JPH01155265A - Assorting apparatus of liquid - Google Patents

Abstract

PURPOSE:To prevent the stay of a liquid due to mixing-in of a vapor and also to shorten a time for a separating operation, by providing a stock liquid cham ber in which a stock liquid is sealed up in a filled-up and flowing state, a sepa rated component chamber and a liquid separator through which an assorted liquid passes. CONSTITUTION:In an assorting apparatus of a liquid, a blood-collecting tube connected to a vein of a rabbit, for instance, is coupled to a stock liquid introduction channel 7. On the occasion, a chemical, e.g. a coagulation preventing agent, is added in the middle of the blood-collecting tube as occasion demands. The blood flowing into a stock liquid chamber (recess) 3 from the stock liquid introduction channel 7 is filled up and flows inside this stock liquid chamber (recess) 3, and it passes through a treated liquid lead-out tube coupled beforehand to a nozzle 44 having a treated liquid lead-out channel 42, and is collected in an appropriate vessel. In this system, a pressure is given to a separator in the main body 1 of a separating chamber. Blood plasma components are divided by this pressure and a shearing force made to act on a separating membrane by a rotary body rotating in the main body 1 of the separating chamber, and they are stored in a blood plasma storing bag E.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Application Field] The present invention relates to an apparatus that continuously separates desired components from a continuously supplied liquid. The present invention relates to a liquid sorting device that is preferably used, for example, to continuously separate plasma components from blood that is continuously collected from a living body.

[Prior Art] As a means of separating liquids, a separation method in which a shear rate is actively applied to the liquid is known, and in particular, a specific device for separating plasma acid from blood is disclosed in Japanese Patent Laid-Open No. 62-2179.
There is a dispute described in Publication No. 73.

This conventional example is a device consisting of a disc or cone-shaped rotating body with an apex angle close to 180° and a separation membrane.The liquid is introduced from near the center of the circular membrane, flows through the gap between the rotating body and the membrane, and rotates. It is derived from near the outer circumference of the body. In this filtration device, a shear rate determined by the rotation speed of the rotating body and the gap distance between the rotating body and the membrane is added to the treated liquid, so it is more effective than a static filtration device using hollow fiber membranes. , a filtration flux (filtration flow rate per unit membrane area) of 10 times or more can be obtained, and the required membrane area is also 1/10 or less.

[Problems to be Solved by the Invention] In the conventional example described above, the processing liquid is introduced from near the center of the circular separation membrane, that is, from near the center of the rotating body, and is led out from near the outer periphery of the rotating body. Although this seems natural since the processing liquid flows in the direction of centrifugal force, it is very inconvenient if gas is mixed into the processing liquid. This is because the gas, which has a significantly lower specific gravity than the processing liquid, gathers near the center of the rotating body, that is, near the processing liquid introduction path, continues to stay in the device, and covers the separation membrane. As a result, the effective area of the separation membrane decreases and the filtration flow rate decreases, making it necessary to interrupt the operation and deal with the gas within the device. In particular, when processing blood or protein solutions, if the rotating body is operated with gas mixed in, the liquid will foam significantly, causing serious problems such as damage to blood cell components and denaturation of proteins. Therefore, when using a conventional device to perform so-called donor plasmapheresis, in which only plasma is continuously collected from the human body and concentrated blood is returned to the human body, physiological saline is filled into the device in advance, and the inside of the device is However, this method requires work to sufficiently handle the gases, which lengthens the installation time, and furthermore, there are problems in that the collected plasma is diluted with physiological saline.

This invention focuses on the problems of the prior art described above, and provides a liquid fractionation device that continuously separates desired components from a continuously supplied liquid.In particular, when blood is collected, liquid stagnation due to gas contamination is provided. The purpose of the present invention is to provide an apparatus for separating blood that prevents deterioration of liquid components.

[Means for Solving the Problems] The configuration of the apparatus of the present invention for achieving this object is as follows.

(a) A raw liquid chamber filled with the raw liquid and sealed so that it can flow; (1) A separated component chamber; (c) A separation wall surface of a certain width, which separates the raw liquid chamber from (2) a liquid separator interposed between the component chamber and through which the fractionated liquid passes; (e) a drive mechanism that engages with the rotating body and rotationally drives the rotating body; (f) provided in communication with the raw liquid chamber; and ( g) a processing liquid outlet path provided in communication with the source liquid chamber and having an opening formed at a position near the axis of the rotating body on the separation wall surface side of the rotating body; ) a separated component outlet path provided in communication with the separated component chamber; and an apparatus for separating a liquid.

Here, in the apparatus of the present invention, the raw liquid is a liquid containing desired components to be separated, and what kind of raw liquid can be processed by the apparatus of the present invention is mainly determined by the raw liquid according to the present invention. It is selected depending on the material, structure, etc. of the liquid separator (separator for separating liquid, separation membrane, separation plate, etc.) used in the device, or the shear rate applied to the liquid.

This liquid separator may be of any type as long as it can separate the desired components from the liquid in a field where a shear rate acts, and of course any currently known separator that can be used effectively for liquid separation under this situation is acceptable. Under these circumstances, separators that are currently under development or will be developed in the future are used that can be effectively used to separate liquids. Incidentally, the first membrane-like separator (separation membrane) shown in Table 1 is preferably used.

Further, in the apparatus of the present invention, when a separation membrane is used as the liquid separator, the surface area of the separation membrane is 10cnf.
200o+f is preferable.

Furthermore, in the device of the present invention, the shear wall surface is
A wall surface that imparts movement to the liquid that fills and intervenes between this wall surface and the separation wall surface of the separator, and that acts to generate a shear rate between the liquid and the separation wall surface due to this movement.

Furthermore, in the device of the present invention, when both the shear wall surface and the separation wall surface are flat, the gap between these flat surfaces is
The diameter is preferably 0.05 mm to 2 mm, and the diameter is preferably 35 mm to 170 mm. In addition, if one or both of the shear wall surface and the separation wall surface is formed of a convex conical surface facing the other side, the intersection angle formed by both wall surfaces should be selected from 0.5 degrees to 3 degrees. is preferable, and the diameter of the conical surface is 3Qmm to 160mm.
It is preferable that

Further, it is preferable that the gap between the rotating body and the inner surface of the raw liquid chamber located on the side opposite to the separation wall side of the rotating body is 0.05 mm to 2 mm. In particular, if the raw liquid is easily damaged by shear force, such as blood, the gap should be closed so that the shear force generated in the gap does not exceed the value of the shear force generated at the shear wall surface and the separation wall surface. Must be set.

The position of the raw liquid introduction path that communicates with the raw liquid chamber is as follows:
An opening must be provided on the opposite side of the rotating body to the separation wall side, at a position that is at least 1/2 the radius of the rotating body from the axis of the rotating body. Note that this opening is 5 mm to 20 m from the outermost periphery of the rotating body in the axial direction of the rotating body.
It is preferable to set it to m.

Further, the processing liquid outlet path provided in communication with the raw liquid chamber must have an opening near the axis of the rotating body on the separation wall side of the rotating body.

Furthermore, in the apparatus of the present invention, it is preferable that the separating wall surface is a flat surface and that the shearing wall surface opposite thereto is a conical surface.

The shear rate used when using the device of this invention is 1000 sec-1 to 18000 sec-1.
1 is preferable, and the number of rotations of the rotating body is 500.
rDIIl to 3000 ram is preferred.

In the device of the present invention configured in this way, the rotating body is rotated in a sealed source liquid chamber by an appropriate rotational drive source, and the rotating body is positioned opposite to the shear wall surface of the rotating body.・The raw liquid is continuously introduced between the raw liquid introduction path that communicates with the raw liquid chamber and the separation wall formed by the liquid separator, and while the raw liquid chamber is filled and flowing, In the processing space between the shearing wall surface and the separation wall surface, the raw liquid undergoes rotational movement due to the rotation of the shearing wall surface, producing a shearing rate between it and the separating wall surface, and under this shearing rate, the liquid separator Depending on the performance, the desired component is separated from the raw liquid through the liquid separator, and this separated component flows into the separated component chamber, is led out from the separated component outlet passage communicating with the separated component chamber, and is transferred to a suitable receiver. On the other hand, the surplus liquid in the raw liquid chamber (mainly the liquid after the desired separation components have been separated) is discharged from the treated liquid outlet path that communicates with the raw liquid chamber. and appropriate containers are collected in a container. Note that, if necessary, the collected liquid is returned to the system from which the original liquid has been continuously collected, either directly or by temporarily stopping the fractionation action and retracing the liquid flow path. .

[Embodiments] Next, preferred embodiments of the apparatus of the present invention will be described with reference to the drawings.

FIG. 1 is a longitudinal sectional view of an apparatus for separating liquid according to an embodiment of the present invention, and FIG. 2 is a side view showing half of the right side of the apparatus shown in FIG.

The separation chamber main body 1 having a raw liquid chamber 3 and a separated component chamber 14 therein includes a cabin 2 made of polycarbonate,
The cover 12 is also made of polycarbonate.

A circular recess (raw liquid chamber) 3 is formed on the right side of the cabin 2 (in FIG. 1), and a shaft hole 4 penetrating into the recess 3 is formed at the center of the left side. On the left end surface of the outer peripheral edge of the cabin 2, there is an annular O.
A groove 5 for a ring is formed, and furthermore, a groove 6 for an O-ring is formed in the middle part of the shaft hole 4. Further, the cabin 2 is provided with a raw liquid introduction path 7 having one end opening into the recess 3 near the outer periphery of the recess 3 and the other end opening into the outer circumferential surface of the cabin 2 . Further, the recess 3
The opening portion is formed on a side of the rotary body opposite to the separation wall surface, at a position spaced from the axis of the rotary body by 1/2 or more of the radius of the rotary body.

Roughly speaking, a plurality of bolt holes 9 are bored in the peripheral edge of the cabin 2, passing through the left and right end surfaces.

In addition, on the left side of the cover 12 (in FIG. 1),
A circular annular recess (separated component chamber) 14 having an apex 13 at the center is formed, and from the right side, a tubular body insertion hole 15 penetrating the recess 14 is formed at the center of the recess 14. An annular gasket groove 16 is formed on the left end surface of the cover 12 outside the recess 14, and an O-ring notch 17 is formed on the right end of the tubular body insertion hole 15. Further, a liquid collection groove 18 is carved in the outer peripheral edge of the recess 14 of the cover 12, and one end is opened to the liquid collection groove 18, and the other end is opened to the outer peripheral surface of the cover 12. A separated component lead-out path 19 is provided. Moreover, furthermore,
A number of bolt holes 20 corresponding to the bolt holes 9 passing through the left and right end faces are bored in the peripheral edge of the cover 12.

Further, on the left end surface of the cover 12, a substantially flat circular perforated plate 3 made of stainless steel is provided, covering the recess 14.
1 is fixed, and a circular separation membrane (liquid separator) 32 made of polycarbonate forming a separation wall surface is placed on the surface of the porous plate 31 opposite to the side facing the recess 14. The outer peripheral edge of the porous plate 31 and the separation membrane 32 is connected to the cover 1.
The center portion thereof has a tubular body insertion hole 33, and the center portion is located on the top portion 13 of the cover 12.

The tubular body insertion hole 15.33 has seven flange 41 at one end.
, and has a processing liquid outlet passage 42 bored through the central portion (near the axis of the rotating body 51).

A nozzle 44 having a threaded groove 43 for nut screwing on a part of the outer peripheral surface connects the separation membrane 32 and the perforated plate 14 to the flange 41.
The nozzle 44 is tightened to the cover 12 by a nut 45 screwed into the thread groove 43 while holding down the O-ring 17A inserted into the O-ring notch 17. , is integrated with the cover 12.

On the other hand, in the recess 3 of the cabin 2, a rotating body (rotor) 51 consisting of a disk-shaped cone protruding toward the separation membrane 32 made of polycarbonate is housed. ), that is, the conical surface forms a shearing wall surface, and a rotating shaft 52 extends from the left side of the rotating body 51, and a rotational drive source (not shown) provided separately is attached to the tip of the rotating shaft 52. ), the rotary shaft 52 is fitted into the shaft hole 4 of the cabin 2 and protrudes from the left side of the cabin 2, and the rotary shaft 52 and the shaft hole 4 are connected to each other. In between, there is an O ring inserted into the O ring groove 6.
A ring 6A is interposed.

A rotating body 51 is housed in the recess 3 of the cabin 2, and the separation membrane 32, the porous plate 31, and the nozzle 44 are attached to the right side of the cabin 2, in which the O-ring 5A is inserted into the O-ring groove 5. The left side surfaces of the cover 12 to which the cover 12 is attached are brought together, and the bolt 61 is inserted into the bolt hole 9.20.
is tightened, the cabin 2 and the cover 12 are integrated, a separation chamber is formed by the recess 3 of the cabin 2 and the recess 14 of the cover 12, and a space surrounded by the recess 3 of the cabin 2 and the separation membrane 32. The space surrounded by the concave portion 14 of the cover 12 and the separation membrane 32 becomes the separated component chamber, and the shear wall surface of the rotating body 51 has a constant gap with respect to the separation wall surface of the separation membrane 32. It can be rotated freely with the .

Note that as a method of driving the rotating body 51, a means of directly driving the rotating shaft 52 has been shown, but it is also possible to attach a magnet to the rotating shaft 52,
This is magnetically coupled with a magnet attached to the drive means of the bar,
The rotating body 51 may be driven. In this case, it is preferable that the rotating shaft 52 to which the magnet is attached is built into the cabin 2.

Next, for reference, the approximate dimensions of the main parts of the above-mentioned implementation device are shown. This device is specifically designed for separating plasma from blood. Rotating body 5
The angle formed by the plane perpendicular to the axis of the rotating shaft 53 and the conical surface of the rotating body 51 has a specific angle selected in the range of 0.5 degrees to 3 degrees. The diameter of the rotating body 51 is approximately 14
0 mm, and the distance in the axial direction between the top of the conical portion of the disc-shaped portion of the rotating body 51 and the back surface of the disc-shaped rest portion is approximately 4 mm.

The depth of the recess 3 of the cabin 2 is approximately 7 mm, and the diameter of the recess 3 is approximately 143 mm. The depth of the recess 14 of the cover 12 is approximately Q, 5 mm, and the diameter of the recess 14 is approximately 143 m.
It is m. The diameter of the separation chamber body formed by integrating the cabin 2 and the cover 12 is approximately 194 mm, and the thickness is approximately 23 mm.
It is mm. The membrane thickness of the separation membrane 32 is approximately 10 μm, the separation permeation pore diameter is approximately 0.8 μm, and the separation permeation porosity is approximately 13%.
The thickness of the perforated plate 31 is approximately Q, 5 mm. Rotating body 51
The tip of the conical part of the disc-shaped body (in the rotating body of Fig. 1,
Although the tip of the cone is cut and deformed, the distance between the tip of the cone (which means the serrated tip of the cone) and the separation wall surface of the separation membrane 32 is approximately Q, 1 mm.

Next, the operation of the above-mentioned implementation apparatus will be explained while explaining the process of actually collecting blood and separating plasma.

The above-mentioned implementation device is used in the state shown in FIG. 1, that is, with the rotating shaft 52 facing vertically, and a blood collection tube (see FIG. (not shown) are combined.

At this time, if necessary, add the drug 1 in the middle of the blood collection tube.
, for example anticoagulants are added. The blood that has flowed into the raw liquid chamber (recess) 3 from the raw liquid introduction path 7 fills the raw liquid chamber (recess) 3 and flows, and the blood flows through the raw liquid chamber (recess) 3, and the processing liquid is connected in advance to the nozzle 44 having the processing liquid outlet path 42. Output tube (
(not shown) and collected in a suitable container (not shown).

At this initial point, the rotary shaft 52, which is connected in a one-touch manner to a suitable rotary drive source (not shown), is rotated by the rotary drive source at a speed of 500 rpm or less, so that the blood is transferred from the raw liquid introduction channel 7. At the same time as the gas in the raw liquid chamber (recess) 3 is continuously supplied to the outer periphery of the raw liquid chamber (recess) 3, the gas in the raw liquid chamber (recess) 3 gathers in the center of the raw liquid chamber (recess) 3 due to the action of centrifugal force. The treatment liquid is discharged into the tube through a nozzle 44 having an outlet passage 42 . On the other hand, the gas on the opposite side of the shearing wall surface of the rotating body 51 stays in the raw liquid chamber (recess) 3 and prevents excess shearing force from being applied to the blood. Such a gas discharge operation is performed promptly, and at the same time as the gas is discharged, the rotational speed of the rotating body 51 is increased from 80 Orpm to 1
Increase to 500 rpm.

The blood that is continuously supplied from the raw liquid introduction path 7 to the outer periphery of the raw liquid chamber (recess) 3 is continuously supplied between the shearing wall surface of the rotating body 51 and the separation wall surface at a rate of 50 I/min to 100 d/min. /
min inflow, the rotating shear wall imparts rotational motion to the blood, and this motion causes a shear rate to act between the blood and the separation wall, and under the action of this shear rate, plasma components , passes through the separation membrane 32 , passes through the holes in the porous plate 31 , flows into the separated component chamber (annular recess) 14 , passes through the separated component outlet path 19 , and the separated component previously bound to the separated component outlet path 19 . It is continuously collected from a discharge tube (not shown) into a suitable container (not shown).

On the other hand, the blood in the raw liquid chamber (concavity) 3, mainly blood from which plasma components have been separated, passes through the processed liquid outlet path 42.
The processing liquid is continuously collected into a suitable container (not shown) from a processing liquid outlet tube (not shown) which is previously connected to a nozzle 44 having the processing liquid outlet passage 42 .

In addition, in the above-mentioned implementation device, a combination format is used in which the shear wall surface is a conical surface convex toward the separation wall surface, and the separation wall surface is a circular plane. A type in which the separation wall surface is a conical surface convex toward the shear wall surface, and the shear wall surface is a conical surface convex toward the separation wall surface, and the separation wall surface is also a conical surface convex toward the shear wall surface. A type of type in which the shear wall surface is a circular plane and the separation wall surface is also a circular plane;
Alternatively, a somewhat modified version of these may be used. However, this penultimate type is not preferred where strict uniformity of shear rate over the radial position of the shear wall is required.

FIG. 3 is a system diagram illustrating an example of a blood sampling system using the device according to the present invention. In this blood collection system, the device shown in FIG. 1 is used as a device for separating liquid (blood). That is, this separation device consists of a separation chamber main body 1 shown in FIG. Liquid (processed blood) outlet path 42
, a separation component (mainly plasma component) lead-out path 19 is provided. A blood flow path 111 is connected to the blood introduction path 7, and a pump (roller pump) is connected to the blood flow path 111.
A is involved. Further, a treated blood flow path 113 is connected to the treated blood outlet path 42, and a treated blood storage bag B is connected to the end thereof, and a clamp mechanism C is interposed between them. The separation chamber main body 1
On the side, a pressure gauge is provided. Moreover, furthermore,
A plasma component flow path 114 is connected to the plasma component outlet path 19, and a plasma component storage bag E is connected to the end thereof. In this system, the raw liquid chamber (blood chamber) within the separation chamber main body 1 is pressurized by pump A, and pressure is applied to the separator (separation membrane) within the separation chamber main body 1. Plasma components are separated by this pressure and the shearing force caused by the rotating body rotating within the separation chamber main body 1 and acting on the separation membrane, and the plasma components are stored in the plasma storage bag E.

The pressure inside the separation chamber main body 1 is detected by a pressure gauge.

Based on this detection signal, a control system (not shown) is installed that automatically adjusts the opening degree of the clamp C or the rotation speed of the pump A, and monitors the separation action inside the separation chamber main body 1. It may also be possible to automatically adjust the operation for discharging the gas in the raw liquid chamber. In addition, if a pump F similar to pump A (shown in parallel with clamp C and indicated by a dotted line in FIG. 3) is provided in place of clamp C to discharge the treated blood, the pressure inside the separation chamber main body 1 can be reduced. It is possible to reduce or eliminate the problem of hemolysis and the problem of piping coming off due to high pressure. Also,
If the treated blood in the treated blood storage bag B is to be sent back and returned to the blood vessel, the pump F provided in place of the pump A and clamp C may be reversed, and at this time, the detection signal of the pressure gauge Accordingly, a control system (not shown) may be provided to automatically control these pumps. Furthermore, by providing a pump G shown in dotted lines in FIG. 3 in the plasma component flow path 114, the operating pressure within the separation chamber main body 1 may be further reduced, and the flow rate of the plasma component may be further reduced. may be controlled.

[Operations and Effects of the Invention 1] The device of the present invention uses a liquid separator and a rotating body, and in particular, the position of the opening of the raw liquid introduction path provided in communication with the raw liquid chamber is determined by separating the liquid from the rotating body. Formed on the side opposite to the wall side, at a position more than 1/2 the radius of the rotating body from the axis of the rotating body,
In addition, since the opening of the processing liquid outlet connected to the raw liquid chamber is formed near the axis of the rotating body on the separating wall side of the rotating body, the rotating body can be By operating this system, it became possible to discharge the gas existing between the liquid separator and the rotating body by the action of centrifugal force.

Therefore, compared to the conventional device described above, the required separation operation time can be shortened. The operation time is about 40 minutes, of which about 10 minutes is spent filling the device with physiological saline, but in the device of this invention, filling the device with physiological saline is not necessary, so the time is 30 minutes. This has the effect that only a short amount of operation time is required.

In addition, in the conventional device, blood fills all the spaces within the device, so extra shearing force is applied to the blood on the side opposite to the liquid separator. There is a problem in that blood cell components such as red blood cells and platelets are damaged due to residence time and continued application of shear force.

In contrast, in the device of the present invention, the space on the opposite side of the liquid separator is filled with gas, which prevents excess shearing force from being applied to the blood and prevents blood from stagnation. Therefore, there is no problem of damage to blood cell components.

Furthermore, compared to the conventional apparatus, the separation speed is 50% faster.
An unexpected effect was also observed, which was an increase of about 1.5%. Incidentally, the hematocrit (volume fraction of blood cell components) was 40% of blood flows into the device at a flow rate of 100 d/min, and the rotation speed of the rotating body is set to aoorpm.
.

Table 2 shows the results of a comparison of the maximum plasma flow rates obtained when the settings were 1000 rpm and 12 oorpm.

[Brief explanation of the drawing]

FIG. 1 is a longitudinal sectional view of a device for separating liquid according to an embodiment of the present invention, FIG. 2 is a side view showing half of the right side of the device shown in FIG. 1, and FIG. FIG. 2 is an explanatory diagram of a blood sampling system in which the device according to the present invention shown in FIG. 1 is used. 1: Separation chamber body 2; Cabin 3: Recess (raw liquid chamber) 4: Shaft hole 5: O-ring groove 6: O-ring groove 7: Raw liquid introduction path 9: Bolt hole 12: Cover 13: Top 14: Annular recess (separated component chamber) 15: Annular body insertion hole 16: Groove for packing 17: Notch for 0 ring 18: Liquid collection groove 19: Separated component outlet path 20: Bolt hole 31: Porous plate 32: Separation membrane (liquid Separation body) (separation wall surface) 33: Annular body insertion hole 41: Flange 42: Processing liquid outlet path 43: Thread groove 44: Nozzle 45: Nut 51: Rotating body (shearing wall surface) 52: Rotating shaft 53: Connection portion 61: bolt

Claims (1)

[Claims] (1) (a) A raw liquid chamber that is sealed so as to be filled with and circulate the raw liquid; (b) a separated component chamber; and (c) a raw liquid chamber that has a separation wall surface of a certain width. and a liquid separator through which the separated liquid passes, which is interposed between the separated component chamber and the separated component chamber; a disk-shaped rotating body rotatably disposed within the raw liquid chamber; (e) a drive mechanism that engages with the rotating body and rotationally drives the rotating body; and (f) communicating with the raw liquid chamber. an undiluted liquid introduction path, the opening being formed at a position on a side of the rotating body opposite to the separation wall side and at a position away from the axis of the rotating body by 1/2 or more of the radius of the rotating body; and (g) a processing liquid outlet path that is provided in communication with the raw liquid chamber and has an opening formed at a position near the axis of the rotating body on the separation wall surface side of the rotating body. (h) a separated component outlet path provided in communication with the separated component chamber; an apparatus for separating a liquid, comprising: