Material separation disc and material separation device comprising the same

Abstract

The material separation device of the present invention comprises: a first motor that rotates a material separation disk including a chamber which is a space for receiving a sample, a channel which provides a passage for the flow of the sample, and a valve which selectively opens and closes the channel; a valve actuator that supplies energy to operate the valve; a third motor that rotates the valve actuator with respect to a concentric axis with respect to the first motor; and a control unit that controls the first motor, the third motor, and the valve actuator to supply energy to a valve material contained in the valve while the material separation disk and the valve actuator are rotated at different rotational speeds.

Description

Technology Field

[0001] The present invention relates to a blood separation disc and a material separation device including the same. Background Technology

[0002] Most deaths associated with malignant tumors are caused by metastasis to tissues and organs far from where the tumor originated. Therefore, early detection of metastasis is a critical determinant of survival probability for cancer patients.

[0003] The diagnosis of cancer generally utilizes diagnostic techniques based on histopathology. Histopathological diagnostic techniques involve diagnosing tumors using tissue samples obtained from biopsies. This histopathological approach allows for the direct observation of tumor cells.

[0004] Meanwhile, circulating tumor cells (CTCs) are known to be found in patients before a tumor is first detected. Therefore, circulating tumor cells can play an important role in the early diagnosis and prediction of cancer. Given that cancer generally metastasizes through the blood, circulating tumor cells can serve as a marker to diagnose whether cancer has metastasized. Taking advantage of this, a disc-type device for extracting circulating tumor cells from samples such as blood is currently under research and development.

[0005] This type of material separation disc device generates centrifugal force by rotating the disc body and utilizes this centrifugal force to separate circulating tumor cells from the blood.

[0006] In the present invention, when configuring the various chambers included in such a material separation disk, the volume of the main chamber is specifically defined to enable accurate separation of the blood layer.

[0007] Meanwhile, such a material separation disc includes multiple chambers, and a valve that opens and closes by external energy is disposed in the channel connecting each chamber. The valve operates by receiving energy from the outside. During the sample analysis process, the rotation of the material separation disc is stopped to operate the valve, energy is supplied to the valve to melt the valve material, and then the disc is rotated again. However, during the process of operating the valve, the sample centrifuged into multiple layers may be mixed again, which can reduce the reliability of the analysis. To resolve this, the prior art (Article No. 10-2176587, Title of Invention: Sample Analysis Device, Sample Analysis Method, and Dynamic Operation Method of a Valve) proposes a configuration in which the valve actuator supplying energy to the valve rotates together with the material separation disc. Normal operation of the valve through efficient melting of the valve material is very important for smooth fluid movement within the material separation disc. However, there is a limitation in that the valve material cannot be completely melted if the shape of the valve does not match the energy irradiation section while irradiating energy to the valve while rotating the material separation disc and the valve actuator at the same speed, so it is necessary to improve this. Prior art literature

[0008] Republic of Korea Published Patent No. 10-2022-0135995 (Title of Invention: Split Disk Device) Republic of Korea Registered Patent No. 10-2176587 (Title of Invention: Sample Analysis Device, Sample Analysis Method, and Dynamic Operation Method of Valve) The problem to be solved

[0009] The present invention aims to provide a material separation disk with improved material separation characteristics by improving the shape of the main chamber and the sample chamber of the material separation disk, and a material separation device including the same.

[0010] In addition, the present invention aims to provide a material separation device capable of efficiently irradiating energy to each valve by controlling the rotational speed of the valve actuator in the material separation device.

[0011] However, the technical problems that this embodiment aims to solve are not limited to the technical problems described above, and other technical problems may exist. means of solving the problem

[0012] As a technical means for achieving the technical problem described above, a blood separation disc used in a material separation device according to one embodiment of the present invention comprises a rotatable disc body and at least one blood separation unit coupled to the disc body, including a plasma separation chamber, a main chamber, and a sample chamber, and including a first channel connecting the plasma separation chamber and the main chamber and a second channel connecting the main chamber and the sample chamber, wherein the main chamber has a cross-section of a predetermined shape when cut parallel to a horizontal plane, and the second channel is connected to one side, and the lower volume of the main chamber, which is determined by the height from the bottom of the cross-section of the main chamber to the point of connection with the second channel, is formed such that it is less than or equal to the sum of the volume of the red blood cell layer of the blood and the volume of the density gradient solution under the condition that a mixture of blood and a density gradient solution corresponding to the total volume of the main chamber is injected.

[0013] In addition, a material separation device according to another embodiment of the present invention includes: a first motor that rotates a material separation disk comprising a chamber which is a space for receiving a sample, a channel which provides a passage for the flow of the sample, and a valve which selectively opens and closes the channel; a valve actuator that supplies energy to operate the valve; a third motor that rotates the valve actuator with respect to a concentric axis with respect to the first motor; and a control unit that controls the first motor, the third motor, and the valve actuator to supply energy to the entire valve material contained in the valve while the material separation disk and the valve actuator are rotated at different rotational speeds. Effects of the invention

[0014] According to an embodiment of the present invention, the shape of the main chamber and the sample chamber of the material separation disk can be improved to enhance material separation characteristics.

[0015] In addition, in a material separation device, the rotational speed of the material separation disk and the valve actuator are rotated together, but configured to have different rotational speeds, so that the energy irradiation of the valve actuator is efficiently carried out across the entire valve within the material separation device, thereby improving the melting of the valve material. Brief explanation of the drawing

[0016] Figure 1 illustrates the configuration of a material separation device according to one embodiment of the present invention. FIG. 2 illustrates a detailed configuration for the movement of a valve actuator in a material separation device according to one embodiment of the present invention. FIGS. 3 and FIGS. 4 illustrate the detailed configuration of a material separation disk according to one embodiment of the present invention. FIG. 5 illustrates the detailed configuration of a blood separation unit according to one embodiment of the present invention. FIG. 6 illustrates the configuration of the main chamber of a material separation disk according to one embodiment of the present invention. FIG. 7 illustrates the configuration of the main chamber of a material separation disk according to another embodiment of the present invention. FIG. 8 illustrates the configuration of a sample chamber of a material separation disk according to one embodiment of the present invention. FIG. 9 illustrates the configuration of a sample chamber of a material separation disk according to another embodiment of the present invention. FIG. 10 illustrates the rotational speed in a material separation device according to one embodiment of the present invention. Specific details for implementing the invention

[0017] Embodiments of the present invention are described below with reference to the attached drawings so that those skilled in the art can easily implement the invention. However, the present invention may be embodied in various different forms and is not limited to the embodiments described herein. Furthermore, in order to clearly explain the present invention in the drawings, parts unrelated to the explanation have been omitted, and similar parts throughout the specification are denoted by similar reference numerals.

[0018] Throughout the specification, when a part is described as being "connected" to another part, this includes not only cases where they are "directly connected" but also cases where they are "electrically connected" with other elements interposed between them. Furthermore, when a part is described as "including" a component, this means that, unless specifically stated otherwise, it does not exclude other components but rather allows for the inclusion of additional components; it should be understood that this does not preclude the existence or addition of one or more other features, numbers, steps, actions, components, parts, or combinations thereof.

[0019] FIG. 1 illustrates the configuration of a material separation device according to one embodiment of the present invention, and FIG. 2 illustrates the detailed configuration for the movement of a valve actuator among the material separation devices according to one embodiment of the present invention.

[0020] Since the basic configuration corresponds to the configuration of Patent No. 10-2176587 introduced earlier, please refer to the contents of that patent.

[0021] The material separation device (10) includes a material separation disk (100), a valve actuator (400), a first motor (500) for rotating the material separation disk, a second motor (600) for adjusting the radial position of the valve actuator (400), and a third motor (700) for rotating the valve actuator (400).

[0022] The first motor (500) generates centrifugal force for centrifuging and moving the sample by rotating the material separation disk (100). For example, a turntable (520) on which the material separation disk (100) is mounted is provided on the rotation axis of the first motor (500). A mounting hole (102) corresponding to the turntable (520) is provided in the material separation disk (100). The mounting hole (102) has the shape of a through hole formed by penetrating the center of the material separation disk (100) so that the turntable (520) can be inserted. In addition, a fixing pin (530) that is inserted into a fixing hole (104) formed in the material separation disk (100) may be formed protruding from the outer edge of the turntable (520). One or more fixing holes (104) and fixing pins (530) may each be formed, and as the fixing pins (530) are inserted into the fixing holes (104), the material separation disk (100) can be more stably fixed to the turntable (520). In the drawing, for convenience of explanation, the fixing holes (104) and fixing pins (530) are shown arranged along the first reference line (L1), but the positions of the fixing holes (104) and fixing pins (530) may be arranged differently. In addition, the number of fixing holes (104) and fixing pins (530) does not necessarily have to be two, and it is possible to have one or three or more. Meanwhile, unlike what is shown, the fixing holes (104) may be formed in the turntable (520), and the fixing pins (530) may be formed on the lower part of the material separation disk (100) to correspond to the fixing holes (104).

[0023] Meanwhile, it is possible for the first motor (500) and the turntable (520) to be directly connected, or the first motor (500) may be connected to the turntable by a power connection element such as a belt, chain, or gear.

[0024] The valve actuator (400) is an example of a valve actuator that supplies energy to the valves (A) to operate the valves (A) of the material separation disk (100). The valve actuator (400) may irradiate electromagnetic waves, for example, laser light, onto the valves (A). The valve actuator (400) may be, for example, a laser diode.

[0025] The second motor (600) aligns the valve actuator (400) with the valve (A). That is, the second motor (600) moves the valve actuator (400) radially along the material separation disk (100) to position it above the valve (A). An embodiment of the second motor (600) is illustrated in FIG. 2. A lead screw (630) that is rotated by the second motor (610) is connected to the second motor (600), and a moving member (620) on which the valve actuator (400) is mounted can move along the radial direction of the rotating member (720) by the lead screw (630). The moving member (620) can be supported, for example, by a guide rail (640) that extends radially along the material separation disk (100). The moving member (620) is provided with an engaging part (621) that engages with the spiral groove of the lead screw (630). With this configuration, when the lead screw (630) is rotated, the moving member (620) moves radially along the guide rail (640). As an example of a method for obtaining a radial reference position of the valve actuator (400), a method utilizing a change in the driving current of the second motor (600) can be used. For example, the moving member (620) is moved radially inward or outward using the second motor (600). When the moving member (620) moves to the end of the lead screw (630), the moving member (620) no longer moves, and at this time, the intensity of the current driving the second motor (610) changes rapidly. When a sudden change in this current is detected, the valve actuator (400) may be recognized as being located at the radial inner end or outer end, and the control unit (800) described later may recognize this position as the radial reference position of the valve actuator (400). As another method, a position detector (650) for detecting the radial reference position of the valve actuator (400) may be further provided. The position detector (650) may detect a moving member (620) at any radial position, for example.The position detector (650) may be a non-contact sensor such as a light sensor or a contact sensor such as a micro switch.

[0026] The material separation disk (100) may include a plurality of chambers for receiving a sample, a channel providing a passage for the flow of the sample, and a valve (A) for selectively opening and closing the channel. The material separation disk (100) may have a rotatable disk shape. The material separation disk (100) may include a lower structure having a microflow structure formed in an intaglio shape, such as chambers forming a fluid receiving space and a channel providing a fluid passage between the chambers, and an upper structure (top plate) coupled to the lower structure to form the upper wall of the microflow structure. The material separation disk (100) may have a two-plate structure in which the top plate and the bottom plate having the microflow structure formed thereon are combined. The joining of the plates can be achieved by various methods, such as bonding using an adhesive or double-sided adhesive tape, ultrasonic welding, or laser welding. The material separation disk (100) may be made of a plastic material such as acrylic or PDMS, which is easy to mold and whose surface is biologically inert. However, it is not limited to this, and any material having chemical and biological stability, optical transparency, and mechanical processability is sufficient.

[0027] Various types of valves (A) may be provided in the material separation disk (100). For example, the valve (A) may be a normally closed valve that closes the channel in a normal state and opens the channel by receiving energy from the outside, a normally open valve that opens the channel in a normal state and closes the channel by receiving energy from the outside, and an open / close type valve that can switch between an open state, a closed state, and an open state.

[0028] FIGS. 3 and 4 illustrate the detailed configuration of a material separation disk according to one embodiment of the present invention, FIG. 5 illustrates the detailed configuration of a blood separation unit according to one embodiment of the present invention, FIG. 6 illustrates the configuration of a main chamber of a material separation disk according to one embodiment of the present invention, FIG. 7 illustrates the configuration of a main chamber of a material separation disk according to another embodiment of the present invention, and FIG. 8 illustrates the configuration of a sample chamber of a material separation disk according to one embodiment of the present invention.

[0029] The material separation disk (100) may include a rotatable disk body (110) and at least one blood separation part (120) disposed on the disk body (110). The disk body (110) and the blood separation part (120) may be injection-molded integrally to form the material separation disk (100).

[0030] In another embodiment, the disc body (110) and the blood separation part (120) may be formed separately from each other, and then the blood separation part (120) may be each connected to the connecting grooves (115) formed in the disc body (110) to form a material separation disc (100). In this way, the blood separation part (120) may be implemented in the form of a modular split disc.

[0031] The material separation disk (100) may include at least one blood separation unit (120) that separates a target substance, e.g., a target cell, from a sample, e.g., whole blood, by utilizing the centrifugal force generated when the disk body (110) rotates. Additionally, at least one fixing hole (104) may be formed in the disk body (110).

[0032] According to one embodiment, the disc body (110) and the blood separation part (120) are included, and the blood separation part (120) is coupled to each coupling groove (115) of the disc body (110), thereby having a divided structure so that over-fusion or partial fusion can be prevented depending on the part as in the prior art, thus preventing variations in mass-produced products and increasing reproducibility.

[0033] The disk body (110) of the present embodiment is provided in the shape of a circular disk overall, and a total of four coupling grooves (115) may be regularly provided along the radial direction. That is, coupling grooves (115) of the same shape are formed on the disk body (110) at 90-degree intervals, and the structure has a structure in which a blood separation part (120) in the form of a modular divided disk corresponding to the shape of the coupling groove (115) is coupled to the coupling groove (115). The disk body (110) and the blood separation part (120) can each be manufactured by injection molding, thereby enabling the disk body (110) and the blood separation part (120) corresponding to the shape to be manufactured accurately and efficiently.

[0034] However, the number and shape of the coupling grooves (115) are not limited to the examples described above, and the manufacturing method of the disk body (110) and the blood separation part (120) is not limited to the methods described above. For example, the number of coupling grooves (115) may be 2 or 6, and it is obvious that a blood separation part (120) corresponding to this number may be provided.

[0035] Referring to FIG. 4, the blood separation part (120) can be easily connected to the disc body (110) by inserting the blood separation part (120) into the coupling groove (115) of the disc body (110). Subsequently, the connection between the two can be made more robust by fusing the contact surface of the coupling groove (115) and the blood separation part (120) using an ultrasonic welding method. However, in addition to ultrasonic welding, methods such as laser welding, heat welding, and hot air welding may be applied to the method of fusing the coupling groove and the blood separation part.

[0036] Meanwhile, the blood separation part (120) of the present embodiment has a structure that separates from the coupling groove (115). To this end, a separation hole (116) may be formed through the bottom of the disk body (110) in which the coupling groove (115) is formed, as shown in FIG. 2. To elaborate, when the blood separation part (120) needs to be separated from the coupling groove (115), the blood separation part (120) can be pressed in a direction of exit through the separation hole (116), and accordingly, the separation of the blood separation part (120) from the coupling groove (115) can be easily achieved. Additionally, although not illustrated, the inner wall of the disk body (110) forming the coupling groove (115) and the outer wall of the blood separation part (120) coupled thereto may have a tapered shape that corresponds to each other in shape. In other words, the inner wall of the disc body (110) forming the coupling groove (115) may have a tapered shape that narrows as it goes downward, and the outer wall of the blood separation part (120) coupled to the coupling groove (115) may have a tapered shape that widens as it goes downward, so that the inner wall of the disc body (110) forming the coupling groove (115) and the outer wall of the blood separation part (120) may correspond in shape. Due to this tapered shape, it is possible to prevent the blood separation part (120) from being arbitrarily separated from the coupling groove (115) when the disc body (110) is rotated.

[0037] To explain the configuration of each blood separation unit (120), the blood separation unit (120) of this embodiment has a plurality of chambers so that it can separate only target cells, namely circulating tumor cells (CTCs) of this embodiment, from whole blood.

[0038] The blood separation unit (120) of the present embodiment may include a split disk body (121) and a plurality of chambers (130, 140, 150, 160, 170) provided therein for separating target cells from whole blood by centrifugal force generated when the disk body (110) rotates.

[0039] The divided disc body (121) provides a basic frame and is provided in a shape corresponding to the shape of the aforementioned coupling groove (115).

[0040] Here, a plurality of chambers (130, 140, 150, 160, 170) may include a main chamber (130), a plasma separation chamber (140), a sample chamber (150), a separation chamber (160), and a receiving chamber (170). Additionally, it includes a first channel (180) connecting the plasma separation chamber (140) and the main chamber (130), a second channel (182) connecting the main chamber (130) and the sample chamber (150), a third channel (184) connecting the sample chamber (150) and the separation chamber (160), and a fourth channel (186) connecting the separation chamber (160) and the receiving chamber (170).

[0041] First, the main chamber (130) of the present embodiment is provided in the central part of the divided disk body (121) and accommodates whole blood and a first density gradient medium (DGM) in a partitioned manner, and layers of plasma, peripheral blood mononuclear cells (PBMC), the first density gradient medium (DGM), and red blood cells (RBC) can be formed by the centrifugal force generated when the disk body (110) rotates. This main chamber (130) may include a whole blood receiving space (131) into which whole blood is introduced and accommodated, and a material receiving space (135) partitioned from the whole blood receiving space (131) by a partition wall into which the first density gradient medium is introduced and accommodated.

[0042] With the configuration of the main chamber (130), when the disk body (110) rotates, the whole blood in the whole blood receiving space (131) and the first density gradient material in the material receiving space (135) can be separated by centrifugal force into a blood layer consisting of plasma, peripheral blood mononuclear cells, the first density gradient material, and red blood cells, respectively.

[0043] The plasma separation chamber (140) is connected to one side of the main chamber (130) by a channel (180) and can receive and accommodate plasma from the main chamber (130) after centrifugal separation. An opening / closing valve is installed in the channel (180) connecting the main chamber (130) and the plasma separation chamber (140). Therefore, if electromagnetic waves, etc. are applied to the opening / closing valve using the aforementioned valve actuator (400), the opening / closing valve can be opened, allowing plasma to be transferred from the main chamber (130) to the plasma separation chamber (140).

[0044] Additionally, the sample chamber (150) is connected to the main chamber (130) so as to face the plasma separation chamber (140) with the main chamber (130) as the center, and peripheral blood mononuclear cells can be separated into the sample chamber (150) from the blood layer formed after centrifugation. Additionally, an opening / closing valve (185) is installed in the channel (182) connecting the main chamber (130) and the sample chamber (150), and when electromagnetic waves are applied to the opening / closing valve (185) using an electromagnetic wave generator, the opening / closing valve (185) can be opened, thereby allowing the peripheral blood mononuclear cells to move from the main chamber (130) to the sample chamber (150).

[0045] Beads that are leukocyte-labeled antibodies, such as CD45-dynabeads, are injected into the sample chamber (150) to selectively remove leukocytes that are mainly present in peripheral blood mononuclear cells, and thus leukocytes labeled with beads and circulating tumor cells from which leukocytes have been removed can be moved through the channel from the sample chamber (150) to the separation chamber (160).

[0046] The separation chamber (160) of this embodiment may contain a second density gradient material, and leukocytes labeled with beads transferred from the sample chamber (150) and circulating tumor cells from which leukocytes have been removed may form different layers with the second density gradient material in between.

[0047] That is, the bead-labeled leukocytes sink below the second density gradient material and the circulating tumor cells form above, so that the circulating tumor cells can be separated into the circulating tumor cell receiving chamber (170) through the channel (186).

[0048] As such, in the case of the present embodiment, each blood separation unit (120) has a plurality of chamber structures, thereby enabling accurate and efficient extraction of target cells, i.e., circulating tumor cells of the present embodiment, from whole blood.

[0049] Meanwhile, in the present invention, the lower volume of the main chamber (130) is specifically defined so that the target material, particularly the mononuclear cell layer, can be accurately separated.

[0050] As illustrated in FIG. 6, the main chamber (130) is formed such that a predetermined volume is determined by the rim (132) of the main chamber, and when the main chamber (130) is cut parallel to a horizontal plane, the rim (132) of the main chamber has a cross-section of a predetermined shape. And, a second channel (182) is connected to one side of the main chamber (130).

[0051] And, when viewed with respect to the cross-section of the main chamber (130), the lower volume of the main chamber (130), which is defined by the height from the bottom (133) of the main chamber (130) to the connection point with the second channel (182), is formed such that it is less than or equal to the sum of the volume of the red blood cell layer of the blood and the volume of the density gradient solution under the condition that a mixture of blood and a density gradient solution corresponding to the total volume of the main chamber (130) is injected. In other words, the feature of the present invention is to specifically define the ratio of the lower volume to the total volume of the main chamber (130). When the volume of the mixture of blood and a density gradient solution capable of filling the entire main chamber (130) is defined as the total volume of the main chamber (130), the lower volume of the main chamber (130) is designed at a ratio such that it is less than or equal to the sum of the volume of the red blood cell layer of the blood and the volume of the density gradient solution in the mixture.

[0052] In the main chamber (130), layers are separated in order of increasing density from the bottom of the main chamber (130) by a density gradient. That is, layers are formed in the order of the red blood cell layer (d ≥ 1.09) with the highest density, the density gradient solution layer (1.077 ≤ d ≤ 1.084) with the next highest density, the mononuclear cell layer (1.067 ≤ d ≤ 1.077), and the plasma layer (d ≈ 1.05), with the layers having the highest density located at the bottom of the main chamber (130).

[0053] And, the main chamber (130) is formed according to the condition 1 below.

[0054] [Condition 1]

[0055] The sum of the volume of the red blood cell layer and the volume of the density gradient solution in the mixture of blood and density gradient solution corresponding to the lower volume of the main chamber ≤ the total volume of the main chamber

[0056] At this time, the volume of the red blood cell layer can be calculated by multiplying the total volume of blood by the hematocrit value, which represents the ratio of the volume of red blood cells to the total volume of blood and is generally 60% or less.

[0057] Therefore, condition 1 can be transformed into condition 2.

[0058] [Condition 2]

[0059] The sum of 60% of the blood volume and the volume of the density gradient solution in the mixture of blood and density gradient solution corresponding to the main chamber lower volume ≤ the total volume of the main chamber

[0060] Although the shape of the material separation disk in FIG. 7 is entirely different from that of FIG. 3, it includes a plasma separation chamber (140'), a main chamber (130'), a sample chamber (150'), a first channel (180'), and a second channel (182'), respectively. Additionally, as previously described, the lower volume of the main chamber (130') is formed to satisfy the previously described condition 1 or condition 2. That is, when the volume of a mixture of blood and a density gradient solution capable of filling the entire main chamber (130') is defined as the total volume of the main chamber (130'), the lower volume of the main chamber (130') is designed to be less than or equal to the sum of the volume of the red blood cell layer of the blood and the volume of the density gradient solution in the mixture, or less than or equal to the sum of 60% of the volume of the blood and the volume of the density gradient solution in the mixture.

[0061] In addition, the shape of the sample chamber (150) is clearly specified in the present invention. Mononuclear cells delivered to the sample chamber (150) are sufficiently mixed with micro beads and then moved to the separation chamber (160) via the third channel (184). In order to move objects (cells, micro beads, etc.) inside the sample chamber (150) to the separation chamber (160) through the third channel (184), a sufficient angle of inclination is required to counteract centrifugal force.

[0062] Referring to FIG. 8, a portion of the outer surface of the sample chamber (150) has a shape where the first outer line (151) and the second outer line (152) meet, and when the third outer line (153) is also considered, it may have a shape connected in the form of an inverted triangle. Then, a third channel (184) is connected at the vertex where the first outer line (151) and the second outer line (152) are connected. At this time, the third channel (184) extends vertically downward from the vertex where the first outer line (151) and the second outer line (152) are connected, and as shown, the first outer line (151) and the second outer line (152) may have a symmetrical relationship with respect to the extension line of the third channel (184). However, the present invention is not limited thereto, and depending on the shape of the sample chamber (150), the first outline (151) and the second outline (152) may have an asymmetric relationship. In this case, the first angle (θ) between the first straight line (154) connecting the vertex and the other end of the first outline (151) and the reference line (156) perpendicular to the extension of the third channel (184), and the second angle (θ) between the second straight line (155) connecting the vertex and the other end of the second outline (152) and the reference line (156) are set to be acute angles of 30° or more. In this case, the first angle (θ) and the second angle (θ) may be set differently.

[0063] At this time, it is preferable that the angle (α) between the first straight line (154) and the extension line of the third channel (184) and the angle (α') between the second straight line (155) and the extension line of the third channel (184) be set to be the same. This also means that the angle (θ) between the reference line (156) perpendicular to the extension line of the first straight line (154) and the third channel (184) and the angle (θ) between the second straight line (155) and the reference line (156) are the same condition.

[0064] However, even if each angle is not the same, the magnitude of the difference between each angle (α - α') is made to be 60° or less.

[0065] Meanwhile, the sample chamber (150') in a modified form, such as the material separation disk of FIG. 7 described above, is made to satisfy the following conditions. FIG. 9 illustrates the configuration of the sample chamber of the material separation disk according to another embodiment of the present invention.

[0066] The sample chamber (150') has a shape in which the sample chamber (150) of FIG. 3 is cut in half along the extension line of the third channel (150). That is, if the sample chamber (150) of FIG. 3 has a shape similar to an isosceles triangle, the sample chamber (150') has a shape similar to a right triangle folded in half. This sample chamber (150') has a shape in which the first straight line (157'), the first outline (152'), and the second outline (153') are connected in a form similar to a right triangle. The second channel (180') is connected to one end of the first straight line (157'), and the third channel (182') is connected to the vertex where the other end of the first straight line (157') meets the first outline (152'). At this time, when considering the reference line (156') that is perpendicular to the first line (157') and passes through the vertex, the angle (θ) between the reference line (156') and the second line (155') connecting the vertex and the other end of the first outline (152') is set to an acute angle of 30° or more. That is, the angle (α) between the first line (157') and the second line (155') is set to an acute angle of less than 60°.

[0067] Referring again to FIG. 1, the material separation device (10) further comprises a third motor (700) that rotates the valve actuator (400). The third motor (700) rotates the valve actuator (400) around a rotation center (RC2) that is coaxial with the rotation center (RC1) of the material separation disk (100). That is, the rotation centers (RC1) and (RC2) are located on a common rotation axis (AX). The third motor (700) rotates the valve actuator (400) in synchronization with the rotation of the material separation disk (100). The third motor (700) rotates the rotating member (720). At this time, the aforementioned second motor (600), guide rail (640), and lead screw (630) may be installed at the bottom of the rotating member (720). Although the third motor (700) and the rotating member (720) are shown as being directly connected, the third motor (700) may also be connected to the rotating member (720) by a power connecting element such as a belt, chain, or gear.

[0068] The control unit (800) controls the first to third motors (500, 600, 700) and controls the sample analysis process overall. The control unit (800) may include a memory (830), a motor drive (820) that drives the first to third motors (500, 600, 700), and a central processing unit (810). Application software for controlling the sample analysis process may be stored in the memory (830). Additionally, position coordinate values ​​of a plurality of valves (A) provided on the material separation disk (100), for example, polar coordinate values ​​(r, θ) based on the rotation center (RC1) and the first reference line (L1), may be stored in the memory (830). The application software and the position coordinate values ​​of the plurality of valves may be downloaded from a host computer connected to the material separation device (10) and stored in the memory (830). In addition, the position coordinate values ​​of multiple valves may be directly entered into memory (830) by the user through an input device not shown.

[0069] The first motor (500) may be a servo motor. The servo motor has an encoder capable of counting rotational speeds and a feedback mechanism for rotational control built into it. Therefore, at any time, the rotational phase of the first motor (500), for example, the angular position relative to the control reference polar coordinate system of the material separation device (10) at the reference position of the encoder, can be known. When mounting the material separation disk (100) on the first motor (500), the reference position of the encoder of the first motor (500) and the first reference line (L1) of the material separation disk (100) are aligned. Then, at any time, the angular position of the valve (A) relative to the control reference polar coordinate system of the material separation device (10) can be known. For example, a first alignment part (103) aligned with a first reference line (L1) may be provided in the mounting hole (102) of the material separation disk (100), and a second alignment part (521) aligned with the reference position of the encoder of the second motor (500) may be provided on the turntable (520) which is coupled with the first alignment part (103). The first alignment part (103) and the second alignment part (521) may have complementary shapes. For example, the first alignment part (103) may be in the form of a groove extending outward from the circular mounting hole (102), and the second alignment part (521) may be in the form of a protrusion inserted into the first alignment part (103).

[0070] The third motor (700) may be a servo motor. The second reference line (L2) of the rotating member (720) may be aligned with the reference position of the encoder embedded in the third motor (700). The second reference line (L2) may coincide with the radial movement trajectory of the valve actuator (400). Additionally, the second reference line (L2) may have a phase difference of θ0 with the radial movement trajectory of the valve actuator (400).

[0071] Additionally, referring to FIGS. 1 and 2, the material separation device (10) may further be equipped with a first phase detector (851) and a second phase detector (852). The first phase detector (851) and the second phase detector (852) can detect a first phase pattern (P1) and a second phase pattern (P2) provided on the material separation disk (100) and the rotating member (720). The first phase pattern (P1) and the second phase pattern (P2) are respectively provided at positions aligned with the first reference line (L1) and the second reference line (L2) of the material separation disk (100) and the rotating member (720). The control unit (800) can calculate the number of rotations of the material separation disk (100) and the rotating member (720), the angular positions of the first reference line (L1) and the second reference line (L2), and the angular positions of the valve (A) and the valve actuator (400) at any time based on the output signals (first and second phase signals) of the first phase detector (851) and the second phase detector (852). The first phase pattern (P1) and the second phase pattern (P2) may be, for example, optically recognizable patterns or magnetically recognizable patterns. The phase pattern (P1) may be a position aligned with the first alignment unit (103).

[0072] [Sample Processing]

[0073] The control unit (800) drives the first motor (500) to rotate the material separation disk (100) at a first speed (V1) to perform sample processing processes, such as centrifuging the sample and mixing the sample with additives, according to the purpose of analysis. For example, the sample is loaded into the material separation disk (100) and rotated to perform centrifugation of the sample. Then, if necessary, the operation of opening the valve (A) is performed to transfer some or all of the centrifuged material layers to another chamber. During the [sample processing] process, the rotating member (720) may remain stationary without rotating.

[0074] [Radical position alignment]

[0075] The control unit (800) drives the second motor (600) to align the radial position of the valve actuator (400) with the radial position of the valve (A). To do this, the control unit (800) reads the radial coordinates (r) of the valve (A) from the memory (830). While driving the second motor (600), the control unit (800) detects a sudden change in the intensity of the current for driving the second motor (600), and can recognize the position where this change is detected as the radial reference position (r0) of the valve actuator (400). As another method, the control unit (800) drives the second motor (600) to move the moving member (620) radially and detects the moving member (620) using the position detector (650). When the moving member (620) is detected, the control unit (800) recognizes that the valve actuator (400) is positioned at the reference position (r0) in the radial direction. The control unit (800) determines the amount of rotation and the direction of rotation of the second motor (600) corresponding to the value r-r0, and based on this, drives the second motor (600) to move the valve actuator (400) in the radial direction. The [radial position alignment] process can be performed in advance while the rotating member (720) is stationary and not rotating during the [sample processing] process described above.

[0076] [Align each position]

[0077] Next, the control unit (800) drives the third motor (700) to rotate the valve actuator (400) in synchronization with the material separation disk (100). The control unit (800) reads the angular position (θ) of the valve (A) from the memory (830). The control unit (800) drives the third motor (700) through the motor drive (820). The control unit (800) controls the third motor (700) based on the encoder output signal (first encoder output signal) of the third motor (700) or the output signal (second phase signal) of the second phase detector (852) to adjust the rotational speed of the rotating member (720) and the rotational speed of the material separation disk (100).

[0078] Then, the control unit (800) calculates the angular position of the valve actuator (400) and the valve (A) with respect to the reference polar coordinate system at any time from the encoder output signals (first and second encoder output signals) of the first motor (500) and the third motor (700) or the output signals (first and second phase signals) of the first phase detector (851) and the second phase detector (852), and determines the difference between the two angular positions. Based on this difference, the control unit (800) matches the angular positions of the valve actuator (400) and the valve (A) with respect to the reference polar coordinate system by feedback controlling the rotational speed of the third motor (700). By doing so, the valve actuator (400) rotates in synchronization with the material separation disk (100).

[0079] FIG. 10 illustrates the rotational speed in a material separation device according to one embodiment of the present invention.

[0080] As illustrated in FIG. 10, when the material separation disk (100) is rotated at a first rotational speed (V2) that is smaller than the rotational speed (V1), the control unit (800) rotates the third motor (700) alternately at a second rotational speed and a third rotational speed. At this time, the second rotational speed is smaller than the first rotational speed (V2), and the third rotational speed has a value greater than or equal to the first rotational speed (V2).

[0081] In addition, the starting timing of the third motor (710) can be determined so that the valve actuator (400) is positioned above the valve (A) on the material separation disk (100) at the time when the rotational speed of the rotating member (720) becomes equal to the first rotational speed, that is, so that the angular positions of the valve actuator (400) and the valve (A) are aligned. In this way, the rotational speed of the rotating member (720) by the third motor (700) is changed to a second rotational speed and a third rotational speed in succession, and when the rotational speed of the third motor (700) matches the first rotational speed of the first motor (500), the angular positions are considered aligned, and the valve actuator (400) is operated.

[0082] And, as illustrated in FIG. 10, the valve material included in the opening / closing valve (185) has a predetermined area, and when the entire area where the valve material is spread is called the valve area, when the material separation disk (100) is rotated at the first rotational speed (V2), the control unit (800) rotates the third motor (700) alternately at the second rotational speed and the third rotational speed, so that the valve actuator (400) can move to position A and position B among the positions in the valve area and supply energy (e.g., laser). That is, as illustrated, assuming the material separation disk (100) rotates to the right, when the third motor (700) rotates at a second rotational speed, the valve actuator (400) irradiates a laser at a first point (B) located slightly behind the center of the valve material with respect to the rotational direction of the material separation disk (100), and when the third motor (700) rotates at a third rotational speed, the valve actuator (400) irradiates a laser at a second point (A) located slightly ahead of the center of the valve material. In other words, with respect to the rotational direction of the material separation disk (100), the first virtual line connecting the rotational axis to the first point (B) is located behind by a predetermined rotational angle compared to the reference line pointing from the rotational axis of the material separation disk (100) toward the center of the valve material, and the second virtual line connecting the rotational axis to the second point (A) is located ahead of the reference line by a predetermined rotational angle, so that each rotational speed is adjusted.

[0083] In this way, the valve actuator (400) can move toward the valve material and efficiently irradiate energy.

[0084] [Valve Operation]

[0085] When the valve actuator (400) is positioned above a specific valve by the aforementioned [radial position alignment] and [angle position alignment] steps, the control unit (800) drives the valve actuator (400) to irradiate the valve material, for example, with a laser beam. Then, the energy of the laser beam is absorbed by the valve material, causing the valve material to melt. Since the material separation disk (100) is in a rotating state, the molten valve material is pushed out of the channel (C) by centrifugal force, and the valve (A) can be opened.

[0086] As described above, by operating the valve (A) while the valve actuator (400) rotates together with the material separation disk (100), the channel (C) can be opened or closed by centrifugal force before the molten valve material solidifies, thereby improving the reliability and speed of operation of the valve (A). In addition, since the material separation disk (100) continues to rotate even while the valve (A) is operating, the centrifuged sample can be maintained in a separated state, preventing mixing of the separated layers. Furthermore, since the process of operating the valve (A) can be performed without stopping the rotation of the material separation disk (100), the time required for sample analysis can be shortened.

[0087] The foregoing description of the present invention is for illustrative purposes only, and those skilled in the art will understand that other specific forms can be easily modified without altering the technical spirit or essential features of the present invention. Therefore, the embodiments described above should be understood as illustrative in all respects and not restrictive. For example, each component described as a single unit may be implemented in a distributed manner, and components described as distributed may likewise be implemented in a combined form.

[0088] The scope of the present invention is defined by the claims set forth below rather than by the detailed description above, and all modifications or variations derived from the meaning and scope of the claims and equivalent concepts thereof should be interpreted as being included within the scope of the present invention. Explanation of the symbols

[0089] 10: Material separation device 100: Material Separation Disk 110: Disk body 120: Blood separation unit 121: Partition disk body 130: Main chamber 131: Whole blood receiving space 135: Material Reception Space 140: Plasma separation chamber 150: Sample chamber 160: Separation chamber 170: Receiving chamber 180: Channel 185: Opening and closing valve 400: Valve actuator 500: 1st motor 600: 2nd motor 700: 3rd motor 800: Control unit

Claims

Claim 1 A blood separation disc used in combination with a material separation device, comprising a rotatable disc body and at least one blood separation section disposed on the disc body, including a plasma separation chamber, a main chamber, and a sample chamber, and including a first channel connecting the plasma separation chamber and the main chamber and a second channel connecting the main chamber and the sample chamber, wherein the main chamber has a cross-section of a predetermined shape when cut parallel to a horizontal plane, and the second channel is connected to one side, and the lower volume of the main chamber, determined by the height from the bottom of the cross-section of the main chamber to the point of connection with the second channel, is formed such that it is less than or equal to the sum of the volume of the red blood cell layer of the blood and the volume of the density gradient solution under conditions where a mixture of blood and a density gradient solution corresponding to the total volume of the main chamber is injected. Claim 2 A blood separation disc according to claim 1, wherein the disc body comprises at least one coupling groove, and the blood separation portion is formed in the form of a modular split disc to be coupled to the coupling groove of the disc body. Claim 3 A blood separation disc according to claim 1, wherein the lower volume of the main chamber is formed such that it is less than or equal to the sum of 60% of the volume of the blood and the volume of the density gradient solution under conditions where a mixture of blood and a density gradient solution corresponding to the total volume of the main chamber is injected. Claim 4 A blood separation disk according to claim 1, wherein the blood separation unit further includes a separation chamber and further includes a third channel connecting the sample chamber and the separation chamber. Claim 5 A blood separation disc according to claim 4, wherein at least a portion of the outer surface of the sample chamber has a shape in which a first outer surface and a second outer surface meet, the third channel is connected at a vertex where one end of the first outer surface and one end of the second outer surface are connected, and the first angle between a first straight line connecting the vertex and the other end of the first outer surface and a reference line perpendicular to the extension line of the third channel and the second angle between a second straight line connecting the vertex and the other end of the second outer surface and the reference line are each set as an acute angle of 30° or more. Claim 6 A blood separation disc according to claim 4, wherein the first outline and the second outline are symmetrical with respect to the extension of the third channel. Claim 7 A blood separation disc according to claim 4, wherein at least a portion of the outer surface of the sample chamber has a shape in which a first straight line and a second straight line meet, the third channel is connected at the vertex where one end of the first straight line and one end of the second straight line are connected, the first straight line and the second straight line are symmetrical with respect to the extension line of the third channel, and the first angle between the first straight line and a reference line perpendicular to the extension line of the third channel and the second angle between the second straight line and the reference line are each set as an acute angle of 30° or more. Claim 8 A blood separation disc according to claim 5, wherein the difference in magnitude between the angle between the first straight line and the extension line of the third channel and the angle between the second straight line and the extension line of the third channel is 60° or less. Claim 9 A blood separation disc according to claim 4, wherein the sample chamber has a shape in which a first straight line, a first outline, and a second outline are connected in the form of a right triangle, wherein the second channel is connected to one end of the first straight line, the third channel is connected to the vertex where the other end of the first straight line and the first outline meet, and the angle between the second straight line connecting the vertex and the other end of the first outline and the reference line perpendicular to the first straight line and passing through the vertex is each set to an acute angle of 30° or more. Claim 10 In claim 4, the blood separation unit further comprises a receiving chamber and a fourth channel connecting the separation chamber and the receiving chamber, a blood separation disk. Claim 11 A blood separation disc according to claim 1, wherein the disc body comprises at least one fixing groove formed to allow a fixing pin formed on the turntable of the material separation device to be inserted and coupled, or at least one fixing pin formed to allow insertion and coupling into a fixing groove formed on the turntable of the material separation device. Claim 12 A material separation device comprising: a first motor for rotating a material separation disk including a chamber which is a space for receiving a sample, a channel which provides a passage for the flow of the sample, and a valve which selectively opens and closes the channel; a valve actuator for supplying energy to operate the valve; a third motor for rotating the valve actuator with respect to a concentric axis with respect to the first motor; and a control unit for controlling the first motor, the third motor, and the valve actuator to supply energy to a valve material contained in the valve while the material separation disk and the valve actuator are rotated at different rotational speeds. Claim 13 In claim 12, the control unit controls the first motor and the third motor to supply energy to the entire valve material by rotating the material separation disk at a first rotational speed through the first motor while operating the valve through the valve actuator, and rotating the valve actuator alternately at a second rotational speed and a third rotational speed, wherein the second rotational speed is smaller than the first rotational speed and the third rotational speed has a value greater than or equal to the first rotational speed. Claim 14 A material separation device according to claim 13, wherein the control unit rotates the valve actuator at the first rotational speed to supply energy to the center of the valve material, rotates the valve actuator at the second rotational speed to supply energy to a first point in the entire area of ​​the valve material, and rotates the valve actuator at the third rotational speed to supply energy to a second point in the entire area of ​​the valve material, wherein, with respect to the rotational direction of the material separation disk, a first virtual line connecting the rotational axis to the first point is located behind the reference line directed toward the center of the valve material by a predetermined rotational angle, and a second virtual line connecting the rotational axis to the second point is located in front of the reference line by a predetermined rotational angle. Claim 15 In claim 12, the material separation disk comprises at least one blood separation unit, wherein the material separation disk comprises a rotatable disk body and disposed on the disk body and including a plasma separation chamber, a main chamber, and a sample chamber, and includes a first channel connecting the plasma separation chamber and the main chamber and a second channel connecting the main chamber and the sample chamber, wherein the main chamber has a cross-section of a predetermined shape when cut parallel to a horizontal plane, and the second channel is connected to one side thereof, and the lower volume of the main chamber, determined by the height from the bottom of the cross-section of the main chamber to the point of connection with the second channel, is formed such that it is less than or equal to the sum of the volume of the red blood cell layer of the blood and the volume of the density gradient solution under conditions in which a mixture of blood and a density gradient solution corresponding to the total volume of the main chamber is injected. Claim 16 A material separation device according to claim 15, wherein the disk body comprises at least one coupling groove, and the blood separation part is formed in the form of a modular split disk so as to be coupled to the coupling groove of the disk body. Claim 17 A material separation device according to claim 15, wherein the lower volume of the main chamber is formed such that it is less than or equal to the sum of the volume of the blood and the volume of the density gradient solution under conditions where a mixture of blood and a density gradient solution corresponding to the total volume of the main chamber is injected. Claim 18 A material separation device according to claim 15, wherein the blood separation unit further comprises a separation chamber and further comprises a third channel connecting the sample chamber and the separation chamber. Claim 19 A material separation device according to claim 18, wherein at least a portion of the outer surface of the sample chamber has a shape in which a first outer surface and a second outer surface meet, the third channel is connected at a vertex where one end of the first outer surface and one end of the second outer surface are connected, and the first angle between a first straight line connecting the vertex and the other end of the first outer surface and a reference line perpendicular to the extension line of the third channel and the second angle between a second straight line connecting the vertex and the other end of the second outer surface and the reference line are each set as an acute angle of 30° or more. Claim 20 A material separation device according to claim 18, wherein the first outline and the second outline are symmetrical with respect to the extension of the third channel. Claim 21 A material separation device according to claim 18, wherein at least a portion of the outer surface of the sample chamber has a shape in which a first straight line and a second straight line meet, the third channel is connected at the vertex where one end of the first straight line and one end of the second straight line are connected, the first straight line and the second straight line are symmetrical with respect to the extension line of the third channel, and the first angle between the first straight line and a reference line perpendicular to the extension line of the third channel and the second angle between the second straight line and the reference line are each set as an acute angle of 30° or more. Claim 22 A material separation device according to claim 19, wherein the difference in magnitude between the angle between the first straight line and the extension of the third channel and the angle between the second straight line and the extension of the third channel is 60° or less. Claim 23 A material separation device according to claim 18, wherein the sample chamber has a shape in which a first straight line, a first outline, and a second outline are connected in the form of a right triangle, wherein the second channel is connected to one end of the first straight line, the third channel is connected to the vertex where the other end of the first straight line and the first outline meet, and the angle between the second straight line connecting the vertex and the other end of the first outline and the reference line perpendicular to the first straight line and passing through the vertex is each set to an acute angle of 30° or more. Claim 24 In claim 18, the blood separation unit further comprises a receiving chamber and a fourth channel connecting the separation chamber and the receiving chamber, a material separation device. Claim 25 A material separation device according to claim 15, wherein the disk body comprises at least one fixing groove formed to allow a fixing pin formed on the turntable of the material separation device to be inserted and coupled, or at least one fixing pin formed to allow insertion and coupling into a fixing groove formed on the turntable of the material separation device.

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