the upper portion of a cartridge (200), and 200 μL of the dissolved solution is injected into the sample cartridge chamber (211) through an injection hole (221, shown in FIG. 10). (See FIG. 16 Step #1)
[0167] Afterwards, the used pipette tip (30) is separated from the pipette (340) by the solution loading section (300) and dropped into a waste container (370, shown in FIG. 1) for storage.
[0168] Here, since there are four sample cartridge chambers (211), the cartridge (200) is rotated 90 degrees by the rotation motor (420) to repeat the above-described process, inject the dissolution solution into the four sample cartridge chambers (211), and wait for 10 minutes for virus dissolution.
[0169] Afterwards, when the rotation motor (420, shown in FIG. 2) rotates the microfluidic chip (100) counterclockwise at 5000 rpm for 60 seconds, the dissolved solution passes through the sample chamber (121) and membrane column (124) of the microfluidic chip (100), so that RNA can be captured in the filter member.
[0170] And, the dissolved solution that has passed through the membrane column (124) flows into the transfer chamber (125), and is biased toward one side of the transfer chamber (125) by centrifugal force and flows into the waste chamber (127, shown in FIG. 1) along the second flow channel (132). (See FIG. 16 Step #2)
[0171] Afterwards, a syringe (20) is used to pierce the film attached to the cartridge (200), and the syringe (20) containing the washing solution is placed on the upper part of the cartridge (200) by the solution loading part (300, shown in FIG. 1) so that the washing solution is injected into the washing and elution cartridge chamber (212) through the injection hole (221). (See FIG. 16 Step #3)
[0172] Thereafter, when the rotation motor (420, shown in FIG. 2) rotates the microfluidic chip (100) clockwise at 5000 rpm for 60 seconds, the washing solution passes through the washing and elution chamber (122) and membrane column (124) of the microfluidic chip (100), washes the RNA captured in the filter member, and then flows into the transfer chamber (125).
[0173] Here, the cleaning solution introduced into the transfer chamber (125) is biased toward one side of the transfer chamber (125) by centrifugal force and can be introduced into the waste chamber (127) along the second flow channel (132). (See step #4 of FIG. 16)
[0174] Afterwards, the used syringe (20) can be separated from the solution loading unit (300) and stored in a waste container (370, shown in FIG. 1).
[0175] Thereafter, the above-described process can be repeated so that the elution solution and the amplification mixture solution can be injected into the washing and elution cartridge chamber (212) and the amplification cartridge chamber (213). (See step #5 of FIG. 16)
[0176] Thereafter, when the rotation motor (420, shown in FIG. 2) rotates the microfluidic chip (100) clockwise at 5000 rpm for 60 seconds, the elution solution passes through the washing and elution chamber (122) and the membrane column (124), and is received in the transfer chamber (125) containing the RNA captured in the filter member.
[0177] And, the amplification mixture solution can pass through the membrane column (124) and be accommodated in the transfer chamber (125).
[0178] Here, the amplification mixture solution and the elution solution flowing into the transfer chamber (125) are biased toward the other side of the transfer chamber (125) by centrifugal force and flow into the collection chamber (126), but the flow is suppressed by the siphon valve (S) so that they do not flow into the reaction chamber (129) and are maintained in the state of being received in the collection chamber (126) so that they can be mixed with each other. (See step #6 of FIG. 16)
[0179] Afterwards, when the rotation motor (420) rotates the microfluidic chip (100) clockwise and counterclockwise 180 degrees repeatedly at 1000 rpm, the amplification mixture solution and the elution solution can be completely mixed to create a mixture. (See step #7 of FIG. 16)
[0180] Thereafter, when the rotation motor (420) rotates the microfluidic chip (100) counterclockwise at 1000 rpm, the mixture can pass through the siphon valve (S) and be distributed to the other end of the fifth flow channel (135). (See step #8,9 of FIG. 16)
[0181] The other end of the fifth flow channel (135) is formed as a microchannel so that the flow rate of the mixture can be suppressed like a siphon valve.
[0182] Afterwards, when the rotation motor (420) rotates the microfluidic chip (100) counterclockwise at 5000 rpm for 10 seconds, the mixture flows into the reaction chamber (129) from the other end of the fifth flow channel (135). (See step #10 of FIG. 16)
[0183] Afterwards, the holder (480, shown in FIG. 2) is introduced into the interior of the housing (410), and the wax chamber (128) melts the wax contained in the wax chamber (128) at 80 degrees for 3 minutes, so that the wax passes through the sixth flow channel (136) and flows into the other end of the fifth flow channel (135), thereby sealing the reaction chamber (129). (See FIG. 16 Step #11)
[0184] Afterwards, the reaction heater (440, shown in FIG. 3) heats the reaction chamber (129) to 64 degrees, the fluorescence detector (460, shown in FIG. 4) sequentially scans the reaction chamber (129) at 3-minute intervals to measure the fluorescence signal, and the control unit can display the fluorescence signal and the analysis value of the fluorescence signal on the display (470, shown in FIG. 2).
[0185] Figure 17 is a diagram showing the results of a clinical sample test for detection of four respiratory viruses using the genetic analysis device illustrated in Figure 1.
[0186] Referring to Figure 17, the performance of the aforementioned genetic analysis was evaluated using 19 clinical samples obtained from real patients, testing 4 influenza A subtype H1N1 samples, 4 influenza A subtype H3N2 samples, 7 influenza B samples, and 4 SARS-CoV-2 samples.
[0187] Total processing time from clinical sample to genetic analysis was 1 hour 30 minutes without manual intervention, and relative quantification was assessed by threshold time, which was calculated based on raw data with a threshold intensity value of 100.
[0188] Test results showed amplification for all 19 clinical samples, with an increase in fluorescence signal before 45 minutes and no nonspecific signal in the reaction chamber.
[0189] The positive control, the 18S rRNA gene (red dot in Figure 17), showed an amplified fluorescent signal 20 minutes before all tests, indicating no negative results in the tests.
[0190] Influenza subtypes H1N1 (orange triangles in Figure 17) and H3N2 (yellow squares in Figure 17) showed relatively early amplification with average threshold times of 25.32 minutes and 21.96 minutes, respectively.
[0191] Seven influenza B samples (gray diamonds in Figure 17) also showed excellent amplification signals with a threshold time of 27.13 minutes, and two individual genes (S gene and orf1ab gene) were simultaneously observed with similar amplification patterns to ensure accurate detection of SARS-CoV-2, with threshold times of 21.52 minutes for S gene and 21.8 minutes for orf1ab gene.
[0192] Most SARS-CoV-2 signals were detected early, except for sample number 2, which was detected after 20 minutes for the S gene and 41 minutes for the orf34.6ab gene, and the late amplification may be mainly due to the low viral load in clinical samples.
[0193] These results may demonstrate the high potential of the genetic analysis device of the present invention for rapid, accurate, and automatic detection of common respiratory viruses.
[0194] FIG. 18 is a diagram showing the LOD test results for influenza A H1N1, influenza A H3N2, and influenza B using the genetic analysis device shown in FIG. 1, and FIG. 19 is a diagram showing the LOD test results for SARS-CoV-2 orf1ab and S genes using the genetic analysis device shown in FIG. 1.
[0195] Referring to FIGS. 18 and 19, a LOD (Limit of detection) test was performed using commercially available samples to evaluate the sensitivity of the genetic analysis device of the present invention.
[0196] Commercial samples of influenza A subtypes H1N1, H3N2, and influenza B were purchased from the Korea Hospital Virus Bank (Republic of Korea) and 10 1 10 in 4 Serial dilutions were performed at various concentrations up to pfu / mL.
[0197] Additionally, SARS-CoV-2 samples were obtained from the American Type Culture Collection (USA) 10 1 , 10 2 , 10 3 and 10 4 Diluted to copies / μL.
[0198] LOD testing was performed by coating 20 μL of diluted virus sample onto a nasopharyngeal swab, and each test was performed in triplicate to generate error bars.
[0199] As shown in Figure 18, all samples of influenza A subtypes H1N1, H3N2 and influenza B had amplification threshold times of 10, 39.62, 35 and 29.35 minutes, respectively. 1 LOD of pfu / mL was shown.
[0200] And, as shown in Figure 19, the LOD sample of SARS-CoV-2 was determined to be 35.87 μL / μL for both the orf10ab gene (threshold time 25.24 minutes) and the S gene (threshold time 35.87 minutes).
[0201] The non-uniformity of the amplification curve at serially diluted concentrations may be due to uncontrollable amplification factors of the amplification reaction, such as the length of the amplification produced.
[0202] The LOD results obtained from each test were compared with other references related to respiratory virus diagnosis (Bukasov et al., 2021; Ribeiro et al., 2020; Tarim et al., 2021), and it was found that the genetic analysis device of the present invention is suitable for respiratory virus diagnosis and exhibits excellent detection sensitivity.
[0203] As described above, the best embodiments have been disclosed in the drawings and specifications. While specific terminology has been used herein, it is solely for the purpose of describing the present invention and is not intended to limit the meaning or scope of the invention as defined in the claims. Therefore, those skilled in the art will understand that various modifications and equivalent embodiments are possible. Accordingly, the true technical protection scope of the present invention should be determined by the technical spirit of the appended claims.
Claims
1. A chamber block is formed on the upper side of a microfluidic chip, in which a chamber in which a solution is positioned is formed, and each chamber formed on the microfluidic chip is connected vertically through a channel having a set diameter, and when rotated in a set direction, the solution is moved by centrifugal force and supplied to the chamber of the microfluidic chip. Cartridge containing .
2. In paragraph 1, The above chamber block is, A plurality of washing and elution cartridge chambers are arranged spaced apart from each other, The above washing and elution cartridge chambers are interconnected through an amplification fractionation channel having a set diameter, When a solution is injected into one of the wash and elution cartridge chambers, it is moved to multiple wash and elution cartridge chambers. Cartridge featuring .
3. In paragraph 1, The above chamber block is, A plurality of chambers are formed, and an injection port is formed that is connected to the chambers and is connected downward to the outside of the chambers, and the injection port and the chamber are connected to a flow path of a set diameter. When the chamber block is rotated in the set direction, the solution positioned in the chamber is supplied to the chamber of the microfluidic chip through the injection port. Cartridge featuring .
4. In paragraph 2, The above chamber block is, A plurality of amplification cartridge chambers are formed spaced apart from the above washing and elution cartridge chambers, The above amplification cartridge chamber is communicated with at least through an amplification fractionation channel that connects the amplification cartridge chamber to the inside of the chamber block, not the surface thereof. Cartridge featuring .
5. In the second paragraph, the microfluidic chip positioned on the lower side of the cartridge is rotatable with the chamber block, and a plurality of chambers are formed, and are connected to the chamber of the cartridge through an injection port. Each chamber of the above microfluidic chip, A plurality of chambers are arranged from the center to the outside, and each chamber is connected to a channel of a set diameter and rotates in a set direction so that the solution in the cartridge can move. A microfluidic chip featuring:
6. In paragraph 5, The above microfluidic chip, Sample chamber and, A membrane column that is connected to the outside of the sample chamber and captures viruses; Including a transfer chamber communicating with the membrane column from the outside of the membrane column, When rotated in the set direction, the solution passing through the sample chamber passes through the membrane column and is transferred to the transfer chamber. A microfluidic chip featuring:
7. In paragraph 6, The above transfer chamber is, It is arranged along the shape of a curve, one side is connected to the reaction chamber, and the other side is connected to the waste chamber located outside the transfer chamber. Transferring the solution to the reaction chamber or waste chamber depending on the direction of rotation; A microfluidic chip featuring:
8. In paragraph 7, The above reaction chamber and the above transfer chamber, Including euros with a set diameter, If the above microfluidic chip does not rotate in a set direction at a set speed or more, the solution located in the transfer chamber does not move to the reaction chamber. A microfluidic chip featuring:
9. In paragraph 7, The above reaction chamber is, It is connected to the above-mentioned transfer chamber through a euro channel formed in the shape of a bow, The above reaction chamber is composed of a plurality of reaction chambers, and is formed externally spaced apart along the euro channel. A microfluidic chip featuring:
10. In paragraph 9, A wax chamber in which wax is placed inside according to the shape of the above-mentioned euro channel, A microfluidic chip further comprising:
11. Microfluidic chip; A cartridge coupled with the above microfluidic chip; A solution loading section for injecting a solution into the cartridge; and A genetic analysis unit in which the microfluidic chip is mounted and which measures a fluorescent signal generated from the microfluidic chip; A genetic analysis device including:
12. In paragraph 11, The above genetic analysis unit, A rotary motor that rotates the microfluidic chip by placing the microfluidic chip thereon; A reaction heater arranged to face the reaction chamber of the microfluidic chip and to apply heat to the reaction chamber; A fluorescence detector that scans the reaction chamber and measures fluorescence signals in real time; A genetic analysis device including:
13. In paragraph 12, A wax heater arranged to face the wax chamber of the microfluidic chip and to apply heat to the wax chamber; and A cooling fan for cooling the above reaction heater and wax heater; A genetic analysis device further comprising:
14. In paragraph 13, The above solution loading section is, robot arm; An elevator installed on the above robot arm; and A support installed on the above-mentioned elevator and on which a syringe or pipette is placed; A genetic analysis device including:
15. In paragraph 14, The above elevator, A first lifting unit coupled with the above robot arm; and A second lifting unit installed in the first lifting unit and raised and lowered by the first lifting unit, and having the support unit installed therein to raise and lower the support unit; A genetic analysis device including:
16. In paragraph 15, The above support part, A pedestal coupling rod installed in the above-mentioned elevator and through which the finger rest of the syringe is slidably coupled or separated; and A button coupling rod installed on the above-mentioned elevator and positioned on the upper part of the above-mentioned pedestal coupling rod, the push button of the above-mentioned syringe being slidably coupled or separated; A genetic analysis device including:
17. In paragraph 16, The above support part, A pipette fixing rod installed in the above-mentioned lifting member, penetrating through the outer tube of the pipette and fixed to the upper end of the outer tube; A pipette tip removal rod installed in the above-mentioned lifting member and separating the pipette tip from the pipette; and A button lifting rod installed in the above lifting section and to which the push button of the pipette is fixed; A genetic analysis device including:
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