Biosensor
Patent Information
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- Filing Date
- 2025-02-10
- Publication Date
- 2026-08-13
Smart Images

Figure KR2025001918_13082026_PF_FP_ABST
Abstract
Description
biosensor
[0001] The present invention relates to a biosensor, and more specifically, to a biosensor that detects biological material and generates an electrical signal.
[0002] With the recent advancement of science and technology and the growing interest in the quality of life, the importance of disease diagnosis and prevention, as well as food and the environment, in human life is expanding day by day. As a result, there is an increasing need to measure the concentration of organic or inorganic substances in samples to diagnose human diseases, for specific processes in the fields of food chemistry and industrial chemistry, or to analyze pollutants in the environmental field, and many efforts are being made to address this.
[0003] A biosensor refers to a device that measures concentration by binding biomaterials, such as enzymes, microorganisms, antibodies, receptors, and DNA probes, to electrical or physicochemical transducers and detecting signals through electrochemical, optical, thermal, or piezoelectric methods based on electrode active substances or physical changes generated from reactions with the analyte to be measured.
[0004] Generally, the detection of biomaterials using biosensors is achieved through a combination of complex processes such as filtering, metering, mixing, transport, reaction, and washing. Therefore, conventionally, the detection of biomaterials is carried out manually at the laboratory level using various equipment.
[0005] Therefore, alongside the advancement of biosensor technology, the simultaneous development of fluid processing technology to automate and standardize the diagnostic process is crucial for low-cost, high-efficiency diagnosis.
[0006] Among these, equipment for detecting biomaterials requires flushing the internal flow paths before measuring each biological sample. Additionally, since large volumes of buffer solution must be stored in tanks to diagnose multiple samples, there is a risk of degradation, and there is the inconvenience of having to periodically empty the waste solution after diagnosis. Using such equipment presents limitations, as it may lead to reduced diagnostic speed and accuracy when a large volume of samples is required.
[0007] To solve this, a disposable biosensor cartridge with a built-in flow path through which buffer solution and sample solution can flow can be used. Since the disposable biosensor cartridge is used only once, a separate cleaning process is unnecessary. Additionally, since a single-use buffer solution is provided for each cartridge, there is no possibility of the buffer solution deteriorating, and the waste solution is emptied along with the cartridge when it is discarded.
[0008] In this regard, Korean published patent KR 10-2022-0047600A discloses a point-of-care molecular diagnostic system.
[0009] The above-described point-of-care molecular diagnostic system includes a cartridge and a diagnostic device, and can accommodate a biological sample in the cartridge and insert it into the diagnostic device to undergo various sample processing steps.
[0010] The above point-of-care molecular diagnostic system is configured to insert the cartridge into the diagnostic instrument by standing it upright.
[0011] In addition, a pneumatic device is provided to flow the buffer solution or sample solution; when a cartridge is inserted, pneumatic pressure is supplied to the inside of the cartridge to flow the buffer solution or sample solution.
[0012] However, as described above, when the cartridge is inserted in a direction perpendicular to the ground, the buffer solution or sample solution may flow due to gravity, so there is a limitation in that the buffer solution or sample solution flows regardless of the operation of the diagnostic device, making precise control impossible.
[0013] In addition, since a relatively bulky pneumatic device must be equipped in the diagnostic device, the volume of the diagnostic equipment may increase, which may cause inconvenience when transporting to the site where diagnosis is required or when installing it at the site.
[0014] In addition, pneumatic devices have limitations in that they are difficult to finely control the output, making it difficult to control the flow rate and velocity of the buffer solution or sample solution flowing inside the cartridge, which leads to errors in the diagnostic data and reduced accuracy.
[0015] Conventional biosensors have a problem in that errors occur and sensing accuracy decreases as the gate potential changes according to changes in the fluid state.
[0016] The present invention was created to improve upon the problems described above, and aims to provide a biosensor capable of reducing measurement noise and improving sensing accuracy by maintaining a constant gate potential.
[0017] In addition, the purpose is to provide a biosensor capable of improving sensing accuracy by increasing the degrees of freedom in the direction of fluid movement.
[0018] To achieve the above-mentioned purpose, the biosensor according to the present invention comprises a substrate, a first gate formed on the substrate, a second gate formed on the substrate, and a potential measuring unit formed between the first gate and the second gate and measuring the potential of the first gate and the potential of the second gate, and a channel portion may be formed between the first gate and the potential measuring unit and between the potential measuring unit and the second gate.
[0019] The above channel section may include a first drain source channel formed between the first gate and the potential measuring section, a second drain source channel formed between the potential measuring section and the second gate, a third drain source channel formed between the first gate and the potential measuring section and located at a certain distance from the first drain source channel, and a fourth drain source channel formed between the potential measuring section and the second gate and located at a certain distance from the second drain source channel.
[0020] The first gate, the potential measuring unit, and the second gate may be formed on the same straight line.
[0021] A first gap is formed between the first gate and the potential measuring unit, and a second gap is formed between the potential measuring unit and the second gate, and the first gap and the second gap may be the same.
[0022] The biosensor may further include a first drain formed on one side of the first drain source channel, a first source formed on the other side of the first drain source channel, a second drain formed on one side of the second drain source channel, a second source formed on the other side of the second drain source channel, a third drain formed on one side of the third drain source channel, a third source formed on the other side of the third drain source channel, a fourth drain formed on one side of the fourth drain source channel, and a fourth source formed on the other side of the fourth drain source channel.
[0023] The biosensor further comprises a first gate electrode connected to the first gate, a second gate electrode connected to the second gate, and a potential measuring unit electrode connected to the potential measuring unit, wherein the first gate electrode and the second gate electrode are electrically connected to one end of a potential compensation unit that compensates the potential of the first gate and the potential of the second gate to a preset potential, and the potential measuring unit electrode may be electrically connected to the other end of the potential compensation unit.
[0024] To achieve the above-mentioned purpose, the biosensor according to the present invention comprises a substrate, a gate formed on the substrate, and a potential measuring unit formed at a certain distance from the substrate and measuring the potential of the gate, and a channel portion may be formed between the gate and the potential measuring unit.
[0025] The above channel portion may include a first drain source channel formed between the gate and the potential measuring portion, and a second drain source channel formed between the gate and the potential measuring portion and formed at a position spaced apart from the first drain source channel by a certain distance.
[0026] The above gate and the above potential measuring unit can be formed on the same straight line.
[0027] To achieve the above-mentioned purpose, the sensing system according to the present invention comprises a biosensor cartridge having a flow path formed therein for a solution to move through, a biosensor disposed in the biosensor cartridge, and a diagnostic device for analyzing a signal received from the biosensor, wherein the biosensor comprises a substrate, a first gate formed on the substrate, a second gate formed on the substrate, and a potential measuring unit formed between the first gate and the second gate and measuring the potential of the first gate and the potential of the second gate, and a channel portion may be formed between the first gate and the potential measuring unit and between the potential measuring unit and the second gate.
[0028] The above channel section may include a first drain source channel formed between the first gate and the potential measuring section, a second drain source channel formed between the potential measuring section and the second gate, a third drain source channel formed between the first gate and the potential measuring section and located at a certain distance from the first drain source channel, and a fourth drain source channel formed between the potential measuring section and the second gate and located at a certain distance from the second drain source channel.
[0029] The first gate, the potential measuring unit, and the second gate may be formed in a straight line direction identical to the direction in which the solution flows.
[0030] A first gap is formed between the first gate and the potential measuring unit, and a second gap is formed between the potential measuring unit and the second gate, and the first gap and the second gap may be the same.
[0031] The above diagnostic device may include a potential compensation unit that compensates the potential to maintain the potential of the first gate and the potential of the second gate at a preset potential.
[0032] The biosensor further comprises a first gate electrode connected to the first gate, a second gate electrode connected to the second gate, and a potential measuring electrode connected to the potential measuring unit, wherein the first gate electrode and the second gate electrode are electrically connected to one end of the potential compensation unit, and the potential measuring electrode may be electrically connected to the other end of the potential compensation unit.
[0033] Since a linear electric field is applied to the channel portion from both the first gate and the second gate, a stable field effect can be generated. In addition, by increasing the degrees of freedom in the direction of fluid movement through the structure of the first gate, the potential measurement portion, and the second gate, sensing accuracy can be improved.
[0034] By placing a first gate at a position below the inlet port formed in the base frame of the biosensor cartridge and a second gate at a position below the outlet port in the base frame of the biosensor cartridge, the potential can be maintained at a constant level, thereby reducing measurement noise and improving sensing accuracy.
[0035] Since it is possible to always maintain the potential of the first gate and the second gate applied to the channel section at a constant level through the potential compensation section, measurement noise can be reduced and sensing accuracy can be improved.
[0036] FIG. 1 is a drawing for explaining a biosensor cartridge and a diagnostic device according to one embodiment of the present invention.
[0037] FIGS. 2 to 4 are drawings for explaining a biosensor cartridge according to an embodiment of the present invention.
[0038] FIG. 5 is a plan view illustrating the state in which the upper housing has been removed from FIG. 4.
[0039] FIG. 6 is an exploded perspective view for explaining a frame according to one embodiment of the present invention.
[0040] FIG. 7 is a plan view for explaining a top frame according to one embodiment of the present invention.
[0041] FIG. 8 is a cross-sectional view of a frame according to one embodiment of the present invention.
[0042] FIG. 9 is a bottom view illustrating a channel formed in a top frame according to one embodiment of the present invention.
[0043] FIG. 10 is a diagram illustrating the combination of a biosensor and a printed circuit board to a frame in a biosensor cartridge according to one embodiment of the present invention.
[0044] FIG. 11 is a drawing for explaining a sensor coupling portion in a biosensor cartridge according to one embodiment of the present invention.
[0045] FIG. 12 is a diagram illustrating the state in which a biosensor is coupled in a biosensor cartridge according to one embodiment of the present invention.
[0046] FIG. 13 is a cross-sectional view illustrating the contact between a biosensor and a printed circuit board in a biosensor cartridge according to one embodiment of the present invention.
[0047] FIGS. 14 and FIGS. 15 are cross-sectional views illustrating the arrangement of a biosensor and a printed circuit board and the arrangement of a flow path flowing over the biosensor in a biosensor cartridge according to an embodiment of the present invention.
[0048] FIG. 16 is a diagram illustrating the process of diagnosing a sample solution introduced into a biosensor cartridge using a diagnostic device according to one embodiment of the present invention.
[0049] FIG. 17 is a cross-sectional view illustrating a biosensor in which a solution flows according to one embodiment of the present invention.
[0050] FIGS. 18 to 20 are drawings for explaining the circuit arrangement of a biosensor according to an embodiment of the present invention.
[0051] FIGS. 21 and FIGS. 22 are drawings for explaining transfer curve noise reduction according to an embodiment of the present invention.
[0052] FIGS. 23 and FIGS. 24 are drawings for illustrating potential compensation according to an embodiment of the present invention.
[0053] Preferred embodiments of the present invention will be described in detail below with reference to the attached drawings.
[0054] The present invention is capable of various modifications and may have various embodiments, and specific embodiments are illustrated in the drawings and described in detail in the detailed description. This is not intended to limit the present invention to specific embodiments, and should be interpreted to include all modifications, equivalents, and substitutions that fall within the spirit and scope of the invention.
[0055] In describing the present invention, terms such as "first," "second," etc., may be used to describe various components, but said components may not be limited by said terms. Such terms are used solely for the purpose of distinguishing one component from another. For example, without departing from the scope of the present invention, the first component may be named the second component, and similarly, the second component may be named the first component.
[0056] The term "and / or" may include a combination of multiple related listed items or any of the multiple related listed items.
[0057] When it is stated that one component is "connected" or "connected" to another component, it can be understood that while it may be directly connected or connected to that other component, there may also be other components in between. On the other hand, when it is stated that one component is "directly connected" or "directly connected" to another component, it can be understood that there are no other components in between.
[0058] The terms used in this application are used merely to describe specific embodiments and are not intended to limit the invention. Singular expressions may include plural expressions unless the context clearly indicates otherwise.
[0059] In this application, terms such as “comprising” or “having” are intended to indicate the existence of the features, numbers, steps, actions, components, parts, or combinations thereof described in the specification, and should be understood as not excluding in advance the existence or addition of one or more other features, numbers, steps, actions, components, parts, or combinations thereof.
[0060] Unless otherwise defined, all terms used herein, including technical or scientific terms, may have the same meaning as generally understood by those skilled in the art to which the present invention pertains. Terms such as those defined in commonly used dictionaries may be interpreted as having a meaning consistent with their meaning in the context of the relevant technology, and may not be interpreted in an ideal or overly formal sense unless explicitly defined in this application.
[0061] In addition, the following embodiments are provided to explain more completely to those with average knowledge in the industry, and the shapes and sizes of the elements in the drawings may be exaggerated for clearer explanation.
[0062]
[0063] FIG. 1 is a drawing for explaining a biosensor cartridge and a diagnostic device according to an embodiment of the present invention. FIG. 2 to 4 are drawings for explaining a biosensor cartridge according to an embodiment of the present invention. FIG. 5 is a plan view for explaining the state in which the upper housing is removed in FIG. 4.
[0064] Referring to FIGS. 1 to 5, a biosensor cartridge (1) according to one embodiment of the present invention is coupled to a diagnostic device (2) to detect biomaterials and thereby diagnose diseases, etc. In one embodiment, the biosensor cartridge (1) may be inserted into the diagnostic device (2) in a state arranged along a horizontal direction. The biosensor cartridge (1) may allow a buffer solution and a sample solution to flow inside, thereby causing the biosensor (400) to undergo an electrochemical reaction with the biomaterials, and the resulting electrical change may be transmitted to the diagnostic device (2) through a printed circuit board (500).
[0065] A biosensor cartridge (1) according to one embodiment of the present invention may include a housing (100), a frame (200), a tank (300), a biosensor (400), a printed circuit board (500), a channel (600), a tube (700), a valve section (800), and a pump section (900).
[0066] A frame (200) is accommodated inside the housing (100), a tank (300) is formed on the upper side of the frame (200), and a channel (600) may be formed inside the frame (200). A tube (700), a valve section (800), and a pump section (900) are coupled to the frame (200), and a biosensor (400) and a printed circuit board (500) may be detachably coupled.
[0067] In the present invention, the direction in which the buffer solution is introduced relative to the frame (200) can be called the upper side, the direction opposite to the upper side relative to the frame (200) can be called the lower side, and the direction in which the biosensor cartridge (1) is inserted into the diagnostic device (2) can be called the front. That is, the direction in which the printed circuit board (500) is placed relative to the housing (100) can be called the front. Also, the direction opposite to the front can be called the rear. Additionally, when looking at the front from the rear end of the housing (100), the direction placed on the left can be called the left, and the direction placed on the right can be called the right.
[0068] The housing (100) forms the outer shape of the biosensor cartridge (1) and can accommodate a frame (200), a tank (300), a biosensor (400), a printed circuit board (500), a channel (600), a tube (700), a valve section (800), and a pump section (900) inside.
[0069] The housing (100) may include an upper housing (110) and a lower housing (120).
[0070] In one embodiment, the upper housing (110) is formed in the shape of a square box with the lower side open, and a buffer solution inlet hole (111), a sample solution inlet hole (112), a valve connection hole (113), and a pump connection hole (114) may be formed on the upper side.
[0071] The buffer solution inlet hole (111) can be formed to allow the buffer solution to flow in. The buffer solution inlet hole (111) can be formed in the blister receiving groove (111a). The blister receiving groove (111a) can be positioned vertically above the buffer solution tank (310). The buffer solution inlet hole (111) is positioned vertically above the buffer solution tank (310), and the buffer solution inlet hole (111) can be formed to communicate with the internal space of the buffer solution tank (310).
[0072] A buffer blister (3) can be coupled to the blister receiving groove (111a). The blister receiving groove (111a) may be formed by being recessed downward on the upper side of the upper housing (110) in correspondence with the shape of the buffer blister (3). In one embodiment, the blister receiving groove (111a) may be formed by being recessed in the shape of a square groove or a circular groove on the upper side of the upper housing (110). Through this configuration, the buffer blister (3) can burst while being received inside the blister receiving groove (111a), allowing the buffer solution to pass through the buffer solution inlet hole (111) and flow into the buffer solution tank (310).
[0073] The pump unit (900) is rotatably coupled to the frame (200) and, as it rotates, pressurizes the tube (700) to generate a flow force in the buffer solution or sample solution flowing through the channel (600).
[0074] The pump unit (900) may include a pump knob (910) and a bearing (920).
[0075] The pump knob (910) can be positioned on the upper surface of the top frame (220). The pump knob (910) can be rotatably coupled within the tube receiving portion (222). The pump knob (910) can be rotatably received within the pump receiving groove (222a).
[0076] Specifically, the pump knob (910) includes a shaft (911), a support (912), and a drive groove (913).
[0077] At least one ventilation hole (111b, 116) may be formed on the upper surface of the upper housing (110). The ventilation holes (111b, 116) may be formed to allow air inside the housing (100) to be discharged to the outside. A first ventilation hole (111b) may be formed on the upper surface of the upper housing (110). The first ventilation hole (111b) may be positioned vertically above the buffer solution tank (310). The first ventilation hole (111b) may be formed to communicate with the internal space of the buffer solution tank (310). When the buffer solution flows into the buffer solution tank (310), the air inside the buffer solution tank (310) may be discharged to the outside through the first ventilation hole (111b). Through this, the air pressure inside the buffer solution tank (310) may be prevented from rising, and the probability of air mixing with the buffer solution may be reduced.
[0078] A first ventilation channel (111c) may be further formed on the upper surface of the upper housing (110). The first ventilation channel (111c) is formed to communicate with the first ventilation hole (111b) and may be formed in a groove shape along the upper surface of the upper housing (110). In one embodiment, the ventilation channel (111c) may be formed as a straight groove, as well as in a shape that is bent multiple times on the upper surface of the upper housing (110). This is to secure the maximum length of the channel within a limited area. When a label (130) is attached to the upper surface of the upper housing (110), the first ventilation channel (111c) can form a space between the upper housing (110) and the label (130) to receive air discharged through the first ventilation hole (111b).
[0079] The sample solution inlet hole (112) may be formed to allow the sample solution to flow in. In one embodiment, the sample solution inlet hole (112) may be positioned vertically above the sample solution tank (320). The sample solution inlet hole (112) may be formed to communicate with the internal space of the sample solution tank (320). In one embodiment, a stopper (112a) may be detachably coupled to the sample solution inlet hole (112). When the stopper (112a) is coupled, the sample solution inlet hole (112) may be blocked. Also, when the stopper (112a) is removed, the sample solution inlet hole (112) is opened so that the sample solution can be injected. After the sample solution is injected, if the sample solution inlet hole (112) is blocked through the stopper (112a), foreign substances may be prevented from flowing into the sample solution inlet hole (112).
[0080] The valve connection hole (113) may be formed so that a part of the valve portion (800) passes through it. The valve connection hole (113) may be positioned on the upper side of the valve coupling portion (223). The valve connection hole (113) may be formed in the shape of a circular hole, and a valve knob (820) may be positioned to pass through the valve connection hole (113). The valve knob (820) may be rotated within the valve connection hole (113).
[0081] At least a portion of the valve knob (820) can be rotatably accommodated inside the valve housing (810).
[0082] A knob groove (823) may be formed in the valve knob (820) so that an external force can be applied. When the biosensor cartridge (1) is coupled to the diagnostic device (2), the knob groove (823) may be coupled to a valve actuator (not shown) provided in the diagnostic device (2).
[0083] The pump connection hole (114) may be formed so that a part of the pump section (900) passes through it. The pump connection hole (114) may be positioned above the valve coupling section (223). The pump connection hole (114) may be positioned above the pump receiving groove (222a). The pump connection hole (114) is formed in the shape of a circular hole, and the pump knob (910) may be positioned to pass through the valve connection hole (113). The pump knob (910) may be rotated within the pump connection hole (114).
[0084] A support projection (115) may be formed protruding from the upper surface of the upper housing (110) to support a printed circuit board (500) into the interior of the housing (100). The support projection (115) may be positioned vertically above the substrate coupling portion (221) of the frame (200). The support projection (115) may contact the upper surface of the printed circuit board (500) to support the printed circuit board (500).
[0085] A second ventilation hole (116) may be further formed on the upper surface of the upper housing (110). The second ventilation hole (116) may be positioned vertically above the waste solution tank (330). The second ventilation hole (116) may be formed to communicate with the internal space of the waste solution tank (330). When a buffer solution or sample solution flows into the waste solution tank (330), air inside the waste solution tank (330) can be discharged to the outside through the second ventilation hole (116). This prevents the air pressure inside the waste solution tank (330) from rising.
[0086] A second ventilation channel (116a) may be further formed on the upper surface of the upper housing (110). The second ventilation channel (116a) is formed to communicate with the second ventilation hole (116) and may be formed in a groove shape along the upper surface of the upper housing (110). The second ventilation channel (116a) may be formed as a straight groove, as well as in a shape that is bent multiple times on the upper surface of the upper housing (110). This is to secure the maximum length of the channel within a limited area. Through this configuration, when a label (130) is attached to the upper surface of the upper housing (110), the second ventilation channel (116a) forms a space between the upper housing (110) and the label (130) to accommodate air discharged through the second ventilation hole (116).
[0087] The lower housing (120) can be combined with the upper housing (110) to form a space that accommodates a frame (200), a tank (300), a biosensor (400), a printed circuit board (500), a channel (600), a tube (700), a valve section (800), and a pump section (900) inside.
[0088] In one embodiment, the lower housing (120) is formed in the shape of a square box with an open top and can be combined with the upper housing (110). A plurality of hooks may be formed protruding toward the upper housing (110) on the side wall of the lower housing (120) and may be fitted into a groove (not shown) formed on the side wall of the upper housing (110) to be combined.
[0089] A sensor insertion hole (121) into which a biosensor (400) can be inserted may be formed on the lower surface of the lower housing (120). In one embodiment, the sensor insertion hole (121) may be formed in the shape of a circular hole, and a pair of cover coupling parts (121a) may be formed protruding radially inward on at least a part of the inner surface. The cover coupling parts (121a) may be coupled with and supported by a hook (122a) of the sensor cover (122).
[0090] A sensor cover (122) may be attached to the lower side of the lower housing (120). The sensor cover (122) can cover the sensor insertion hole (121) and prevent the biosensor (400) attached to the frame (200) from coming off.
[0091] The sensor cover (122) may include a hook (122a), a sensor support (122b), and a coupling guide (122c). The sensor cover (122) may be formed in the shape of a disc overall, with the hook (122a) and the sensor support (122b) protruding from the upper surface of the sensor cover (122), and the coupling guide groove (122c) recessed from the lower surface of the sensor cover (122). The diameter of the sensor cover (122) may be formed to correspond to the diameter of the sensor insertion hole (121). In one embodiment, the diameter of the sensor cover (122) may be formed to be the same as the diameter of the sensor insertion hole (121).
[0092] The hook (122a) is formed to protrude upward from the upper surface of the sensor cover (122), and the upper portion may be formed to protrude radially outward. A pair of hooks (122a) may be formed in a position facing each other and may be formed along the circumferential direction for a predetermined angle range. After the hook (122a) is inserted into the sensor insertion hole (121) where the cover coupling part (121a) is not formed, the hook (122a) may be positioned above the cover coupling part (121a) when the sensor cover (122) is rotated. Through this, the cover coupling part (121a) is positioned between the hook (122a) and the upper surface of the sensor cover (122), thereby preventing the sensor cover (122) from coming off.
[0093] The sensor support (122b) may be formed to protrude upward along the circumferential direction from the upper surface of the sensor cover (122). The sensor support (122b) may be formed to protrude in the shape of a circular rib with the radial center of the sensor cover (122) as the origin. The sensor support (122b) may be formed to protrude so as to contact and support the lower surface of the biosensor (400). When the sensor cover (122) is coupled to the lower housing (120) and blocks the sensor insertion hole (121), the sensor support (122b) can contact and support the biosensor (400). Through this, the biosensor (400) is prevented from shaking, thereby preventing errors from occurring in the measurement value of the biosensor (400).
[0094]
[0095] FIG. 6 is an exploded perspective view illustrating a frame according to an embodiment of the present invention. FIG. 7 is a plan view illustrating a top frame according to an embodiment of the present invention. FIG. 8 is a cross-sectional view of a frame according to an embodiment of the present invention.
[0096] Referring to FIGS. 6 to 8, the frame (200) is placed inside the housing (100) and can form a channel (600) through which a buffer solution and a sample solution flow.
[0097] A biosensor (400) and a printed circuit board (500) are detachably coupled to the frame (200) so that the biosensor (400) can detect biomaterials in a sample solution flowing through a channel (600).
[0098] The frame (200) may include a base frame (210), a top frame (220), a hydrophilic adhesive layer (230), and a microchannel forming adhesive layer (240). In one embodiment, a hydrophilic adhesive layer (230) may be laminated on the upper side of the base frame (210), a microchannel forming adhesive layer (240) may be laminated on the upper side of the hydrophilic adhesive layer (230), and a top frame (220) may be laminated on the upper side of the microchannel forming adhesive layer (240).
[0099] The base frame (210) can be detachably coupled to the biosensor (400). The base frame (210) can be coupled to the biosensor (400) to support the biosensor (400). In one embodiment, the base frame (210) may be formed in the shape of a roughly rectangular flat plate, and a sensor coupling portion (211) coupled to the biosensor (400) may be formed.
[0100] The sensor coupling portion (211) can be detachably coupled to the biosensor (400). The sensor coupling portion (211) is formed in the shape of a hole corresponding to the shape of the biosensor (400) overall, and a frame may be formed that crosses the hole along the short axis direction. A pair of ports (631, 632) may be formed in the frame. In one embodiment, the sensor coupling portion (211) is formed in the shape of a square hole, and the front-rear diameter and left-right diameter may be formed to be equal to the front-rear length and left-right width of the biosensor (400).
[0101] A biosensor (400) can be fitted and coupled to the sensor coupling portion (211). At least a portion of the side wall surrounding the sensor coupling portion (211) can be formed to be larger than the thickness of the biosensor (400). Through this, the biosensor (400) can be stably supported while fitted into the sensor coupling portion (211).
[0102] A hole may be formed in the base frame (210) to fix the valve part (800) and the pump part (900), and a fixing member such as a screw may pass through the hole and be coupled with the valve part (800) and the pump part (900) positioned on the upper side of the top frame (220).
[0103] A tank (300) may be formed on the top frame (220). In one embodiment, a tank (300) may be formed on the upper surface of the top frame (220).
[0104] A channel (600) may be formed in the top frame (220). In one embodiment, a channel (600) may be formed on the lower surface of the top frame (220).
[0105] The top frame (220) can be formed from a resin material. In one embodiment, the top frame (220) can be formed from PMMA (Polymethyl methacrylate) resin. Through this, it is possible to mass-produce while forming fine channels (600) through injection molding. In addition, the top frame (220) and the base frame (210) can be easily bonded together using tape.
[0106] A substrate coupling portion (221) may be formed on the upper surface of the top frame (220). A printed circuit board (500) may be detachably coupled to the substrate coupling portion (221). The substrate coupling portion (221) may be positioned facing the sensor coupling portion (211). That is, at least a portion of the substrate coupling portion (221) may be positioned above the sensor coupling portion (211). Through this, the distance between the biosensor (400) and the printed circuit board (500) can be minimized, and information detected by the biosensor (400) can be transmitted quickly and accurately to the printed circuit board (500).
[0107] The substrate coupling portion (221) may include a coupling guide portion (221a) that guides the slide coupling of the printed circuit board (500). The coupling guide portion (221a) may be formed by protruding a pair facing upward from the upper surface of the top frame (220), and then being bent and extended in a direction facing each other. In one embodiment, the gap between the pair of coupling guide portions (221a) may be equal to the width of the printed circuit board (500). By stably supporting the printed circuit board (500), the pair of coupling guide portions (221a) can prevent the printed circuit board (500) from shaking in the horizontal direction. In one embodiment, the protrusion height of the pair of coupling guide portions (221a) may be equal to or slightly larger than the thickness of the printed circuit board (500). Through this, the printed circuit board (500) can be prevented from moving in the up and down direction.
[0108] The substrate coupling portion (221) may further include a substrate support portion (221b) that guides the coupling position of the printed circuit board (500) and supports the printed circuit board (500). A pair of substrate support portions (221b) may be formed protruding upward from the upper surface of the top frame (220). The substrate support portions (221b) may be formed corresponding to the shape of both ends in the width direction (short axis direction) of the printed circuit board (500). In one embodiment, when semicircular grooves are formed at both ends in the width direction of the printed circuit board (500), a pair of substrate support portions (221b) may be formed in a shape that protrudes in a semicircular manner toward the direction facing each other. In one embodiment, the shortest distance between a pair of substrate support portions (221b) may be formed to be the same as the shortest distance in the width direction of the printed circuit board (500). Through this, when the printed circuit board (500) is coupled, it can guide the coupling position by being fitted with the board support (221b), and prevent the printed circuit board (500) from moving along the insertion direction.
[0109] Consequently, the substrate coupling portion (221) can prevent the printed circuit board (500), which is coupled through the coupling guide portion (221a) and the substrate support portion (221b), from shaking in the horizontal and vertical directions. By stably supporting the coupled printed circuit board (500), the substrate coupling portion (221) has the effect of preventing errors in data from occurring as the printed circuit board (500) shakes.
[0110] A clip receiving hole (221c) for receiving a contact clip (450) may be formed in the substrate coupling portion (221). A pair of clip receiving holes (221c) may be disposed on the substrate coupling portion (221). In one embodiment, at least a portion of one of the pair of clip receiving holes (221c) may be disposed between a pair of coupling guide portions (221a), and at least a portion of the other of the pair of clip receiving holes (221c) may be disposed between a pair of substrate support portions (221b). This prevents the contact clip (450) received in the clip receiving hole (221c) from being dislodged from a predetermined position.
[0111] A pair of clip receiving holes (221c) may be formed to communicate with the sensor coupling portion (211). At least a portion of each of the pair of clip receiving holes (221c) may be positioned facing the sensor coupling portion (211). In one embodiment, the sensor coupling portion (211) may be positioned between the pair of clip receiving holes (221c), such that a portion of both ends in the longitudinal direction (front-back direction) of the sensor coupling portion (211) overlaps with at least a portion of each of the pair of clip receiving holes (221c). Through such a configuration, a stage to which the contact clip (450) is coupled can be formed when the base frame (210) and the top frame (220) are stacked. Through this, the contact clip (450) itself can directly contact the biosensor (400) and the printed circuit board (500), and the accuracy of data transmission via the contact clip (450) can be improved.
[0112] A tube receiving portion (222) may be formed in the top frame (220). The tube receiving portion (222) may be formed to protrude upward from the upper surface of the top frame (220). The tube receiving portion (222) may guide the position where the tube (700) is placed on the top frame (220).
[0113] The tube receiving portion (222) is formed to protrude in a block shape from the upper surface of the top frame (220), and a pump receiving groove (222a) and a tube guide groove (222b) may be formed inside.
[0114] The pump receiving groove (222a) may accommodate at least a portion of a tube (700) and a pump unit (900) inside. The tube (700) is arranged along the circumferential direction, and at least a portion of the pump unit (900) may be rotatably accommodated inside the wound tube (700). At least a portion of the pump unit (900) may be placed within the pump receiving groove (222a) in contact with the tube (700). In one embodiment, the pump receiving groove (222a) is formed in the shape of a circular groove, the tube (700) is wound along the inner surface, and the pump unit (900) may be rotatably accommodated inside the tube (700). When the pump unit (900) is rotated, the tube (700) placed between the side wall of the pump receiving groove (222a) and the pump unit (900) may be compressed.
[0115] The tube guide groove (222b) is formed to communicate with the pump receiving groove (222a) and can accommodate at least a portion of the tube (700). The tube guide groove (222b) can accommodate one side and the other side of the tube (700) wound in the pump receiving groove (222a), respectively. The tube guide groove (222b) can accommodate the one side and the other side of the tube (700) so that they intersect each other. That is, the groove accommodating one side of the tube (700) and the groove accommodating the other side of the tube (700) can be joined together, and the joined point (222c) can be formed to communicate with the pump receiving groove (222a). Through this, when the pump unit (900) rotates, at least a portion of the tube (700) can maintain contact with the pump unit (900), and prevent backflow from occurring in the solution flowing through the tube (700) when the pump unit (900) rotates.
[0116] A valve coupling portion (223) may be formed on the top frame (220). The valve coupling portion (223) may be formed to protrude upward from the upper surface of the top frame (220). In one embodiment, the valve coupling portion (223) may be formed to protrude in a rib shape from the upper surface of the top frame (220). The valve coupling portion (223) may be formed to surround the outer side of at least a portion of the valve portion (800). Through this, the valve coupling portion (223) can guide the position where the valve portion (800) is coupled.
[0117] A plurality of ports may be formed in the top frame (220). The ports may provide a space through which a buffer solution or sample solution passes to flow into the channel (600), or through which the buffer solution or sample solution is discharged from the channel (600). A buffer solution inlet port (315), a buffer solution port (615), a sample solution port (625), a sensing port (635), a prefill port (645), a waste solution port (655), a first tube connection port (660), and a second tube connection port (670) may be formed in the top frame (220). The buffer solution inlet port (315) may be placed within the buffer solution tank (310) to allow the buffer solution within the buffer solution tank (310) to flow into the channel (600).
[0118] The buffer solution port (615), sample solution port (625), sensing port (635), and prefill port (645) may be arranged to be connected by the valve section (800). In one embodiment, the buffer solution port (615), sample solution port (625), and prefill port (645) may be arranged on concentric circles with the sensing port (635) as the origin. In this case, the buffer solution port (615), sample solution port (625), and prefill port (645) may be arranged with a predetermined angle difference with the sensing port (635) as the origin.
[0119] The first tube connection port (660) and the second tube connection port (670) may be provided to be connected to the tube (700). The first tube connection port (660) and the second tube connection port (670) may be positioned adjacent to the pump unit (900). In one embodiment, the second tube connection port (670) may be positioned on one side in the longitudinal direction of the top frame (220) relative to the pump unit (900), and the first tube connection port (660) may be positioned on the other side in the longitudinal direction of the top frame (220) relative to the pump unit (900).
[0120] In the case of conventional biosensor cartridges, channels were formed inside the frame to allow liquid to flow, but there was a limitation in that the accuracy of sensing was low because the flow rate of the solution was not constant each time the sample solution was tested.
[0121] To address this, hydrophilic coatings were applied to the base frame; however, while the addition of the coating process increased production costs, it had the disadvantage of raising the defect rate due to coating non-uniformity.
[0122] Accordingly, in the present invention, the flow rate of the solution can be maintained constant through the hydrophilic adhesive layer (230), while minimizing the increase in production costs and the defect rate.
[0123] A hydrophilic adhesive layer (230) can be placed between the base frame (210) and the top frame (220). A hydrophilic adhesive layer (230) can be placed between the base frame (210) and the microchannel forming adhesive layer (240). For example, the hydrophilic adhesive layer (230) may be a hydrophilic tape or a hydrophilic film. The hydrophilic adhesive layer (230) can be placed on the upper side of the base frame (210) to facilitate the flow of fluid flowing through the channel (600). Additionally, the hydrophilic adhesive layer (230) has the effect of stably maintaining the flow rate of the solution. Furthermore, there is an advantage that adhesion can be achieved through a simple process of placing the hydrophilic adhesive layer (230), the microchannel forming adhesive layer (240), and the top frame (220) on the upper side of the base frame (210) and applying pressure, without a separate heating process during the manufacturing process.
[0124] A shape corresponding to the shape of the top frame (220) may be formed in the hydrophilic adhesive layer (230). In one embodiment, a clip receiving hole (231) may be formed in the hydrophilic adhesive layer (230). The clip receiving hole (231) of the hydrophilic adhesive layer (230) may be formed at a position facing the clip receiving hole (221c) of the top frame (220) and may be formed in a shape of the same size.
[0125] The hydrophilic adhesive layer (230) may be formed with a shape corresponding to the shape of the base frame (210). In one embodiment, a port may be formed in the hydrophilic adhesive layer (230). The port of the hydrophilic adhesive layer (230) may be formed in a position facing the port (631a, 632a) of the base frame (210) and may be formed in a shape of the same size.
[0126] A microchannel forming adhesive layer (240) can be placed between a hydrophilic adhesive layer (230) and a top frame (220). The microchannel forming adhesive layer (240) can bond the hydrophilic adhesive layer (230) and the top frame (220). The microchannel forming adhesive layer (240) can be formed with a shape corresponding to the shape of the top frame (220).
[0127] The micro-channel forming adhesive layer (240) may have a channel slit (242) formed in communication with the channel (600) formed in the top frame (220). The channel slit (242) may be formed at a position facing the channel (600). In one embodiment, the width of the channel slit (242) may be formed to be larger than the width of the channel (600). This prevents errors in the flow of the solution even if errors occur in the positions of the channel (600) and the channel slit (242).
[0128] A clip receiving hole (241) may be formed in the micro-channel forming adhesive layer (240). The clip receiving hole (241) of the micro-channel forming adhesive layer (240) may be formed in a position facing the clip receiving hole (221c) of the top frame (220) and may be formed in the same size.
[0129] The tank (300) is formed on the upper surface of the frame (200) and can provide a space in which a buffer solution and / or a sample solution can be received. In one embodiment, the tank (300) may be formed to protrude from the upper surface of the top frame (220) and form a shape that surrounds a predetermined space.
[0130] The tank (300) may include a buffer solution tank (310). The buffer solution tank (310) may receive a buffer solution, at least temporarily contain the buffer solution, and allow the buffer solution to flow into a channel (600).
[0131] The buffer solution tank (310) may be positioned on the rear side (one side in the longitudinal direction) of the frame (200). The buffer solution tank (310) may be positioned on the opposite side of the substrate coupling portion (221) on the frame (200).
[0132] The buffer solution tank (310) may be placed on the left side (one side in the short direction) of the frame (200). The buffer solution tank (310) may be placed on the opposite side of the waste solution tank (330) on the frame (200).
[0133] The buffer solution tank (310) may be formed to protrude in the form of a wall on the upper side of the top frame (220). In one embodiment, the buffer solution tank (310) may be formed to protrude in the form of a square wall. A buffer solution inlet port (315) may be formed in the top frame (220), and the buffer solution inlet port (315) may be formed to communicate with the buffer solution channel (610). The buffer solution inlet port (315) may be formed within the buffer solution tank (310).
[0134] An inclined surface (311) and a guide groove may be formed within the buffer solution tank (310) to guide the buffer solution to flow into the buffer solution inlet port (315). In one embodiment, the inclined surface may be formed to slope downward from the rear end of the buffer solution tank (310) toward the front. The inclined surface may be formed to slope downward from both sides in the left and right directions toward the center in the left and right directions. A guide groove may be formed along the front and rear directions on the inner bottom surface of the buffer solution tank (310). A buffer solution inlet port (315) may be formed on the guide groove.
[0135] The buffer solution tank (310) can surround the perimeter of the space into which the buffer solution is introduced. Accordingly, the buffer solution can be contained in the buffer solution tank (310), and the buffer solution can be discharged into the channel (600) according to the operation of the pump unit (900).
[0136] The tank (300) may include a sample solution tank (320). The sample solution tank (320) may receive a sample solution, at least temporarily receive the sample solution, and allow the sample solution to flow into a channel (600).
[0137] The sample solution tank (320) may be placed on the rear side of the frame (200). The sample solution tank (320) may be placed on the opposite side of the substrate coupling portion (221) on the frame (200).
[0138] At least a portion of the sample solution tank (320) may be positioned in the left-right central part of the frame (200). The sample solution tank (320) may be positioned between the buffer solution tank (310) and the waste solution tank (330).
[0139] The sample solution tank (320) may be formed to protrude in the form of a wall from the upper side of the top frame (220). In one embodiment, the sample solution tank (320) may be formed to protrude in the form of a circular wall. The top frame (220) may be formed such that the lower side of the internal space of the sample solution tank (320) is at least partially open. The internal space of the sample solution tank (320) may be formed to communicate with the sample solution channel (620).
[0140] The sample solution tank (320) can surround the perimeter of the space into which the sample solution is introduced. Accordingly, the sample solution can be contained in the sample solution tank (320), and the sample solution can be discharged into the channel (600) according to the operation of the pump unit (900).
[0141] The tank (300) may include a waste solution tank (330). The waste solution tank (330) may receive waste solution and store waste solution.
[0142] The waste solution tank (330) may be positioned at the rear side of the frame (200). The waste solution tank (330) may be positioned on the frame (200) on the opposite side of the substrate coupling portion (221). The waste solution tank (330) may be positioned on the right side of the frame (200).
[0143] The waste solution tank (330) may be formed protruding in the form of a wall on the upper side of the top frame (220). In one embodiment, the waste solution tank (330) may be formed protruding in the form of a square wall. A waste solution port (655) may be formed in the top frame (220), and the waste solution port (655) may be formed to communicate with the waste solution channel (650). The waste solution port (655) may be formed within the waste solution tank (330).
[0144] The waste solution tank (330) can surround the perimeter of the space into which the waste solution flows. Depending on the operation of the pump unit (900), the waste solution can flow from the channel (600) into the waste solution tank (330) and be stored.
[0145]
[0146] FIG. 9 is a bottom view illustrating a channel formed in a top frame according to one embodiment of the present invention.
[0147] Referring to FIG. 9, the channel (600) is formed inside the frame (200) and can provide a flow path through which a buffer solution or sample solution can flow. The channel (600) can be formed on the lower side of the top frame (220).
[0148] The channel (600) may include a buffer solution channel (610) through which the buffer solution flows, and which is connected to the buffer solution tank (310). One side of the buffer solution channel (610) may be in communication with the buffer solution inlet port (315). One side of the buffer solution channel (610) may be in communication with the internal space of the buffer solution tank (310) through the buffer solution inlet port (315). The other side of the buffer solution channel (610) may be in communication with the buffer solution port (615). The other side of the buffer solution channel (610) may be in communication with the sensing channel (630) through the buffer solution port (615) according to the operation of the valve section (800).
[0149] The buffer solution channel (610) can guide the buffer solution introduced into the buffer solution tank (310) to the valve section (800). In one embodiment, the buffer solution channel (610) can be formed along the longitudinal direction (long axis direction) of the frame (200).
[0150] The buffer solution channel (610) may be formed in a shape that is bent at least once at a predetermined angle. In one embodiment, the buffer solution channel (610) may be formed along the length direction (long axis direction) of the frame (200) in its entirety, but may have a portion that is bent twice.
[0151] The buffer solution inlet port (315) can serve as an inlet for the buffer solution channel (610), and the buffer solution port (615) can serve as an outlet for the buffer solution channel (610).
[0152] The buffer solution channel (610) may be formed with a width on the inlet side and a width on the outlet side that are different. In one embodiment, the buffer solution channel (610) may be formed with a width on the outlet side that is larger than the width on the inlet side. Through this, the buffer solution can be sufficiently present on the outlet side of the buffer solution channel (610), preventing a decrease in the flow rate of the buffer solution passing through the valve section (800), and maintaining a stable flow rate of the buffer solution.
[0153] The channel (600) may include a sample solution channel (620) through which the sample solution flows, which is connected to the sample solution tank (320). One side of the sample solution channel (620) may be in communication with the internal space of the sample solution tank (320). The other side of the sample solution channel (620) may be in communication with the sample solution port (625). The other side of the sample solution channel (620) may be in communication with the sensing channel (630) through the sample solution port (625) according to the operation of the valve part (800).
[0154] The sample solution channel (620) can guide the sample solution introduced into the sample solution tank (320) to the valve section (800). In one embodiment, the sample solution channel (620) may be formed along a direction intersecting the longitudinal direction (long axis direction) of the frame (200) from the sample solution tank (320), then folded to form along the longitudinal direction of the frame (200), and subsequently folded to form along a direction intersecting the longitudinal direction. The internal space of the sample solution tank (320) may serve as an inlet for the sample solution channel (620), and the sample solution port (625) may serve as an outlet for the sample solution channel (620).
[0155] The diameter of the internal space of the sample solution tank (320) may be formed to be larger than the width of the discharge side of the sample solution channel (620). The width of at least a portion of the sample solution channel (620) may be changed. In one embodiment, the sample solution channel (620) may be formed such that the width of the inlet side and the width of the discharge side are the same, while having a section where the width narrows between them. Through this, the flow rate of the sample solution flowing through the sample solution channel (620) can be prevented from decreasing instantaneously according to the operation of the pump unit (900), and the flow velocity of the sample solution can be maintained stably.
[0156] The channel (600) may include a sensing channel (630) that is connected to a buffer solution channel (610) or a sample solution channel (620) and guides the buffer solution or sample solution to the biosensor (400).
[0157] One side of the sensing channel (630) may be in communication with the sensing port (635). The other side of the sensing channel (630) may be in communication with the first tube connection port (660). The other side of the sensing channel (630) may be in communication with a flow path formed inside the tube (700) through the first tube connection port (660) according to the operation of the valve part (800).
[0158] The sensing channel (630) can guide the buffer solution or sample solution introduced through the valve section (800) to the biosensor (400) and allow it to pass through the biosensor (400).
[0159] The sensing channel (630) may include a first sensing channel (631) and a second sensing channel (632).
[0160] The first sensing channel (631) can guide the buffer solution or sample solution that has passed through the valve section (800) to the biosensor (400). The first sensing channel (631) can be formed along the length direction (long axis direction) of the frame (200) from the sensing channel (630), then folded to form along a direction intersecting the length direction. In one embodiment, the first sensing channel (631) can be formed along the width direction by being formed along the length direction (long axis direction) of the frame (200) from the sensing port (635), then folded. The other side of the first sensing channel (631) can be in communication with the internal space of the sensor coupling section (211). The first sensing channel (631) can flow the buffer solution or sample solution into the internal space of the sensor coupling section (211) through the inlet port (631a) formed in the base frame (210).
[0161] The buffer solution or sample solution that has passed through the first sensing channel (631) can flow on the upper surface of the biosensor (400).
[0162] The sensing port (635) can serve as an inlet for the first sensing channel (631), and the sensor coupling part (211) can serve as an outlet for the first sensing channel (631).
[0163] The width of the inlet side of the first sensing channel (631) can be formed to be larger than the width of the outlet side of the first sensing channel (631). Through this, the buffer solution or sample solution can be sufficiently present on the inlet side of the first sensing channel (631), and the flow rate of the buffer solution or sample solution flowing through the first sensing channel (631) can be prevented from decreasing instantaneously according to the operation of the pump unit (900), and the flow rate of the buffer solution or sample solution can be maintained stably.
[0164] The second sensing channel (632) can guide the buffer solution or sample solution that has passed through the biosensor (400) into the tube (700). In one embodiment, the second sensing channel (632) may be in communication with the discharge port (632a) formed in the base frame (210) and may be formed along the left and right directions to be in communication with the first tube connection port (660). The second sensing channel (632) may be positioned in a straight line downstream of the first sensing channel (631). By forming the flow path passing through the biosensor (400) in a straight line, the flow rate and / or flow rate of the buffer solution or sample solution flowing through the biosensor (400) can be stably maintained, and the sensing accuracy for the biomaterial can be improved.
[0165] The channel (600) may include a prefill channel (640) through which the sample solution flows, which is in communication with the sample solution channel (620). One side of the prefill channel (640) may be in communication with the sample solution channel (620). One side of the prefill channel (640) may be in communication with the sample solution port (625). The other side of the prefill channel (640) may be in communication with the prefill port (645).
[0166] The prefill channel (640) can guide the sample solution that has passed through the sample solution channel (620) to the prefill port (645). In one embodiment, the prefill channel (640) is formed to communicate with the sample solution channel (620) and can be formed by bending it multiple times to communicate with the prefill port (645).
[0167] The width of at least a portion of the prefill channel (640) may be changed. In one embodiment, the prefill channel (640) may be formed such that the width of the inlet side and the width of the outlet side are the same, while having a section in between where the width narrows.
[0168] The prefill channel (640) may be equipped with a valve (641) formed to be wider than the inlet and outlet. The valve (641) may be formed to be the widest in the prefill channel (640), while the width of the inlet entering the valve (641) may be formed to be the narrowest in the prefill channel (640). Through this, when a large amount of sample solution is instantaneously introduced into the prefill channel (640), the sample solution may be prevented from being discharged into the prefill port (645).
[0169] The channel (600) may include a waste solution channel (650) that guides the buffer solution or sample solution passing through the tube (700) to the waste solution tank (330). Specifically, one side of the waste solution channel (650) may be in communication with a second tube connection port (670). The other side of the waste solution channel (650) may be in communication with a waste solution port (655). When the pump unit (900) is operated, the buffer solution or sample solution passing through the tube (700) may be stored in the waste solution tank (330).
[0170]
[0171] FIG. 10 is a diagram illustrating the coupling of a biosensor and a printed circuit board to a frame in a biosensor cartridge according to an embodiment of the present invention. FIG. 11 is a diagram illustrating a sensor coupling portion in a biosensor cartridge according to an embodiment of the present invention. FIG. 12 is a diagram illustrating the state in which a biosensor is coupled in a biosensor cartridge according to an embodiment of the present invention. FIG. 13 is a cross-sectional view illustrating the contact between a biosensor and a printed circuit board in a biosensor cartridge according to an embodiment of the present invention. FIG. 14 and FIG. 15 are cross-sectional views illustrating the arrangement of a biosensor and a printed circuit board and the arrangement of a flow path flowing over the biosensor in a biosensor cartridge according to an embodiment of the present invention.
[0172] Referring to FIGS. 10 to 15, the biosensor (400) is detachably coupled to the frame (200) and can detect biomaterials. The biosensor (400) can be inserted through the sensor insertion hole (121) of the lower housing (120), and the biosensor (400) can be coupled to the sensor coupling part (211) of the base frame (210).
[0173] A biosensor (400) can selectively detect a minute amount of biomaterial to be analyzed by combining a bioreceptor having a recognition function for a specific biomaterial with an electrical transducer to convert biological interactions and recognition responses into electrical signals.
[0174] In one embodiment, a sensing portion may be provided on the upper surface of the biosensor (400). A bio-receptor may be disposed in the sensing portion. A buffer solution and a sample solution may flow through the sensing portion. The sensing portion may be connected to a circuit to transmit an electrical signal generated in the sensing portion.
[0175] A circuit may be placed on the biosensor (400) and may be electrically connected to the printed circuit board (500) by a contact clip (450).
[0176] A sealer (410) may be disposed on the upper side of the biosensor (400). The sealer (410) may be disposed on the sensor coupling portion (211). A flow path forming portion (411) may be formed in the sealer (410). In one embodiment, the sealer (410) may be formed in the shape of a rectangular parallelepiped, and the flow path forming portion (411) may be in the shape of a slit formed along the left and right directions.
[0177] The flow path forming part (411) may be positioned on the lower side of the frame formed in the sensor coupling part (211). The flow path forming part (411) may be positioned on the lower side of the inlet port (631a) and the outlet port (632a) formed in the sensor coupling part (211), and may be in communication with the inlet port (631a) and the outlet port (632a). The buffer solution and sample solution flowing through the first sensing channel (631) may flow through the flow path inside the flow path forming part (411) via the inlet port (631a), pass through the outlet port (632a), and be introduced into the second sensing channel (632).
[0178] The flow path forming part (411) may be positioned above the sensing part of the biosensor (400). The sealer (410) may be formed to surround the outer edge of the sensing part. The sealer (410) seals the outer edge of the flow path forming part (411) to prevent the buffer solution and sample solution flowing inside the flow path forming part (411) from leaking out.
[0179] The printed circuit board (500) can be detachably coupled to the frame (200). At least a portion of the biosensor (400) can be inserted into the upper housing (110) and detachably coupled to the substrate coupling portion (221) of the top frame (220). The printed circuit board (500) can be supported by the coupling guide portion (221a) and the substrate support portion (221b).
[0180] The printed circuit board (500) may include a board body (510), a connector (520), and a guide portion (530). In one embodiment, the board body (510) may be formed in the shape of a roughly rectangular flat plate. A circuit may be mounted on the board body (510) and electrically connected to the biosensor (400).
[0181] A connector (520) may be provided at the front end of the substrate body (510). The connector (520) may be connected to a circuit provided in the substrate body (510). When the biosensor cartridge (1) is coupled to the diagnostic device (2), an electrical signal can be transmitted to the diagnostic device (2) through the connector (520). When the biosensor cartridge (1) is coupled to the diagnostic device (2), power can be applied to the printed circuit board (500) and the biosensor (400) through the connector (520).
[0182] The guide portion (530) may be formed at both ends of the substrate body (510) in the left and right directions and may be coupled with the substrate support portion (221b) of the substrate coupling portion (221). In one embodiment, the guide portion (530) may be formed as a recessed shape in the left and right directions of the substrate body (510). Through this, it may be coupled with the protruding shape of the substrate support portion (221b) to guide the accurate coupling position of the printed circuit board (500) and stably support the printed circuit board (500) in the coupled state.
[0183] A contact clip (450) may be placed between the biosensor (400) and the printed circuit board (500). The contact clip (450) is coupled to the sensor coupling portion (211) and may come into contact with the printed circuit board (500) and the biosensor (400). The contact clip (450) is positioned to pass through the clip receiving hole (221c) and to pass through the hole of the sensor coupling portion (211), but at least a portion may be supported by the base frame (210).
[0184] A plurality of contact clips (450) may be provided. An even number of contact clips (450) may be provided. A plurality of pairs of contact clips (450) may be arranged side by side, and one pair may be symmetrically arranged in a position facing each other. In one embodiment, six contact clips (450) may be provided, and three pairs may be arranged side by side, and each pair may be symmetrically arranged in a position facing each other.
[0185] The contact clip (450) may be formed of a conductive material. In one embodiment, the contact clip (450) may be formed of a metal material. Each contact clip (450) may include a substrate contact portion (451), a sensor contact portion (452), and a connection portion (453).
[0186] The substrate contact portion (451) may be positioned to pass through the clip receiving hole (221c). The substrate contact portion (451) may be in contact with a terminal (not shown) provided on the printed circuit board (500). That is, the substrate contact portion (451) may be electrically connected to a circuit mounted on the printed circuit board (500). In one embodiment, the substrate contact portion (451) may be in the form of a plate extending along the front-rear direction.
[0187] The sensor contact portion (452) is positioned to pass through a hole formed in the sensor coupling portion (211) and can come into contact with a terminal (not shown) provided in the biosensor (400). That is, the sensor contact portion (452) can be electrically connected to a circuit mounted on the biosensor (400). In one embodiment, the sensor contact portion (452) may be in the form of a plate that is formed extending downward from the coupling portion (453), then folded and extended upward.
[0188] The total height of the contact clip (450) in the vertical direction can be formed to be longer than the shortest distance between the biosensor (400) and the printed circuit board (500). Through this, when the sensor contact portion (452) comes into contact with the biosensor (400), the sensor contact portion (452) can apply pressure to the biosensor (400) while elastically deforming, and can maintain a strong contact state while minimizing the contact area with the biosensor (400).
[0189] The connecting portion (453) may be formed to connect the substrate contact portion (451) and the sensor contact portion (452). The connecting portion (453) is formed by bending and extending downward from the substrate contact portion (451), then being bent and extended along the front-rear direction, and may be connected to the sensor contact portion (452) by bending and extending downward. The connecting portion (453) may be supported by contacting the base frame (210).
[0190] The contact clip (450) is seated on the frame (200), so that its upper side contacts the printed circuit board and its lower side contacts the biosensor (400). Through the contact clip (450), the buffer solution and sample solution can be flowed between the printed circuit board (500) and the biosensor (400), while the electrical signal generated from the biosensor (400) can be transmitted to the printed circuit board over the shortest distance.
[0191]
[0192] FIG. 16 is a diagram illustrating the process of diagnosing a sample solution introduced into a biosensor cartridge using a diagnostic device according to one embodiment of the present invention.
[0193] Referring to FIGS. 1, FIGS. 2, and FIGS. 16, the biosensor cartridge (1) may have a biosensor (400) and a printed circuit board (500) combined therein. However, if there is an error in the biosensor (400) and the printed circuit board (500), the user may replace them.
[0194] The user can inject the buffer solution into the biosensor cartridge (1). The user can inject it into the buffer solution injection hole (111). In the present invention, the buffer solution can be injected into the buffer solution injection hole (111) using a buffer blister (3).
[0195] In one embodiment, the buffer blister (3) may be formed with a circular dome shape at the top and a flat shape at the bottom. The top of the buffer blister (3) may be formed of a deformable material, and the bottom surface of the buffer blister (3) may be formed of a tearable material.
[0196] The buffer blister (3) can be received in the blister receiving groove (111a). The buffer blister (3) may be provided in a fixed state in the blister receiving groove (111a), and the buffer blister (3) may also be detachably coupled to the blister receiving groove (111a).
[0197] With the buffer blister (3) placed inside the blister receiving groove (111a), the user can press the buffer blister (3) downward using a finger or the like. In this case, the upper part of the dome-shaped buffer blister (3) is deformed downward, and as the internal pressure of the buffer blister (3) increases, the lower surface bursts, and the buffer solution stored inside the buffer blister (3) flows downward due to gravity and can be introduced into the buffer solution injection hole (111).
[0198] The buffer solution that has passed through the buffer solution inlet hole (111) can be contained in the buffer solution tank (310). It can then flow into the buffer solution inlet port (315) along the inclined surface (311). Additionally, some of the buffer solution contained in the buffer solution tank (310) can flow along the buffer solution channel (610). However, unless the pump unit (900) is operating, it may not flow into the sensing channel (630).
[0199] The user can inject the sample solution into the sample solution inlet hole (112). The user can inject the sample solution into the sample solution inlet hole (112) using a sample injection tool (4) including a dropper.
[0200] It is possible to inject the buffer solution and the sample solution simultaneously, to inject the sample solution first and then the buffer solution, or to inject the buffer solution first and then the sample solution.
[0201] The sample solution that has passed through the sample solution inlet hole (112) can be received in the sample solution tank (320). And, some of the sample solution received in the sample solution tank (320) can flow along the sample solution channel (620). However, unless the pump unit (900) is operated, it may not flow into the sensing channel (630).
[0202] After the buffer solution and sample solution are introduced, the user can insert the biosensor cartridge (1) into the diagnostic device (2).
[0203]
[0204] FIG. 17 is a cross-sectional view illustrating a biosensor through which a solution flows according to one embodiment of the present invention. FIG. 18 to 20 are drawings illustrating the circuit arrangement of a biosensor according to one embodiment of the present invention.
[0205] Referring to FIGS. 17 to 19, a biosensor (400) according to one embodiment of the present invention comprises a substrate (401), a first gate (421), a second gate (422), a potential measuring unit (423), a first drain (431), a first source (432), a first drain source channel (433), a second drain (441), a second source (442), a second drain source channel (443), a third drain (461), a third source (462), a third drain source channel (463), a fourth drain (471), a fourth source (472), a fourth drain source channel (473), a first gate electrode (481), a second gate electrode (482), a potential measuring unit electrode (483), a first drain electrode (484), a second drain electrode (485), a third drain electrode (486), a fourth drain electrode (487), and a source electrode (488). It is possible.
[0206] As one embodiment, the substrate (401) may be in a single crystal state and may include silicon (Si) material. As one embodiment, the substrate (401) may be a thinned substrate through a thinning process.
[0207] The first gate (421) may be formed on the substrate (401). The first gate (421) may be positioned or formed at the central portion of the substrate (401).
[0208] The first gate (421) can be positioned or formed at a lower position of the inlet port (631a) formed in the base frame (210) of the biosensor cartridge (1) when coupled to the biosensor cartridge (1).
[0209] The second gate (422) may be formed on the substrate (401). The second gate (422) may be positioned or formed at the central portion of the substrate (401). The second gate (422) may be positioned or formed on the same straight line at a location spaced apart from the first gate (421) by a certain distance.
[0210] The second gate (422) can be positioned or formed at the lower position of the discharge port (632a) on the base frame (210) of the biosensor cartridge (1) when combined with the biosensor cartridge (1).
[0211] The first gate (421) and the second gate (422) may include polysilicon or a metallic material (e.g., tungsten (W), copper (Cu), aluminum (Al), gold (Au), palladium (Pd)).
[0212] The first gate (421) and the second gate (422) can be formed by a photolithography patterning method, a deposition process such as CVD, etc.
[0213] The potential measuring unit (423) is formed between the first gate (421) and the second gate (422) and can measure the potential of each of the first gate (421) and the second gate (422).
[0214] Channel sections (433, 443, 463, 473) may be formed between the first gate (421) and the potential measuring section (423), and between the potential measuring section (423) and the second gate (422).
[0215] The first gate (421), the potential measuring unit (423), and the second gate (422) can be formed on the same straight line and can be formed to have a symmetrical sandwich structure. Through this, a straight electric field is applied to the channel portions (433, 443, 463, 473) from both the first gate (421) and the second gate (422), thereby generating a stable electric field effect. In addition, by increasing the degrees of freedom in the fluid movement direction through the structure of the first gate (421), the potential measuring unit (423), and the second gate (422), the sensing accuracy can be improved.
[0216] A first gap (16) may be formed between the first gate (421) and the potential measuring unit (423), and a second gap (17) may be formed between the potential measuring unit (423) and the second gate (422). In one embodiment, the first gap (16) and the second gap (17) may be the same. Through this, the deviation between each channel can be effectively reduced.
[0217] By placing the first gate (421) at a position below the inlet port (631a) formed in the base frame (210) of the biosensor cartridge (1) and placing the second gate (422) at a position below the outlet port (632a) in the base frame (210) of the biosensor cartridge (1), the potential can be kept constant, thereby reducing measurement noise and improving sensing accuracy.
[0218] The channel section may include a first drain source channel (433), a second drain source channel (443), a third drain source channel (463), and a fourth drain source channel (473).
[0219] The first drain source channel (433) is formed in the first drain (431) and the first source (432), and can be formed between the first gate (421) and the potential measuring unit (423).
[0220] The second drain source channel (443) is formed in the second drain (441) and the first source (442), and can be formed between the potential measuring unit (423) and the second gate (422).
[0221] The third drain source channel (463) is formed in the third drain (461) and the third source (462), and can be formed between the first gate (421) and the potential measuring unit (423).
[0222] The fourth drain source channel (473) is formed in the fourth drain (471) and the fourth source (472), and can be formed between the potential measuring unit (423) and the second gate (422).
[0223] The first drain source channel (433), the second drain source channel (443), the third drain source channel (463), and the fourth drain source channel (473) may include graphene as in one embodiment. The first drain source channel (433), the second drain source channel (443), the third drain source channel (463), and the fourth drain source channel (473) may be formed through a patterning and graphene deposition process as in one embodiment.
[0224] The first drain (431) may be formed on one side of the first drain source channel (433), and the first source (432) may be formed on the other side of the first drain source channel (433).
[0225] The second drain (441) may be formed on one side of the second drain source channel (443), and the second source (442) may be formed on the other side of the second drain source channel (443).
[0226] A third drain (461) may be formed on one side of the third drain source channel (463), and a third source (462) may be formed on the other side of the third drain source channel (463).
[0227] The fourth drain (471) may be formed on one side of the fourth drain source channel (473), and the fourth source (472) may be formed on the other side of the fourth drain source channel (473).
[0228] The first drain (431), second drain (441), third drain (461), fourth drain (471), first source (432), second source (442), third source (462), and fourth source (472) may, as in one embodiment, include polysilicon or a metallic material (e.g., tungsten (W), copper (Cu), aluminum (Al), gold (Au), palladium (Pd)).
[0229] The first drain (431), second drain (441), third drain (461), fourth drain (471), first source (432), second source (442), third source (462), and fourth source (472) can be formed by a deposition process such as photolithography patterning or CVD as in one embodiment.
[0230] The first gate electrode (481) is formed on one side corner of the substrate (401) and can be electrically connected to the first gate (421). When coupled to the biosensor cartridge (1), the first gate electrode (481) can be electrically connected to the contact clip (450) of the biosensor cartridge (1).
[0231] The second gate electrode (482) is formed on the other side corner of the substrate (401) and can be electrically connected to the second gate (422). When coupled to the biosensor cartridge (1), the second gate electrode (482) can be electrically connected to the contact clip (450) of the biosensor cartridge (1).
[0232] The potential measuring electrode (483) is formed on the substrate (401) and is formed at a position spaced apart from the first gate electrode (481) at a certain distance, and can be electrically connected to the potential measuring unit (423). When coupled to the biosensor cartridge (1), the potential measuring electrode (483) can be electrically connected to the contact clip (450) of the biosensor cartridge (1).
[0233] The first drain electrode (484) is formed on the substrate (401), is formed between the first gate electrode (481) and the potential measuring electrode (483), and can be electrically connected to the first drain (431). When coupled to the biosensor cartridge (1), the first drain electrode (484) can be electrically connected to the contact clip (450) of the biosensor cartridge (1).
[0234] The second drain electrode (485) is formed on the substrate (401), is formed at a position spaced apart from the potential measuring electrode (483) at a certain distance, and can be electrically connected to the second drain (441). When coupled to the biosensor cartridge (1), the second drain electrode (485) can be electrically connected to the contact clip (450) of the biosensor cartridge (1).
[0235] The third drain electrode (486) is formed at the opposite corner of the first gate electrode (481) or the second gate electrode (482) of the substrate (401) and can be electrically connected to the third drain (461). When coupled to the biosensor cartridge (1), the third drain electrode (486) can be electrically connected to the contact clip (450) of the biosensor cartridge (1).
[0236] The fourth drain electrode (487) is formed on the substrate (401), is formed at a position spaced apart from the second gate electrode (482) by a certain distance, and can be electrically connected to the fourth drain (471). When coupled to the biosensor cartridge (1), the fourth drain electrode (487) can be electrically connected to the contact clip (450) of the biosensor cartridge (1).
[0237] The source electrode (488) is formed on the substrate (401) and is formed between the third drain electrode (486) and the fourth drain electrode (487), and can be electrically connected to the first source (432), the second source (442), the third source (462), and the fourth source (472). When coupled to the biosensor cartridge (1), the source electrode (488) can be electrically connected to the contact clip (450) of the biosensor cartridge (1).
[0238] Referring to FIG. 20, as an embodiment, the biosensor (400) may further include a potential compensation unit (27).
[0239] One end of the potential compensation unit (27) may be electrically connected to the first gate electrode (418) and the second gate electrode (482), and the other end of the potential compensation unit (27) may be electrically connected to the potential measurement unit electrode (483).
[0240] The potential compensation unit (27) may include a feedback circuit (Negative Feedback) comprising a first input terminal (+), a second input terminal (-), and an output terminal. The first input terminal (+) of the potential compensation unit (27) is electrically connected to a power source, the second input terminal (-) of the potential compensation unit (27) is electrically connected to a potential measurement unit electrode (483), and the output terminal of the potential compensation unit (27) may be electrically connected to a first gate electrode (418) and a second gate electrode (482).
[0241] The potential applied to the first gate (421) and the second gate (422) can pass through the channel section via the fluid and be fed back through the potential measuring section (423).
[0242] Since it is possible to always maintain the potential of the first gate (421) and the second gate (422) applied to the channel section (433, 443, 463, 473) through the potential compensation section (27), measurement noise can be reduced and sensing accuracy can be improved.
[0243] In the present invention, the potential compensation unit (27) may be included in the biosensor (400), but is not limited thereto, and may be included in the printed circuit board (500) of the biosensor cartridge (1) or the diagnostic device (2).
[0244] Although not illustrated in a separate drawing, a biosensor (400) according to one embodiment of the present invention may include a substrate, a gate, a potential measuring unit, a first drain, a first source, a first drain source channel, a second drain, a second source, a second drain source channel, a gate electrode, a potential measuring unit electrode, a first drain electrode, a second drain electrode, and a source electrode. In FIG. 20
[0245] The potential measuring unit is formed at a position spaced apart from the substrate at a certain interval and can measure the potential of the gate.
[0246] The channel portion may be formed between the gate and the potential measurement portion, and the channel portion may include a first drain source channel and a second drain source channel.
[0247] A first drain source channel can be formed between a gate and a potential measuring unit, and a second drain source channel can be formed between a gate and a potential measuring unit and at a position spaced apart from the first drain source channel by a certain distance.
[0248] The gate and the potential measuring section can be formed on the same straight line.
[0249]
[0250] FIGS. 21 and FIGS. 22 are drawings for explaining transfer curve noise reduction according to an embodiment of the present invention.
[0251] FIG. 21 is a diagram showing a transfer curve representing the relationship between drain current (ids) and gate voltage (Vgs) of a conventional biosensor, and FIG. 22 is a diagram showing a transfer curve of a biosensor according to the present invention.
[0252] Referring to FIGS. 21 and 22, according to the present invention, transfer curve noise is significantly reduced compared to conventional biosensors.
[0253] FIGS. 23 and FIGS. 24 are drawings for illustrating potential compensation according to an embodiment of the present invention.
[0254] FIG. 23 is a diagram showing the gate potential of a conventional biosensor, and FIG. 24 is a diagram showing the gate potential of a biosensor according to the present invention.
[0255] Referring to FIGS. 23 and 24, compared to conventional biosensors, according to the present invention, by compensating for the gate potential, a voltage drop between the system gate potential and the gate does not occur, and it is possible to maintain the gate potential at a constant level, thereby reducing measurement noise and improving sensing accuracy.
[0256]
[0257] Although the present invention has been described in detail through specific embodiments, this is for the purpose of specifically explaining the invention and is not limited thereto. It is evident that modifications or improvements to the present invention are possible by those skilled in the art within the technical scope of the invention.
[0258] All simple variations or modifications of the present invention fall within the scope of the present invention, and the specific scope of protection of the present invention will be clarified by the appended claims.
Claims
1. Substrate, A first gate formed on the above substrate, A second gate formed on the above substrate, and A potential measuring unit formed between the first gate and the second gate, which measures the potential of the first gate and the potential of the second gate. Includes, A biosensor in which a channel portion is formed between the first gate and the potential measuring portion and between the potential measuring portion and the second gate.
2. In Paragraph 1, The above channel section is, A first drain source channel formed between the first gate and the potential measuring unit, A second drain source channel formed between the above potential measuring unit and the second gate, A third drain source channel formed between the first gate and the potential measuring unit, and formed at a position spaced apart from the first drain source channel by a certain distance, and A biosensor comprising a fourth drain source channel formed between the potential measuring unit and the second gate, and formed at a position spaced apart from the second drain source channel by a certain distance.
3. In Paragraph 1, The first gate, the potential measuring unit, and the second gate are, A biosensor formed on the same straight line.
4. In Paragraph 1, A first gap is formed between the first gate and the potential measuring unit, and A second gap is formed between the above-mentioned potential measuring unit and the above-mentioned second gate, and The above first interval and the above second interval are the same, biosensor.
5. In Paragraph 2, A first drain formed on one side of the first drain source channel, A first source formed on the other side of the first drain source channel, A second drain formed on one side of the second drain source channel, A second source formed on the other side of the second drain source channel, A third drain formed on one side of the third drain source channel, A third source formed on the other side of the third drain source channel, A fourth drain formed on one side of the fourth drain source channel, and A biosensor further comprising a fourth source formed on the other side of the fourth drain source channel.
6. In Paragraph 1, A first gate electrode connected to the first gate, A second gate electrode connected to the second gate, and It further includes a potential measuring electrode connected to the above potential measuring unit, The first gate electrode and the second gate electrode are, It is electrically connected to one end of a potential compensation unit that compensates the potential of the first gate and the potential of the second gate to a preset potential, and The above potential measuring electrode is, A biosensor electrically connected to the other end of the above-mentioned potential compensation unit.
7. Substrate, A gate formed on the above substrate, and A potential measuring unit formed at a position spaced apart at a certain interval on the substrate and measuring the potential of the gate Includes, A biosensor in which a channel portion is formed between the above gate and the above potential measuring portion.
8. In Paragraph 7, The above channel section is, A first drain source channel formed between the gate and the potential measuring unit, and A biosensor comprising a second drain source channel formed between the gate and the potential measuring unit, and formed at a position spaced apart from the first drain source channel by a certain distance.
9. In Paragraph 7, The above gate and the above potential measuring unit are, A biosensor formed on the same straight line.
10. A biosensor cartridge in which a flow path for the solution is formed, A biosensor disposed in the above biosensor cartridge, and Diagnostic device for analyzing signals received from the above biosensor Includes, The above biosensor is, substrate, A first gate formed on the above substrate, A second gate formed on the above substrate, and A potential measuring unit formed between the first gate and the second gate, which measures the potential of the first gate and the potential of the second gate. Includes, A sensing system in which a channel is formed between the first gate and the potential measuring unit and between the potential measuring unit and the second gate.
11. In Paragraph 10, The above channel section is, A first drain source channel formed between the first gate and the potential measuring unit, A second drain source channel formed between the above potential measuring unit and the second gate, A third drain source channel formed between the first gate and the potential measuring unit, and formed at a position spaced apart from the first drain source channel by a certain distance, and A sensing system comprising a fourth drain source channel formed between the above-mentioned potential measuring unit and the above-mentioned second gate, and formed at a position spaced apart from the above-mentioned second drain source channel by a certain distance.
12. In Paragraph 10, The first gate, the potential measuring unit, and the second gate are, A sensing system formed in a straight line direction identical to the direction in which the above solution flows.
13. In Paragraph 10, A first gap is formed between the first gate and the potential measuring unit, and A second gap is formed between the above-mentioned potential measuring unit and the above-mentioned second gate, and A sensing system in which the first interval and the second interval are identical.
14. In Paragraph 10, The above diagnostic device is, A sensing system comprising a potential compensation unit that compensates for potentials to maintain the potential of the first gate and the potential of the second gate at preset potentials.
15. In Paragraph 14, The above biosensor is, A first gate electrode connected to the first gate, A second gate electrode connected to the second gate, and It further includes a potential measuring electrode connected to the above potential measuring unit, The first gate electrode and the second gate electrode are electrically connected to one end of the potential compensation unit, and A sensing system in which the electrode of the potential measuring unit is electrically connected to the other end of the potential compensation unit.