JP6877745B2 - Plasma separator and plasma separation method - Google Patents

Description

The present invention relates to devices and methods for separating liquid components from body fluids or blood, in particular for separating plasma (or serum) components from blood. More specifically, the present invention can separate arbitrary plasma (or serum) easily and inexpensively without the need for a centrifuge, a suction / pressurizing pump, or the like. Plasma (or serum) separation. The present invention relates to an apparatus and a plasma (or serum) separation method.

Medical diagnosis by blood tests is routinely performed because various clinical conditions of a patient can be determined based on the presence and / or concentration of substances that dissolve in body fluids, especially in the blood. ing.
Blood samples, especially plasma or serum, can be analyzed after collection to obtain a lot of medically useful information such as, for example, chemical composition / properties, hematology, or coagulation, eg, related to a disease. Thus, the physiological and biochemical status of the patient, such as mineral content, specific DNA content, drug efficacy, and organ function, can be determined. Such a blood test can generally be performed in a clinical laboratory of a hospital, a testing company, or the like.
It should be noted that the plasma or serum that is the subject to be tested lacks fibrinogen or some other coagulation factor in which the serum obtained from the coagulated blood sample is lost as a result of the blood coagulation process. Aside from the points, they are similar.

Conventionally, in order to analyze plasma or serum, it is necessary to separate the plasma or serum to be analyzed from the components in the blood. For that purpose, a doctor or the like usually collects about 10 mL of venous blood with a syringe. It was then sent to a laboratory where a centrifugation step had to be performed to separate and prepare the liquid components of plasma or serum from the blood cells or clot components. This method is a general method for centrifuging cell components such as erythrocytes and leukocytes or blood clots in blood and plasma or serum by a difference in specific gravity, and when this centrifugation method is used, hemolysis occurs. If not, in a centrifuge, heavy red blood cells are generally in the lower layer (about 41% of the total blood) and lighter plasma are in the upper layer (of the whole blood) when anticoagulants are added. Approximately 55%), platelets, leukocytes, etc. are separated neatly into the intermediate layer (approximately 4% of the total blood). When no anticoagulant is added, the upper layer is separated into serum and the lower layer into blood clots by centrifugation.

However, since blood collection must be performed by a medical worker, the burden on the test subject (subject) and the medical institution is large, and the cost is high. In addition, the inspection requires a centrifuge device for the centrifuge step and personnel and time for the centrifuge, which is costly and time-consuming.
Preparation of plasma or serum by centrifugation also often causes hemolytic problems. The development of hemolysis is undesirable as it results in the release of enzymes, hemoglobin, other pigments and stromas into the liquid components of the blood. This interferes with many clinical trials.

Therefore, conventionally, even if the user or the person concerned is not a medical worker, even if he / she does not go through the centrifugation step, the suction / pressurization step, etc., no training is required, and the user or the person concerned can quickly and efficiently. There has been a need for plasma or serum separators and plasma or serum separation methods that enable the analysis of plasma or substances contained in serum accurately.
In addition, there has been a need for a simple and inexpensive plasma or serum separation device or plasma or serum separation method that can be used for worldwide healthcare including developing countries.

As an invention for such a purpose, for example, a blood separator capable of separating without using a centrifuge such as Patent Document 1 and Patent Document 2 has been proposed.
Patent Document 1 is composed of a filter member that moves plasma more rapidly than blood cells and plasma or serum separation membrane that is connected in series to the subsequent stage of the filter member, or moves plasma faster than blood cells. It is composed of a first filter member, a second filter member which is a plasma or serum separation membrane, and a third filter member which supplements fibrin and the like. Mechanism / equipment and personnel were required.
In Patent Document 2, the separation of the liquid portion from the cellular component of blood occurs by the flow through the first and second matrices, and the first porous separation matrix contains a binder for the cellular component of blood. The second matrix is a configuration in which a liquid portion of blood can flow into the first matrix by capillary action or chromatographic separation. However, the current situation is that such a type of plasma separator is difficult to put into practical use due to problems such as long separation time, clogging of cell components such as erythrocytes, and hemolysis.

In such a conventional technique, even if a centrifuge device is not required, a device for depressurizing or pressurizing is required, a plurality of filter members or a porous matrix are combined, and there is a risk of hemolysis. There is no guarantee that blood liquid components can be recovered quickly, easily, and inexpensively in the amount required for testing, even if other devices / tools or personnel are required or no other device is required. There wasn't.

Further, in medical diagnosis, it is required that analysis can be performed easily, in a short time, and at low cost, and in particular, the amount of sample required for analysis is an important issue. Once a system is established that can collect a small amount of blood with a blood collection tool that can be used at home and prepare a sample for biochemical tests, it will be quickly transported to a blood test institution and the test results will be obtained in a short time. It will be possible to become a very useful system not only in home medical care but also in areas without medical institutions and even in developing countries, and the demand for total healthcare worldwide is increasing now. Although it can be satisfied, the current situation is that practical and useful systems have not yet been developed.

In this way, due to social demands in recent years, special devices and tools such as centrifuges and suction / pressurization have been used not only for medical institutions but also for developing countries and clinical care at home. There was a need for a method or device (equipment) that does not require personnel and can easily separate plasma or serum from blood components for blood tests, etc., even in trace amounts. "Plasma or serum" is also simply referred to as "plasma" below.
A plasma separator and a plasma separation method for separating plasma (or serum) from a trace amount of blood have already been filed by the present inventors with Patent Document 3 as the content, but a trace amount of plasma (or a trace amount of 100 μL or less) has already been filed. It was effective in separating (serum), but was unsuitable for separating more plasma (or serum).

Japanese Unexamined Patent Publication No. 2004-344874 Japanese Unexamined Patent Publication No. 2006-177970 Japanese Patent Application No. 2016-196059

An object of the present invention is that, in view of the current state of the prior art described above, it is not necessary to use a centrifuge, a suction / pressurizing pump, or the like, and anyone can reliably, inexpensively, and promptly use blood anywhere. It is an object of the present invention to provide a plasma separator and a plasma separation method capable of separating a predetermined amount of plasma components from a plasma.

In order to solve the above problems, the invention of claim 1 is a plasma separation device having a blood separation unit composed of a fibrous filter that separates blood cells and plasma, and a plasma collection unit that collects the separated plasma. hand,
The blood separation unit has a plasma impregnation receiving portion that impregnates plasma at the lower end, and the plasma collecting portion has a tip portion that comes into contact with the lower surface of the plasma impregnation receiving portion so as to bite into the lower end portion. Is formed by combining a plurality of hydrophilic members to form a gap portion that generates a capillary force, and the gap portion is formed by a contact portion between a flat portion of a first flat plate and a side surface portion of a second flat plate of the hydrophilic member, and the capillary force is formed. It is a plasma separation device characterized by sucking and taking out plasma by means of.
The invention of claim 2 states that in the plasma separator according to claim 1, the side surface portion of the second flat plate extends downward beyond the contact portion, and the area of the lower tip is gradually reduced. It is a feature.

The invention of claim 3 is a blood separation region composed of a fibrous filter that separates blood cells and plasma, a plasma impregnation receiving region that impregnates and temporarily holds the separated plasma, and a capillary tube from the plasma impregnation receiving region. It is a plasma separation method in which plasma is sucked and taken out by providing a plasma suction region that is sucked by a gap that generates force.
The gap is formed by a contact portion between the flat surface portion of the first flat plate and the side surface portion of the second flat plate of the hydrophilic member, and is a plasma separation method characterized by sucking and taking out plasma by capillary force.
According to the invention of claim 4, in the plasma separation method according to claim 3, the side surface portion of the second flat plate extends downward beyond the contact portion to form a plasma recovery region, and the side surface portion of the second flat plate is formed. The portion is characterized in that the area of the lower tip is gradually reduced.

The plasma or serum separation device and method of the present invention do not require a centrifuge, a suction / pressurization device, electric power, or the like, and even a general person who has not been trained in the procedure can easily, quickly, and inexpensively. In addition, it is possible to safely prepare a sample for a blood test.
According to this device and method, it is easy to operate, does not require specialized skills, and can easily, quickly, and inexpensively hemolyze even in areas without advanced analytical instruments such as centrifuges. The liquid component (plasma or serum) can be safely separated from a small amount of blood or from any amount of blood without worry. Moreover, not only the separated liquid component but also the cell component can be used as a blood test sample.

Overall external perspective view of an embodiment of the plasma separator of the present invention, An enlarged perspective view of the plasma separator with the plasma collection unit 7 removed. Enlarged perspective view of the blood separation section of FIG. An enlarged perspective view of the filter unit main body 31 of FIG. An enlarged perspective view of the blood introduction section 2 and the upper portion of the blood separation section 3 in FIG. Enlarged perspective view of the plasma impregnation receiving section 4, the plasma suction section 5, the plasma droplet section 6, and the plasma recovery section of FIG. An enlarged perspective view of the joint portion between the plasma impregnation receiving portion and the plasma suction portion 5 of FIG. Bottom view showing a state in which plasma is exuded as seen from the lower side of the plasma impregnation receiving portion in FIG. 7. 9 (a) is a cross-sectional view taken along the line (a)-(a) of FIG. 8, and FIG. 9 (b) is a cross-sectional view taken along the line (b)-(b) of FIG. It is a bottom view which shows the state which plasma exudes from the lower side of the plasma impregnation receiving part of another Example.

The plasma separator and method of the embodiment of the present invention include a blood introduction section for temporarily storing blood after blood collection in the present plasma separation device, a blood separation section connected to the blood introduction section and having a blood separation member, and a blood separation section. It is connected to a plasma impregnation receiving part that impregnates and sucks the separated and retained plasma from the blood separation part, a plasma suction part that sucks plasma from the plasma impregnation receiving part through a slight gap having a capillary force of the capillary phenomenon, and a plasma suction part. A plasma droplet having an edge-like portion for efficiently guiding the collected plasma by suction with a capillary force to the collection portion, and a droplet-shaped plasma dropped from the tip of the tip of the plasma droplet. Alternatively, it is a plasma separation device and method for separating plasma from blood, which comprises a plasma collection unit for transmitting and storing plasma on a wall surface or the like.

Hereinafter, description will be made with reference to the figures of preferred examples of the present invention.
First, the apparatus and method for plasma separation in the examples of the present invention, as a whole, is as shown in FIG. 1, which functions for the separation of components in a liquid, and the liquid is preferably blood. The components to be separated are roughly classified into cell components (blood cell components) such as red blood cells and white blood cells trapped in the blood separation member, and substances suitable for various biochemical tests (including DNA, RNA, etc.). Is a liquid component such as plasma or serum containing. The plasma separator and method of the present invention can, for example, separate 200 μL to 600 μL of liquid components such as plasma or serum from 2 mL of blood in 10 minutes.

Examples of the suitable plasma separation device 1 and the method thereof of the present invention include, as shown in FIGS. 1 and 2, at least the blood introduction section 2 forming the blood introduction region A, and blood. Blood separation part 3 that connects to the introduction part 2 and forms a blood separation region B that separates blood K into plasma S or serum from the blood cell component, and plasma that is connected to the blood separation part 3 and separated and held is sucked and impregnated and temporarily held. Plasma impregnation receiving portion 4 forming the plasma impregnating receiving region C, plasma aspirating portion 5 forming a plasma suction region D that contacts the plasma impregnating receiving portion 4 and sucks plasma by the capillary force of the capillary phenomenon, the plasma portion Plasma collection 6 that forms a plasma droplet region E that is placed on an extension of 5 and takes out plasma by its own weight or the like and drops it, and plasma collection that is located below the plasma droplet 6 and forms a plasma collection region F. It is composed of a part 7.

Next, the details of each configuration of the plasma separator 1 described above will be described.
[Blood introduction part 2]
As shown in FIGS. 1, 2 and 5, a blood introduction unit 2 is provided in the upper part of the plasma separation device 1, and this blood introduction unit 2 forms a blood introduction region A, and a housing cover is provided in the upper part. A portion (lid portion) 21 is provided, a blood reservoir region (blood reservoir) 22 is formed inside the blood introduction portion 2, and a flat portion 211 on the upper surface of the housing cover portion (lid portion) 21 is shown in FIG. As shown in 2, an opening 23 for supplying blood K is arranged, a shutter 231 that moves left and right to open and close the opening 23 is provided in the vicinity of the opening 23, and a liquid contact on the inner wall of the housing cover portion 21 is provided. The portion to be treated is locally water-repellent and has a shape for guiding blood to the plasma separation portion 3 of the blood separation region B in the next step without waste.

[Blood separation unit 3]
A blood separation unit 3 forming a blood separation region B is arranged below the blood introduction unit 2, and as shown in FIGS. 2, 3 and 4, the filter unit main body 31 in the filter housing 32 of the blood separation unit 3 is housed. A filter unit storage unit 34 is provided, and the filter unit storage unit 34 is a rectangular shape composed of left and right side plate 341, front plate 342, and back plate 343 in an open state so as not to leak blood to the outside. It is made of a water-repellent synthetic resin or a water-repellent fiber laminate.
The filter of the blood separation unit 3 is a similar material of fibrous laminate and is composed of a material used for a plasma separation device (for example, GE Healthcare Japan Co., Ltd., trade name MF1 (material: bound glass fiber), and swells. The mechanical strength that does not become flexible is maintained, and the housing opening / closing door 33 is opened to enable inspection and replacement as needed.
The blood separation unit filter unit main body 31 supports a blood reservoir region 22 and holds a blood retention / plasma separation filter 311 (width 13 mm × length 120 mm × thickness 0.37 mm (width 13 mm × length 120 mm × thickness 0.37 mm) for separating plasma while retaining blood. Folded side length 15 mm)), blood cell trap prefilter 312 (width 13 mm x length 15 mm x thickness 0.37 mm) that impregnates blood and traps blood cells, acting as a prefilter, only plasma and liquid components It is composed of a plasma transfer filter 313 (width 13 mm × length 31 mm × thickness 0.37 mm) that moves downward.
Both ends of the blood retention / plasma separation filter 311 of the blood separation section are in contact with the blood reservoir region 22 of the blood introduction section 2 and are shaped so as to introduce all of the supplied blood. The central part of the separation filter 311 located at the lower part forms a zigzag-folded folded part 3111, and the area of the blood retention / plasma separation filter 311 in contact with blood is dramatically expanded and supplied. It is designed to handle large amounts of 1 mL to 5 mL of blood.

The material of the filter member of the blood separation unit 3 and the plasma impregnation receiving unit 4 described later is not particularly limited to the embodiment, but for example, a fiber made of a synthetic polymer or glass having a desired fiber diameter or a highly porous material. It can be used as long as it has a function and effect as a blood separation member in a laminated body such as a paper-like material or a thin non-woven fabric made of molecules.
However, when the measurement component in blood is adsorbed, it is desirable to surface-treat the material constituting the filter member. The surface treatment agent is not particularly limited, but is such as a lubricant such as a polyether or silicone type, a hydrophilic polymer such as polyvinyl alcohol or polyvinylpyrrolidone, a natural hydrophilic polymer, or a polymer surfactant. Can be used. The blood separation member also includes a member to which a special binder such as an antibody that captures a cell component of blood is bound.
On the other hand, when blood, blood cell components, and plasma are not positively adsorbed on the blood separation member and the impregnated area is limited, it is desirable to surface-treat the material constituting the filter member. The surface treatment agent is not particularly limited, but a fluorine-based or silicone-based material exhibiting water repellency may be used.

A blood cell trap prefilter (plasma separation prefilter) 312 that also functions as a prefilter is inserted into the upper surface side of the folded portion 3111 of the blood retention / plasma separation filter 311, and plasma movement having a function of sucking out plasma components is inserted on the lower surface side. The filter 313 is inserted.
Therefore, when the blood sample is supplied to the blood introduction unit 2, blood is received in the blood reservoir region (blood reservoir) 22 of the blood introduction unit 2, and at the same time, in the region surrounded by the blood retention / plasma separation filter 311, on the upper surface side. A part of blood cells is trapped in the inserted blood cell trap pre-filter 312, and the blood permeated by the blood retention / plasma separation filter 311 is separated into plasma and cell components. Further, the separated plasma moves the plasma and the liquid component downward while the blood is separated into the plasma and the cell component by the plasma movement filter 313 inserted under the side.
At the lower end of the plasma transfer filter 313, a plasma impregnation receiving portion 4 forming the plasma impregnation receiving region C in the next step is provided.

[Plasma impregnation receiving part 4]
The plasma impregnation receiving unit 4 is connected to the plasma transfer filter 313 of the blood separation unit 3 and efficiently impregnates and sucks the plasma exuded from the upper part to the lowermost surface of the plasma transfer filter 313 to move the separated plasma. This plasma is impregnated to form a plasma impregnation receiving region C that is temporarily held. Therefore, the plasma impregnation receiving portion 4 needs an area for receiving the plasma transfer filter 313, which is a rectangular plasma having a length of 10 mm, a width of 15 mm, and a thickness of 0.37 mm covering the plasma transfer filter 313 in this embodiment. The impregnation filter 41.
The plasma impregnation receiving portion 4 receives plasma that comes into contact with the plasma moving filter 313 and moves downward inside the plasma moving filter 313. For example, in the embodiment, the same material (GE Healthcare) of the blood separating portion 3 is used. Japan Co., Ltd., trade name MF1 (material: bound glass fiber). This material is not limited to the examples, but must be a material sufficiently impregnated with moving plasma. The plasma impregnation receiving portion 4 must be such that the upper tip of the plasma suction portion 5 in the next step is in contact with the lower surface and the plasma suction portion 5 sucks plasma by the capillary force.

[Plasma suction unit 5]
In this embodiment, the plasma suction portion 5 forming the plasma suction region D is housed in a removable cylindrical hollow housing 55 as shown in FIGS. 6, 7 and 8, and the tip portion thereof is a plurality of flat plate-shaped members. The first flat plate 51 and the plate-shaped glass which is the second flat plate 52 are combined in a T-shaped cross section to have a proximity portion 53 with respect to the plasma impregnation receiving portion 4, and the plate-shaped glass is pressed so as to bite into the plasma impregnation receiving portion 4. The upper tip portion 512 and 522 are provided, and the proximity portion 53 has a fine gap 541 to form the gap portion 54. As shown in FIG. 8, the contact surface of the proximity portion 53 with the plasma impregnation receiving portion 4 is the flat surface portion 511 of the first flat plate 51, and the side surface portion 521 of the second flat plate 52. It is T-shaped, and the gap 54 is formed without the contact surfaces of the first flat plate 51 and the second flat plate 52 forming the T-shape being in close contact with each other.
The plasma suction unit 5 may have a plate-like hydrophilic plate shape, may be a plastic such as polycarbonate other than glass, or may have a surface treated with hydrophilicity.
Then, as shown in FIGS. 8 and 9, when the upper tip is brought into contact with the lower surface of the plasma impregnation receiving portion 4 so as to bite into the lower surface of the plasma impregnated receiving portion 4, and the plasma impregnated receiving portion 4 is sufficiently impregnated with the plasma S, the plasma S becomes the lower surface. Plasma S is sucked one after another from the gap 54 having a fine interval for generating the capillary force formed in the proximity portion 53 by exuding to the vicinity including the flat plate-shaped members 51 and 52. The plasma suction region D is also a contact region where the first flat plate 51 and the second flat plate 52 come into contact with each other, but when the vertical distance of the plasma suction region D becomes long, a gravitational action is added and the suction force increases as a result. To do. However, if it becomes too long, the influence of the suction force weakens. Therefore, in consideration of the size of the entire device, in this embodiment, the length of the plasma suction area D is 100 mm cm in consideration of the suction force and the size of the device. It was about.
The gap between the gaps 54 in the above is preferably about 0.05 to 0.3 mm at which capillary force is generated in plasma S, and is about 0.1 mm at the distance in this example. However, if necessary, the gap 54 may be formed by interposing a fine spacer.
The configuration of the plasma absorbing portion 5 is not limited to the present embodiment having a T-shaped cross section, and other configurations may be used as long as a minute gap is formed to generate capillary force, such as a blood introduction portion, a blood separation portion, and plasma. It can also be applied to a plasma separator having an impregnation receiving portion or the like.

[Plasma droplet part 6]
The plasma S drawn from the plasma suction unit 5 is continuously located on the extension 61 of the side surface of the second flat plate 52 in the plasma suction unit 5, and drops the plasma while continuously wetting downward along the hydrophilic surface. Has a sharp edge shape. The plasma dropleting section 6 forming the plasma dropletation region E from which the plasma is taken out by its own weight or the like and dropletized will be described.
The plasma droplet unit 6 forming the plasma droplet region E releases the capillary force and causes the plasma to fall and move by its own weight, that is, allows free movement.
Then, the plasma that has become freely movable is guided to the spear-tip-shaped lower tip portion 62 on the extension portion 61 of the side surface portion 521 of the second flat plate 52. The length of the side surface of the second flat plate 52 in the plasma dropletation region E was set to about 40 mm in this example.
In this way, utilizing the movement of plasma separation by capillary force and natural weight makes it difficult to extract the separated plasma without using capillary force, and blood cells are separated by sucking air. It was found by experiments that plasma was also mixed. Therefore, it was found that it is important to utilize capillary force and natural weight drop for plasma separation.
Further, plasma is guided from the gap portion 54 of the plasma suction portion 5 to the lower tip portion 62 of the plasma droplet portion 6 at high speed in a short time. The first flat plate may be shorter than the second flat plate.

[Plasma collection unit 7]
The plasma collection unit 7 is located below the plasma droplet unit 6 to form a plasma collection region F, and is dropleted from the lower tip portion 62 or along the inner wall surface of the plasma collection unit 7 in the reverse manner in this embodiment. Although it is a conical portion 71, it is collected by the inverted conical portion 71. Further, the plasma recovery unit 7 is made removable after the plasma S is collected and is used for inspection. However, the cylindrical housing 55 and the plasma collection unit 7 are removed as a unit, or only the inverted conical portion 71 is used. May be removed.
The plasma collection unit 7 may have a shape for collecting the plasma S droplets formed by the plasma droplet unit 6 or a shape for accommodating a container for various purposes. For example, it may be directly connected to a dedicated sample cup such as an automatic biochemical analyzer or a collection container such as a vacuum blood collection tube.

As described above, the recovery of the recovered plasma and the amount of the recovered plasma were inspected using the plasma separation device of the above-mentioned example.
First, using this example, the amount of plasma (S) taken out after 10 minutes has passed from the amount of supplied blood (K) is examined and shown in [Table 1].

[Table 1]
Amount of blood supplied (K) Amount of plasma (S) taken out Separation time Example 1 100 μL 0 μL 10 minutes Example 2 1 mL 150 μL 10 minutes Example 3 2 mL 300 μL 10 minutes Example 4 5 mL 750 μL 10 minutes Example 5 6 mL Overflow Experiment impossible

As can be seen from [Table 1], when 1 mL to 5 mL of blood was supplied to the apparatus of this example, 150 μL to 750 μL of plasma was obtained in 10 minutes.
From the results of this experiment, it can be seen that when the amount of supplied blood (K) is about 100 μL as in Example 1, plasma stays in the filter and does not drip and is not suitable for a small amount of blood, and conversely, it is 6 mL or more. Blood overflows from the blood reservoir region 22 and plasma separation cannot be performed. In this example, the range of 1 mL to 5 mL is suitable for plasma separation, and preferably, when 2 mL to 5 mL of blood is supplied, 300 μL to 750 μL of plasma is obtained in 10 minutes.

［表２］に示されるように。本実施例３による血漿と比較例の遠心分離法による血漿の残留血球成分を比較しても遜色ない結果が得られ、本実施例の血漿分離装置の血液中細胞成分分離性能が示された。 Next, the plasma components of this example will be compared with the plasma components obtained by the centrifugation method and described in [Table 2].
In [Table 2], blood components from which plasma has not been separated and plasma collected by a conventional centrifugation method are compared with a comparative example (conventional example) and the above-mentioned Example 3 of the present invention to examine the components. It was.
That is, 300 μL of plasma was obtained from 2 mL of blood, and residual blood cells and the like of plasma were measured. In the experiment, hematocrit value 43.9%, red blood cell count 477 × 104 / μL, heparin as an anticoagulant, and blood to which no preservative solution was added were used. Blood cells were measured with a multi-item automatic blood cell analyzer (Sysmex Corporation: XE-5000). Plasma by the centrifugation method was collected using a small cooling centrifuge (Hitachi, Ltd .: HITACHI CF15 RXII) under the conditions of a temperature of 4 ° C., a centrifugal force of 2500 g, and 5 minutes.
[Table 2]

As shown in [Table 2]. Comparing the residual blood cell components of the plasma according to Example 3 and the plasma by the centrifugation method of Comparative Example, the results were comparable, and the blood cell component separation performance of the plasma separator of this Example was shown.

本実施例による血漿（同一仕様のもので４個で実施）と従来の遠心分離法による血漿の残留血球成分を比較しても希釈血漿測定データを比較しても、希釈倍率補正値を勘案しても、本実施例により得られた値は、遠心分離法による比較例の値と、かなり近似していることが分かり、本発明の実施例により回収された血漿の生化学的性状に問題は無いことが示された。
以上のことから、本発明の実施態様の血漿分離装置は、血液生化学的検査の検体採取のための装置として有効性が示された。
[Biochemical test results of recovered plasma]
In addition, the results of biochemical property analysis of plasma separated and recovered from blood using the plasma separator of the above-mentioned example are shown in [Table 3].
Similar to Example 3 above, each test target in this experiment was plasma obtained by obtaining 300 μL of plasma from 2 mL of blood and collected by plasma centrifugation (Comparative Example) and plasma collected in Example 3. Samples 1 to 4 of No. 1 to 4 were diluted 3-fold with physiological saline, and a general biochemical test was performed using this as an assay sample with an automatic biochemical analyzer (Hitachi High Technologies Co., Ltd .: HITACHI 7180 type). Biochemical tests were performed on 9 items: T-CHO, LDH, HDL, LDL, TG, T-BIL, CRE, UA, and UN. Plasma by the centrifugation method was collected using a small cooling centrifuge (Hitachi, Ltd .: HITACHI CF15 RXII) under the conditions of a temperature of 4 ° C., a centrifugal force of 2500 g, and 5 minutes.
[Table 3]

Whether comparing the residual blood cell components of the plasma according to this example (implemented with 4 pieces of the same specifications) and the residual blood cell components of the plasma by the conventional centrifugation method or comparing the diluted plasma measurement data, the dilution ratio correction value is taken into consideration. However, it was found that the values obtained in this example were fairly close to the values in the comparative example by the centrifugation method, and there was a problem with the biochemical properties of the plasma recovered by the examples of the present invention. It was shown that there was none.
From the above, the plasma separation device of the embodiment of the present invention has been shown to be effective as a device for collecting a sample for a blood biochemical test.

According to an embodiment of the plasma separation apparatus of the present invention, a plurality of hydrophilic members are combined to provide a proximity portion having a gap that generates capillary force, and plasma is sucked and taken out from the gap by the capillary force. As another example, as shown in FIG. 10, it is a bottom view showing a state in which plasma is exuded when viewed from the lower side of the plasma impregnation receiving portion 4, but the gap portion 54 is largely removed. If (specifically, two gaps 54 are provided), a large amount of plasma can be taken out at a higher speed. For example, if the number is increased to two, the recovery performance can be increased by about 1.5 times. Since other configurations are the same as those in the above-described embodiment, the description thereof will be omitted.

As described above, the plasma or serum separation device and method of the embodiment of the present invention do not require a centrifuge, a suction / pressurization device, electric power, etc. at all, and even a general person who has not received training in the procedure can use it. It is possible to prepare a sample for a blood test easily, quickly, inexpensively and safely.
With this device and method, it is easy to operate, does not require specialized skills, and can easily, quickly, and inexpensively hemolyze even in areas without advanced analytical instruments such as centrifuges. The liquid component (plasma or serum) can be safely separated from a predetermined amount of blood without worry. Moreover, not only the separated liquid component but also the cell component can be used as a blood test sample.

INDUSTRIAL APPLICABILITY The present invention does not require a centrifuge or the like in a blood test, and even a general person can easily, safely, and inexpensively separate blood components, which is useful as a test sample.

A ... Blood introduction area, B ... Blood separation area, C ... Plasma impregnation receiving area,
D ... Plasma suction area (contact area), E ... Plasma droplet area,
F ... Plasma recovery area, K ... Blood, S ... Plasma,
2 ... Blood introduction part, 21 ... Housing cover part,
211 ... Flat part,
22 ... Blood reservoir area, 23 ... Opening, 231 ... Shutter,
3 ... Blood separation part, 31 ... Filter unit body,
311 ... Blood retention / plasma separation filter,
3111 ... Folded part 312 ... Blood cell trap prefilter (plasma separation prefilter),
313 ... Plasma transfer filter,
32 ... Filter housing, 33 ... Housing opening / closing door,
34 ... Filter unit storage, 341 ... Side plate, 342 ... Front plate,
343 ... back plate,
4 ... Plasma impregnation receiving part, 41 ... Plasma impregnation filter,
5 ... Plasma suction part,
51 ... 1st flat plate part (flat plate-shaped member), 511 ... Flat surface part,
512 ... Upper tip,
52 ... 2nd flat plate part (flat plate-shaped member), 521 ... side surface part,
522 ... Upper tip,
53 ... Proximity, 54 ... Gap, 55 ... Cylindrical housing 6 ... Plasma droplets, 61 ... Extension, 62 ... Lower tip 7 ... Plasma recovery, 71 ... Inverted cone Department

Claims (4)

A plasma separator having a blood separation unit composed of a fibrous filter that separates blood cells and plasma, and a plasma collection unit that collects the separated plasma.
The blood separation section has a plasma impregnation receiving section that impregnates plasma at the lower end thereof.
The plasma collecting portion has a tip portion that comes into contact with the lower surface of the plasma impregnation receiving portion so as to bite into the plasma collecting portion, and the tip portion forms a gap portion that generates capillary force by combining a plurality of hydrophilic members.
The gap is formed by a contact portion between the flat surface portion of the first flat plate and the side surface portion of the second flat plate of the hydrophilic member.
A plasma separator characterized by sucking and taking out plasma by capillary force. The plasma separation apparatus according to claim 1, wherein the side surface portion of the second flat plate extends downward beyond the contact portion, and the area of the lower tip thereof is gradually reduced. It is aspirated by a blood separation region consisting of a fibrous filter that separates blood cells and plasma, a plasma impregnation receiving region that impregnates and temporarily holds the separated plasma, and a gap that generates capillary force from the plasma impregnation receiving region. This is a plasma separation method in which a plasma suction region is provided to suck and remove plasma.
The gap is formed by a contact portion between the flat surface portion of the first flat plate and the side surface portion of the second flat plate of the hydrophilic member.
A plasma separation method characterized by sucking and taking out plasma by capillary force. The plasma separation according to claim 3, wherein the side surface portion of the second flat plate extends downward beyond the contact portion to form a plasma recovery region, and the area of the lower tip is gradually reduced. Method.

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