In vitro diagnostic device using chemiluminescence

Abstract

The present invention relates to a chemiluminescent in vitro diagnostic device using a cartridge having a plurality of wells. The in vitro diagnostic device of the present invention comprises: a syringe having an outlet part at a lower end thereof; a plunger configured to move up and down in a state of being in close contact with the inside of the syringe; a magnet rod attached to the lower portion of the plunger in a height direction and configured such that the lower end thereof can pass through the outlet part of the syringe; a first driving unit for moving the syringe up and down; and a second driving unit for moving the syringe up and down.

Description

In vitro diagnostic equipment using chemiluminescence

[0001] The present invention relates to an in vitro diagnostic device utilizing chemiluminescence, and in particular to an in vitro diagnostic device that is easy to miniaturize.

[0002] A device is known for qualitatively or quantitatively analyzing specific components from biological specimens based on immunoassays, utilizing a disposable cartridge loaded with reagents and configured by connecting various wells. In particular, analysis with very high precision is possible when using chemiluminescent reagents. The chemiluminescent cartridge is equipped with reaction wells, washing wells, and measurement wells, in addition to reagent wells for loading various reagents. Specifically, in the measurement well, the biological specimen reacts with the chemiluminescent reagent to generate light with an intensity determined by the concentration of the target component. An optical system can measure the light intensity by placing it in close proximity to the measurement well.

[0003] Meanwhile, conventional in vitro diagnostic equipment using the above cartridge has the problem of being structurally complex and large because it is equipped with a dispensing module, a pump module, a magnetic bead collection module, a punching module, etc., separately. When multiple devices are used in a small workspace, securing installation space becomes a very important factor for large equipment. In addition, large equipment has the problem of being difficult to use in medical settings due to poor accessibility for on-site medical care.

[0004] Therefore, the present invention has one objective of miniaturizing an in vitro diagnostic device utilizing chemiluminescence.

[0005] In addition, another objective of the present invention is to provide an in vitro diagnostic device that can be easily used in a medical setting due to its high on-site medical accessibility.

[0006] The present invention, for achieving the aforementioned purpose, is characterized in that it comprises a chemiluminescent in vitro diagnostic device using a cartridge having a plurality of wells, wherein the device comprises: a syringe having an outlet portion at the bottom; a plunger configured to move up and down while in close contact with the inside of the syringe; a magnetic rod attached in the height direction to the lower part of the plunger and configured such that its bottom part can pass through the outlet portion of the syringe; a first driving unit for moving up and down the syringe; and a second driving unit for moving up and down the plunger.

[0007] Preferably, the second driving unit drives the up-and-down movement of the plunger relative to the syringe.

[0008] Preferably, the outer diameter of the outlet portion of the syringe is smaller than the outer diameter of the well so that it can be inserted into the interior of the well of the cartridge for well punching. Additionally, the well punching is performed with the lower end of the magnetic rod aligned at a position higher than the lower end of the outlet portion of the syringe.

[0009] Preferably, a dispensing tip is coupled to the outlet portion of the syringe, wherein the upper inner diameter of the dispensing tip is larger than the lower inner diameter, and the magnetic rod has an outer diameter capable of pushing out the upper portion of the dispensing tip without contacting the solution at the lower portion of the dispensing tip. Additionally, the dispensing tip is provided with a threshold portion formed in the middle portion of its interior.

[0010] Preferably, the well punching or dispensing tip coupling is performed by the first driving unit driving the syringe downward.

[0011] Preferably, the solution is drawn into the dispensing tip by driving the plunger upward relative to the syringe. Additionally, the dispensing tip is separated from the outlet portion of the syringe by driving the plunger downward relative to the syringe.

[0012] Preferably, an elastic body is further provided installed between the plunger and the magnetic rod, and a magnetic tip is coupled to the outlet portion of the syringe, and the lower end of the magnetic rod is attached to the bottom of the magnetic tip.

[0013] Preferably, the magnetic tip coupling is performed by the first driving unit driving the syringe downward. Additionally, bead collection with the magnetic tip is performed by the second driving unit driving the plunger downward to a first position relative to the syringe. Additionally, the magnetic tip is separated from the outlet portion of the syringe by the second driving unit driving the plunger downward to a second position lower than the first position relative to the syringe.

[0014] The present invention, with the aforementioned configuration, miniaturizes an in vitro diagnostic device utilizing chemiluminescence. The present invention facilitates securing space for equipment installation when multiple devices are used in a small workspace. Furthermore, the present invention reduces the weight and volume of the in vitro diagnostic device, thereby reducing logistics costs. Additionally, the present invention makes it very easy to move the device within a workspace. Moreover, the present invention improves the on-site medical accessibility of the device, thereby enabling the device to be easily utilized in medical settings.

[0015] FIG. 1 is a configuration diagram of an in vitro diagnostic device according to one embodiment of the present invention.

[0016] Figure 2 is a drawing illustrating an example of a cartridge used in the in vitro diagnostic equipment shown in Figure 1.

[0017] Figure 3 is a diagram showing the configuration of a dispensing tip mounted on the cartridge shown in Figure 2.

[0018] Figure 4 is a diagram showing the configuration of a magnetic tip mounted on the cartridge shown in Figure 2.

[0019] Figure 5 is a diagram illustrating the state of a cartridge equipped with a dispensing tip and a cleaning tip.

[0020] FIG. 6 is a configuration diagram of a sample processing module of an in vitro diagnostic device according to one embodiment of the present invention.

[0021] Figure 7 is a diagram illustrating the process of processing a sample in the sample processing module shown in Figure 6.

[0022] Figure 8 is a diagram illustrating the well punching step performed in the sample processing module shown in Figure 6.

[0023] FIG. 9 is a diagram illustrating the state in which a dispensing tip according to another embodiment of the present invention is coupled to a sample processing module shown in FIG. 6.

[0024] FIG. 10 is a cross-sectional view of a dispensing tip according to another embodiment of the present invention.

[0025] FIG. 11 is a cross-sectional view of a dispensing tip according to another additional embodiment of the present invention.

[0026] FIG. 12 is a diagram illustrating the process of processing a sample in a sample processing module of an in vitro diagnostic device according to another embodiment of the present invention.

[0027] FIG. 13 is a cross-sectional view of a magnetic tip according to another embodiment of the present invention.

[0028] FIG. 14 is a cross-sectional view of a magnetic tip according to another embodiment of the present invention.

[0029] To fully understand the present invention, preferred embodiments of the invention are described with reference to the accompanying drawings. Embodiments of the present invention may be modified in various forms, and the scope of the present invention should not be interpreted as being limited to the embodiments described in detail below. These embodiments are provided to more completely explain the present invention to those with average knowledge in the art. Accordingly, the shapes of elements in the drawings may be exaggerated to emphasize clearer explanations. It should be noted that in each drawing, identical components may be depicted with the same reference numeral. Detailed descriptions of known functions and configurations that are deemed to unnecessarily obscure the essence of the present invention are omitted.

[0030] In a drawing, the "upper end" of a component refers to the end portion of the upper part as depicted, and the "lower end" refers to the end portion of the lower part as depicted.

[0031] FIG. 1 is a configuration diagram of an in vitro diagnostic device (1) according to an embodiment of the present invention. As shown, the in vitro diagnostic device (1) is provided with a display unit (3) and an inlet / outlet port (4) in a housing (2). A cartridge (10) provided into the interior of the in vitro diagnostic device (1) through the inlet / outlet port (4) is provided with a plurality of wells, and the wells accommodate a sample, a dispensing tip, a magnetic tip, etc. The in vitro diagnostic device (1) performs a sandwich immune reaction, a competitive immune reaction, etc., using magnetic beads on the sample accommodated in the cartridge (10).

[0032] A sandwich immunoassay refers to an immune reaction in which a capture antibody and a detector antibody are sandwiched together. An enzyme is chemically bound to the detector antibody to induce a quantitative reaction with the substrate. In this process, the capture antibody is chemically or physically bound to magnetic beads, while the detector antibody utilizes a conjugate bound to the enzyme. Sandwich reactions using magnetic beads can be broadly classified into two types: a 1-step assay or a 2-step assay, depending on the number of washing steps. In a 2-step assay, the sample is reacted with the capture antibody first, followed by washing and then the reaction with the detector antibody. In a 1-step assay, the capture antibody and the detector antibody are reacted simultaneously.

[0033] Competition assays, which are widely used to detect small amounts of protein molecules along with sandwich immune responses, are also divided into two methods. Depending on whether a competing protein or antibody is conjugated to magnetic beads, they are divided into indirect or direct competition assays, and depending on the stages of the immune response, they are divided into 1-step and 2-step reactions.

[0034] In this embodiment, chemiluminescence is used for the detection of reaction products. Chemiluminescence is light emitted as excited electrons generated by a chemical reaction return to the ground state. It does not require a light source and is measured in relative light units (RLU) per hour, which is used to determine the concentration of analytes in a sample. Examples of enzymes and substrates include peroxidase and its substrates luminol, polyphenols (e.g., pyrrogalol, peroperogallin, gallic acid, and umbelliferone, etc.), and acridine esters or luciferin (referred to as bioluminescence when used), but are not limited thereto. Other examples of enzymes and substrates include ALP and AMPPD (3-(2'-spiroadamantyl)-4-methoxy-4-(3″-phosphoryloxy)-phenyl-1,2-dioxetane), but are not limited thereto.

[0035] In such analyses, high-sensitivity detection with particularly high specificity is required, and to achieve this, the removal of non-specific or unreacted substances is necessary. That is, after the reaction between a reagent and a sample during the inspection process, purification or separation of the reaction product is required for accurate detection of the reaction product, and the device according to the present invention is optimized for the effective removal of such unreacted substances.

[0036] Specifically, the device according to the present embodiment is a device optimized for removing unreacted material through physical washing using magnetism, separating and concentrating only the product of a specific reaction into the form of magnetic beads using a permanent magnet, selectively attaching a detector with an enzyme attached to the reaction product, and finally reacting the enzyme with a substrate to detect the signal of the reaction product.

[0037] The above-described reaction used in the in vitro diagnostic equipment according to the present embodiment is performed in a liquid state within a cartridge mounted in the equipment. The device according to one embodiment of the present invention is optimized for performing an optimized reaction step by considering the characteristics of various parameters performed in the reaction to perform the above-described reaction in the cartridge and to detect the reaction result.

[0038] FIG. 2 is a diagram showing the structure of a cartridge (10) according to one embodiment of the present invention. FIG. 3 is a diagram showing the configuration of a dispensing tip (20) according to one embodiment of the present invention, and FIG. 4 is a diagram showing the configuration of a magnetic tip (30) according to one embodiment of the present invention.

[0039] The cartridge (10) used in the automated in vitro diagnostic device (1) according to the present embodiment is used for a reaction to detect an analyte contained in a sample, wherein a reaction between the sample and the reagent is performed in the cartridge, a reaction product is generated, and said reaction product is washed. The cartridge (10) may have an elongated shape extending in the front-rear direction. Additionally, the cartridge (10) may include one or more fitting holes and a plurality of chambers. These chambers may also be referred to as wells.

[0040] The insertion hole is a place where the magnetic tip (30) and the dispensing tip (20) are inserted and wait until the inspection starts or during the inspection process, and the magnetic tip insertion hole (21) and the dispensing tip insertion hole (31) are each provided.

[0041] The above chamber may be configured to include, in order, a sample filling chamber (12), a buffer and dilution chamber (13a, 13b, 13c, and 13d), a reaction chamber (14), a washing chamber (15), and a detection chamber (16). The chamber may be sealed by a predetermined sealing membrane (not shown) to prevent denaturation or contamination of the reagent. The sample filling chamber (12) is provided to be filled with various samples, for example, biological samples to be analyzed, and may be formed in front of or behind the magnetic tip fitting hole (21) and the dispensing tip fitting hole (31) as previously mentioned. The buffer and dilution chambers (13a, 13b, 13c) are each filled with a magnetic bead (MB) buffer, a detection buffer, and a sample dilution buffer, and the sample is diluted in the buffer and dilution chamber (13d).

[0042] The reaction chamber (14) is configured to perform a reaction between the sample and the reagent and is formed behind the buffer and dilution chambers. The washing chamber (15) is a chamber where the reaction product can be washed after the reaction in the reaction chamber and may include multiple chambers, and in one embodiment of the present invention, three chambers (15a, 15b, and 15c) are included. The detection chamber (16) is a place where the reaction product generated by the reaction between the sample and the reagent is detected, and is configured to detect the presence of an analyte in the reaction product after washing in the washing chamber (15). The detection chamber (16) is formed behind the washing chamber (15) and may be configured to have light transmittance for the detection of a fluorescent signal.

[0043] In this embodiment, the cartridge (10) may additionally include a barcode or QR code (not shown), which is used in conjunction with the chip described below that is inserted into the automated in vitro diagnostic device (1) of the present invention. In the present invention, the barcode includes, but is not limited to, UPC-A, UPC-E, EAN, Code 3 of 9, Interleaved 2 of 5, Code 128, UCC / EAN-128, Codabar, PostNet, Pharmacode, or PDF-417, or includes, but is not limited to, 1D barcodes or 2D barcodes. The barcode or QR code is an encoding of the type of analyte according to the type of sample.

[0044] FIG. 5 illustrates the state of a cartridge (10) equipped with a dispensing tip (20) and a magnetic tip (30) according to an embodiment of the present invention. The dispensing tip (20) may be configured to include a disposable microtip (e.g., a micropipette tip with a capacity of 2-1000 μl) which is connected to a collection arm (556) described below for dispensing or dispensing a reagent between a sample and / or the chambers described above, i.e., from one chamber to another chamber. The dispensing tip (20) may have a tubular shape, and its diameter may gradually decrease toward the end, so that the end portion has a pointed shape. Such a dispensing tip (20) can be used with equipment that does not have a separate reagent supply device and means for cleaning contamination, thereby simplifying the operation of the equipment.

[0045] The plurality of cartridges used in the equipment according to the present embodiment are configured to each have a dispensing tip (20) and a magnetic tip (30) attached, so that they can be used separately from the tips used in other cartridges, thereby preventing contamination. In the case of automated equipment using conventional metal injection needles, a cleaning device must be provided to prevent contamination, which results in a larger volume due to the separate device configuration, requires a separate cleaning process, and has the problem of increasing inspection costs.

[0046] The dispensing tip (20) is inserted and seated in the dispensing tip fitting hole (21) of the cartridge (10), and when the inspection process begins, it is connected to the collection arm (556) described later and, together with the pump unit (506), serves to suck in or discharge for the distribution or dispensing of samples or reagents between chambers. Additionally, during the inspection process, while a reaction is taking place in the first cartridge, the dispensing tip (20) used in the first cartridge can be temporarily stored in the fitting hole (21) to perform a reaction in the second or third cartridge. This allows only one tip to be used in a single cartridge until the inspection is completed without replacing the tip in the middle, thereby providing the advantage of being convenient and reducing the reaction time. This is explained in more detail during the operation process of the device according to one embodiment of the present invention.

[0047] The magnetic tip (30) is a member having a tubular shape with a predetermined height and width, with the bottom sealed, and has an insertion hole formed at the top with a predetermined depth and inner diameter. The magnetic tip (30) is made of a non-magnetic material to transmit magnetism, and may be made of a flexible material to facilitate fixing to the cleaning arm and separating from the cleaning arm. The magnetic tip (30) is also inserted and seated in the magnetic tip insertion hole (21) of the cartridge (10), and when the inspection process begins, it is connected to the diagnostic equipment to perform cleaning as described below. Furthermore, during the inspection process, while a reaction is occurring in the first cartridge, the magnetic tip (30) used in the first cartridge can be stored in the insertion hole (31) to perform a reaction in the second or third cartridge, so that only one tip can be used in one cartridge, which has the advantage of being convenient and reducing the reaction time. This is explained in more detail during the operation process of the device according to one embodiment of the present invention.

[0048] FIG. 6 is a configuration diagram of a sample processing module (100) of an in vitro diagnostic device (1) according to one embodiment of the present invention. As shown, the sample processing module (100) is equipped with a syringe (102), a plunger (106), a magnetic rod (108), a first driving unit (150), and a second driving unit (160).

[0049] The syringe (102) has an outlet (104) at the bottom. In this embodiment, the syringe (102) may be cylindrical or polygonal. The central part of the syringe (102) acts as a pump. The plunger (106) is configured to move up and down while in close contact with the inside of the syringe (102). The magnetic rod (108) is attached to the lower part of the plunger (106) in the height direction and is configured so that its lower end can pass through the outlet (104) of the syringe (102). The magnetic rod (108) is positioned on the same axis in a vertical direction as the plunger (106) and moves up and down together with the plunger (106).

[0050] The first drive unit (150) drives the up and down movement of the syringe (102). A drive motor (116) that generates rotational motion is installed on a mounting base (111). The mounting base (111) is attached to a support (110) installed vertically on the base (109) of the in vitro diagnostic equipment (1). The rotational motion generated by the drive motor (116) is transmitted to a conversion mechanism (122) through a drive shaft (120). The conversion mechanism (122) is composed of a lead screw, etc., and converts the rotational motion generated by the drive motor (116) into linear motion to drive the mounting base (112) in the up and down direction. In the drawing, "UP" indicates movement in the upward direction, and "DOWN" indicates movement in the downward direction.

[0051] The second drive unit (160) drives the up-and-down movement of the plunger (106) relative to the syringe (102). The drive motor (122) constituting the second drive unit (160) is installed on the mounting base (112). The rotational motion generated by the drive motor (122) is transmitted to the conversion mechanism (126) through the drive shaft (124). The conversion mechanism (126) is composed of a lead screw, etc., and converts the rotational motion generated by the drive motor (122) into linear motion to drive the mounting base (114) in the up-and-down direction. Since the plunger (106) is installed on the mounting base (114), the plunger (106) moves up and down according to the up-and-down movement of the mounting base (114).

[0052] FIG. 7 is a diagram illustrating the process of processing a sample in the sample processing module (100) illustrated in FIG. 6. The cartridge (10) is mounted on the cartridge mounting base (300) and moves horizontally by the horizontal movement of the cartridge mounting base (300). FIG. 7 (a) illustrates the basic state of the sample processing module (100). In this embodiment, the magnetic rod (108) and the outlet part (104) are arranged so as not to be approximately concentric or to come into contact with each other.

[0053] In FIG. 7, (b) illustrates the well punching state. FIG. 8 is a diagram that explains the well punching step in detail. In this embodiment, well punching is performed by driving the first driving unit (150) without driving the second driving unit (160) to move the syringe (102) downward (DOWN). The well (or chamber) (302) is sealed by a predetermined sealing membrane (302a) to prevent denaturation or contamination of the reagent. Well punching is the process of punching this sealing membrane (302a). The outer diameter of the outlet portion (104) of the syringe (102) must be larger than the inner diameter of the well (302) so that it can be inserted into the interior of the well (302) for punching. The first driving unit (150) is driven so that the top of the syringe (102) is positioned at a height (H1) so that the outlet part (104) and the magnetic rod (108) are not contaminated by the solution contained in the well (302).

[0054] The sealing membrane (302a) is torn off at the bottom of the outlet section (104). The bottom of the magnetic rod (108) is positioned higher than the bottom of the outlet section (104) by “h”. This is to more effectively prevent the magnetic rod (108) from being contaminated by the solution or magnetic beads contained in the well (302) during the well punching process. If magnetic beads are attached to the magnetic rod (108), they are difficult to remove physically. In addition, magnetic beads attached to the magnetic rod (108) hinder the magnetic rod (108) from adhering to the magnetic tip (30), thereby reducing the efficiency of magnetic bead collection.

[0055] Meanwhile, since the bottom of the magnet rod (108) is higher than the bottom of the outlet section (104), the punched sealing film can be fitted into the entrance of the outlet section (104). Therefore, before proceeding to the next step after well punching, the sealing film fitted into the entrance of the outlet section (104) can be removed by driving the magnet rod (108) so that the bottom of the magnet rod (108) is positioned lower than the bottom of the outlet section (104).

[0056] Figure 7 (c) describes the step of attaching the dispensing tip (20). As shown in (b), after well punching is performed, the cartridge (10) moves horizontally by the cartridge holder (300), and the dispensing tip fitting hole (31) is positioned at the bottom of the syringe (102). In this state, similar to the well punching step, the first driving unit (150) is driven without driving the second driving unit (160) to move the syringe (102) downward (DOWN) so that the top of the syringe (102) is positioned at a height (H1), thereby attaching the dispensing tip (20) to the outlet unit (104).

[0057] Figure 7 (d) describes the solution aspiration step. After moving the syringe (102) with the dispensing tip (20) attached upward, the cartridge (10) is moved horizontally through the cartridge holder (300) so that the well (302) is positioned at the bottom of the syringe (102). Next, the first drive unit (150) is driven so that the top of the syringe (102) is positioned at height (H2), and the plunger (106) is driven upward (UP) through the second drive unit (160) to aspirate the solution in the well (302) into the dispensing tip (20). The dispensing tip (20) is longer in the height direction than the well (302). Therefore, in the solution suction step, the top of the syringe (102) is positioned at a higher height (H2) than the height (H1) in the well punching step or the dispensing tip joining step so that the bottom of the dispensing tip (20) does not come into close contact with the bottom of the well (302).

[0058] Figure 7 (e) describes the solution discharge step. With the solution drawn into the dispensing tip (20), the syringe (102) is moved upward via the first driving unit (150), and the cartridge driving unit (300) is driven so that another well is positioned at the bottom of the syringe (102). In this state, the first driving unit (150) is driven to move the syringe (102) downward so that the top of the syringe (102) is positioned at a height (H3), and then the second driving unit (160) is driven to move the plunger (106) downward to discharge the solution drawn into the dispensing tip (20) into another well. At this time, in the solution discharge step, the top of the syringe (102) is positioned at a higher height (H3) than the height (H2) in the solution drawing step so that the bottom of the dispensing tip (20) is not contaminated by the discharged solution.

[0059] Even if the magnetic rod (108) moves up and down during the solution suction and discharge phase, there is no change in volume within the closed internal space of the syringe (102), so it does not affect the dispensing volume. Since the dispensing tip (20) is an open space, the internal pressure does not increase due to the up-and-down movement of the magnetic rod (108) before it comes into contact with the substance and closes.

[0060] In FIG. 7, (f) describes the dispensing tip separation step. With the top of the syringe (102) positioned at height (H3) by the first driving unit (150), the second driving unit (160) is driven to move the plunger (106) downward so that the magnetic rod (108) protrudes from the outlet (104). At this time, the plunger (106) can be lowered to the maximum extent within the syringe (102). In order for the magnetic rod (108) to protrude from the outlet (104), the inner diameter of the outlet (104) must be larger than the outer diameter of the magnetic rod (108).

[0061] The dispensing tip (20) is configured such that the inner diameter of the upper portion is larger than the inner diameter of the lower portion, and the lower portion of the dispensing tip (20) is contaminated by the solution during the solution suction stage. Therefore, in order to prevent the magnetic rod (108) from touching the inner surface of the lower portion of the contaminated dispensing tip (20) during the dispensing tip separation stage, the magnetic rod (108) has an outer diameter capable of pushing out the upper portion of the dispensing tip (20).

[0062] FIG. 9(a) illustrates a state in which a dispensing tip (902) according to another embodiment of the present invention is coupled to a sample processing module (100) illustrated in FIG. 6, and FIG. 9(b) illustrates a step in which the sample processing module (100) separates the dispensing tip (902). Additionally, FIG. 9(c) is a horizontal cross-sectional view of the dispensing tip (902) at the height of the threshold portion (904). As illustrated, the dispensing tip (902) has a threshold portion (904) formed in the middle portion of the interior. The threshold portion (904) has two separated thresholds (904a, 904b) protruding from the inner wall of the dispensing tip (902) toward the center. The thresholds (904a) and (904b) are spaced apart from each other to allow airflow. The gap between the threshold (904a) and the threshold (904b) is smaller than the outer diameter of the magnetic rod (108) so that the magnetic rod (108) cannot pass through. The sample processing module (100) is driven so that the solution is sucked only up to the lower part of the threshold section (904) during the solution suction stage. During the dispensing tip separation stage, the movement of the lower part of the magnetic rod (108) is restricted by the upper part of the threshold section (904), so the magnetic rod (108) can be more reliably prevented from being contaminated by the solution adhering to the inner surface of the lower part of the dispensing tip (902).

[0063] FIG. 10 is a cross-sectional view of a dispensing tip (950) according to another embodiment of the present invention, FIG. 10(a) is a vertical cross-sectional view, and FIG. 10(b) is a horizontal cross-sectional view obtained at the height of the threshold portion (954). The body portion (952) is funnel-shaped and has a threshold portion (954) on its inner wall. The threshold portion (954) is a continuous single structure. The threshold portion (954) has a hole (956) in the center that enables airflow. The inner diameter of the hole (956) is smaller than the outer diameter of the magnet rod (108) so that the magnet rod (108) cannot pass through.

[0064] FIG. 11 is a cross-sectional view of a dispensing tip (960) according to another embodiment of the present invention. FIG. 11(a) is a vertical cross-sectional view, and FIG. 11(b) is a horizontal cross-sectional view obtained at the height of a threshold portion (964). The dispensing tip (960) has a body portion (962) that is coupled to the outlet portion (104) of a syringe (102) and a discharge portion (964) having a discharge port (963) at its tip. A threshold portion (965) is provided at the bottom portion of the body portion (962) to which the discharge portion (964) is attached. The threshold portion (965) is a continuous single structure. The threshold portion (965) has a hole (966) that communicates with the discharge port (963). The inner diameter of the hole (966) is smaller than the outer diameter of the magnet rod (108) so that the magnet rod (108) cannot pass through.

[0065] In FIG. 7, (g) describes the magnetic tip coupling step. The cartridge (10) is positioned by the cartridge holder (300) so that the magnetic tip fitting hole (31) is located at the bottom of the syringe (102). As in the well punching step or the dispensing tip coupling step, the first driving unit (150) drives the syringe (102) downward so that the top of the syringe (102) is positioned at a height (H1). (h) describes the magnetic bead collection step. The first driving unit (150) is driven so that the top of the syringe (102) is positioned at a height (H2). To increase the collection efficiency in the magnetic bead collection step, the second driving unit (160) drives the plunger (106) downward with respect to the syringe (102) so that the bottom of the magnetic rod (108) is in close contact with the bottom of the magnetic tip (30). When the lower end of the magnetic rod (108) is close to or in contact with the bottom of the magnetic tip (30), the magnetic bead (306) is attached to the bottom of the magnetic tip (30) and the collection of the magnetic bead (306) is performed.

[0066] In FIG. 7, (i) describes the magnetic bead separation step. As in the magnetic bead collection step, the first drive unit (150) is driven so that the top of the syringe (102) is positioned at height (H2). The second drive unit (160) drives the plunger (106) upward so that the bottom of the magnetic rod (108) is separated from the magnetic tip (30), thereby separating the magnetic bead (306) from the magnetic tip (30) and dispersing it into the well. (j) describes the magnetic tip separation step. As in the dispensing tip separation step, with the top of the syringe (102) positioned at height (H3) by the first drive unit (150), the second drive unit (160) is driven to move the plunger (106) downward relative to the syringe (102) so that the magnetic rod (108) protrudes from the outlet (104). Since the magnetic tip (30) has the same or similar diameter at the top and bottom and does not have the same contamination problem as the dispensing tip (20), the bottom of the magnetic tip (30) is pushed with the bottom of the magnetic rod (108) to separate the magnetic tip (30) from the outlet part (104).

[0067] FIG. 12 is a diagram illustrating the process of processing a sample in a sample processing module of an in vitro diagnostic device (1000) according to another embodiment of the present invention. As illustrated, the in vitro diagnostic device (1000) according to the present embodiment is equipped with a syringe (1002), a plunger head (1006), a plunger rod (1007), and a magnetic rod (1008).

[0068] The plunger head (1006) is provided with a through hole in the center. The plunger rod (1007) has a tunnel (1010) formed in the center along the length from the bottom. The tunnel (1010) is in communication with the through hole of the plunger head (1006).

[0069] A magnet rod fixing block (1012) is installed at the top of the magnet rod (1008). A concave portion (1012a) is formed on the upper part of the magnet rod fixing block (1012). An elastic body (1014), such as a spring, is installed between the ceiling of the tunnel (1010) and the concave portion (1012a) of the magnet rod fixing block (1012). The magnet rod fixing block (1012) guides the movement of the magnet rod (1008) in the tunnel (1010) and prevents the elastic body (1014) from coming off. Additionally, the magnet rod fixing block (1012) prevents excessive compression of the elastic body (1014) and directly transmits the force of the plunger (1006, 1007) to the magnet rod (1008).

[0070] The elastic body (1014) maintains appropriate tension while the lower end of the magnetic rod (1008) is in close contact with the bottom of the magnetic tip (1016), thereby improving the reproducibility of the collection efficiency. The magnetic bead (1020) is relatively very small compared to the magnetic rod (1008). Therefore, even if there is a small gap of about 0.5 mm to 0.1 mm between the magnetic rod (1008) and the magnetic tip (1016), the collection rate decreases rapidly. Without a tension structure that forces close contact like the elastic body (1014), a minute gap is likely to occur between the lower end of the magnetic rod (1008) and the bottom of the magnetic tip (1016) due to drive unit backlash, clearance, etc.

[0071] In FIG. 12, (a) describes the state in which the magnetic tip (1016) is attached to the outlet of the syringe (1002), and (b) and (c) describe the state in which the magnetic bead (1020) is collected. In (b), the lower end of the magnetic rod (1008) is shown as being in close contact with the bottom of the magnetic tip (1016), but the plunger (1006) is driven to move further downward. During this process, the elastic body (1014) is compressed. If the magnetic rod (1008) is directly attached to the plunger (1006) without the elastic body, it is difficult to maintain a constant degree of contact, and if the magnetic rod (1008) is excessively attached to the bottom of the magnetic tip (1016) to maintain the degree of contact, the magnetic tip (1016) may be separated from the syringe (1002).

[0072] In FIG. 12, (d) describes the step of moving the magnetic rod (1008) upward to separate the magnetic bead (1020) from the magnetic tip (1016), and (e) and (f) describe the step of separating the magnetic tip (1016) from the syringe (1002). In (e), the bottom of the magnetic rod (1008) is shown as being in close contact with the bottom of the magnetic tip (1016), but since the elastic body (1014) has not yet been compressed, the magnetic tip (1016) is not separated from the syringe (1002). As in (f), when the magnetic rod (1008) is moved further downward and the elastic body (1014) is sufficiently compressed, the magnetic tip (1016) is separated from the syringe (1002). The degree of compression of the elastic body (1014) is greater in (f) than in (c).

[0073] FIG. 13 is a vertical cross-sectional view of a magnetic tip (1300) according to another embodiment of the present invention. The magnetic tip (1300) has a cup-shaped body portion (1302), and the body portion (1302) has a vent hole (1304). The vent hole (1304) is formed at a height of the magnetic tip (1016) such that the vent hole (1304) is not submerged in the solution contained in the chamber (or well) of the cartridge (10) during the sample processing process. Additionally, the vent hole (1304) is formed in the body portion (1302) so as to be located below the bottom of the outlet portion (104) when the magnetic tip (1300) is normally fitted into the outlet portion (104) of the syringe (102). The vent hole (1304) prevents the magnetic tip (1300) from detaching from the syringe (102) by expelling air from inside the magnetic tip (1300) to the outside when the magnetic rod (1008) moves downward while the magnetic tip (1300) is fitted into the outlet (104) of the syringe (102).

[0074] FIG. 14 is a cross-sectional view of a magnetic tip (1400) according to another embodiment of the present invention, wherein (a) is a vertical cross-sectional view and (b) is a horizontal cross-sectional view obtained at the height of the vent hole (1404). The magnetic tip (1400) has a cup-shaped body portion (1402), and the body portion (1402) has a vent hole (1404). The vent hole (1404) is formed in the body portion (1402) so as to be located below the bottom of the outlet portion (104) when the magnetic tip (1400) is normally fitted into the outlet portion (104) of the syringe (102). The magnetic portion (1400) has a duct portion (1406) formed on the outside of the body portion (1402) to cover the vent hole (1404). The duct section (1406) is provided with an upward outlet (1408) so that the vent hole (1404) is not submerged in the solution contained in the chamber (or well) of the cartridge (10) during the sample processing process. When the magnetic rod (1008) moves downward while the magnetic tip (1400) is fitted into the outlet section (104) of the syringe (102), the air inside the magnetic tip (1400) is discharged to the outside through the vent hole (1404) and the duct section (1406), thereby preventing the magnetic tip (1400) from detaching from the syringe (102). Since the outlet (1408) of the duct section (1406) is formed at a higher position than the vent hole (1404), the magnetic tip (1400) can have its length in the height direction reduced compared to the magnetic tip (1300) shown in FIG. 13.

[0075] The embodiments of the present invention described above are merely illustrative, and those skilled in the art will readily understand that various modifications and equivalent alternative embodiments are possible therefrom. Therefore, it will be understood that the present invention is not limited only to the forms mentioned in the detailed description above. Accordingly, the true technical scope of protection of the present invention should be determined by the technical spirit of the appended claims. Furthermore, the present invention should be understood to include all modifications, equivalents, and substitutions within the spirit and scope of the present invention as defined by the appended claims.

Claims

1. In a chemiluminescent in vitro diagnostic device using a cartridge having multiple wells, A syringe having an outlet at the bottom, and A plunger configured to move up and down while in close contact with the inside of the above syringe, and A magnetic rod attached in the height direction to the lower part of the plunger and configured so that its lower end can pass through the outlet of the syringe, and A first driving unit that drives the up-and-down movement of the above syringe, and A second driving unit that drives the up-and-down movement of the plunger In vitro diagnostic equipment characterized by including 2. In Paragraph 1, An in vitro diagnostic device characterized by the second driving unit driving the up-and-down movement of the plunger relative to the syringe.

3. In Paragraph 1, An in vitro diagnostic device characterized in that the outer diameter of the outlet portion of the syringe is smaller than the outer diameter of the well so that it can be inserted into the interior of the well of the cartridge for well punching.

4. In Paragraph 3, An in vitro diagnostic device characterized in that the well punching is performed with the lower end of the magnetic rod aligned at a position higher than the lower end of the syringe outlet.

5. In Paragraph 1, A dispensing tip is attached to the outlet of the above syringe, and The above dispensing tip has an upper inner diameter larger than the lower inner diameter, and An in vitro diagnostic device characterized in that the magnetic rod has an outer diameter capable of pushing out the upper part of the dispensing tip without contacting the solution at the lower part of the dispensing tip.

6. In Paragraph 1, An in vitro diagnostic device characterized in that the dispensing tip has a threshold formed in the middle part of the interior.

7. In Paragraph 3 or 5, An in vitro diagnostic device characterized in that the well punching or dispensing tip coupling is performed by the first driving unit driving the syringe downward.

8. In Paragraph 5, An in vitro diagnostic device characterized in that the solution is aspirated into the dispensing tip by the second driving unit driving the plunger upward relative to the syringe.

9. In Paragraph 5, An in vitro diagnostic device characterized in that the dispensing tip is separated from the outlet portion of the syringe by the second driving unit driving the plunger downward relative to the syringe.

10. In Paragraph 1, Further comprising an elastic body installed between the plunger and the magnetic rod, A magnetic tip is attached to the outlet of the above syringe, and An in vitro diagnostic device characterized by the elastic body such that the lower end of the magnetic rod is attached to the bottom of the magnetic tip.

11. In Paragraph 10, An in vitro diagnostic device characterized in that the magnetic tip coupling is performed by the first driving unit driving the syringe downward.

12. In Paragraph 10, An in vitro diagnostic device characterized by bead collection being performed with the magnetic tip by driving the plunger downward to a first position relative to the syringe by the second driving unit.

13. In Paragraph 10, An in vitro diagnostic device characterized in that the magnetic tip is separated from the outlet portion of the syringe by the second driving unit driving the plunger downward to a second position below the first position relative to the syringe.

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