CN101095040A

CN101095040A - Body fluid analyte meter &amp, cartridge system for performing combined general chemical and specific binding assays

Info

Publication number: CN101095040A
Application number: CN 200580013969
Authority: CN
Inventors: 乌尔斯·A·拉梅尔; 迪兰·塔伊; 卡罗勒·R·斯蒂弗斯; 乔尔·M·布拉特; 本杰明·R·欧文
Original assignee: Metrika Inc
Current assignee: Bayer Healthcare LLC
Priority date: 2004-03-08
Filing date: 2005-03-07
Publication date: 2007-12-26
Also published as: ZA200607521B; AP2006003742A0

Abstract

A combination body fluid analyte meter and cartridge system, having: (a) a body fluid analyte meter, with: a housing; a logic circuit disposed within the housing; a visual display disposed on the housing; and a measurement system disposed within the housing; and (b) a cartridge, having: at least one lateral flow assay test strip, the lateral flow assay test strip having: (i) a lateral flow transport matrix; (ii) a specific binding assay zone on the transport matrix for receiving a fluid sample and performing a specific binding assay to produce a detectable response, and (iii) a general chemical assay zone on the transport matrix for receiving the fluid sample and performing a general chemical assay to produce a detectable response; wherein the cartridge is dimensioned to be receivable into the body fluid analyte meter such that the measurement system is positioned to detect the responses in the specific binding assay zone and the general chemical assay zone in the lateral flow assay test strip.

Description

Be used to implement the body fluid analysis thing meter and the card, kit system of general chemistry and specific bond combinatory analysis

The cross reference of related application

It is the U.S. Provisional Patent Application case the 60/551st of " Multi-Use Body FluidAnalyte Meter and Associated Cartridges " that the application's case advocates to have precedence over the exercise question of filing an application on March 8th, 2004, No. 595, its full text disclosure is incorporated herein with way of reference for all purposes.

Technical field

Generally speaking, the present invention relates to body fluid analysis thing metering system, and in an exemplary embodiments, relate to hemoglobin A lc (HbAlc) metering system.

Background technology

Quantitative and semidefinite is measured examination and is applicable to such as many analytes such as conceived and the labels of ovulating.Yet there is accurately quantitative analyte of multiple needs.These analytes comprise glucose, cholesterol, HDL cholesterol, triglyceride, multiple medicine (for example theophylline), vitamin level and other healthy indicant.Generally speaking, it quantitatively can be reached by instrument.Although be applicable to clinical analysis, these methods do not conform with the requirement that medical spot check is tested in doctor clinic and the family because of instrument is expensive.

So-called " quantitatively " analytic type analysis in fact can not produce real quantitative result in the prior art.For example, the United States Patent (USP) of giving Swanson discloses " analyte location survey amount is fixed " that is undertaken by the cascade in many threshold testings district for the 5th, 073, No. 484.Each test section represents that with dualistic manner the amount of analyte is higher or lower than a certain predetermined concentration in the sample.Therefore the fiducial value with respect to threshold value only can be determined in each test section, rather than accurate analyte concentration.Between the follow-on test district, only can measure the analyte concentration of certain limit.Even compare the result of each test section, people also can't determine accurate analyte concentration.Do not disclose a kind of real quantitative test.In addition, the calibration curve that Swanson analyzes is discontinuous, and only identification does not have the discrete data of interpolation to each other.

Needing another concrete analysis thing of accurate quantification is hemoglobin A lc (HbAlc), a kind of glycosylated hemoglobin form, and it can indicate the glycemic control of patient in the first two months to three month.When can not being combined into stable glycosylated hemoglobin with intending, glucose in the blood and haemoglobin form HbAlc.Because the erythrocytic normal existence phase is 90 days to 120 days, so only can eliminate HbAlc when red blood cell is replaced.Therefore, red blood cell in whole life cycle the HbAlc value be directly proportional with concentration of glucose in the blood and can not experience and follow the every day blood-glucose to monitor being seen fluctuation.

ADA (ADA) recommends HbAlc is tested to find out whether patient's blood sugar is in the control in time as the best.Recommend every three months to implement once described test for the patient of insulinize, can be during treatment changes or blood-glucose implement when raising.For the stable patient of medicinal preparation for oral administration, recommended frequency is every year at least twice.

Although the HbAlc value is the blood-glucose index in the first two months to three month, it can bias toward nearest dextrose equivalent.This preference is by the natural destruction of erythrocytic health with due to substituting.Because red blood cell often wrecks and substitutes, do not need 120 days so after average blood glucose generation significant change, detect significant clinically HbAlc variation.Therefore, the average glucose concentration in about 50% the HbAlc value representative just pass by 30 days, the average glucose concentration in preceding 60 days of about 25% the HbAlc value representative and all the other HbAlc values of 25% are represented the average glucose concentration in preceding 90 days.

American National glycosylated hemoglobin standardization progam (NGSP) has authenticated HbAlc laboratory and check program, and has set up accurate scheme and other standardized program.Study emphasis recently and point out directly in the examination scope of doctor clinic, to obtain HbAlc result's clinical and therapeutic value.At present, the patient that need carry out the HbAlc test must submit to the blood sample chamber of experimentizing to analyze.The two time span that must wait for of patient and medical professional depends on the practicality of lab resources.Patient's potential treatment is delayed to obtaining test result.This becomes and reduces the consuming time and expensive treatment procedure renderd a service.

Because of having supported disease, numerous health care organizations administer, so the demand real quantitative and timely diagnostic analysis that can use in the test of medical center has been had bigger importance at present.Being used for one of the use rationalization that makes disease improvement and the method that proves its gain on investments at present is clinical risk stratification.This relates to evaluation and analyzes the patient colony and the subgroup of the order of severity that has similar symptom and variation in the disease that it suffers and evaluate the risk that it experiences some bad result.Risk stratification provides based on following factor one colony is divided into the ability of similar group and subgroup, and described factor especially its following apparent wind is dangerous: suffer concrete bad result (for example heart attack, apoplexy, cancer, gestational diabetes, or the like); Need to be in hospital, first-aid room or doctor clinic observe; Cause the diagnosis and the treatment spending of some level; And mortality ratio, the incidence of disease and other complication.Organize and according to the different clinical risk level of patient it has been carried out layering when one, then described organizing subsequently can be designed, research and develop and implement more to have an opportunity to improve patient result's concrete intervention to save into the manner.

Therefore, need a kind of method and apparatus that is used for accurate quantification analyte (for example HbAlc) at diagnostic field, described method and apparatus must be enough cheap, in time, effectively, lasting and reliably to be used to allow through training and indiscipline personnel at the diagnostic device that carries out the medical center use such as other place beyond place such as family, medical emergency place, medical professionalism clinic and the clinic.No matter described device is disposable or reusable, satisfies these demand needs and carry out a plurality of analyses simultaneously by the single sample source.

Summary of the invention

In first preferred embodiment, the invention provides a kind of knockdown body fluid analysis thing meter and card, kit system, it comprises: (a) body fluid analyte meter and (b) wherein have the cartridge of at least one lateral flow analytical test strip, and described lateral flow analytical test strip has: (i) lateral flow transportation matrix; A (ii) specific bond analysis area that is positioned on the described transportation matrix, it is used to receive a fluid sample and implements a specific bond analysis and can detect response to produce one, a (iii) general chemical analysis domain that is positioned on the described transportation matrix, it is used to receive described fluid sample and implements a general chemical analysis and can detect response to produce one; Wherein said cartridge has suitable dimension and can be received in the described body fluid analysis thing meter, so that place correct position to detect the response of described specific bond analysis area and described general chemical analysis domain at described lateral flow analytical test strip this measuring system.Preferably, described measuring system is an optical measuring system.Best, described measuring system is an albedo measurement optical system.

In second preferred embodiment, the invention provides a kind of cartridge of using with a body fluid analyte meter, described cartridge is in wherein having at least one lateral flow analytical test strip, and described lateral flow analytical test strip has: (i) lateral flow transportation matrix; A (ii) specific bond analysis area that is positioned on the described transportation matrix, it is used to receive a fluid sample and implements a specific bond analysis and can detect response to produce one, a (iii) general chemical analysis domain that is positioned on the described transportation matrix, it is used to receive described fluid sample and implements a general chemical analysis and can detect response to produce one; Wherein said cartridge has that suitable dimension can be included body fluid analyte meter in so that place correct position to detect the response of described specific bond analysis area and described general chemical analysis domain at described lateral flow analytical test strip the measuring system in the described body fluid analysis thing meter.

In the 3rd preferred embodiment, the invention provides a kind of lateral flow analytical test strip, it has: (i) transportation matrix; A (ii) specific bond analysis area that is positioned on the described transportation matrix, it is used to receive a fluid sample and implements a specific bond analysis and can detect response to produce one, a (iii) general chemical analysis domain that is positioned on the described transportation matrix, it is used to receive described fluid sample and implements a general chemical analysis and can detect response to produce one, and wherein said lateral flow analytical test strip is formed by individual layer continuous material film.

In the 4th preferred embodiment, the invention provides a kind of cross-current analytical test strip, it has: one comprises the transportation matrix of a pile film; One is positioned at the specific bond analysis area on the described transportation matrix, and it is used to receive a fluid sample and implements a specific bond analysis and can detect response to produce one; With a general chemical analysis domain that is positioned on the described transportation matrix, it is used to receive described fluid sample and implements a general chemical analysis and can detect response to produce one.

In the 5th preferred embodiment, the invention provides a kind of lateral flow analytical test strip, it has: lateral flow transportation matrix; One is positioned at the specific bond analysis area on the described transportation matrix, and it is used for receiving a fluid sample and implements a specific bond analysis to detect the human albumin level that described fluid sample exists; With a general chemical analysis domain that is positioned on the described transportation matrix, it is used for receiving described fluid sample and implements a general chemical analysis to detect the creatinine levels that described fluid sample exists.

Description of drawings

Figure 1A is the perspective exploded view of the meter diagnostic device preferred embodiment of single use of the present invention;

Fig. 2 A is the side view of HbAlc dried reagent analysis transportation matrix one embodiment, and it schematically illustrates the function element that relates in specific bond analysis and the general chemical analysis;

Fig. 2 B is the plan view from above of the transportation matrix of graphic extension among Fig. 2 A;

Fig. 2 C adopts specific bond analysis area wherein to be positioned the side view of alternative transportation matrix of the single film of general chemical analysis domain upstream;

Fig. 2 D adopts specific bond analysis area wherein to be positioned the side view of alternative transportation matrix of the single film in general chemical analysis domain downstream;

Fig. 2 E adopts conjugate wherein to be arranged in the side view of the alternative transportation matrix of the single membrane material between specific bond analysis area and the general chemical analysis domain;

Fig. 2 F adopts specific bond analysis area wherein and general chemical analysis domain to be arranged in the side view of the alternative transportation matrix of the PAA-CN-CA film on the cellulose nitrate;

Fig. 2 G is similar to Fig. 2 F but wherein with the side view of the alternative transportation matrix of specific bond analysis and the transposing of general chemical analysis domain;

Fig. 2 H is that wherein conjugation district and specific bond analysis area are arranged on first film and general chemical analysis domain is arranged in the side view of the alternative transportation matrix on second film.

Fig. 2 I adopts the conjugate be positioned on first film to remove the side view of alternative transportation matrix that district and extension layer (spreader layer) position are furnished with second film below of general chemical analysis domain thereon;

Fig. 2 J is similar to Fig. 2 I but the side view that adopts the alternative transportation matrix of a conjugate pad;

Fig. 2 K is similar to Fig. 2 I but adopts additional layer to form the side view of the alternative transportation matrix of conjugate trapping layer below extension layer;

Fig. 2 L is the side view that the alternative transportation matrix of an extension layer is adopted in first film below that has the specific bond analysis area thereon.General chemical analysis domain is arranged on second film.

Fig. 3 A is that graphic extension adopts the present invention of the function element that relates in the specific bond analysis of cross-current and the general chemical analysis to transport the decomposition side view of matrix alternate embodiment;

Fig. 3 B adopts the present invention of side direction and cross-current to transport the decomposition side view of matrix alternate embodiment;

Fig. 4 is the skeleton view of an embodiment of disposable cassette of the present invention and reused meter system.

Fig. 5 A is the perspective exploded view of cartridge one embodiment of the present invention.

Fig. 5 B is the plan view from above that described single uses the cartridge bottom, shows the test-strips of wherein taking in.

Fig. 5 C is the flat sheet of the bottom view that described single uses the cartridge top.

Fig. 5 D is that the single that is received in the reused meter uses the top plan view of cartridge to block figure, the alignment of fluorescence detector in test-strips and the meter in the demonstration cartridge.

Fig. 6 is the perspective exploded view of reused meter.

Fig. 7 is the sample standard curve of analyte 2, and display density is to reflectivity;

Fig. 8 illustrates to be used for by detection zone 1 reflectance readings and to be determined algorithm graphic of analyte 1 concentration by analyte 2 concentration that detection zone 2 (general chemical analysis domain) is measured.

Fig. 9 is that to illustrate the %HbAlc data collection linear graphic;

Figure 10 A illustrates graphic to the influence of HbAlc test result of hematocrit in low %HbAlc (non-diabetic) sample;

Figure 10 B illustrates graphic to the influence of HbAlc test result of hematocrit in high %HbAlc (diabetes) sample;

Figure 11 A is %HbAlc correlativity graphic that illustrates the finger tip sample that the medical worker that freely accepts professional training obtains; And

Figure 11 B is graphic from the %HbAlc correlativity of the finger tip sample that is directly obtained by the user.

Reference number identical in whole alterations refers to similar elements.

Embodiment

Operation of the present invention and advantage

In its various aspects, the invention provides a kind of system and method, it together implements a specific bond analysis and a general chemical analysis with the lateral flow analytical form, thereby quantitatively determines one or more analyte level from the single sample source.

According to circumstances, a kind of measurement of analyte can be used for obtaining or proofreading and correct the measurement of another analyte in the same sample.In particular instance, provide a kind of system that is used for quantitatively determining glycosylated hemoglobin (HbAlc) amount by total hemoglobin (Hb) level of using specific bond analyzing and testing HbAlc level and use general chemical analysis test sample to exist.

The invention provides a kind of system that is used for determining a plurality of analyte levels of a sample.Preferable at least one test-strips that comprises of this system, its have be configured to removable across the transportation matrix of sample in the lateral flow of transportation matrix.The present invention can be that independently (disposable apparatus that for example, is the single type of service) can comprise that maybe one has a succession of reusable meter that contains the disposable cassette of one or more transportation matrix according to circumstances.

The preferable specific bond analysis area that comprises of each transportation matrix, it is used to receive sample and implements a specific bond analysis and can detect response to produce one.The preferable general chemical analysis domain that also comprises of each transportation matrix, it is used to receive sample and implements a general chemical analysis directly or by chemical modification generation one can detect response.The present invention also comprises and is used for can detecting the system that analyte level in the sample is determined in response by described specific bond analysis and general chemical analysis domain.

The present invention also provides a kind of system that is used for measuring a sample first and second analyte levels, carries out chemical reaction to produce the chemical indicator of a testing result but contain in the described sample to be useful on described second analyte.Described system comprises that one or more is used for moving the transportation matrix across its lateral flow sample.Each transportation matrix is preferable comprise one receive sample and make it with scatter be fixed thereon through conjugation district that mark indicator reagent contacts.Described can the reaction in the presence of first analyte to form one through mark indicator reagent contained one first analyte: through the potpourri of mark indicator complex.Each transportation matrix is preferable to comprise that one receives from the potpourri in described conjugation district and makes it to be fixed in the trapping region (that is: specific bond analysis area) that first reagent on the described transportation matrix contacts with non-scattering.First reagent can react in the presence of described potpourri to be formed one by the level through mark indicator reagent that is fixed in trapping region and can detect response and form one and can detect response by being present in the trapping region second analyte level in the potpourri.In specific embodiment of the present invention, transportation matrix comprises further that according to circumstances one disturbs removal (conjugate removal) district, and described district can receive and secure first analyte from remaining mixture: through mark indicator reagent complex.The remaining mixture that measurement zone on each transportation matrix (that is: general chemical analysis domain) can receive self-interference to remove the district is also measured from the detected response of reacting between chemical indicator and described second analyte.Perhaps, can be simply with through the mark indicator reagent and first analyte: through the flushing of mark indicator complex by measurement zone to arrive trapping region.In these embodiments, can be further with described analyte: through the flushing of mark indicator complex to terminal absorption pad.The present invention is used for can detecting the system that first and second analyte levels in the sample are determined in response by trapping region and measurement zone preferable comprising.Show that as meeting these systems can comprise optics (for example, albedo measurement) detecting device.Yet should be appreciated that the present invention is not limited thereto.For example, other optics and non-optical measurement/detection system also can be used for detecting described specific bond analysis and general chemical analysis reaction, and all are covered by in the scope of the invention.

The present invention also provides the analysis measuring apparatus of single use or has the reused meter that the single that can be received into wherein uses cartridge, to analyze a plurality of analytes.The embodiment that single uses is preferable to comprise that the monobasic shell and that has an outside surface and seal an interior zone can receive the sample receiver of the sample that contains a plurality of analytes through selecting to be used to measure its existence.Described sample receiver is positioned on the outer surface of outer cover.In optional embodiment, the card, kit system that meter system that single uses and reused meter and single use also comprises sample processing system, but described sample processing system can make sample and the amount relevant physically change detected of self-contained reagent reacting with one of selected analyte in generation and the sample.Described sample processing system is salable according to circumstances also can be communicated with the sample receiver fluid in shell, maybe it can be included in one and be arranged in the outside sampling receptacle of described instrument (and cartridge).The present invention further comprises following detecting device, but it can be to change detected generation response physically and the generation electric signal relevant with the amount of selected analyte in the sample in a plurality of detection zones.These detecting devices are sealed in the shell of described meter.The present invention also comprises a processor, and it is used for storing and has specific characteristic for the analytic set information of determining first and second analyte levels in the sample by the detected response of specific bond analysis and general chemical analysis detection zone.Described processor can utilize the further described detecting device of calibration of the detecting device calibration information of storage and convert the electrical signal to display analysis result's numeral output.Described processor is sealed in the shell and with detecting device and links to each other.The present invention comprises that also one is delivered to the output unit of housing exterior with numeral output.Described output unit links to each other with processor.

Use therein in the embodiment of the invention of disposable cassette, the cartridge that described single uses comprises that according to circumstances the monobasic shell and that has an outside surface and seal an interior zone can receive the sample receiver of the sample that contains a plurality of analytes through selecting to be used for to determine its existence.Described sample receiver is positioned on the outside surface of cartridge shell.Cartridge also comprises sample processing system, but described sample processing system can make sample and the amount relevant physically change detected of self-contained reagent reacting with one of selected analyte in generation and the sample.Described sample processing system is sealed in the cartridge shell and can be communicated with the sample receiver fluid, maybe it can be included in a sampling receptacle that is arranged in described instrument and cartridge outside.

Use therein in the embodiment of the invention of reused meter, described reused meter comprises following detecting device, but it can be to change detected generation response physically and the generation electric signal relevant with the amount of selected analyte in the sample in a plurality of detection zones.Described detecting device is sealed in the meter shell.Described meter comprises a processor, and it can use analytic set information stores to the independent single that is equipped with meter with specific characteristic in the cartridge for determining first and second analyte levels in the sample by the detected response in specific bond analysis and the general chemical analysis detection zone.Described processor can utilize the further calibrated detector of detecting device calibration information of storage and convert the electrical signal to display analysis result's numeral output.Described processor is sealed in the tool housing and with detecting device and links to each other.Described meter comprises that also one is delivered to the output unit of housing exterior with numeral output.Described output unit links to each other with processor.

A kind of diagnostic kit that is used for measuring a sample first and second analyte levels is contained in the present invention.Described kit comprises that but one contains and is useful on by producing a testing result and sample is implemented the sampling receptacle of general chemico-analytic chemical indicator and meter or reused meter and the aforesaid disposable cassette that a single uses with second analyte response.

A kind of transportation matrix that is used for measuring a plurality of analyte levels of a sample is contained in the present invention.In one embodiment, described transportation matrix comprises that at least one is used for moving the film across its lateral flow sample.The specific bond analysis area can receive sample and implements a specific bond analysis and can detect response to produce one on the described film, and general chemical analysis domain can receive sample and implement a general chemical analysis directly or by chemical modification generation one can detect response on the described film.In various structures, general chemical analysis domain can be positioned at specific bond analysis area upstream or downstream.

The present invention transports matrix and can be used for measuring first and second analyte levels in the sample.But described sample contains one and is used for carrying out chemical reaction to produce the chemical indicator of a testing result with second analyte.Described transportation matrix comprises that according to circumstances one deck is used for mobile film across sample described in the lateral flow of described transportation matrix at least.Described film comprise one can receive sample and make it with scatter be fixed on the described film through conjugation district that mark indicator reagent contacts.Describedly can in the presence of first analyte, react to form first analyte that contains through mark: the potpourri of indicator complex through mark indicator reagent.Described film comprises that also one can receive the potpourri in self-conjugate district and make it and is fixed in the trapping region that first reagent on the film contacts in the trapping region (that is: specific bond analysis area) with non-scattering.

Preferably, first reagent can react in the presence of described potpourri with by being fixed in forming through mark indicator level and can detecting response and form and can detect response by being present in the trapping region second analyte level in the potpourri of trapping region.An optional interference is removed (conjugate removals) and is distinguished and can receive and secure first analyte on the described film: through mark indicator complex and arbitrary non-compound through mark indicator reagent from remaining mixture.In a preferred construction, a measurement zone on the described film (that is: general chemical analysis domain) can receive self-interference to remove the remaining mixture in district and can detect response by the response measurement of the chemical indicator and second analyte.In another preferred construction, measure (that is: general chemical analysis) district and be positioned at and catch upstream, (that is: specific bond) district, and can be with through the mark indicator reagent and first analyte: through the flushing of mark indicator complex by measurement zone to arrive trapping region.In this second preferred construction, can be further with analyte: through the flushing of mark indicator complex to terminal absorption pad.

Replace the above-mentioned preferable competitive specific bond analysis that suppresses, another selection is the specific bond analysis that transportation matrix can be provided as direct competitive analysis or sandwich analysis.The various alternate embodiments that the present invention transports matrix comprise that transposing is used to implement the order of specific bond analysis and general chemico-analytic specific bond and general chemical analysis domain and increase each the district's sum that exists on the transportation matrix.

The present invention also provides a kind of and uses dissimilar analyses to measure method from the existence of at least one first and second analyte in a plurality of analytes of a sample on same sample, but described method comprises the steps: to handle described sample to give birth to a testing result by vague generalization credit division with a chemical indicator that can carry out chemical reaction with second analyte or modify second analyte; Use once the same sample of mark indicator agent treated part forming conjugate, or combine a specific bond partner with described analyte competition with first analyte, thereby but by specific bond analysis generation testing result; Transporting described sample makes it successively by a plurality of districts to detect from the response of the first analyte conjugate in the district and to detect response from chemical indicator second analyte in second district; And by detecting analyte level in the definite sample of response in described first and second districts.

The present invention includes the method that another is used for measuring at least two kinds of analyte levels of a sample.Described method comprises the steps: to make sample to contact with the end portion of the transportation matrix with a plurality of districts; With described sample be transported to scatter be fixed on the described transportation matrix through mark indicator reagent place; Make through mark indicator reagent and in the presence of first analyte, react to form a potpourri; Described potpourri is transported to non-scattering is fixed in the first reagent place that transports on the matrix; Make described first reagent in the presence of described potpourri, react with form through the first fixing reaction product with sample in relevant the detected response of one or more analyte level; Be transported to non-scattering and be fixed in the second reagent place on the transportation matrix not containing remaining mixture through the mark indicator; Make chemical indicator and all the other example reactions with form second reaction product and with sample in relevant the detected response of second analyte level; Determine one or more analyte level in the described sample by the detected response in the reactions steps of carrying out with first and second reagent.

The other method that the present invention is contained can use following steps to measure one or more analyte level in the sample: move across the sample in the lateral flow of a transportation matrix; Being positioned at specific bond analysis area on the described transportation matrix one implements the specific bond analysis to sample and can detect response to produce one; Being positioned at general chemical analysis domain on the described transportation matrix one implements general chemical analysis to sample and can detect response to produce one; And by the level of one or more analyte in the definite described sample of the detected response in described specific bond analysis and the general chemical analysis domain.Perhaps, interchangeable specific bond and general chemico-analytic order.

In preferred embodiment, meter of the present invention can be measured hemoglobin A lc (HbAlc), but is not limited only to this.In each preferred aspect of the present invention, to be analyzed one liquid of bleeding can be placed disposable cassette, wherein described cartridge is received in the described meter.

Another advantage provided by the invention is that the ability that produces quantitative result in single step-only need import sample in the described device and gets final product to activate its operation.Can in several minutes, produce numeric results by treated or unprocessed sample.Electronic equipment, detector system (for example, reflectance measurement systems), high resolution Digital to Analog Converter, integrated temperature measuring system (so that automatic temperature control to be provided when needed), be used for the electronic communication port that clear and definite sense analysis thing result's digital indicator and being used for is sent to the result computer or laboratory or hospital information system and all can include the present invention in.Also can use other system that is used for analysis result communication, include but not limited to acoustics or acoustics (comprising spoken words) and haptic device (comprising Braille (Braille)).

The present invention can avoid the limitation of prior art system in its some preferred embodiment, described prior art system needs certain type sample preparation or pre-service before putting on sample in the analytical equipment.Originally the sample preparation example of implementing in the analytical equipment outside is removal, the dilution of blood separation (to produce blood plasma), accurate and accurate cubing, interfering material (chemical chaff interference, sediment), or the like.Perhaps, described sample can extract another device of handling from sampling.The present invention does not get rid of described processing, and handles the use that can comprise professional sample processing device.The example of described device includes but not limited to that small size blood wherein is through the air mix facilities of dilution and/or cracking with wherein can produce the blood sampling and/or the tripping device of small size blood plasma.Described device can separate with the present invention fully or link to each other (permanent or temporary) with the present invention.

To have specific processing example be to be diluted to a solution in measurement to HbAlc, described solution contains the sodium ferricyanide, surfactant and pH buffering agent, comprises that according to circumstances extra salt, protein or other polymeric material are with the Improvement Analysis performance or to the resistance of interfering material.Described diluent solution can be included in the screw-cap bottle (preferably, volume is below 2mL) and provide as the part of assay kit, described kit also can comprise the capillary device that is used for obtaining from finger tip whole blood small sample (be preferably 10 μ L or still less).This kapillary can be used for blood sample is transported in the thinning agent subsequently.After the mixing, can utilize transfer pipet(te) or dropper to place sample port of the present invention through dilute sample.

Reused meter of the present invention and disposable cassette embodiment can provide plurality of advantages, include but not limited to following advantage.

The first, although described cartridge is disposable, meter self can use repeatedly.So, can including in the meter with described system than expensive component (comprising logical circuit, electronic equipment and optical measuring system).Equally, these assemblies need not to abandon after each the use.This can save cost for manufacturer and user.

Second advantage of cartridge of the present invention is its use that can avoid the inner drying agent of meter self.This should be owing to the following fact, and sensitive test-strips is in each independent cartridge.Because of independent cartridge can being enclosed in the damp-prrof packing (can just before use with its removal), so wherein test-strips is kept dry and need not in the meter shell, to add drying agent.On meter of the present invention, remove drying agent and can facilitate the saving space, thereby obtain device small-sized, that cost reduces.

The 3rd advantage of card, kit system of the present invention is that blood sample to be analyzed can not pollute meter (repeatedly user's) internal work district.On the contrary, blood sample can be included in (disposable) cartridge self always.The described advantage of this system is that it can change the analysis that presents blood sample simply with the form that is read by the meter inner optical system into, and need not decontamination or processing meter.

The 4th advantage of card, kit system of the present invention be, in the embodiment that described cartridge and meter match each other, need not to present calibration information by disposable cassette to meter, thereby save cost.

Definition and to the explanation of accuracy described herein, sensitivity and definition

As indicated above, the invention provides a kind of novelty and unconspicuous analytical equipment and method, described analytical equipment and method can be utilized specific bond analysis and the quantitative simultaneously a plurality of analytes identified in the same sample of general chemical analysis.By the present invention reach quantitatively can be by the definition of measuring that comprises precision of analysis, sensitivity and definition.

Term body fluid analysis thing is used for representing any desire amalyzing substances, includes but not limited to be stored in hemoglobin A lc, cholesterol, triglyceride, albumin, kreatinin, human chorionic gonadotrophin (hCG) or like that in arbitrary body fluid (for example blood, urine, sweat, tears or like that) and the bodily tissue liquid extract (no matter be directly apply or as being applied to the present invention through dilute solution).

As defined herein, sensitivity is the detection lower limit of analysis or clinical chemistry.But described detection lower limit is to distinguish over zero amount of an analyte in the sample or the minimum detection limit of complete non-existent analyte.Calculate by illustrating the calibration curve of analytic signal but the minimum detection limit of analyte is preferable analyte concentration.At first determine the standard deviation of the average signal of zero point correction device.In average signal value, add or therefrom deduct twice of standard deviation according to circumstances.Subsequently, the analyte concentration that is directly read or calculated by calibration curve is the detection lower limit.

Should be appreciated that the present invention is not limited to measure arbitrary method or any other quantitative measurement system of sensitivity.For example, spendable alternative method is to determine the mean value and the standard deviation (comprising zero point) of some calibrating devices.The least concentration that is different from the zero point correction device can be determined with experimental technique with acceptable statistics degree of confidence (for example 95% or higher).The version of the method be determine can be given the analyte least concentration that records of inaccuracy level (for example 15% or lower).This analyte concentration value often is called quantitative limit.

The method operational analysis chemical method that another determines analytical sensitivity relates to the slope of a curve of comparative analysis signal and analyte concentration.The absolute value of rate of curve is big approximately, and sensitivity is just strong more.For example, but with reflectivity when measuring the method for the change detected physically of showing by test result provided herein, represent bigger per unit analyte concentration and change that the curve of reflectance varies can be sensitiveer down.Yet analytic signal is normally nonlinear to the analyte concentration curve.Therefore, described curve has the higher or lower zone of sensitivity, directly impact analysis result's validity.Another problem is whether the method for the definite sensitivity of this kind not will consider and compare given signal with noise level in the described measuring system and change remarkable.

In the mode that defines sensitivity (detection lower limit) definition used herein is defined as described test and distinguishes the closely ability of analyte concentration approaching but inequality that changes with total inaccuracy (total CV).The overall noise of described test or inaccuracy low more (CV is low more), explanation ability or definition are just strong more.Each component of definition comprises the noise and the intrinsic noise (comprising flow irregularity, material changeability, assembling changeability and composite changeability) of chemical system of analog-digital conversion definition (can be used for being formed by simulating signal the bit number of numerical coding numerical value), instrument measuring system simulation part.

Accuracy defined herein is to analyze the ability that produces the result who is closely related with the result who comes self-reference or forecast analysis.Particularly, accuracy is defined according to the mean value preference with respect to reference.Described preference is the difference between experiment value and the reference value.If described preference is zero (that is, the two is identical), then described test is 100% accurate.For error that is caused by inexactness and the error that is caused by inaccuracy or preference are distinguished, can use mean value from a series of repeated measures.Certainly, this definition supposition forecast analysis can produce true value.

Accurate parameters value and equation that the accuracy that the present invention analyzes can be further be provided for calibrating by the microprocessor to analytical equipment and the accurate parameters value of proofreading and correct variation in the output of LED spectrum are improved.During the present invention makes, these accurate calibration parameters and equation are loaded in the analytical equipment (that is: meter or cartridge, or the two) with electronics method.The inventive method can be eliminated another source of error to the constant or the equational dependence of the discrete type predetermined programmed in the reusable instrument of packing into by avoiding prior art.

The present invention can improve precision of analysis by proofreading and correct the error that occurs under some levels.For example, the preferable use of the present invention helps by reduce the analysis of mean value preference at the factory calibrated of standard material and laboratory reference method.The use of reference analysis on the plate that carries out when the inventive method can be avoided disclosing in the prior art, described reference analysis can be to introducing uncorrectable error with reference to test.It also can be avoided the inherent error in the use of secondary standard material by the user of palpus periodic calibration instrument in the clinical labororatory.

Another example is by the preferable use of the present invention to the clinical sample that is used to calibrate.By calibrating with clinical sample or synthesizing calibrating device (when it produces identical value with clinical sample) calibration, the error result that is caused by clinical settings or matrix effect can be minimized.

Another example is that measurement background or error can produce by described measuring system is inner.It comprises the amplification of the analog electrical signal that transportation matrix alignment error (in whole three dimensions), LED spectrum changeability (regulator during the manufacturing), LED energy emission changeability, optical alignment's changeability and described detecting device produce and the changeability in the measurement.In fact, all these effects can be eliminated by the reference strategy,, obtain detector output signal and the ratio of the detector signal that is obtained by initial dried bar reading and the ratio of exporting with reference detector that is.

The reference strategy of albedo measurement is illustrated in hereinafter in the equation 1.This strategy provides the in-discard that comes across major part gain in the two of optical device (or other detector system) and electronic equipment (slope, or proportional) and be offset (intercept, or fixed value) error, and can be used for all analyses.The use of equation 1 can make the reflectivity changeability reduce about 10 times.In this equation, " R " is reflectivity.Initial reading reads and asks for subsequently the ratio of all follow-up readings and initial value behind blank (dark current, " the OFF ") reading of deduction on dried bar.Behind blank (dark current) reading of deduction, ask for all readings and the ratio of locating signal with reference to photodetector (" ref ") equally.Equation 1 is as follows:

The exemplary definition of described transportation matrix function can comprise (for example) but be not limited to:

Trapping region, but wherein change detected is confined to specific bond with simplified measurement, but and the best capture district the even distribution of change detected is provided;

The conjugation district, wherein conjugate, antibody, antigen and like that be scatter fixing and wherein its at first with sample fluid in analyte response or experience.Best conjugation district can produce the uniform mix that conjugate and other scatter immobilization material and described sample fluid, and preferably can detect the close described trapping region in the compatible location of response with suitable sensitivity.Dissociating of these materials preferablely finished in analysis time or finished substantially;

Non-specific or general chemical measurement zone, wherein but change detected (but as under situation of indicator with detected characteristics (for example light absorption under the specific wavelength) or analyte) is not clearly located, and uses for measurement of concetration with the representative part of presenting sample to detecting device but be evenly distributed in the whole material;

Disturb to remove the district, but wherein material can be through removing or improving so that it no longer changes the order of magnitude of change detected in the subsequent captured district in the sample fluid.One or more interfering material can be removed or improve in best interference removal district makes it to reach specific concentrations, so that it no longer applies preference or apply acceptable preference the analyte result;

The sample pretreatment district, wherein the Chemical composition that of sample through improving so that it is more compatible with follow-up function element of analyzing.Other important chemical property of sample pretreatment district scalable self when the best, for example pH, ionic strength and like that are so that it adapts to the normal operation of other chemical component on described;

The blood separation district, wherein with red blood cell by removing in the described sample fluid to produce blood plasma or similar colourless fluids.Other cell component (when needing) of red blood cell and whole blood can be removed by preferable blood separation district, so that only has these components that can accept number to be retained in the gained blood plasma, and haemocylolysis is atomic.For example, whether acceptable haemocylolysis level (release of free hemoglobin) can be detected by detecting device by the haemoglobin color and define and preferable the expression near the haemocylolysis level of 0 (＜＜1%) to about 2% during some were analyzed;

The sample overflow area provides wide sample volume tolerance, wherein surpasses the volume required excess sample volume of enforcement analysis and is absorbed.Preferable sample overflow area can hold above the sample volume of specialized range and clearly can accept or the tolerance scope in can in the analyte result, not introduce preference;

The sediment filtrating area, wherein microparticle material obtains removing the fluid of clarifying on the optics to produce in the sample.Can in the analyte result of report, not produce unacceptable preference but preferable sediment filtrating area can disturb fluid to flow or the microparticle material of change detected generation is removed to a certain degree so that have sedimentary sample;

Conjugate is removed the district, wherein can be similar to disturbing removal district and the described mode of sediment filtrating area to remove through mark indicator reagent and complex thereof.Preferable conjugate remove the district can remove may disturb that but change detected produces through mark indicator reagent and complex thereof, so that it can not apply any remarkable preference to analysis result;

Be various sample fluids or analyte (whole blood, blood plasma, serum, urine, saliva, vaginal swab, brush,throat, from the health each several part mucus secretion, sweat, through the digestion tissue sample, or the like) exclusive person.

The preferred materials that is used for these functions can change and can comprise with required concrete function:

The cellulose nitrate as mentioned above that is used for sample pretreatment district, detection zone and other each district that does not spell out;

Evenly (symmetry or non-) the microporosity filtering membrane that is used for non-specific measurement zone to becoming, for example nylon membrane of producing by Pall Gelman and CUNO and the poly (ether sulfone) film of producing by Pall Gelman, thus its not modified or through chemical modification with the special adsorptive hindrance thing of the adsorption property that changes described film or prevent analyte absorption;

Be used for the glassfiber composite through adhesive treatment in sediment filtrating area and blood separation district, compound, " sharkskin " sample material and the microporosity filtering membrane of the cellulose glassfiber composite, polyester and the glass fibre that mix with bonding agent, for example the nylon membrane that provides by Pall Gelman, Millipore and CUNO and asymmetric polysulfone membrane of producing by Memtec and the Presence  poly (ether sulfone) film of producing by Pall Gelman;

The open design material that is used for the conjugation district, for example polyester non-woven composite, cellulose acetate membrane and have the glass fibre of bonding agent-handle separately or through conjugate releasable material (polyvalent alcohol, surfactant, hydrophilic polymer, multipolymer or like that);

Be used to disturb removal and conjugate to remove the ion exchange material in district, Whatman GF/QA for example, contain and scatter fixing interference removal material (for example different preferendum blocking agent, anti--HAMA (human-anti--mouse-antibody) material and chaotropic agent) polymer film, and through the glass fibre of adhesive treatment, the cellulose glass fibre that mixes with bonding agent, the compound of polyester and glass fibre, " sharkskin " sample material and microporosity filtering membrane, for example nylon membrane that provides by Pall Gelman and CUNO and asymmetric polysulfone membrane of producing by Memtec and the Presence  poly (ether sulfone) film of producing by Pall Gelman; With

The absorbing material that is used for the sample overflow area, for example the Transorb  that produces by Filtrona Richmond.

In an exemplary embodiments, measurement has specific multistage transportation matrix and comprises to HbAlc:

The material that is used for the conjugation district, cellulose acetate membrane;

Be used to catch the material in (specific bond) district, nitrocellulose filter; With

The material that is used for non-specific (general chemistry) measurement zone, nylon.Measure in the instantiation of HbAlc at this, described material also can be used as the conjugate removal district that can filter out the particulate conjugate and prevent its color interference total hemoglobin measurement.The filtering property of this kind material can depend on but be not limited to membrane aperture, described film surface charge and for based on but be not limited to the chemical attraction of ion, dipole-dipole and hydrophobic interaction or repel the interpolation of the chemicals of create openings.

Yet as shown here, various embodiments of the invention need play the required function of more than one transportation matrix with same material.For example, nitrocellulose filter can be exercised the conjugation district, be caught the function of (specific bond) district and non-specific (general chemical) measurement zone.Perhaps, cellulose nitrate can be exercised the function of catching (specific bond) district and non-specific (general chemical analysis) measurement zone, and cellulose acetate can be exercised conjugation district function.In another example kind, cellulose nitrate is exercised the conjugation district and is caught the function in (specific bond) district, and the function of nylon form non-specific (general chemical analysis) measurement zone.

General chemical analysis comprises the reaction that analyte (including but not limited to glucose, kreatinin, cholesterol, HDL cholesterol, LDL cholesterol, triglyceride and urea nitrogen (BUN)) is implemented through definition.For general chemical analysis, the preferable use enzymic catalytic reaction of the present invention is to produce detected response or a signal relevant with the unique value of analyte level in the sample in each detection zone.Be used for producing other system that can detect response and also be applicable to the present invention at detection zone.For example (but being not limited to), analyte can detect product to generate by reduction, oxidation, pH variation, gas generation or precipitation with a kind of enzyme or a series of enzyme reaction.Enzymatic reaction also can take place or replace in non-enzymatic reaction (no matter being through catalysis or without catalysis person) simultaneously with enzymatic reaction.The example that can detect product comprises that they can be by fluorescence, product luminous or that detected by the reflectivity or the absorptivity of characteristic light wavelength (wavelength that comprises ultraviolet, visible light, near infrared and the infrared part of spectrum).This paper be used for general chemico-analytic term " indicator " desire to comprise can with analyte or relevant analyte response product reaction and produce and can indicate the detected response of sample analyte level or all compounds of signal on stoichiometry with analyte.

The specific bond analysis comprises reaction between the specific bond partner through definition, includes but not limited to that agglutinin-carbohydrates is in conjunction with the immunoassay reaction between interaction, hormone-receptor response, streptavidin-biotin combination and the antigen and the antibody of, complementary nucleic acid chain.For the specific bond analysis, the detection of particles that the preferable use of the present invention is carried out detected response relevant with analyte level in the sample in each reaction zone or signal.In described specific bond district, provide other system that can detect response also to be applicable to the present invention.For example (but being not limited to), can be directly or indirectly by the second antibody conjugate or with other association reaction labelled analyte or its specific bond partner of indicator, to measure the reflectivity or the absorptivity of fluorescence or luminous or characteristic light wavelength.This paper is used for that " indicator " that specific bond analyzes desire to comprise can labelled analyte or its specific binding agents or its conjugate and produce and can indicate the detected response of sample analyte level or all compounds of signal.

Although the present invention chemistry and structure can be used in the integrated analysis device, the present invention can be used as replaceable dose and is used for arbitrary other and reflectivity of instrument is housed or transmits meter.Therefore, integrated analysis instrument and analytic type analytical instrument are also contained in the present invention, comprise the replaceable cartridge that is stored in can limited reusable analytical instrument (comprising analytical equipment of the present invention).

Graphic detailed description

The preferred embodiment that is used for measuring the meter diagnostic device 100 that the single of HbAlc uses is illustrated in Fig. 1.Meter 100 comprises a shell 102 and lid 104, and described lid 104 has a receiver, and for example import 106, and it is extended to the enclosure 110 that is used to receive the sample 112 that contains one or more selected analyte to be determined by lid outside surface 108.

Import 106 allows sample 112 is included in the sample receiving device 114 that links to each other with the inside surface 116 of lid 104.Sample receiving device 114 comprises that one analyzes with two that the bar fluids are communicated with and responsible sample is allocated in two two-layer pads between the bar.According to circumstances, sample receiving device 114 can comprise that also one removes the sample filtering pad of not expecting pollutant in sample.The sample filtering pad can be identical with the reception pad, and one of them pad can be exercised two kinds of functions.Meter 100 can comprise the sample filtering pad of the dissimilar pollutants of more than one removal along the sample flow path.Analyze bar for two and contain the chemical reagent that is useful on definite one or more selected analyte existence.

Enclose a reflectometer 126 in the inside 110 of shell, described reflectometer comprises that one has the printed circuit assembly of printed circuit board (PCB) (PCB) 128.Reflectometer 126 also comprises an optical module 130 and a shade 132.PCB128 has a surface 134, has on the described surface to be directly installed on a top reference detector 136 and district's detecting device 138,140.The surface 134 of PCB also has two 135,137, one of light emitting diodes (LED) that directly are installed on the PCB and is used for a pair of illumination channel.LED135,137 preferablely is naked crystal grain form and does not have complete camera lens, shell or shell.Therefore, LED135,137 can provide the illumination of all directions above 134 on the surface and only by optical module 130 orientations.Similarly, district's detecting device 138,140 and reference detector 136 is the naked crystal grain that is directly installed on the surface 134 of PCB.LED135,137 and detecting device 136,138,140 all be positioned at same level.

Fig. 1 goes back the position of graphic extension shade 132 with respect to PCB 128.Provide the aperture 142 that sees through shade 132 to prevent to block LED135,137 and reference detector 136.Provide opening 144 to prevent blocked-off region detecting device 138,140.Shade 132 comprises upstanding wall 146, and it can prevent that stray radiation from entering district's detecting device 138,140.When reflectometer 126 installed fully, upstanding wall 146 was positioned in the reflection and refracting element adjoining position with optical module 130.

Optical module 130 is common stilts in a plane, and it has an at least one end face 148 and a bottom surface 150.Bottom surface 150 is configured to receive from LED135,137 illumination and optical module 130 and illumination orientations can be arranged in the one 154 and the 2 156 sampling area of analyzing on the bar 152 at one or more.The diffuse reflection optical radiation that the end face 148 of optical module also can be configured to be returned by sampling area 152 is sent in one or more district's detecting device 138,140.

Analyzing bar 154 and 156 is installed in respectively in bar carrier 158 and 160.Carrier 158,160 is installed in optical module end face 148 tops and firmly is fixed on correct position will analyze bar 154 and 156.

Meter 100 is included as the battery 168 that PCB 128 and LCD (LCD) 162 provide electric power.Also can advance in the shell 102 being used for drying agent 164 and absorbent material 169 envelopes that the excess sample volume overflows.

Fig. 2 A and 2B graphic extension are used for specific bond analysis and general chemico-analytic lamination transportation matrix 200, and described lamination transportation matrix is applicable to the preferred embodiment (that is, being used for analytical test strip 154 and 156) of above-mentioned diagnostic device 100.In this embodiment of the present invention, on the fluid mobile route of transportation matrix 200, have 4 different porosints, each sheet is laminated on the liner of being made by suitable plastic-like PET 202, accurately alignment each other.Fig. 2 A shows vertical transversal section (side view) of longshore current body mobile route and Fig. 2 B shows corresponding plan view from above.Sample is displaced sideways and enters respectively first detection zone 206 and second detection zone 208 along transportation matrix 200 by capillary action with direction shown in the arrow 204.Transportation matrix 200 keeps alignment by the pin that is fit to sprocket hole 210 with the guide piece relative with the bar side.

Transportation matrix 200 comprises a sample pad 212, and it is used for receiving sample by the import (not shown) on the top side 214 of the pad 212 that is positioned at transportation matrix 200 near-ends 216 places.In the example that uses diagnostic device shown in Figure 1, the preferable sample pad that does not link to each other with the remainder of analyzing bar physically can receive sample and it is distributed between two the transportation matrix of separating 154,156.

In an optional preferred embodiment, transportation 200 preferable comprising by first detection zone pad of making such as materials such as cellulose nitrate 220 of matrix, it has about 70 to about 240 μ m and preferable about 135 uniform thickness to about 165 μ m.Capillary excreting dampness rate in about 4cm should be about 0.1 to about 0.6mm/sec scope, and preferably mean value is about 0.2 to about 0.4mm/sec.The opacity of material is preferable should to make any gasket material invisible, and perhaps, gasket material can be white reflecting material, for example white PET.In some cases, the black gasket material can be preferable.Material also should have the dried wet strength that helps making.Protein portion must non-distribution be fixed in the situation that specific bond analysis on the film or other specific bond analyze therein, and material should have high protein adsorption capacity, and described capacity is at about 1 to 200 μ g/cm ²Scope is interior and preferable at 80 to 150 μ g/cm ²In the scope.

In various preferred embodiments, the transportation matrix 200 preferable multistage different materials that comprise fluid communication with each other.The multistage material carries out optimized every section material to specific function can for plan dirigibility is provided.Multistage transportation matrix can help avoiding using " trading off " material that can implement all required test functions but not have optimum.Yet (, transportation matrix can change into by the individual layer continuous material that can implement all required test functions to be made.) fluid is communicated with and comprises: cross the transportation substrate plane and sample in the lateral flow is moved and/or by making sample flow cross transportation substrate plane and/or vertical current through transportation matrix.The present invention is further contained, and is communicated with by transportation substrate plane and/or vertical described two dimension or three dimensional fluid by the transportation substrate plane that move can be in regular turn or generation simultaneously.

In a preferred embodiment, described sample pad 212 is preferable to be made for No. 1660 or No. 1662 by the CytoSep for cellulose and glass fiber compound material from Gelman Sciences.Described sample pad has about 7 to 10mm approximate square size, and wherein thickness is about 0.012 to 0.023 inch.Another suitable material is 1281 grades of Ahlstrom filtering materials, and it consists of the polyamide wet-strength resins and the polyacrylamide dry strength numerical value of about 90% cellulose fiber peacekeeping, 10% rayon and trace.Its basis weight is 70g/m ²And thickness is about 0.355mm.

Two transportation matrix 154,156 shown in previous link to each other or are in fluid communication with it among sample pad 212 and Fig. 1.Sample is flow on the conjugate pad 218 by sample pad 212, and in a preferred embodiment, described conjugate pad 218 is made in order to scatter the conjugate of fixing a resisting-HbAlc and an indicator by cellulose acetate.Conjugate pad 218 can be that about 7mm is long, 3mm is wide, about 0.005 to 0.010 inch thick.Conjugate pad 218 can link to each other with the PET liner by bonding agent.Another appropriate materials that is used for conjugate pad 218 is from No. 14 to 20, the Accuwik of Pall Biosupport.

In a preferred embodiment, be arranged in the conjugate that the fixing conjugate 225 of distribution on the conjugate pad 218 can comprise an anti--HbAlc and an indicator.Other possibility of conjugate 225 comprises the anti-conjugate antibody of absorption (that is: no matter conjugate whether all can be in conjunction with the material of conjugate in conjunction with other thing).Instantiation can include but not limited to: (1) with can in conjunction with and the fixing material soaking of conjugate; (2) at the antibody of conjugate, and (3) can bridge between the conjugate particulate and the fixing polymkeric substance of conjugate particulate.

The conjugate pad 218 and first detection zone pad 220 are overlapping and be in fluid communication with it.The about 7mm of described first detection zone pad 220 are long, about 3mm wide, about 0.006 to about 0.008 inch thick.First detection zone pad 220 can make sample 112 flow through first detection zone 206 until arriving transportation matrix far-end 220.

In preferred aspect of the present invention, conjugate 225 is preferably as close as possible with the overlay region of conjugate pad 218 and detection (that is, catching) district pad 220.Making the as close as possible advantage of the conjugate 225 and first detection zone pad 220 is that it can prevent wherein color striped.Particularly, when fluid sample at first arrived conjugate 225, its viscosity can increase.Therefore, originally fluid sample and conjugate potpourri tend to accumulate in just immediately following on the conjugate pad 218 behind the overlay region of the conjugate pad 218 and first detection zone pad 220.Then, fluid sample and conjugate potpourri are spilled on first detection zone pad 220 in the mode that even side direction strides across first detection zone pad, 220 width.

First detection zone pad 220 and second detection zone pad 222 are overlapping and be in fluid communication with it.In one embodiment, second detection zone pad 222 by nylon membrane (for example from the Immobilon Nylon+ of Millipore, 0.45 μ m or from the Biodyne C of Pall Gellman) make, it has uniformly still retainable opacity after with indicator and enzymatic mixture dipping and follow-up drying.The about 7mm of second detection zone pad 222 are long, about 3mm wide, about 0.006 to about 0.008 inch thick.It allows sample 112 to flow through second detection zone 208 until the far-end 220 that arrives transportation matrix.

First detection zone pad 220 can effectively capture the conjugate that combines indicator with the face that connects 226 of second detection zone pad 222.Therefore, can prevent to scatter the indicator that is combined in the conjugate pad 218 enters in second detection zone pad 222.Perhaps, the order interchangeable of first and second detection zones.In this case, the indicator conjugate 225 that distribution is fixed in the conjugate pad 218 washes by first detection zone pad 220 (it can comprise the non-specific chemical measurement district of total hemoglobin), arrives second detection zone pad 222 (it can comprise the specific bond analysis area of catching in conjunction with the conjugate of indicator).

Second detection zone pad 222 and absorption of sample pad 224 are overlapping and be in fluid communication with it, and described absorption of sample pad 224 allows sample flow to cross the far-end 230 that second detection zone 206 arrives the transportation matrix.

The various different embodiment that the present invention transports matrix 200 can be covered by in the category of the present invention.Fig. 2 C to 2L shows that the present invention transports the example of matrix 200 various embodiment.These exemplary embodiments have specific characteristic and advantage separately, and are as mentioned below.Should be appreciated that the present invention transports matrix 200 and is not limited to the specific embodiment shown in Fig. 2 A to 2L.Can include other transportation matrix system in, it all is covered by in the scope of the invention.

Fig. 2 C is the side view that adopts the alternative transportation matrix of single membrane material, and wherein the specific bond analysis area is positioned at general chemical analysis domain upstream.Particularly, show single detection zone pad 221.Detection zone pad can be made by cellulose nitrate, but is not limited to this.Shown in conjugate 225 is arranged on the detection zone pad 221 on the position.In a preferable manufacture method, conjugate 225 is applied to the top of detection zone pad 221 by atomizer spray as striped.

(Fig. 1) is accommodated on the sample pad 212 with fluid sample 112.Fluid sample passes through transportation matrix 220 (along direction 204) by capillary action then, thereby flows through conjugate 225.Thereafter, sample at first flows through first detection zone 206 and flows through second detection zone 208 subsequently.Any remaining conjugate is all removed 227 places, district at conjugate and is hunted down, and it has an opportunity to arrive second detection zone 208 then.Then simply with the excess fluid sample wash to absorption of sample pad 224.

Fig. 2 D is similar to Fig. 2 C, but specific bond analysis area 206 and described general chemical analysis domain 208 are changed.

The major advantage of system is among Fig. 2 C and the 2D, and it only needs can not only implement the specific bond analysis but also implement general chemico-analytic single film on it.The use of single film can be eliminated the mobile heterogeneity that the slight variation by the film overlapping dimension causes.Overlapping lacking also can increase the efficient of conjugate flushing by described between conjugation district and the detection zone.

Fig. 2 E is similar to Fig. 2 D, but originally conjugate 225 changes into and being arranged between general chemical analysis domain 208 and the specific bond analysis area 206.The special benefits of this transportation matrix 200 embodiment is not have conjugate 225 to flow through general chemical analysis domain 208.(by contrast, embodiment uses film overlapping to prevent that conjugate 225 from entering general chemical analysis domain 208 meeting face 226 places among Fig. 2 A.) this structure can solve the problem that conjugate disturbs the reaction implemented in the general chemical analysis domain (or detection).Since neither need overlappingly may not need chemical conjugation thing trapping layer 227 again meeting face 226 places, thus can keep the homogeneity of liquid flow, and avoid interference the risk of general chemistry in any chemical conjugation thing trapping layer.

Fig. 2 F shows a following embodiment of transportation matrix 200, wherein conjugate 225 is arranged on the conjugate pad 218; And the two is arranged in the single detection zone pad 221 with specific bond analysis area 206 and general chemical analysis domain 208.

Fig. 2 G is similar to Fig. 2 F, but the order of specific bond analysis area 206 and general chemical analysis domain 208 is changed.

The major advantage of system is among Fig. 2 F and the 2G, and it only needs not only to implement the specific bond analysis but also implement general chemico-analytic single film on it.In addition, can mode mentioned above by adopting conjugate pad 218 that conjugate 225 is applied near the overlay region with single detection zone pad 221 to prevent striped therein.Because many conjugate cushion materials have coarse relatively character, so it is vulnerable to the damage of liquid flow unevenness.Can avoid this risk near conjugate 225 placed the overlay region.

Fig. 2 H shows the following embodiment of transportation matrix 200, and wherein the two is arranged on first detection zone pad 220 with conjugate 225 and specific bond analysis area 206; And general chemical analysis domain 208 is arranged on second detection zone pad 222.Overlay region 226 can capture conjugate 225, thereby guarantees that conjugate 225 can not arrive second detection zone pad 222 (thereby and can not disturb in the general chemical analysis of wherein implementing and can not disturb general chemico-analytic reading yet).

Fig. 2 I is the side view of following alternative transportation matrix 200, and it has first detection zone pad 220 that contains specific bond analysis area 206 above tool; With top second detection zone pad 222 that contains general chemical analysis domain 208.Extender/processing/filtering layer 228 is arranged in second detection zone pad, 222 belows.The operation of extension layer 228 can guarantee that sample kept lateral distribution before moving to detection zone pad 222.Conjugate removal district 227 adopts in conjunction with conjugate or material formation and its operation of conjugate gathering can be fixed conjugate, thereby prevents that it from moving to second detection zone pad, 222 places.This transportation matrix 200 embodiment are applicable to the detection kreatinin ideally, but are not limited to this.Be applicable to that conjugate removes the material in district and include but not limited to membrane matrix through chemical modification, for example modified nylon with positive charge or negative charge functional group; Polymkeric substance with positive charge or negative charge, for example polyethyleneimine or polyacrylic acid; With anti-conjugate antibody.

Fig. 2 J is similar to Fig. 2 I, but change into conjugate 225 is arranged on the conjugate pad 218.As mentioned above, conjugate pad 218 can be used for preventing the sample striped.

Fig. 2 K is similar to Fig. 2 I, but additional layer 209 is arranged in extension layer 228 belows.The face that connects 226 between first detection zone pad 220 and the layer 209 plays the effect of conjugate trapping layer, can prevent that conjugate from arriving extension layer 228 (with second detecting pad 222).

Fig. 2 L is the side view with alternative transportation matrix 200 of the extension layer 228 that is arranged in first detection zone pad, 220 belows.General chemical analysis domain 208 is arranged on first detection zone pad 220.Specific bond analysis area 206 is arranged on second detection zone pad 222.

Fig. 3 A and 3B graphic extension are used for specific bond analysis and general chemico-analytic stacked transportation matrix, and described stacked transportation matrix is applicable to the alternate embodiment of above-mentioned preferable diagnostic device 100.Fig. 3 A shows the decomposition side view of the alternate embodiment 300 of transportation matrix, and wherein fluid communication path mainly is stored in the cross-current perpendicular to porous material surface.In preferred embodiment, along the different porosint of plural pieces is arranged on the fluid mobile route of stacked transportation matrix 300, direct each other fluid is communicated with or is communicated with by other porosint, passage or fluid connecting device between each sheet porosint.Described transportation matrix 300 comprises sample pad 312, and it is used for receiving sample by the import (not shown) on the top side 314 of the pad 312 that is positioned at transportation matrix 300 near-ends 316 places.Described sample pad 312 is preferable to be made by cellulose and glass fiber compound material.

Sample pad 312 covers on the conjugate pad 318 that is used for first analyte and is in fluid communication with it, and described conjugate pad 318 is made to scatter the conjugate of fixing resisting-HbAlc and indicator by cellulose acetate according to circumstances.Conjugate pad 318 cover be used for first analyte catch with first detection zone pad 320 on and be in fluid communication with it, described catching with first detection zone pad 320 can be made by the cellulose nitrate substrate according to circumstances.First detection zone pad is provided for first detection zone (specifically not being illustrated among Fig. 3 A) of first analyte.In the situation by the preferable detection system of optical reflection, the detection of first analyte can obviously be improved so that the minimization of loss of optical reflectivity by isolation first detection zone in first detection zone pad.Therefore, transportation matrix 300 can provide isolation film 322 according to circumstances, and it can make the reflected light minimization of loss that sees through the porosint that is positioned at transportation matrix far-end 324.Optional isolation film 322 is communicated with first detection zone pad, 320 fluids and allows sample 302 to flow to conjugate removes pad 326 places, district, and described conjugate removal district pad 326 can effectively capture in conjunction with the conjugate of indicator and prevent that it from entering any detection zone that is positioned at away from the transportation matrix of first detection zone.

According to circumstances, the second isolation film 328 covers on the sediment filtrating area pad 326 and is in fluid communication with it.Sample 302 flows through non-specific measurement zone pad 330 places that the second isolation film 328 and then arrival are communicated with near-end pad and membrane fluid.Still retainable opacity after using indicator and enzymatic mixture dipping and follow-up drying uniformly can be made and have to measurement zone pad 330 according to circumstances by plain weave nylon.Measurement zone pad 330 allows sample 302 to flow through second detection zone (specifically not being illustrated among Fig. 3 A) until arriving transportation matrix far-end 324.Separately measuring of reflectivity can be by reaching with optical mode inquiry membrane stack top and bottom respectively in the

detection zone pad

320 and 330.

Fig. 3 B shows that the present invention transports the decomposition side view of another alternate embodiment 350 of matrix, wherein fluid communication path be in respectively with porosint plane parallel and vertical side direction and cross-current in.Generally speaking, have the different porosint of plural pieces along the fluid mobile route that transports matrix 350, direct each other fluid is communicated with or is communicated with by other porosint, passage or fluid connecting device between each sheet porosint.Transportation matrix 350 comprises sample pad 362, and it is used for receiving sample by the import (not shown) on the top side 364 of the pad 362 that is positioned at transportation matrix 350 near-ends 366 places.Sample pad 362 can be made by cellulose and glass fiber compound material according to circumstances.

Sample pad 362 and sample distribution pad 354 that sample 352 is distributed between one or more extra transportation matrix (not shown) in abutting connection with and be in fluid communication with it.Sample distribution pad 354 covers the conjugate pad 368 that is used for first analyte, the described conjugate pad 368 preferable conjugates of fixing anti--HbAlc and indicator to scatter of being made by cellulose nitrate.Conjugate pad 368 cover be used for first analyte catch with first detection zone pad 370 on and be in fluid communication with it, described catching with first detection zone pad 370 is preferable made by the cellulose nitrate substrate.First detection zone pad is provided for first detection zone (specifically not being illustrated among Fig. 3 B) of first analyte.

Transportation matrix 350 can provide isolation film 372 according to circumstances, and it can make the reflected light minimization of loss that sees through the porosint that is positioned at transportation matrix far-end 374.Optional isolation film 372 is communicated with first detection zone pad, 370 fluids and allows sample 352 to flow to conjugate removes pad 376 places, district, and described conjugate removal district pad 376 can effectively capture in conjunction with the conjugate of indicator and prevent that it from entering any detection zone that is positioned at away from the transportation matrix of first detection zone.

According to circumstances, the second isolation film 378 covers on the sediment filtrating area pad 376 and is in fluid communication with it.Sample 352 flows through non-specific measurement zone pad 380 places that the second isolation film 378 and then arrival are communicated with near-end pad and membrane fluid.Measurement zone pad 380 is preferable to be made and is had uniformly a still retainable opacity after with indicator and enzymatic mixture dipping and follow-up drying by plain weave nylon.Measurement zone pad 380 allows sample 352 to flow through second detection zone (specifically not being illustrated among Fig. 3 A) until arriving transportation matrix far-end 374.

What the need emphasis was noted is that side direction and the laterally use of arbitrary combination of sample flow arrangement are contained in the present invention.Transportation matrix can use be stored in described pad, film or suchlike plane parallel or vertical liquid stream in replace or continuous pad, film or like that.

One of preferred embodiment of the present invention is to implement the examination of the location survey amount of HbAlc.For move test chemical and specific bond analysis on the current test bar in the same side, detection zone should only read an analyte.Measurement in other detection zone can reflect the combination from the result of two analytes.Yet method must be determined the contribution of each analyte to the combine detection district.For example, if analyte 2 is enzyme or coloured analyte, and analyte 1 is that its existence must be via the definite protein of immuno-chemical reaction, then detection zone 2 (for example, general chemical analysis domain) only reads analyte 2, but detection zone 1 (for example, specific bond analysis area) need not only read analyte 1 but also read analyte 2.The concentration of analyte 1 can be proofreaied and correct with the contribution of considering analyte 2 in detection zone 1 is measured and be calculated.

Thereby detection zone 2 can be drawn a circle to approve any contribution that detection zone 1 reacts by the several different methods structure.In a preferred embodiment, use vittate protein capture district and blue emulsion particle to implement immune response at detection zone 1 (that is: the specific bond analysis area 206).Blue emulsion particle must be blocked along described move, so that it is invisible in detection zone 2 (that is: general chemical analysis domain 208).Be shown among the embodiment of Fig. 2 A, 2B, 2H and 2K in the present invention, select less nylon membrane with

positive charge

222 or 209 the trapping regions in aperture as blue emulsion particle.For the situation that lacks the sample chromatography at sample when described test-strips flows, the coating that positive charge is the highest produces optimum.

The concentration of analyte 2 can be determined by reflectivity in the detection zone shown in Figure 72.Be the contribution of analyte 2 in the correct detection district 1, this algorithm of analyte 1 concentration of utilizing the mathematics algorithm to define with reflectivity in the detection zone 1 and analyte 2 concentration change is illustrated among Fig. 8.This algorithm is by analyzing a series of analyte 1 concentration and measuring gained detection zone 1 reflectivity and derive under a series of analyte 2 concentration.

The diagnostic kit that is used for working sample first and second analyte levels is contained in the present invention.Described kit comprises the sampling receptacle that contains chemical indicator, but described indicator comes sample is implemented a general chemical analysis by producing a testing result with second analyte response; With aforesaid device.The term container includes but not limited to screw-cap bottle, Bottle with snap-on cap, reservoir, pouch and like that.

Fig. 4 to 6 graphic extension a preferred embodiment of the present invention, it comprises the disposable cassette 430 that can be received in the reused meter 420.Meter 420 comprises the shell 422 that wherein has logical circuit 424 and optical system 426.Visual displays 425 is arranged on the outside surface of shell 422.Cartridge 430 comprises sample pad 432; With at least one test-strips 434 that contacts with sample pad 432.Explain as being about to, thereby cartridge 430 can be received in the body fluid analysis thing meter 420 test-strips 434 is all placed correct position read by shell 422 optical systems 426.

Test-strips 434 preferable any of transporting as mentioned above among matrix 200,300 or 350 embodiment that comprise.Therefore, analytical test strip 434 can with analytical test strip 154 and 156 identical trans functionatings as mentioned above.In a preferred embodiment, but test-strips 434 comprise can with the reagent of blood sample reaction with produce with blood sample in the relevant change detected physically of selected amount of analyte.Best, the reagent on each test-strips can react to indicate the concentration of hemoglobin A lc (HbAlc) with blood sample.Be applicable to that the detection system example of measuring hemoglobin A lc (HbAlc) is found in United States Patent (USP) the 5th, 837, No. 546; The 5th, 945, No. 345 and the 5th, 580, No. 794, the full text content of described 3 patents all is incorporated herein with way of reference for all purposes.Yet, should be appreciated that the present invention is not limited to use described reagent and reaction.Also can contain other and analyze possibility, all are all contained within the scope of the present invention.

Seen in Fig. 5 A, can provide a pair of test-strips 434.In the operation, at first receive blood sample and directly drip to sample pad 432 subsequently by apical pore 431 (in the cartridge 430).Each test-strips 434 contacts with sample pad 432 so that blood sample is arrived on each test-strips 434 by sample pad 432 by capillary action.Therefore, blood and desiring is embedded in the test-strips or the parallel reactor coated between the reagent on the test-strips can appear in a pair of test-strips 434.

In alternate embodiment, hole 431 is positioned at meter 420 outer surveys fully when being received into cartridge 430 in the meter shell 422.The advantage of this embodiment is that blood sample never flows through meter 420, reduces thereby make system be subjected to contamination of heavy.

In a word, the end 450 of cartridge 430 and top 460 are clipped in the middle sample pad 432 firmly with the sample strip 434 of supporting test-strips 434 and make it to be in correct position.At the bottom of the cartridge 450 and cartridge push up the various patterns shown in 460 inside surfaces can be used for making test-strips 434 to remain on correct position so that in itself and the optical module (system 426) light source and detector lens be arranged in a straight line rightly, as described below.

As by Fig. 5 B finding, sample pad 432 and test-strips 434 are positioned at the end 450.Fluid on the sample pad 432 arrives on the parallel test-strips 434 by capillary action.A series of ribs 452 protrude upward and place test-strips 434 belows by the end 450.As by Fig. 5 C finding, a series of ribs 462 are stretched out downwards by top 460 and are placed test-strips 434

tops.Ribs

452 and 462 can be brought into play the effect of pushing test-strips 434 gently.This helps guaranteeing that fluid transfers to next part fully by a test-strips part.Particularly, described ribs can be used for pushing gently overlay region, first detection zone pad 220 and second detection zone pad 222 (meeting face 226 places) of the conjugate pad 218 and first detection zone pad 220 and the overlay region of absorption of sample pad 224.(referring to Fig. 2 A).In preferred embodiment,

rib

452 and 462 stretches out across test-strips 434 along the side, thus any left side/right side flow in the restriction test-strips 434.In addition,

ribs

454 and 464 can be used for the contact region between sample pad 432 and the test-strips 434 is pressed together, thereby guarantees that fluid is easy to therefrom flow through.

In the cartridge 430 extra fluid control pattern can comprise around the clamping wall 456 of

sample pad

432 and 466 in case fluid stopping body sample in inside or splashes around the cartridge 430.Can further around aperture 431, use clamping wall 468 fluid sample is remained on better position (with the end adjacency of test-strips 434).

As shown in Fig. 5 D, optical system 426 comprises the optical readings device that can measure/detect the reaction that takes place on each test-strips 434.For example, optical system 426 can be used to the blood/analyte response of generation on the detector bar 434, and described reaction is relevant with hemoglobin A lc (HbAlc) concentration in the blood sample.Logical circuit 424 can analyze the result of optical detection and subsequently on the visual displays on the shell 422 425 with the visual manner display result.After having shown this concentration results, remove cartridge 430 on the self-measuring device 420 then and abandon.When carrying out new test, new cartridge 430 is received in the shell 422 of meter 420.

Also as seen, when cartridge 430 is received into meter 420 fully, need to place correct position to read test-strips 434 in the cartridge 430 by optical system 426.In addition, when being received into cartridge 430 in the meter 420, directly sample reception aperture 421 (being arranged in cartridge 430) is placed sample reception aperture 421 (being arranged in meter 410) below.Therefore, when with blood sample drops via hole 421, it flows through hole 431, and arrives on the sample pad 432.Blood sample is arrived in the test-strips 434 by sample pad 432 by capillary action, and begins reaction in test-strips.The result of this reaction can be measured by optical system 426, and described optical system 426 can be sent to information logical circuit 424, and logical circuit 424 is transferred display result (for example hemoglobin A lc concentration) confession user observation on visual displays 425.This helps the arbitrary blood/fluid sample that enters meter 410 (by sample reception aperture 421) is included in the disposable cassette 430.Therefore, blood/fluid sample will never pollute the internal work district of meter 420.

Also as seen, when cartridge 430 is received into shell 422 fully, with respect to including V-connected in star 433 in the cartridge 430 in the V-shape stop part 423 of shell 422 inner optical systems 426 adjacency.Equally, when including in cartridge 430 in the shell 422 fully, directly each test-strips 434 is placed optical readings device 426 tops (perhaps below).Should be appreciated that V-shape stop part 423 can comprise the limit of optical system 426 simply as shown, it can change into and comprise additional element of the present invention (for example, wall or inside surface).

As seen, V-shape stop part 423 and V-connected in star 433 together move so that cartridge 430 placed in the middle and alignment in shell 420.Should be appreciated that can adopt alternative geometric configuration, all are covered by in the scope of the invention.For example, the V-connected in star can change into and being positioned on the shell 422 and complementary accessory V-shape limit or wall can change into and being positioned on the cartridge 430.Have many alternative geometric configuratioies to use, all are covered by in the scope of the invention.

" V " shape of cartridge 430 need accurately with optical module on " V " limit of swelling in line (that is: with optical system 426 in abutting connection with or the position thereon) to guarantee correct alignment.According to circumstances, can in the side of cartridge 430, provide the detent that is complementary with meter 420 inner spring sample patterns when correctly placing cartridge 430 in the meter 420, to produce positive snap-in effect.

Optical system 426 changes operation by detecting can measure in the test-strips 434 when test-strips 434 is exposed to blood sample.Shown among the optional embodiment, can use a pair of test-strips 434 and by the optical readings device reading that separates in the system 426.The advantage of this embodiment of the present invention is, by on two test-strips 434, convert simultaneously same reaction and subsequently comparative result can obtain more accurate and accurate result.Yet should be appreciated that the present invention is not limited to have the embodiment of the invention of two test-strips 434.On the contrary, can contain one, two or more test-strips, all are covered by in the scope of the invention.In addition, wherein different test-strips comprise a plurality of test-strips that are used to test the different different analytes of analyzing and also are covered by in the scope of the invention.

According to the present invention, the analyte calibration information can be stored in the logical circuit 424 in advance.For example, since with arbitrary given meter 420 all disposable cassettes 430 packaging together that can repeatedly use can be from identical manufacturing batch, so its calibration parameter can be pre-programmed in the storer of meter 420.After finishing, test can will remove on the cartridge 430 self-measuring devices 420 with mistake simply.Meter 420 can use with the new cartridge 430 from same batch again.Each cartridge 430 can be according to circumstances with In Aluminium Foil Packing to guarantee stability (preventing to make moist).Perhaps, the analyte calibration information can be stored in (and being read by logical circuit 424 subsequently) in the cartridge 430 in advance when being received into cartridge 430 in the meter 420.This alternate embodiment can allow single metering device 420 to use with the cartridge of being made by various batches of cartridges 430.This embodiment can prolong the serviceable life of meter 420 greatly.

In the present invention's one optional preferred embodiment, identification label 480 is installed in cartridge 430 outsides.This identification label can comprise the optically machine-readable sign indicating number, and described code-reading can be read by detecting device in the process of inserting cartridge.Bar code for example.Perhaps, identification label 480 can be the RF label that is arranged in the cartridge 430.

According to circumstances, also can provide the automatic starting circuit that is configured to when sample being applied in the cartridge or being received into described cartridge in the shell, to activate meter.The example of this automatic start up system is found in United States Patent (USP) the 5th, 837, and No. 546, the 5th, 945, in one or more in the 345 and the 5th, 580,794, the full text of described patent is incorporated herein with way of reference for all purposes.

Sketch as mentioned, integrated sampling device can be used for initially importing blood sample by hole 421 according to circumstances.Described integrated sampler can be used for mixing of initial blood sample and diluted sample buffering agent, makes blood by hole 421 and enter cartridge 430 afterwards.In the embodiment of an integrated sampler, the diluted sample buffering agent can be included in the reservoir that is stored in integrated sampler.According to circumstances described integrated sampler is received in the port (hole 421) in the meter 420.

Example 1:

The a series of researchs of enforcement are used to measure the preferred means of HbAlc with assessment according to known laboratory (non-clinical) performance characteristic (comprise the selected user of analyzing rectilinearity (recoverys) and hematocrit tolerance and can running in laboratory, doctor clinic (POL) or family expenses are provided with operate).When these researchs of design, consider the directive document authorization standard that is used to evaluate glycohemoglobin (saccharification or glycosylation) of FDA, haemoglobin is in vitro diagnosed equipment, (the Hemoglobin In Vitro Diagnostic Devices of medical equipment and radiation health center, Center for Devicesand Radiological Health) (HFK-440 NChace/chron 2/24/91, version 9/27/91).

The research of non-clinical performance is with two kinds of one of trans enforcements.First method adopts the preferred embodiment of assembling fully of 100 the HbAlc parts of above-mentioned analytical equipment that contain in advance " uploading " calibration factor.In the method, sample is applied on the described parts for assessing and downloading data on the personal computer subsequently.For reaching download, described parts are placed on " extended base ", described " extended base " can be linked described parts on the standard computer with machinery and electrical way via preferable device connector and serial port adapter.Then the reflectance value that will download be sent to and be shown in EXCEL  spreadsheet (Microsoft company, Redmond, WA) in and convert %HbAlc unit to.In this case, download can be carried out any time after reaction is finished.As long as battery has effect just " can download " information can be retained in the device feature.After the download step, discard described parts.

Second method is used " reusable " parts.In the method, the HbAlc test-strips is placed parts and tightly be locked in as mentioned above on the extended base.Sample is applied on the described parts for assessment, and downloads reflectivity data automatically with trans (difference is that this is that " in real time " carries out) that be similar to said method.

Rectilinearity (recovery) research is carried out according to modified NCCLS scheme (NCCLS file EP-6-P the 6th volume, No.18, " Evaluation of Linearity of Quantitative Analytical Methods ").Identification represents the clinical sample of low and high %HbAlc.Be defined as in the HbAlc dynamic range that analyte concentration wherein is in device or near sample with " low ", and " height " define with opposite way.With described low and high sample mix and be marked as the rectilinearity of 9 prepared products shown in the table 1 with evaluation %HbAlc.

All with quintuplicate formal testing, pure sample product (potpourri 1 and 9) are only arranged for all specimen with 10 parts of formal testings of the same form.The %HbAlc mean value of observation is with expected results compares and analyzed according to % recovery.Implement linear regression (Fig. 9) to evaluate rectilinearity and to obtain correction coefficient.Use the result who tests from pure sample product (potpourri 1 and 9) as with reference to value, calculate desired value by described reference value.Following calculating % reclaims: observed reading multiply by 100 again divided by desired value.The recovery of concluding the results are shown in the table 1.

Digital proof %HbAlc analyze 2.5 and 14.5%HbAlc between be linear, shown in graphic among Fig. 9.Therefore, the dynamic range of %HbAlc is 3% to 15% (being rounded to integer).

Implement another research to determine that different hematocrit levels are to preferable HbAlc analytical equipment Effect on Performance.The result of this research is shown in Table 2 with form and with among the graphic Figure 10 of being shown in A and the 10B.By the red blood cell in the centrifugal and resuspended autologous plasma whole blood sample of two kinds of %HbAlc levels (diabetes and non-diabetic) is adjusted to different hematocrit levels.By standard program these samples are tested then.Each test condition and each contrast (natural) sample are implemented five replicate analysis.99% fiducial interval is calculated the upper and lower bound (UL and LL) of total error with respect to natural sample value (± [preference]+3xSEM]).

PCV refers to that the long-pending and SEM of red blood cell pressure-volume refers to the standard error of mean value.In Figure 10 A and 10B, upper and lower bound (UL and LL) is represented with dotted line (----).For the data point of solid stain () from the sample in the HbAlc proving installation total hemoglobin scope of the present invention of regulation not.

On behalf of total hemoglobin wherein, the result be in sample outside the total hemoglobin scope (68 to 200mg/mL) of the regulation that is used to analyze in table 2 bracket.Therefore, its LCD that can not be reported in device goes up and the user can be overflowed (OR) error code.It is only reported with message form herein.

These results show that the analytical equipment of the present invention that is in regulation produces equal value to all samples in total blood red egg tolerance (68 to the 200mg/mL) scope of HbAlc.All be in 99% fiducial interval for total error all values with respect to average control (natural sample) value.Therefore, analytical equipment is 20% to 60%PCV for the hematocrit scope of HbAlc.As implied above, the sample in this scope can provide reliable result.

Figure 11 A shows to come the medical personnel that freely accept professional training to use the test result of patient's finger tip sample operation analytical equipment of the present invention.The %HbAlc result who obtains in these researchs is of equal value substantially with the result that the empirical tests laboratory testing method that is called DiaSTAT obtains.Figure 11 B shows that the selftest patient uses the graphic of data that assay kit of the present invention obtains.In addition, the result who is obtained by non-medical personnel is suitable with empirical tests laboratory testing method DiaSTAT.

The inaccuracy of clinical decision scope is originally with generally low at the 5.0%CV that is shown in seen in the data of table 3 hereinafter in the test in two days.Not essence decline of performance when test enlarged in 5 days day by day is described in hereinafter table 4.

Example 2:

The preparation (for example, as shown in Fig. 2 I, 2J, 2K and 2L) that is used for the general chemical part of the test-strips that kreatinin detects can be carried out with 3 self-contained process according to the present invention.Following exemplary process can be used for preparing the vague generalization school district.

First process is with 15% tio_2 suspension dipping, one volume nylon membrane.This suspending liquid is by mixing following component preparation successively in super mixer: 0.25g/mL 1%PVA186K; 0.5966g/mL distilled water; 0.00075g/mL tripolyphosphate; 0.00075g/mL aerosil; With 0.15g/mL titania.After the coating, with film 37 ℃ dry 10 minutes and make it under dry room temperature condition balance and carry out at least 8 hours after being coated with the second time down.

Second process is to use the platform with volume pump to be coated with bar device (for example, by North Springfield, the IVEK person of making of VT) and adds the enzyme solutions striped.Be applicable to that other applicator of the present invention includes but not limited to fountain pen, pad printer (pad printer), pipette, air-brush, metering-type proportioning pump and nozzle system or like that.Other applicator that can accurately measure reagent in the predetermined suitable district that distributes also is fit to.By adding the enzyme solutions striped in the length that plays 5.25mm with one side of titanic oxide impregnation through the processing nylon material.Described solution comprises: 1000U/mL kreatinin amidino groups hydrolytic enzyme; 4000U/mL methyl amimoacetic acid amidino groups hydrolytic enzyme; The 1000U/mL sarcosine oxidase; The 1000U/mL horseradish peroxidase; 22.92g/L TES; 10g/L sucrose; 10g/L Triton X-100; With the 0.1g/mL xanthans.

Last process is to add the indicator solution striped in the district that is added with the enzyme striped.This coating process is similar to said process.Described indicator solution comprises: 0.0620g/mL pair-MAPS-C3; 0.25mL/mL isopropyl alcohol; 0.005g/mL sucrose; 0.05mL/mL surfactant 10G; 0.05mL/mL20%PVP40K; With 0.65mL/mLMiffi-Q water.

The metering rete prepares by the wide nylon membrane of an about 7mm of volume be impregnated in the buffer agent solution of being made up of 250mM MOPSO pH 7.5 and 0.5% (W/V) PVA 186K.This dip process is similar to dipping and the dry run that is used for titania.

The kreatinin district 208 of Fig. 2 I to 2L prepares according to following correction.Nylon shown in Fig. 2 I to 2L comprises a metering rete (about 5 * 3mm).(2.18 * 3mm) stick together with white PET liner with enzyme membrane according to order shown in Fig. 2 I to 2K with bonding agent (ARcare 8072,22.46 * 3 mils).

Be chosen in 15 and 30mM kreatinin standard model (K/S) between produce the condition of optimal proportion as top condition.Implement to analyze by in the diagnostic device that is similar to the described device of Fig. 1, loading the known kreatinin standard model of 60 μ L.The monitoring enzymatic reaction process, until reach terminal point, it typically is apply sample after 3 to 5 minutes.By in the time of being checked, selecting the final R/R that minimum value obtains the test section ₀Value.

For the mensuration of kreatinin, two test-strips that repeat can be placed the breadboard reflectance readings device that can analyze disposable.Described reader can read the terminal point reflectance readings of test section 1 and test section 2.The unknown concentration that the calibration curve (test section 2) of kreatinin formation is used for determining analyte.The calibration curve of formed curve in the time of can being similar to definite total hemoglobin (going up among Fig. 8 " analyte 2 ") to test section 2 draftings.

Test section 1 can be configured to can be used for detecting and measuring the albumin or the analysis of another analytes of interest analytes enforcement specific bond of microalbuminuria.

Can do multiple modifications and changes to the present invention according to above-mentioned teaching.Therefore, should be appreciated that, in claims scope of enclosing, can be different from the concrete mode of setting forth of this paper and implement the present invention.

Table 1.%HbAlc reclaims

The potpourri numbering	The sample ratio		The %HbAlc of observation	N	The %HbAlc of expection	Reclaim (%)
The potpourri numbering	The sample ratio		The %HbAlc of observation		The %HbAlc of expection	Reclaim (%)		Low	High
1	10	-	2.46		10	-		Low	High					-
1	10	-	2.46	2	10	-	9	1	3.75	5	3.62	103.7		-
3	8.5	1.5	4.45	2	5	4.20	9	1	3.75	5	3.62	103.7	105.9
3	8.5	1.5	4.45	4	5	4.20	7.5	2.5	6.00	5	5.37	111.7	105.9
5	5	5	8.86	4	5	8.34	7.5	2.5	6.00	5	5.37	111.7	106.2
5	5	5	8.86	6	5	8.34	2.5	7.5	12.95	5	11.38	113.8	106.2
7	1.5	8.5	12.85	6	5	12.61	2.5	7.5	12.95	5	11.38	113.8	101.9
7	1.5	8.5	12.85	8	5	12.61	1	9	13.70	5	13.23	103.5	101.9
9	-	10	14.48	8	10	-	1	9	13.70	5	13.23	103.5	-
9	-	10	14.48	Mean value	10	-						106.7	-

Table 2: hematocrit tolerance result concludes

Sample	Hematocrit (PCV)	DRx  (total Hb)	DRx (％HbAlc)	Lower limit (%HbAlc)	The upper limit (%HbAlc)
Sample	Hematocrit (PCV)	DRx  (total Hb)	DRx (％HbAlc)	Lower limit (%HbAlc)	The upper limit (%HbAlc)	Low %HbAlc (non-diabetic)	(60)	(204.8)	(5.1)	4.1	5.7
	52	184.6	4.7			Low %HbAlc (non-diabetic)	(60)	(204.8)	(5.1)	4.1	5.7
	52	184.6	4.7				46	162.4	4.9
	40	141	4.9				46	162.4	4.9
	40	141	4.9				32	122.3	5.1
	24	86.5	4.9				32	122.3	5.1
	24	86.5	4.9				(17)	(64.8)	(5.6)
High %HbAlc (diabetes)	70	193.8	9.4	7.0	9.8		(17)	(64.8)	(5.6)
High %HbAlc (diabetes)	70	193.8	9.4	7.0	9.8		61	189.2	8.6
	54	169.7	8.5				61	189.2	8.6
	54	169.7	8.5				46	127.7	8.4
	37	13.1	8.7				46	127.7	8.4
	37	13.1	8.7				29	93.4	8.5
	(20)	(58.8)	(8.1)				29	93.4	8.5

Table 3

Level		％HbAlc		CV(％)	N (2 days)
		％HbAlc				Mean value	Standard deviation
	1	5.9	0.29			Mean value	Standard deviation	4.97	15
2	1	5.9	0.29	10.3	0.80	7.81	15	4.97	15

Table 4

Level	％HbAlc		CV(％)	N (5 days)
	％HbAlc				Mean value	Standard deviation
	1	6.12			Mean value	Standard deviation	0.47	7.66	30
2	1	6.12	11.34	1.02	8.95	30	0.47	7.66	30

Claims

1, a kind of knockdown body fluid analysis thing meter and card, kit system, it comprises:

(a) a body fluid analyte meter, described body fluid analysis thing meter comprises:

One shell;

One is arranged in the logical circuit in the described shell;

One is arranged in the visual displays on the described shell; With

One is arranged in the measuring system in the described shell; With

(b) cartridge, it comprises:

At least one lateral flow analytical test strip, described lateral flow analytical test strip comprises:

(i) lateral flow transportation matrix;

A (ii) specific bond analysis area that is positioned on the described transportation matrix, its be used to receive a fluid sample and implement a specific bond analysis with produce one can detect response and

A (iii) general chemical analysis domain that is positioned on the described transportation matrix, it is used to receive described fluid sample and implements a general chemical analysis and can detect response to produce one;

Wherein said cartridge has suitable dimension so that can be received in the described body fluid analysis thing meter, so that place correct position to detect the described response of described specific bond analysis area and described general chemical analysis domain at described lateral flow analytical test strip described measuring system.

2, the system as claimed in claim 1, wherein said measuring system are optical measuring systems.

3, system as claimed in claim 2, but wherein said optical measuring system measurement of reflectivity.

4, the system as claimed in claim 1, wherein said cartridge are configured to and can be received in the described meter before introducing described fluid sample in the described cartridge.

5, the system as claimed in claim 1, wherein said cartridge are the disposable apparatus that a single uses.

6, the system as claimed in claim 1, wherein said body fluid analysis thing meter is a reused device.

7, the system as claimed in claim 1, wherein said cartridge further comprises:

One sample receives pad, and wherein said at least one lateral flow analytical test strip comprises a pair of lateral flow analytical test strip, each lateral flow analytical test strip contacts with described sample pad, so that when receiving to described fluid sample on the described sample pad, described fluid sample can arrive on each described lateral flow analytical test strip by capillary action, makes parallel reactor appear on the described a pair of lateral flow analytical test strip.

8, the system as claimed in claim 1, wherein said lateral flow analytical test strip further comprises:

One is arranged in the conjugate in the one conjugation district, described specific bond analysis area upstream, described conjugate can be in a plurality of analytes first in the presence of react, to form the described response that detects in the described specific bond analysis area on described transportation matrix.

9, system as claimed in claim 8, wherein said conjugate is configured to can be in conjunction with HbA1c.

10, system as claimed in claim 8, wherein said specific bond analysis area is positioned described general chemical analysis domain upstream, and wherein said lateral flow analytical test strip further comprises:

One conjugate between described specific bond analysis area and described general chemical analysis domain is removed the district.

11, system as claimed in claim 10, wherein said conjugate is removed the district and is formed by adsorbing anti-conjugate antibody.

12, system as claimed in claim 10, wherein said conjugate is removed the district and can be formed in conjunction with the material soaking of also fixing described conjugate by using.

13, system as claimed in claim 12, wherein said conjugate bond material is the antibody at described conjugate.

14, system as claimed in claim 12, wherein said conjugate bond material is one can bridge between the conjugate particulate and the fixing polymkeric substance of conjugate particulate.

15, system as claimed in claim 8, wherein said general chemical analysis domain is positioned described specific bond analysis area upstream.

16, system as claimed in claim 15 does not wherein exist conjugate to remove the district between described general chemical analysis domain and described specific bond analysis area.

17, system as claimed in claim 15, wherein said conjugation district are arranged between described general chemical analysis domain and the described specific bond analysis area.

18, system as claimed in claim 8, wherein said conjugate comprises:

One scatter be fixed on the described transportation matrix through mark indicator reagent.

19, system as claimed in claim 18 wherein saidly comprises coloured particulate through mark indicator reagent.

20, system as claimed in claim 18 wherein saidly comprises fluorescent particle through mark indicator reagent.

21, system as claimed in claim 8, wherein said through mark indicator reagent be one with coloured particulate of anti--HbA1c antibody conjugation.

22, system as claimed in claim 18, wherein said first analyte is a HbA1c antigen.

23, system as claimed in claim 18, wherein said through mark indicator reagent be one with the particle of a specific bond partner conjugation of described first analyte.

24, system as claimed in claim 18, wherein said through mark indicator reagent be one with the analyte of described first analyte or the particle of analog conjugation.

25, system as claimed in claim 18, wherein said can the reaction to form one in the presence of described first analyte through mark indicator reagent contained first analyte: through the potpourri of mark indicator complex.

26, system as claimed in claim 8, it further comprises:

One is arranged in the chemical indicator of described general chemical analysis domain upstream.

27, system as claimed in claim 26, wherein said chemical indicator is configured to and can forms one in the described general chemical analysis domain on described transportation matrix and can detect response carrying out chemical reaction in the presence of second analyte.

28, system as claimed in claim 27, can detect response described in the wherein said specific bond analysis area and form, and can detect response described in the described general chemical analysis domain and only form by described second analyte by described first analyte and described second analyte.

29, system as claimed in claim 26, wherein chemical indicator can change into the met-haemoglobin with any haemoglobin that exists in the described sample.

30, the system as claimed in claim 1, wherein said specific bond analysis are competitive immunoassays that suppresses.

31, the system as claimed in claim 1, wherein said specific bond analysis are direct competitive immunoassay.

32, the system as claimed in claim 1, wherein said specific bond analysis are sandwich immunoassays.

33, the system as claimed in claim 1, wherein said general chemical analysis adopts the chemical indicator that uses for direct colo(u)rimetry.

34, the system as claimed in claim 1, wherein said specific bond analysis are used for detecting described sample HbA1c level, and described general chemical analysis is used for detecting the total hemoglobin level that described sample exists.

35, the system as claimed in claim 1, wherein said specific bond analysis are used for detecting the human albumin level that described sample exists, and described general chemical analysis is used for detecting the creatinine levels that described sample exists.

36, the system as claimed in claim 1, wherein said measuring system be configured to determine in the described specific bond analysis area selected analyte level and with described general chemical analysis domain in can detect overall response accordingly and compared.

37, the system as claimed in claim 1, wherein said logic configured be in the described specific bond analysis area of recoverable selected analyte level and with described general chemical analysis domain in can detect response accordingly and compared.

38, the system as claimed in claim 1, wherein said logical circuit comprises: Cun Chu analyte calibration information in advance.

39, system as claimed in claim 38, wherein said logic configured read in the described cartridge production batch identifying information for can be in described cartridge is received into described shell the time to confirm with described correct coupling of storing calibration information in advance.

40, the system as claimed in claim 1, wherein said body fluid analysis thing meter further comprises: an automatic starting circuit, it is configured to activate described meter when described humoral sample being included in the described lateral flow test-strips of in the described cartridge at least one.

41, the system as claimed in claim 1, wherein:

Described shell comprises that one makes the V-shape stop part of the placed in the middle and alignment of described cartridge, and wherein,

Described cartridge comprises a V-connected in star, and it is configured to be included into described shell against described V-shape stop part can be in described cartridge being received into described body fluid analysis thing meter the time.

42, the system as claimed in claim 1, wherein said shell has a fluid sample reception opening, and described cartridge has a fluid sample reception opening, and wherein when being received into described cartridge in the described shell the described aperture arrangement in the described shell above opening described in the described cartridge.

43, the system as claimed in claim 1, it further comprises:

One is configured to described fluid sample to be dispensed to the sample preparation apparatus in the opening described in the described cartridge.

44, the system as claimed in claim 1, it further comprises:

One is configured to described fluid sample to be dispensed to the sample preparation apparatus in the opening described in the described shell.

45, system as claimed in claim 43, wherein said sample preparation apparatus comprises a thinning agent.

46, system as claimed in claim 43, wherein said sample preparation apparatus comprises at least one in the group that is made up of surfactant, buffering agent and the sodium ferricyanide.

47, the system as claimed in claim 1, wherein said transportation matrix is the elongate strip form, and described elongate strip has the far-end that core and that a near-end, that contains described conjugation district contains described specific bond analysis area contains described general chemical analysis domain.

48, the system as claimed in claim 1, wherein said transportation matrix is the membrane stack form, and described membrane stack has first film that contains described conjugation district, contain second film of described general chemical analysis domain and contain the tertiary membrane of described specific bond analysis area.

49, system as claimed in claim 48, wherein said first film is positioned at described second film top and described second film is positioned at described tertiary membrane top.

50, the system as claimed in claim 1, wherein said fluid sample are the whole bloods through cracking.

51, the system as claimed in claim 1, wherein said transportation matrix comprise an individual layer continuous film that is manufactured from the same material.

52, the system as claimed in claim 1, wherein said transportation matrix comprise at least two films of being made by different materials of physics contact each other.

53, system as claimed in claim 52, wherein said at least two films are end-to-end contact.

54, system as claimed in claim 52, the adjacent end of wherein said at least two films is overlapping.

55, system as claimed in claim 52, top that is positioned at another in wherein said at least two films.

56, system as claimed in claim 52, wherein said conjugation district and described specific bond analysis area are positioned on first film, and described general chemical analysis domain is positioned on second film.

57, system as claimed in claim 52, wherein said first film is a cellulose nitrate, and wherein said second film is a nylon.

58, system as claimed in claim 52, wherein said conjugation district is positioned on first film, and described specific bond analysis area and described general chemical analysis domain are positioned on second film.

59, system as claimed in claim 56, wherein said conjugate is removed the district and is formed by the face that connects between described first film and described second film.

60, system as claimed in claim 8, wherein said transportation matrix comprise at least two films of being made by different materials of physics contact each other, and wherein said conjugate is arranged in and contacts with described first film and be positioned on the tertiary membrane of its upstream.

61, system as claimed in claim 60, wherein said conjugate is arranged on the adjacent described tertiary membrane in the position that contacts with each other with described first film and described tertiary membrane.

62, system as claimed in claim 61, wherein said conjugate places on the described tertiary membrane as the striped cloth that sprays thereon.

63, system as claimed in claim 61, wherein said tertiary membrane is a cellulose acetate.

64, the system as claimed in claim 1, wherein said cartridge further comprises:

One sample absorption pad, its downstream end with described lateral flow analytical test strip contacts in order to therefrom to absorb excessive fluid sample.

65, the common cartridge of using of a kind of and body fluid analysis thing meter, described cartridge comprises:

(a) at least one lateral flow analytical test strip, described lateral flow analytical test strip comprises:

(i) lateral flow transportation matrix;

Wherein said cartridge has suitable dimension so that can be received in the body fluid analyte meter, so that place correct position to detect the described response of described specific bond analysis area and described general chemical analysis domain at described lateral flow analytical test strip the measuring system in the described body fluid analysis thing meter.

66, as the described cartridge of claim 65, wherein said cartridge is the disposable apparatus that a single uses.

67, as the described system of claim 65, wherein said cartridge further comprises:

One sample receives pad, and wherein said at least one lateral flow analytical test strip comprises a pair of lateral flow analytical test strip, each lateral flow analytical test strip contacts with described sample pad, so that described fluid sample can arrive by capillary action on each described lateral flow analytical test strip when receiving to described fluid sample on the described sample pad, make parallel reactor appear on the described a pair of lateral flow analytical test strip.

68, as the described system of claim 65, wherein said lateral flow analytical test strip further comprises:

One is arranged in the conjugate in the one conjugation district, described specific bond analysis area upstream, described conjugate can be in a plurality of analytes first in the presence of reaction to form the described response that detects in the described specific bond analysis area on described transportation matrix.

69, as the described system of claim 68, wherein said conjugate is configured to can be in conjunction with HbA1c.

70, as the described system of claim 68, wherein said specific bond analysis area is positioned described general chemical analysis domain upstream, and wherein said lateral flow analytical test strip further comprises:

71, as the described system of claim 70, wherein said conjugate is removed the district and is formed by adsorbing anti-conjugate antibody.

72, as the described system of claim 70, wherein said conjugate is removed the district and can be formed in conjunction with the material soaking of also fixing described conjugate by using.

73, as the described system of claim 72, wherein said conjugate bond material is the antibody at described conjugate.

74, as the described system of claim 72, wherein said conjugate bond material is one can bridge between the conjugate particulate and the fixing polymkeric substance of conjugate particulate.

75, as the described system of claim 68, wherein said general chemical analysis domain is positioned described specific bond analysis area upstream.

76,, wherein between described general chemical analysis domain and described specific bond analysis area, do not exist conjugate to remove the district as the described system of claim 75.

77, as the described system of claim 75, wherein said conjugation district is arranged between described general chemical analysis domain and the described specific bond analysis area.

78, as the described system of claim 68, wherein said conjugate comprises:

One scatter be fixed on the above transportation matrix through mark indicator reagent.

79,, wherein saidly comprise coloured particulate through mark indicator reagent as the described system of claim 78.

80,, wherein saidly comprise fluorescent particle through mark indicator reagent as the described system of claim 78.

81, as the described system of claim 68, wherein said through mark indicator reagent be one with coloured particulate of anti--HbA1c antibody conjugation.

82, as the described system of claim 78, wherein said first analyte is a HbA1c antigen.

83, as the described system of claim 78, wherein said is particle with a specific bond partner conjugation of described first analyte through mark indicator reagent.

84,, wherein saidly be and the analyte of described first analyte or the particle of analog conjugation through mark indicator reagent as the described system of claim 78.

85, as the described system of claim 78, wherein said can the reaction to form one in the presence of described first analyte through mark indicator reagent contained first analyte: through the potpourri of mark indicator complex.

86, as the described system of claim 68, it further comprises:

87, as the described system of claim 86, wherein said chemical indicator is configured to and can forms one in the described general chemical analysis domain on described transportation matrix and can detect response carrying out chemical reaction in the presence of second analyte.

88, as the described system of claim 87, can detect response described in the wherein said specific bond analysis area and form, and can detect response described in the described general chemical analysis domain and only form by described second analyte by described first analyte and described second analyte.

89, as the described system of claim 86, wherein chemical indicator can change into the met-haemoglobin with any haemoglobin that exists in the described sample.

90, as the described system of claim 65, wherein said specific bond analysis is a competitive immunoassay that suppresses.

91, as the described system of claim 65, wherein said specific bond analysis is a direct competitive immunoassay.

92, as the described system of claim 65, wherein said specific bond analysis is a sandwich immunoassay.

93, as the described system of claim 65, wherein said general chemical analysis adopts the chemical indicator that uses for direct colo(u)rimetry.

94, as the described system of claim 65, wherein said specific bond analysis is used for detecting described sample HbA1c level, and described general chemical analysis is used for detecting the total hemoglobin level that described sample exists.

95, as the described system of claim 65, wherein said specific bond analysis is used for detecting the human albumin level that described sample exists, and described general chemical analysis is used for detecting the creatinine levels that described sample exists.

96, as the described system of claim 65, wherein said transportation matrix is the elongate strip form, and described elongate strip has the far-end that core and that a near-end, that contains described conjugation district contains described specific bond analysis area contains described general chemical analysis domain.

97, as the described system of claim 65, wherein said transportation matrix is the membrane stack form, and described membrane stack has first film that contains described conjugation district, contain second film of described general chemical analysis domain and contain the tertiary membrane of described specific bond analysis area.

98, as the described system of claim 97, wherein said first film is positioned at the top of described second film and the top that described second film is positioned at described tertiary membrane.

99, as the described system of claim 65, wherein said fluid sample is the whole blood through cracking.

100, as the described system of claim 65, wherein said transportation matrix comprises an individual layer continuous film that is manufactured from the same material.

101, as the described system of claim 65, wherein said transportation matrix comprises at least two films of being made by different materials of physics contact each other.

102, as the described system of claim 101, wherein said at least two films are end-to-end contact.

103, as the described system of claim 101, the adjacent end of wherein said at least two films is overlapping.

104, as the described system of claim 101, top that is positioned at another in wherein said at least two films.

105, as the described system of claim 101, wherein said conjugation district and described specific bond analysis area are positioned on first film, and described general chemical analysis domain is positioned on second film.

106, as the described system of claim 101, wherein said first film is a cellulose nitrate, and wherein said second film is a nylon.

107, as the described system of claim 101, wherein said conjugation district is positioned on first film, and described specific bond analysis area and described general chemical analysis domain are positioned on second film.

108, as the described system of claim 107, wherein said conjugate is removed the district and is formed by the face that connects between described first film and described second film.

109, as the described system of claim 68, wherein said transportation matrix comprises at least two films of being made by different materials of physics contact each other, and wherein said conjugate is arranged in and contacts with described first film and be positioned on the tertiary membrane of its upstream.

110, as the described system of claim 109, wherein said conjugate is arranged on the adjacent described tertiary membrane in the position that contacts with each other with described first film and described tertiary membrane.

111, as the described system of claim 110, wherein said conjugate places on the described tertiary membrane as the striped cloth that sprays thereon.

112, as the described system of claim 110, wherein said tertiary membrane is a cellulose acetate.

113, as the described system of claim 65, wherein said cartridge further comprises:

114, as the described cartridge of claim 65, wherein said cartridge further comprises:

One is configured to the identification label that can be read by described meter.

115, as the described cartridge of claim 114, wherein said identification label is an optical scanning bar code.

116, a kind of lateral flow analytical test strip, it comprises:

(i) a transportation matrix;

A (iii) general chemical analysis domain that is positioned on the described transportation matrix, it is used to receive described fluid sample and implements a general chemical analysis and can detect response to produce one, and wherein said lateral flow analytical test strip is formed by the individual layer continuous film of a material.

117, as the described lateral flow analytical test strip of claim 116, wherein said specific bond analysis area is positioned at the upstream in described general analysis district.

118, as the described test-strips of claim 117, it further comprises:

One conjugate that is arranged between described specific bond analysis area and the described general chemical analysis domain is removed the district.

119, as the described test-strips of claim 118, wherein said conjugate is removed the district and is formed by adsorbing anti-conjugate antibody.

120, as the described test-strips of claim 119, wherein said conjugate is removed the district and can be formed in conjunction with the material soaking of also fixing described conjugate by using.

121, as the described test-strips of claim 120, wherein said conjugate bond material is the antibody at described conjugate.

122, as the described test-strips of claim 120, wherein said conjugate bond material is one can bridge between the conjugate particulate and the fixing polymkeric substance of conjugate particulate.

123, as the described test-strips of claim 116, wherein said specific bond analysis area is positioned at the downstream in described general analysis district.

124, as the described test-strips of claim 116, wherein said transportation matrix is made by cellulose nitrate.

125, as the described system of claim 116, wherein said lateral flow analytical test strip further comprises:

126, as the described system of claim 125, wherein said conjugate is configured to can be in conjunction with HbA1c.

127, as the described system of claim 125, wherein said specific bond analysis area is positioned described general chemical analysis domain upstream, and wherein said lateral flow analytical test strip further comprises:

128, as the described system of claim 127, wherein said conjugate is removed the district and is formed by adsorbing anti-conjugate antibody.

129, as the described system of claim 127, wherein said conjugate is removed the district and can be formed in conjunction with the material soaking of also fixing described conjugate by using.

130, as the described system of claim 129, wherein said conjugate bond material is the antibody at described conjugate.

131, as the described system of claim 129, wherein said conjugate bond material is one can bridge between the conjugate particulate and the fixing polymkeric substance of conjugate particulate.

132, as the described system of claim 125, wherein said general chemical analysis domain is positioned described specific bond analysis area upstream.

133,, wherein between described general chemical analysis domain and described specific bond analysis area, do not exist conjugate to remove the district as the described system of claim 132.

134, as the described system of claim 132, wherein said conjugation district is arranged between described general chemical analysis domain and the described specific bond analysis area.

135, as the described system of claim 125, wherein said conjugate comprises:

136,, wherein saidly comprise coloured particulate through mark indicator reagent as the described system of claim 135.

137,, wherein saidly comprise fluorescent particle through mark indicator reagent as the described system of claim 135.

138, as the described system of claim 125, wherein said through mark indicator reagent be one with coloured particulate of anti--HbA1c antibody conjugation.

139, as the described system of claim 135, wherein said first analyte is a HbA1c antigen.

140, as the described system of claim 135, wherein said is particle with a specific bond partner conjugation of described first analyte through mark indicator reagent.

141,, wherein saidly be and the analyte of described first analyte or the particle of analog conjugation through mark indicator reagent as the described system of claim 135.

142, as the described system of claim 135, wherein said can the reaction to form one in the presence of described first analyte through mark indicator reagent contained first analyte: through the potpourri of mark indicator complex.

143, as the described system of claim 125, it further comprises:

144, as the described system of claim 143, wherein said chemical indicator is configured to and can forms one in the described general chemical analysis domain on described transportation matrix and can detect response carrying out chemical reaction in the presence of second analyte.

145, as the described system of claim 144, can detect response described in the wherein said specific bond analysis area and form, and can detect response described in the described general chemical analysis domain and only form by described second analyte by described first analyte and described second analyte.

146, as the described system of claim 143, wherein chemical indicator can change into the met-haemoglobin with any haemoglobin that exists in the described sample.

147, as the described system of claim 116, wherein said specific bond analysis is a competitive immunoassay that suppresses.

148, as the described system of claim 116, wherein said specific bond analysis is a direct competitive immunoassay.

149, as the described system of claim 116, wherein said specific bond analysis is a sandwich immunoassay.

150, as the described system of claim 116, wherein said general chemical analysis adopts the chemical indicator that uses for direct colo(u)rimetry.

151, as the described system of claim 116, wherein said specific bond analysis is used for detecting described sample HbA1c level, and described general chemical analysis is used for detecting the total hemoglobin level that described sample exists.

152, as the described system of claim 116, wherein said specific bond analysis is used for detecting the human albumin level that described sample exists, and described general chemical analysis is used for detecting the creatinine levels that described sample exists.

153, a kind of cross-current analytical test strip, it comprises:

One comprises the transportation matrix of a pile film;

One is positioned at the specific bond analysis area on the described transportation matrix, its be used to receive a fluid sample and implement a specific bond analysis with produce one can detect response and

One is positioned at the general chemical analysis domain on the described transportation matrix, and it is used to receive described fluid sample and implements a general chemical analysis and can detect response to produce one.

154, as the described cross-current analytical test strip of claim 153, wherein said transportation matrix comprises:

One membrane stack, it has the tertiary membrane that second film and that first film, that contains described conjugation district contains described general chemical analysis domain contains described specific bond analysis area.

155, as the described test-strips of claim 154, wherein said first film is positioned at the top of described second film and the top that described second film is positioned at described tertiary membrane.

156, as the described test-strips of claim 155, can detect response described in the wherein said vague generalization school district can be recorded by the film that is positioned at described heap top, and can detect response described in the described specific bond analysis area and can be recorded by the film that is positioned at described heap bottom.

157, as the described test-strips of claim 153, can detect response described in the wherein said vague generalization school district can be recorded by the film that is positioned at described heap bottom, and can detect response described in the described specific bond analysis area and can be recorded by the film that is positioned at described heap top.

158, a kind of lateral flow analytical test strip, it comprises:

One lateral flow transportation matrix;

One is positioned at the specific bond analysis area on the described transportation matrix, its be used for receiving a fluid sample and implement a specific bond analysis with the human albumin level that detects described fluid sample and exist and

One is positioned at the general chemical analysis domain on the described transportation matrix, and it is used for receiving described fluid sample and implements a general chemical analysis to detect the creatinine levels that described fluid sample exists.