WO2005087001A1

WO2005087001A1 - A method for the dryness preservation of biological fluid samples and the device thereof

Info

Publication number: WO2005087001A1
Application number: PCT/CN2005/000286
Authority: WO
Inventors: Ge Chen
Original assignee: Ge Chen
Priority date: 2004-03-18
Filing date: 2005-03-09
Publication date: 2005-09-22
Also published as: CN1670190A; CN1311070C

Abstract

The present invention provided a method for the dryness preservation of biological fluid samples comprising the steps of contacting the said samples with a particle support with an average diameter from 0.l mm to 5 mm and removing the aqueous solution from the particle support which has absorbed the samples. The invention also provided a device for the method.

Description

Method and device for preserving biological liquid samples

The present invention relates to a method for drying and preserving a biological liquid sample based on a particulate material, particularly a method for preserving a small amount of a biological sample. The invention also relates to a device for drying and storing biological liquid samples.

Background technique

The collection, preservation, transportation, reorganization, and recovery of biological samples in scientific research are prerequisites for conducting various practical scientific research and testing of various clinical indicators. Liquid biological samples are the most widely used biological sample form in life science research. How to use the simplest and most cost-effective method to maintain the effective activity (including binding activity and biological activity), integrity (such as cells and other The accuracy of the concentration after the sample is recombined and recovered, and the safety of the entire process of biological sample processing are one of the basic problems to be solved in the fields of biology, medicine, medicine, and biotechnology. Over the years, scientists have worked tirelessly for this.

At present, the preservation methods of liquid samples are mainly divided into liquid cryopreservation (2-8 degrees Celsius); cryopreservation (-20 ~ -200 degrees Celsius); frozen (below -60 degrees Celsius) dry storage; cryogenic dry preservation (2 degrees Celsius) -8 degrees); and dry storage at normal temperature (10 ~ 30 degrees Celsius or ambient temperature).

The existing methods described above each have different disadvantages: For example, in a normal temperature environment, the components contained in a biological liquid sample are likely to be rapidly degraded in a short period of time or the bacteria and mold are propagated to cause changes in the properties of the original liquid sample; liquid samples in a low temperature environment are not suitable for long-term storage; Frozen liquid samples need to be kept in a low-temperature refrigerator to keep the temperature below zero degrees Celsius, which brings inconvenience to sample transportation. Although freeze-dried liquid samples can obtain satisfactory sample recovery efficiency, their cost is too high for single or small batch liquid samples Although the current method for storing dry samples at room temperature solves the problem of drying, storing, and transporting liquid samples, there are many shortcomings in sample liquid recovery, recombination, and subsequent analysis and processing.

Robert Guthrie first used Schleicher & Schuell Bioscience in 1963 Company (S & S) 's 903 filter membrane (hereinafter referred to as Guthrie Card) has collected newborn blood samples for PKU screening. This filter membrane has been widely used for the preservation of biological liquid samples. However, because the sample absorption matrix is composed of cellulose, when a liquid sample such as blood is dried, it becomes a fiber / sample solid structure, which causes great difficulties in reorganizing and recovering the liquid sample, and limits its application range. Taken together, the main disadvantage of using cellulose membrane as a liquid sample absorption matrix is that the sample reorganization is time-consuming, usually at least 30 minutes to several hours, and requires heat treatment to promote the reconstitution of the sample; the recovery efficiency is low, due to the formation of The cellulose membrane matrix of the sample has a gap-free solid shield structure, so it is extremely difficult to hydrate the dried sample again; and the absorption and adsorption of the cellulose component on the sample component results in a low recovery rate, and the optimal recovery rate is 4 氐At 50%.

In addition, the recovery of cellular components in dried biological blood is a necessary prerequisite for cytological research. Joseph (USA; Pat. No .: 5432,097) described in 1993 the use of the enzyme-digested cellulose membrane (Guthrie Card) method for the recovery of white blood cells from dried blood. However, this method requires cellulase to degrade the cellulose membrane, so it is time-consuming and costly.

Therefore, there is a need in the art for a method for drying and preserving liquid samples that is convenient, fast, and has a high sample recovery rate. Summary of the invention

The invention provides a method for drying and preserving a biological liquid sample, which comprises contacting the liquid sample with a particulate carrier having an average particle diameter of 0.1 mm to 5 mm; and removing liquid components from the particulate carrier that has absorbed the liquid sample. .

According to one embodiment of the present invention, the particulate carrier is composed of one or more materials selected from the group consisting of a polymer material, a material of biological origin, a metal material, and an inorganic non-metal material.

According to another embodiment of the present invention, the biological liquid sample is a biological fluid, a biologically prepared biological liquid sample or a liquid biological reagent.

The present invention also provides a device for drying and storing a biological liquid sample, which includes a particulate carrier having an average particle pore size of 0.1 mm to 5 mm.

According to the method and device of the present invention, quick and easy drying of liquid samples can be achieved. It can be stored dry, and samples can be recovered quickly and efficiently compared to the prior art methods. BRIEF DESCRIPTION OF THE DRAWINGS

The invention is described in detail below with reference to the drawings and specific embodiments.

FIG. 1 is a schematic diagram showing a blood sample drying, storage, recovery, and reconstruction process using the method of the present invention. Figures 1A-D show the reconstruction of the particulate carrier before loading, the particulate carrier after absorbing a liquid sample (whole blood), the dehydrated loaded particulate carrier, and the blood sample.

Figure 2 is an electrophoresis diagram of genomic DNA recovered from a blood sample stored in accordance with the method of the present invention. In the figure, M is a molecular weight marker; "1-4" are DNA extracted from 4 blood samples dried and stored on the solid carrier of the present invention. The load of each sample was 1 microgram (DNA). detailed description

After extensive research, the inventors of the present invention found that using a particulate carrier within a certain particle size range not only can quickly absorb and dry a liquid sample, but also the dried sample can be easily eluted from the carrier with water or other solvents, thereby quickly and efficiently Recover and reconstruct samples.

Therefore, the present invention provides a dry storage method for a liquid sample, which comprises contacting the liquid sample with a particulate carrier having an average particle diameter of about 0.1 mm to about 5 mm; and from the particulate carrier that has absorbed the liquid sample. Removes liquid components.

In the method of the present invention, the average particle diameter of the particulate carrier used is preferably between about 0.5 mm and about 3 mm, and more preferably between about 1 mm and about 2 mm.

The particulate carrier in the present invention may be made of any material, such as one or more materials selected from the group consisting of: polymer materials, chemically treated or untreated materials of biological origin, metallic materials, and inorganic non-organic materials. metallic material. In a preferred embodiment, the porous solid material of the present invention is an inorganic non-metallic material.

The carrier particles of the present invention may be solid or hollow. The carrier particles of the present invention may be non-porous on the surface or open-celled on the surface. When the carrier particles of the present invention have a surface open-pore structure, the pore diameter of the open holes is preferably in the range of 0.05-1 mm, and most preferably in the range of 0.1-0.5 mm. Preferably, the openings on the surface of the particles are open, that is, The diameter of the openings gradually increases from the inside of the particle to the surface of the particle. When the carrier particles of the present invention are porous particles, it is preferred that the particles have a certain hardness to avoid the collapse of the porous structure due to the gravity of the liquid or the drying process after carrying the liquid, resulting in the porosity of the sample-loaded particles after drying being lower than 20% of the original particle porosity is not conducive to the reconstruction of the sample.

The particulate carrier of the present invention may be hydrophobic or hydrophilic. In one embodiment of the invention, the particulate carrier is hydrophilic.

The particulate carrier of the present invention may be made of a polymer material. The polymer material may be non-biocompatible and / or biodegradable, or it may be biocompatible and / or biodegradable. For environmental considerations and for preservation of living cell and microbial samples, it is preferred that the polymer material of the present invention is biocompatible and / or biodegradable.

Examples of biocompatible and / or biodegradable polymer materials are: hydroxycarboxylic acid esters, such as poly (3-hydroxybutyrate) (PHB), 3-hydroxybutyrate and 3-hydroxyhexanoate Copolymer (PHB-HH), polylactic acid (PLA), lactic acid-glycolic acid copolymer (PLGA), polycaprolactone; polyorthoester, polyacid liver, etc. For blood compatibility, polymer materials having excellent anticoagulant properties include, for example, hydrophilic materials such as β-hydroxyethyl methacrylate, polyvinyl alcohol, polymethacrylamide, and polyvinylpyrrolidone; Hydrophobic materials such as silicone rubber; polymer materials with microphase-separated structure surfaces such as polyetherurethane; and materials with negatively charged surfaces such as polyester and foamed polytetrafluoroethylene with smooth carbon films on the surface.

Examples of non-biodegradable materials are: polyvinyl acetate, polyethylene, polystyrene, polyvinyl chloride, polyurethane, polycarbonate, and the like.

The polymer particulate material can be conveniently obtained according to the prior art method, and the particle size of the polymer particulate material can also be controlled according to a conventional method, so as to obtain a particulate material suitable for a specific application.

It is known to those skilled in the art that almost all thermosetting and thermoplastic resins can be made into particulate polymer materials. Polymers often used in the preparation of particulate polymer materials are: polystyrene, polyurethane, polyvinyl chloride, polyethylene, polypropylene, polyamide, polycarbonate, polyoxymethylene, polyester, polyphenylene ether, polysulfone, phenolic Resin, fluororesin, urea resin, melamine resin, unsaturated polyester resin, epoxy resin, silicone resin, etc.

Conventional methods for producing polymer particulate materials include extrusion molding, compression molding, Injection molding, etc.

The particulate material as a carrier of the present invention may be made of a metal or an alloy.

Inorganic non-metal materials that can be used as the carrier of the present invention include ceramics, glass, cement, refractories, various ores, grit, and the like. These materials can be made into particulate materials by conventional methods in the art. The chemical composition of inorganic non-metallic materials includes silicates, other oxoates, oxides, nitrides, carbons and carbides, borides, fluorides, chalcogenides, silicon, germanium, II-V and II-VI Family compounds, etc.

The carrier particles of the present invention can be prepared by a crushing and sieving method, that is, the material is first crushed by a crushing device, and then the required material particles are classified and screened by a sieve. The pulverizing equipment includes a mechanical pulverizer, a jet pulverizer, a self-crushing crusher, an impact crusher, a ball mill, a grinder, a sand mill, and the like. Self-crushing crusher is suitable for fine and medium crushing of refractory materials, cement, quartz sand, steel sand, slag powder, copper ore, iron ore, gold ore, concrete aggregate, asphalt aggregate and other hard and brittle materials. broken. Impact crusher is suitable for medium hardness materials such as limestone, dolomite, shale, sandstone, coal, asbestos, graphite and rock salt.

The carrier particles of the present invention can also be prepared by agitation granulation, pressure molding granulation, spray and dispersion mist granulation, hot melt molding granulation and other methods.

For example, the carrier particles of the present invention can be quartz stone particles, marble, mica stone particles, diamond particles, ceramic particles, wax particles, 'glass particles (glass microspheres), various rubber particles, various plastic particles (plastic microspheres) ), Various nylon particles, various resin particles, polyethylene particles, polypropylene particles, polystyrene particles, various dextran particles (Sephadex; Sepharose), various metal particles, magnetic particles, etc.

The diameter of spherical particles is the diameter, and the diameter of cubic particles is the length of one side. For irregularly shaped particles, the particle size is defined as the statistical average of the lengths of the line segments connecting two points on the surface of the particle through the center of gravity of the particle. In actual measurement, a certain number of particles, that is, a particle system, is often used as an object, and some physical characteristics related to the particle size are measured to calculate the particle size value. When the physical property or physical behavior of the measured particle is closest to the diameter of the same shield sphere (or combination thereof), the diameter of the sphere (or combination thereof) is used as the equivalent particle size of the measured particle (or Particle size distribution).

The average particle diameter of the particulate carrier of the present invention can be measured according to a conventional method in the art. example For example, screening method, image analysis method, sedimentation analysis method, electrical analysis method, optical analysis method, etc. When measuring the particle size distribution of particles by the sieving method, select the size of the sieve holes according to the size range and particle size distribution interval required for the measurement, and place the sieves together in the order of "upper and lower" of the sieve. at the bottom. Weigh the sample accurately (usually 100g sample is weighed to 0.1g, 50g sample is weighed to 0.05g), and the sample is transferred to the top layer of the sieve. After sealing the screen, the screen is installed on a shaker and shaken and screened. After sieving, carefully remove each sieve from the sleeve sieve, and pour the powder on the sieve surface onto smooth paper. Clamp the powder in the mesh and the bottom seam of the frame, and sweep it into the adjacent lower (small) first-level sieve with a soft brush. The weight of the powder collected on the sieve surface and in the chassis of each sieve was weighed. 100 g samples were weighed to 0.1 g, 50 g samples were weighed to 0.05 g. The sum of the powders taken is not less than 99% of the sampling mass. From the ratio of the mass of the particles obtained on each sieve surface to the total amount of collected powder, calculate the mass fraction of the particles within the size range of the sieve holes (greater than the sieve diameter of the layer and smaller than the sieve diameter of the previous layer), and draw Distribution diagram of particle size and number of particles under different particle sizes. The particle size corresponding to the peak in the distribution curve is the average particle size.

The granular carrier of the present invention can be used without any treatment. However, in order to prevent contamination of the sample, it is preferable to wash it with water, an aqueous detergent solution, or soak it with an acid or alkali solution. For example, the pH of the acidic solution used is below 5.0, and the pH of the alkaline solution is above 8.0. The solid support treated with acid or alkali can be washed with water to remove residual acid or alkali components. It is also possible to leave the solid support in an acid or alkali environment until it is dehydrated and dry, without cleaning after treating with an acid or alkali.

Depending on the specific application purpose, the granular carrier of the present invention may be specially treated by one or more of the following methods.

Heat treatment of the particulate carrier; autoclaving; ultraviolet irradiation; radioactive irradiation; preservative treatment; antibiotic treatment; antimycin treatment; organic solvent treatment; examples of organic solvents are ethanol, isopropyl alcohol, acetone , Chloroform, phenols, ethers, etc .; detergent treatment, examples of detergents are Tween (TWEEN-20, TWEEN-60, TWEEN-80, TWEEN-100), sodium lauryl sulfate ( SDS), Tritons (Triton X-100, Triton X-114 Triton X-200), etc .; anticoagulant treatment, examples of anticoagulants include heparin, sodium citrate (salt), ethylenediamine tetra Acetic acid (EDTA) and the like.

For example, protein-containing liquids can be used to block the protein-binding sites on the inner and outer surfaces of the particulate carrier. Point to prevent the adsorption of protein molecules in the sample leading to a decrease in sample recovery efficiency.

As another example, various chemical groups can be chemically linked to the surface of the particulate carrier to facilitate adsorption of contents in a liquid sample, such as amino, carboxyl, hydroxyl, alkyl, or other chemical groups.

It is also possible to coat or link appropriate molecules such as various protein molecules, nucleic acid molecules, acid-acid substrates, etc. on the carrier by physical or chemical methods to specifically or non-specifically capture the corresponding components contained in the sample. Conducive to the specific recovery of one or a certain type of biological sample components.

A biological liquid sample in the present invention is defined as any mixture containing a biological substance or a biological agent to be stored in an aqueous or non-aqueous solvent in a liquid state. The sample mixture may be in the form of a solution, suspension, emulsion or any other liquid.

For example, the biological fluid samples of the present invention may be physiological or pathological biological fluids: blood, sweat, urine, cerebrospinal fluid, spinal fluid, joint cavity fluid, vaginal fluid, semen, plasma, serum, amniotic fluid, milk, pleural fluid, abdominal cavity Fluid, bone marrow fluid, saliva, bile, tears, and other fluids produced under normal physiological and disease states.

The biological liquid sample of the present invention may also be a manually prepared liquid sample, such as a liquid containing bacteria, molds, fungi, parasites, etc., liquid extracts of various biological tissues such as various cells or / and tissues of organisms. (Liquid extracts of heart, liver, spleen, lung, kidney, etc.) and liquid extracts of various plant cells.

The biological liquid sample of the present invention may also be a liquid biological reagent containing a solid solute, such as various buffers and liquids prepared therefrom. The liquid prepared by the liquid reagent is, for example, a liquid containing proteins, nucleic acids, cells, platelets, bacteria, plasmids, virus particles, parasites, semen, vaginal secretions, and the like.

In the process of using the method of the present invention to dry and store a biological liquid sample, a protective agent capable of improving the resistance of the biologically active substance to drying and improving the storage ability may be added. Such protective agents are known to those skilled in the art. For example, polyols such as glucose, maltose, sucrose, xylulose, ribose, mannose, fructose, raffinose, trehalose and other sugars; sugar derivatives such as sorbitol; synthetic polymers, such as polyethylene glycol, Hydroxyethyl starch, polyvinylpyrrolidone, polyacrylamide; polysaccharides such as polysucrose and dextran; proteins; and the above Combination of shields.

For preservation of platelets, examples of protective agents that can be added include serum proteins, casein hydrolysates, polyvinylpyrrolidone, and hydroxyethyl starch.

For storage of nucleic acids such as RNA, DNA, and oligonucleotides, SDS, guanidines, TWEENs, Tritons, urea, Tris, phenols, EDTA, ethanol, etc. can be added.

In a preferred embodiment of the present invention, the biological liquid sample is a human or animal whole blood sample or a blood component sample.

The dehydration and drying of biological liquid samples after adding the solid carrier can be carried out under natural room temperature evaporation conditions, or it can be heated (such as in an oven at 37-100 degrees Celsius), hot air (such as a hair dryer), and accelerated liquid under liquid pressure Removal of the ingredients forms a dry sample.

The method of the invention is particularly suitable for the drying and storage of small amounts of biological liquid samples. For example, the volume of the liquid sample before drying is about 500 ml or less, preferably about 100 ml or less, more preferably 50 ml or less, and most preferably 10 ml or less.

As described above, the present invention also provides a device for drying and storing a biological liquid sample, which includes a particulate carrier having an average particle diameter of 0.1 to 5 mm. The above description and preferred conditions regarding the method of the present invention are equally applicable to the apparatus of the present invention.

In the device of the present invention, the particle carrier may have any three-dimensional shape, such as a spherical shape, a cylindrical shape, a cubic shape, a rectangular parallelepiped shape, a triangular shape, a circular or semi-circular shape, a spiral shape, a prism shape, a triangular shape, and a polygon shape. Body shape or irregular shape, etc.

In the device of the present invention, the particle carrier of the present invention can be contained in a support or container of any shape, preferably a container commonly used in the art for sampling, storage, transportation, processing, and subsequent processing of biological samples, such as test tubes, Centrifuge tubes, dialysis tubes, cultures, sample storage cards, etc. Preferably, the surface of the particulate carrier of the present invention is covered with a sheet-like material that allows the passage of a biological liquid sample while preventing the passage of the particulate carrier. More preferably, the particulate carrier of the present invention is enclosed in a closed space composed of the support or container and the sheet-like material. There are no restrictions on the properties of the sheet-like material, but it is preferably composed of a non-adsorbent material, such as a metal mesh, a sintered glass mesh, a fabric, a nylon mesh, or a mesh structure made of other polymer materials.

The dry sample absorbed in accordance with the present invention can be easily removed from the solid by conventional operations such as washing and centrifugation. The bulk carrier is recovered and the liquid sample is reconstituted. The reconstituted liquid sample can be used for subsequent operations and applications such as detection and purification of sample contents, such as detection and purification of various proteins, ions, vitamins, antigens, antibodies, cells, and nucleic acids.

According to the method of the present invention, the content of the sample is recovered quickly and the recovery rate is high. For example, sample recovery can be completed in seconds to minutes. The recovery rate of samples stored dry according to the present invention can reach at least about 70%, preferably at least 80%, more preferably at least 90%, and most preferably at least 95%.

The method and device of the present invention are preferably applicable to dry storage of various biological cells. For example, the red blood cells (RBC), white blood cells (WBC), and platelets in the blood are stored dry. Before absorbing liquid samples containing cells, it is preferred to pre-treat the solid support, such as encapsulation with protein-containing liquid, treatment with a certain concentration of cell fixatives such as formalin, aldehydes, ethers, alcohols and other organic solvents . When the cell component in the sample is contacted with the preservative or the fixing agent, the cell component can be fixed and then dehydrated to form an immobilized, dehydrated and dried cell sample. After adding the appropriate solvent to the sample, the cells can be hydrated again and the original structure can be restored. It can be further applied to histochemical staining, immunohistochemical staining, immunofluorescent staining, detection of cell surface molecules, and specific cells. Sorting or purifying, such as sorting cells or sorting by magnetic beads or using flow cytometry.

The method and device of the present invention are preferably applied to various protein molecules, especially various antigens, antibodies, and various enzymes for dehydration, drying or vitrification in combination with appropriate stabilizers. An advantage of the method of the present invention is that the above-mentioned molecules can stably maintain their binding activity and / or enzyme activity for a long period of time when they are in a dehydrated, dried state or a vitrified state. When the solvent is added, the above components can be quickly hydrated in a short period of time (usually within 5 minutes) and uniformly distributed in the liquid phase, so that they can effectively react with the corresponding ligand or substrate.

The method and device of the present invention are also preferably applied to the collection, drying and storage of blood samples. Before the blood sample is collected, the solid carrier may be treated with an anticoagulant or directly mixed with an anticoagulant, such as heparin, EDTA disodium. Blood samples were collected by finger puncture or foot puncture (infant) blood collection. Blood droplets are allowed to drip directly into the particulate carrier, and then dehydrated to form a mixture of anticoagulated dried blood particles and a solid carrier. The blood can also be collected by conventional venipuncture, and the blood is quantitatively transferred to the porous carrier using a sampler. When the sample is reconstituted, For example, adding a solvent (usually pure water or distilled water) approximately equal to the volume of the original blood sample can quickly obtain a reconstructed blood sample close to the original sample, which can be used for subsequent processing such as further detection and analysis. Depending on the purpose of the application, blood samples can also be made by dripping blood directly into the particulate carrier that has not been treated with the anticoagulant without using an anticoagulant. Examples

Example 1

Preserving blood samples with glass particles

Take 2 ml of glass beads with an average particle size of about 2 mm. The glass beads were fixed to the inner surface of the lid of the centrifuge tube with a metal mesh. 0.5 ml of heparin-added whole blood was evenly loaded on the above glass beads. The device loaded with the blood sample was placed in a ventilated place and dried at room temperature. Close the cap containing the dry sample to the centrifuge tube until use.

In parallel, another 0.5 ml blood sample from the same source was used directly to determine the hemoglobin content.

Example 2

Recovery of dried blood samples

The centrifuge tube with the dried sample obtained in Example 1 was opened, and about 0.6 ml of deionized water was added to the centrifuge tube. Close the cap, invert the centrifuge tube, and let the water contact the glass beads for about 5 minutes. Then, shake the tube a few times or slightly centrifuge with the lid facing up to obtain a reconstituted blood sample.

By measuring the hemoglobin content of the sample and comparing it with the control hemoglobin content of the example, the recovery rate of the bleeding sample was calculated to be about 96%.

Example 3

Preserving blood samples using grit drying

Follow the same procedure as in Example 1, but replace the glass beads with sand with a particle size range of 0.8-2.0 mm. A blood sample was recovered in the same manner as in Example 2. Based on the amount of hemoglobin, the recovery of the blood sample was about 93%.

Example 4

Genomic DNA extraction from dried blood samples A 0.25 ml blood sample was dried and stored as described in Example 1. 1 ml of red blood cell lysate was added to a 1.5 ml centrifuge tube with a blood sample carrier, and it was allowed to contact the solid sample carrier for 5 minutes. Shake the test tube and centrifuge for 15 seconds at maximum speed on an Eppendorf centrifuge. Aspirate the supernatant. Add 1 ml of red blood cell lysate, shake the tube, centrifuge, and aspirate the supernatant.

Add 0.3 liters of DNA release solution to the test tube, mix with the white blood cell pellet and let stand for 5 minutes. Then, add 0.1 ml of protein precipitation solution, mix well, and centrifuge for 5 minutes.

The supernatant containing the genomic DNA was transferred to a test tube, and the DNA concentration was measured. Perform electrophoresis according to the conventional method to identify the amount of DNA (see Figure 2 for the results).

A 0,25 liter fresh blood sample from the same source was used as a parallel control.

Results The average amount of DNA recovered from 4 experiments was 354 g, and the average amount of fresh blood recovered was 36 micrograms.

Example 5

Recovery of serum T3, Τ4 and TSH

0.2 ml of serum was added to the same carrier as in Example 1 and dried at room temperature for 3 hours. After sealing, store at room temperature for 1 month.

The above granular carrier with the dried serum sample was contacted with 0.2 l of distilled water for 10 minutes. Remove the supernatant after centrifugation. The concentrations of T3, T4 and TSH were measured by chemiluminescence immunoassay. At the same time, the same assay was performed on frozen serum samples of the same source.

It was found that the average recoveries (relative to frozen samples) of the three experiments for each of the above factors were close to 98%.

Claims

Rights request

A dry storage method for a biological liquid sample, comprising contacting the liquid sample with a particulate carrier having an average particle diameter of 0.1 mm to 5 mm; and removing a liquid component from a solid carrier that has absorbed the liquid sample.

2. The method according to claim 1, wherein the average particle diameter of the particulate carrier is 0.5 mm to 3 mm.

3. The method according to claim 2, wherein the particulate carrier has an average particle diameter of 1 mm to 2 mm.

4. The method according to claim 1, wherein the particulate carrier is composed of one or more materials selected from the group consisting of a polymer material, a material of biological origin, a metal material, and an inorganic non-metal material.

5. The method according to claim 1, wherein the granular carrier is obtained by a sieving method, agitation method granulation, pressure forming granulation, spray and dispersion mist granulation, and hot melt molding granulation.

6. The method according to claim 4, wherein the polymer material is polymer particles prepared by extrusion molding, compression molding, and injection molding.

7. The method according to claim 4, wherein the inorganic non-metallic material is a particulate material made of ceramic, glass, cement or refractory material.

8. The method according to claim 1, wherein said removing liquid components from the solid support is performed by air-drying.

The method according to claim 1, wherein said removing a liquid component from a solid support is performed under reduced pressure.

10. The method according to claim 1, wherein the liquid sample is a biological fluid, an artificially prepared biological liquid sample, or a liquid biological reagent.

11. The method of claim 8, wherein the biological fluid is blood or a component thereof.

12. An apparatus for drying and storing a liquid sample, comprising a granular carrier having an average particle diameter of 0.1 mm to 5 mm.