Substance separation device

Abstract

The substance separation apparatus of the present application includes a first motor that rotates a substance separation disk including a chamber that is a sample-receiving space, a passage that provides a flow of a sample, and a valve that selectively opens and closes the passage; a valve driver that supplies energy that operates the valve; a third motor that rotates the valve driver with the first motor as a reference for a concentric axis; and a control section that controls the first motor, the third motor, and the valve driver to supply energy to a valve substance included in the valve in a state in which the substance separation disk and the valve driver rotate at different rotational speeds.

Description

Technical Field

[0001] This invention relates to a substance separation device. Background Technology

[0002] Deaths associated with malignant tumors are primarily due to metastasis to tissues and organs distant from the original site of the tumor. Therefore, early detection of metastasis is a crucial determinant of survival probability for cancer patients.

[0003] Cancer diagnosis typically utilizes histopathology-based diagnostic techniques. Histopathological diagnostic techniques use tissue samples obtained from biopsies to diagnose tumors. This histopathological approach allows for direct observation of tumor cells.

[0004] Furthermore, circulating tumor cells (CTCs) are known to be found in patients before tumors are initially detected. Therefore, CTCs can play an important role in the early diagnosis and prediction of cancer. Since cancer primarily metastasizes through the bloodstream, CTCs can be a marker for diagnosing whether cancer has metastasized. Based on this, disk-type devices for extracting circulating tumor cells from samples such as blood are being researched and developed.

[0005] This material separation disc device uses a rotating disc body to generate centrifugal force, and uses this centrifugal force to separate circulating tumor cells from the blood.

[0006] In this invention, when constructing the multiple chambers of such a material separation disc, the volume of the main chamber is specifically specified, thereby enabling accurate separation of the blood layer.

[0007] Furthermore, this material separation disc includes multiple chambers, and valves that are opened and closed by external energy are arranged in the channels connecting the chambers. The valves receive energy from the outside to operate. During sample analysis, the rotation of the material separation disc is stopped to operate the valves, and energy is supplied to the valves to melt the material before restarting the rotation. However, during valve operation, the sample, which has been centrifuged into multiple layers, is remixed, potentially reducing the reliability of the analysis. To address this problem, existing technology (No. 10-2176587, Invention Title: Sample Analysis Apparatus, Sample Analysis Method, and Dynamic Operation Method of Valve) proposes a configuration where the valve actuator, which supplies energy to the valve while the material separation disc rotates, also rotates. For smooth fluid movement within the material separation disc, proper valve operation, including effective melting of the material, is crucial. However, when the material separation disc and valve actuator rotate at the same speed while energy is irradiated onto the valve, if the valve shape and the energy irradiation section are inconsistent, there is a limitation that the material cannot be completely melted. Therefore, it is necessary to improve this limitation.

[0008] [Existing Technical Documents] Korean Patent Publication No. 10-2022-0135995 (Invention Title: Dividing Disc Device) Korean Patent No. 10-2176587 (Invention Title: Sample Analysis Apparatus, Sample Analysis Method, and Dynamic Operation Method of Valve) Summary of the Invention

[0009] The purpose of this invention is to provide a material separation disk that improves material separation characteristics by modifying the shape of the main chamber and the sample chamber of the material separation disk, and a material separation device including the material separation disk.

[0010] Furthermore, the object of the present invention is to provide a material separation device that adjusts the rotational speed of the valve actuator in order to effectively irradiate energy onto each valve.

[0011] However, the technical problem to be solved in this embodiment is not limited to the technical problem described above, and other technical problems may also exist.

[0012] As a technical solution for solving the above-mentioned technical problems, a material separation disk used in conjunction with a material separation device according to an embodiment of the present invention includes a rotatable disk body and one or more blood separation sections. The one or more blood separation sections are arranged in the disk body and include a plasma separation chamber, a main chamber, and a sample chamber. They also include a first channel connecting the plasma separation chamber and the main chamber, and a second channel connecting the main chamber and the sample chamber. When the main chamber is cut into a cross-section parallel to a horizontal plane, it has a cross-section of a predetermined shape. The second channel is connected to one side of the main chamber. The lower volume of the main chamber, defined by the height from the lower end of the cross-section of the main chamber to the connection point between the main chamber and the second channel, is such that, under the condition of injecting a mixture of blood and density gradient solution equivalent to the total volume of the main chamber, the volume of the red blood cell layer of the corresponding blood is less than the sum of the volume of the density gradient solution.

[0013] Furthermore, according to another embodiment of the present invention, a material separation device includes: a first motor for rotating a material separation disk, the material separation disk including a chamber serving as a sample receiving space, a channel providing a flow path for the sample, and a valve for selectively opening and closing the channel; a valve actuator for supplying energy to operate the valve; a third motor for rotating the valve actuator and the first motor about a concentric axis; and a control unit for controlling the first motor, the third motor, and the valve actuator to supply energy to the valve material included in the valve when the material separation disk and the valve actuator are rotating at different speeds.

[0014] According to embodiments of the present invention, the material separation characteristics can be improved by modifying the shape of the main chamber and the sample chamber of the material separation disk.

[0015] Furthermore, in the material separation device, the material separation disc and the valve actuator rotate together, and their rotational speeds are configured to be different, so that the energy of the valve actuator can be effectively irradiated throughout the valve in the material separation device to improve the melting of the valve material. Attached Figure Description

[0016] Figure 1 The configuration of a material separation apparatus according to an embodiment of the present invention is shown.

[0017] Figure 2 The detailed configuration of a movable valve actuator in a material separation apparatus according to an embodiment of the present invention is shown.

[0018] Figure 3 and Figure 4 The detailed configuration of the material separation disk according to an embodiment of the present invention is shown.

[0019] Figure 5The detailed configuration of the blood separation section according to an embodiment of the present invention is shown.

[0020] Figure 6 The structure of the main chamber of the material separation disc according to an embodiment of the present invention is shown.

[0021] Figure 7 The configuration of the main chamber of the material separation disc according to another embodiment of the present invention is shown.

[0022] Figure 8 The configuration of the sample chamber of a material separation disk according to an embodiment of the present invention is shown.

[0023] Figure 9 The configuration of the sample chamber of a material separation disk according to another embodiment of the present invention is shown.

[0024] Figure 10 The rotational speed in a material separation apparatus according to an embodiment of the present invention is shown.

[0025] Explanation of reference numerals in the attached figures Detailed Implementation

[0026] Hereinafter, embodiments of the present invention will be described in detail with reference to the accompanying drawings, enabling those skilled in the art to readily implement the invention. However, the present invention can be implemented in many different forms and is not limited to the embodiments described herein. Furthermore, for the purpose of clearly illustrating the invention, parts unrelated to the description are omitted in the drawings, and similar reference numerals are used for similar parts throughout the specification.

[0027] Throughout the specification, when one part is "connected" to another, this includes not only "direct connection" but also "electrical connection" with other components in between. Furthermore, when a part "includes" a constituent element, unless otherwise stated, it means that other constituent elements may also be included, rather than excluding them. This should be understood as not precluding the existence or additional possibilities of one or more other features, figures, steps, operations, constituent elements, components, or combinations thereof.

[0028] Figure 1 The structure of a material separation apparatus according to an embodiment of the present invention is shown. Figure 2 The detailed configuration of a movable valve actuator in a material separation apparatus according to an embodiment of the present invention is shown.

[0029] The basic structure corresponds to that of Patent No. 10-2176587 described above, therefore refer to the contents of that patent.

[0030] The material separation device 10 includes a material separation disc 100, a valve actuator 400, a first motor 500 that rotates the material separation disc 100, a second motor 600 that adjusts the radial position of the valve actuator 400, and a third motor 700 that rotates the valve actuator 400.

[0031] The first motor 500 rotates the material separation disk 100, thereby generating centrifugal force for the centrifugal separation and movement of the sample. For example, a turntable 520 for mounting the material separation disk 100 is provided on the rotation shaft of the first motor 500. The material separation disk 100 is provided with a mounting hole 102 corresponding to the turntable 520. The mounting hole 102 has the shape of a through hole formed through the center of the material separation disk 100, so that the turntable 520 can be inserted. Furthermore, a fixing pin 530 may be formed protruding on the outer contour of the turntable 520, which is inserted into a fixing hole 104 formed in the material separation disk 100. More than one fixing hole 104 and fixing pin 530 may be formed respectively, and the material separation disk 100 can be more stably fixed to the turntable 520 as the fixing pin 530 is inserted into the fixing hole 104. In the accompanying drawings, for ease of explanation, the fixing holes 104 and fixing pins 530 are shown arranged along the first reference line L1. However, the positions of the fixing holes 104 and fixing pins 530 can also be arranged differently. Furthermore, the number of fixing holes 104 and fixing pins 530 does not necessarily have to be two; there can be one or more. Additionally, unlike the illustration, the fixing holes 104 can be formed in the turntable 520, and the fixing pins 530 can be formed in the lower part of the material separation disk 100 in a manner corresponding to the fixing holes 104.

[0032] In addition, the first motor 500 and the turntable 520 can be directly connected, and the first motor 500 can be connected to the turntable 520 via power connection elements such as belts, chains, and gears.

[0033] Valve actuator 400 is an example of a valve actuator that supplies energy to valve A to operate the material separation disk 100. Valve actuator 400 can irradiate valve A with electromagnetic waves (e.g., laser light). For example, valve actuator 400 can be a laser diode.

[0034] The second motor 600 aligns the valve actuator 400 with valve A. That is, the second motor 600 moves the valve actuator 400 along the radial direction of the material separation disk 100, thereby positioning the valve actuator 400 above valve A. Figure 2An embodiment of the second motor 600 is shown. The second motor 600 is connected to a lead screw 630 that rotates by means of the second motor 600, and a moving member 620 equipped with a valve actuator 400 can move in the radial direction of the rotating member 720 by means of the lead screw 630. For example, the moving member 620 can be supported by a guide rail 640 extending in the radial direction of the material separation disc 100. The moving member 620 is equipped with a joint 621 that engages with the helical groove of the lead screw 630. With this configuration, if the lead screw 630 rotates, the moving member 620 moves in the radial direction along the guide rail 640. As an example of a method for obtaining a reference position of the valve actuator 400 in the radial direction, a method utilizing the change of the drive current of the second motor 600 can be used. For example, the moving member 620 can be moved inward or outward in the radial direction by means of the second motor 600. If the moving part 620 moves to the end of the lead screw 630, the moving part 620 stops moving, and at this time, the intensity of the current driving the second motor 600 changes drastically. If this drastic change in current is detected, it can be identified that the valve actuator 400 is located at the inner or outer end in the radial direction, and the control unit 800, described later, can identify this position as the reference position of the valve actuator 400 in the radial direction. Alternatively, a position detector 650 for detecting the reference position of the valve actuator 400 in the radial direction can also be arranged. For example, the position detector 650 can detect the moving part 620 at any position in the radial direction. For example, the position detector 650 can be a non-contact sensor such as an optical sensor or a contact sensor such as a microswitch.

[0035] The material separation disk 100 may include multiple chambers for containing samples, channels providing pathways for sample flow, and valves A for selectively opening and closing the channels. The material separation disk 100 may be a rotatable disk shape. The material separation disk 100 may include: a lower structure, a micro-flow structure with recessed features such as channels providing pathways for fluid flow formed between the chambers forming the fluid-containing space; and an upper structure (upper plate), an upper wall attached to the lower structure and forming the micro-flow structure. The material separation disk 100 may be a two-plate structure combining the upper plate and the lower plate with the micro-flow structure. The plates can be joined using various methods such as bonding with adhesives or double-sided adhesive tape, ultrasonic welding, or laser welding. The material separation disk 100 is easy to mold, and its surface can be made of biologically inactive plastic materials such as acrylic acid or polydimethylsiloxane (PDMS). However, it is not limited to these; any material with chemical and biological stability, optical transparency, and machinability is acceptable.

[0036] The material separation disc 100 can be equipped with various types of valves A. For example, valve A can be a normally closed valve that closes the channel in the normal state and receives energy from the outside to open the channel, a normally open valve that opens the channel in the normal state and receives energy from the outside to close the channel, and an on-off valve that can switch between the states of open channel, closed channel, and reopened channel.

[0037] Figure 3 and Figure 4 The detailed configuration of the material separation disk according to an embodiment of the present invention is shown. Figure 5 The detailed structure of the blood separation unit according to an embodiment of the present invention is shown. Figure 6 The diagram illustrates the configuration of the main chamber of the material separation disc according to an embodiment of the present invention. Figure 7 The configuration of the main chamber of the material separation disk according to another embodiment of the present invention is shown. Figure 8 The configuration of the sample chamber of a material separation disk according to an embodiment of the present invention is shown.

[0038] The material separation disc 100 may include a rotatable disc body 110 and one or more blood separation sections 120 disposed on the disc body 110. The disc body 110 and the blood separation section 120 may be integrally injection molded to form the material separation disc 100.

[0039] In another embodiment, after the disk body 110 and the blood separation section 120 are formed separately, the blood separation section 120 is combined with the connecting groove 115 formed in the disk body 110 to form a material separation disk 100. In this way, the blood separation section 120 can be implemented in the form of a modular dividing disk.

[0040] The material separation disc 100 may include one or more blood separation sections 120, which use the centrifugal force generated when the disc body 110 rotates to separate target substances (e.g., target cells) from a sample (e.g., whole blood). Furthermore, the disc body 110 may have one or more fixing holes 104.

[0041] According to one embodiment, the material separation disc 100 includes a disc body 110 and a blood separation section 120, and has a segmented structure in which the blood separation section 120 is coupled to each coupling groove 115 of the disc body 110. Therefore, it can prevent over-welding or partial welding from occurring in the parts as in the prior art, and thus can prevent product deviation and improve reproducibility.

[0042] In this embodiment, the disk body 110 can be configured with an overall circular disk shape, and a total of four connecting grooves 115 can be regularly arranged radially. That is, connecting grooves 115 of the same shape are formed on the disk body 110 at 90-degree intervals, and a structure is formed in which a modular segmented disk shape corresponding to the shape of the connecting grooves 115 is coupled to the connecting grooves 115. The disk body 110 and the blood separating part 120 can be manufactured by injection molding, thereby enabling accurate and efficient manufacturing of the disk body 110 and the blood separating part 120 with corresponding shapes.

[0043] However, the number and shape of the connecting grooves 115 are not limited to the examples described above, and the manufacturing method of the disc body 110 and the blood separation section 120 is not limited to the methods described above. For example, the number of connecting grooves 115 can be two or six, and of course, a blood separation section 120 corresponding to that number can also be provided.

[0044] Reference Figure 4 By placing the blood separation part 120 into the mating groove 115 of the disk body 110, the mating of the blood separation part 120 and the disk body 110 becomes easier. Subsequently, the contact surfaces of the mating groove 115 and the blood separation part 120 are fused together by ultrasonic welding, thereby making the bond between the two more secure. However, in addition to ultrasonic welding, laser welding, thermal welding, hot air welding, and other methods can also be used to weld the mating groove and the blood separation part.

[0045] Furthermore, the blood separation section 120 of this embodiment has a structure that is separated from the binding groove 115. Therefore, as follows: Figure 4 As shown, a separation hole 116 can be formed through the bottom of the disc body 110 where the connecting groove 115 is formed. To further explain, when it is necessary to separate the blood separation portion 120 from the connecting groove 115, pressure can be applied through the separation hole 116 in the direction of withdrawing the blood separation portion 120, thus easily achieving separation of the blood separation portion 120 from the connecting groove 115. Furthermore, although not shown, the inner wall of the disc body 110 constituting the connecting groove 115 and the outer wall of the blood separation portion 120 connected thereto can be tapered shapes with corresponding shapes. In other words, the inner wall of the disc body 110 forming the connecting groove 115 can have a tapered shape with a gradually decreasing width towards the bottom, and the outer wall of the blood separation portion 120 connected to the connecting groove 115 has a tapered shape with a gradually increasing width towards the bottom, thereby allowing the shapes of the inner wall of the disc body 110 forming the connecting groove 115 and the outer wall of the blood separation portion 120 to correspond. Due to this conical shape, when the disc body 110 rotates, it can prevent the blood separation section 120 from arbitrarily separating from the connecting groove 115.

[0046] The configuration of each blood separation unit 120 will be described. The blood separation unit 120 of this embodiment has multiple chambers, which can separate only target cells (i.e., circulating tumor cells (CTCs) of this embodiment) from whole blood.

[0047] The blood separation unit 120 of this embodiment may include a dividing disc body 121 and a plurality of chambers 130, 140, 150, 160, 170 disposed on the dividing disc body 121 and used to separate target cells from whole blood by means of the centrifugal force generated when the disc body 110 rotates.

[0048] The dividing disc body 121 provides a basic framework and is equipped with a shape corresponding to the shape of the aforementioned connecting groove 115.

[0049] Here, the multiple chambers 130, 140, 150, 160, and 170 may include a main chamber 130, a plasma separation chamber 140, a sample chamber 150, a separation chamber 160, and a containment chamber 170. Furthermore, the material separation disk 100 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 containment chamber 170.

[0050] First, in this embodiment, the main chamber 130 is located in the central portion of the dividing disc body 121, and it contains whole blood and a first density gradient medium (DGM) in a separated manner. The centrifugal force generated when the disc body 110 rotates forms layers of plasma, peripheral blood mononuclear cells (PBMCs), the first density gradient medium (DGM), and red blood cells (RBCs). This main chamber 130 may include: a whole blood containing space 131 for receiving and containing whole blood; and a substance containing space 135, separated from the whole blood containing space 131 by a partition wall, for receiving and containing the first density gradient medium.

[0051] Due to this configuration of the main chamber 130, when the disk body 110 rotates, the whole blood in the whole blood containing space 131 and the first density gradient substance in the substance containing space 135 can be separated by centrifugal force into blood layers composed of plasma, peripheral blood mononuclear cells, first density gradient substance, and red blood cells, respectively.

[0052] The plasma separation chamber 140 is connected to one side of the main chamber 130 via a channel 180, and can receive and contain plasma from the main chamber 130 after centrifugal separation. An on / off valve is installed in the channel 180 connecting the main chamber 130 and the plasma separation chamber 140. Therefore, if an electromagnetic wave or the like is applied to the on / off valve using the valve actuator 400, the valve can be opened, thereby enabling the movement of plasma from the main chamber 130 to the plasma separation chamber 140.

[0053] Furthermore, the sample chamber 150 is connected to the main chamber 130 with the plasma separation chamber 140 facing it, with the main chamber 130 as the center. Peripheral blood mononuclear cells in the blood layer formed after centrifugation can be separated into the sample chamber 150. Additionally, an on / off valve 185 is installed in the channel 182 connecting the main chamber 130 and the sample chamber 150. If an electromagnetic wave is applied to the on / off valve 185 using an electromagnetic wave generator or the like, the valve can be opened, allowing peripheral blood mononuclear cells to move from the main chamber 130 to the sample chamber 150.

[0054] To selectively remove leukocytes, which are mainly present in peripheral blood mononuclear cells, microbeads (e.g., CD45-dyed microbeads) that serve as leukocyte marker antibodies are injected into the sample chamber 150. Thus, leukocytes labeled with microbeads and circulating tumor cells that have been de-labeled can move from the sample chamber 150 to the separation chamber 160 through a channel.

[0055] In this embodiment, the separation chamber 160 may include a second density gradient material, and the microbead-labeled leukocytes and leukocyte-removed circulating tumor cells moving from the sample chamber 150 may form different layers by inserting the second density gradient material between them.

[0056] That is, leukocytes labeled with microbeads settle below the second density gradient material, and circulating tumor cells form above the second density gradient material, so that the circulating tumor cells can be separated into the circulating tumor cell containment chamber 170 through the fourth channel 186.

[0057] As described above, in this embodiment, each blood separation unit 120 has a plurality of chamber structures, thus allowing for accurate and efficient extraction of target cells (i.e., circulating tumor cells in this embodiment) from whole blood.

[0058] Furthermore, in this invention, the lower volume of the main chamber 130 is specifically specified so that the target material, especially the mononuclear cell layer, can be precisely separated.

[0059] like Figure 6As shown, the main chamber 130 is formed such that its predetermined volume is determined by its edge 132, and when the main chamber 130 is cut parallel to a horizontal plane, the edge 132 of the main chamber 130 has a predetermined cross-section. Furthermore, a second channel 182 is connected to one side surface of the main chamber 130.

[0060] Furthermore, when viewed with reference to a cross-section of the main chamber 130, the lower volume of the main chamber 130, defined by the height from the lower end 133 of the main chamber 130 to the connection point with the second channel 182, is such that, under the condition of injecting a mixture of blood and density gradient solution equivalent to the total volume of the main chamber 130, the volume of the corresponding blood's erythrocyte layer and the volume of the density gradient solution are less than or equal to the sum of their volumes. In other words, the present invention is characterized by specifically specifying the ratio of the lower volume of the main chamber 130 to its total volume. When the volume of the mixture of blood and density gradient solution capable of completely filling the 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 a ratio less than or equal to the sum of the volumes of the blood's erythrocyte layer and the density gradient solution in the corresponding mixture.

[0061] The main chamber 130 is layered from its lower end by a density gradient, in order of increasing density. That is, a layer of red blood cells with the highest density (d≥1.09) is formed, followed by a density gradient solution layer with a high density (1.077≤d≤1.084), a mononuclear cell layer (1.067≤d≤1.077), and a plasma layer (d≒1.05), with high-density components located at the lower end of the main chamber 130.

[0062] Furthermore, the main chamber 130 is formed according to the following conditional formula 1.

[0063] [Conditional expression 1] The volume of the lower part of the main chamber is less than or equal to 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 total volume of the main chamber.

[0064] At this point, the volume of the red blood cell layer can be calculated by multiplying the total blood volume by the red blood cell volume ratio (Hematocrit) value, which represents the ratio of red blood cell volume to the total blood volume, roughly equivalent to less than 60%.

[0065] Therefore, condition 1 can be modified into condition 2.

[0066] [Conditional expression 2] The volume of the lower part of the main chamber is ≤ the sum of 60% of the blood volume in the mixture of blood and density gradient solution corresponding to the total volume of the main chamber and the volume of density gradient solution.

[0067] exist Figure 7In the middle, the shape of the material separation disk and Figure 3 The shapes of the material separation disks are generally different, but they include a plasma separation chamber 140', a main chamber 130', a sample chamber 150', a first channel 180', and a second channel 182'. Furthermore, as described above, the lower volume of the main chamber 130' is formed to satisfy either condition 1 or condition 2. That is, when the volume of the mixture of blood and density gradient solution capable of completely filling the 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 a ratio less than or equal to the sum of the volumes of the red blood cell layers of the blood and the density gradient solution in the corresponding mixture, or a ratio less than or equal to 60% of the blood volume and the sum of the volumes of the density gradient solution in the corresponding mixture.

[0068] Furthermore, in this invention, the shape of the sample chamber 150 is specifically specified and proposed. After the mononuclear cells transferred to the sample chamber 150 are thoroughly mixed with the microbeads, they are moved to the separation chamber 160 via the third channel 184. In order to move the objects (cells, microbeads, etc.) in the sample chamber 150 to the separation chamber 160 through the third channel 184, a sufficient tilt angle is required to counteract the centrifugal force.

[0069] Reference Figure 8 A portion of the outer contour surface of the sample chamber 150 has a shape where the first outer contour line 151 and the second outer contour line 152 intersect. Considering the third outer contour line 153, it can have a shape where they are connected in an inverted triangular form. Furthermore, a third channel 184 is connected to the vertex connecting the first outer contour line 151 and the second outer contour line 152. In this case, the third channel 184 extends vertically downward from the vertex connecting the first outer contour line 151 and the second outer contour line 152, as shown in the figure. The first outer contour line 151 and the second outer contour line 152 can have a symmetrical relationship with respect to the extension line of the third channel 184. However, the invention is not limited to this; depending on the shape of the sample chamber 150, the first outer contour line 151 and the second outer contour line 152 can also have an asymmetrical relationship. At this time, 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 acute angles of 30° or more. At this time, the first angle θ and the second angle θ can be set to be different from each other.

[0070] Preferably, the angle α between the first straight line 154 and the extension of the third channel 184, and the angle α' between the second straight line 155 and the extension of the third channel 184 are set to be the same. This also means that the angle θ between the first straight line 154 and the reference line 156 perpendicular to the extension of the third channel 184, and the angle θ between the second straight line 155 and the reference line 156 are under the same conditions.

[0071] However, even if the angles are not the same, the difference between the angles (α-α') is less than 60°.

[0072] In addition, for the above-mentioned Figure 7 The sample chamber 150' of the deformed shape shown in the material separation disk should meet the following conditions. Figure 9 The configuration of the sample chamber of a material separation disk according to another embodiment of the present invention is shown.

[0073] The sample chamber 150' has the ability to hold Figure 3 The sample chamber 150 is cut in half along the extension line of the third channel 184. That is, if Figure 3 If the sample chamber 150 has a shape similar to an isosceles triangle, then the sample chamber 150' has a shape similar to a right triangle obtained by folding the sample chamber 150 in half. This sample chamber 150' has a shape in which a first straight line 157', a first outer contour line 152', and a second outer contour line 153' are connected in a shape similar to a right triangle. One end of the first straight line 157' is connected to a second channel 182', and the vertex where the other end of the first straight line 157' intersects with the first outer contour line 152' is connected to a third channel 184'. At this time, considering the reference line 156' which is perpendicular to the first straight line 157' and passes through its vertex, the angle θ between the second straight line 155' connecting the vertex and the other end of the first outer contour line 152' and the reference line 156' is set to an acute angle of 30° or more. That is, the angle α between the first straight line 157' and the second straight line 155' is set to an acute angle of less than 60°.

[0074] Refer again Figure 1The material separation device 10 is also equipped with 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 synchronously with the rotation of the material separation disk 100. The third motor 700 rotates the rotating component 720. At this time, the aforementioned second motor 600, guide rail 640, and lead screw 630 can be provided at the lower part of the rotating component 720. Although the third motor 700 and the rotating component 720 are shown as directly connected, the third motor 700 can also be connected to the rotating component 720 via a power connection element such as a belt, chain, or gear.

[0075] The control unit 800 controls the first motor 500, the second motor 600, and the third motor 700, and provides overall control of the sample analysis process. The control unit 800 may include a memory 830, a motor driver 820 driving the first motor 500 to the third motor 700, and a central processing unit 810. The memory 830 may store application software for controlling the sample analysis process. Furthermore, the memory 830 may store the position coordinate values ​​(e.g., polar coordinate values ​​r, θ based on the rotation center RC1 and the first reference line L1) of multiple valves A equipped on the material separation disk 100. The application software and the position coordinate values ​​of the multiple valves can also be downloaded from a host computer connected to the material separation device 10 and stored in the memory 830. Additionally, the user can directly input the position coordinate values ​​of the multiple valves into the memory 830 via an input device (not shown).

[0076] The first motor 500 can be a servo motor. The servo motor incorporates an encoder capable of counting revolutions and a feedback mechanism for controlling rotation. Therefore, the angular position of the rotational phase of the first motor 500 (e.g., the encoder's reference position) relative to the control reference polar coordinate system of the material separation device 10 at any given time can be known. When the material separation disk 100 is mounted on the first motor 500, the reference position of the encoder of the first motor 500 is aligned with the first reference line L1 of the material separation disk 100. Therefore, the angular position of valve A relative to the control reference polar coordinate system of the material separation device 10 at any given time can be known. For example, a first alignment portion 103 aligned with the first reference line L1 is provided in the mounting hole 102 of the material separation disk 100, and a second alignment portion 521, which is combined with the first alignment portion 103 and aligned with the reference position of the encoder of the first motor 500, is provided on the turntable 520. The first alignment portion 103 and the second alignment portion 521 can have complementary shapes. For example, the first alignment portion 103 may be a groove extending outward from the circular mounting hole 102, and the second alignment portion 521 may be a protrusion inserted into the first alignment portion 103.

[0077] The third motor 700 can be a servo motor. The second reference line L2 of the rotating component 720 can be aligned with the reference position of the encoder built into the third motor 700. The second reference line L2 can coincide with the radial movement trajectory of the valve actuator 400. Furthermore, the second reference line L2 can also have a phase difference equivalent to θ0 with the radial movement trajectory of the valve actuator 400.

[0078] Furthermore, referring to Figure 1 and Figure 2 The material separation device 10 may also 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 disposed on the material separation disk 100 and the rotating component 720. The first phase pattern P1 and the second phase pattern P2 are respectively disposed on the material separation disk 100 and the rotating component 720 at positions aligned with the first reference line L1 and the second reference line L2. The control unit 800 can calculate the number of revolutions of the material separation disk 100 and the rotating component 720, the angular positions of the first reference line L1 and the second reference line L2, and the angular positions of the arbitrary time valve A and the valve actuator 400 based on the output signals (first phase signal and second phase signal) of the first phase detector 851 and the second phase detector 852. For example, the first phase pattern P1 and the second phase pattern P2 can be optically recognizable patterns or magnetically recognizable patterns. The phase pattern P1 can be a position aligned with the first alignment part 103.

[0079] [Sample Processing] The control unit 800 drives the first motor 500 to rotate the material separation disc 100 at a first rotational speed V1, thereby performing sample processing procedures such as centrifugation of samples and mixing of samples with additives according to the analytical purpose. For example, sample centrifugation is performed by loading a sample into the material separation disc 100 and rotating it. Then, as needed, the valve A is opened to transfer some or all of the centrifuged material layers to other chambers. During the [sample processing] process, the rotating component 720 may remain stationary without rotating.

[0080] [Position alignment in the radial direction] 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 coordinate r of the valve A from the memory 830. While driving the second motor 600, the control unit 800 detects a sharp change in the intensity of the current used to drive the second motor 600 and identifies the location where this change is detected as the reference position r0 of the valve actuator 400 in the radial direction. Alternatively, the control unit 800 drives the second motor 600 to move the moving member 620 radially and detects the moving member 620 using a position detector 650. If the moving member 620 is detected, the control unit 800 identifies the valve actuator 400 as being at the reference position r0 in the radial direction. The control unit 800 determines the amount and direction of rotation of the second motor 600 corresponding to the r-r0 value, and based on this, drives the second motor 600 to move the valve actuator 400 radially. The [radial alignment] process can be performed in advance during the [sample processing] process described above, while the rotating component 720 is stopped and not rotating.

[0081] [Corner alignment] Then, the control unit 800 drives the third motor 700, causing the valve actuator 400 to rotate synchronously with the material separation disc 100. The control unit 800 reads the angular position θ of valve A from the memory 830. The control unit 800 drives the third motor 700 via the motor actuator 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 component 720 and the rotational speed of the material separation disc 100.

[0082] Then, the control unit 800 calculates the angular positions of the valve actuator 400 and valve A relative to the reference polar coordinate system at any given time based on the encoder output signals (first encoder output signal, second encoder output signal) of the first motor 500 and the third motor 700, or the output signals (first phase signal, second phase signal) of the first phase detector 851 and the second phase detector 852, and determines the difference between the two angular positions. The control unit 800 controls the rotation speed of the third motor 700 based on this difference, thereby aligning the angular positions of the valve actuator 400 and valve A relative to the reference polar coordinate system. Thus, the valve actuator 400 rotates synchronously with the material separation disk 100.

[0083] Figure 10 The rotational speed in a material separation apparatus according to an embodiment of the present invention is shown.

[0084] like Figure 10As shown, when the material separation disc 100 rotates at a first speed V2, which is less than the rotational speed V1, the control unit 800 causes the third motor 700 to rotate alternately at a second speed and a third speed. At this time, the second speed is less than the first speed V2, and the third speed has a value greater than or equal to the first speed V2.

[0085] Furthermore, at the point when the rotational speed of the rotating component 720 is the same as the first rotational speed V2, the valve actuator 400 is positioned above valve A on the material separation disc 100. That is, the start-up time of the third motor 710 can be determined, so that the angular positions of the valve actuator 400 and valve A are aligned. As described above, by continuously and alternately changing the second and third rotational speeds by the rotational speed of the rotating component 720 of the third motor 700, and when the rotational speed of the third motor 700 is the same as the first rotational speed of the first motor 500, it can be considered that the angular positions are aligned and the valve actuator 400 is operated.

[0086] And, as Figure 10 As shown, the valve material included in the opening / closing valve 185 has a predetermined area. When the entire area of ​​the valve material is spread out is called the valve domain, when the material separation disc 100 rotates at a first rotational speed V2, if the control unit 800 causes the third motor 700 to rotate alternately at a second rotational speed and a third rotational speed, the valve actuator 400 can move between positions A and B in the entire valve position and supply energy (e.g., laser). That is, as shown, assuming the material separation disc 100 rotates to the right, if the third motor 700 rotates at the second rotational speed, the valve actuator 400 irradiates a laser at a first position B located slightly behind the center of the valve material, based on the rotation direction of the material separation disc 100. If the third motor 700 rotates at the third rotational speed, the valve actuator 400 irradiates a laser at a second position A located slightly forward of the center of the valve material. In other words, the angular rotation speed is adjusted as follows: with the rotation direction of the material separation disk 100 as a reference, compared with the reference line from the rotation axis of the material separation disk 100 toward the center of the valve material, the first virtual line connecting the first position B from the rotation axis is located behind by a predetermined rotation angle, and the second virtual line connecting the second position A from the rotation axis is located in front of the reference line by a predetermined rotation angle.

[0087] As described above, the valve actuator 400 can move relative to the valve material and effectively irradiate energy.

[0088] [Valve Operation] By employing the aforementioned [radial alignment] and [angular alignment] steps, if the valve actuator 400 is located above a specific valve section, the control unit 800 drives the valve actuator 400 (for example, by irradiating the valve material with a laser beam). Then, the energy of the laser beam is absorbed into the valve material, causing it to melt. The material separation disc 100 is rotating, thus the molten valve material is pushed out of channel C by centrifugal force, thereby opening valve A.

[0089] As described above, valve A is operated while the valve actuator 400 rotates together with the material separation disk 100. This allows the channel C to be opened or closed by centrifugal force before the molten valve material solidifies, thereby improving the reliability and speed of valve A's operation. Furthermore, the material separation disk 100 continues to rotate during valve A's operation, thus maintaining the separated samples and preventing mixing of the separated layers. Moreover, the valve A operation can be performed without a rotation stop of the material separation disk 100, thus shortening the time required for sample analysis.

[0090] The above description of the invention is for illustrative purposes. Those skilled in the art will understand that other specific forms can be readily derived without altering the technical concept or essential features of the invention. Therefore, it should be understood that the above embodiments are exemplary in all respects and not restrictive. For example, the constituent elements described in a single form may also be implemented separately, and similarly, the constituent elements described in a distributed form may also be implemented in a combined form.

[0091] The scope of this invention is defined by the appended claims rather than the detailed description provided, and all changes or modifications derived from the meaning and scope of the claims and their equivalents shall be interpreted as being included within the scope of this invention.

Claims

1. A substance separation device, comprising: A first motor rotates a material separation disk, the material separation disk including a chamber serving as a sample receiving space, a channel providing a flow path for the sample, and a valve selectively opening and closing the channel. Valve actuator, supplying energy to operate the valve; The third motor causes the valve actuator to rotate with the first motor around a concentric axis. as well as The control unit controls the first motor, the third motor, and the valve actuator to supply energy to the valve material included in the valve while the material separation disc and the valve actuator rotate at different speeds.

2. The material separation device according to claim 1, wherein, The control unit controls the first motor and the third motor in the following manner: during valve operation via the valve actuator, the first motor rotates the material separation disc at a first rotational speed, and the third motor alternately rotates the valve actuator at a second and a third rotational speed, thereby supplying energy to the entire material distribution area of ​​the valve. The second rotational speed is less than the first rotational speed, and the third rotational speed has a value greater than or equal to the first rotational speed.

3. The material separation device according to claim 2, wherein, The control unit is configured as follows: The valve actuator is rotated at the first rotational speed to supply energy to the center of the valve material. The valve actuator is rotated at the second rotational speed to supply energy to a first position throughout the entire range of the valve material. The valve actuator is rotated at the third rotational speed to supply energy to a second position throughout the entire range of the valve material. With the rotation direction of the substance separation disc as a reference, compared with the reference line from the rotation axis of the substance separation disc toward the center of the valve substance, the first virtual line connecting the first position from the rotation axis is located behind by a predetermined rotation angle, and the second virtual line connecting the second position from the rotation axis is located in front of the reference line by a predetermined rotation angle.

4. The material separation device according to claim 1, wherein, The material separation disk includes: A rotatable disc body; and One or more blood separation units are arranged in the disk body and include a plasma separation chamber, a main chamber, and a sample chamber, and include 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, when the main chamber is cut into a cross-section parallel to the horizontal plane, it has a predetermined shape, and one side of the main chamber is connected to the second channel. The lower volume of the main chamber, defined by the height from the lower end of the cross-section of the main chamber to the connection point between the main chamber and the second channel, is such that, under the condition of injecting a mixture of blood and density gradient solution equivalent to the total volume of the main chamber, it forms a red blood cell layer of the corresponding blood and a density gradient solution that is less than the sum of the volume of the density gradient solution.

5. The material separation device according to claim 4, wherein, The disk body includes one or more mating grooves. The blood separation section is formed in the shape of a modular dividing disc, which is combined with the connecting groove of the disc body.

6. The material separation device according to claim 4, wherein, Under the condition of injecting a mixture of blood and density gradient solution equivalent to the total volume of the main chamber, the lower volume of the main chamber is formed to be less than 60% of the volume of the blood and the volume of the density gradient solution.

7. The material separation device according to claim 4, wherein, The blood separation unit also includes a separation chamber and a third channel connecting the sample chamber and the separation chamber.

8. The material separation device according to claim 7, wherein, At least a portion of the outer contour of the sample chamber has a shape where a first outer contour line and a second outer contour line intersect, and the third channel is connected to the vertex where one end of the first outer contour line and one end of the second outer contour line meet. The first angle between the first straight line connecting the vertex to the other end of the first outline and the reference line perpendicular to the extension of the third channel, and the second angle between the second straight line connecting the vertex to the other end of the second outline and the reference line, are both set to acute angles of 30° or more.

9. The material separation device according to claim 8, wherein, The first and second outlines are symmetrical with respect to the extension of the third channel.

10. The material separation apparatus according to claim 7, wherein, At least a portion of the outer contour of the sample chamber has a shape in which a first straight line and a second straight line intersect. The third channel is connected to the vertex where one end of the first straight line and one end of the second straight line meet. The first straight line and the second straight line are symmetrical with respect to the extension line of the third channel. The first angle between the first straight line and the reference line perpendicular to the extension of the third channel and the second angle between the second straight line and the reference line are both set to acute angles of 30° or more.

11. The material separation apparatus according to claim 8, wherein, The difference 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 less than 60°.

12. The material separation apparatus according to claim 7, wherein, The sample chamber has a shape in which a first straight line, a first outer contour line, and a second outer contour line are connected in the form of a right-angled triangle. One end of the first straight line is connected to the second channel, and the third channel is connected to the vertex where the first straight line intersects the first outer contour line. 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 set to an acute angle of 30° or more.

13. The material separation apparatus according to claim 7, wherein, The blood separation unit also includes a receiving chamber and a fourth channel connecting the separation chamber and the receiving chamber.

14. The material separation device according to claim 4, wherein, The disc body includes one or more fixing slots formed for insertion into fixing pins formed on the turntable of the material separation device, or includes one or more fixing pins formed for insertion into fixing slots formed on the turntable of the material separation device.

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