JPS6011166A - Sampling method of blood plasma for clinical inspection - Google Patents

Abstract

PURPOSE:To sample quickly and easily several 100mul-several ml blood plasma necessary for an inspecton from the whole blood of several ml-10ml by feeding the whole blood into the hollow parts of hollow fibers and filtering the blood plasma on the outside surface of the hollow fibers. CONSTITUTION:A filter cartridge at least one end of which is fixed by an adhesive resin 2 is used and the whole blood is fed from the stationary open end into the hollow parts of hollow fibers 1 and is led out of the other open end so that the blood plasma is filtered and separated on the outside surface of the filbers 1, thereby sampling the blood plasma for an inspection. The blood is sampled from a patient into a syringe then the injection needle is removed and the syringe 6 is coupled via a suitable adapter 5 to a main cartridge 7. The inside cylinder of the syringe is then moved to feed the blood in the syringe into the cartridge. The blood which is forced to the other open end and contains much blood cell component is discarded. The fibers having the membrance structure as mentioned above has high mechanical strength and provides a high rate of separating the blood plasma and therefore the quick and sure analysis of a small amt. of specimen (blood) is made possible without errors.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for separating and collecting plasma from the entire surface for use as a specimen for clinical testing.

So-called biochemical tests that measure components in blood are widely used in the diagnosis and follow-up of various diseases, and occupy an important position as clinical tests. Analytical technology has advanced significantly in recent years, and with the development of various types of automatic analysis equipment, it has become possible to analyze large amounts of specimens quickly and accurately. However, in the field of biochemical testing, serum is widely used as a specimen, and to obtain it, blood is collected from a patient, coagulated, centrifuged, and the supernatant is transferred to the serum, which requires remarkable technology. There has been no progress in the field, and the operation is complicated and takes an hour.Due to specimen errors, etc., the mission of clinical testing, which is accurate, quick, and simple, cannot be met. As a method for solving this problem, Japanese Patent Laid-Open No. 53-7J2691 proposes a method for separating plasma from blood using a fine tube-shaped filter element with one end closed.

However, with this method, blood cell components etc. adhere to the filter surface and it takes an extremely long time to filter plasma, the permeability of proteins and membrane components is poor, and hemolysis occurs when the filtration pressure is increased to speed up the filtration rate. It was difficult to put it into practical use because of the problems that occurred.

The present inventors have arrived at the present invention as a result of intensive research to solve these drawbacks.

That is, the present invention uses a filtration cartridge in which both ends of a hollow fiber bundle are open and at least one end is fixed, and the entire surface of the bundle is fed into the hollow part of the hollow fibers from the fixed open end, and is led out from the other open end. The present invention provides a method for collecting plasma for testing by filtering and separating plasma on the outer surface of hollow fibers.

The filter cartridge having hollow fibers used in this method is not particularly limited as long as both ends thereof are open and at least one end is fixed so that blood can be introduced into the hollow ionization hollow part. For example, as shown in FIG. 1, only one end of a hollow fiber bundle 1 is fixed with an adhesive resin 2. Fig. 2 shows a hollow fiber bundle 1 inserted into a cylindrical outer cylinder 3 with one end fixed, and Fig. 3 shows a hollow fiber bundle 1 fixed at both ends in a cylindrical outer cylinder 3 with adhesive resin or the like. However, it is conceivable to have an opening 4 in the outer cylinder for taking out the plasma, or a fixed one as shown in Fig. 4. As shown in FIG. 5, the device used to introduce blood into the cartridge is one that collects blood from a patient into a syringe, removes the needle, and connects the syringe 6 and the cartridge via an appropriate adapter 5 as the case requires. A syringe that is directly connected to 7 and moves the inner cylinder of the syringe manually or mechanically to send the blood in the syringe to the cartridge can be adopted, and the blood with a large number of blood cells pushed out to the other open end is discarded. Plasma can be collected more effectively by sending it back in the opposite direction as necessary (a syringe is also attached to the blood cell waste outlet in FIG. 5). Another possible method for introducing blood into this adapter is to collect it from a patient by directly connecting it to a blood circuit or the like.

In addition, the entire surface used is coated with heparin-ACDS to prevent coagulation.
It is desirable to add a commonly used anticoagulant such as EDTA.

The hollow fiber used in the present invention has a pore diameter of 0.05 to
A value of 1μ is appropriate; if it is less than 0.05μ, the permeation of high-volume components such as proteins and fats in the blood will be poor; if it is more than 1μ, problems such as hemolysis will occur. There are no particular limitations on the inner diameter, film thickness, and number of fibers, but usually the inner diameter is 100 μm to 1 mm, the film thickness is 50 μm to 200 μm, and the effective fiber length is 2 crg to 20 cm.
The number of hollow fibers can range from several to 100. There are no particular limitations on the material used to make the hollow fibers, and cellulose diacetate-cellulose triacetate-polymethyl methacrylate, polypropylene, polyethylene, polysulfone, and the like can be used.

Further, the hollow fibers preferably used in the separation method of the present invention are as follows. That is, the outer surface of the hollow fiber is smooth and has a pore area of 1°3 x 10-2 m [the following pores are evenly distributed and the porosity is less than 40%], and the inner surface of the hollow fiber is the pore surface '4t41 ．． The pores of s
% or more and a film thickness of 100 microns or less is preferably used. Note that 1. Surface smoothness refers to the average distribution of pores observed in an electron micrograph at 5000x magnification, and porosity refers to the total number of pores actually measured in the surface layer observed in an electron micrograph at 5000x magnification. to the area, 100 to the surface area of
Refers to the fractional ratio (%).

When such a membrane is used for the separation and collection of plasma for testing according to the present invention, the following advantages are often found. That is, during one test, whole blood is sent to the separator by manually operating the inner cylinder of the syringe, but depending on the feeding pressure at this time, there is a risk that leakage may occur on the hollow fiber wall and blood cells may be mixed into the test plasma. . The fibers of the present invention having the above-mentioned macrostructure have high mechanical strength and a high plasma separation rate, so that a small amount of specimen (blood) can be reliably analyzed in a short time and without mistakes.

By the method of the present invention, the several 1,007 ml of plasma necessary for testing can be easily collected in a short period of time from several to 110" of whole blood with almost no hemolysis or change in composition, which is a bottleneck in biochemical tests. This will greatly help streamline sample collection.

Examples of the present invention will be described below, but the present invention is not limited in any way by the description of the examples.Example 1゜Pore diameter: 0.4 μm, inner diameter: 400 μS, film thickness: 80 μm, effective length: 4
C+++ cellulose triacetate (maximum pore surface on outer surface II 13.0 x 10-3+d, porosity 30%
, and the maximum hole area of the inner surface of the hollow part is 1B, OXYO""md
, porosity 65%) were filled into a polycarbonate cylindrical container with an inner diameter of lc+g, and both open ends were fixed with urethane adhesive. Using the type of cartridge shown in Figure 3, connect a disposable syringe containing pre-collected heparin north face 5- to it via a dabter, and manually push out the inner cylinder of the syringe in 30 seconds. Plasma without hemolysis of approximately 1- was obtained. The urea nitrogen total protein-total cholesterol concentration of this sample was compared with that of centrifuged plasma. The results of the analysis were favorable as shown below.

Comparative Example A cartridge was made that was the same as in Example 1, except that the same hollow fiber as in Example 1 was used, and only the blood inlet side was open. 1 The other open ends were closed with adhesive. N The same blood flow test was carried out. Although some blood could be introduced into the hollow fiber, very little plasma was obtained.The syringe was activated even more forcefully, and the small amount of plasma that was obtained dissolved and turned red. 0 ”?/dt % total protein 3.2
The g/d1 s total cholesterol was 85 Q/dt, which was lower than that of centrifuged plasma.

[Brief explanation of drawings]

Figures 1 to 5 show hollow fiber bundles used in the method of the present invention.
This figure shows an example of an IJ and a device using it. 1; Hollow fiber 2; Fixing resin 3; Outer tube 4; Plasma extraction port 5; Adapter 6; Syringe tube;

Claims (1)

[Claims] Using a hollow fiber bundle with both ends open - using a filtration cartridge with at least one end fixed, whole blood is fed into the hollow part of the hollow fiber from the fixed open end and led out from the other open end. A method for collecting plasma for clinical testing, characterized by filtering plasma through the outer surface of hollow fibers.