JPS58174849A - Novel bioliquid carrier - Google Patents

Abstract

PURPOSE:To obtain a bioliquid carrier in place of filter paper for carrying the bioliquid by a method wherein a layer of hydro-swelling fibrous substance is provided on the carrier where a hydrophilic inorganic substance has been dispersed in gaps between hydrophobic porous substances. CONSTITUTION:The bioliquid carrier is prepared by providing a layer of a hydro-swelling fibrous substance on a carrier where a hydrophilic inorganic substance has been dispersed in gaps between hydrophobic porous substances. When it is used, the bioliquid is first taken in the upper layer becuase of the hydrophile property with which the hydro-swelling fibrous substance has been provided and gradually allowed to penetrated in the lower layer, whereas the moisture as a whole is dried, so that it can offer dryness superior to filter paper. Moreover, when the carrier is used for blood, because the fibrous substance in the upper layer is expansive and because it is not allowed to contact the blood component while being hard and fibrous and because there exists no hard fibrous substance even in the lower layer formed with the porous substance, the blood component is not damaged and preserved in a good condition as a whole. In addition, because the bioliquid is prevented from disseminating in its surface direction, it is readily extracted and traces of fiber are hardly mixed with the extracted liquid.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a new biological fluid carrier for transporting collected biological fluids.

One type of testing for biological fluids such as blood, plasma, serum, etc. is called mass screening testing. For example, H5 congenital carp abnormality test for newborns,
This includes tests for perinatal infections performed on pregnant women and newborns.

Since these tests involve mass screening, test subjects are distributed over a wide area, and unless there is a system to collect and deliver specimens (for example, blood) to the testing center, it is difficult to increase the test take rate. Therefore, it is characteristic that both Europe, the United States, and Japan use the p-paper blood collection method. Normally, a piece of thick paper is used as a blood carrier, and blood (whole blood) is placed on that piece of paper.
The test center soaks it in water, dries it, and then mails it to a testing center.The testing center takes out a section of the dried blood spot on the paper and soaks it in an aqueous extractant (liquid or gel), and then tests the extracted portion. .

This one-paper method has several advantages as well as disadvantages. Considering that the normal method of collecting and delivering specimens at hospitals is via test tubes, the simplicity of collecting and delivering specimens can be cited as an advantage. However, the specimen collection and delivery method using this blood carrier has some drawbacks with the currently available ν paper, so improvements are desired in terms of both the testing method and collection and delivery. Various types can be found. P paper has excellent blood absorption properties, and its advantage is that it can be made with various specifications in terms of absorption capacity by changing its thickness.

This property is thought to be due to the deep affinity that P paper has for blood and its homogeneity as a medium, but as a phenomenon observed when blood is dripped onto P paper and absorbed, blood components move toward the surface from the point of drop. Diffuses and has poor stopping properties. Regarding this point, when inspecting a certain amount of paper inside the cutout and outside the cutout and inspected each, one of the pieces outside the cutout
The blood test values were also reversed from the paper, proving that the paper in the paper did not accurately represent blood. Furthermore, in terms of collection and delivery, P paper, which is a blood carrier, has excellent blood absorption properties, but has low drying properties, and improvements are desired. In addition, various drawbacks are enumerated in terms of testing, such as low extractability, low integrity of blood components, and contamination of microfibers into the extract.

Of course, it is better for regeneration by extraction to occur in a short period of time, but since it generally takes a long time in the case of one piece of paper, the extraction is usually promoted by cutting the paper sections into small pieces, but this is not always sufficient. In addition, for paper, which is a blood carrier, it is desirable that blood components that can be used for testing are preserved and regenerated after extraction, but generally blood cell components are easily damaged (hemolysis phenomenon).
, the phenomenon of contamination of hemolysate into the extract has been observed, which interferes with testing. Furthermore, there are fine particles of P paper as a contaminant in the extract, which is also unfavorable for testing.

An object of the present invention is to provide a new biological fluid carrier to replace E-paper for transporting biological fluids such as blood. In other words, it is a biological fluid carrier that dries easily, has excellent biofluid absorption properties, has little surface direction diffusion of biofluid components, has good extractability, does not mix fine fibers into the extracted solution, and is less likely to cause blood damage. The goal is to provide the following.

That is, the present invention provides a biological fluid carrier comprising a layer of water-swellable fibrous material provided on a carrier in which a hydrophilic inorganic material is dispersed in the pores of a hydrophobic porous material. It is related to.

Biological fluid components are adsorbed and retained across both layers.

Furthermore, by layering the upper fibrous material layer and/or the lower carrier layer, it is possible to make the entire structure more multilayered.

A bottom layer may be further provided under the carrier of the lower layer to reinforce the mechanical strength of the entire sheet, or the entire surface for attaching symbols may be provided on the upper layer, the lower layer, or the bottom layer.

Biological fluids are first absorbed into the upper layer by the hydrophilic power of the water-swellable fibrous material, and eventually permeate into the lower layer, drying the water as a whole, but the drying properties are superior to that of P paper. ing. This means that the biological fluid components that have reached the lower layer are inside the layer'g! When the biological fluid components penetrate through the action of hydrophilic inorganic substances (for example, substances dispersed in the form of inorganic particles) dispersed in the gaps, the biological fluid components become adsorbed and retained in the voids of the porous and hydrophobic substances. Therefore, the moisture in the lower layer dries quickly, which in turn promotes the drying of the upper fibrous layer, resulting in quick drying as a whole.

j- In this carrier, the pattern of movement of biological fluid components is vertical, and there is little diffusion toward the surface, but this is because the upper layer fibers are water-swellable and the fibers cause capillary movement of water. In the lower layer, since the hydrophilic inorganic substance is in a dispersed state, diffusion of water toward the surface is thought to be difficult.

Furthermore, when the biological fluid carrier of the present invention is used for blood, there is little damage to blood cell components, but this is because the upper layer string-like material is swellable and comes into contact with blood cell components while remaining in a hard fibrous form. This seems to be because there are few cases. Even in the carrier portion of the porous material in the lower layer, there is no hard fiber-like material that could damage blood cells, and blood components are well preserved as a whole.

Extraction with the aqueous extractant occurs rapidly, probably because the lower layer fibrous material becomes swollen and exchange with water in the extractant occurs more rapidly than with non-swollen fibers. When the extractant water is replaced by the pores of the hydrophobic substance in the lower layer, the biological fluid component is hydrophilic and tends to elute and migrate into the water rather than coexist with the hydrophobic substance. It seems that the extractability is good. In addition, in the case of extraction with an aqueous extraction solution,
In this carrier, the fibrous material is water-swellable, so fine fibers do not float in the extract solution and are difficult to remove, and the centrifugation method clearly separates the cut section of the carrier and the extraction supernatant in the lower layer. can do.

The water-swellable fibrous material in the present invention is a material that takes the form of a fiber and has the characteristics of a material that absorbs water, swells into a gel-like state, and becomes hydrated. As a definition of swelling degree, use swelling degree (times) = (absorbed water weight) / (own weight),
Swelling degree when water is 1% salt solution is 3
~jO times the range is used, and is used for absorbing biological fluids, drying,
In view of the balance of various functions such as extraction, it is preferable to use j-21 times. Specifically, 411i-Kaishoit-/jr'1. !
A carboxymethylated product of regenerated cellulose as described in the TR publication, a fibrous material obtained by crosslinking and polymerizing acrylonitrile hydrolyzate known as Exlan-WAF (sold by Japan Exlan Kogyo Co., Ltd.), and Aqualon (sold by Perculase). This includes fibrous materials made of carboxymethylated cross-linked natural cellulose known as .

The method of forming this fibrous material into a sheet shape does not limit the effects of the present invention, but forming a sheet can be achieved by knitting or weaving or non-woven fabric processing.

In addition, the thickness, fiber density, fiber diameter, etc. of the fibrous sheet each affect the absorption, drying, and extraction of biological fluids, but for a practical biological fluid carrier, the thickness is 0. /~0.7rata,
Preferably 0. λ~OOS, fiber density IO? -/2
0 ff/ml, preferably Hiroo, ioo ff/
lr? , Ml fibers of 174IOμ to jθμ, preferably 72 to 2jμ are used.

Examples of hydrophobic porous materials include plastics, calcium silicate boards, glass sintered bodies, alumina sintered bodies, and porous ceramics that can be made from aluminum, aluminum silicate, diatomaceous earth, carbon, etc. Can be used.

In sheets in which hydrophilic inorganic substances, such as fine particles thereof, are dispersed in the pores of a porous and hydrophobic substance, porosity means that the sheet has a network structure consisting of communicating pores, which allows for good blood retention, drying, and extraction. For the average pore size o, oi + o, rμ,
Preferably 0.0/, 0. It has pores of λμ. More preferably, the porosity defined by the following formula is 30
-40%, preferably in the range porosity -C (pore volume)/(porous plastic volume)
]X100 However, the wall pore volume is calculated from water-containing weight - dry weight. A preferred material is a hydrophobic plastic. Preferred hydrophobic plastics are those whose main constituent elements are C, H, and halogen elements, and which have almost no water absorption or moisture permeability as plastics. Therefore, instead of absorbing and retaining moisture, they dry out. Specifically, polyethylene, polypropylene, polybutene, mixtures thereof, copolymers of two or more of ethylene, propylene butene, hexene, polyvinyl chloride, etc. are commercially available products. Since the manufacturing method is well known, it is easy to implement.

Such material can be used as a sheet with a thickness of 0.0J--OJ
Dragons, preferably o, 1z-o, ≠, are used, but this is within the range where the functions can be demonstrated in a well-balanced manner,
It is not intended to limit the scope of the invention. The hydrophilic inorganic substance can impart water wettability to the hydrophobic plastic and is hydrophilic, but must not be soluble in water. Preferred examples of inorganic substances that can be used in the present invention include fine particles of silica, alumina, clay, titanium oxide, calcium carbonate, and the like. The particle size and dispersion density are
From the viewpoint of imparting appropriate wettability, the particle average diameter j−jθ
0 mμ, preferably 10-100 mμ, and an apparent dispersion density defined by the following formula: j-1.0%, preferably j-1.

Apparent dispersion density (%) - [(Preliminary examination of fine particles *) / (Porous plastic volume) )
×100 A preferable lower layer of the present invention, that is, a sheet in which hydrophilic inorganic fine particles are dispersed in porous and hydrophobic plastic voids, is a sheet made of a hydrophobic plastic and a hydrophilic plastic, as described in Japanese Patent Application Laid-open No. 52-1sA7yAg. As described in Japanese Patent Publication No. 37-2922-No. θ~, there is a method in which hydrophilic inorganic fine particles and a plasticizer are mixed, melt-molded, and then the plasticizer is extracted and removed. Although it can be produced by a method of mixing and drying a solvent plasticizer, etc., the effect of the present invention is not dependent on the specific method. Further, hydrophilic fine particles can be supported on a porous inorganic substance by, for example, immersing the porous inorganic substance in an aqueous slurry of fine particles such as silica or alumina, and then drying the porous inorganic substance. Further, a small amount of an organic binder such as an epoxy emulsion may be added to the slurry liquid to improve the ability to support the fine particles.

Although the integration of both the upper and lower layers is not necessarily essential for the present invention, it is easier to use if they are integrated in practice. For example, in the case of plastic, the upper layer can be separated by instantaneous heating and pressure near the melting temperature of the lower plastic layer. The fibrous material gets stuck,
Since a practical integrated product can be obtained, it is possible to create an integrated product with upper and lower layers.

As a practical example, when the two layers are stacked and applied to two layers of heat rolls in the thermocompression bonding method, embossing method, etc., they become integrated.For example, polyethylene is used as the plastic. In case, upper roll (fiber side)
/60-170℃, lower roll (plastic side) 1
0~IOθ℃, roll gap 0.2~0. j i
im, low /l/linear velocity is J--, 20m/II
It can be made with.

EXAMPLES Next, in order to show embodiments of the present invention, examples will be described in detail.

Example/ Unexamined Japanese Patent Publication J'+ -iJ'ii in the upper layer as a blood carrier
A water-swellable cuprammonium rayon nonwoven fabric produced by the method of Example/of Publication No. Then, as a nonwoven fabric obtained by washing with methanol water,
Fiber diameter ll voice, #J! Michihiro Otlrd, thickness 0.3
I used one from Mitsuru.

In the lower layer, a silica-dispersed porous polyethylene sheet (i.e., polyethylene mixed with silica having an average diameter of 1 mμ and a plasticizer (dioctyl phthalate) produced by the method described in Example 77J of Publication No. 77J) was used. After dipping in trichloroethane and extracting and removing the plasticizer, the sheet had an apparent silica dispersion density of 3r and an average pore diameter of 0.0.
2μ, porosity: 0. /1III was used.

The two are integrated by thermocompression bonding, with the upper roll set at ljO℃ and the lower roll lOO℃, with a gap of 0.26+u between the two rolls.
The test was performed using tx, roll linear velocity, and tm. ℃, humidity 5
Although it was made under 0%, it was not particularly dried, and a square sheet piece with a length of lj was cut out and used as it was. Healthy human blood (hematocrit value: 5%) collected in a syringe is dripped onto the sheet piece so that it soaks into the sheet to a size of about 10 ru in diameter and 1 g. It took o, ii, 1.

When the entire body was air-dried for 10 minutes under the above indoor conditions, the percentage loss in incremental mass immediately after blood drop reached 7j%, which was determined to be in a dry state for practical use.

As an extract, a phosphoric acid buffer solution was prepared as follows.

NaC1O, ≠ f/l KH, Po, 0.0/ t/l13- Na, HPO4'/, 2'H400, /4'j f/
LKC10,01f/L P H7,Ir This extract 0. A diameter of 10w1 was obtained by drying the above blood carrier sheet that had absorbed healthy human blood by taking Hiroshi in a test tube.
Cut out and add a 300-mm thick disk, let it stand for 10 minutes, and then centrifuge it at 3,000 rpm for 5 minutes.A sheet residue was observed at the bottom of the test tube, and a clear extract was observed above it, which could be visually determined. It was confirmed that there was no hemolysis and that no fiber or plastic pieces were floating.

Next, in order to quantify the amount of extracted transfer of plasma components in this extract, the total protein amount was measured using the refracting needle method.]
Igaku Shoin, edited by Kamo Ishii [Clinical Chemistry Test II J p, 27
) Solutions o and 11 obtained by adding the same amount of plasma from the same sample to the same extract were measured in the same manner and compared using - as the standard solution.

As a result, the total protein content in the extract from the blood carrier sheet was 1. θf/a! -% total protein in standard solution /, /f7
It was at.

Next, using this carrier sheet, healthy human blood was absorbed and dried in the same way, and a certain amount of the accelerated part with a diameter of 10 gm and the part immediately outside the keratin was cut out, and after extraction in the same way, it was tightened. The amount of each was measured, and the diffusibility of blood components toward the surface was observed. Result: 100 (inside the part)
It was against O (just outside Kakei).

Comparative Example 1 Blood was absorbed in the same manner as in Example 1 using P paper (Daiichi Kagaku Yakuhin Co., Ltd.) with a thickness of O1j as a blood carrier and dried.

As a result, it took 2 hours for the incremental mass reduction to reach 7j immediately after the blood was dropped. Further, when extraction was performed in the same manner as in Example 1, a clear red color was observed in the extract after centrifugation, indicating that damage to blood cells had occurred. Also,
Floating of thin fibers was clearly observed.

Next, the total amount of tanned water in the extract was measured and found to be θ, ff/dt. When the total protein was measured between the Kakebe and the area immediately outside the Kakei S, it was 1OO (Kakebe) versus male (the area immediately outside the Kakebe).

Example 2 As a blood carrier, the same copper ammonia rayon nonwoven fabric as in Example/ was prepared for the upper layer, and JP-A-32-#A7 was prepared for the lower layer.
A porous, hydrophobic plastic sheet was produced in the same manner as in Example 77, except that polypropylene was used as the resin instead of polyethylene, and alumina was dispersed as the hydrophilic particles. The porosity was 60%, the average pore diameter was 0.02μ, the sheet thickness was 0.2μ, the average particle diameter of the alumina particles was 20μ, and the apparent dispersion density of alumina was 140%. The upper and lower layers are integrated by embossing, with the upper roll set at iro°C, the lower roll set at 3-0°C, and the gap between both rolls o-5mm.
The test was carried out at a roll linear velocity of 10 m/mvr. A sheet piece was made under the same conditions as in Example 1, and blood was dropped onto it. The whole was then air-dried, but it took ≠θ minutes for the rate of increase in weight loss to reach 7j immediately after the blood was dropped. As in Example 1, no hemolysis was observed in the extracted solution after centrifugation.
It was confirmed that no fiber or plastic pieces were floating.

The total tan-day amount in the extract was /, /ff/at.

The ratio of the total daily tanning amount in the acceleration part and the area immediately outside the recessed part is l.
The difference was θθ (in the recess) versus θ (immediately outside the recess).

Example 3 A cross-linked polymerized fiber of acrylonitrile hydrolyzate produced by the method of Example 1 of JP-A No. 316-3, ie, acrylonitrile and methyl acrylate, was used as a blood carrier in the upper layer. Acrylic fibers made of acrylic fibers were immersed in caustic soda, boiled, washed with water, and then dried. Fibers with a diameter of 1μ were obtained by a wet nonwoven fabric manufacturing method to a thickness of 0. ．． 2J-111 was processed into a sheet-like product with a fiber density of 100 ff/I. The wet nonwoven fabric manufacturing method uses the above-mentioned dried acrylic fiber (fiber length 2I).
ll+i) methanol slurry (fiber concentration is defined as the percentage of fiber volume to slurry volume, 0.0J
%) to a glass filter (pore distribution IOθ~7.
The methanol was removed by heating under p overpressure and fOuImHg for 1 hour, followed by air drying at 2 J'°C and 50% humidity. The lower layer contains a silica-dispersed porous polyvinyl chloride sheet produced by the method described in the example of Japanese Patent Publication No. 37-1 Kota No. 22, i.e., 7-fuvinyl chloride, silica with an average diameter of 1 mμ, a solvent (cyclohexanone and quidylol), and a plasticizer. (dioctyl phthalate), etc., and then dried to obtain a sheet with an apparent silica dispersion density of 70% and an average pore size of 0. O/μ, porosity yo%, sheet thickness 0.2mm
I prepared something for you.

To integrate the two, use the embossing method to set the upper roll/gθ℃ and lower roll/jO℃ of the embossing roller, and set the temperature between the two rolls to 0. rrn, and the roll linear velocity was 20 m/M. The integrated sheet was made at 23° C. and 50% humidity, but was not particularly dried, and square sheet pieces with a length of /jTIJm were cut out and used as they were. Phenylalanine is separately added to healthy human blood (hematocrit value pt%) collected into a syringe from the sheet piece so that the syringe becomes thick, and then infiltrated into a syringe with a diameter of about 10 m/m. drip like this. It took O1//-. The whole was then air-dried, but it took pt minutes for the incremental mass reduction rate to reach 7j% immediately after blood was dropped.

Using agar as an extraction gel, for the purpose of knowing the rate at which phenylalanine is extracted from the blood carrier into the agar, the journal Medloal Technology Vo.
The time required for phenylalanine measurement was measured by the phenylalanine scanning method described in J', Ari p7341--p7#.

That is, when a disk (diameter 3 cranes) of the blood carrier was placed in agar and the time required to produce a growth circle indicating phenylalanine extraction was measured, it was 7 hours.

Comparative Example Blood was absorbed in the same manner as in Example 3 using P paper (manufactured by Daiichi Kagaku Yakuhin Co., Ltd.) with a thickness of 0.3-fin as a blood carrier and dried. As a result, it took one hour for the incremental mass reduction rate to reach 7j% immediately after the blood was dropped. When the father was extracted in the same manner as in Example 3, it took 20 hours to produce a growth circle indicating phenylalanine extraction.

Example ≠ The same blood carrier as in Example was prepared. Collected healthy human blood (hematocrit value 5%) was left to stand for 1 hour and centrifuged at 93,000 rpm for lj minutes, and the obtained upper layer was taken as serum into a syringe barrel and applied to a piece of blood carrier sheet. Drop it so that it is about 1 orn in diameter. It took O1/-. When the sheet piece was air-dried for ≠θ minutes under the same indoor conditions as in Example 1, the incremental weight loss rate immediately after serum drop reached 81, which was determined to be in a practically dry state. Extraction was carried out in the same manner as in Example 1, but observation of the extract after centrifugation revealed that no fiber pieces or plastic pieces were floating.

The total tan-day amount in the extract was 7 f/at. In addition, the total protein content of the standard solution obtained by adding the same amount of the same serum to the same extract is 1. It was ri/at. The ratio of the total daily amount of tan to the serum part and immediately outside the serum part was ioo to O.

Comparative Example 3 Using the same blood carrier as in the comparative example of Example 1, serum was absorbed and dried in the same manner as in Example≠. As a result, it took 2 hours for the incremental mass reduction rate to reach 1196 immediately after dropping the serum. In addition, fine fibers were noticeably suspended in the extract after centrifugation. Next, the total amount of tanned water in the extract was measured, and it was 5V.
It was aL.

When the total tanned amount was measured in the serum area and the area immediately outside the serum area, it was ioθ vs. O.

Patent applicant: Asahi Medical Co., Ltd. Representative Patent Attorney Hoshino Toru 21-

Claims (4)

[Claims] (1) A biological fluid carrier comprising a water-swellable fibrous material layer provided on a carrier in which a hydrophilic inorganic material is dispersed in the pores of a hydrophobic porous material. (2) Claim 1 in which the conveyor shape is sheet-like
The biological fluid carrier described in Section 1. (3) The biological fluid carrier according to claim 1, wherein the porous substance is made of a hydrophobic plastic material. (4) The biological fluid carrier according to claim 1, wherein the biological fluid is blood.