JPS59168843A - Method and filter for sampling serum specimen - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION The subject of the invention is a method for collecting plasma samples from patients, in particular during hemodialysis treatment, and a filter therefor.

Patients with defective or diseased kidneys may require regular hemodialysis to remove from the blood, the plasma component of the blood, the buildup of waste products that are constantly removed by the kidneys in healthy individuals. It is well known that this is necessary. The dialysis machine used is usually referred to as an artificial kidney. Such hemodialysis is effective in removing waste products from the blood stream through the purifying action of the hemodialysis membrane. Dialyzate, a purifying fluid containing the necessary salt solution, flows along the side of a thin membrane pond as the patient's blood power ζ is constantly pumped through the artificial kidney during treatment, typically from ≠ hours to hours. It is pushed out using a pump. Chemicals that accumulate daily due to kidney failure are transported from the blood through the N membrane by diffusion and are washed out by dialydate.

Fluid that accumulates in the blood when urine is not excreted also
The generation of hydrostatic pressure from the blood to the fialysate causes this thin film to be removed by IV+1. This treatment is usually required three times a week and is very effective.

However, adequate recovery in patients with kidney disease is limited by the 11°C anemia that is so common in these patients. This is due to a lack of hormones normally produced by healthy kidneys that stimulate the production of the reverse Jl'l1 bulb. Despite years of research seeking ways to reverse the deficiency of this substance due to kidney disease, this deficiency
: Unable to recover.

The blood of the individual was collected for chemical analysis of the plasma in order to monitor the effectiveness of the treatment and to determine the need for any adjustments that may be necessary due to the individual's deviation from the dietary restrictions. It is necessary to take frequent samples of
Anemia in children becomes significantly worse.

Current practice is to collect whole blood samples directly from the patient at the beginning, end, and occasional intervals of hemodialysis treatment.

In each case of sample collection, the plasma is then separated from the blood (MJJ, a component of the cytoplasm that contains the red blood cells, which forms a pool), generally by centrifugation, and the plasma is analyzed to determine its components, especially its waste product content. Determine.

This current procedure of taking multiple samples of a patient's whole blood has the significant drawback that a significant amount of erythrocytic cells are lost from the patient.

Although the traditional method used to separate plasma from the cellular components of blood, at least in connection with blood dialysis, is centrifugation, pore sizes that prevent the passage of cells but allow the passage of plasma It is known to separate plasma from cellular components by filtering blood through a cross-flow filter having a filtration medium with a filtration medium of 100%. U.S. Patent No. 3.7 (B
;, No. 100 discloses such a filtration method. The method of this patent No. 3.703.100 is based on a method in which the patient's plasma is removed, processed, and returned to the patient. 7 o v 7 x (plasmaphores
is) and to obtain plasma from blood donors.

It is an object of the present invention to develop a method in which there is no loss of patient blood cells and minimal loss of plasma, and the analytical results of each plasma sample accurately reflect the actual composition of the patient's plasma at the time it is taken. Another object of the present invention is to provide a method for periodically collecting plasma samples from patients undergoing hemodialysis, and a filter for the same. This objective is achieved as follows. That is, as the patient's blood enters or exits the hemodialyzer, a filtration medium (i.e., a galvanometric filter) disposed approximately parallel to the direction of blood flow through the flow chamber ( cross
The above objects of the present invention are achieved by flowing the patient's blood through a flow chamber having a filtration medium having a pore size that blocks the passage of cellular components of the blood but allows the passage of plasma. is achieved. Therefore, there is no loss of blood cells in the patient and there is only a slight loss of plasma at too much pressure.

Approximately 2 mm IJ IJ to collect the plasma passing through the filtration media on the side of the filtration media located opposite from the flow chamber.
There is a plasma chamber with a small volume of less than a liter. A sealable opening is provided within the plasma chamber for withdrawing a plasma sample from the plasma chamber.

In a preferred method of operation, the plasma chamber is first filled with a saline solution. When the plasma chamber is filled with saline solution and the entrance to the plasma chamber is sealed, nothing is removed from the blood flowing through the flow chamber because the plasma does not flow through the filtration media. When it is desired to collect a plasma sample, the saline solution is withdrawn from the plasma chamber through the sealable opening, while the plasma flows through the filtration media, and this flow continues until the plasma chamber is filled with plasma. This plasma is then withdrawn as a sample for analysis through the sealable opening, during which time additional plasma can flow into the plasma chamber.

However, after withdrawal of the plasma sample, the saline solution is forced into the plasma chamber through the sealable opening, thereby passing the plasma total filtration media within the plasma chamber back into the blood;
It is then passed through a flow chamber. This procedure is repeated each time a plasma sample is desired. Repeating this procedure ensures that the plasma sample taken from the plasma chamber does not in any case contain any plasma taken from the blood during previous sample withdrawals. Since the volume of the plasma chamber is small and preferably does not significantly exceed the volume of the plasma sample required for analysis, the volume of hydrochloric acid solution required to be injected and subsequently withdrawn is not large and therefore the volume of the saline solution is The time required for injection and withdrawal and withdrawal of each plasma sample is minimal.

The filter and method of the present invention therefore enable accurate periodic analysis of a patient's plasma and allow the patient to obtain the required suppressed plasma sample without losing any red blood cells and with only a small loss of plasma. The time required to obtain is the least.

The above and other features and advantages of the invention, as well as its preferred embodiments, will become more apparent from the following detailed description.

FIG. 1 will be explained. The illustrated hemodialysis apparatus comprises a dialyzer 2, which may be of conventional construction, having a blood port 4, a blood outlet 6, a dialydate port 8, and a dialydate outlet 10, for withdrawing blood from a patient 14. Serves as a conduit 12 for conveying the blood population 4 of the dialyzer? Fr.
Blood from patient 14 through the blood tube and blood outlet of 1 dialyzer.
There are seven more flexible tubes that serve as conduits 16 for return to the tube.

The apparatus includes a suitable meter control device, schematically shown at 18, which is well known to those skilled in the art, and a blood pumper for flowing the patient's blood through the dialyzer and then back to the patient. The blood ring is conventionally of the roller type as shown schematically at 20.

A filter 22 embodying the invention is provided as a component of one of the conduits carrying the patient's blood to or from the dialyzer.

In the illustrated device, filter 22 is a component of the conduit that carries blood from the dialyzer to the patient. Besides the filter 22, hemodialysis devices and their operation for removing labor waste from the patient's blood are well known to those skilled in the art and do not require further explanation Q).

Next, Fig. λ to Fig. z will be explained. The filter 22 has a blood flow chamber 24 with a blood inlet 26 and a blood outlet 28 connected to the conduit 16 such that the blood flow chamber 24 forms part of the conduit 16, and a plasma chamber 30. Equipped with Uzing.

Plasma chamber 30 is separated from blood flow chamber 24 by a filtration medium 32, preferably a porous membrane, extending parallel to the direction of blood flow through blood flow chamber 24. The filtration media 32 has a pore size that allows the passage of detergent but inhibits the passage of red blood cells and other cellular components of the blood, as well as platelets, with the preferred pore size being nominally about 0.5 mm. It is micron.

In the illustrated preferred embodiment, Howsong 2
3 has two cast plastic components 34 and 3
6. Preferably made of transparent thermoplastic, the upper component 34 provides a blood flow chamber and the lower component 36 provides a drainage chamber with an opening 38, which is preferably made of a soft entomer. It is closed with an object 40 made of material or similar resilient material. The blood flow chamber opening 26 and outlet 28 are provided by tubular plastic moldings 27 and 29, respectively, which are inserted into openings at the axial ends of the upper plastic moldings 34. Adhesively sealed,
The ends of the flexible conduit 16' are secured to the moldings 27, 29, and the inherent resiliency of the conduit 16 provides a fluid-tight sealing fit.

Each of the filter housing components 34 and 36 has an outwardly extending peripheral flange 42 and 44, respectively, which peripheral flange 42, 44 has a periphery of the FM media 32 adhesively sealed therebetween. provide opposing surfaces adhesively sealed together such that the only communication between the blood flow chamber and the plasma chamber is through the filtration media.

As shown and described above, the filter is of the cross-flow type (a cr
oss-flow type). That is, the blood flows through the blood flow chamber in a direction approximately parallel to the surface of the filtration medium with a component of the flow force in the flow type and the blood flow chamber and plasma chamber (if the plasma chamber is not filled and (when unsealed) causes plasma to pass through the filtration media and into the plasma chamber. To improve efficiency, the blood flow chamber should be such as to provide a high ratio of the surface area of the filtration medium to the volume of the 1 m liquid flow chamber and to provide a high velocity flow of blood over the surface of the filtration medium. preferable. To this end, in the illustrated preferred embodiment, the central portion 45 of the blood flow chamber is flat (so that the filtration medium is also flat) and of low height, with the top wall of the blood flow chamber and the filtration medium being flat. The distance between is approximately 7.3 mm or less,
Ideally it is approximately / mm.

Also, the cross-sectional area (transverse to the direction of blood flow) of the central portion 45 of the blood flow chamber is equal to the blood inlet 26 and blood outlet 28.
is preferably not less than, and most preferably equal to, the cross-sectional area of K, so that the blood flow chamber does not act to restrict the flow of blood through the conduit and the blood flow rate is within the conduit. It is preferable not to reduce the size significantly.

In conventional hemodialysis machines, the blood flow rate is approximately /jO ~
300 ml/min, and the blood flow rate, that is, the flow rate, is the lower limit of this range CI! It is fast enough to provide excellent performance by the filter as the plasma flow passes through the membrane. Although shown to an enlarged scale in the illustrated preferred embodiment, the actual dimensions of the central flat portion 45 of the blood flow chamber are approximately 63 mm long. ! ;mrns width is about 2/, Im
The door has a height of approximately 0.2 rrtm. The nominal flow rate of blood through the blood flow chamber is approximately /jO~300 mi!
l liter/min.

The plasma chamber 30 is rectangular in shape, as best seen in FIG. 2, and is very shallow to support the filtration media, as best seen in FIGS. A groove 48 is formed between the ribs 46, and all of the grooves 48 extend through a channel 48 provided at one end of the groove 48 to the outlet of the plasma chamber. It communicates with the opening 38. The volume of the plasma chamber for receiving plasma is therefore the additional volume of the grooves and channels plus the d-area of the exit passage 49 between the inner surface of the elastomer body in the opening and the yannenel. . According to the invention, this volume of the plasma chamber is very small, less than about 2 milliliters, ideally only about 0.3 milliliter.

The upper surface of the plasma chamber loop 46 forms a flat surface against which the flat rectangular central portion of the filtration medium rests. This flat surface formed by the upper surface of the ribs is flush with the entire rectangular perimeter of the component 36 surrounding the plasma chamber.

Blood flow ¥24 will be explained again. Ends 50 and 52
are each shaped so that its cross-sectional area (transverse to the direction of blood flow) is not less than and preferably approximately the same as the cross-sectional area of the central portion 45 of the blood flow chamber, and likewise approximately the same diameter as the inner diameter of the conduit 16. The cross-sectional areas of the blood population 26 and the blood outlet 28 are desirably shaped to be not less than, but preferably approximately the same, again, this ensures that the blood flow chamber is shaped such that at any point along the flow chamber, the
'M - Guaranteed that it does not act as a restriction on the flow of blood through the full-pass device.

As best shown in FIG. 3, in the illustrated preferred embodiment, the height H of the end 50 extends from the opening 26 to the longitudinal end 54 of the rectangular central portion 45 of the blood flow chamber. However, the end width W (see No. 41.) gradually increases from the opening 26 to the longitudinal end 54 of the central portion 45. The end 52 is of the same shape as the end 56 of the central portion of the blood flow chamber and the opening 2.
8 and are squared in height and inverted in width to provide the desired substantially uniform cross-sectional area across the direction of blood flow. It has become. In addition to providing a uniform cross-sectional area, this end shape reduces turbulence in the blood flow as it enters, passes through, and exits the blood flow chamber, as shown and discussed above. This helps to avoid or reduce the occurrence of flow. This is achieved by providing a relatively gradual transition in the cross-sectional shape of the flow path between the flat central portion of the blood flow chamber and the cylindrical conduit. That is, as blood enters the flow chamber through the cylindrical inlet 26 and exits the flow chamber through the outlet 28, it is inevitable that there will be some turbulence; By configuring and 52 as shown and described above, better assurance is obtained that turbulence is minimized. To further reduce turbulence in the blood flow as blood enters, passes through, and exits the blood flow chamber, a tapered section 50 (from the edge 5 of the rectangular section 26 to
4) whose length is at least 3 the diameter of the cylindrical population 26
Preferably, it is twice as large, and most preferably about 5 times. Similarly, it is preferred that the end 52 be of such length with respect to the outlet 28 and therefore the same length as the end 50 and that the opening 28 be of the same diameter as the opening 26.

It will be noted that in the illustrated preferred embodiment, the rectangular central portion 50 of the blood flow chamber is elongated in the direction of blood flow, and the length of this rectangular portion is greater than twice its width. The elongated shape of the rectangular portion 50 is desirable to provide a desirable thin flow chamber (i.e., small dimension from the filtration media to the soil wall) and a high ratio of filtration media area to flow chamber volume and to avoid turbulence. .

Apart from the filter 22, the start-up and operation of the hemodialysis machine as a whole is well known in the art for such machines. At start-up, it is conventional to eliminate all air in the system by filling the entire blood circulation system, ie the conduits and dialyzer, with saline solution. energizing the bong f20 to drain some or all of the saline solution before connecting the conduit 16 to the patient, or connecting the conduit 16 to the patient before draining some or all of the saline solution; The salt solution remaining in the system can be added as a component to the patient's blood, but this can vary from patient to patient;
It depends on what is desirable as determined by the patient's physician. With respect to filter 22, since the blood flow chamber is a component of conduit 16, it is filled with saline solution upon start-up of the device, following conventional procedures.

In practicing the preferred method of the invention, the plasma chamber 30 is filled with a saline solution before or after connecting the filter 22 to the conduit, but before circulating the patient's blood through the conduit and device. This is done by inserting the hypodermic needle of a syringe (not shown) filled with saline solution through the elastomeric object and injecting the saline solution through the needle and into the plasma chamber by pressing on the gland of the syringe in the conventional manner. Achieved easily and conveniently 6.
To best ensure that no air accumulates in the plasma chamber during saline solution injection, the filter should be oriented with the plasma chamber toward the bottom and the blood flow chamber toward the top as shown during saline solution injection. is the best. The salt solution can and should be injected until completely penetrated through the ~E filtration media. After the plasma chamber has been filled with the saline solution and all air has been purged from the device, the patient's blood is forced through the device in a conventional manner by activation of the blood pump.

Since it is desirable to collect and analyze the patient's plasma at the beginning of the hemodialysis process, the saline solution in the plasma chamber is withdrawn immediately after the patient's blood has finished circulating through the device (during this withdrawal, the plasma is A plasma sample is then withdrawn from the plasma chamber by flowing through the filtration media into the plasma chamber to replace the saline solution. All this is done by inserting the hypodermic needle of an empty syringe (not shown) through the elastomeric object. It is convenient to withdraw the saline solution from the plasma chamber by withdrawing the granger of the syringe in the conventional manner and then inserting the hypodermic needle of the empty syringe into the elastomeric object and withdrawing the plasma sample into this syringe. Of course, variations of this procedure may be used; for example, if the patient's blood is passed through the device through the hypodermic needle of the syringe originally used to fill the plasma chamber with the saline solution, The saline solution can be left in place until it circulates and then withdrawn using the same syringe without withdrawing the hypodermic needle from the elastomeric object.Furthermore, instead of using the elastomeric object and the syringe or syringes, a suitable A valve device comprising one or more valves connected to a small container by a conduit is used in place of the plasma chamber opening 38 to inject the saline solution from one of the containers into the plasma chamber. The saline solution can be drawn into the same container and the plasma sample into another container. By creating a slight suction in the plasma chamber when withdrawing the saline solution and when withdrawing the plasma sample, the pressure difference across the filtration media during withdrawal is balanced by the applied pressure of the patient's heart and that of the hemodialysis machine. It is preferred that the pressure difference resulting from the additional pressure of the blood pump and the pressure of the blood in the blood flow chamber created by the blood flow chamber be somewhat greater than or less than the pressure difference.In conventional dialysis machines, the pressure of the blood flow is about /!0. -260-26
O, and this pressure is sufficient to force the plasma to flow through the membrane into the plasma chamber, and the suction force exerted on the plasma chamber during withdrawal from the plasma chamber is added to this pressure, so that the suction force acts. During this period, the flow rate of plasma through the membrane increases. With said small volume of the plasma chamber and said dimensions of the central part of the blood flow chamber, at the blood flow rates mentioned, sufficient plasma flows through the membrane when the saline solution is withdrawn and thereafter.
- The time required for the plasma chamber to fill up is only about 1 minute to 1 minute.

After each plasma sample is withdrawn and the plasma chamber is filled with additional plasma that has passed through the filtration media, forcing the saline solution into the plasma chamber, such as through a hypodermic needle passed through the elastomer body. The plasma chamber is refilled with salt solution. As the saline solution is forced into the plasma chamber, the plasma therein is forced back through the filtration media into the blood flowing through the blood flow chamber. To ensure that all the plasma in the plasma chamber is forced through the filtration media into the blood flow chamber, the volume of saline solution injected is at least somewhat larger than the volume of the plasma chamber, so that some saline solution is It is desirable to force plasma through the filtration media into the blood flow chamber, thereby flooding the filtration media with plasma.

The above procedure is repeated each time it is desired to collect a plasma sample. And it will be appreciated that in any case, the plasma sample collected will not include any previously collected plasma sample. Therefore, the analytical results of each plasma sample accurately reflect the composition of the patient's plasma at the time the sample is taken, and the loss of patient plasma is minimized. More importantly,
Plasma samples can be obtained without loss of the patient's red blood cells.

The aforementioned method is preferred because it best ensures that each plasma sample drawn does not contain any of the same plasma as the previous sample. However, because the plasma chamber has such a small volume, it is possible to collect one or more plasma samples without using a saline solution to fill the plasma chamber. That is, using salt solution g, 4(
However, the initial plasma sample drawn from the plasma chamber at the beginning of hemodialysis contains only plasma of the same composition as is present in the patient's blood at that time. For subsequent plasma samples to be drawn (without filling the plasma chamber with salt solution in the middle), draw the first plasma of the carp equal to at least the volume of the plasma chamber before drawing each sample of desired plasma. You can throw it away.

This discarded plasma is that which filled the plasma chamber during and immediately after withdrawal of the previously collected plasma sample.

During the initial withdrawal of plasma to be discarded, the plasma chamber is
It is then refilled with plasma from the blood flowing through the blood flow chamber. This is the plasma that is drawn as a sample for analysis.

Therefore, each plasma sample drawn for analysis has substantially the same composition as the plasma in the patient's blood at the time the sample is taken. However, as the plasma is discarded, there is a greater loss of patient plasma compared to the preferred method (where a saline solution is used). However, as mentioned above,
There are no serious disadvantages since the volume of the plasma chamber is small 1 so that only a small volume of plasma has to be discarded in order to avoid contaminating the sample with the same plasma as the previous sample.

Although in the embodiment shown and described above, the filter is for connection to the blood conduit midway between the ends of the blood conduit, if desired, the filter may be a component of a hemodialyzer. It will be appreciated that all of the changes and modifications to the reservoir described above may be connected directly to either the blood inlet or the blood outlet of the hemodialyzer.
It may be practiced within the scope of the claims.

[Brief explanation of the drawing]

FIG. 1 is a schematic diagram of a dialysis machine incorporating a filter for carrying out the method of the invention. FIG. 2 is an enlarged exploded view of the filter shown as a component of the apparatus of FIG. 3 is an enlarged side cross-sectional view of the filter of the apparatus of FIG. 1; FIG. FIG. 5 is a top view of the filter shown in FIG. 3. FIG. 5 is a sectional view taken along line j--j in FIG. 3. FIG. 4 is a sectional view taken along the line 1 in FIG. 3. 22... Filter 1 24... Blood flow chamber, 30... Plasma chamber, 32... Filtration medium, 23... Housing, 26... Blood population of blood flow chamber 24, 28... Face number outlet of blood flow chamber 24, 38...opening, 46...rib, 48...groove, 40...elastic material object, 27.29...molded body, 16...・Conduit.

Claims (1)

[Claims] B. A filter particularly useful for collecting plasma samples from a patient's blood as it is carried through a conduit during hemodialysis, the filters being separated from each other by a filtration medium. a blood flow chamber and a plasma chamber, the filtration medium extending generally parallel to the direction of blood flow through the blood flow chamber and permitting the passage of plasma but blocking the passage of red blood cells; It has small pores of a size that
The blood flow chamber has a blood inlet and a blood outlet for connection to a conduit, whereby blood being carried flows through the blood flow chamber, and the plasma chamber has a blood inlet for connection to a conduit and a blood outlet for drawing blood plasma therefrom. A filter comprising an opening and a volume of about 2 milliliters or less. 2. A filter according to claim 1, characterized in that the plasma chamber has a volume of approximately 0.3 mm IJ liters. 3. The filter of claim 1, wherein the blood flow chamber has a central portion of substantially uniform height of about 1.3 mm or less above the filtration media. The central portion of the blood flow chamber has an elongated rectangular shape in the direction of blood flow, the blood flow chamber and the blood outlet have circular cross sections, and the blood flow chamber extends from one end of the central portion of the elongated rectangle to the blood flow chamber. and an end extending from the other end of the elongated rectangular central portion to the blood outlet, each of the ends substantially equal to at least approximately a cross-sectional area of the central portion of the blood flow chamber. 4. The filter according to claim 3, wherein the filter has a uniform cross-sectional area. Left The plasma chamber has a wall with an elongated chair f disposed opposite the filtration medium, the lyso having an upper surface in contact with and supporting the filtration medium, and an opening of the plasma chamber. 2. The filter according to claim 1, further comprising a groove between the lips that communicates with the lip. B, characterized in that the opening of the plasma chamber is provided with a penetrable, self-sealing object made of soft resilient material, thereby allowing plasma to be withdrawn from the opening through a syringe needle; A filter according to claim 1. 7. A patient undergoing hemodialysis through a blood flow chamber separated from the plasma chamber by a permeable medium having small holes sized to block the passage of the flow of red blood cells in the blood but allow the passage of plasma into the plasma chamber. A method for collecting a plasma sample from the blood of a patient undergoing hemodialysis, comprising flowing the blood of a patient and withdrawing a sample of plasma from a plasma chamber. B. The method according to claim 7, characterized in that the plasma chamber is filled with a saline solution before withdrawing the plasma sample, and then the saline solution is withdrawn from the plasma chamber before withdrawing the plasma sample. 2. Before beginning to flow the patient's blood through the blood flow chamber,
Filling the plasma chamber with a saline solution'f: Method according to claim g, characterized in: 10. After withdrawing the plasma sample from the plasma chamber, the plasma chamber is refilled with a saline solution, whereby the plasma within the plasma chamber is forced back through the filtration media into the blood flow chamber by the incoming saline solution. The method according to claim 7. //, the saline solution that refilled the plasma chamber is subsequently withdrawn from the plasma chamber, allowing plasma to flow back into the plasma chamber through the filtration media, and then another seven plasma samples are withdrawn from the plasma chamber. 11. The method of claim 10. /2 After the plasma sample is withdrawn, the plasma further passes through the filtration medium to fill the plasma chamber, then a volume of plasma at least equal to the volume of the plasma chamber is withdrawn from the plasma chamber, and then another
8. A method according to claim 7, characterized in that two plasma samples are withdrawn from the plasma chamber.