JP2011075420A - Centrifugal separator - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a centrifugal separator capable of performing centrifugal separation at a time. <P>SOLUTION: Introduction ports (openings 25) of blood which is a measurement object liquid and air holes 27 are connected to a planer disk 24, and assuming that the opening 25 is an upstream of blood and that the air hole 27 is a downstream, grooves 26 which are a plurality of U-shaped channels formed extendedly from the inside to the outside in the radial direction of the disk 24, and after folding back extendedly again from the outside to the inside in the radial direction of the disk 24 are formed from the upstream to the downstream, thus performing the centrifugal separation at a time. <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

  The present invention relates to a centrifuge for centrifuging collected liquid to be measured.

  The centrifuge is formed as part of the liquid collection device. As an example of the liquid collection device, a blood collection device that collects blood, that is, collects blood will be described. The blood collection device is used for quantitative analysis in nuclear medicine diagnosis (for example, PET (Positron Emission Tomography), SPECT (Single Photon Emission CT), etc.), and in particular, the radioactivity concentration in arterial blood of small animals (eg, mice, rats, etc.). Used for measurement.

  Specifically, arterial blood sampling is performed at a predetermined time while imaging a small animal to which a radiopharmaceutical has been administered with the above-described nuclear medicine diagnostic apparatus, and the radioactivity concentration in whole blood is measured. Further, the whole blood collected at each predetermined time is centrifuged to remove the plasma component, and the plasma radioactivity concentration is also measured. In blood collection using small animals, the amount of blood that can be collected from one animal is limited, so that the amount of blood that can be collected at one time is very small. As a technique for obtaining plasma from blood, there is a technique for separating blood into plasma and blood cells (that is, plasma separation) by centrifugation in a U-shaped flow path (see, for example, Patent Document 1).

  There is a method of separating plasma by centrifugation other than the above U-shaped flow path (for example, see Patent Document 2). In addition, there is a method of preparing a sample by centrifugation even when performing a cell assay in the field of optical biodiscs (see, for example, Patent Document 3).

JP 2004-109082 A US Pat. No. 5,061,381 Japanese Patent Publication No. 2005-509882

[Problem 1] Problem of frequent blood collection However, the above-described device of Patent Document 1 requires one blood analyzer for one blood collection, and also performs centrifugation of one blood analyzer at a time. Only operation is possible. In the case of an actual small animal, a plurality of blood samples are collected in a predetermined time while imaging with a nuclear medicine diagnostic apparatus. In particular, immediately after the start of imaging, blood is collected at intervals of several seconds, so there is no time to replace the blood analyzer. Moreover, it is not possible to perform a centrifugal separation operation on a plurality of samples at once.

[Problem 2] Problems related to blood introduction into the flow path Since blood is viscous, it is difficult to enter the flow path with a small volume. In the apparatus of Patent Document 1 described above, the pump is pulled in, but it is necessary to incorporate the pump into the apparatus and control it.

[Problem 3] Problems relating to separation of plasma and blood cells When the flow volume of the device of Patent Document 1 described above is small in blood volume relative to the blood cell reservoir, plasma may also enter the blood cell reservoir. Conversely, when the blood volume is large relative to the blood cell reservoir, the blood cells overflow from the blood cell reservoir, and only the plasma on the blood outlet side can be taken out. In order to solve these problems, it is conceivable that the size of the flow path must be changed in accordance with the amount of blood collected.

  This invention is made | formed in view of such a situation, Comprising: It aims at providing the centrifuge which can perform centrifugation at once.

In order to achieve such an object, the present invention has the following configuration.
That is, the centrifugal separator according to the present invention connects a liquid inlet and an air hole to be measured to a flat disk, and the inlet is an upstream part of the liquid and the air hole is a downstream part. In addition, the U-shape formed from the upstream portion to the downstream portion extends from the inner side to the outer side in the radial direction of the disk and is folded to extend from the outer side to the inner side in the radial direction of the disk. A centrifuge provided with a plurality of flow channels of a mold, wherein the collected liquid to be measured is introduced from the introduction port and centrifuged.

  [Operation / Effect] According to the centrifugal separator according to the present invention, the measurement target collected by connecting the liquid inlet and the air hole of the measurement target in the flow path provided in the flat disk. Even if this liquid is introduced from the introduction port, air in the flow channel is released from the air hole, so that the liquid can be smoothly flowed to the flow channel through the introduction port. This flow path extends from the inner side to the outer side in the radial direction of the disk from the upstream part to the downstream part when the inlet is the upstream part of the liquid and the air hole is the downstream part. It is formed in a U-shaped shape that extends from the outside toward the inside in the radial direction. Therefore, when the liquid to be measured is introduced from the inlet and centrifuged, the component having a high specific gravity accumulates and the component having a low specific gravity is collected in the return of the flow channel on the outermost side in the radial direction. Since it flows to a place other than the folding, it becomes easy to centrifuge the liquid. In addition, since the flow path is formed in a U-shape, the distance between the introduction port and the return of the flow path is almost equal to the distance between the return of the flow path and the air hole, and a component having a small specific gravity is used. The liquid can be diffused throughout the flow path, and the length of the liquid after centrifugation can be made uniform with reference to the return of the flow path. Centrifugation can be performed at a time by providing the disc with a plurality of such U-shaped flow paths.

  In the centrifugal separator according to the present invention described above, a rotating means for rotating the disk is provided at the center of the disk, and the liquid to be measured is centrifuged using the centrifugal force of the disk by the rotating means. preferable. By providing a rotating means for rotating the disk at the center of the disk, the plurality of U-shaped flow paths can be rotated at the same rotational speed.

  In the above-described centrifuges according to these inventions, it is preferable that the plurality of flow paths are respectively arranged radially along the radial direction of the disk. In particular, when the rotating means for rotating the disk is provided at the center of the disk as described above, a plurality of U-shaped flow paths can be rotated at the same rotational speed and the same centrifugal force. Variations in centrifugation can be suppressed.

  In the centrifuges according to these inventions described above, each of the plurality of channels is preferably formed by grooving a disk with a predetermined dimension. That is, since the groove is processed with a predetermined dimension, if the groove length or groove region of the liquid fed into the flow path is known, it is based on the cross-sectional area or depth of the groove processed with the predetermined dimension. Thus, the volume of the liquid fed into the flow path can be defined. In addition, by performing groove processing with a predetermined dimension, the size of the flow path can be predicted and designed in accordance with the sampling amount.

  In the centrifuges according to these inventions described above, it is preferable to apply hydrophilic processing to the inner walls of the plurality of flow paths. By applying a hydrophilic process, it is possible to enter the flow path by simply dropping the liquid into the inlet. Therefore, the conventional pump becomes unnecessary and it is not controlled. By subsequent centrifugation, the liquid is introduced to the folded portion of the flow path, components having a large specific gravity gather at the folded portion, and components having a small specific gravity come to both ends thereof.

  In the above-described centrifuges according to these inventions, the inlets of the plurality of flow paths are preferably formed in a tapered shape in which the upper surface is formed wider than the lower surface. Since the introduction port is formed in a tapered shape in which the upper surface is formed wider than the lower surface, it is possible to enter the inside of the flow path just by dropping the liquid into the introduction port, as in the case of hydrophilic processing. As in the case of hydrophilic processing, a conventional pump is no longer necessary and is not controlled. By subsequent centrifugation, the liquid is introduced to the folded portion of the flow path, components having a large specific gravity gather at the folded portion, and components having a small specific gravity come to both ends thereof.

  In the centrifugal separators according to these inventions described above, an example of the liquid to be measured is blood. In this case, plasma separation is performed by centrifuging blood to separate it into plasma and blood cells. As long as it is a liquid to be measured, it is not limited to blood, but may be a liquid containing a radioactive substance or a fluorescent agent, or a mixed liquid used in an analyzer.

  If the liquid to be measured is blood, connecting the inlet and the air hole allows the collected blood (that is, the collected blood) to be introduced from the air hole into the flow path even if it is introduced from the inlet. Therefore, blood can flow smoothly through the inlet through the flow path. When blood is introduced from the inlet and centrifuged, blood cells with a high specific gravity accumulate in the fold of the flow channel on the outermost side in the radial direction, and plasma with a low specific gravity flows to a place other than the fold. , It makes it easier to centrifuge blood (ie plasma separation). In addition, since the flow path is formed in a U-shape, the distance between the introduction port and the return of the flow path is almost equal to the distance between the return of the flow path and the air hole, so that plasma with a small specific gravity can be obtained. It is possible to diffuse the entire flow path, and the length of the blood after centrifugation can be made uniform with reference to the return of the flow path. Centrifugation can be performed at a time by providing the disc with a plurality of such U-shaped flow paths.

  When the liquid to be measured is blood, the inner wall of each of the plurality of flow paths is subjected to hydrophilic processing, or the inlet is formed in a tapered shape with the upper surface wider than the lower surface. It is possible to enter the inside of the flow path simply by dropping the liquid into the inlet. Therefore, the conventional pump becomes unnecessary and it is not controlled. By subsequent centrifugation, blood is introduced to the folded portion of the flow path, blood cells having a large specific gravity gather at the folded portion, and plasma having a small specific gravity comes to both ends thereof.

  When the liquid to be measured is blood, set the radius of curvature of the curved portion to set the radius of curvature of the curved portion under the condition that the volume of the curved portion at the turn of the flow passage satisfies the volume of blood cells contained in the blood to be centrifuged. Preferably formed. As a result of intensive studies by the inventors, under conditions where the width and depth of the flow path, the diameter of the disk and the rotational speed of the disk are constant, changing the radius of curvature changes the volume of the curved part, It came to the knowledge that even with the same blood collection volume, separation failure may occur. That is, when the volume of the curved part is larger than the volume of blood cells, it is considered that the plasma also approaches the folded curved part and causes separation failure. Therefore, when the flow path is formed by setting the radius of curvature of the curved portion under the condition that the volume of the curved portion in the flow path fold is less than the volume of blood cells contained in the blood to be centrifuged, the curved portion of the plasma is turned back. Plasma separation can be performed without entering. Therefore, the flow path can be formed by setting the radius of curvature of the curved portion according to the blood collection amount.

  When the liquid to be measured is a liquid containing a radioactive substance, each of the plurality of flow paths is preferably processed to be thin enough to allow β rays to pass through either the upper surface or the lower surface. By making the upper surface or lower surface of the flow path thinner, it is possible to reduce the absorption of the β-rays radiated from the radioactive material liquid that has entered the flow path into the material forming the disk, so that the flow is lower. Radiation measurement can be performed from the outside of the disk even if the liquid has a radioactive concentration.

  According to the centrifugal separator according to the present invention, when the liquid inlet and the air hole of the liquid to be measured are connected to the flat disk, the inlet is the upstream part of the liquid, and the air hole is the downstream part. A plurality of U-shaped flow paths formed from the upstream part to the downstream part, extending from the inner side to the outer side in the radial direction of the disk, and folded to extend from the outer side to the inner side in the radial direction of the disk. By providing, centrifuge can be performed at a time.

(A), (b) is a schematic perspective view of the blood collection apparatus which concerns on an Example, the disc with which it was equipped, and its peripheral device. It is a schematic plan view of the disc which concerns on an Example. (A) is a schematic plan view of the U-shaped groove | channel which concerns on an Example, (b) is a schematic expanded sectional view of the U-shaped groove | channel which concerns on an Example. (A) is a schematic plan view of the opening part concerning an Example, (b) is a schematic sectional drawing of the opening part concerning an Example. It is the graph which showed the relationship of the volume of the curve part when changing a curvature radius. It is the flowchart which showed the flow of a series of blood collection processes which concern on an Example. It is a schematic perspective view of the scanner in the imaging part of a measuring device. It is the graph which showed the relationship between the radiation dose and the pixel value (imaging plate pixel value) read by the imaging plate when changing the β-ray transmission distance from the lower surface of the groove to the imaging plate.

Embodiments of the present invention will be described below with reference to the drawings.
FIG. 1 is a schematic perspective view of a blood collection apparatus according to an embodiment, a disc provided in the blood collection apparatus, and peripheral devices therefor. In the present embodiment, blood will be described as an example of a liquid to be measured, a blood sampling device will be described as an example of a liquid sampling device, and a disk will be described as an example of a centrifugal separator.

  As shown in FIG. 1, the blood collection apparatus 10 according to the present embodiment collects blood to be measured by separating it in time series. In addition, a measuring device 30 that measures radiation (for example, β rays, γ rays, etc.) contained in blood collected by the blood collecting device 10 is provided around the blood collecting device 10. In this embodiment, blood after administration of a radiopharmaceutical into the body of a mouse is collected (ie, blood is collected), and the radiation contained in the blood is measured. In addition, plasma separation is performed, and radiation contained in the plasma and blood cells separated from each other is measured.

  The blood collection apparatus 10 includes a liquid dividing device 40 configured by vertically stacking PDMS substrates 11 and 12 made of two PDMS resins (Polydimethylsiloxane). The PDMS substrates 11 and 12 are grooved with a predetermined dimension, and the main flow path 13 and the side paths 41, 42, and 43 are formed by the grooves. Here, the material of the blood collection device 10 is not limited to PDMS, and may be any material that is optically transparent such as acrylic, polycarbonate, COP (cycloolefin polymer).

  A catheter 14 is disposed on the blood inlet side of the main channel 13, and the main channel 13 and the catheter 14 are connected via a connector 15. Blood is continuously fed from the catheter 14 into the main channel 13 and the amount of inflow is controlled by a valve (not shown). A blood pipe 16 is disposed on the blood outlet side of the main flow path 13, and the main flow path 13 and the blood pipe 16 are connected via a connector 17.

  A light source 21 and a photodiode 22 are disposed across the main flow path 13. The blood flowing in the main flow path 13 or heparin solution described later is irradiated with light from the light source 21, and the photodiode 22 detects the light shielding by the blood, so that the blood or heparin solution is optically monitored (monitored) as described later. Measure length information of blood or heparin solution. Here, the light source 21 and the photodiode 22 have been described as an example of the optical measurement means. However, any means for measuring the liquid interval while optically monitoring the liquid to be measured can be used as the light source 21 and the photodiode 22. It is not limited. For example, volume information of the liquid to be measured may be acquired by a CCD camera. In addition, the light source 21 and the photodiode 22 are so-called “transmission type sensors” that are arranged to face each other with the main flow channel 13 interposed therebetween as shown in FIG. On the other hand, a so-called “reflective sensor” may be used in which light detection means typified by a photodiode is provided on the same side, and detection is performed using reflected light from blood.

  On the other hand, a dispenser 23 is connected to the downstream side of the blood piping 16 described above. A disc (also referred to as “CD well”) 24 for receiving and storing blood dropped from the dispenser 23 is provided. A plurality of openings 25 for receiving the dropped blood are arranged radially on the center side of the disc 24. Similarly to the PDMS substrates 11 and 12 described above, the circular plate 24 is grooved, and a plurality of U-shaped grooves 26 are formed radially by the grooves. Each U-shaped groove 26 is connected to the outer end of the above-described opening 25 on a one-to-one basis, and each U-shaped groove 26 is formed to extend in the radial direction of the disk 24. Yes. Thus, by interposing the dispenser 23, the disc 24 is formed so that blood can flow through the main flow path 13. The disc 24 corresponds to the centrifugal separator in the present invention, the opening 25 corresponds to the introduction port in the present invention, and the groove 26 corresponds to the flow path in the present invention. A specific configuration of the disc 24 will be described later with reference to FIG.

On the other hand, the measuring device 30 includes a reading unit 31. The reading unit 31 is provided with a cover for inserting the exposed imaging plate IP, and detects β ⁺ rays contained in the blood by reading the light excited from the imaging plate IP. . Specifically, as shown in FIG. 1B, the reading unit 31 includes a laser light source 32 and a photomultiplier tube (photomultiplier tube) 33, and a laser is applied from the laser light source 32 to the imaging plate IP. , And the photomultiplier tube 33 converts the light excited by the laser irradiation of the imaging plate IP into electrons and multiplies them, thereby detecting β ⁺ rays simultaneously two-dimensionally.

  As described above, the liquid dividing device 40 includes the main flow path 13 for feeding blood, the side path 41 for feeding a heparin solution which is a kind of anticoagulant for preventing the occurrence of blood coagulation, and the side path for feeding air or gas. 42 and a side passage 43 for discharging blood or heparin solution.

  A cleaning liquid pipe 44 is disposed on the solution inlet side of the side path 41, and the side path 41 and the cleaning liquid pipe 44 are connected via a connector 45. If necessary, the heparin solution is poured into the main flow path 13 from the cleaning liquid pipe 44 via the side path 41 to clean the flow path. The inflow of heparin solution is controlled by a valve. Anticoagulants are not limited to heparin solutions.

  A bubble piping 46 is disposed on the gas inlet side of the side passage 42, and the side passage 42 and the bubble piping 46 are connected via a connector 47. The inflow time of air or gas controlled by a pressure generator (not shown) is adjusted by a valve and sent to the main flow path 13 through the side path 42. With these bubbles, blood is taken out based on blood length information and waste liquid (blood, heparin solution or a mixture thereof) remaining in the flow path of the liquid dividing device 40 is discharged. Here, the gas to be fed is not limited, and may be any gas that does not react with blood or heparin solution, as exemplified by rare gas such as helium, neon, and argon, or nitrogen gas.

  The bubble pipe 46 sends gas (for example, air or gas) through the side passage 14 to the main flow path 13 and inserts the gas as bubbles at a specified predetermined interval, whereby the blood to be measured is timed. Separated in series and sent to the disc 24. That is, the bubbles serve as a separator. In addition, although gas was used as a separator, it is not limited to gas, and there is little possibility of mixing with the liquid to be measured (blood in this embodiment), or if there is no possibility, the liquid to be measured May use another liquid as a separator. When the liquid to be measured is blood as in this embodiment, a liquid that does not mix with blood, such as mineral oil or fluorine oil, may be used as the separator. However, when a liquid is used as a separator, it can be used as a separator because it comes into contact with blood, but it is not desirable in that it is sent to the disk 24 and collected.

  A waste liquid pipe 48 is provided on the side of the waste liquid outlet side of the side path 43, and the side path 43 and the waste liquid pipe 48 are connected via a connector 49. The discharge amount is adjusted by a valve, and blood other than blood to be collected, heparin solution after channel cleaning, or a mixed solution thereof is discharged as waste liquid.

  Further, a valve is disposed downstream of the connector 15 of the main flow path 13, and a valve is disposed upstream of the connector 17, the light source 21, and the photodiode 22 of the main flow path 13. A valve is disposed downstream of the connector 45 of the side passage 41, and a valve is disposed downstream of the connector 47 of the side passage 42. A valve is disposed upstream of the connector 49 in the side passage 43.

  Next, a specific configuration of the disc 24 will be described with reference to FIGS. 2 to 5 including FIG. 2 is a schematic plan view of a disk according to the embodiment, FIG. 3A is a schematic plan view of a U-shaped groove according to the embodiment, and FIG. 3B is a plan view of the embodiment. FIG. 4A is a schematic enlarged cross-sectional view of such a U-shaped groove, FIG. 4A is a schematic plan view of an opening according to the embodiment, and FIG. 4B is a schematic cross-section of the opening according to the embodiment. FIG. 5 is a graph showing the volume relationship of the curved portion when the radius of curvature is changed.

  As shown in FIGS. 2 to 4, the groove 26 of the disk 24 is formed by connecting the opening 25 and the air hole 27 described above. When the opening 25 that is the blood inlet is the upstream part of the blood and the air hole 27 is the downstream part, the groove 26 extends from the inside to the outside in the radial direction of the disk 24 from the upstream part to the downstream part. The U-shape is formed by extending and folding back and extending from the outside toward the inside in the radial direction of the disk 24. A plurality of such U-shaped grooves 26 are provided. The air hole 27 corresponds to the air hole in the present invention.

  As shown in FIG. 1, a motor 28 that rotates the disc 24 is provided at the center of the disc 24. By connecting the rotating shaft 29 of the motor 28 to the disc 24, the centrifugal force of the disc 24 by the motor 28 is used to perform blood separation to separate blood into plasma and blood cells.

  In this embodiment, the plurality of grooves 26 are arranged radially along the radial direction of the disk 24 as shown in FIG. As described above, each of the plurality of grooves 26 is formed by machining the disk 24 with a predetermined dimension.

More specifically, as shown in the plan view of FIG. 3 (a) and the plan view of FIG. 4 (a), the width of the groove 26 is w, the cross-sectional view of FIG. 3 (b), and FIG. 4 (b). As shown in the cross-sectional view of FIG. Further, as shown in FIG. 4, the opening 25 is formed in a tapered shape in which the diameter of the upper surface 25A of the opening 25 is t _U , the diameter of the lower surface 25B is t _B , and the upper surface 25A is wider than the lower surface 25B. . Further, as shown in the plan view of FIG. 3A, the radius of curvature of the curved portion when the groove 26 is folded is R. Here, the radius of curvature is the distance to the center of the groove 26.

In this embodiment, the circular plate 24 includes an acrylic plate having a thickness of 0.1 mm and 36 grooves 26 each having a width w of 0.5 mm, a depth d of 0.2 mm, and a length of 40 mm. It is formed by overlapping and pressing a 2 mm acrylic plate on top and bottom to form 36 U-shaped grooves 26 (U-shaped minute volume flow paths). The diameter of the disk 24 is 50 mm, and the radius of curvature R of the curved portion when the groove 26 is folded is 0.75 mm. The inner wall of the groove 26 is subjected to hydrophilic processing using an excimer lamp. Further, the diameter _{t U} of the upper surface 25A of the opening 25 is 2.6 mm, that the diameter _{t B} of the lower surface 25B is formed at 1.5 mm, has an upper surface 25A and wider the tapered shape from the lower surface 25B. The hydrophilic processing is not limited to the excimer lamp, and is not particularly limited as long as it is a commonly used hydrophilic processing such as chemical processing, plasma processing, and hydrophilic processing by ultraviolet irradiation.

  As actual experimental data, 1 μL of blood was dropped into the groove 26 and centrifuged at 14000 rpm for 5 minutes to perform plasma separation. As a result, blood cells gathered in the folded curve portion of the groove 26 and were more than the blood cells. It has been confirmed that light plasma exists on both sides of the blood cells. The radius of curvature R of the curved portion (here, the radius of curvature R is 0.75 mm) is set under the condition that the volume of the folded curved portion of the groove 26 satisfies the volume of the blood cell contained in the blood to be centrifuged. A groove 26 is formed.

  As a result of intensive studies by the inventors, under conditions where the width w and depth h of the groove 26, the diameter of the disk 24, the rotation speed of the disk 24, and the like are constant, the curvature radius R is changed accordingly. As a result, it was found that separation failure may occur even with the same blood collection volume. That is, when the volume of the curved part is larger than the volume of blood cells, it is considered that the plasma also approaches the folded curved part and causes separation failure. When the volume of the curved portion is V and the width w, the depth h, and the radius of curvature R are used, the volume V of the curved portion is expressed by the following equation (1).

V = πh / 2 {(R + w / 2) ² − (R−w / 2) ² }
= ΠhwR (1)
However, π in the above equation (1) is a circumference ratio. When the width w and the depth h are constant, the equation (1) shows that the volume V of the curved portion changes when the radius of curvature R is changed, as shown in the graph of FIG. Here, since about 45% of the blood is blood cells, 0.45 μL of blood is 1 μL of blood. The straight line of the alternate long and short dash line in FIG. 5 is a boundary where the blood cell becomes 0.45 μL. According to this graph and the above equation (1), the radius of curvature R at the beginning of the study is larger than 0.45 μL when R is 1.5 mm. I will stop by.

From the above examination, it can be said that the volume of the curved curve portion of the groove 26 needs to be equal to or less than the volume of blood cells contained in the blood to be centrifuged. When the volume of blood to be separated is V _b , the above equation (1) can be modified and expressed by the condition of the following equation (2).

πhwR ≦ 0.45V _b (2)
The right side (= 0.45V _b ) in the above formula (2) indicates the volume of blood cells representing about 45% of the blood, and the left side (= πhwR) in the above formula (2) is the curve of the folding of the groove 26. The volume of the part is shown, and the above equation (2) is a condition in which the volume of the curved part of the turn of the groove 26 satisfies the volume of the blood cell contained in the blood to be centrifuged. As described above, when the groove 26 is formed by setting the curvature radius R of the curved portion under the condition satisfying the above expression (2), the plasma can be separated without the plasma entering the folded curved portion. Therefore, the groove 26 can be formed by setting the curvature radius R of the curved portion according to the blood collection amount.

  Next, a series of blood collection processes will be described with reference to FIGS. FIG. 6 is a flowchart showing a flow of a series of blood collection processes according to the embodiment, FIG. 7 is a schematic perspective view of a scanner in the imaging unit of the measurement apparatus, and FIG. 8 is a view from the bottom surface of the groove to the imaging plate. It is the graph which showed the relationship between the radiation dose when changing the transmission distance of (beta) rays, and the pixel value (imaging plate pixel value) read by the imaging plate.

(Step S1) Feeding blood into the main flow path The catheter 14 (see FIGS. 1 and 2) is inserted into the mouse artery, and the arterial blood self-exposed by the mouse blood pressure is passed through the catheter 14 through the main flow path 13 ( By referring to FIG. 1 and FIG. 2), blood is continuously fed into the main channel 13.

(Step S2) Separation Control of Separator When blood is not flowing through the main flow path 13 (see FIGS. 1 and 2), the separator is disposed opposite the light source 21 (see FIGS. 1 and 2) with the main flow path 13 in between. Since the light emitted from the light source 21 is incident on the photodiode 22 (see FIGS. 1 and 2), the detector signal photoelectrically converted by the photodiode 22 becomes a high level and is output from the photodiode 22. . Conversely, when blood is flowing through the main flow path 13, the light emitted from the light source 21 is blocked by the blood, so that the light is not incident on the photodiode 22, and the detector signal becomes a low level and photo Output from the diode 22. In this way, when the photodiode 22 detects light shielding by blood, the blood length information is measured while optically monitoring the blood, and the valve is turned on based on the measurement result by the photodiode 22. Control. By controlling the valve, the interval of air or gas sent from the side passage 42 to the main channel 13, that is, the interval of the separator is controlled. Since the main channel 13 is formed by grooving with a predetermined dimension, the volume of blood to be taken out can be obtained from the blood length information obtained by optical monitoring (monitoring).

(Step S3) Transfer to Disk The trace amount of blood taken out in step S2 is sent to the dispenser 23 (see FIGS. 1 and 2) through the blood piping 16 (see FIGS. 1 and 2). The dispenser 23 drops each of the micro blood taken out into an opening 25 (see FIG. 1) of a disc (CD well) 24 (see FIGS. 1 and 2). By this dripping, the extracted trace blood is transferred to the disc 24.

(Step S4) Plasma Separation When blood is transferred to the disc 24 (see FIGS. 1 and 2) in step S3, plasma separation is performed by rotating the disc 24 to separate it into plasma and blood cells.

(Step S5) Imaging of disk As each sample of the disk 24 (see FIGS. 1 and 2) plasma-separated into plasma and blood cells, a cassette (not shown) is opened and accommodated, and an imaging plate IP is placed thereon. (See FIG. 1) and close the cassette. After a certain time, the disk 24 is taken out from the cassette, and exposure is performed by irradiating the imaging plate IP with light. By this exposure, electrons are captured by lattice defects of the phosphor (not shown) of the imaging plate IP due to the ionizing ability of β ⁺ rays contained in the blood. The exposed imaging plate IP is taken out from the cassette and inserted into the cover portion of the reading unit 31 (see FIG. 1) of the measuring device 30 (see FIG. 1).

A laser is emitted from the laser light source 32 (see FIG. 1) of the reading unit 31 (see FIG. 1) to the imaging plate IP (see FIG. 1). The trapped electrons are excited to the conductor by this irradiation and recombine with holes, and are excited as light from the phosphor. The photomultiplier tube 33 (see FIG. 1) converts the light excited by the laser irradiation to the imaging plate IP into electrons and multiplies it, so that it is simultaneously detected and counted two-dimensionally as an electric pulse. . In addition, after irradiating the imaging plate IP from the laser light source 32, the captured electrons are erased by irradiating the imaging plate IP with light from an erasing light source (not shown) for reuse. Based on the count information of the obtained beta ⁺ line in the imaging plate IP and reading unit 31, obtains the radiation dose in the blood which is count information on beta ⁺ line.

  As shown in FIG. 7, the imaging unit 34 of the measuring device 30 (see FIG. 1) images the disc 24. In this embodiment, a flat head scanner is employed as the imaging unit 34. A flat head scanner is composed of a linear light source 34a having at least a length corresponding to the diameter of the disc 24 and a linear photodiode array (that is, a line sensor) 34b arranged to face the light source 34a with the disc 24 in between. Constitute. The disk 24 is imaged by scanning the disk 24 with a flat head scanner, and an image of the disk 24 is acquired. The blood volume is calculated from the image of the disk 24, and the blood radioactivity concentration is determined from the radiation dose in the blood determined from the image and the imaging plate IP (see FIG. 1).

  In the present embodiment, preferably, the plurality of flow paths (grooves 26 in the embodiment) are processed to be thin enough to allow β rays to pass through either the upper surface or the lower surface. By thinning the upper surface or the lower surface of each of the plurality of channels, β rays radiated from the liquid to be measured (blood in the embodiment) containing a radioactive substance are absorbed by the material forming the disk 24. This can be reduced, and radiation measurement can be performed from outside the disk even with a lower radiation dose.

  As shown in FIG. 8, the transmission distance of β rays from the lower surface of the groove 26 to the imaging plate is t. When the circular plate 24 is an acrylic plate having a thickness of 1 mm, the transmission distance t is 800 nm when the depth d of the groove 26 is 200 nm, and the transmission distance t is 500 nm when the depth d of the groove 26 is 500 nm. The relationship between the radiation dose and the pixel value read by the imaging plate IP (imaging plate pixel value) when the transmission distance t is changed to 800 nm and 500 nm is as shown in the graph of FIG. From the graph of FIG. 8 as well, since the β-ray transmission distance t from the lower surface of the groove 26 to the imaging plate is 800 nm in the flow path (groove 26), β-rays are absorbed more than in the case of 500 nm. It has been confirmed that it cannot be measured at low radioactivity concentrations. Therefore, when the transmission distance t is processed to 500 nm, it is possible to reduce the absorption of β rays emitted from blood by the material forming the disk 24.

  If necessary, the catheter 14 (see FIGS. 1 and 2) is washed or a heparin solution, air or gas is fed into the waste liquid (blood, heparin solution or The mixed solution is discharged.

  According to the centrifugal separator (disk 24) according to this embodiment, the liquid to be measured (blood in this embodiment) in the flow path (groove 26 in this embodiment) provided in the planar disk 24. By connecting the inlet (opening 25 in this embodiment) and the air hole 27, the collected liquid (blood) to be measured flows from the air hole 27 even if it is introduced from the inlet (opening 25). Since air in the passage (groove 26) is released, the liquid (blood) can flow smoothly through the introduction port (opening 25) into the flow path (groove 26). This flow path (groove 26) has a radial direction of the disk 24 from the upstream part to the downstream part when the inlet (opening 25) is the upstream part of the liquid (blood) and the air hole 27 is the downstream part. It is formed in a U-shape that extends from the inside to the outside and is folded back and extends from the outside to the inside in the radial direction of the disk 24. Therefore, when the liquid (blood) to be measured is introduced from the inlet (opening 25) and centrifuged, the liquid ( The component (blood cell in this embodiment) with a high specific gravity accumulates in the blood), and the component (plasma in this embodiment) with a low specific gravity flows to a place other than the return, so that the liquid (blood) can be easily centrifuged. Become. Further, since the flow path (groove 26) is formed in a U-shape, the distance between the return of the introduction port (opening 25) and the flow path (groove 26), and the return of the flow path (groove 26). The distance between the air holes 27 is substantially equal, and it is possible to diffuse a component (plasma) having a small specific gravity throughout the channel (groove 26), and the length of the liquid (blood) after centrifugation is The flow paths (grooves 26) can be aligned with reference to the return. Centrifugation can be performed at a time by providing the disc 24 with a plurality of such U-shaped flow paths (grooves 26).

  In the present embodiment, preferably, a rotating means (motor 28 in this embodiment) for rotating the disk 24 is provided at the center of the disk 24, and the centrifugal force of the disk 24 by the rotating means (motor 28) is used. Thus, the liquid to be measured (blood in this embodiment) is centrifuged. By providing a rotating means (motor 28) for rotating the disc 24 at the center of the disc 24, a plurality of U-shaped flow paths (grooves 26 in this embodiment) can be rotated at the same rotational speed.

  In the present embodiment, preferably, a plurality of flow paths (grooves 26 in the present embodiment) are respectively arranged radially along the radial direction of the disk 24. In particular, as described above, when the rotating means (the motor 28 in this embodiment) for rotating the disc 24 is provided at the center of the disc 24, the plurality of U-shaped flow paths (grooves 26) are provided with the same rotational speed and the same. It can be rotated by centrifugal force, and variation in centrifugal separation between the respective flow paths (grooves 26) can be suppressed.

  In this embodiment, each of the plurality of flow paths (grooves 26 in this embodiment) is formed by grooving the disk 24 with a predetermined dimension. That is, since the groove is processed with a predetermined dimension, if the groove length or groove region of the liquid (blood in this embodiment) fed into the flow path (groove 26) is known, the groove is processed with the predetermined dimension. Based on the cross-sectional area of the groove 26 or the depth of the groove 26, the volume (blood) of the liquid fed into the flow path can be defined. In addition, by machining the groove with a predetermined dimension, the size of the flow path (groove 26) can be predicted and designed in accordance with the amount to be collected.

  In the present embodiment, preferably, the inner wall of each of the plurality of flow paths (grooves 26 in the present embodiment) is subjected to hydrophilic processing. By applying the hydrophilic processing, the liquid (blood in the present embodiment) can be made to enter the flow path (groove 26) simply by dropping it into the inlet (opening 25 in the present embodiment). Therefore, the conventional pump becomes unnecessary and it is not controlled. By subsequent centrifugation, the liquid (blood) is introduced to the folded portion of the flow path (groove 26), and a component having a large specific gravity (blood cell in this embodiment) gathers at the folded portion, and a component having a small specific gravity (the main component) In the example, plasma) comes at both ends.

  In the present embodiment, the introduction port (opening 25 in the present embodiment) of each of the plurality of flow paths (grooves 26 in the present embodiment) is preferably formed in a tapered shape in which the upper surface 25A is formed wider than the lower surface 25B. ing. Since the introduction port (opening 25) is formed in a tapered shape in which the upper surface 25A is formed wider than the lower surface 25B, the liquid (blood in this embodiment) is introduced into the introduction port (opening) as in the case of hydrophilic processing. It is possible to enter the flow path (groove 26) only by dropping into the portion 25). As in the case of hydrophilic processing, a conventional pump is no longer necessary and is not controlled. By subsequent centrifugation, the liquid (blood) is introduced to the folded portion of the flow path (groove 26), and a component having a large specific gravity (blood cell in this embodiment) gathers at the folded portion, and a component having a small specific gravity (the main component) In the example, plasma) comes at both ends.

  In this embodiment, an example of the liquid to be measured is blood. In this case, plasma separation is performed by centrifuging blood to separate it into plasma and blood cells.

  The present invention is not limited to the above-described embodiment, and can be modified as follows.

  (1) In the above-described embodiments, blood has been described as an example of the liquid to be measured in the centrifugal separator. However, as long as the liquid to be measured is used, a radioactive substance or a fluorescent agent is not limited to blood. It may be a contained liquid or a mixed solution used in an analyzer.

  (2) In the above-described embodiment, the rotating means (the motor 28 in the embodiment) for rotating the disk 24 is provided at the center of the disk 24. However, the rotating means is not necessarily provided at the center of the disk. You may provide a rotation means in the edge part of a disc.

  (3) In the embodiment described above, the plurality of flow paths (grooves 26 in the embodiment) are arranged radially along the radial direction of the disk 24, but are not necessarily arranged radially. For example, you may arrange | position in parallel mutually.

  (4) In the embodiment described above, the inlet (in the embodiment, the opening is formed by applying a hydrophilic process to the inner wall of each of the plurality of flow paths (grooves 26 in the embodiment) or by forming the upper surface wider than the lower surface. By forming the portion 25), the liquid to be measured (blood in the example) is allowed to enter the flow path (groove 26) simply by dropping it into the inlet (opening 25). It is not limited to a tapered shape.

24 ... Disc 25 ... Opening 25A ... Upper surface 25B ... Lower surface 26 ... Groove 27 ... Air hole V ... Volume of curved portion R ... Radius of curvature of curved portion

Claims (11)

  When the liquid inlet and the air hole of the liquid to be measured are connected to a flat disk, and the inlet is the upstream part of the liquid and the air hole is the downstream part, the upstream part to the downstream part is A centrifugal separation device comprising a plurality of U-shaped flow paths formed to extend from the inner side to the outer side in the radial direction of the disk and to be folded back and extend from the outer side to the inner side in the radial direction of the disk. An apparatus for centrifuging, wherein the collected liquid to be measured is introduced from the inlet and centrifuged.   2. The centrifuge according to claim 1, further comprising a rotating means for rotating the disk at the center of the disk, and using the centrifugal force of the disk by the rotating means to centrifuge the liquid to be measured. A centrifugal separator characterized by that.   The centrifuge according to claim 1 or 2, wherein the plurality of flow paths are arranged radially along the radial direction of the disc.   The centrifuge according to any one of claims 1 to 3, wherein each of the plurality of flow paths is formed by grooving the disk with a predetermined dimension. Centrifugal device.   The centrifugal separator according to any one of claims 1 to 4, wherein the inner walls of the plurality of flow paths are subjected to hydrophilic processing.   The centrifuge according to any one of claims 1 to 5, wherein the introduction port of each of the plurality of flow paths is formed in a tapered shape in which an upper surface is formed wider than a lower surface. Centrifugal device.   The centrifuge according to any one of claims 1 to 6, wherein the liquid to be measured is blood, and plasma separation is performed by centrifuging the blood to separate it into plasma and blood cells. Centrifuge.   The centrifuge device according to claim 7, wherein a radius of curvature of the curved portion is set under a condition that a volume of the curved portion at the folding of the flow path satisfies a volume of the blood cell included in the blood to be centrifuged. And forming the flow path. The centrifuge according to any one of claims 1 to 6, wherein the liquid to be measured is a liquid containing a radioactive substance, and the liquid to be measured is centrifuged. . 10. The centrifugal separator according to claim 9, wherein the upper surface or the lower surface of the flow path is processed to be thin enough to allow β-rays to pass therethrough. 7. The centrifuge according to claim 1, wherein the liquid to be measured is a liquid containing a fluorescent agent, and the liquid to be measured is centrifuged. .

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