CN1311070C - Method and device for dry conservation of biological liquid sample - Google Patents
Method and device for dry conservation of biological liquid sample Download PDFInfo
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- CN1311070C CN1311070C CNB2004100295235A CN200410029523A CN1311070C CN 1311070 C CN1311070 C CN 1311070C CN B2004100295235 A CNB2004100295235 A CN B2004100295235A CN 200410029523 A CN200410029523 A CN 200410029523A CN 1311070 C CN1311070 C CN 1311070C
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- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 239000011044 quartzite Substances 0.000 description 1
- MUPFEKGTMRGPLJ-ZQSKZDJDSA-N raffinose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO[C@@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O2)O)O1 MUPFEKGTMRGPLJ-ZQSKZDJDSA-N 0.000 description 1
- 229920003987 resole Polymers 0.000 description 1
- 229910052895 riebeckite Inorganic materials 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000004062 sedimentation Methods 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 229920002050 silicone resin Polymers 0.000 description 1
- 229920002379 silicone rubber Polymers 0.000 description 1
- 239000002893 slag Substances 0.000 description 1
- 238000002791 soaking Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- FCZYGJBVLGLYQU-UHFFFAOYSA-M sodium;2-[2-[2-[4-(2,4,4-trimethylpentan-2-yl)phenoxy]ethoxy]ethoxy]ethanesulfonate Chemical compound [Na+].CC(C)(C)CC(C)(C)C1=CC=C(OCCOCCOCCS([O-])(=O)=O)C=C1 FCZYGJBVLGLYQU-UHFFFAOYSA-M 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 239000004575 stone Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 210000004243 sweat Anatomy 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- 210000001138 tear Anatomy 0.000 description 1
- BFKJFAAPBSQJPD-UHFFFAOYSA-N tetrafluoroethene Chemical group FC(F)=C(F)F BFKJFAAPBSQJPD-UHFFFAOYSA-N 0.000 description 1
- 229920005992 thermoplastic resin Polymers 0.000 description 1
- 229920001187 thermosetting polymer Polymers 0.000 description 1
- 150000003625 trehaloses Chemical class 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229920006337 unsaturated polyester resin Polymers 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 238000009423 ventilation Methods 0.000 description 1
- 210000002845 virion Anatomy 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N1/00—Preservation of bodies of humans or animals, or parts thereof
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N1/00—Preservation of bodies of humans or animals, or parts thereof
- A01N1/10—Preservation of living parts
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N1/00—Preservation of bodies of humans or animals, or parts thereof
- A01N1/10—Preservation of living parts
- A01N1/12—Chemical aspects of preservation
- A01N1/128—Chemically defined matrices for immobilising, holding or storing living parts, e.g. alginate gels; Chemically altering living parts, e.g. by cross-linking
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Dentistry (AREA)
- General Health & Medical Sciences (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Environmental Sciences (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Abstract
The present invention provides a method for storing a biological liquid sample in a dry way. The method comprises the steps that the biological liquid sample is in contact with a particle carrier with the average particle diameter of 0.1 to 5 millimeters; the particle carriers in the liquid sample are absorbed, and the liquid ingredients are removed. The present invention also provides a device for the method.
Description
Technical field
The present invention relates to a kind of method for drying and storing of the biological fluid based on particulate material, particularly the method for drying and storing of biological sample in a small amount.The invention still further relates to the device that is used for biological fluid drying, preservation.
Background technology
Biological sample collection in the scientific research, preservation, transportation, reorganization, recovery are the prerequisites of carrying out various experimental science researchs, the various indexs detections of clinical medicine.Liquid biological sample is the biological sample form that the most extensively adopts in the life science, and to reclaim security in its concentration accuracy of back and the biological sample processing whole process be one of biology, medical science, medicine, biological technical field basic problem that need solve for effective active (comprising in conjunction with activity and biological activity), integrity (as cell and other formed elements), the sample reorganization of product content how to use the easiest cost-effective method to keep intact.For many years, scientific workers have made effort untiringly for this reason.
At present, the store method of liquid sample mainly is divided into liquid cryopreservation (2-8 degree Celsius); Freezing preservation (-20～-200 degree Celsius); Freezing (-60 degree Celsius are following) kept dry; (2-8 degree Celsius) preserved in cryodrying; Preserve (10～30 degree or envrionment temperatures Celsius) with Air drying.
There is different shortcomings separately in existing aforesaid method: for example cause rapid in a short time degraded of branch that biological fluid synthesizes or bacterium mold propagates etc. to cause the change of initial liquid properties of samples in the normal temperature environment easily; Liquid sample should not be made prolonged preservation in the low temperature environment; The frozen liq sample retention needs cryogenic refrigerator to continue to make temperature to remain on below the zero centigrade, and transportation is made troubles to sample; Though the freeze drying liq sample can obtain satisfied sample organic efficiency, its cost is too high and be unsuitable for processing single or the short run liquid sample; Though present Air drying sample retention method has solved the kept dry transportation problem of liquid sample, when handling, sample liquids recovery, reorganization and subsequent analysis have a lot of defectives.
Robert Guthrie utilized Schleicher﹠amp first in 1963; Schuell Bioscience (the S﹠amp of company; S company) 903 filter membranes (back claims Guthrie Card) are collected newborn infant's blood sample and have been carried out since the PKU examination, and this filter membrane is the kept dry of widespread use biological fluid.But constitute because this absorption of sample matrix is Mierocrystalline cellulose, go after drying into a kind of fiber/sample entity structure, cause very big difficulty for the reorganization and the recovery of liquid sample, its range of application is very limited when absorbing liquid sample such as blood.Integrate, this is that the sample reorganization is time-consuming with cellulose membrane as the main drawback of liquid sample absorption base, generally needs 30 minutes at least to a few hours, and needs heat treated to redissolve to promote sample; Organic efficiency is low, because the plain membrane matrix of the sample fiber that dry back forms is a no gap substantial structure, so the utmost point is difficult to make once more the dry sample aquation; And cellulose membrane causes the low rate of recovery to the absorption and the adsorption of sample composition, and its optimum recovery rate is lower than 50% at short notice.
In addition, the cellular constituent in the dry artifact blood being reclaimed is the prerequisite of carrying out cytology research.Joseph (USA; Pat.No.:5432,097) having described the white corpuscle that utilizes zymetology digest cellulose film (Guthrie Card) method to carry out dry blood in 1993 reclaims.But this method program need be used the cellulose degraded cellulose membrane, and is therefore time-consuming, cost is high.
Therefore, this area needs a kind of easy, quick and liquid sample method for drying and storing that sample recovery rate is high.
Summary of the invention
The invention provides a kind of method for drying and storing of biological fluid, it comprises described liquid sample and a kind of median size, and to be 0.1mm contact to the particulate vector of 5mm; With from the particulate vector that has absorbed liquid sample, remove liquid component.
According to one embodiment of the invention, described particulate vector is to be made of one or more materials that are selected from down group: the material of polymer materials, biogenetic derivation, metallic substance and ceramic.
According to another embodiment of the present invention, described biological fluid is the biological fluid or the liquid bio reagent of biological fluid, artificial preparation.
The present invention also provides a kind of device that is used for the kept dry biological fluid, and it comprises that a kind of averageparticle aperture is the particulate vector of 0.1mm to 5mm.
According to method and apparatus of the present invention, can realize quick, the easy kept dry of liquid sample, and compare recovery sample fast and efficiently with art methods.
Description of drawings
Describe the present invention in detail below in conjunction with the drawings and specific embodiments.
Fig. 1 shows to utilize method of the present invention to carry out the synoptic diagram of blood sample drying, preservation and recovery, restructuring procedure.Figure 1A-D represents not application of sample particulate vector, the particulate vector behind the absorption liquid sample (whole blood), the load sample particulate vector after the dehydration and the reconstruct of blood sample before respectively.
Fig. 2 is the electrophorogram from the genomic dna of preserving by the inventive method that blood sample reclaims.Among the figure, M is the molecular weight sign; " 1-4 " is respectively the DNA that extracts from the blood sample of 4 parts of kept dry on solid carrier of the present invention.The applied sample amount of each sample is 1 microgram (DNA).
Embodiment
The present inventor is through extensive studies, discovery utilize the particulate vector in certain particle size range not only can rapid absorption, the drying liquid sample, and the exsiccant sample easily from the carrier water or other solvent elutions get off, thereby reclaim fast and efficiently, the reconstruct sample.
Therefore, the invention provides a kind of method for drying and storing of liquid sample, it comprises described liquid sample and a kind of median size is contacted to the particulate vector of about 5mm for about 0.1mm; With from the particulate vector that has absorbed liquid sample, remove liquid component.
In the inventive method, the median size of particles used carrier is preferably about 0.5mm between about 3mm, more preferably arrives between about 2mm at about 1mm.
Particulate vector among the present invention can be made by any material, for example is selected from down one or more materials of group: polymer materials, through material, metallic substance and the ceramic of the material of chemical treatment or untreated biogenetic derivation.In a preferred embodiment, cellular solid of the present invention is a ceramic.
Carrier granule of the present invention can be solid, also can be hollow.Carrier granule of the present invention can be surperficial atresia, also can be that the surface has perforate.When carrier granule of the present invention was surperficial open-celled structure, the aperture of preferred described perforate was at 0.05-1mm, most preferably in the 0.1-0.5mm scope.The perforate of preferred described particle surface is open, i.e. the diameter of perforate increases from the granule interior to the particle surface gradually.When carrier granule of the present invention is porous particles, preferred this particle has certain rigidity, after avoiding load bearing fluid, because liquid gravity effect or drying process are subsided vesicular structure, cause dry back load sample particulate porosity to be lower than 20% of the former porosity of particle, be unfavorable for the reconstruct of sample.
Particulate vector of the present invention can be hydrophobic or hydrophilic.In one embodiment of the invention, described particulate vector is hydrophilic.
Particulate vector of the present invention can be made by polymer materials.Described polymer materials can be non-biocompatible and/or biodegradability, also can be biocompatibility and/or biodegradable.Be in the consideration of environmental protection and for the preservation of viable cell, microbiological specimens, preferred polymer materials of the present invention is a biocompatibility and/or biodegradable.
The example of biocompatibility and/or biodegradability polymer materials has: hydroxycarboxylic acid esters, as poly-(3-butyric ester) (PHB), 3-butyric ester and 3-hydroxycaproic acid ester copolymer (PHB-HH), poly(lactic acid) (PLA), poly lactic coglycolic acid (PLGA), polycaprolactone; Poe, poly-acid anhydrides etc.For blood compatibility, the polymer materials with good anticoagulant property for example has: hydrophilic material such as polymethyl acrylic acid beta-hydroxy ethyl ester, polyvinyl alcohol, PMAm and Polyvinylpyrolidone (PVP); Hydrophobic material such as silicon rubber; Macromolecular material such as poly(ether-urethene) with micro phase separation structure surface; With the material on electronegative surface such as the terylene and the spumescence tetrafluoroethylene of the level and smooth carbon film of surperficial evaporation.
The example of abiotic degradable materials has: polyvinyl acetate (PVA), polyethylene, polystyrene, polyvinyl chloride, urethane, polycarbonate etc.
Described polymer beads material can obtain easily by art methods, and the particle diameter of described polymer beads material also can be controlled according to a conventional method, thereby obtains to be suitable for the concrete particulate material of using.
It is known to those skilled in the art that nearly all thermoset and thermoplastic resin can both make the particulate polymers material.Polymkeric substance through being usually used in preparing the particulate polymers material has: polystyrene, urethane, polyvinyl chloride, polyethylene, polypropylene, polymeric amide, polycarbonate, polyoxymethylene, polyester, polyphenylene oxide, polysulfones, resol, fluoro-resin, urea-formaldehyde resin, melamine resin, unsaturated polyester resin, Resins, epoxy, silicone resin etc.
The method that routine is used to produce the polymer beads material comprises extrusion moulding, compression molding, injection molding etc.
Particulate material as carrier of the present invention can be made by metal or alloy.
Can comprise pottery, glass, cement, refractory materials, various ore, sand grains etc. as the ceramic of carrier of the present invention.These materials can be made particulate material by the ordinary method of this area.The chemical constitution of ceramic comprises silicate, other oxysalt, oxide compound, nitride, carbon and carbide, boride, fluorochemical, chalcogenide compound, silicon, germanium, II-V and II-VI compounds of group etc.
Carrier granule of the present invention can promptly at first use disintegrating apparatus with the material fragmentation by crushing and screening the method preparation, filters out the material particles that needs with screen fractionation then.Disintegrating apparatus comprises mechanical crusher, jet mill, self-impacting crusher, impact breaker, ball mill, shredder, sand mill etc.The self-impacting crusher be applicable to the in small, broken bits of multiple hard, crisp material such as refractory materials, cement, quartz sand, steel sand, pulverized slag, copper mine stone, iron ore, Gold Ore, aggregate, asphalt aggregate with in broken.Impact breaker is applicable to medium hardness materials such as Wingdale, dolomite, shale, sandstone, coal, asbestos, graphite and rock salt.
Carrier granule of the present invention also can pass through method preparations such as paddling process granulation, compression moulding method granulation, spraying and the granulation of dispersion vapodusting, the granulation of the heat fusing method of forming.
For example, carrier granule of the present invention can be quartzite particle, marble, Muscovitum particle, diamond particles, ceramic particle, Wax particles, glass particle (glass microsphere), various rubber grain, various plastic grain (plastic microsphere), various nylon particle, various resin particle, polyethylene particle, polypropylene GRANULES, granules of polystyrene, various glucan particles (Sephadex; Sepharose), various metallic particles, magnetic-particle etc.
The particle diameter of spheroidal particle is its diameter, and the cube particle grain size is the length on its one side.Particle in irregular shape, its particle diameter are defined as by the particle center of gravity, link the statistical average value of all line segment lengths of point-to-point transmission on the particle surface.In actual measurement, often the particle with some amount is that particle system is an object, measures some physical property amount relevant with its particle diameter and calculates particle size values.When the homogenous spheres of certain physical property of tested particulate or physical behavior and a certain diameter (or its combination) is the most close, just the diameter of this spheroid (or its combination) as tested particulate equivalent grain size (or size distribution).
The median size of particulate vector of the present invention can be measured by the ordinary method of this area.For example, method of sieving, image analytical method, sedimentation analysis, electricity analysis method, Optical Analysis Method etc.When measuring particle grain size distribution with method for sieving, according to the particle size range and the size distribution interval of measurement requirement, select then screen size, by sieve " upward big, following little " order with screen jacket together, catch tray is placed on the bottom.Accurate weighing sample (the 100g sample claims that to 0.1g the 50g sample claims to 0.05g usually) goes to sample in the last layer sieve of bushing screen.After sealing bushing screen bushing screen is contained in jolting screening on the sieve shaker.Sieve is finished, and carefully takes off each only sieve from bushing screen, and the powder on the compass screen surface is poured on the slick paper.Be clipped at the bottom of mesh and the screen frame powder in the seam, sweep in the adjacent sieve of (little) one-level down with banister brush.Every of weighing is sieved on the compass screen surface and the powder quality of collecting in the chassis, and the 100g sample claims that to 0.1g the 50g sample claims to 0.05g.Adding and measuring of the powder that takes by weighing is being not less than 99% of sampling quality.Ratio by institute's granular mass that obtains on each grade compass screen surface and collection powder total amount, calculate particle in this size of mesh scope (greater than this layer mesh size, less than the last layer mesh size) massfraction, draw the thus distribution plan of particle number under particle diameter and the different-grain diameter, the particle size of peak value correspondence is a median size in the distribution curve.
Particulate vector of the present invention can directly use without any processing.But in order to prevent contaminated samples, preferred water, aqueous detergent solution are cleaned, or with acid or aqueous slkali soaking.For example the PH of used acidic solution is below 5.0, and the PH of basic solution is more than 8.0.Continue to clean with the solid carrier used water after acid or the alkaline purification, to remove remaining acid or alkali composition.Can after with acid or alkaline purification, not clean according to circumstances yet, solid carrier is still remained in acid or the alkali environment until dehydrating.
According to the difference of concrete application purpose, particulate vector of the present invention can be through following one or more method special processings.
Particulate vector is carried out heat treated; Autoclaving is handled; Uviolizing; Radio exposure; Antiseptic kind is handled; The antibiotic class is handled; The antimycoin class is handled; The organic solvent class is handled, and representative examples of organic has ethanol, Virahol, acetone, chloroform, phenols, ethers etc.; The washing agent class is handled, and the example of washing agent has Tweens (TWEEN-20, TWEEN-60, TWEEN-80, TWEEN-100), sodium lauryl sulphate (SDS), Triton class (Triton X-100, Triton X-114, Triton X-200) etc.; The anti-coagulant class is handled, and the example of anti-coagulant has heparin, Sodium Citrate (salt), ethylenediamine tetraacetic acid (EDTA) (EDTA) etc.
For example can be with the protein binding site of protein-contg liquid sealing particulate vector surfaces externally and internally, prevent that the absorption of protein molecular in the sample from causing the decline of sample organic efficiency.
Again for example, can on the surface of particulate vector, connect various chemical groups by chemical process and be beneficial to inclusion in the adsorptive liquid sample, for example amino, carboxyl, hydroxyl, alkyl or other chemical group.
Also may by physics or chemical process on carrier, wrap by or connect suitable molecule such as various protein molecular, nucleic acid molecule, sour substrate etc., so as to specificity or non-specific catch corresponding composition contained in the sample.Help reclaiming specifically a certain or a certain class biological sample composition.
Biological fluid among the present invention is defined as and anyly contains the mixture that remains to be preserved biological substance or biological reagent with what liquid state existed in water-based or non-aqueous solvent.Described sample mixture can be solution, suspension, emulsion or other any liquid forms.
Biological fluid for example of the present invention can be physiology or pathologic biological fluid: any liquid that other biological bodies such as blood, sweat, urine, cerebrospinal fluid, spinal fluid, arthral fluid, vaginal secretion liquid, seminal fluid, blood plasma, serum, amniotic fluid, milk, pleural fluid, peritoneal fluid, bone marrow fluid, saliva, bile, tear are produced under normal physiological state and morbid state.
Biological fluid of the present invention also can be through artificial formulated liquid sample, the liquid that for example contains bacterium, mould, fungi, parasite etc., the various cells of the liquid extract of various biological tissues such as biology are or/and the liquid extract of tissue extract (liquid extracts of the heart, liver, spleen, lung, kidney etc.) and various vegetable cells etc.
Biological fluid of the present invention can also be the liquid bio reagent that contains solid solute, as various damping fluids and by the liquid of its preparation.Liquid by described liquid reagent preparation for example is the liquid that contains protein, nucleic acid, cell, thrombocyte, bacterium, plasmid, virion, parasite, seminal fluid, vaginal secretions etc.
Utilize method of the present invention to carry out in the process of biological fluid kept dry, can add the protective material that can improve biologically active substance tolerance drying and improve hold capacity.Such protective material is well known by persons skilled in the art.Polyvalent alcohol for example is as carbohydrates such as glucose, maltose, sucrose, xylulose, ribose, seminose, fructose, raffinose, trehaloses; Sugar derivativess such as Sorbitol Powder; Synthetic polymer is as polyoxyethylene glycol, hydroxyethylamyle, polyvinylpyrrolidone, polyacrylamide; Saccharan such as ficoll and dextran; Protein; And the combination of above-mentioned substance.
For hematoblastic preservation, protectant example that for example can add has serum protein, casein hydrolysate, Polyvinylpyrolidone (PVP) and hydroxyethylamyle.
For the preservation of nucleic acid such as RNA, DNA, oligonucleotide etc., can add SDS, guanidine class, TWEEN class, Triton class, urea, Tris, phenol, EDTA, ethanol etc.
In a preferred embodiment of the invention, described biological fluid is human or animal's the whole blood sample or the sample of blood ingredient.
Dehydrating and can carry out under the natural room temperature evaporation conditions behind the biological fluid adding solid carrier, the removal that also can heat the liquid component that quickens liquid sample under (as in the baking oven of 37-100 degree Celsius), hot blast (as blower), the reduced pressure forms dry sample.
Method of the present invention is particularly suitable for the dry and preservation of biological fluid in a small amount.The volume of liquid sample is about below 500 milliliters before for example dry, and is preferred about below 100 milliliters, more preferably below 50 milliliters, most preferably below 10 milliliters.
As mentioned above, the present invention also provides a kind of device that is used for the kept dry biological fluid, and it comprises that a kind of median size is the particulate vector of 0.1-5mm.Above-mentioned description and optimum condition about the inventive method is equally applicable to device of the present invention.
In device of the present invention, particulate vector can be any three-dimensional shape, for example spherical, cylindrical, cube shaped, cuboid, the triangle bodily form, annulus or semi-annular shape, spirrillum, the two rib bodily forms, prism-shaped, multiple edge body shape or irregularly shaped etc.
In the device of the present invention, particulate vector of the present invention can be accommodated in the support or container of Any shape, the preferably commonly used biological sample sampling in this area, preserve, transportation, handle, and the used container of subsequent disposal, for example test tube, centrifuge tube, dialysis tubing, culture dish, sample retention card (card) etc.The surface of preferred particulate vector of the present invention is covered by a kind of flaky material that allows biological fluid to pass through to stop particulate vector to pass through.Particulate vector more preferably of the present invention is encapsulated in the enclosed space that is made of described support or container and described flaky material.To the character of above-mentioned flaky material without limits, but preferably constitute, for example reticulated structure of making of wire netting, sintered glass net, fabric, nylon wire or other macromolecular materials etc. by non-sorptive material.
Be easy to from solid carrier, reclaim according to the sample of absorption dehydration of the present invention by washing, routine operation such as centrifugal, and the reconstruct liquid sample.The liquid sample of reconstruct can be used for subsequent operations and application such as the detection, purification of sample inclusion, the detection and the purifying of for example various albumen, ion, VITAMIN, antigen, antibody, cell, nucleic acid etc.
According to the inventive method, gain quick return for the sample inclusion, rate of recovery height.For example the reclaimer operation of sample can be finished in several minutes time in the several seconds.According to the sample of kept dry of the present invention, the rate of recovery can reach at least about 70%, and preferably at least 80%, more preferably at least 90%, most preferably at least 95%.
Method and apparatus of the present invention is preferably applicable to the kept dry of various biomass cellss.The kept dry of the red corpuscle in the blood (RBC), white corpuscle (WBC), thrombocyte etc. for example.Before absorbing celliferous liquid sample, preferably solid carrier is handled in advance, as being closed, using organic solvent processing such as certain density cell fixation agent such as formalin, aldehydes, ethers, alcohols with containing the protein liquid bag.Cellular constituent is fixed and the subsequent dewatering drying, forms the immobilized cell sample that dehydrates.This sample is after adding appropriate solvent, cell can be able to aquation once more, again recover original structure formation, can further be applied to the histochemical stain, immunohistochemical staining, immunofluorescence dyeing, the detection of cell surface molecule, the sorting or the purifying of specific cells of cell, as with magnetic bead or utilize selected by flow cytometry apoptosis cell or classification and Detection etc.
The suitable stablizer of method and apparatus preferred combination of the present invention is applied to dehydrating of range protein molecule, especially various antigen, antibody, various enzymes or vitrifying is preserved.The advantage of the inventive method is can keep steadily in the long term when above-mentioned molecule is in the state of dehydrating or vitrifying state it in conjunction with activity and/or enzymic activity.When adding solvent mentioned component at short notice (in common 5 minutes) rapidly aquation, be evenly distributed in the liquid phase, thereby can carry out effecting reaction with corresponding part or substrate.
Method and apparatus of the present invention also preferably is applied to collection, the drying of blood sample and preserves.Before the blood sample collection, can carry out antithrombotics and handle or directly sneak into antithrombotics, for example heparin, EDTA disodium solid carrier.Blood specimen collection directly takes to point puncture blood collecting or sole puncture (baby) blood-sampling method.Allow drop of blood directly splash into particulate vector, dehydrate the mixture that forms dried blood particulate of anti-freezing and solid carrier then.Also can use sample injector that blood is quantitatively transferred on the above-mentioned porous support by conventional venipuncture blood sampling.When sample reconstruct, for example add and be equivalent to former blood sample volumetrical solvent (being generally pure water or distilled water) approximately and can obtain the reconstruct blood sample approaching rapidly with raw sample, can be used for subsequent disposal such as further check and analysis.According to the application purpose difference, also can not use antithrombotics directly drop of blood not to be gone into and make dried blood sample in the particulate vector with the antithrombotics processing.
Embodiment
Embodiment 1
Utilize glass particle material kept dry blood sample
Getting 2 milliliters of median sizes is about 2 millimeters glass bead.Described glass bead is fixed in the internal surface of centrifuge tube lid with wire netting.0.5 milliliter of whole blood sample that is added with heparin evenly is carried on the above-mentioned glass bead.The above-mentioned device that has loaded blood sample is placed the ventilation drying at room temperature.The lid and the centrifuge tube driving fit of dry sample will be loaded with, when using.
Parallel therewith, 0.5 milliliter of blood sample in a same source is directly used in the mensuration content of hemoglobin in addition.
Embodiment 2
The recovery of dry blood sample
To open by the centrifuge tube that has dry sample that embodiment 1 obtains, in centrifuge tube, add about 0.6 ml deionized water.Build lid, centrifuge tube is put upside down, make water contact about 5 minutes with glass bead.Then, lid promptly obtains the blood sample of reconstruct up with the centrifuge tube whipping several times or centrifugal a little.
By the content of hemoglobin of working sample, and with the contrast content of hemoglobin of embodiment relatively, the rate of recovery that calculates blood sample is about 96%.
Embodiment 3
Utilize sand grains kept dry blood sample
Operate according to method similarly to Example 1, but be the sand replacement glass bead of 0.8-2.0mm with particle size range.According to the same quadrat method operation of embodiment 2, reclaim blood sample.In the amount of oxyphorase, the rate of recovery of blood sample is about 93%.
Embodiment 4
From dry blood sample, extract genomic dna
With the dry and preservation of 0.25 milliliter of blood sample according to the method for embodiment 1.In having 1.5 milliliters of centrifuge tubes that carry the blood sample carrier, add 1 milliliter of erythrocyte lysate, make it contact 5 minutes with the load sample solid carrier.The jolting test tube, on the Eppendorf whizzer with maximum velocity centrifugation 15 seconds.Supernatant liquor is abandoned in suction.Add 1 milliliter of erythrocyte lysate again, centrifugal behind the jolting test tube, inhale and abandon supernatant.
In test tube, add 0.3 milliliter of DNA and discharge liquid, with white corpuscle precipitation mixing and left standstill 5 minutes.Then, add 0.1 milliliter of albumen precipitation liquid, mixing, centrifugal 5 minutes.
The supernatant liquor that will contain genomic dna is transferred in the test tube, measures DNA concentration.Carry out electrophoresis according to a conventional method, the quality of identification of dna (the results are shown in Figure 2).
With 0.25 milliliter of fresh blood sample in identical source as parallel control.
The average dna yield of 4 experiments is 35 micrograms as a result, and is 36 micrograms from the average yield of fresh blood.
Embodiment 5
The recovery of serum T 3, T4 and TSH
In 0.2 milliliter of serum adding carrier similarly to Example 1, drying is 3 hours under the room temperature.At room temperature preserved 1 month after the sealing.
The above-mentioned particulate vector that has dry serum sample is contacted 10 minutes with 0.2 ml distilled water.Supernatant is taken out in centrifugal back.Measure the concentration of T3, T4 and TSH respectively with the chemiluminescence immunoassay method.Serum sample to frozen identical source carries out same mensuration simultaneously.
Found that the average recovery rate (with respect to frozen sample) of three experiments of above-mentioned each factor is all near 98%.
Claims (10)
1. the method for drying and storing of a biological fluid, it comprises described liquid sample and a kind of median size, and to be 0.1mm contact to the particulate vector of 5mm; With from the solid carrier that has absorbed liquid sample, remove liquid component; Wherein said biological fluid is blood or its moiety.
2. according to the process of claim 1 wherein that the median size of described particulate vector is that 0.5mm is to 3mm.
3. according to the method for claim 2, the median size of wherein said particulate vector is that 1mm is to 2mm.
4. according to the process of claim 1 wherein that described particulate vector is to be made of one or more materials that are selected from down group: the material of polymer materials, biogenetic derivation, metallic substance and ceramic.
5. according to the process of claim 1 wherein that described particulate vector obtains by grinding screen point-score, paddling process granulation, compression moulding method granulation, spraying and the granulation of dispersion vapodusting, the granulation of the heat fusing method of forming.
6. according to the method for claim 4, wherein said polymer materials is the polymer beads by extrusion moulding, compression molding, injection molding preparation.
7. according to the method for claim 4, wherein said ceramic is the particulate material of being made by pottery, glass, cement or refractory materials.
8. according to the process of claim 1 wherein that the described liquid component of removing is undertaken by air-dry from solid carrier.
9. according to the process of claim 1 wherein that the described liquid component of removing under reduced pressure carries out from solid carrier.
10. device that is used for the kept dry liquid sample, it comprises that a kind of median size is the particulate vector of 0.1mm to 5mm; Wherein said liquid sample is blood or its moiety.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2004100295235A CN1311070C (en) | 2004-03-18 | 2004-03-18 | Method and device for dry conservation of biological liquid sample |
| PCT/CN2005/000286 WO2005087001A1 (en) | 2004-03-18 | 2005-03-09 | A method for the dryness preservation of biological fluid samples and the device thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2004100295235A CN1311070C (en) | 2004-03-18 | 2004-03-18 | Method and device for dry conservation of biological liquid sample |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1670190A CN1670190A (en) | 2005-09-21 |
| CN1311070C true CN1311070C (en) | 2007-04-18 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2004100295235A Expired - Fee Related CN1311070C (en) | 2004-03-18 | 2004-03-18 | Method and device for dry conservation of biological liquid sample |
Country Status (2)
| Country | Link |
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| CN (1) | CN1311070C (en) |
| WO (1) | WO2005087001A1 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN119756979A (en) * | 2024-12-18 | 2025-04-04 | 浙江清华长三角研究院 | A system, method and application for preserving human body fluids and excrement |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5776563A (en) * | 1991-08-19 | 1998-07-07 | Abaxis, Inc. | Dried chemical compositions |
| US5939259A (en) * | 1997-04-09 | 1999-08-17 | Schleicher & Schuell, Inc. | Methods and devices for collecting and storing clinical samples for genetic analysis |
| US20030073932A1 (en) * | 2001-09-05 | 2003-04-17 | Mark Varey | Body fluid sample preparation |
-
2004
- 2004-03-18 CN CNB2004100295235A patent/CN1311070C/en not_active Expired - Fee Related
-
2005
- 2005-03-09 WO PCT/CN2005/000286 patent/WO2005087001A1/en not_active Ceased
Non-Patent Citations (4)
| Title |
|---|
| 冷冻干燥保存血小板的研究进展 曹伟等，中国输血杂志，第16卷第5期 2003 * |
| 冷冻干燥保存血小板的研究进展 曹伟等，中国输血杂志，第16卷第5期 2003;微生物的促成方法 王成怀，微生物学免疫学进展 1979;微生物实验室菌种的保管与保存 孙炜，医学理论与实践，第15卷第10期 2002 * |
| 微生物实验室菌种的保管与保存 孙炜，医学理论与实践，第15卷第10期 2002 * |
| 微生物的促成方法 王成怀，微生物学免疫学进展 1979 * |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2005087001A1 (en) | 2005-09-22 |
| CN1670190A (en) | 2005-09-21 |
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