CN1084045A - Oral collection and corollary apparatus - Google Patents
Oral collection and corollary apparatus Download PDFInfo
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- CN1084045A CN1084045A CN 93109746 CN93109746A CN1084045A CN 1084045 A CN1084045 A CN 1084045A CN 93109746 CN93109746 CN 93109746 CN 93109746 A CN93109746 A CN 93109746A CN 1084045 A CN1084045 A CN 1084045A
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Abstract
A kind ofly be used to obtain comprise the apparatus of substances at interior mouth liquid.In one embodiment, this apparatus comprises a syringe that has plunger, fixes one in the end of plunger and inhales pad.A kind of assay device that comprises this apparatus is also disclosed.
Description
The present invention relates to obtain mouthful liquid so that equipment of testing and method.
List of references:
Parry，J.V.，et al.，Lancet 2：72-75（1987）.
Thieme，T.，et al.，J.Clin.Microbiol.20：1076-1079（1992a）.
Thieme，T.，et al.，"Oral Fluid Sampling for Determination of HIV-I Antibody Serostatus，"Abstract from Ⅷ Int′1.Conf.on AIDs，pg.C328（1992b）.
Generally be used for checking body fluid many kinds to be arranged with analytical method and the equipment that the material that obtains diagnostic value exists.Blood and urine all are the selected body fluid that comes out.The concentration that blood is analyte as an advantage of test(ing) liquid is quite high usually, measures the information that these concentration can provide relevant patient health situation usually.When sense was concentrated during the blood constituent (as low-molecular-weight medicine or hormone) of interest is being urinated formation, urine was exactly of great use for diagnostic test.But the concentration of analyte in urine does not often reflect the physiological activity amount of analyte in the blood.
Although not being used as body fluid usually in medical diagnosis, saliva do not use, but many research (Parry, et al., Thieme, et al., 1992 a, b) verified: the mouth liquid of saliva and other type can provide reliable sample for diagnostic test, comprising antigen or the antibody special to human or animal's various cause of diseases.In the body of level and medicine and other medicines during level, mouthful liquid also is proved to be useful in measuring the body of natural hormone.
It is very convenient that the aspect that the sampling of mouthful liquid is better than blood and urine sampling is to obtain sample.The sampling of mouth liquid does not need the well-trained blood drawing personnel as blood, unlike urine yet
Sampling need be exclusively used in the special utensil of sample collection and keeping like that.Have again, collect the trouble that mouthful liquid sample also can avoid handling the syringe needle that dyed by blood stains and needle tubing and so on.
The equipment of collecting mouthful liquid was described.United States Patent (USP) 4,418,702 and 4,580,577 disclose a kind of suction pad that absorbs mouthful liquid, and from inhaling the syringe-plunger mechanism of pad extraction mouthful liquid.
United States Patent (USP) 4,774,962 have described a kind of suction pad that absorbs saliva, and centrifuge tube and pipe insert, are used for going up conveying end liquid by centrifugal action from inhaling pad.
United States Patent (USP) 5,056,521 have described a kind of mouthful equipment of liquid glucose that is used for monitoring.This equipment comprises a syringe-plunger mechanism, and there is a non-reacted absorption swab that is fixed on the plunger in this mechanism.With syringe and plunger liquor sample is clamp-oned the glucose monitoring instrument from swab.
One aspect of the present invention comprises a kind ofly collects mouthful liquid so that the apparatus of diagnosing.This apparatus comprises a suction pad, is used for extracting substances from mouth liquid, also comprises a structure (device), is used for going up extraction from the suction pad and has absorbed the mouth liquid that fills up.
Specifically, comprise that from inhaling structure that pad extracts the mouth liquid that has absorbed syringe with a syringe and one are with the plunger of inhaling pad.
Inhale pad and can comprise various additives, for example antiseptic, salt, spice and protective agent are used for anti-seam fluid component to inhaling the non-specific combination of pad.In a preferred embodiment, soak into the hyperosmotic solution of salt and to inhale pad, will be further described this below.
In a further advantageous embodiment, this syringe further comprises a fluid path that is positioned at the syringe port of export, and detectable (one or more) is included in this path, and very moment liquid is when syringe is discharged, and this reagent can enter in mouthful liquid effectively.This path can determine that this reagent pipe is installed on the syringe by dismountable mode by a reagent pipe.
By related fields of the present invention, the present invention includes a determinator, be used for measuring the substances of mouthful liquid.This device comprises above-mentioned suction pad-syringe construction and a detecting unit that is used to admit from the mouth liquid of this structure discharge.This detecting unit comprises a solid phase carrier and attached to the bonding agent on this carrier, and when very moment liquid was drained into this detecting unit from syringe, this bonding agent can be attached on the substances in mouthful liquid effectively specially.This detecting unit can be connected to the port of export of syringe, or can be used as a structure of independently admitting liquid.
This device comprises that further one becomes the path that links to each other with syringe of fluid connection with detecting unit.This path can comprise detectable (one or more), and very moment liquid is when syringe is discharged, and this reagent can enter in mouthful liquid effectively.Detectable (one or more) preferably can be reacted effectively with the experiment material in the mouth liquid, can detected signal so that on carrier, produce one, and this signal depends on the concentration of substances in mouthful liquid.
In a preferred embodiment of this device, solid phase carrier is a permeable film, and this detecting unit further comprises an absorption piece, and this absorption piece can contact with film, thereby can extract the mouth liquid that passes this membrane carrier.
By a kind of structure, this substances is a kind of antibody, and this antibody is by the diagnosis of known pathogen infection.Bonding agent can be a kind of antigen, this antigen can be tested antibody generation immunoreation with this, this device further comprises the reagent of a report information substance markers in this case, and when this reagent was attached on the solid phase carrier, this reagent can be attached on this substances antibody effectively.
In addition, this bonding agent can be selectively in conjunction with people's antibody, and this device may further include a kind of antigen of report information substance markers in this case, this antigen can with substances antibody generation immunoreation.A kind of typical combination agent in conjunction with substances antibody is a protein A.
By another kind of structure, this substances is a kind of antigen, and this antigen is by the diagnosis of known pathogen infection.Bonding agent can be a kind of antibody, this antibody can with test antigen generation immunoreation, this device can further comprise a kind of reagent of report information substance markers in this case, and this reagent is when being incorporated into solid phase carrier, and this reagent can be attached on this substances antigen effectively.
Press another aspect of the present invention, comprise a surface of solid phase carriers, be used for that the two identifies that simultaneously mark substance promptly is the material that can provide reliable indication to the mouth liquid that is verified to the substances of a mouth liquid sample and mark substance.First and second bonding agent in conjunction with substances and mark substance can be positioned at the not overlapping region of this surface to small part respectively.It is rectangular that two lands are preferably formed as two of symbol "+".
When reading following detailed description of the present invention in conjunction with the accompanying drawings, these and other objects of the present invention and feature will be clearer.
Figure 1A and 1B are the cross sectional side views by the oral collection of one embodiment of the invention, (Figure 1A) and the situation of (Figure 1B) afterwards before being illustrated in this apparatus plunger and syringe engaging:
Fig. 2 is the plunger of Fig. 1 apparatus and the assembly drawing of inhaling pad;
Fig. 3 A and 3B represent another reagent pipe and syringe embodiment;
Fig. 4 represents the cross sectional side view by assay device of the present invention;
Fig. 5 represents the cross sectional side view by another embodiment of assay device of the present invention;
Fig. 6 A-6C represents to be used for detecting by the present invention the typical solid phase form of mouthful liquid substances;
Fig. 7 represents the layout of a surface of solid phase carriers, and the substances and the mark substance that are used for boil on the nape opposite the mouth liquid are measured simultaneously.
A. oral collection
Figure 1A and 1B represent an oral collection 8 by the present invention's structure.This catcher in general comprise one play collect mouthful suction pad 10 of liquid effect, be attached to a plunger inhaling on the pad 10 11, a syringe 12 and a dismountable reagent pipe 13 in the embodiment shown.Plunger 11 comprises: plunger rod 14, sealing gasket 15(are positioned at plunger the inner), push pedal 16(is positioned at the plunger outer end).
Fig. 2 represents plunger and inhales the assembly drawing of pad.As shown in Figure 2, the plunger rod practice routinely comprises a pair of radial extension piece 18,20 near plunger rod the inner, and its end is a finger-like outthrust 22.In the usual way, preferably form plunger rod and push pedal by the suitable polymer of injection molding.
Inhaling pad can be made by any material in a series of absorbing materials that are suitable for using in the oral cavity.Fill up preferably a kind of thick absorbability cotton-wool or paper, for example dental procedure is normally used the sort of.An example of this suction pad is: Patterson Dental Co.(Minneapolis, 1.5 English, the 2 medium cotton-wools of MN) selling.Also can use the material such as cellulose, polyurethane, polyester and staple fibre.
In one embodiment of the invention, soak into the hyperosmotic solution of salt and to inhale pad, the amount of solution is effective to the substances (for example immunoglobulin) that reclaims high concentration in mouth liquid.As at United States Patent (USP) 5,103, (here with reference to having introduced this patent) like that described in detail in 836, the result who uses hyperosmotic solution can produce immunoglobulin in other source from the oral cavity, these sources still indefinite now all clear Chu consistently.Compare with the use distilled water, the immunoglobulin that uses hyperosmotic solution to obtain may improve 8-16 times more than.
Hyperosmotic solution is the saline solution that a kind of ion concentration surpasses the ion concentration in the blood.Generally speaking, the quantity of used salt is from about 1.5% to about 5%(by weight in preparation hyperosmotic solution of the present invention), be preferably 3.5%(by weight).
Operable salt comprises alkali metal compound in the preparation hyperosmotic solution, and alkaline earth metal compound.Preferred salt comprises: sodium chloride, potassium chloride, magnesium sulfate, magnesium chloride and calcium chloride.Find, the toxicity minimum of sodium chloride, price is the most cheap, and mouthfeel is best.
Hyperosmotic solution also can comprise excretory chemical compound of a kind of saliva stimulating or composition.We find to have tart flavour by the excretory chemical compound of saliva stimulating.These chemical compounds comprise weak organic acid.In the middle of weak organic acid preferably: citric acid, ascorbic acid, acetic acid.The optium concentration of using citric acid and ascorbic acid about 0.05% and 0.5%(by weight) between.The optimum range of acetic acid about 0.5% and 3.0%(by weight) between.
Reduce to minimum for the rotten probability of sample that will collect, can comprise antiseptic in the hyperosmotic solution.A kind of like this effect of antiseptic is the activity of Profilin catabolic enzyme, and the activity of this kind of enzyme may cause antibody molecule to destroy.Expectation comprises as the chemical compound of antiseptic: antibacterial agent, antifungal, bacteriostatic agent, fungistat and enzyme inhibitor.In a preferred embodiment, make antifungal with benzoic acid, sorbic acid or their salt.As bacteriostatic agent, expectation is used the salt of high concentration and can keep the chemical compound of hyperosmotic solution under low pH value.Such salt comprises: thiomersalate (or thimerosal), phenylmercuric acetate, phenylmercuric nitrate and Hydrazoic acid,sodium salt.Other preferred preservative is included in medicine neutralization normally used those antiseptic in the medicine of gargling.For example ethanol and chlohexidine gluconate.The preferred antimicrobial of another kind of type and antiviral agent are can be as topical germicide's detergent that use or that use in the medicine of gargling, for example benzalkonium chloride.Use the scope of these antiseptic to be preferably about 0.01% to about 0.2%(by weight).
To inhale pad by existing method with hyperosmotic solution soaks into.Hyperosmotic solution of the present invention is added to the method for inhaling on the pad can be: be impregnated in the hyperosmotic solution of salt inhaling pad, inhale on the pad thereby the salt in the solution is absorbed in the pad neutralization, will inhale pad and take out and make its drying from solution.In general, immerse in the hyperosmotic solution, can absorb about 1ml(milliliter if will inhale pad) this solution.In addition, hyperosmotic solution can be sprayed onto and inhale on the pad, when inhaling pad and absorb the solution of sufficient amount (preferably about 1ml) till.The unnecessary liquid of inhaling on the pad is rocked, will inhale pad then and put into 50 ℃ forced air convection baking oven two hours, perhaps under the situation of not forcing the air existence, put into 80 ℃ baking oven 6-12 hour.After the oven dry, promptly formed a suction pad saliniferous hyperosmotic solution of bag, the process special handling.In the preparation process of pad, preferably use following salt as antiseptic: benzalkonium chloride, acetyl chloride pyridine or chlohexidine gluconate.
Can make most of materials of inhaling pad all may be in unspecific mode in conjunction with holding onto protein.Therefore, immunoglobulin just can be incorporated into to be inhaled on the pad, and this does not expect; Expectation stops protein to the combination of inhaling pad by using protective agent.Because blood comprises its protective agent (that is, the human serum albumin), therefore the nonspecific combination in blood sample collection generally is out of question.
In order in oral fluid sample is collected, to reduce unspecific combination, can in hyperosmotic solution, add protective agent, be added in the suction pad thereby be about to protective agent.Protective agent generally is a kind of soluble protein, prevents the nonspecific combination of another kind of albumen to the surface of solids with it.The chemical compound that can be used as the protective agent adding comprises albumin and gelatin, but any water-soluble nontoxic protein all can be used as protective agent, and condition is that this albumen does not have adverse influence to the mensuration that will adopt.Preferably use Bos taurus domesticus Gmelin.In general, the protectant concentration that is added to hyperosmotic solution of the present invention about 0.01% and 0.2%(by weight) between.By the above component contained in the hyperosmotic solution is added to then and inhales on the pad.
The preferred solution of use is composed as follows when pad is inhaled in preparation:
Concentration of component (%, by weight)
Sodium chloride 3.5%
Citric acid 0.3%
Sodium benzoate 0.1%
Potassium sorbate 0.1%
Bos taurus domesticus Gmelin 0.1%
Distilled water
Add the 0.1N sodium hydroxide
PH value is increased to about 6.5
Now referring again to Figure 1A and 1B.Syringe 12 has been determined an inwall 24; Inwall 24 can be admitted in the longitudinal direction and inhale pad and plunger pad (shown in Fig. 2 A), and can hold pad 15 on diametric(al) compactly, thereby forms a fluid-tight sealing between them.Syringe 12 has opening 26 protrusion or that radially strengthen, is convenient to will inhale pad and puts into syringe after collecting mouthful liquid.In relative the inner of syringe a sintered plate 28 is set, its effect is a filter that can see through liquid, when forcing plunger to enter syringe, allows to inhale the mouth liquid that absorbs in the pad and passes through, and discharges from syringe.The outlet 30 that is positioned at the syringe end provides the socket of admitting reagent pipe 13.In the embodiment of the equipment that does not comprise reagent pipe 13, the syringe construction of the port of export image scale standard of syringe is such, can be tapered, and forms a narrow thin outlet.Syringe also refers to the device that extraction has absorbed the mouth liquid in the suction pad into here.
Typical sizes by plunger of the present invention-suction pad mechanism and syringe is: the length of plunger 11 comprises the length of sealing gasket 15 being about 3 inches that diameter is about 0.12 inch; The length of inhaling pad 10 is about 1.5 inches, and diameter is about 0.375 inch.If use soft picture glue sealing gasket, the sealing gasket of 0.5 inch diameter and about 0.25 inchage is suitable for forming liquid-tight sealing in internal diameter is about 0.4375 inch syringe so.
In Fig. 3 A and 3B, express other embodiment of reagent pipe and syringe.For example as shown in Figure 3A, pin hole outlet 38 can be an insertion (Luer
TM) connector 39, what be used for connecting reagent pipe 42 accepts connector 40 accordingly.The reagent pipe comprises a rigidity sintered plate 44 that soaks into detectable (one or more).Express a similarly device among Fig. 3 B, just the insertion connector 46(Luer of syringe outlet 48
TM) directly be recessed in the main body of syringe.Fig. 3 B also expresses a syringe cylinder structure, and the inwall of syringe wherein is tapered towards its port of export, so that reduce remaining mouthful of liquid quantity in the syringe when pad is inhaled in extrusion.
Band 50 in the reagent pipe is the reagent strips that can get wet, when it is got wet by the mouth liquid of syringe, exists in mouth liquid under the situation of analyte, and band 50 produces the change color that can detect.Use known enzyme can detect analyte (for example glucose), these enzymes for example are and peroxidase system, coupled glucoseoxidase together that it can be at H
2O
2Producing effectively under the situation about existing can detected change color.In each the reagent pipe embodiment shown in Fig. 1-3, an interior chamber determines a path, the internal path 33 in the reagent chamber 13 for example, this path can comprise detectable (one or more) or reagent device, detectable was discharged into (Fig. 1 and 2) in mouthful liquid when very moment liquid was discharged from syringe, perhaps with by this path the mouth liquid mix (Fig. 3) effectively.
On the other hand, can be included in the port of export of syringe, for example, therefore just not need independent reagent pipe along the sidewall of syringe outlet comprising the path that detects the examination survey.
In order to collect the material in the oral cavity with catcher (for example equipment shown in Figure 1A and the 1B), plunger-suction pad mechanism is put into patient's mouth, so that allow suction padding body all be in the mouth.Place to inhale between jowl and gingiva that pad is convenient to that absorption derives from the adenoid secretions of gum and from tela submucosa lymphoid tissue and the adenoid secretions of salivary gland.When collecting sample, be preferably between the gingiva erasing back and forth and inhale pad about 10 seconds, inhaled the pad location then motionless about 30 seconds to 2 minutes.After the suction pad soaks into mouthful liquid, will inhale pad and from mouth, extract out, then plunger-suction pad mechanism is put into syringe, put earlier to inhale and fill up the end, so that can extract a mouthful liquid by the self-priming pad.
Mouth liquid can be stored, analyze a little later again, mouthful liquid preferably is stored in the suitable impregnating fluid.In addition, mouthful liquid can mix with detectable (one or more), perhaps directly discharges (not detecting through reagent), is perhaps discharging on the solid phase checkout equipment with after detectable is mixed again, and this will be described in the B section below.
In addition, can measure mouthful liquid analyte by the solution homogeneous assay method and design reagent in the intake liquid.For example the mensuration of using in the antigen-specific antibody that exists in detecting mouthful liquid can be according to various homogeneous determination forms, for example according to coupled enzyme, Quenching of fluorescence or EMIT structure (Gosling, J., Clin Chem, 36(8): 1408(1990)).In addition, this mensuration may relate to the immunoprecipitation of analyte in mouthful liquid, thus produce a kind of can detected coagulation product, for example be surrounded by the colored bead of immune precipition.
Be appreciated that as previously mentioned how each purpose of the present invention and feature satisfy.This apparatus all is very easily for hospital, clinic even domestic, and the collection of oral fluid sample is easy to, and can measure immediately.Because plunger-suction pad mechanism can insert behind sample collection in the syringe, can be placed on and be wrapped in the syringe.Therefore this equipment can reduce the danger of sample contact user.
B. mouthful liquid determinator
By the present invention on the other hand, comprise a device that detects substances in mouthful liquid.This device generally comprises suction pad needle cylinder mechanism and detecting unit that is suitable for admitting the mouth liquid of inhaling the pad discharge of a above-mentioned type.This detecting unit has the solid phase carrier and a kind of bonding agent that is attached on this carrier that are included in the detecting unit, and when very moment liquid entered this unit from syringe, this bonding agent can be attached on the experiment material in mouthful liquid effectively specially.Then by analyte such as antigen or immunoglobulin concentration in the definite mouthful of liquid of quantity that is attached to the analyte on the carrier.In one embodiment, this the device as described in the above-mentioned A section, comprise a path, this path comprises detectable (one or more), (a) very moment liquid this reagent when syringe is discharged can be discharged effectively, and (b) this reagent comprises one or more reagent component, these components be produce can detected solid phase association reaction necessary, comprising the analyte that is attached to solid phase surface.
The substances of mensuration is depended in the selection of mensuration form.This substances comprises various immunoreation analytes, the metabolite of medicine and medicine for example, as cocaine or nicotine or their metabolite, and virus and bacterial antigens such as hbs antigen, immunoglobulin, particularly IgG and IgM, hormone in addition, as β-HCG.Absorb or be well-known to the method on the solid phase carrier covalently in conjunction with selected bonding agent, this method comprises: biology miniature (biotinylated) albumen (for example ovalbumin) is adsorbed onto on the film, adhere to bonding agent with streptavidin derivation form subsequently, the antibody of Fc part that will bonded antibody by specific for example opposing is attached to antibody on the carrier, but and for example uses various available difunctional coupling reagent to be covalently bound on the surface derivation group on the film.
Figure 4 and 5 are represented two embodiment by determinator of the present invention.The bottom of all expressing syringe collecting device 52 in these two figure is comprising syringe 54 and reagent pipe 56.The structure of describing in the structure of this collecting device and the above-mentioned A section is identical.In the embodiment of Fig. 4, detecting unit (representing with 60) can be connected on the reagent pipe, is used to admit the mouth liquid that goes out from the reagent bank of tubes.The reagent pipe can comprise detectable (one or more), the molecule of report information substance markers for example, and the analyte molecule that their can and be attached on the solid phase carrier be competed effectively.
Unit 60 generally comprises has inlet 63 shell 62, this inlet can be connected to the reagent pipe outlet side and with this outlet side fluid connection, as shown in the figure.Solid phase carrier or film 64 are fixed in this shell, and its position is suitable for holding the mouth liquid of discharging from syringe device.In the structure 68 of accordion shape and below film 64, suspend one and inhale pad 66, so that when inhaling the following side contacts of pad and film, aspirate the mouth liquid that passes film.
Fig. 5 represents to have the detecting unit 70 of film 72, can observe film 72 by window 74, and film 72 and window 74 all are fixed in the overcoat 75.The suction pad 76 that is positioned at film 72 belows by make the jacket bottom distortion can with the following side contacts of film so that extract the mouth liquid that passes film 72.
Though the detecting unit among the combination embodiment shown in the Figure 4 and 5 can be fixed to the mouth liquid of directly admitting on the syringe device from syringe, but the present invention also expects to have a kind of device, detecting unit wherein is an independent structures, for example admits a mouthful liquid by the mode that is coated with liquid suitable for reading and other detectable on the film in this unit.
In Fig. 6 A, 6B and 6C, express the various mensuration structures that in this device, to use.In Fig. 6 A, a kind of substances 80(antibody) be to carrier-bound antigen 84, to be captured on the solid phase carrier 82 by immune specific bond.The analyte of capturing then can detect by the non-human body antibody 86 of report information substance markers again.
Fig. 6 B represents to detect the solid phase carrier 88 of test antibody 90.By at the bonding agent 92(that carries on the solid phase carrier such as protein A and non-human immunoglobulin) analyte antibody is attached on the immobilon-p.By the antigen 94 of immunoreactive labelling report information taking place, can detect bonded analyte antibody with test antibody.
Fig. 6 C represents to be used for detecting mouthful solid phase carrier 96 of liquid antigenic analysis thing 98.Bonding agent in this unit is a kind of antibody 100 of antigen-specific.Detectable with a kind of antibody that comprises the report information substance markers (the second epi-position generation immunoreation on it and the analyte) can detect the antigen-analyte that is attached on this carrier.On the other hand, this detectable can be a kind of antigen of report information substance markers, and this antigen can be competed with analyte antigen, so that be attached on the bonding agent of solid phase carrier.
Routinely, the report information thing in the above-mentioned testing reagent is that the suitable material of a kind of adding can detected enzyme, or a kind of fluorescence report information thing.
Identify when the mensuration of the substances in the boil on the nape opposite the mouth liquid can comprise a kind of mark substance, will be further described this below.In the typical case who uses surface of solid phase carriers of the present invention that oral fluid sample is carried out identified, substances was a kind of and the HIV-1 peptide plays immunoreactive antibody, and mark substance is a transferrins.Surface of solid phase carriers includes the protein A that is attached to first district, film surface, is used for the antibody in conjunction with the people, also includes the anti-transferrins antibody that is attached to second district, film surface, and it is effective to capturing transferrins.In order to detect HIV-1 antibody and transferrins, this mensuration comprises the horseradish peroxidase conjugate of HIV-1 peptide, concerning it, test HIV-1 antibody is special, and the horseradish peroxidase conjugate of anti-transferrins antibody, it can be in conjunction with transferrins, and no matter whether the first anti-transferrins antibody also has been attached on the same transferrin molecules).The second anti-transferrins antibody preferably comes from chicken, because the not conjugated protein A of chicken antibody.The reagent of report information substance markers can be immersed in the reagent dish with dried forms, then the reagent dish is put in the reagent pipe.Afterwards, the reagent pipe is fixed on the oral collection of the present invention.Use this equipment in disease population, to collect oral fluid sample, from syringe and reagent pipe extrusion liquid by joining with it.Very moment liquid is during by the reagent pipe, and the reagent of report information substance markers is absorbed by mouth liquid, and is dissolved in mouthful liquid, thereby produces the reaction of reagent and corresponding substances and mark substance.The direction of reagent pipe outlet should make reagent/mouth liquid mixture supply on the surface of solid phase carriers.Several (about 300 μ l) this mixture just should be enough.Allow this mixture on surface of solid phase carriers, stay for some time (about 5 minutes), just be enough to allow substances and mark substance be attached on the relevant detection reagent, and be attached to the land of the correspondence on the surface of solid phase carriers.Then, remove this mixture from this surface.
In another embodiment, substances is a kind of " Helicobacter pylori " antibody, and the reagent of report information substance markers is a kind of report information substance markers " Helicobacter pylori " antigen.
If surface of solid phase carriers is the part of detecting unit of the determinator of the invention described above, the method for removing this mixture so is to allow a following side contacts of inhaling pad and the solid phase carrier of extraction opening liquid.At last, the solution that will comprise the chromogen substance (being tetramethyl-benzidine in this example) of hydrogen peroxide and horseradish peroxidase is delivered on this film.Any horseradish peroxidase that is attached on the solid phase carrier by substances or mark substance can both produce the precipitate of being with color in the bonded zone of peroxidase.Then, the pattern that produces from surface of solid phase carriers is determined the existence of mark substance and/or substances.
By a special aspects of the present invention,, identify simultaneously the mark substance that always is present in the oral fluid sample in order to examine measurement result to substances.This label mass-energy in the test sample provides a kind of reliable indication: this sample comprises a mouthful liquid.Suitable mark substance for example comprises: and transferrins, albumin, ceruloplasmin and amylase (referring to: " Human Saliva ": Clinical Chemstry and Microbiology, vols. I and II, Tenovuo, J.O., Ed., CRC Press, Boca Raton, Florida(1989)].When substances also is (for example IgG) when being derived by blood, be very useful by the deutero-mark substance of blood (for example albumin and transferrins).
Preferably use a determinator come determination test material and mark substance the two, solid phase carrier comprises a flat surface in this device.Preferably a kind of microporous membrane of solid phase carrier, the material of making this film for example can be nitrocellulose or polyvinyl iodide difluoride.First and second bonding agent that correspond respectively to substances and mark substance are positioned to different (nonoverlapping) surf zone of small part, thereby can distinguish substances and the mark substance that is attached on the surface of solid phase carriers.Mode by covalency and non-covalent mode all are well-known in conjunction with the method for some bonding agent so in the art.Discernible pattern can be produced when being preferably formed as these zones, measurement result can be obtained easily at a glance.
Although aforesaid case description use the situation of horseradish peroxidase as the report information thing, it should be understood that the enzyme that can also use other and the report information thing of non-enzyme.Though using identical report information thing is easily, the report information thing that is used for detecting substances needn't be with to be used for the report information thing of certification mark material identical.In addition, also can adopt other combination.For example, in the evaluation of hbs antigen, the bonding agent on solid phase carrier can be to carry out immunoreactive first antibody with this antigen in boil on the nape opposite the mouth liquid, and detectable can be the second antibody of report information substance markers.
Fig. 7 expresses the picture on surface of a typical solid phase carrier passing on measurement result.Slab region 104 and 106 among the figure be in the solid phase carrier 108 by the bonding agent derivation or the zone of handling, these bonding agent and selected mouthful of liquid label (for example transferrins) and selected mouth liquid analyte (for example analyte of antigen-specific) be respectively immunologic opsonin or talk about reaction.As shown in the figure, two zones are aligned to the symbol of "+" shape.Can recognize that if colour developing but do not develop the color in analyte district 106 in label district 104 then produces a pattern "-", this shows: contain mouthful liquid label in the sample liquids but do not contain the analyte that will test.When such analyte exists, can be observed symbol "+".
Though described the present invention at specific embodiments, should be realized that, can also carry out various changes and modifications without departing from the invention.
Claims (23)
1, a kind of being used to obtains to comprise the apparatus of substances at interior mouth liquid, it is characterized in that comprising:
Inhale pad, be used for reclaiming a kind of substances for one from mouth liquid;
Be used for from inhaling the mechanism that pad extracts the mouth liquid that has absorbed in the pad, wherein said mechanism comprises that one has the syringe that inner plunger is formed by syringe and one, and suction is filled up and is fixed on this inner.
2, apparatus as claimed in claim 1 is characterized in that said suction pad soaks into the hyperosmotic solution of salt.
3, apparatus as claimed in claim 2 is characterized in that this substances is a kind of antibody, and this hyperosmotic solution comprises about 3.5% sodium chloride, about 0.3 citric acid, about 0.1% potassium sorbate, about 0.1% sodium benzoate and about 0.1% Bos taurus domesticus Gmelin.
4, apparatus as claimed in claim 1 is characterized in that wherein syringe has an opening that radially strengthens that holds plunger.
5, apparatus as claimed in claim 1, it is characterized in that further comprising a fluid path that is positioned at the syringe port of export, and further comprise a detectable device that is included in the said path, very moment liquid is when syringe is discharged, and this detectable can be discharged in mouthful liquid effectively.
6, apparatus as claimed in claim 5 is characterized in that fluid path wherein is definite by a reagent pipe, and this reagent pipe is installed on the syringe by dismountable mode.
7, apparatus as claimed in claim 5 is characterized in that reagent device wherein comprises reagent, and this reagent can effectively react with the substances in the mouth liquid, and generation can detected change color.
8, apparatus as claimed in claim 5 is characterized in that detectable device wherein comprises reagent, and this reagent can carry out effecting reaction with the substances in the mouth liquid, and this substances of coagulation effectively, and generation can detected precipitate.
9, apparatus as claimed in claim 5, it is characterized in that further comprising the absorption band that becomes fluid connection with fluid path, said band includes detectable, and when existing substances and this band to be got wet by mouth liquid in the very moment liquid, this band can produce effectively can detected change color.
10, a kind of device that detects substances in mouthful liquid is characterized in that comprising:
Inhale pad for one, be used for from mouth liquid recovery test material,
A syringe is made up of syringe and plunger, and plunger has a inner, inhales to fill up to be fixed on this inner, has been absorbed in the interior mouthful liquid of pad so that go up extraction from the suction pad; And
A detecting unit, be suitable for admitting from inhaling the mouth liquid that pad is discharged, there is a solid phase carrier said unit, this solid phase carrier is included in this detecting unit, said unit also has a kind of bonding agent, bonding agent is attached on the solid phase carrier, and when very moment liquid entered this unit from syringe, this bonding agent can be attached on the substances in mouthful liquid effectively specially.
11, device as claimed in claim 10 is characterized in that said suction pad soaks into the hyperosmotic solution of salt, and the quantity of the said salt that exists in inhaling pad should be able to reclaim the substances of high concentration from mouth liquid.
12, device as claimed in claim 10, it is characterized in that wherein substances is a kind of antibody, this antibody is a kind of by the diagnosis of known pathogen infection, this bonding agent is a kind ofly can immunoreactive antigen take place with a kind of like this antibody, this device further comprises a kind of reagent of report information substance markers, when the substances antibodies was to this solid phase carrier, this reagent can be attached on this substances antibody effectively.
13, device as claimed in claim 10, it is characterized in that wherein substances is a kind of antibody, this antibody is a kind of by the diagnosis of known pathogen infection, bonding agent is effective to the antibody in conjunction with the people selectively, and this device further comprises the antigen of a report information substance markers, this antigen can with substances antibody generation immunoreation.
14, device as claimed in claim 12 is characterized in that bonding agent wherein is a protein A.
15, device as claimed in claim 13 is characterized in that substances is a HIV-1 antibody, and the reagent of report information substance markers is the HIV-1 peptide of report information substance markers.
16, device as claimed in claim 13 is characterized in that substances is a Helicobactor antibody, and the reagent of report information substance markers is the Helicobacter pylori antigen of report information substance markers.
17, device as claimed in claim 10, it is characterized in that it comprises that a path is connecting the syringe that becomes fluid connection with detecting unit, and said path includes the detectable device, and very moment liquid is when syringe is discharged, and this detectable can enter in mouthful liquid effectively.
18, device as claimed in claim 17 is characterized in that said path is definite by a reagent pipe, and this reagent pipe is connected on said syringe and the detecting unit by removably.
19, device as claimed in claim 17, it is characterized in that the detectable device comprises a kind of reagent, this reagent can be effectively with mouth liquid in substances react, thereby produce the substances of certain level and combining of solid phase carrier, bonded level depends on the concentration of substances in mouthful liquid.
20, device as claimed in claim 10 it is characterized in that solid phase carrier wherein is a permeable film, and detecting unit further comprises the adsorbing material that can contact with film.
21, device as claimed in claim 10 is characterized in that substances in the oral fluid sample and mark substance are measured simultaneously, and solid phase carrier wherein is a film, and this film comprises:
One first film district, a kind of first bonding agent is attached to this first film district, and first bonding agent can be attached on the substances in mouthful liquid effectively specially;
One second film district, a kind of second bonding agent is attached to this second film district, and second bonding agent can ad hoc be attached on the mark substance in mouthful liquid effectively, and this second film district and the first film district are not overlapping at least in part;
Be used to observe the device of the substances that is attached to the said first film district; And
Be used to observe the device of the mark substance that is attached to the said second film district;
Therefore, comprise mark substance but the mouth liquid that do not comprise substances will produce a kind of pattern on surface of solid phase carriers, this pattern and distinguish to some extent by the pattern that comprises mark substance and comprise the mouth liquid generation of substances.
22, a kind of surface of solid phase carriers, the substances and the mark substance that are used for boil on the nape opposite the mouth liquid are measured simultaneously, it is characterized in that it comprises:
One first district, a kind of first bonding agent is attached to this first district, and first bonding agent can be attached on the substances in mouthful liquid effectively specially;
One second district, a kind of second bonding agent is attached to this second district, and second bonding agent can be attached on the mark substance in mouthful liquid effectively specially, and this second district and first district are not overlapping at least in part;
Be used to observe the device of the substances that is attached to said first district; And
Be used to observe the device of the mark substance that is attached to said second district;
Therefore, comprise mark substance but the mouth liquid that do not comprise substances will produce a kind of pattern on surface of solid phase carriers, this pattern and different by comprising mark substance and comprising the pattern of mouth liquid generation of substances.
23, surface of solid phase carriers as claimed in claim 22 is characterized in that said first and second districts are bar shapeds, and is piled up formation symbol "+".
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US07/935,845 US5339829A (en) | 1989-09-21 | 1992-08-25 | Oral collection device |
| US935,845 | 1993-08-03 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1084045A true CN1084045A (en) | 1994-03-23 |
Family
ID=25467773
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 93109746 Pending CN1084045A (en) | 1992-08-25 | 1993-08-24 | Oral collection and corollary apparatus |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN1084045A (en) |
| MX (1) | MX9305156A (en) |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2007062575A1 (en) * | 2005-11-30 | 2007-06-07 | Inverness Medical Switzerland Gmbh | A device for detecting the presence or amount of an analyte in a fluid sample and method thereof |
| US7837939B2 (en) | 2003-11-14 | 2010-11-23 | Alere Switzerland Gmbh | Rapid sample collection and analysis device and methods of use |
| CN101963613A (en) * | 2009-07-23 | 2011-02-02 | 艾博生物医药(杭州)有限公司 | Detecting device |
| US8071394B2 (en) | 2006-07-26 | 2011-12-06 | Alere Switzerland Gmbh | Test device for detecting an analyte in a liquid sample |
| CN105015891A (en) * | 2014-04-16 | 2015-11-04 | 深圳华大基因研究院 | Sample storage device and method for storing and taking liquid sample by using same |
| CN107290548A (en) * | 2016-04-11 | 2017-10-24 | 福因德科技（武汉）有限公司 | Ectopic pregnancy detection means |
| CN108272473A (en) * | 2018-03-02 | 2018-07-13 | 杭州霆科生物科技有限公司 | A kind of electronic spittle collector |
| CN110582353A (en) * | 2017-03-02 | 2019-12-17 | 英雄科学有限公司 | method for detecting microparticles |
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-
1993
- 1993-08-24 CN CN 93109746 patent/CN1084045A/en active Pending
- 1993-08-25 MX MX9305156A patent/MX9305156A/en unknown
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| US7837939B2 (en) | 2003-11-14 | 2010-11-23 | Alere Switzerland Gmbh | Rapid sample collection and analysis device and methods of use |
| CN101326443B (en) * | 2005-11-30 | 2012-05-30 | 阿莱瑞士股份有限公司 | Apparatus and method for detecting analysis article in fluid sample |
| US8871155B2 (en) | 2005-11-30 | 2014-10-28 | Alere Switzerland Gmbh | Devices for detecting analytes in fluid sample |
| WO2007062575A1 (en) * | 2005-11-30 | 2007-06-07 | Inverness Medical Switzerland Gmbh | A device for detecting the presence or amount of an analyte in a fluid sample and method thereof |
| US8071394B2 (en) | 2006-07-26 | 2011-12-06 | Alere Switzerland Gmbh | Test device for detecting an analyte in a liquid sample |
| CN101963613A (en) * | 2009-07-23 | 2011-02-02 | 艾博生物医药(杭州)有限公司 | Detecting device |
| CN105015891B (en) * | 2014-04-16 | 2018-11-09 | 深圳华大基因研究院 | Sample storage device and method for storing and taking liquid sample by using same |
| CN105015891A (en) * | 2014-04-16 | 2015-11-04 | 深圳华大基因研究院 | Sample storage device and method for storing and taking liquid sample by using same |
| CN107290548A (en) * | 2016-04-11 | 2017-10-24 | 福因德科技（武汉）有限公司 | Ectopic pregnancy detection means |
| US11577238B2 (en) | 2017-03-02 | 2023-02-14 | Hero Scientific Ltd. | Testing for particulates |
| CN110582353A (en) * | 2017-03-02 | 2019-12-17 | 英雄科学有限公司 | method for detecting microparticles |
| US11890614B2 (en) | 2017-03-02 | 2024-02-06 | Hero Scientific Ltd. | Testing for particulates |
| CN108272473B (en) * | 2018-03-02 | 2020-11-27 | 杭州霆科生物科技有限公司 | Electric saliva collector |
| CN108272473A (en) * | 2018-03-02 | 2018-07-13 | 杭州霆科生物科技有限公司 | A kind of electronic spittle collector |
| US11885722B2 (en) | 2021-01-06 | 2024-01-30 | Hero Scientific Ltd. | Filtration sampling devices |
| US11921018B2 (en) | 2021-01-06 | 2024-03-05 | Hero Scientific Ltd. | Filtration sampling devices |
Also Published As
| Publication number | Publication date |
|---|---|
| MX9305156A (en) | 1994-05-31 |
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