CN1332848A - Methods for providing liquid solid components of sample for use in assay methods - Google Patents
Methods for providing liquid solid components of sample for use in assay methods Download PDFInfo
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- CN1332848A CN1332848A CN99815096A CN99815096A CN1332848A CN 1332848 A CN1332848 A CN 1332848A CN 99815096 A CN99815096 A CN 99815096A CN 99815096 A CN99815096 A CN 99815096A CN 1332848 A CN1332848 A CN 1332848A
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- sample
- aliquot
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- sampling thief
- liquid
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/569—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
- G01N33/56911—Bacteria
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/5302—Apparatus specially adapted for immunological test procedures
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/195—Assays involving biological materials from specific organisms or of a specific nature from bacteria
- G01N2333/33—Assays involving biological materials from specific organisms or of a specific nature from bacteria from Clostridium (G)
Abstract
A method for providing an aliquot of a sample comprising liquid and solid components for use in an assay method comprising contacting the sample with a sampling device configured and arranged to hold an aliquot of both liquid and solid components of the sample in proportion to the liquid and solid composition of the sample, under conditions in which the sampling device holds the aliquot of the sample and providing the aliquot for use in an assay method.
Description
Invention field
The present invention relates to be used for the collection and the transmission field of the sample of various tests and assay method.
Background of invention
Below be the discussion of correlation technique, any technology is not a claims identification
Prior art.
United States Patent (USP) 5,709,838 have described a kind of sampling thief, and it can gather a kind of material, then the sample of gathering is delivered to the testing tool place.This sampling thief is made up of a spatula and a handle.The spatula part can be separated with handle, so that it can be stayed in the test container.This device is intended to the particle specimens that is used for doing and is dissolved in the material of volatile medium.
United States Patent (USP) 5,460,781 have described a kind of sampling thief of gathering haemoglobin from ight soil.This device comprises a kind of fibrous bundle that can absorb water, and therefore can obtain haemoglobin from the fecal sample of different denseness, but any solid constituent can not taken in the analyzing and testing instrument.This device must be placed on a plurality of sites of fecal sample, enough gets sample to guarantee to collect.
United States Patent (USP) 4,225,557 disclose a kind of device that the diagnostic test band is arranged, and it can cover or seal sample so that be sealed in the fecal sample then directly with the fecal sample contact before analyzing.
United States Patent (USP) 4,492,124 have described the method for another kind of transmission fecal sample.This method comprises the device that uses long handle and cylindric inner core is arranged.The device of this belt carcass is pushed in the sample, just can make in-core be full of sample.Then the device of this belt carcass is removed from sample, separated, enter suitable containers and be used for transmitting and/or test from handle.By in the device of this belt carcass, promoting the device of a mobile sample, or from this device that core arranged, wash sample, sample can be removed.
United States Patent (USP) 5,543,115 disclose a kind of device of sample process, comprise a long handle and a groove sample collection device.The sample of gathering is collected between the groove of device.This device is intended to be used to gather the sample of solid and semi-solid material.
United States Patent (USP) 5,066,463 disclose a kind of stool examination instrument, comprise a raker stirrer, are used to collect fecal sample, then it are delivered to the hollow space of instrument.
WO97/32529 has described a kind of instrument of mobile patient's fecal impaction, comprises the long handle of a flexible thorn, is used to the ight soil of flattening and wrapping up.
United States Patent (USP) 5,238,847 and 5,215,713 disclose a kind of testing tool, are used to check pasty state, the analyte in the sample that can be coated with, wherein sample can be coated on the sample area with spatula.
Summary of the invention
The present invention relates to provide the method for the aliquot of sample, this sample is made up of liquid and solid constituent.The method of sampling of claim has improved repeatability and the simple and easy degree that transmits the sample matrix of difficult fortune, can be used for multiple analysis or medical detection method.This method of sampling is applicable to very large-scale sample viscosity and solids content.This method of sampling can be collected the solid and the liquid component of sample simultaneously, therefore can collect the sample of representative former sample composition.Therefore under-represented sample, the analyte that detect may show a under-represented concentration, test leakage or record low probably.This method of sampling can make sample be used for multiple detection method.Analytical approach can be qualitative or one or more compositions of quantitative measurment sample.This analysis detection method includes, but are not limited to, simple spectrophotometric analysis, emitting isotope analysis, chemical analysis, immunoassays, foranalysis of nucleic acids and chromatographic technique.If sample is from patient, these method of testings can detect the multinomial analyte of sample, comprise and occulting blood, clostridium difficile toxin or other infectant, the perhaps chemical constitution of all right analyzing samples.
No matter the viscosity and the denseness of sample, the present invention can be used in the uniform of detection method, and reproducible sample transmits becomes possibility.The method of sampling of the present invention is better than the existing method of sampling.Method of the present invention is also very simple, and minimum exposure sample material is because before delivering to reaction or test container, sample is stayed in the sampling thief always.
On the one hand, a kind of method of aliquot that providing of assay method contains the sample of liquid and solid constituent that is used for is provided, comprise sample is contacted with sampling thief, this sampling thief is configured and is mounted to the aliquot of obtaining liquid and solid constituent according to the ratio of the liquid of sample and solid constituent, get at sampling thief under the condition of aliquot of sample, provide this aliquot to be used for assay method then.
Analyte of interest the present invention relates to obtain contain the aliquot of the sample of liquid and solid constituent, because may be dispersed in the liquid and solid constituent of sample simultaneously.The example of the sample of the method for the statement that can be used for sampling comprises, but be not limited to, check the slip in the abiotic source that one or more compositions exist or the sample of suspending liquid and biogenetic derivation, as ight soil, sputum, nasal wash, nasal cavity aspirate, whole blood, fester or other transudate or tissue homogenate." aliquot of sample " is the part of the previous sample of gathering, in position as the position of burn or wound, or the part of the sample gathered of nasal meatus, or the part of the sample of from the container of making or preparing, gathering.Those those skilled in the art are familiar with the method for a variety of collection samples.Those those of ordinary skills need can determine the sample size of collection according to the sensitivity of analyte that will detect and used assay method.Assay method can be any method, to detect existing and/or measuring of analyte of interest in the aliquot that can be contained in sample.Those those of ordinary skills can determine suitable assay method at selected analyte of interest.
Sample contacts with sampling thief, and this sampling thief can be placed in the sample or the surface of sample, so that be exposed in the liquid and/or solid constituent of sample, the liquid of sample and/or solid constituent just can be attached on the sampling thief.Requirement with respect to sample from the side or mobile rotatably sampling thief, to guarantee to be sent to and attached to being the pro rata liquid and/or the solid constituent of representative sample on the sampling thief.Sampling thief is assembled into the aliquot of obtaining liquid and solid constituent according to the ratio of the liquid of sample and solid constituent, if promptly have liquid and solid constituent to exist in the sample, but the liquid of the aliquot of sampling thief retain sample and solid constituent, up to they be transferred into be used for assay method before aliquot can not lack any material.Pro rata method can make the relative quantity of these compositions in the liquid of aliquot and the solid constituent representative sample.
In case sampling thief has been gathered an amount of sample, just provide aliquot to be used for assay method, promptly take out aliquot and be used for assay method from sampling thief.The taking-up of aliquot can directly contact the sampling thief that has the aliquot of sample with the surface of using in assay method, or sampling thief is immersed in the solution that uses in assay method subsequently.Solution can be contained in the reactor.Solution can increase the extraction of analyte from the aliquot of sample, perhaps can contain a kind of test agent (test solution) that is used for assay method, can be a kind of liquid only perhaps, is used for removing aliquot from sampling thief.As the sampling thief in stirring, vibration and/or the squeezing reactor, the aliquot in the sampling thief is moved in the solution by physical process.
In preferred embodiments, sampling thief is a brush; This brush is that a design is used for the brush of collecting cell; Sample is an ight soil; Assay method is to be used for detecting clostridium difficile toxin; Assay method is a kind of optics immunoassay; Sample is the slip or the suspended matter of non-biogenetic derivation; Sample is selected from sputum, nasal wash, nasal cavity aspirate, whole blood, fester, cellular exudate and organize slip; The aliquot that provides comprises the sampling thief that is immersed in the test solution; Contact comprises sampling thief pushed in the sample, rotation sampling thief and remove sampling thief from sample in sample; Aliquot is transferred in the reactor; Aliquot directly is sent to the check surface.
Brush is preferred sampling thief, although those it will be appreciated by those skilled in the art that sampling thief can be catching and the liquid of collection sample and the material of solid constituent with the amount of composition in the expression sample of arbitrary shape.Brush has attached to the bristle on the handle.Those those of ordinary skill in the art can be at an easy rate according to the feature of described brush, it is the shape of brush part, the shape of bristle in the brush, the density of bristle in the brush, the length of bristle in the length of brush part, brush, the diameter of bristle, the material of bristle is formed, and the mode that the brush part bristle distributes and the design of brush handle are determined how to select the brush that can buy or made a brush that is used to provide the aliquot of specific sample.
In preferred embodiments, brush is designed to collecting cell." brush is designed to collecting cell " is meant that one is used for, for example from cervix, and the brush of collecting cell.These brushes are called as cytological brush.For example, one is such brush CYTOBRUSH
TMThe cytology brush (Medscand, AB, Malmo, Sweden).Have and all plant the design proposal that is applicable to the cytology brush perhaps.Some designs are included in United States Patent (USP) 3,881,464, described in the United States Patent (USP) 4,759,376, United States Patent (USP) 5,133,361, United States Patent (USP) 5,713,369, WO91/16855.Design these brushes and be used for anti-cancer inspection, from cervix and the sampling of canal of uterine cervix inner membrance.Brush can be made into very straight shape, and uniform bristle lengths and density are arranged.Can determine the profile and the shape of brush by length and the distribution that improves bristle.Perhaps bristle can be helical around the handle of brush.The length of brush can change.
The purposes of the preferred method of sampling is to be used for fecal sample, and the especially reproducible transmission of Fu Hong fecal sample is because these samples contain liquid and solid constituent simultaneously.
Use the people of these technology to know to be used to the assay method that detects the toxin that clostridium difficile produces, comprise, but be not limited to, cytotoxic assay, immunoassays and optics immunoassays (OIA
).
The interactional method based on light and film has been described in the optics immunoassays.With film the adjusting that interactional light can experience some types taking place, normally lags behind (phase delay) mutually, but also may be other effect.According to the style of film instrument, light can experience destructive interference, produces a kind of visible color change, perhaps light can experience the change of polarity, this change can be compared the elliptic polarization method by the elliptic polarization method, and fixed angle elliptic polarization method or other elliptic polarization method are measured.When the visible color change took place, simple reflectometer can replace the monitor of eyes as color change.Use profilometry, scanning tunneling microscopic method or atomic force microscopy detect the surface of film.Because with the interaction of film, light is decayed, and causes the inhibition or the expansion of one or more light wavelengths, the change of monochromatic light or heterogeneous light intensity, the change of the polarity of light (intensity and/or wavelength or degree of polarity), or other measurable phenomenon.Decay also may be the compound result of these changes of light.Film can be an inoranic membrane, organic membrane or organic/inorganic composite membrane.Film is fixed on the optics support.Select with assay method mutually the optics support of compatibility be used for finally measuring mode.Select and the optics support the compatible mutually film of other composition (as the antibody receiving layer) of the detection method and the system of mensuration.At United States Patent (USP) 5,550,063, United States Patent (USP) 5,482,830, United States Patent (USP) 5,541,057, United States Patent (USP) 5,468,606, United States Patent (USP) 5,639,671 and R.M.Ostroff etc., Clin.Chem., 44,2031-2035 has stated the selection of material and the standard of material compatibility in 1998.
Preferred sample is a kind of slip or suspended matter of abiotic source." slip " is meant a kind of liquid that contains tiny solid constituent." suspended matter " be one by the tiny separating solids that is dispersed in the liquid, the diphasic system of forming such as a kind of liquid preparation." abiotic source " refers to any source of non-plant or animal.Sample also can be the material of any biogenetic derivation, preferred sputum, nasal wash, nasal cavity aspirate, whole blood, fester, cellular exudate and organize slip.
Be contained in aliquot in the sampling thief and can be sent to one for being used in " reactor " that assay method prepares.Reactor is some containers, and it comprises, but is not limited to, polypropylene test tube and by glass, tygon or the quartzy container of making.In case sample is admitted in the reactor, sample Chang Bixu is dissolved in a kind of test solution.This can be by sample will be housed the sampling thief of aliquot partly be immersed in the test solution and finish.Another kind method is, the aliquot of sample directly can be delivered to " check surface ", should " check surface " can be any surface, on it, implement assay method, as, be used for the film on the analyzer of immunoassays or foranalysis of nucleic acids, be used for the microscopy microslide of fluorometric assay or microexamination, perhaps be used for the solid agar plate of microbiological analysis.
In another preferred embodiment, this method provides the aliquot of fecal sample, to be used to the optics immunoassay of check clostridium difficile toxin, this method comprises makes ight soil contact with the sampling brush, sampling brush is assembled into the liquid and the solid constituent that can obtain fecal sample according to the ratio of the liquid of fecal sample and solid constituent, get at sampling thief under the aliquot and condition of sample, then this aliquot is used for the optics immunoassays of clostridium difficile toxin.
In still another preferred embodiment, before carrying out the optics immunoassays, earlier aliquot is sent in the reactor; Brush is that a design is used for the brush of collecting cell.
From the description and claim of following relevant embodiment preferred, other advantage of the present invention and feature are conspicuous.
All articles of quoting in this application, publication and patent all are incorporated herein by reference.The description of embodiment preferred
The following example is provided,, will be limited in this scope anything but further to illustrate different aspect of the present invention and embodiment.Embodiment 1: the selection of brush and structure
Preferred sampling thief is a brush, as cytology brush (Oosina, Englewood, NJ; Hardwood Products, Co., Guilford, ME; Medical Packaging Corp., Camarillo, CA), it is used to from the cervix collecting cell.Yet concerning the people who implements this technology, the brush of number of different types and design all is applicable to the method for statement obviously.Those of ordinary skills are according to the liquid of sample and solid constituent and the performance of considering the brush of being discussed, and in the brush that can determine to have bought, which is applicable to specific sample.In addition, those of ordinary skills can design a suitable brush according to the performance of the composition and the described brush of sample.Among the present invention, brush is directly inserted in the sample, and is used for taking out the sample of specified quantitative.Then brush is inserted in test tube or other reactor, and mix with liquid reagent.Sample on the brush is mixed in the solution, discharges the analyte of wanting, and produces a kind of uniform sample matrix for further checking.The main advantage of using brush to gather sample is that the special bristle of brush has and catches solid between bristle, the ability of stickum and liquid.Material is retained in the brush safely, is sent in the suitable reactor, and can be exposed to the people who samples.If from health, as wound site and nasal meatus, sampling aliquot originally, brush can be sterilized before using.
A variety of cytology brushes can have been bought.Selecting commercially available pattern or designing a new brush being used for will turning over many factors when sample obtains aliquot, described sample is to being the sample of liquid mainly from the solid sample of low content liquid.The brush of selecting should be considered the shape of sampling thief brush part, the shape of bristle in the brush, the density of bristle in the brush, the length of brush part, the length of bristle in the brush, the mode that bristle distributes in the diameter of bristle, the material composition of bristle and brush part.Also need consider the pattern of brush handle.The necessary long enough of handle, the user just can not run into sample.But handle also must enough solidly can connect sample, and no matter how thick sample have, and requires under any pressure, can both connect sample and does not fracture.Handle also must be compatible with reactor, and sample is sent in the reactor, and can mix with reaction medium at an easy rate.If directly gather sample, require to have a more resilient handle from wound site and nasal cavity.
The shape of sampling thief brush part can limit the sample size (aliquot) that is sent in the reactor.The length of bristle in the length of brush part, brush, the density of bristle, the mode that bristle distributes in the brush part can determine the shape of brush.Bristle can spirality pass through brush part.This has just formed the continuous distribution of bristle.Bristle also can discontinuously be arranged.The length of unique bristle further defines the shape of brush part.Bristle can be one or more length, and length can change by arrange or change bristle etc.
The stiffness of bristle depends on the composition and the diameter of the material that is used to prepare bristle.The bristle of most of commercially available brushes is a nylon.The material that is used for preparing bristle can also be controlled the hydrophobic property of brush.Bristle must keep the stiffness of certain level to assist to connect and gather sample.
In preparation process, can cut bristle and become to comprise a blunt end or a tip.The tip has superiority, because it is convenient to the sample perforation and keeps the sample that contains more solid thickness.
For the more sample of liquid, the density of bristle must be enough to produce collection point.Liquid is retained between bristle because of electrostatic interaction, and formation is better than the interactional fluid-tight of gas/liquid on bristle.The sample that solid is more is because viscosity is easier to adhesion.
According to empirical observation, select to be used to gather the style of the suitable brush of special sample as the performance of the brush that transmits sample.In mensuration, should use the sample denseness and the composition of the certain limit of given sample type.This will guarantee sampling thief can collect might the sample denseness the capacity sample.Required sample size depends primarily on analysis determining method and its intrinsic detection limit.Highstrung analytical approach is lacked than the not too responsive required sample size of method.Highstrung analytical approach is also more insensitive to adding in the reactor with the liquid reagent amount of the sample of separated and collected from brush, but the amount that should optimize reagent is to guarantee to finish with minimum interpolation reagent the recovery of sample.Testing reagent can comprise damping fluid, solvent, washing agent, acid, alkali, calibrating reagent etc.Testing reagent can dissolve the sample of collection, the sample of help to suspend collecting or be next step detection modification sample composition.Assess the repeatability that sample reclaims according to the scope of sample denseness with the dosage measured of the verifiable analyte minimum of analytical approach.
Selected brush must be compatible with sample and testing reagent.This means that brush can not be discharged into a kind of material in sample or the testing reagent, and disturb or the inhibition analysis method.Brush can not be dissolved in testing reagent, does not influence the recovery of the analyte that is used for assay method unless can prove dissolving.Brush can not retain sample (aliquot) or is combined and the susceptibility of reduction method with other testing reagent in removing process.
According to above-mentioned factor, those of ordinary skill in the art can select or design a brush, is used for providing aliquot to be used for different assay methods from the multiple sample of different denseness.
The process of gathering sample with brush is very simple.Hold the handle of brush, brush part is pushed in the sample to cover the brush part of sampling thief.When the brush part that uses is very long, the sample of capacity can be collected and sample needn't be connected fully.Yet, allow brush material not be exposed to and can cause too many sampling changeability in the sample.In case brush connects sample, rotary handle allows all brush parts contact with sample, improves the collection of sample.Then brush is removed from sample, in the aliquot immigration reactor with sample.In some cases, as be used for direct immunofluorescence, the available sampling device directly is coated onto the check surface with sample, on the microslide as microscopy.Reactor can comprise one or more testing reagents so that discharge the sample of adhesion from the bristle of brush.Available sampling device or brush mixing testing reagent or sample.May need outside stirring the (as stirring, shake or be out of shape) according to the sample brush makes all aliquots of sample all enter reaction mixture.A kind of method of routine is that sampling thief or reactant liquor are put into a pliable and tough polypropylene in vitro, and the user can push the limit of test tube, and the therefore bristle distortion of brush.Because during the brush distortion, the aliquot of sample just can discharge.In case obtained uniform potpourri, just can handle sampling thief.Processing must meet rule and the environmental requirement by the sample type decision of being analyzed.Just obtained according to previously selected analytical approach the test liquid that can be used to analyze then.Embodiment 2: the purposes of the method for sampling
Multiple sampling condition provides multiple sample denseness for possible sampling thief.Following example has been set forth the purposes of the method for statement, but does not want to be limited.Sampling thief can be used for obtaining the aliquot of the previous sample of gathering, and perhaps sampling thief can be used to directly to gather sample from burn or wound site or nasal meatus and is used for further cultivating or analyzing, and perhaps directly gathers from the preparation container.Sampling thief should not stay fiber, as enter the collection position in the body from swab.
Preparation process can produce a kind of viscosity or the different slip of solid constituent.Before next step preparation process or be necessary to determine the composition of slip before handling or handling, as the function of one or more compositions in the slip.Sample can be the synthetic slip in centre that obtains from the medication preparation process, and slip needs with the analytical approach check, as measuring the HPLC method of active pharmaceutical ingredient ratio.
Soil sample depends on that the moisture of sample areas and pollutant can have different denseness.Therefore sample may be a kind of contaminated soil sample, therefrom can extract or analyze one or more pollutants, to instruct decontamination process.Can measure residual noble metal or toxicant in the mine tailing of putting of digging up mine.Also can be determined at the recovery of the mineral slip in the processing procedure, pollutant etc.The collection that the yeast that the method for sampling also can be used for using in beer or the wine fermentation process is stuck with paste.Also can measure yeast stick with paste in the viability of pollutant and/or biosome.Active substance can be recycled to and is used for sweat next time in the fermentation tank.In the medicine sweat, can gather or measure the pollutant and/or the viability of the recombinant organisms of pharmacy.The method of sampling also can be used for checking the bacterium in the unprocessed meat or the pollutant of other types.This method of sampling can also be packed before whole packing or by selective sampling eventually, other type that is used to sample add formula Food ﹠ Drink, especially baby food.The preferred application is the sampling and the transmission of ight soil.
The example of sampling problem that runs into the sample of different denseness is illustrated by fecal sample.In multiple disease, the collection of fecal sample is very important.For example, occult blood prompting colon or the carcinoma of the rectum or precancerous lesion.The handle of safety and very difficult to effective transmission of the fecal sample of assay method.Fecal sample, when diarrhoea companion especially, can change to very laxly from tangible ight soil, denseness almost is the ight soil of liquid.The invention provides a kind of unidirectional transfer system collection at the sample of the different denseness of clinical findings sample is described, so that the analyte of interest that exists in the liquid of fecal sample and the solid constituent is sent to assay method.
Sputum has been represented the material of another biogenetic derivation that is difficult to gather, because its viscosity difference.Detect the inspection that sputum helps respiratory tract infection.The type of respiratory tract infection comprises tuberculosis, Respiratory Syncytial Virus(RSV) (RSV) and influenza virus.This method is particularly useful to gathering sputum.Embodiment 3: the mensuration of clostridium difficile toxin
Preferred analyte is the toxin that clostridium difficile produces, a kind of known virulence factor of suffering from diarrhoea in some ill crowd.The mensuration of toxin can be according to the cytotoxicity assay of standard, immunoassay, or most preferably use known method such as optics immunoassay (OIA
) (seeing United States Patent (USP) 5,486,606, United States Patent (USP) 5,541,057, United States Patent (USP) 5,550,063).
In order to carry out the optics immunoassays of clostridium difficile toxin, need following ingredients.At first must select a kind of optical base-substrate.The glass of selecting the catoptrics substrate such as the silicon of known refractive index or scribbling amorphous silicon is used for this mensuration.Because this check is designed to use separately, preferred a kind of visual signal interpretation of quantitative measurement.In order to produce optical signal, must scribble anti--reflection (AR) layer on the optical base-substrate.For the existence of next biostrome, the material that is elected to be the AR layer must be relevant with the optics substrate by refractive index, and must adjust its theoretic throat (optical computing with standard is determined).The AR layer can be a silicon nitride, silicon oxynitride, silicon monoxide, zirconium dioxide, titania and other suitable equally material of making this coating.In this case, use is the silicon nitride steam of precipitation.
When design optics instrument, a kind of adsorbed layer of siloxane of branched structure is applied to optical surface.This adsorbed layer can be made a kind of environment, helps the absorption of biological capture reagent, reservation and stable.This capture reagent or accept material and can be selected from the biological composition that specific reaction takes place for any and analyte of interest.In this case, be the polyclonal antibody of the toxin that produces at clostridium difficile.Immerse by the optics instrument that will scribble adsorbed layer that a preset time applies antibody layer in the solution contain antibody.When the optics instrument takes out from coating solution, use distilled water flushing, drying for more stable, add and is coated with layer protective layer.The optics instrument that to finish then inserts on the check surface, and inserts on the plastics analyzers (plastic assay device).Those of ordinary skills are according to United States Patent (USP) 5,418, and the 136 disclosed optics immunoassays instrument that also can produce optical signal that can make other, these optics immunoassays instrument produce the signal that can be read by instrument.
The optics immunoassays of clostridium difficile (CdTOX A OIA) are carried out as follows.The brush of will sampling inserts fecal sample and rotates so that fill with fecal materials in the bristle.The bristle of brush is removed it after carrying full ight soil from ight soil, against the rotation of the wall of sample container to remove unnecessary material.Then brush is transplanted on 300 μ l antibody is housed---in the pliable and tough polypropylene reaction tube of enzyme conjugates.With brush mixing sample and bond, test tube is extruded, then brush is lost.One or two sample/bond potpourri dripped to the OIA surface at room temperature hatched then 5 minutes, carry out OIA and measure.If there is clostridium difficile toxin in the sample, at enzyme conjugates, toxin and be combined between the antibody on OIA surface and can form a kind of compound.With buffer salt solution stream flushing OIA surface, then it is blotted.Add the substrate of a precipitation enzyme on the OIA surface, at room temperature hatched then 5 minutes.If previous described compound exists, enzyme will form precipitated product with substrate interaction.But sedimentary existence will produce the film of an optical detection on the OIA surface.Embodiment 4: the purposes of sampling brush
The performance of the brush that can buy of 4 kinds of different sizes (seeing Table 1) being gathered suspending liquid compares.The brush that uses be Medical Devices company (MPC) (Camarillo, weak point CA) and (std) standard and Oosina (Englewood, weak point N.J.) with standard.Brush is used for gathering suspending liquid, and suspending liquid is by protein, and particle and other material are formed, so that the viscosity of sample is with the similar of sample of suffering from diarrhoea.The denseness of sample is a kind of thick pastel.In the mensuration of clostridium difficile, gather above-mentioned suspending liquid and used 10 every type brush.From the brush that ight soil is housed, deduct the weight of brush itself, calculate and report out the weight (seeing Table 1) of the material of collection.%CV represents to use mean value divided by standard deviation, is the measurement of sampling error.As shown in table 1, the amount of the sample that brush is captured (aliquot) changes with the style of brush, and what the people was taken aback in addition is that the method that application one is gathered brush in sample is very little to the collection influence of sample, the reproducible amount that promptly can obtain gathering sample.
Table 1
| The short standard of MPC-Qosina-MPC-standard Qosina- | |
| Length diameter-base diameter-tip | 12.0mm??????12.0mm?????19.0mm????????21.0mm ?6.5mm???????6.5mm??????6.5mm?????????8.0mm ?5.5mm???????5.0mm??????5.0mm?????????5.0mm |
| Quality (g) | ?0.26????????0.28???????0.38??????????0.50 ?0.34????????0.31???????0.38??????????0.54 ?0.29????????0.32???????0.38??????????0.64 ?0.31????????0.32???????0.39??????????0.57 ?0.29????????0.34???????0.41??????????0.56 ?0.31????????0.29???????0.40??????????0.62 ?0.31????????0.30???????0.36??????????0.52 ?0.29????????0.25???????0.38??????????0.60 ?0.27????????0.24???????0.35??????????0.57 ?0.24????????0.33???????0.46??????????0.52 |
| Mean standard deviation %CV | ?0.29????????0.30???????0.39??????????0.56 ?0.029???????0.033??????0.030?????????0.046 ?9.91％?????11.16％?????7.80％????????8.11％ |
Other embodiment in the claims.
Claims (15)
1. the method for aliquot that providing of assay method comprises the sample of liquid and solid constituent is provided, and this method comprises:
Described sample is contacted with sampling thief, sampling thief is configured and is mounted to the aliquot of obtaining the liquid and the solid constituent of described sample according to the ratio of the liquid of described sample and solid constituent, gets access at described sampling thief under the condition of described aliquot of described sample; And
Provide described aliquot to be used for assay method.
2. method according to claim 1, wherein said sampling thief are brushes.
3. method according to claim 2, wherein said brush is designed to collecting cell.
4. method according to claim 1, wherein said sample is an ight soil.
5. method according to claim 4, wherein said assay method is used to detect clostridium difficile toxin.
6. method according to claim 1, wherein said assay method are the optics immunoassays.
7. method according to claim 1, wherein said sample are the slip or the suspending liquid of non-biogenetic derivation.
8. method according to claim 1, wherein said sample is selected from: sputum, nasal wash, nasal cavity aspirate, whole blood, fester, cellular exudate and tissue homogenate.
9. method according to claim 1 wherein provides described aliquot to comprise described sampling thief is immersed in the detection solution.
10. method according to claim 1, wherein said contact comprise described sampling thief pushed in the described sample, the described sampling thief of rotation and remove described sampling thief from described sample in described sample.
11. method according to claim 1, wherein said aliquot is sent in the reactor.
12. directly being sent to, method according to claim 1, wherein said aliquot detect the surface.
13. in the optics immunoassay that is used for detecting clostridium difficile toxin, provide the method for the aliquot of fecal sample, this method comprises:
Described ight soil is contacted the sampling brush with one, this sampling brush is configured and is mounted to liquid and the solid constituent that obtains described fecal sample according to the ratio of the liquid of described fecal sample and solid constituent, gets access at described sampling thief under the condition of described aliquot of described sample; And the optics immunoassays that provide described aliquot to be used for described clostridium difficile toxin.
14. method according to claim 13, wherein before carrying out described optics immunoassays, described aliquot is sent in the reactor.
15. method according to claim 13, wherein said brush are brushes that is designed to collecting cell.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US22306698A | 1998-12-29 | 1998-12-29 | |
| US09/223,066 | 1998-12-29 |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2007101359878A Division CN101025421A (en) | 1998-12-29 | 1999-12-17 | Method of providing liquid component and solid component of sample used in analytical technique |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1332848A true CN1332848A (en) | 2002-01-23 |
Family
ID=22834874
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2007101359878A Pending CN101025421A (en) | 1998-12-29 | 1999-12-17 | Method of providing liquid component and solid component of sample used in analytical technique |
| CN99815096A Pending CN1332848A (en) | 1998-12-29 | 1999-12-17 | Methods for providing liquid solid components of sample for use in assay methods |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2007101359878A Pending CN101025421A (en) | 1998-12-29 | 1999-12-17 | Method of providing liquid component and solid component of sample used in analytical technique |
Country Status (9)
| Country | Link |
|---|---|
| EP (1) | EP1141707A4 (en) |
| JP (2) | JP2002533725A (en) |
| CN (2) | CN101025421A (en) |
| AU (1) | AU770194B2 (en) |
| HK (1) | HK1038794A1 (en) |
| ID (1) | ID28979A (en) |
| MY (1) | MY130846A (en) |
| TW (1) | TW468047B (en) |
| WO (1) | WO2000039584A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1313285C (en) * | 2003-09-19 | 2007-05-02 | 林震能 | Colorizing method of decoration board as background of aquarium |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2014145698A (en) * | 2013-01-30 | 2014-08-14 | Nitto Denko Corp | Sample fixing member for raman spectroscopic analyzer |
| CN103292545B (en) * | 2013-05-06 | 2016-04-13 | 四川长虹电器股份有限公司 | For method and the device of the defrosting pressurize of refrigerator |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1408140A (en) * | 1971-12-09 | 1975-10-01 | Levene M M | Sampling device |
| US4759376A (en) * | 1984-05-29 | 1988-07-26 | Nils Stormby | Endocervical sampling brush and smear method |
| US4963325A (en) * | 1988-05-06 | 1990-10-16 | Hygeia Sciences, Inc. | Swab expressor immunoassay device |
| US5882942A (en) * | 1995-02-15 | 1999-03-16 | Wako Pure Chemical Industries, Ltd. | Method for sampling feces |
| US5965375A (en) * | 1997-04-04 | 1999-10-12 | Biosite Diagnostics | Diagnostic tests and kits for Clostridium difficile |
| AUPP323798A0 (en) * | 1998-04-28 | 1998-05-21 | Chandler, Howard Milne | Sample collection method |
-
1999
- 1999-12-17 ID IDW00200101340A patent/ID28979A/en unknown
- 1999-12-17 AU AU21941/00A patent/AU770194B2/en not_active Ceased
- 1999-12-17 TW TW088122268A patent/TW468047B/en not_active IP Right Cessation
- 1999-12-17 CN CNA2007101359878A patent/CN101025421A/en active Pending
- 1999-12-17 JP JP2000591432A patent/JP2002533725A/en not_active Withdrawn
- 1999-12-17 EP EP99966392A patent/EP1141707A4/en not_active Withdrawn
- 1999-12-17 CN CN99815096A patent/CN1332848A/en active Pending
- 1999-12-17 WO PCT/US1999/030142 patent/WO2000039584A1/en active IP Right Grant
- 1999-12-21 MY MYPI99005641A patent/MY130846A/en unknown
-
2002
- 2002-01-17 HK HK02100371.7A patent/HK1038794A1/en unknown
-
2006
- 2006-12-05 JP JP2006328455A patent/JP4117577B2/en not_active Expired - Fee Related
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1313285C (en) * | 2003-09-19 | 2007-05-02 | 林震能 | Colorizing method of decoration board as background of aquarium |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2000039584A1 (en) | 2000-07-06 |
| EP1141707A1 (en) | 2001-10-10 |
| AU770194B2 (en) | 2004-02-12 |
| TW468047B (en) | 2001-12-11 |
| JP4117577B2 (en) | 2008-07-16 |
| AU2194100A (en) | 2000-07-31 |
| CN101025421A (en) | 2007-08-29 |
| HK1038794A1 (en) | 2002-03-28 |
| MY130846A (en) | 2007-07-31 |
| JP2007057549A (en) | 2007-03-08 |
| EP1141707A4 (en) | 2005-01-12 |
| JP2002533725A (en) | 2002-10-08 |
| ID28979A (en) | 2001-07-19 |
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