Combined measuring system to analyse substances in biological fluids and cartridges to perform combined general chemical and specific analyses of binding

FIELD: instrument making.

SUBSTANCE: set of invention relates to devices to determine the level of analysed substances in biological fluids. Proposed system comprises (a) measuring device with housing, logical circuit arranged in said housing, visual display arranged on said housing and measuring system arranged therein. It comprises also (b) cartridge incorporating at least one test strip to analyse lateral flow. Note here that said test strip incorporates (i) lateral flow transport matrix, (ii) zone of analysing specific binding on transport matrix to take up fluid specimen to produce required reaction, and (iii) zone of general chemical analysis on transport matrix to take up fluid specimen to produce required reaction. Note also that sizes of cartridges are selected to allow arranging analysed biological fluid substances in measuring device so that measuring system in above described zones on test strip. Mind that transport matrix first and second segments are made from different materials and bound so that said segments does not allow the product formed on first segment to contribute into reaction on second segment. Proposed invention covers other versions of aforesaid device.

EFFECT: higher efficiency, accuracy and reliability.

162 cl, 27 dwg

 

Related applications

The present application claims the priority date of the provisional patent application, U.S. serial No. 60/551,595, filed March 8, 2004 and entitled "Measuring device level of the analyzed substances in biological fluids reusable and associated cassette, full details of which are included here by reference for all purposes.

The technical field

The present invention relates to a device for measuring the level of the analyzed substances in biological fluids in General and, in one illustrative embodiment, to a device for measuring the level of hemoglobin A1C (HbA1c).

Background of the invention

For many of the analyzed substances, such as markers of pregnancy and ovulation, suitable qualitative or semi-quantitative tests. However, there are a variety of analyte that require accurate quantitative determination. They include glucose, cholesterol, cholesterol HDL (high-density lipoprotein, triglyceride, a variety of therapeutic drugs, such as theophylline, vitamins and other health indicators. In General, their quantification was achieved through the use of a tool. Although these methods are suitable for clinical analysis,they are generally undesirable for testing at the point of care in medical offices and at home due to the high cost of the instrument.

The so-called "quantitative analytical determination in the prior art does not really give a true quantitative results. For example, in U.S. patent No. 5073484, issued to Swanson, solved "quantitative determination of an analyte using cascade multiple threshold areas of testing. Each zone test shows a binary image that the amount of analyte in the sample, or above or below a certain predetermined concentration. Thus, each zone test determines only the relative comparison threshold, and not the exact concentration of the analyte. Between successive areas of testing can only detect the range for the concentration of an analyte. Even comparing the results of each of the areas of testing, it is impossible to determine the exact concentration of the analyte. Valid quantitative analysis is not compromised. In addition, the calibration curve analysis Swanson intermittent identifying discrete data points without interpolation between them.

Other specific analyzed substance that requires precise quantification is the hemoglobin A1C (HbA1c), a form of glycated hemoglobin, which indicates the regulation of blood sugar of the patient within sight of the previous two - week period. HbA1c is formed when glucose in the blood irreversibly combined with hemoglobin for education for sustainable glycated hemoglobin. Since the normal life span of red blood cells ranges from 90 to 120 days, HbA1c will be displayed only when the red blood cells are replaced. Thus, the value of HbA1c is directly proportional to the concentration of glucose in the blood throughout the full life span of erythrocytes and is not subject to the fluctuations that occur with daily monitoring of blood glucose.

The American diabetes Association (ADA) recommends that HbA1c as the best test to detect whether is it possible to adjust the blood sugar of the patient over time. The test is recommended every 3 months for patients treated with insulin, during the change of treatment or when blood glucose increases. For patients in stable condition, receiving oral agents recommended frequency is at least twice a year.

Although the value of HbA1c is a measure of average blood glucose during the previous two-week period, it is weighted towards the most recent glucose levels. This bias is due to the natural destruction and replacement of red blood cells in the body. Because aritri what you are destroyed and replaced, no need 120 days to detect clinically significant changes in HbA1c after a significant change in the average level of blood glucose. Accordingly, approximately 50% of the value of HbA1c represents the average concentration of glucose within the immediate past 30 days, about 25% of the value of HbA1c represents the average concentration of glucose during the previous 60 days and the remaining 25% of the value of HbA1c represents the average concentration of glucose during the previous 90 days.

National programme the national glycohemoglobin standardization (NGSP) certified laboratory and test procedures for HbA1c and establishes a precise Protocol and other standardized program. Recent studies have emphasized the clinical and therapeutic value immediate availability of results of determination of HbA1c in the context of a visit to the doctor's office. Currently, patients requiring testing HbA1c must submit blood samples for laboratory analysis. The length of time during which the patient and the health worker must wait depends on the availability of laboratory resources. Potential treatment of the patient is delayed pending the outcome of the test. This becomes time-consuming and expensive treatment, which has reduced the efficiency.

Need to change the industry in a truly quantitative and timely diagnostic analysis, which can be used in place of treatment, has recently gained a lot of importance because of the numerous health organization has started treating this disease. One of the methodologies currently used to justify the use of treatment and demonstrate return on investment, is a stratification of clinical risk. This includes the identification and analysis of populations and subpopulations of patients with the same conditions and varying degrees of severity of the disease, which they suffer, and assess the risk of certain adverse outcomes. Risk stratification provides the ability to split the population into homogeneous groups and subgroups on the basis of these factors (along with others), as the relative risk of occurrence of certain adverse outcomes (for example, heart attacks, strokes, cancer, diabetes, pregnancy and so on); the necessity of hospitalization, visits to the emergency room or doctor's office; exposure to certain levels of the costs of diagnostics and treatment, and the morbidity, mortality, and other complications. When the organization held stratification of patients according to different levels of clinical risk, it can then create, develop and apply the definition is by interference, which are far more likely to improve outcomes in patients with cost-effectiveness.

Thus, in the diagnostic field, there is a need for method and device for accurately quantifying the analyzed substances, such as HbA1c, which are quite cheap, timely, effective, robust and reliable for use in the diagnostic device, which then would provide the possibility of use in the treatment place and trained, and trained individuals in places such as the house, the areas of emergency care, medical workers and other places outside the clinic. Regardless of whether this device is disposable or reusable, fulfilling this need requires simultaneous, multiple analyses on the same sample source.

A summary of the present invention

In the first preferred embodiment, the present invention provides a combined measuring device of the analyzed substances in biological fluids and cassette device, comprising: (a) the measuring device of the analyzed substances in biological fluids and (b) a cartridge having at least one test strip analysis of lateral flow is within: (i) transport matrix lateral flow; (ii) the area of analysis of specific binding on the transport matrix for receiving the liquid sample and the analysis of specific binding to ensure a detectable reaction, and (iii) the area of General chemical analysis on the transport matrix for receiving the liquid sample and perform chemical analysis to ensure a detectable reaction; where the size of the cassette selected for premises in the measuring device of the analyzed substances in biological fluids, so that the measuring system can be accessed to identify reactions in the area of specific binding in the area of General chemical analysis test strip analysis of lateral flow. Preferably the measuring system is an optical measurement system. Most preferably, the measuring system is an optical device that measures reflectivity.

In the second preferred embodiment, the present invention provides a cartridge for use with analytical measuring device of substances in biological fluids, and the cassette has at least one test strip analysis of lateral flow having: (i) transport matrix lateral flow; (ii) the area of analysis of specific binding on the transport matrix DL is receiving the liquid sample and the analysis of specific binding to ensure a detectable reaction, and (iii) the area of General chemical analysis on the transport matrix for receiving the liquid sample and perform General chemical analysis to ensure a detectable reaction; where the size of the cassette selected for premises in the measuring device of the analyzed substances in biological fluids, so that the measuring system of the measuring device of the analyzed substances in biological fluids placed to identify reactions in the area of specific binding in the area of General chemical analysis test strip analysis of lateral flow.

In the third preferred embodiment, the present invention provides a test strip analysis of lateral flow having: (i) transport matrix; (ii) the area of analysis of specific binding on the transport matrix for receiving the liquid sample and the analysis of specific binding to ensure a detectable reaction, and (iii) the area of General chemical analysis on the transport matrix for receiving the liquid sample and perform chemical analysis to ensure a detectable reaction, where the test strip for the analysis of lateral flow is formed from one continuous membrane material.

In the fourth preferred embodiment, the present invention provides a test strip for the analysis of cross flow, with: transport matrix comprising a stack of membranes; zone Ana is the study of specific binding on the transport matrix for receiving the liquid sample and the analysis of specific binding to ensure a detectable reaction and the General area of chemical analysis of transport the matrix for receiving the liquid sample and perform chemical analysis to ensure a detectable response.

In the fifth preferred embodiment, the present invention provides a test strip for the analysis of lateral flow, with: transport matrix lateral flow; zone analysis of specific binding on the transport matrix for receiving the liquid sample and the analysis of specific binding to identify the level of human albumin present in the sample fluid, and the area of General chemical analysis on the transport matrix for receiving the liquid sample and perform chemical analysis for the detection of creatinine present in the sample fluid.

The operation and advantages of the present invention

In its various aspects the present invention provides a device and method for analysis of specific binding and total chemical analysis together in the format of the analysis of lateral flow, thereby quantitatively determining the level of one or more of the analyzed substances from a single source sample.

Optionally, the measurement of the same analyte can be used to obtain or correct measurement of another analyte in the same sample. In certain examples, the Ah is provided a device for quantitatively determining the amount of glycated hemoglobin (HbA1c) detection of HbA1c levels using analysis of specific binding and detection of the level of total hemoglobin (Hb)present in the sample, using a General chemical analysis.

The present invention is a device for determining the level multiple of the analyzed substances in the sample. This device preferably includes at least one test strip having a transport matrix, configured to move the sample through her lateral flow. The present invention can be optionally does not require additional devices (such as devices for single use), or may include a reusable measuring device with a number of disposable cartridges that contain one or more of the transport matrix.

Each transport matrix preferably includes the area of analysis of specific binding for receiving the sample and the analysis of specific binding to ensure a detectable reaction. Each transport matrix also preferably includes an area of General chemical analysis for the reception of the sample and perform chemical analysis to ensure detectable reactions directly or by chemical modification. The present invention also includes a system for determining the levels of the analyzed substances in the sample detected by the reactions in the areas of analysis specific swazilan the I and General chemical analysis.

The present invention also provides a device for determining the level of the first and second analyte in the sample, which contains a chemical indicator for chemical interaction with the second target substance to obtain a detected result. The device includes one or more transport matrix to move the sample through them in lateral flow. Each transport matrix preferably includes an area conjugate, which receives and provides a contact of the sample with a labeled indicator reagent, diffusely immobilized on it. Labeled indicator reagent interacts in the presence of the first analyte with the formation of a mixture containing the complex of the first analyte: labeled indicator reagent. Each transport matrix preferably includes a zone of capture (i.e., the area of analysis of specific binding), which receives and keeps the mixture from the zone conjugate with the first reagent, not diffusely immobilized on the transport matrix. The first reagent interacts in the presence of the mixture to obtain a detectable response on the level of the labeled indicator reagent immobilized in the capture zone, and identify the reaction level of the second analyte present in the mixture in areas the trap. In certain embodiments of the invention, the transport matrix is not necessary, furthermore, includes an area of interference suppression (removal conjugate), which adopts and immobilized complex of the first analyte: labeled indicator reagent from the remaining mixture. The measurement area (i.e. the area of General chemical analysis) on each transport matrix takes the remaining mixture from the zone of interference is eliminated and measures identify the reaction of the interaction between the chemical indicator and the second of the analyzed substance. Alternatively, the labeled indicator reagent and the complex of the first analyte: labeled indicator reagent just washed for the measurement zone to the zone of capture. In such scenarios, the implementation of the complex of the first analyte: labeled indicator reagent can then be washed off in the final absorbent pad. The present invention preferably includes a system for determining the levels of the first and second of the analyzed substances in the sample detected by the reactions in the zone of capture and the measurement zone. As will be shown, such systems may include optical (for example, measuring reflectivity) detectors. However, it should be understood that the present invention is not limited to this. For example, other optical, and not Opticheskie system measurement/detection can also be used to identify reactions analysis of specific binding and total chemical analysis, all of which are within the scope of the present invention.

The present invention also provides or disposable device for measuring the results of the analysis, or reusable measuring device inserted into his disposable cassettes for analysis of many of the analyzed substances. Options for one-time use preferably include a common housing having an outer surface, the inner sealing region, and the receptor model, which takes a sample containing many of the analyzed substances selected to determine their presence. The receptor sample is located on the outer surface of the casing. In optional embodiments, implementation and disposable measuring device and the measuring device is reusable cassette single-use device also includes a system for processing a sample, which provides the interaction of the sample with independent reagent to obtain a physically detectable change which correlates with the amount of one selected from the analyzed substances in the sample. This system of processing of the sample can be optionally sealed inside the casing and through the liquid to communicate with the receptor of the sample, or it may be contained in the receiver for the sample, which is output outside from the instrument (and cassettes). The present invention also includes detectors that react to a physically detectable change in many areas identify and produce an electrical signal which is correlated with the amount of selected analyte in the sample. Such detectors are sealed inside the housing of the measuring device. The present invention also includes a processor that stores a unique calibration information characteristic to determine the level of the first and second analyte in the sample detected by the reactions in the areas of analysis of specific binding and total chemical analysis. The processor also calibrates the detector, using the continuing calibration information, and converts the electric signal into a digital output signal that represents the display of the analysis results. The processor is hermetically sealed inside the casing and connected to the detectors. The present invention also includes an output device that delivers a digital output signal out from the casing. Output device connected to the processor.

In the embodiment of the invention, which uses disposable cartridges, these cartridges are single use does not necessarily include a single casing having an outer surface and sealing vnutrennyaya, and the receptor model, which takes a sample containing many of the analyzed substances, selected to detect their presence. The image receptor is located on the outer surface of the casing of the cassette. The cassette also includes a system for processing a sample, which provides the interaction of the sample with independent reagent to obtain a physically detectable change which correlates with the amount of one selected from the analyzed substances in the sample. The processing system sample is hermetically sealed inside the casing and through the fluid communicates with the receptor of the sample, or it can be contained in the receiver for the sample, which is outside of the tool and cassettes.

In the embodiment of the invention, which uses a measuring device, reusable measuring device reusable includes detectors that react to a physically detectable change in many areas identify and produces an electrical signal which correlates with the amount of selected analyte in the sample. Detectors are hermetically sealed inside the casing of the measuring device. The measuring device includes a processor, which stores calibration information that is exclusively characteristic of the set of disposable cassettes use the Oia, supplied with a measuring device for determining the level of the first and second of the analyzed substances in the sample detected by the reactions in the zone of detection of the analysis of specific binding and total chemical analysis. The processor also calibrates the detector, using the continuing calibration information, and converts the electric signal into a digital output signal that represents the display of the analysis results. The processor is hermetically sealed inside the casing of the instrument and connected to the detectors. The measuring device also includes an output device that delivers a digital output signal out from the casing. Output device connected to the processor.

Diagnostic kit included in the present invention to determine the levels of the first and second of the analyzed substances in the sample. The kit includes receiver sample containing a chemical indicator for General chemical analysis of the sample, the interaction with the second target substance to obtain a detected result, and measuring single-use device or the measuring device is reusable and disposable cassette as described above.

The transport matrix to determine the level of many of the analyzed substances in the sample included in the present izaberete is selected. In one embodiment, the transport matrix comprises at least one membrane to move through her specimen in lateral flow. Area analysis of specific binding to the membrane takes the sample and performs the analysis of specific binding to obtain a detectable reaction, and the area of General chemical analysis takes a sample and performs chemical analysis to obtain a detectable reaction directly or through chemical modification. In various configurations, area General chemical analysis can be located in or upstream or downstream from the zone of analysis of specific binding.

This transport matrix is used to determine the level of the first and second analyte in the sample. The sample contains a chemical indicator for chemical interaction with the second target substance to obtain a detected result. The transport matrix optionally includes at least one membrane to move the sample in a lateral flow transport through the membrane. The membrane includes an area conjugate, which receives and provides a contact of the sample with a labeled indicator reagent, diffusely immobilized on the membrane. Labeled indicator reagent interacts in the presence of the first analyzed ve is estva with the formation of the mixture, containing a complex of the first analyte indicator. The membrane also includes a zone of capture (i.e., the area of analysis of specific binding), which receives and keeps the mixture from the zone conjugate with the first reagent, not diffusely immobilized on the membrane in the area of capture.

Preferably the first reagent interacts in the presence of the mixture to obtain a detectable response on the level of labeled indicator immobilized in the capture zone, and identify the reaction level of the second analyte present in the mixture in the zone of capture. Optional area interference suppression (removal of the conjugate on the membrane adopts and immobilized complex of the first analyte: labeled indicator, as well as any not included in the complex of the labeled indicator reagent from the remaining mixture. In one preferred configuration, the measurement area (i.e. the area of General chemical analysis) on the membrane takes the remaining mixture from the zone of interference is eliminated and measures identify the reaction of the interaction between the chemical indicator and the second of the analyzed substance. In another preferred configuration, the measurement area (i.e. the total chemical analysis) is located upstream from the zone of capture (i.e., specific binding), and labeled indicator reagent is a complex of the first analyte: labeled indicator washed for a measurement in the area of capture. In this second preferred configuration, the complex of the analyte: labeled indicator is then washed away in the final absorbent pad.

Instead of the preferred analysis of the competitive inhibition of specific binding, as described above, the transport matrix can alternatively provide an analysis of specific binding, which is a direct competitive analysis or sandwich assay. Various alternative embodiments of the transport matrix according to the invention include reverse zones analysis of specific binding and total chemical analysis for analysis of specific binding and total chemical analysis, as well as the increase in the total number of zones present on the transport matrix.

The present invention also provides a method of determining the presence of at least first and second of the analyzed substances from many of the analyzed substances in the sample using different types of analyses of the same sample, and the method comprises the stages: sample processing chemical indicator chemical interaction with the second analyzed the substance or its modification for receiving the detected result, the total chemical analysis; processing the same part of the sample labeled in equatorium reagent to create a conjugate with the first of the analyzed substance, or competition with the analyzed substance for binding to the specific binding partner, for receiving the detected result of the analysis of specific binding; transport of the sample sequentially through multiple zones for detecting the reaction of the conjugate of the first analyte in the same area, and detecting the reaction of the chemical indicator of the second analyte in the second zone; and determining the levels of the analyzed substances in the sample detected by the reactions in the first and second zones.

The present invention includes another method of determining the level of at least two of the analyzed substances in the sample. The method comprises the stages: ensure contact of the sample with the end part of the transport matrix, which has many facilities; transportation of the sample to the labeled indicator reagent, diffusely immobilized on the transport matrix; the interaction of the labeled indicator reagent in the presence of the first analyte for the formation of the mixture; transporting the mixture to the first reagent, not diffusely immobilized on the transport matrix; the interaction of the first reactant in the presence of the mixture for the formation of immobilized first product of the interaction and identify reaction associated with one or more of the level of analyte in the sample; transport is irowiki remaining mixture without labeled indicator to the second reagent, not diffusely immobilized on the transport matrix; the chemical interaction of the indicator with the remaining sample for the formation of the second product of the interaction and identify reactions associated with the level of the second analyte in the sample; determining levels of one or more of the analyzed substances in the sample detected by the reactions in the stages of interaction with the first and second reagents.

Another method included in the present invention, determines the level of one or more of the analyzed substances in the sample, using the stage: move the sample to the lateral flow through the transport matrix; analysis of specific binding in the sample in the area of analysis of specific binding on the transport matrix for receiving the detected response; perform chemical analysis on the sample in the area of General chemical analysis on the transport matrix for receiving the detected response; and detecting levels of one or more of the analyzed substances in the sample detected by the reactions in the areas of analysis of specific binding and total chemical analysis. Alternatively, the sequence analysis of specific binding and total chemical analysis may be reversed.

In preferred embodiments, the implementation of the present measuring device measures hemogl the bin A1c (HbA1c), but is not limited to this. In various preferred aspects of the present invention be a drop a blood sample is placed in a disposable cassette, the cassette is placed in the measuring device.

Another advantage provided by the present invention, is the ability to provide quantitative results in one step, requiring only the introduction of the sample into the device to activate it. The digital result is within minutes or processed, or from the raw sample. Electronics, detector device (for example, the device reflectivity measurements), analog-to-digital signal Converter with high resolution, built-in devices temperature measurement (to ensure, if necessary, automatic temperature correction), digital display for clear reading of the results of determining the level of the analyzed substances and electronic communication port for transferring results to a computer or laboratory or hospital information system - all of these elements can be included in the present invention. You can use other devices for the transmission of test results, including, but not limited to, acoustic or audible means (including jaw words) and tactile means (including Braille).

An example of processing that is specific for the measurement of HbA1c is diluted in a solution containing ferrocyanide sodium, surfactant and pH buffer, including optional additional salts, proteins or other polymeric substances, to improve implementation and what she or resistance to pollutants. The diluent solution may be contained in a small bottle with a screw cap (preferably less than 2 ml) and delivered as part of the test kit, which may also include a capillary device to obtain a small sample of whole blood (preferably 10 μl or less) of the capillary tubes for collection of blood from a finger puncture. This capillary can then be used to transfer the blood sample in the diluent. After mixing, you can use the pipette or dropper to transfer to place of the diluted sample in the channel for introduction of the sample according to the present invention.

Embodiments of the present invention in the form of mnogorazovogo measuring device and a disposable cartridge offers numerous advantages, including, but not limited to, the following.

First, although the cartridges are disposable, self measuring device can be used again and again. Thus, many of the more expensive components of the device, including logic, electronics and optical measurement system may be included in the measuring device. These components should not be discarded after each use. This leads to cost savings for the manufacturer and user.

The second advantage of cassettes for real what the invention is, they do not require the use of desiccant inside the measuring device. This is because sensitive test strips are placed inside each of the individual cassettes. Since this is a separate cartridge may be enclosed in a waterproof wrapper (which can be removed immediately prior to use), then it contains test strips can be kept dry without the need for desiccant in the housing of the measuring device. Remove desiccant from the measuring device according to the present invention leads to save space, providing a compact device at a reduced cost.

The third advantage of the present cassette device is that a valid blood sample to be examined does not contaminate the internal working components of metering device (reusable). Rather, a sample of blood is always contained within the (disposable) cartridge. The advantage of this device is that it is instead simply presents the analysis of a blood sample format for reading optical system of the measuring device without the need for cleaning or removal of the measuring device.

The fourth advantage of the present cassette device is that in the variants of implementation, where Cass is you and the measuring device are matched to each other, does not require the representation of the measuring device calibration information disposable cassette, thereby reducing costs.

Described here is the definition and explanation of the accuracy, sensitivity and resolution

As indicated above, the present invention provides a new and unobvious analytical device and method for quantitative identification of multiple analysed substances using analysis of specific binding and total chemical analysis of the same sample at the same time. Quantitative determination obtained by the present invention, is defined measures, including accuracy, sensitivity and resolution analysis.

The term "an analyte in biological fluid" is used to refer to any substance that represents the analytical interest, including, but not limited to, hemoglobin A1C, cholesterol, triglycerides, albumin, creatine, human chorionic gonadotropin (cCG), or the like, in biological fluids, such as blood, urine, sweat, tears or the like, and liquid extracts of tissues of the body, directly used in the present invention, or used in the form of a dilute solution.

As defined here, sensitivity is the lower limit of detection of Ana who study or clinical biochemical studies. The lower limit of detection represents the lowest detectable amount of analyte that can be distinguished from zero on the number or total absence of the analyte in the sample. The lowest detectable amount of the analyte is preferably calculated by a calibration curve which is a plot of the analytical signal from the analytical concentration of the substance. First, determine the standard deviation of the signal for the zero calibrator. Then double the standard deviation of the add or subtract from the average value of the signal depending on the specific situation. Subsequently, the concentration of the analyte, which is read directly or calculated by the calibration curve represents the lower limit of detection.

It should be understood that this invention is not limited in any way determine the sensitivity, which can be used to determine the average value and standard deviation of several calibrators, including zero. The lowest concentration that can be distinguished from the zero calibrator, experimentally determined with an acceptable degree of statistical confidence, such as 95% or more. Changing this approach is to define the research Institute of the lowest concentration of an analyte, which can be measured at a given level of inaccuracy, for example 15% or less. This value is the concentration of an analyte is often referred to as the limit of quantitation.

In another method of determining the sensitivity analysis uses the approach using analytical chemistry to refer to the slope of the curve that compares the analytical signal with the concentration of the analyte. The larger the absolute value of the slope of the curve, the greater the sensitivity. For example, when using the reflectivity as a way of measuring the physically detectable change, presented here demonstrated by the results of the test, more sensitive would be a curve, showing a greater change in reflectance per unit change in the concentration of the analyte. However, the curve of the dependence of the analytical signal from the concentration of the analyte is usually nonlinear. As a result, the curve has areas that are more or less sensitive, having a direct impact on the possibility of using the results of the analysis. Another problem is that this method of determining the sensitivity does not take into account whether this change is significant compared to the noise level of the measurement device.

Used herein, the term "israsena" is defined as the ability of the test to distinguish close in value, but not identical to, the concentration of an analyte as a function of the total imprecision (total CV) in the way that is determined by the sensitivity (lower limit of detection). The lower the overall noise or inaccuracy of the test (the lower the CV, the greater the value of the resolving power or resolution. The individual components of the resolution include the resolution of the analog-to-digital conversion (number of bits available for the creation of the encoded digital value by an analog signal), the noise in the analog part of the tool measuring device and the noise inherent chemical device (including non-uniformity of the flow, the variability of the material, the variability of the device and the variability of the preparative form).

"Accuracy", as defined here, represents the ability of the analysis to produce results that closely correlated with the benchmark results, or predictive analysis. In particular, the accuracy is determined from the point of view of the average systematic deviations from the standard. Bias is the difference between the experimental and reference data. If bias is zero (i.e. they are identical), then the accuracy of the test is 100%. To distinguish between errors due to errors from errors due to inaccurate or systematic deviations is used for the average number of re-definitions. Of course, this definition assumes that the predicative analysis gives true value.

The accuracy of the analysis according to the invention, moreover, is enhanced by applying analytical microprocessor device with the exact values of the parameters and equations for calibration, as well as the exact values of the parameters for adjustment to changes in the spectral output of the LED (light emitting diode). These accurate calibration parameters and equations are loaded electronically into the analytical device (i.e. measuring device or tape or both) at the time of manufacture of the device of the present invention. This method according to the invention eliminates another source of error by eliminating the supports of the prior art on a discrete number of pre-programmed constants or equations embedded in a reusable tool.

The present invention improves the accuracy of analysis by correcting errors that may occur on several levels. For example, in the present invention preferably uses analysis, which mainly reduces the average bias by factory calibration using standard materials and laboratory reference methods. The method according to the invention avoids using simultaneous integrated the s reference analyses, disclosed in the prior art, which make the background error for the reference test, which cannot be corrected. It also avoids the errors inherent in the use of secondary reference materials by the user, which must be periodically calibrate the instrument in the clinical laboratory.

Another example is a preferred use of the present invention clinical samples for calibration. By calibration of clinical samples or synthetic calibrators, if they give the same values as the clinical samples, minimizes the problem of errors caused by the effects of the clinical background or matrix.

Another example is the measurement of background or errors that may occur within the measuring device. It includes the superposition errors of the transport matrix (all three dimensions), the spectral variability LED (calibrated during manufacture), the variability of the emitted power LED, the variability of the optical alignment and variability amplification and measurement of analog electric signals from the detectors. In essence, all of these effects can be eliminated by using ratiometric strategy - the ratio of detector output signals to the signal detector received on the initial indications of the dry strips and the output signal of the reference detector.

Ratiometric measurement strategy reflectivity is illustrated in equation 1 below. This strategy provides an internal suppression error gain (steep or proportional) and the error in the offset (delay or fixed rate), which arise in the optics (or other peripheral devices), and in electronics, and is used for all analyses. Using equation 1 reduces the variability of reflectivity about 10 times. In this equation, R represents the reflectivity. Initial indications get on dry strip, and then all subsequent readings correlate with this initial value after subtracting the blank readings (dark current, shutdown ("OFF"). All readings are correlated with the signal in the reference photodetector ("ref") after subtracting the "empty" indication (dark current). The equation looks as follows:

Illustrative definitions of the functions of the transport matrix can include, for example, and without limitation:

zone capture, identify where change is localized specific binding to facilitate the measurement, and optimized area capture ensures even distribution of the detected change;

the conjugate zone, where the conjugates, antibodies which, the antigens and the like diffuse immobilized and where they first communicate with the analyzed substance or encounter it in the liquid sample. Optimized area conjugate gives a homogeneous mixture of conjugate and other diffuse immobilized materials with the liquid sample, and preferably is located so close to the zone of capture, as compatible with appropriately sensitive detectable reaction. The dissolution of these materials is preferably a complete or essentially complete within the time period of analysis;

area measuring nonspecific or General chemical parameters, where the detected change, as in the case of the indicator or the analyte having a detectable characteristic (such as the absorption of light at a certain wavelength), definitely not localized, but rather evenly distributed through the material in order to present a representative portion of the sample to the detector (detectors) to measure concentration;

zone to eliminate noise, where the substance in the liquid sample are removed or modified so that they could no longer change the value of the detected changes in the following areas of capture. Optimized area to eliminate noise can eliminate or modify the interference-causing substance or substances to determine the Noy concentration with the so they did not cause systematic deviations, or had a reasonable systematic error of the measurement result of the level of analyte;

zone pre-treatment of the sample, where the chemical composition of the sample is modified to make it more compatible with subsequent functional analysis. When optimizing area sample pretreatment adjusts his other important chemical properties such as pH, ionic strength and the like, so that they match the correct function of other chemical elements on the strip;

zone separation of blood, where blood cells are removed from the liquid sample to obtain plasma or similar colored liquid. Preferred area of separation of blood removes erythrocytes and, if necessary, other cellular components of whole blood, so that only a reasonable number of these components remains in the resulting plasma, and minimal hemolysis. For example, acceptable levels of hemolysis (release of free hemoglobin) in some tests can determine, however, reveals whether the color of the hemoglobin detector, and it may be preferable to indicate the level of hemolysis, which is close to zero (<<1%), up to about 2%;

the area of the overflow of the sample provide a tolerance of a wide range of sample volumes is, where excess sample volume, in excess of that required for analysis is absorbed. The preferred area of the overflow of the sample takes the volume of the sample within a certain range without introducing systematic errors in the determination of the analyte, which should be within a definitely acceptable or allowable error range;

zone sediment filtration, where the materials in the form of particles in the sample are removed to obtain the optically transparent fluid. Preferred area sediment filtration removes materials in the form of particles, which can interfere with the uniform flow of liquid or identify changes to such an extent that the samples with sediment did not cause unacceptable systematic error present results determine the level of the analyte;

zone removal conjugates, where the labeled indicator reagent and its complexes are removed in the same manner as described for zones to eliminate noise and filtering the precipitate. The preferred removal area conjugates should delete labeled indicator reagent and complexes, which can interfere with the receipt of the detected changes, so that they did not influence causing any systematic error of the analysis;

and others that may have a specific design is an instruction with a variety of samples of liquids or decomposed substances (whole blood, plasma, serum, urine, saliva, vaginal swabs, swabs from the throat, mucous secrets from various parts of the body, the sweat fluid samples digested tissue and so on).

Preferred materials for these functions vary depending on the specific function and may include:

for the area sample pretreatment, zone detection, and other specifically designated areas nitrocellulose, as described above;

for non-specific measurement zones homogeneous (symmetric or asymmetric) microporous filtration membrane, such as nylon membranes manufactured by Pall Gelman and CUNO, and polyethersulfone membrane manufactured by Pall Gelman, or unmodified or chemically modified to change the absorption properties of the membrane in order to specifically absorb impurity or prevent absorption of the analyte;

for zones sediment filtration and separation of blood processed fiberglass composites with bonding agent, a mixture of cellulose and fiberglass composites with bonding agent, composites of polyester and fiberglass materials such as "shark skin", and microporous filtration membrane, such as a nylon membrane, supplied by Pall Gelman, Millipore and CUNO, as well as asymmetric polysulfone membrane produced by Memtec, and poliey the sulfonic membrane Presence(R), produced by Pall Gelman;

for materials with an open zone structure conjugates, such as polyester nonwoven composites, celluoseacetate membrane and glass fiber material and the binding agent separately or processed conjugate releasing materials (polyols, surfactants, hydrophilic polymers, copolymers or similar);

for areas of interference suppression and removal of conjugates of ion-exchange materials, such as Whatman GF/QA, polymeric membranes, which contain a diffusion-immobilized materials to eliminate noise, such as heterophile blockers, anti-HAMA (human anti-mouse antibodies) materials and chaotrope agents, and treated fiberglass composites with bonding agent, a mixture of cellulose and fiberglass composites with bonding agent, composites of polyester and fiberglass materials such as "shark skin", and microporous filtration membrane, such as a nylon membrane, supplied by Pall Gelman and CUNO, as well as asymmetric membrane polysulfone produced by Memtec, and polyethersulfone membrane Presence(R), produced by Pall Gelman; and

for areas of the flow of the sample absorbing materials, such as Transorb(R)manufactured by Filtrona Richmond.

In one illustrative embodiment, the multi-segment transport matrix spec is specific for the measurement of HbA1, includes:

for zone cojugate membrane of cellulose acetate;

for the zone of capture (specific binding) microcellulose membrane; and

for the material of the zone of non-specific (General chemical) measurement nylon. In this particular example, the measurement HbA1 material also serves as a zone of removal of the conjugate, which filters out the conjugate in the form of particles and prevents interference colors the measurement of total hemoglobin. Filtration properties of this material can depend on, but are not limited to, pore size membrane surface charge of the membrane and the addition of chemical substances, which can create opportunities for chemical attraction or repulsion on the ground without limitation, ionic, dipole-dipole and hydrophobic interactions.

However, as will be shown here, various embodiments of the present invention entail the use of one and the same material for multiple functions required from the transport matrix. For example, nitrocellulose membrane may serve to perform the functions of the conjugate zone, the capture zone (specific binding) and zones of non-specific (General chemical) measurements. Alternatively, the nitrocellulose can be used to perform the functions of the zone of capture (specific binding) and zone nonspecific (BEGO chemical measurements, and the cellulose acetate can be used to perform the function of the conjugate zone. In another example, the nitrocellulose is used to perform the functions of the conjugate zone and trap zones (specific binding), and nylon is used to perform the function area non-specific (General chemical) measurements.

Total chemical analyses, by definition, include reactions that are performed for the analyzed substances, such as without limitation, glucose, creatine, cholesterol, cholesterol HDL (high-density lipoprotein), LDL cholesterol (low-density lipoprotein), triglycerides, and urea nitrogen, blood (BUN). For General chemical analyses in the present invention are preferably used in the reaction catalyzed by enzymes, to obtain a detectable response or signal in each zone identification associated with a particular level of the analyte in the sample. Other systems to obtain a detectable reaction in the areas of detection are also suitable for use in the present invention. For example, without limitation, an analyte may interact with the enzyme or series of enzymes to obtain a detectable product recovery, oxidation, pH, gas production, or the production of sediment. Non-enzymatic reaction catalyzed or not, can also occur or VM the CTE, or instead of enzymatic reactions. Examples of detectable products include products that can be detected by fluorescence, luminescence or reflective or spectral absorption capacity characteristic wavelengths, including wavelengths in the ultraviolet, visible, near-infrared and infrared parts of the spectrum. Used here for General chemical analysis, the term "indicator" is intended to include all compounds capable of interacting with the analyzed substance or reaction product of the analyte, which stehiometrichesky associated with the analyzed substance, and to generate a detectable response or signal indicating the level of the analyte in the sample.

Analyses of specific binding is defined as including interactions between specific binding partners, such as, without limitation, the binding lectin with hydrocarbon, the interaction between complementary strands of nucleic acids, the interaction of hormones with receptors, the binding of streptavidin with Biotin and immunoanalytical interaction between antigens and antibodies. For analyses of specific binding in the present invention preferably uses the identification of the particles for detecting the detected interaction or signal in each the first reaction zone, associated with the level of analyte in the sample. Other systems to ensure a detectable reaction in areas of specific binding suitable for use in the present invention. For example, without limitation, an analyte or a specific binding partner can metalsa either directly or indirectly by the conjugate of the second antibody or other binding assays with the indicator for measuring fluorescence or luminescence, or reflectivity or absorption of light waves characteristic length. Used here for analysis of specific binding of the term "indicator" is intended to include all compounds capable of labelling an analyte, or agents of its specific binding, and to generate a detectable response or signal indicating the level of the analyte in the sample.

Although the chemistry and the configuration of the present invention can be used in an integrated analytical device, the present invention can be used in any other instrumental measuring reflectivity or transmission in the form of the replaced reagent. Thus, the present invention also encompasses an integrated analytical tools and instruments analytical measurements, including a replaceable cartridge in the analysis is an instrument of limited re-use, including the present analytical device.

Brief description of drawings

Figa is a perspective view with a spatial separation of parts of the preferred option implementation measuring diagnostic device disposable according to the present invention;

Figa is a side view of a variant of implementation of the transport matrix for analysis of dry reagent HbA1c, schematically illustrating the functional elements involved in the analysis of specific binding and total chemical analysis;

FIGU is a top view in plan of the transport matrix, shown in figa;

Figs is a side view of an alternative transport matrix, using one membrane with area specific binding upstream from the area of General chemical analysis;

Fig.2D is a side view of an alternative transport matrix, using one membrane with area specific binding downstream from the area of General chemical analysis;

Fige is a side view of an alternative transport matrix, using one membrane with the conjugate, located between the area of specific binding and area General chemical analysis;

Fig.2F is a side view of the Alt ERN transport matrix, where used nitrocellulose and cellulozata membrane with area specific binding and area General chemical analysis, located on the nitrocellulose;

Fig.2G is a side view of an alternative transport matrix, similar fig.2F, but placed in reverse order area specific binding and area General chemical analysis;

Fign is a side view of an alternative transport matrix having an area conjugate and area specific binding, located on the first membrane, and the area of General chemical analysis, located on the second membrane;

Fig is a side view of an alternative transport matrix, which is the removal area conjugate to the first membrane with a layer of spacers under the second membrane, which is the General area of chemical analysis;

Fig.2J is a side view of an alternative transport matrix, similar Fig, but where used gasket conjugate;

FIGC is a side view of an alternative transport matrix, similar Fig, but where there is a further layer, forming a trap conjugate, under a layer of spacers;

Fig.2L is a side view of an alternative transport matrix, which uses a layer of spacers under the first membrane with RA who put on it area specific binding. Area General chemical analysis is located on the second membrane;

Figa is a side view with a spatial separation of parts of an alternative implementation of the transport matrix according to the invention, illustrating the functional elements involved in the analysis of specific binding and total chemical analysis, which uses cross-flow;

FIGU is a side view with a spatial separation of parts of an alternative implementation of the transport matrix according to the invention, which uses a combination of lateral and transverse flow;

Figure 4 is a perspective view of a variant of implementation of the disposable cartridge and the device measuring device reusable according to the present invention;

Figa is a perspective view with the spatially separated parts of a variant of implementation of the cassette according to the present invention;

FIGU is a top view in plan of the lower part of the cartridge single use, showing adopted in it testing strips;

Figs is a bottom view in plan of the upper part of the cartridge single use;

6 is a perspective view with a spatial separation of the parts of the measuring device INR is Orazova use;

7 is a standard curve sample for analyte 2, showing the dependence of the reflectivity on the concentration;

Fig is a graph depicting the algorithm for determining the concentration of an analyte 1 according to the testimony reflectivity in the area of detection of 1 and the concentration of an analyte 2 according to the definition in the zone of detection 2 (area General chemical analysis);

Fig.9 is a graph showing the linearity of the obtained data for %HbA1c;

Figa is a graph showing the effect of hematocrit on the HbA1c test results for the sample with low %HbA1c (adiabaticheskogo);

FIGU is a graph showing the effect of hematocrit on the HbA1c test results for the sample with low %HbA1c (diabetes);

Figa is a graph showing the correlation of %HbA1c of samples from a finger puncture, received professionally trained medical personnel;

FIGU is a graph showing the correlation of %HbA1c of samples from a finger puncture, obtained directly by users.

In all the accompanying drawings the same items refer to the same elements.

Detailed description of drawings

The preferred implementation of the diagnostic device in the form of izmeritelnaya 100 single use for the measurement of HbA1c is illustrated in figure 1. The measuring device 100 includes a housing 102 and a cover 104 having a receptor, such as the inlet channel 106, which extends from the outer surface 108 of the cover to the interior space 110 of the housing for receiving the sample 112 containing one or more selected subject determination of the analyzed substances.

The inlet channel 106 provides the possibility of introducing a sample 112 in the receiving master device 114, which is attached to the inner surface 116 of the cover 104. Receiving the master device 114 includes a two-layer lining which is in liquid communication with the two analytical strips and serves to distribute the sample between the two strips. Optionally, receiving the master device 114 may also include a gasket for filter sample, which removes impurities from the sample. Gasket for filter design may be the same as the receiving strip, one strip can perform both functions. The measuring device 100 may include more than one strip to filter the sample along the flow channel of the sample, which remove different types of contaminants. Two analytical strips contain chemical reagents for determining the presence of one or more selected of the analyzed substances.

The inner space of the housing 110 includes reflex is Omer 126, which includes a device with a printed circuit Board having a printed circuit Board (PCB) 128. The reflectometer 126 also includes an optical device 130 and the display 132. Printed circuit Board 128 has one surface 134 with a reference detector 136 and the band detectors 138, 140, directly installed on it. The surface 134 of RSV also has 2 light emitting diode (LED) 135, 137, one for each pair of channels of lighting mounted directly on the circuit Board. LED 135, 137 are preferably presented in the form of isolated matrix without built-in lens, the shell or casing. As a result, LED 135, 137 provide light in all directions above the surface 134 and is directed only optical device 130. Similarly, zone detectors 138, 140 and the reference detector 136 are uninsulated matrix, installed directly on the surface 134 of RSV. All LED 135, 137 and detectors 136, 138, 140 are located in the same plane.

Figure 1 also illustrates the position of the screen 132 relative to the printed circuit Board 128. In the screen 132 is executed hole 142 to prevent overlap LED 135, 137, and the reference detector 136. Holes 144 are made to prevent overlap detectors zones 138, 140. The screen 132 includes a vertical wall 146, which prevent the admission of scattered radiation detectors in areas 138, 140. Vertical the s wall 146 is located adjacent to the reflecting and refracting elements of the optical device 130 when fully assembled reflectometer 126.

The optical device 130 is a generally planar support having at least the upper surface 148 and the bottom surface 150. The bottom surface 150 is configured to receive light from the LED 135, 137, and an optical device 130 sends illumination in one or more areas 152 sampling on the first 154 and second 156 analytical strip. The upper surface 148 of the optical device is also configured to transmit diffuse reflected optical radiation returning from areas 152 sampling to one or more detectors zones 138, 140.

Analytical strips 154 and 156 respectively installed in the media strips 158 and 160. Media 158, 160 is positioned on the top surface 148 of the optical device for rigid retention in position of analytical strips 154 and 156.

The measuring device 100 includes a battery 168, which nourish the circuit Board 128 and the liquid crystal display (LCD) 162. The desiccant 164 and an absorbent material 169 for flowing the excess volume of the sample also included in the housing 102.

Figa and 2B illustrate a layered transport matrix 200 for analysis of specific binding and total chemical analysis, which is suitable for use in the preferred embodiment, the diagnostic device 100 described in the above (i.e. for use in analytical test strips 154 and 156). In this embodiment of the invention there is 4 separate pieces of porous material in the channel migration of fluid transport matrix 200, each of which is laminated to the substrate 202 made of a suitable plastic, such PET, in exact alignment with each other. On figa shows a longitudinal section side view along the canal fluid migration, while figv shows the corresponding top view in plan. Sample seeps in the lateral direction, as shown by the arrow 204, along the transport matrix 200 and respectively in the first zone of detection 206 and the second area identification 208. The transport matrix is held in combination with a peg that fits tightly into the hole of the sprocket 210, and guides that are tight to the sides of the strips.

The transport matrix 200 includes a gasket 212 for the sample to receive a sample through the inlet channel (not shown) on the upper side of the strip 214 212 at the proximal end 216 of the transport matrix 200. In the example of the use of the diagnostic device illustrated in figure 1, the gasket sample, preferably not physically attached to the rest of the analytical strip, takes a sample and divides it between the two individual transfer matrices 154, 156.

In the optional is positive the preferred embodiment, the transport matrix 200 preferably includes a gasket 220 first zone of detection of such material, as nitrocellulose, which has a uniform thickness from about 70 to about 240 microns, and preferably from about 135 to about 165 microns. The rate of impregnation should be in the range of from about 0.1 to about 0.6 mm/s at a distance of approximately 4 cm, and preferably from about 0.2 to about 0.4 mm/s in average. The opacity of the material preferably is such that any lining material, invisible, or, alternatively, the lining material may be a white, reflective material such as white PET. In some cases, may be preferred black lining material. The material must also have sufficient strength in dry and wet condition for ease of manufacture. In the case of analyses of specific binding or analyses of specific binding, where the protein portion should not be diffusely immobilized on the membrane, the material must have a high ability of adsorption of protein in the range of from about 1 to 200 μg/cm2and preferably from 80 to 150 g/cm2.

In various preferred embodiments, the implementation of the transport matrix 200 preferably includes multiple segments of different materials, which are in liquid communication with each other. Multiple segments materials provide better flexibility m the material of each segment for a particular function. The transport matrix from a variety of segments may be preferable to avoid the use of "compromise" of material that can perform all the functions required of the test, though not with the best results. (However, the transport matrix can instead be formed from one continuous piece of material, which can perform all the functions required of the test.) Liquid message includes the movement and/or movement of the sample in a lateral flow through the transport matrix by allowing the sample to flow along the plane and/or perpendicular to the plane of the transport matrix. In addition, as provided by the present invention, it is two - or three-dimensional movement in liquid communication on the plane and/or perpendicular to the plane of the transport matrix can occur sequentially or simultaneously.

In a preferred embodiment, the spacer 212 for sample preferably made of CytoSep No. 1660 or 1662 from Gelman Sciences, which is a composite material made of cellulose and fiberglass. Gasket sample has approximately square dimensions approximately 7 to 10 mm at a thickness of from about 0,012 up is 0.023 inches. Another suitable material is a filter material Ahlstrom grade 1281, which has a composition primer is 90% cellulose fibers and 10% of the hydrated cellulose fibers with traces of polyamide resin, durable wet, and polyacrylamide resin, durable in dry condition. He has a basic weight of 70 g/cm2and a thickness of about 0,355 mm

Strip 212 for sample attached and is in fluid communication with two traffic matrices 154, 156, previously illustrated in figure 1. The sample flows from the pad 212 for sample to the lining 218 to conjugate, which in one preferred embodiment, is made of cellulose acetate for diffusive immobilization of the conjugate anti-HbA1c indicator. Lining 218 for conjugate may have a length of about 7 mm and a width of 3 mm at a thickness of about 0.005 to 0.010 inch. Lining 218 for the conjugate can be attached by adhesive to the substrate of the RET. Another suitable material for the lining 218 for conjugate is a Accuwik No. 14-20 from Pall Biosupport.

In one preferred embodiment, diffusion of immobilized conjugate 225 located on the lining 218 for conjugate may include anti-HbA1c indicator. Other opportunities for conjugate 225 include adsorption of antibodies against the conjugate (i.e. materials that are associated with the conjugate regardless of whether the associated conjugate with something else). Specific examples may include without limitation (1) the impregnation of the material that is associated with the conjugate and immobilized it is, (2) the antibody directed against the conjugate, and (3) a polymer that can form bridges between particles, immovable conjugate.

Lining 218 for conjugate overlaps the gasket 220 of the first detection zone and it is in liquid communication. Strip 220 of the first detection zone has a length of about 7 mm and a width of about 3 mm at a thickness of from about 0,006 to about 0.008 inches. Strip 220 of the first detection zone allows the sample 112 to flow through the first zone of detection 206 toward the distal end 220 of the transport matrix.

In preferred aspects of the invention, the conjugate 225 preferably is located as close as possible to the ceiling lining 218 for conjugate pads 220 of the detection zone (i.e. trapping). The advantage of conjugate 225 as close as possible to the strip 220 of the first detection zone is that it prevents it colored stripes. In particular, when the first liquid sample reaches the conjugate 225, its viscosity increases. Thus, the mixture of liquid sample and conjugate tends initially to gather on the strip 218 to conjugate immediately for its overlap with the strip 220 of the first detection zone. Then the mixture of liquid sample and conjugate poured evenly on the gasket 220 of the first detection zone in a lateral direction p is the width of the strip 220 of the first zone of detection.

Strip 220 of the first detection zone overlaps the pad 222 of the second detection zone and it is in liquid communication. Strip 222 of the second zone of detection in one embodiment, made of nylon membrane, such as Immobilon Nylon+, 0.45 µm, Millipore or Biodyne C from Pall Gellman, which has a uniform opacity, continued after impregnation mixtures indicator and enzyme and subsequent drying. Strip 222 of the second detection zone has a length of about 7 mm and a width of about 3 mm at a thickness of from about 0,006 to about 0.008 inches. This allows the sample 112 to flow across the second detection zone 208 toward the distal end 220 of the transport matrix.

Connection 226 strip 220 of the first detection zone and strip 222 of the second detection zone effectively captures associated with the indicator conjugate. This prevents the occurrence of the indicator associated diffuse in the strip 218 to conjugate, in the gasket 222 of the second detection zone. Alternatively, the sequence of the first and second zones of detection can be reversed. In this case, the indicator conjugate 225, diffuse immobilized in the strip 218 to conjugate, washed through the gasket 220 of the first detection zone (which may include area nonspecific chemical measurements for the determination of total hemoglobin) to seal 222 W the Roy zone identification (which may include the area of analysis of specific binding, which catches associated with the indicator conjugate).

Strip 222 of the second zone of identifying overlaps and is it in liquid communication with gasket 224 absorber sample, allowing the sample to flow across the second detection zone 206 toward the distal end 230 of the transport matrix.

A variety of different ways to implement this transport matrix 200 is included within the scope of the present invention. On figs-2L shows examples of various embodiments of the present transport matrix 200. Each of these illustrative embodiments have specific characteristics and advantages, as will be described below. It should be understood that the present transport matrix 200 is not limited to specific variants of the implementation shown in figa-2L. There may be other transport matrix, all of which remain within the scope of the present invention.

Figs is a side view of an alternative transport matrix, using the same membrane material with the area of analysis of specific binding, which is located upstream from the area of General chemical analysis. In particular, it is shown one spacer 221 zone detection. Strip zone detection can be made of nitrocellulose, but is not limited to it. Conjugate 225 RA is placed on the gasket 221 zone detection in the specified location. In one preferred method of making the conjugate 225 is applied by spraying in the form of a strip over the strip 221 zone detection.

The sample fluid 112 (1) is received at the gasket for the sample 212. Then, the sample liquid seeps through the transport matrix 220 (204), passing through the conjugate 225. After that, the sample passes first through the first area identification 206 and then through a second zone identification 208. Any remaining conjugate is captured in the zone 227 deleting conjugate before he will be able to reach the second detection zone 208. Then the excess liquid sample is simply washed off in the gasket 224 absorber sample.

Fig.2D similar pigs, but has the reverse zone analysis of specific binding 206 and common chemical analysis 208.

The main advantage of the device shown in figs and 2D, is that they require only one membrane which is used to execute and analyze specific binding, and General chemical analysis. The use of a single membrane eliminates uneven flow, which can lead to small changes in the size of the overlap of the membrane. The lack of overlap between the area of the conjugate and the zones of detection also increases the efficiency with which the conjugate is washed through the strip.

File similar fig.2D, h is conjugate 225 instead, the source is located between the area of General chemical analysis 208 and area analysis of specific binding 206. A particular advantage of this variant implementation of the transport matrix 200 is that the conjugate 225 passes through the area of General chemical analysis 208. (In contrast, in the embodiment shown in figa, we used the overlap of the membrane in connection 226 to prevent conjugate 225 in the area of General chemical analysis 208.) This configuration solves the problem of interference conjugate reaction (or detection)is performed in the area of General chemical analysis. Because there is no need to overlap the connection 226, potentially not required and chemical trap 227 conjugate remains the uniformity of fluid flow and eliminates the risk of interference General chemical analysis from any chemical traps conjugate.

On fig.2F shows a variant implementation of the transport matrix 200, in which the conjugate 225 is located on the strip for conjugate 218; and area analysis of specific binding 206, and the area of General chemical analysis 208 are located on the same strip 221 zone detection.

Fig.2G similar fig.2F, but has the reverse zone analysis of specific binding 206 and common chemical analysis 208.

The main advantage of the device shown in fig.2F and 2G, is that they require only one membrane which is used to execute and analyze specificationsimage, and General chemical analysis. In addition, by using a strip 218 to conjugate conjugate 225 can be applied about overlap with one strip 221 zone detection to prevent it strips as described above. Since many materials gaskets for conjugate have a relatively coarse nature, they are subject to non-uniformity of fluid flow. Accommodation conjugate 225 about overlap allows to avoid the risk.

On fign shows a variant implementation of the transport matrix 200, in which the conjugate 225, and area analysis of specific binding 206 are located on the strip 220 of the first detection zone; and area General chemical analysis 208 is located on the strip 222 of the second detection zone. Overlap 226 catches conjugate 225, thus ensuring that the conjugate 225 reaches strip 222 of the second zone identification (and, thus, does not interfere with any General chemical analysis, nor read the testimony of General chemical analysis).

Fig is a side view of an alternative transport matrix 200 with the gasket 220 of the first detection zone with the area of analysis of specific binding 206; and a gasket 222 of the second detection zone located on the area of General chemical analysis 208. Layer distributor/processing/filter 228 is podprogrammy 222 of the second detection zone. Layer dispenser 228 operates to provide lateral distribution of the sample before migrating to the strip 222 of the second detection zone. Area 227 removal of the conjugate is formed by deposition of material that is associated with the conjugate or causes its aggregation and operates for its immobilization, thus preventing migration into the pad 222 of the second detection zone. This option is the implementation of the transport matrix 200 is ideally suited for the detection of creatinine, but is not limited to this. Materials that are suitable for zone removal of the conjugate include, without limitation chemically modified membrane matrix, such as nylon, modified for the presence of positively or negatively charged functional groups, positively or negatively charged polymers, such as polyethylenimine or polyacrylic acid, and antibodies against the conjugate.

Fig.2J similar pig, but at the location of the conjugate 225 instead on the strip 218 to conjugate. As described above, the spacer 218 can be used to conjugate to prevent the formation of colored bands.

FIGC similar pig, but with an additional layer 209, located under the layer of valve 228. Connection 226 between the gasket 220 of the first detection zone and the layer 209 acts as a trap conjugate, preventing stijene conjugate layer dispenser 228 (and pads 222 of the second detection zone).

Fig.2L is a side view of an alternative transport matrix 200 with a layer of the distributor 220, located under the strip 220 of the first detection zone. Area General chemical analysis 208 is located on the strip 220 of the first detection zone. Area analysis of specific binding 206 is located on the strip 222 of the second zone of detection.

Figa and 3B illustrate arranged in a stack transport matrix for analysis of specific binding and total chemical analysis, which is suitable for use in alternative embodiments, the implementation described above is the preferred diagnostic device 100. On figa shows a side view with a spatial separation of parts of an alternative implementation 300 of the transport matrix with the liquid channel messages, mainly with cross-flow perpendicular to the plane of porous materials. In preferred embodiments, implementation, there are many individual pieces of porous material in the channel migration of fluid transport matrix 300 in a stack, each of which is in liquid communication with each other either directly or through other porous materials, channels, or liquid device messages. The transport matrix 300 includes gasket 312 for sample for receiving sample 302 through the exhaust channel (not shown) on the top side 314 strip 312 at the proximal end 316 of the transport matrix 300. Strip 312 for sample preferably made of composite material based on cellulose and fiberglass.

Strip 312 for sample overlaps and is in liquid communication with gasket 318 to conjugate for the first analyte, which may be optionally made of cellulose acetate for diffusive immobilization of the conjugate anti-HbA1c indicator. Gasket 318 for conjugate overlaps and is in fluid communication with the spacer 320 capture and the detection of the first analyte, which may be optionally made of nitrocellulose substrate. Laying the first zone provides a first detection zone detection (not specifically delineated on figa) for the first analyte. When the preferred device detection optical reflection of the detection of the first analyte in the laying of the first zone of detection can be significantly improved optical isolation of the first detection zone in order to minimize the loss of optical reflectivity. Accordingly, the transport matrix 300 may optionally include an optical insulating membrane 322, which minimizes the loss of reflected light through the porous material at the distal end 324 of the transport matrix. Optional the national optical insulating membrane 322 is in fluid communication with the spacer 320 of the first detection zone and allows the sample 302 to flow to the pad 326 zone removal conjugate, which effectively captures associated with the indicator conjugate and prevents its occurrence in any detection zone on the transport matrix distal first zone of detection.

Optionally, the second optical insulating membrane 328 overlaps and is in fluid communication with the spacer 326 zone sediment filtration. Sample 302 flows through the second optical insulating membrane 328 to the gasket 330 zone nonspecific measure, which is in fluid communication with the proximal gaskets and membranes. The gasket 330 area measurements may not necessarily be made of a simple nylon and has a uniform opacity, which is retained after impregnation mixtures indicator and enzyme and subsequent drying. The gasket 330 area measurement allows the sample 302 to flow across the second zone detection (not specifically delineated on figa) towards the distal end 324 of the transport matrix. Individual reflectivity measurements pads 320 and 330 zones of detection can be optimized by the direction of optical signals respectively at the top and bottom of the stack of membranes.

On FIGU shows a side view with a spatial separation of the components of another alternative implementation 350 transport matrix according to the invention with the liquid channel messages and lateral the nom, and in cross flow, respectively parallel and perpendicular to the plane of porous materials. In General, there are many individual pieces of porous material in the channel migration of fluid transport matrix 350, each of which is in liquid communication with each other either directly or through other porous materials, channels, or liquid device messages. The transport matrix 350 includes gasket 362 for sample for receiving the sample 352 through the inlet channel (not shown) on the upper side 364 strip 362 at the proximal end 366 of the transport matrix 350. Gasket 362 for sample does not need to be made of composite material based on cellulose and fiberglass.

Gasket 362 for sample abuts and is in liquid communication with gasket 354 distribution of the sample, which divides the sample 352 between the one or more additional transport matrices (not shown). Gasket 354 distribution of the sample overlaps the gasket 368 to conjugate for the first analyte, which is preferably made of nitrocellulose to diffuse immobilization of the conjugate anti-HbA1c indicator. Gasket 368 for conjugate overlaps and is in liquid communication with gasket 370 capture and the detection for the first analyzed the th substance, preferably made of nitrocellulose substrate. The laying of the first detection zone provides the first area detection (not specifically delineated on figv) for the first analyte.

The transport matrix 350 may not necessarily provide an optical insulating membrane 372, which minimizes the loss of reflected light through the porous material at the distal end 374 of the transport matrix. Optional optical insulating membrane 372 is in fluid communication with the spacer 370 of the first detection zone and allows the sample 352 leak to seal 376 zone removal conjugate, which effectively captures associated with the indicator conjugate and prevents it from entering any area of detection on the transport matrix distal first zone of detection.

Optionally, the second optical insulating membrane 378 overlaps and is in liquid communication with gasket 376 zone sediment filtration. The sample 352 flows through the second optical insulating membrane 378 to seal 380 zone nonspecific measure, which is in fluid communication with the proximal gaskets and membranes. Gasket 380 zone measurement is preferably made of a simple nylon and has a uniform opacity, which is retained after impregnation mixtures lights the RA and enzyme and subsequent drying. Gasket 380 area measurement allows the sample 352 to flow across the second zone detection (not specifically delineated on figv) towards the distal end 374 of the transport matrix.

It is important to note that the present invention provides for the use of any combination of lateral and transverse directions of flow of the sample. In the transport matrix can be used alternating or sequential gaskets, membranes or the like, in the stream which is directed or in parallel, or perpendicular to the plane of these gaskets, membranes or the like.

One of the preferred embodiments of the present invention is a process of quantitative test of HbA1c. For chemical test and analysis of specific binding in the same strip lateral flow, one of the sources must read only one of the analyzed substance. Measurement in another zone detection may reflect a combination of the results for two of the analyzed substances. However, the method should determine the combination of each analyte for a zone of combined detection. For example, if an analyte 2 is an enzyme or painted an analyte and an analyte 1 is a protein whose presence must be ODA is divided by immunochemical reaction, area identification 2 (for example, area General chemical analysis) only reads an analyte 2, but the zone of detection of 1 (for example, the area of analysis of specific binding) reads an analyte and 1, and 2. The concentration of the analyte 1 can be calculated by making correction to the dimension in the area of detection of 1 to account for the concentration of an analyte 2.

Area identification 2 can be constructed in a variety of ways to block any contribution reactions in the zone of detection of 1. In a preferred embodiment, the striped area of the capture protein and blue latex microparticles are used to perform immune response in the area of detection of 1 (i.e. the area of analysis of specific binding 206). Movement blue latex microparticles up the strip you want to block, so they were not visible in the zone of detection of 2 (i.e. the area of General chemical analysis 208). In variants of the implementation shown in figa, 2B, 2H, and 2K, nylon membrane 222 or 209 with a small pore size with a positive charge was selected as the zone of capture of the blue latex particles. The coating with the highest positive charge gave the best results regarding the absence of chromatography sample as it reaches the strip.

The concentration of the analyte 2 is determined by reflecting athelney ability in the area of detection of 2, as shown in Fig.7. To correct for the contribution of the analyte 2 in the zone of detection of 1 used a mathematical algorithm to determine the concentration of an analyte 1 as a function of the reflectivity in the area of detection of 1 and the concentration of an analyte 2. This algorithm is presented in graphical form on Fig. This algorithm was obtained by analysis of a series of concentrations of the analyte of 1 at a series of concentrations of the analyte 2 and defining the obtained reflectivity zone detection 1.

Diagnostic kit included in the present invention to determine the levels of the first and second of the analyzed substances in the sample. The kit includes receiver sample containing a chemical indicator for General chemical analysis of a sample interaction with the second target substance to obtain a detected result, and the device, as described above. The term "receiver" includes and is not limited to bottles with screw caps, vials with snap caps, containers, pouches and the like.

4 to 6 illustrate the preferred embodiment of the invention includes a disposable cassette 430, which is inserted into the measuring device 420 repeated use. Visual display 425 is located on Nar is mportant surface of the housing 422. Cassette 430 includes gasket 432 for sample and at least one test strip 434 in contact with the gasket 432 for the sample. As will be explained, cassette 430 can be inserted into the housing of the measuring device 420 liquid analyte, so that each of the test strips 434 is located for reading optical device 426 in the housing 422.

Test strips 434 preferably include any of the embodiments of the transport matrices 200, 300 or 350, as described above. Thus, analytical test strips 434 operate in the same way as the analytical test strips 154 and 156, as described above. In a preferred embodiment, the test strips 434 include a reagent that interacts with the blood sample to obtain a physically detectable change which correlates with the amount of selected analyte in the blood sample. Most preferably the reagent on each test strip interacts with the blood sample in order to specify the concentration of hemoglobin A1C (HbA1c). Examples of detection devices, suitable for use in the measurement of hemoglobin A1C (HbA1c), is presented in U.S. patent No. 5837546, 5945345 and 5580794, for any purpose fully incorporated here by reference. However, it should be understood that the present and the finding is not limited to the use of such reagents and interactions. There are also other analytical capabilities, all of which are within the scope of the present invention.

As seen on figa may be provided a pair of test strips 434. When the blood sample is first taken through the upper hole 431 (cassette 430) and then drips right on the strip 432 for the sample. Each test strip 434 is in contact with the gasket 432 for sample, so the sample of blood seeps from the strip 432 for the sample for each of the test strips 434. Thus, parallel communication happens in a couple of test strips 434 between the blood and the reagent is pre-filled into the coating test strips.

In alternative embodiments, the implementation of the hole 431 is completely outside of the measuring device 420, when the cartridge 430 is inserted into the housing 422 of the measuring device. The advantage of this alternative implementation is that the blood sample never passes through the measuring device 420, leading thus to a receiving device with a reduced possibility of contamination.

Gasket 432 for sample and test strips 434 is placed between the bottom of the 450 and riding 460 cassette 430 and tightly hold the test strips 434 in the desired position. The various elements shown on the inner surface is t the bottom 450 of the cassette and the top 460 tape serve as anchors for the test strips 434 in place to ensure that they were correctly lined up with the light source and lens detection in outdoor module (device 426)as follows.

As seen on FIGU, strip 432 for sample and test strips 434 are located in the bottom of 450. Liquid gasket 432 for sample parallel seeps on test strips 434. A number of support ribs 452 extends upward from the bottom 450, and they are under test strips 434. As seen on figs, a number of support ribs 462 extends down from the top of the 460, and they are located above the test strips 434. The supporting ribs 452 and 462 function for gentle compression test strips 434. It has the advantages of providing full transfer of fluid from one part of the test strip to the next. In particular, such support ribs can be used for gentle compression of the overlap strip 218 to conjugate and pads 220 of the first detection zone, overlapping strip 220 of the first detection zone and strip 222 of the second detection zone (compound 226) and pads 224 of the absorber sample (see figa). In the preferred embodiment, ribs 452 and 462 extend in a lateral direction across the test strips 434, through this hold any systematic deviations in the left side/right side on asterousia strips 434. In addition, the supporting ribs 454 and 464 can be used for squeezing together of contact between the gasket 432 for sample and test strips 434, thus providing easy transportation of liquid through them.

Additional controls fluid in the cassette 430 may include retaining walls 456 and 466 around the strip 432 for the sample to prevent splashing of the liquid sample through the internal space of the cartridge 430. Another retaining wall 468 around the hole 431 can be used for holding the sample fluid in the preferred location (adhering to the ends of the test strips 434).

As shown in Fig. 5A-6, the optical system 426 includes optical(s) reading(s) device(s)that(s) measures/detects the reaction occurring on each of the test strips 434. For example, the optical device 426 can be used to identify the reaction of blood/the analyzed fluid occurring on the strip 434, which correlates with the concentration of hemoglobin A1c (HbA1c) in the blood sample. Logic circuit 424 analyzes the results of optical detection and then visually represents the result on the visual display 425 on the housing 422. After submission of this result to determine the concentration of the cartridge 430 is then removed from the measuring device 420 and vibrasivautsa will perform a new test, new cartridge 430 is inserted into the housing 422 of the measuring device 420.

As can be seen, when the cartridge 430 is completely pushed into the measuring device 420, test strips 434 in the cassette 430 are placed for reading optical device 426. In addition, when the cartridge 430 is placed in the measuring device 420, the receiving sample hole 421 (cassette 430) is located directly below the receiving sample hole 421 (meter 410). Thus, when a blood sample is buried through hole 421, it passes through hole 431 and gets on the pad 432 for the sample. From there the sample of blood seeping onto test strips 434, and the reaction begins in the testing strips. The results of this reaction are measured by the optical system 426, which transmits the information in a logical circuit 424, which in turn is the result (for example, the concentration of hemoglobin A1C) on the visual display 425 for viewing by the user. This has the advantage that any sample of blood/fluid flowing in the measuring device 410 (through the receiving sample hole 421), is held in a disposable cassette 430. Thus, samples of blood/fluid never contaminate the internal working elements of the measuring device 420.

Also as you can see, when the cartridge 430 is fully inserted into the housing 422, V-shaped, the groove 433 in the cassette 430 rests in the V-shaped stopper 423, adjacent to the optical system 426 inside the housing 422. Essentially, when the cartridge 430 is fully inserted into the housing 422, each of the test strips 434 is located directly above the optical scanning device 426 (or, alternatively, under it). It should be understood that the V-shaped stopper 423 may simply include the edge of the optical system 426, as shown, or it may instead include an additional element (e.g., wall or inner surface) according to the invention.

As can be seen, the V-shaped stopper 423 and V-groove 433 work together for centering and aligning the cartridge 430 inside the housing 420. You should understand that you can use alternative geometric solutions that are within the scope of the present invention. For example, a V-shaped groove may instead be located on the housing 422, and optional mounting V-shaped edge or wall may instead be located on the cartridge 430. It may be many alternative geometric solutions that are within the scope of the present invention.

"V-shaped" form of a cassette 430 accurately attached to a raised "V-shaped" edges on the optical module (i.e. in the vicinity of the optical system 426 or her) to ensure correct alignment. Optionally, the side edges of the cassette 430 can be pre is usmarine latch, which is adjusted to such spring elements on the meter 420 to provide a positive locking action when the cartridge 430 is correctly placed in the measuring device 420.

The optical system 426 operates by identifying measurable changes to the test strip 434, when the test strip 434 is in contact with the blood sample. In the shown optional embodiment uses a pair of test strips 434 and read separate optical scanning device in the system 426. The advantage of this variant embodiment of the invention is that more accurate and precise result is obtained by simultaneous execution of the same reactions to both test strips 434 and then compare results. However, it should be understood that the present invention is not limited to variants of the invention with two test strips 434. Rather, it has 1, 2 or more test strips, which are within the scope of the present invention. Moreover, it is envisaged that many test strips with different testing strips, including a variety of analyte to test different analyses, are also within the scope of the present invention.

In accordance with this izopet the calibration of information about the analyzed substance may be pre-stored in the logic circuit 424. For example, since all disposable cassette 430, Packed with any data measuring device 420 reusable, will be from the same fabrication batch, the calibration parameters can be pre-programmed in the memory device measuring device 420. Used cartridge 430 is simply removed from the measuring device 420 after completion of the test. Then the measuring device 420 can be reused with a fresh cartridge 430 from the same batch. Each cassette 430 may optionally be individually foil-wrapped for stability (protect from moisture). Alternatively, the calibration information about the analyzed substance may be pre-stored in the cassette 430 (and then read logic 424, when the cartridge 430 is inserted into the measuring device 420). This alternative implementation would use the same measuring device 420 tape 430 from different batches manufactured cartridges. This option of a significantly extended the term of the measuring device 420.

In an optional preferred embodiment of the invention the identification label 480 is mounted on the outer surface of the cartridge 430. Such identification label can include please take the by the optical code, is suitably placed detector during insertion of the cassette, for example a bar code. Alternatively, the identification label 480 may be a radio frequency (RF) marking, which is located inside the cassette 430.

Optional, can also be provided by the scheme autostart is configured to activate the measuring device when the sample is applied to the cartridge or cassette is inserted into the housing. An example of such a device autostart can be found in one or more U.S. patents No. 5837546, 5945345 and 5580794, for any purpose fully incorporated here by reference.

As briefly mentioned above, the embedded device for sampling may not necessarily be used for the initial introduction of the blood sample through the opening 421. This built-in device for taking samples you can use for mixing the blood sample with a buffer with the purpose of dilution of the sample before the introduction of blood through the opening 421 in the cartridge 430. In one embodiment, the embedded device for sampling, a buffer for diluting the sample may be contained in the tank in the embedded device for sampling. Built-in device for taking samples can optionally be inserted into the duct (hole 421) in the meter 420.

Example 1:

Was performed a number of studies which s to assess the preferred device for measuring HbA1c levels from the point of view of ordinary laboratory (non-clinical) performance, including linearity analysis (extraction) and the tolerance values of hematocrit and the manipulation of the user that you may encounter in the laboratory, doctor's office (POL) or in the home. When planning these studies took into account the recommendations of the FDA (the Administration of medicines and food products) according to the criteria of analysis of documents for assessment of national glycohemoglobin (glycated or glycosylated) in diagnostic devices in vitro device Center and radiation hygiene (HFK-440 Nchace/chron 2/24/91 Version 9/27/91).

Non-clinical functional studies were performed in one of two ways. In the first method used the preferred implementation of the fully assembled units described above analytical device 100 HbA1c containing the pre-loaded calibration coefficients. In this method, the samples were applied to the blocks to be evaluated, and the data were later downloaded to a personal computer. For loading the blocks placed in the "filling station", which are mechanically and electrically connected them with a standard PC via the preferred communication port of the device and the serial port adapter. In turn, the loaded value of the reflectivity has been transferred and presented in an EXCEL® spreadsheet (Microsoft Inc., Redmond, WA) and re is odilis in units of %HbA1c. In this scenario, the loading may occur at any time after completion of the reactions. "Downloaded" information held in the device's blocks, while working battery. After the boot stage, the blocks were removed.

The second method uses "re-used" blocks. In this way test strips HbA1c were placed in blocks and pinched at the loading station, as described above. Samples were applied to the units to assess, and reflectivity data were automatically loaded manner similar to the above-described method, except that it was in "real" time.

The linearity study (extraction) was performed according to the modified Protocol NCCLS (National Center for clinical laboratory services) (Document NCCLS EP-6-P Vol.6, No. 18, “Evaluation of Lineraity of Quantitative Analytical Methods” (evaluation of the linearity of quantitative analytical methods)). Identified clinical samples representing low and high %HbA1c. "Low" was defined as samples with concentrations of analyte near the lower limit of the dynamic range of HbA1c device, and "high" was defined Vice versa. Samples with low and high contents were mixed and put on 9 drugs, as shown in table 1, to evaluate the linearity of the definition of %HbA1c.

The samples were tested in five repetitions for all the test is in, except for the pure samples (mixtures 1 and 9), which was tested in 10 repetitions. The observed average values of %HbA1c compared with the expected results and analyzed from the point of view of the extraction percentage. Analysis of linear regression (figure 9) was performed to assess the linearity and to obtain the correlation coefficient. The test results pure samples (mixtures 1 and 9) were used as reference values, which were calculated expected values. The extraction percentage was calculated as the observed value, multiplied by 100 and divided by the expected value. The final results of the extraction are shown in table 1.

The data demonstrate that the analysis of %HbA1c is linear from 2.5 to 14.5 %HbA1c, as shown graphically in figure 9. Thus, the dynamic range for %HbA1c ranges from 3% to 15% (rounded to the nearest whole number).

Another study was conducted to determine the effects of different hematocrit levels on the operation of the preferred analytical device for determining the level of HbA1c. The results of this study are shown in tabular form in table 2 and graphically in figa and 10V. Samples of whole blood at two levels of %HbA1c (diabetes and medicationscom) customized to different levels of hematocrit by centrifugation and resuspending of red blood cells in autologous plasma. the ATEM they were tested by standard procedures. Five replicate analyses were performed for each test condition and for each control sample (native). The upper and lower limits (UL and LL) was calculated for 99% confidence interval for the total error (±[system error+3×SEM]) largest native sample. PCV refers to the volume of erythrocyte mass, and SEM is the standard error of the mean. On figa and 10B of the upper and lower limits (UL and LL) are shown as dashed lines (----). Data points that are marked in bold black dots (●), obtained from samples not within the range of total hemoglobin for testing devices HbA1c according to the invention.

Results in parentheses in table 2 represent samples where the level of total hemoglobin falls out certain limits on the total hemoglobin analysis (68-200 mg/ml). Therefore, they should not be presented on the liquid crystal display device, and the user should get an error code is outside the range (OR). They are presented here for information only.

These results indicate that all samples within a certain tolerance of total hemoglobin for analytical devices determine the level of HbA1c according to the invention (68-200 mg/ml) gave equivalent value. All values fell under 99% confidence interval for the total error of the average control value (the exploring of the sample). Thus, the hematocrit range for analytical device HbA1c ranges from 20% to 60% PCV. As shown above, the samples in this range will give reliable results.

On figa shows test data obtained by the analytical device according to the invention, which worked professionally trained medical personnel using samples obtained from the patient by the puncture of a finger. The results determine the percentage of HbA1c obtained in these studies were essentially equivalent to the results obtained certified laboratory method of testing is known as DiaSTAT. On FIGU shows a graph of the data self-testing patients using the analytical kit according to the present invention. And again, the results obtained by non-medical personnel, were comparable to a certified laboratory method of testing DiaSTAT.

The inaccuracy of clinical decisions at the time of the adoption of more than two days of testing source accounted for only 5.0%CV, as shown by the data presented in table 3 below. The work is not substantially deteriorated when testing continued day after day for more than 5 days, as shown in table 4 below.

Example 2:

Obtaining General chemical side strips for the detection of creatinine (for example, as shown in Fig, 2J, 2K and 2L) monoprotic in accordance with the present invention, using 3 separate process. The following illustrative methods were used to obtain General chemical zone.

The first method consists in the impregnation of the roll nylon membrane suspension 15% of titanium dioxide. This suspension is obtained by mixing in a high speed mixing device the following components in sequential order: 0.25 g/ml 1% PVA 186K; 0,5966 g/ml of distilled water; 0.00075 grams/ml of sodium tripolyphosphate; 0.00075 grams/ml finely dispersed silicon dioxide and 0.15 g/ml of titanium dioxide. After coating the membrane is dried at 37°C for 10 min and she will be given the opportunity to balanced in terms of dry space for at least 8 h prior to the second floor.

The second way is to apply strips of enzyme solution, using a stationary stripper with a measuring pump, such as strippers, made IVEK o North Springfield, VT. Other applicators suitable for use with the present invention include, but are not limited to, fountain pens, Tambopata machine, eyedropper, paint sprayers, measuring feed pumps and devices with nozzles, or the like. Suitable other applicators, which accurately measure the reagents to the appropriate zone to a predefined distribution. The enzyme solution is applied by the strip 5.25 mm from one edge of the treated nylon mother is La, impregnated with titanium dioxide. The solution includes: 1000 U/ml creatinine-amidinohydrolase; 4000 U/ml creatine-amidohydrolase; 1000 U/ml sarcosin-oxidase; 1000 U/ml horseradish peroxidase; 22,9 g/l TES; 10 g/l sucrose, 10 g/l Triton X-100 and 0.1 g/ml xanthan resin.

The final process consists in applying a strip of indicator solution over the area coated with the enzyme band. This coating process is similar to the above described process. The indicator solution includes: 0,0620 g/ml bis-MAPS-C3; 0.25 ml/ml of isopropyl alcohol; 0.005 g/ml sucrose; 0.05 ml/ml surfactant 10G; 0.05 ml/ml of 20% PVP 40K and 0.65 ml/ml water Milli-Q.

The dimensional layer of the membrane is obtained by impregnation of the roll nylon membrane width of about 7 mm in a buffer solution consisting of 250 mm MOPSO pH 7.5 and 0.5% (wt./about.) PVA 186K. This method of impregnation is similar to the immersion and drying for titanium dioxide.

Zone creatinine 208 on Fig and 2L receive in accordance with the following variants of implementation. Nylon, shown in Fig and 2L, includes a layer of dimensional membrane (approximately 5×3 mm). The enzyme membrane (2,18×3 mm) is attached to the substrate of the white PET glue (Arcare 8072, 22,46×3 mils) in order of the sequence shown in Fig-2K.

As the best were selected conditions, giving a better proportionality between the standards 15 and 30 mm creatinine (K/S). Analysis of Prov is Dili loading 60 µl of a known standard creatinine diagnostic device, similar to the device described in figure 1. The development of the enzymatic reaction control to the end point, which usually occurred within 3-5 min after application of the sample. The final values of R/ROfor zone testing were obtained by selecting the minimum value during the period of the study.

For determination of creatinine 2 strips in two repetitions can be placed in a mock reader reflectivity, which can analyze disposable strips. The reader takes the final readings reflectivity and zone test 1, and for test 2. The calibration curve constructed for creatinine area (test 2), is used to determine the unknown concentration of the analyte. A calibration curve similar to the curve for the determination of total hemoglobin ("an analyte 2" Fig above), can be obtained for test 2.

Zone test 1 can be constructed for analysis of specific binding to albumin for the detection and measurement of microalbuminuria or for a different analyte of interest.

In light of the above provisions, there are numerous modifications and changes of the present invention. Therefore, it should be understood that within the Ah volume of the attached claims, the invention can be implemented differently than specifically described in this description.

Table 1.
Removing the HbA1c percentage
No. mixturesThe proportion of the sampleObserved %HbA1cNExpected %HbA1cExtract (%)
LowHigh
110-2,4610--
2913,7553,62103,7
38,51,5of 4.4554,20105,9
47,52,5 6,005lower than the 5.37111,7
5558,865to 8.34106,2
62,57,512,95511,38113,8
71,58,512,85512,61101,9
81913,70513,23103,5
9-1014, 48mm10--
Average 106,7

Table 2.
The final results of the tolerance values of haematocrit
SampleHaematocrit(Shared Hb)(Shared Hb)The lower limitThe upper limit
Low %HbA1c (nediabeticescoy)(60)(204,8)(51)4,1the 5.7
52184,6the 4.7
46162,4a 4.9
40141a 4.9
32122,35,1
2486,5a 4.9
(17)(64,8)(5,6)
High %HbA1c (diabetes)70193,89,47,09,8
61189,28,6
54169,78,5
46127,78,4
37113,18,7
29for 93.48,5
(20)(58,8)(8,1)

Table 3
%HbA1cCV (%)N (2 days)
LevelAverageThe standard deviation
15,90,29equal to 4.9715
210,30,807,8115

Table 4
Level%HbA1cCV (%)N (2 d the I)
AverageThe standard deviation
16,120,477,6630
211,341,028,9530

1. The combined system of the measuring device of the analyzed substances in biological fluids and magazines, including
(a) the measuring device of the analyzed substances in biological fluids, including
case;
the logical circuit located inside the enclosure;
a visual display located on the housing, and the measuring system located inside the housing, and
(b) a cartridge including
at least one test strip for the analysis of lateral flow, and a test strip for the analysis of lateral flow includes
(i) multi-segment transport matrix lateral flow;
(ii) the area of analysis of specific binding on the transport matrix for receiving the liquid sample and the analysis of specific binding to ensure a detectable reaction, and
(iii) the area of General chemical analysis on the second segment of the transport matrix d is I receive liquid sample and perform chemical analysis to ensure a detectable response;
where the size of the cassette selected for premises in the measuring device of the analyzed substances in biological fluids, so that the measuring system can be accessed to identify reactions in the area of specific binding in the area of General chemical analysis test strip for the analysis of lateral flow, and the first and second segments of the transport matrix made of different materials so that the connection of the first and second segments of the transport matrix prevents the contribution of the product formed on the first segment of the transport matrix, in response to the second segment of the transport matrix.

2. The system according to claim 1, where the measuring system is an optical measurement system.

3. The system according to claim 2, where the optical measuring system measures the reflectivity.

4. The system according to claim 1, where the cartridge is made with the possibility of inserting into the measuring device before introduction of the sample liquid in the cartridge.

5. The system according to claim 1, where the cartridge is a single-use device.

6. The system according to claim 1, where the measuring device of the analyte in the biological fluid is a reusable system.

7. The system according to claim 1, where the cartridge further includes
the gasket receiving the sample, ihde, at least one test strip for the analysis of lateral flow includes a couple of test strips for analysis of lateral flow, and each test strip for the analysis of lateral flow is in contact with the gasket for the sample, so that when the liquid sample is fed to the strip for sample, the sample fluid seeps on each of the test strips for analysis of lateral flow, so that parallel reactions occur in a pair of test strips for analysis of lateral flow.

8. The system according to claim 1, where the test strip for the analysis of lateral flow further includes
conjugate, located in an area conjugate upstream from the zone of analysis of specific binding, and the conjugate will react in the presence of the first of many of the analyzed substances to obtain a detectable reaction in the area of analysis of specific binding on the transport matrix.

9. The system of claim 8, where the conjugate is configured to associate HbAlc.

10. The system of claim 8, where the area of analysis of specific binding is located upstream from the area of General chemical analysis, and test strip for the analysis of lateral flow further includes
the removal area of the conjugate between the area of analysis of specific binding and area General chemical anal is for.

11. The system of claim 10, where the removal area conjugate formed by the adsorption of antibodies against the conjugate.

12. The system of claim 10, where the removal area conjugate formed by impregnation of the material that is associated with the conjugate and immobilized it.

13. System according to clause 12, where binding of the conjugate material is an antibody directed against the conjugate.

14. System according to clause 12, where binding of the conjugate material is a polymer that can form bridges between particles conjugate and mobilitat them.

15. The system of claim 8, where the area of General chemical analysis is located upstream from the zone of analysis of specific binding.

16. The system of clause 15, where between the area of General chemical analysis and area analysis of specific binding area removal conjugate.

17. The system of clause 15, where the area of the conjugate is located between the area of General chemical analysis and area analysis of specific binding.

18. The system of claim 8, where the conjugate includes
labeled indicator reagent, diffusely immobilized on the transport matrix.

19. System p, where the labeled indicator reagent includes colored microparticles.

20. System p, where the labeled indicator reagent comprises a fluorescent microparticles.

21. The system of claim 8, where the labeled indicator reagent performance, which provides a colored microparticle, a conjugate associated with the antibody against HbAlc.

22. System p, where first an analyte is an antigen HbAlc.

23. System p, where the labeled indicator reagent is a molecule, a conjugate is associated with a specific binding partner to the first analyte.

24. System p, where the labeled indicator reagent is a molecule, a conjugate associated with the analyzed substance or analogue of the first analyte.

25. System p, where the labeled indicator reagent interacts in the presence of the first analyte for the formation of a mixture containing the complex of the first analyte: labeled indicator.

26. The system of claim 8, additionally including
chemical indicator located upstream from the area of General chemical analysis.

27. System p, where the chemical indicator configured to chemical interaction in the presence of the second analyte to obtain a detectable reaction in the area of General chemical analysis on the transport matrix.

28. The system according to item 27, where the detectable response in the area of analysis of specific binding is formed from the first and from the second analyte, and the detectable response in the area of General chemical analysis is formed only of the second analyte.

29. System p, where the chemical indicator turns any hemoglobin present in the sample, in met-hemoglobin.

30. The system according to claim 1, where the analysis of the specific binding represents an immune analysis of competitive inhibition.

31. The system according to claim 1, where the analysis of specific binding is a direct competitive immune analysis.

32. The system according to claim 1, where the analysis of specific binding is a sandwich immune analysis.

33. The system according to claim 1, where in the General chemical analysis used chemical indicator for direct colorimetry.

34. The system according to claim 1, where the analysis of specific binding is used to detect the level of HbAlc in the sample, and the total chemical analysis is used to identify levels of total hemoglobin present in the sample.

35. The system according to claim 1, where the analysis of specific binding is used to identify the level of human albumin present in the sample, and the total chemical analysis is used to identify the level of creatinine present in the sample.

36. The system according to claim 1, where the measuring system is configured to determine the level of the selected analyte in the area of analysis of specific binding compared with the corresponding total detectable reaction in the area of General chemical analysis.

37. Sist the mA according to claim 1, where the logic circuitry is configured to adjust the level of the selected analyte in the area of analysis of specific binding compared with the corresponding total detectable reaction in the area of General chemical analysis.

38. The system according to claim 1, where the logic circuitry includes
pre-stored calibration information for the analyzed substance.

39. System § 38, where the logic circuitry is configured to read identification information of the party making the cassette when the cassette is inserted into the housing, to confirm the correct compliance with the pre-stored calibration information.

40. The system according to claim 1, where the measuring system of the analyte in the biological fluid, in addition, includes
the scheme autostart is configured to activate the measuring system when the sample is a biological fluid passed at least one test strip is a lateral flow cassette.

41. The system according to claim 1, where
the housing includes a V-shaped limiter for centering and aligning the cartridge, where the cartridge includes a V-neckline, configured to receive reference in the V-shaped limiter in the housing when the cassette is inserted in a measuring system of the analyte in the biological fluid.

42. The system according to claim 1, where ARPUs has a hole for receiving the liquid sample and the cassette has an opening for receiving the sample fluid, and the hole in the housing is located above the holes in the cassette when the cassette is inserted into the case.

43. The system according to claim 1, additionally including
device for sample preparation, configured to supply the liquid sample into the hole in the cartridge.

44. The system according to claim 1, additionally including
device for sample preparation, configured to supply the liquid sample into the hole in the hull.

45. The system according to item 43, where the device for sample preparation includes a diluent.

46. The system according to item 43, where the device for sample preparation includes at least one substance from the group consisting of surfactants, buffers and ferricyanide sodium.

47. The system according to claim 1, where the transport matrix is presented in the form of elongated strips having a proximal end, containing an area conjugate, the Central portion containing the area of analysis of specific binding, and the distal end, containing an area of General chemical analysis.

48. The system according to claim 1, where the transport matrix is presented in the form of a stack of membranes with the first membrane, containing an area conjugate, a second membrane, containing an area of General chemical analysis, and the third membrane, containing an area of analysis of specific binding.

49. System p, where the first membrane is located on top of the second membrane, and the other is a membrane located over the third membrane.

50. The system according to claim 1, where the sample fluid is a lysed whole blood.

51. The system according to claim 1, where the transport matrix comprises one continuous membrane made of the same material.

52. The system according to claim 1, where the contribution of the product formed on the first segment of the transport matrix, in response to the second segment of the transport matrix is prevented by chemical compounds.

53. The system according to paragraph 52, where at least 2 of the membrane are in contact the end-to-end.

54. The system according to paragraph 52, where the adjacent ends of the at least two membranes overlap.

55. The system according to paragraph 52, where at least 2 of the membrane are located one on top of another.

56. The system according to paragraph 52, where the area of the conjugate and area analysis of specific binding are located on the first membrane, and the area of General chemical analysis is located on the second membrane.

57. The system according to paragraph 52, where different materials are nitrocellulose and nylon.

58. The system according to paragraph 52, where the area of the conjugate is located on the first membrane and the area of analysis of specific binding and area General chemical analysis are located on the second membrane.

59. System p where removal area conjugate formed by the connection between the first and second membranes.

60. The system of claim 8, where the conjugate is located on the third material is e, in contact upstream from the first material.

61. System p, where the conjugate is located on the third material near the area where the first and second materials are in contact with each other.

62. System p, where the conjugate is located on the third membrane in the form of spray bars.

63. System p, where the third membrane is a cellulose acetate.

64. The system according to claim 1, where the cartridge further includes
the absorbent sample pad in contact with the downstream end of the test strips for analysis of lateral flow for absorption with her excess sample fluid.

65. Cassette for use with analytical measuring system of substances in biological fluids, including
(a) at least one test strip analysis of lateral flow, including
(i) multi-segment transport matrix lateral flow;
(ii) the area of analysis of specific binding in the first segment multi-segment transport matrix for receiving the liquid sample and the analysis of specific binding to ensure a detectable reaction, and
(iii) the area of General chemical analysis on the second segment of the transport matrix for receiving the liquid sample and perform chemical analysis to ensure a detectable response;
where the size of the s cassette selected for premises in the measuring system of the analyzed substances in biological fluids, so that the measuring system is placed in the measuring device of the analyzed substances in biological fluids for the detection of reactions in the area of specific binding in the area of General chemical analysis test strip analysis of lateral flow, and
the first and second segments of the transport matrix made of different materials so that the connection of the first and second segments of the transport matrix prevents the contribution of the product formed on the first segment of the transport matrix, in response to the second segment of the transport matrix.

66. The tape p, where the cartridge is a single-use device.

67. The tape p where the cartridge further includes
receiving a sample strip, and where at least one test strip for the analysis of lateral flow includes a couple of test strips for analysis of lateral flow, and each test strip for the analysis of lateral flow is in contact with the gasket for the sample so that when a liquid sample is taken at the gasket for the sample, the sample fluid seeps on each of the test strips for analysis of lateral flow, so that parallel reactions occur in a pair of test strips for analysis of lateral flow.

68. The tape p, where asterousia the assay lateral flow further includes
conjugate, located in an area conjugate upstream from the zone of analysis of specific binding, and the conjugate will react in the presence of the first of many of the analyzed substances to obtain a detectable reaction in the area of analysis of specific binding on the transport matrix.

69. The tape p, where the conjugate is configured to associate HbAlc.

70. The tape p, where the area of analysis of specific binding is located upstream from the area of General chemical analysis, and test strip for the analysis of lateral flow further includes
the removal area of the conjugate between the area of analysis of specific binding and area General chemical analysis.

71. Cassette according to item 70, where the removal area conjugate formed by the adsorption of antibodies against the conjugate.

72. The system according to item 70, where the removal area conjugate formed by impregnation of the material that is associated with the conjugate and immobilized it.

73. Cassette according to item 72, where binding of the conjugate material is an antibody directed against the conjugate.

74. Cassette according to item 72, where binding of the conjugate material is a polymer that can form bridges between particles conjugate and mobilitat them.

75. The tape p, where the area of General chemical analysis is located upstream from the analysis of specific binding.

76. Cassette according to item 75, where there is no zone of removal of the conjugate between the area of General chemical analysis and area analysis of specific binding.

77. Cassette according to item 75, where the removal area of the conjugate is located between the area of General chemical analysis and area analysis of specific binding.

78. The tape p, where the conjugate includes
labeled indicator reagent, diffusely immobilized on the transport matrix.

79. The tape p, where the labeled indicator reagent includes colored microparticles.

80. The tape p, where the labeled indicator reagent comprises a fluorescent microparticles.

81. The tape p, where the labeled indicator reagent is a colored microparticle, a conjugate associated with the antibody against HbAl.

82. The tape p, where first an analyte is an antigen HbAl.

83. The tape p, where the labeled indicator reagent is a molecule, a conjugate is associated with a specific binding partner to the first analyte.

84. The tape p, where the labeled indicator reagent is a molecule, a conjugate associated with the analyzed substance or analogue of the first analyte.

85. The tape p, where the labeled indicator reagent interacts in the presence of the first analyte for which obrazovaniya mixture, containing a complex of the first analyte: labeled indicator.

86. The tape p, including additional
chemical indicator located upstream from the area of General chemical analysis.

87. The tape p, where the chemical indicator configured to chemical interaction in the presence of the second analyte to obtain a detectable reaction in the area of General chemical analysis on the transport matrix.

88. The tape p, where detectable reaction in the area of analysis of specific binding is formed from the first and from the second of the analyzed substances, and detectable reaction in the area of General chemical analysis is formed only from the second analyte.

89. The tape p, where the chemical indicator turns any hemoglobin present in the sample, in met-hemoglobin.

90. The tape p, where the analysis of the specific binding represents an immune analysis of competitive inhibition.

91. The tape p, where the analysis of specific binding is a direct competitive immune analysis.

92. The tape p, where the analysis of specific binding is a sandwich immune analysis.

93. The tape p, where in the General chemical analysis used chemical indicator for direct colorimetry.

94. Cassette according to claim 5, where is the analysis of specific binding is used to detect the level of HbAlc in the sample, and the total chemical analysis is used to identify levels of total hemoglobin present in the sample.

95. The tape p, where the analysis of specific binding is used to identify the level of human albumin present in the sample, and the total chemical analysis is used to identify the level of creatinine present in the sample.

96. The tape p, where the transport matrix is presented in the form of elongated strips having a proximal end, containing an area conjugate, the Central portion containing the area of analysis of specific binding, and the distal end, containing an area of General chemical analysis.

97. The tape p where the transport matrix is presented in the form of a stack of membranes with the first membrane, containing an area conjugate, a second membrane, containing an area of General chemical analysis, and the third membrane, containing an area of analysis of specific binding.

98. The tape p, where the first membrane is located on top of the second membrane and the second membrane is in front of the third membrane.

99. The tape p, where the sample fluid is a lysed whole blood.

100. The tape p, where the transport matrix comprises one continuous membrane, manufactured by Garrett, Borg is nnow from the same material.

101. The tape p where the transport matrix includes at least 2 membranes made of different materials in physical contact with each other.

102. The tape p, where at least 2 of the membrane are in contact the end-to-end.

103. The tape p, where the adjacent ends of the at least two membranes overlap.

104. The tape p, where at least two diaphragms are arranged one on top of another.

105. The tape p, where the area of the conjugate and area analysis of specific binding are located on the first membrane, and the area of General chemical analysis is located on the second membrane.

106. The tape p, where the first membrane is a nitrocellulose, and where the second membrane is a nylon.

107. The tape p, where the area of the conjugate is located on the first membrane and the area of analysis of specific binding and area General chemical analysis are located on the second membrane.

108. The tape p where removal area conjugate formed by the connection between the first and second membranes.

109. The tape p where the transport matrix includes at least 2 membranes made of different materials in physical contact with each other, and where the conjugate is located on the third membrane in contact upstream the t first membrane.

110. The tape p, where the conjugate is located on the third membrane near the site where the first and third membranes are in contact with each other.

111. The tape p, where the conjugate is located on the third membrane in the form of spray bars.

112. The tape p, where the third membrane is a cellulose acetate.

113. The tape p where the cassette also includes
the absorbent sample pad in contact with the downstream end of the test strips for analysis of lateral flow for absorption with her excess sample fluid.

114. The tape p where the cassette also includes
identification label configured for reading the measuring system.

115. The cartridge according to § 114, where the identification label is an optically scanned bar code.

116. Test strip for the analysis of lateral flow, including
(i) transport matrix;
(ii) the area of analysis of specific binding on the transport matrix for receiving the liquid sample and the analysis of specific binding to ensure a detectable reaction, and
(iii) the area of General chemical analysis on the transport matrix for receiving the liquid sample and perform chemical analysis to ensure a detectable reaction, where the transport matrix formed Isogei continuous membrane material, and prevents the contribution of the product formed in the first zone, the reaction in the other zones.

117. Test strip for the analysis of lateral flow on p, where the area of analysis of specific binding is upstream from the General analysis area.

118. The testing strip p, including additional
the removal area of the conjugate between the area of analysis of specific binding and area General chemical analysis.

119. The testing strip p where removal area conjugate formed by the adsorption of antibodies against the conjugate.

120. The testing strip p where removal area conjugate formed by impregnation of the material that is associated with the conjugate and immobilized it.

121. The testing strip p where the binding of the conjugate material is an antibody directed against the conjugate.

122. The testing strip p where the binding of the conjugate material is a polymer that can form bridges between particles conjugate and mobilitat them.

123. The testing strip p, where the area of analysis of specific binding is located downstream from the area of General chemical analysis.

124. The testing strip p where the transport matrix is made of nitrocellulose.

125. The testing strip p, where the test strip for the analysis is the study of the lateral flow further includes
conjugate, located in an area conjugate upstream from the zone of analysis of specific binding, and the conjugate will react in the presence of the first of many of the analyzed substances to obtain a detectable reaction in the area of analysis of specific binding on the transport matrix.

126. The testing strip p, where the conjugate is configured to associate b1.

127. The testing strip p, where the area of analysis of specific binding is located upstream from the area of General chemical analysis, where the test strip for the analysis of lateral flow further includes
the removal area of the conjugate between the area of analysis of specific binding and area General chemical analysis.

128. The testing strip p where removal area conjugate formed by the adsorption of antibodies against the conjugate.

129. The testing strip p where removal area conjugate formed by impregnation of the material that is associated with the conjugate and immobilized it.

130. The testing strip p where the binding of the conjugate material is an antibody directed against the conjugate.

131. The testing strip p where the binding of the conjugate material is a polymer that can form bridges between particles conjugate and mobilitat them.

132. The test is the dominant band p, where the area of General chemical analysis is located upstream from the zone of analysis of specific binding.

133. The testing strip p, area General chemical analysis and area analysis of specific binding area removal conjugate.

134. The testing strip p, where the area of the conjugate is located between the area of General chemical analysis and area analysis of specific binding.

135. The testing strip p, where the conjugate includes
labeled indicator reagent, diffusely immobilized on the transport matrix.

136. The testing strip p, where the labeled indicator reagent includes colored microparticles.

137. The testing strip p, where the labeled indicator reagent comprises a fluorescent microparticles.

138. The testing strip p, where the labeled indicator reagent is a colored microparticle, a conjugate associated with the antibody against HbAlc.

139. The testing strip p, where first an analyte is an antigen b1.

140. The testing strip p, where the labeled indicator reagent is a molecule, a conjugate is associated with a specific binding partner to the first analyte.

141. The testing strip p, where the labeled indicator reagent is a is asticou, a conjugate associated with the analyzed substance or analogue of the first analyte.

142. The testing strip p, where the labeled indicator reagent interacts in the presence of the first analyte for the formation of a mixture containing the complex of the first analyte: labeled indicator.

143. The testing strip p, in addition, includes
chemical indicator located upstream from the area of General chemical analysis.

144. The testing strip p, where the chemical indicator configured to chemical interaction in the presence of the second analyte to obtain a detectable reaction in the area of General chemical analysis on the transport matrix.

145. The testing strip p, where detectable reaction in the area of analysis of specific binding is formed from the first and from the second analyte, and the detectable response in the area of General chemical analysis is formed only from the second analyte.

146. The testing strip p, where the chemical indicator turns any hemoglobin present in the sample, in met-hemoglobin.

147. The testing strip p, where the analysis of the specific binding represents an immune analysis of competitive inhibition.

148. The testing strip p,where the analysis of specific binding is a direct competitive immune analysis.

149. The testing strip p, where the analysis of specific binding is a sandwich immune analysis.

150. The testing strip p, where in the General chemical analysis used chemical indicator for direct colorimetry.

151. The testing strip p, where the analysis of specific binding is used to detect the level of HbAlc in the sample, and the total chemical analysis is used to identify levels of total hemoglobin present in the sample.

152. The testing strip p, where the analysis of specific binding is used to identify the level of human albumin present in the sample, and the total chemical analysis is used to identify the level of creatinine present in the sample.

153. Test strip for the analysis of cross flow, including
the transport matrix comprising a stack of membranes;
the area of analysis of specific binding on the transport matrix for receiving the liquid sample and the analysis of specific binding to ensure a detectable reaction, and the area of General chemical analysis on the transport matrix for receiving the liquid sample and perform chemical analysis to ensure a detectable response.

154. Test strip for the analysis of cross flow on p where the transport matrix includes one hundred the ku membrane to the first membrane, containing an area conjugate, a second membrane, containing an area of General chemical analysis, and the third membrane, containing an area of analysis of specific binding.

155. The testing strip p, where the first membrane is located on top of the second membrane and the second membrane is in front of the third membrane.

156. The testing strip p, where detectable reaction in the area of General chemical reaction can be measured by the membrane in the upper part of the pile, and identify the reaction in the area of analysis of specific binding can be measured at the bottom of the stack.

157. The testing strip p, where detectable reaction in the area of General chemical reactions can be measured in the membrane at the bottom of the pile, and identify the reaction in the area of analysis of specific binding can be measured at the top of the stack.

158. Test strip for the analysis of lateral flow, including
the transport matrix of the lateral flow;
the area of analysis of specific binding on the transport matrix for receiving the liquid sample and the analysis of specific binding to identify the level of human albumin present in the sample fluid, and
area General chemical analysis on the transport matrix for receiving the liquid sample and perform chemical analysis to identify the level create the ina, present in the sample fluid.

159. The testing strip p where the specified transport matrix lateral flow formed from one continuous membrane material.

160. The combined system of the measuring device of the analyzed substances in biological fluids and disposable cassette including
(a) a reusable measuring device of the analyzed substances in biological fluids, including
i) a housing;
ii) an optical system located inside the enclosure;
iii) the limiter adjacent to the optical system or on it; and
b) a disposable cartridge, made with the possibility of accommodation in reusable measuring device of the analyzed substances in biological fluids, including
i) at least one multi-test strip for the analysis of lateral flow, containing an area of analysis of specific binding to the first segment and the area of General chemical analysis on the second segment, the first and second segments are made of different materials so that the connection of the first and second segments of the transport matrix prevents the contribution of the product formed on the first segment of the transport matrix, in response to the second segment of the transport matrix, and this creates a detectable reaction in each CE is the COP, and
ii) a groove made with the possibility of receiving limiter for direct combining test strips for analysis of lateral flow from the optical system.

161. System p, in which the limiter is located on the optical system.

162. System p, where disposable cassette contains two test strips for analysis of lateral flow.



 

Same patents:

FIELD: veterinary.

SUBSTANCE: claimed is test-system of immuno-enzyme analysis, which allows to determine antibodies to viruses of infectious rhinotracheitis (IRT), viral diarrhea-disease of mucous membranes (VD-DMM), parainfluenza viruses -3 (PIV-3), respiratory syncytial (RS) and adenoviral (AVI) infections of livestock. Serological examination of animals allows to detect zones of infection spreading and estimate post-vaccination immunity.

EFFECT: application of claimed test-system IEA will allow to carry out simultaneously epizootological monitoring of five important infections of livestock, retrospective diagnostics of respiratory infections, and estimation of immunity stress in animals resulting from application of vaccines, determination of level of colostral antibodies in young animals in the first weeks or days of life, estimation of therapeutic medicine quality.

10 tbl

FIELD: medicine.

SUBSTANCE: group of inventions refer to medical diagnostics and covers diagnostics of early myocardial infarction by direct determination of myoglobin from human myocardium. Said biosensor represents a disposable graphite electrode modified by colloidal gold and monoclonal antibodies to myoglobin from human myocardium. It is produced the way as follows. A three-contact graphite main electrode is covered with colloidal gold solution stabilised with didodecyl methylammonium bromide in chloroform. It is dried at room temperature. The electrode structure is modified by antibodies to myoglobin from human myocardium by covering the main graphite electrode to myoglobin from human myocardium modified with didodecyl methylammonium bromide and colloidal gold. Then it is dried, settled at +2°÷+6°C, rinsed with water, processed with a blocking buffer, dried, settled at room temperature and rinsed with water.

EFFECT: possibility to determine myoglobin in aqueous solutions.

3 cl, 2 dwg, 5 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, immunology and biotechnology. Substance of the invention consists in developing the method to lower the content of thyroid hormone antibodies by blood passage through prepared original granulated magnetic agent with immobilised forms of thyroid hormones on the basis of polyacrylamide granules with magnetic properties.

EFFECT: improved effectiveness and reduced consumption of the agent as compared to a prototype, owing to higher specific activity and effective multiple regenerability, simplified manipulations with the agent and maintained suspension of granules thereof in sorption process ensured by constant magnetic field that improves the active sorption area, and reduced destruction of perfused blood corpuscles.

5 ex, 2 tbl

FIELD: chemistry.

SUBSTANCE: invention refers to the biochemistry and molecular biology, in particular to the immunochemical analysis. The claimed microchip for multiple parallel immunological analysis of the compounds represents the array of three-dimensional hydrogel elements with specified volume formed on the support by the photo- or chemically induced polymerisation and containing the biological molecules (ligands) of identical or different nature. The method of quantitive immunoassay implies microchip incubation to the reaction media including the analysed sample for the purpose of complex generation. The biological microchips for quantitive immunological analysis and method for implementation of multiple parallel quantitive analysis of the compounds can be used in the analysis of the wide range of low- and high-molecular compounds, in medicine, pharmacology, food industry, environmental protection, scientific researches including proteomics.

EFFECT: possibility of multiple parallel immunological analysis of the compounds.

33 cl, 12 ex, 2 tbl, 11 dwg

FIELD: medicine.

SUBSTANCE: invention concerns medicine, in particular to medical diagnostics. A nano-biochip for registration of proteins and albuminous complexes and a way of its reception is offered. As a biochip substrate a non-stratified material, for example polycarbonate or polystyrene with a relief grid, is used and then the surface is leveled by means of a die providing equal surface with the size of roughnesses not more than 1 mm; after that updating and immobilisation of the molecules-probes capable to cooperate with investigated proteins and albuminous complexes on a surface of the chip specifically is carried out.

EFFECT: way allows to raise reliability of the received biochip at the expense of exception of its stratification and to raise reliability of diagnostics at the expense of rising of registration sensitivity of specific proteins and albuminous complexes.

12 cl, 2 dwg, 1 ex

FIELD: veterinary science.

SUBSTANCE: invention refers to veterinary microbiology and biotechnology can be used for development of specific diagnostic aids. According to the invention the method covers producing antigen erythrocytic colibacillosis diagnosticum by extracting an adhesive antigen from Escherichia cultures, centrifuging the extract, and separating the supernatant. Thereafter formalinised tanninised animal erythrocytes are sensitised with the produced antigen. Extraction is performed in culture fluid containing Escherichia cell culture with phosphate-carbamide buffer 1.8-2.0 M of pH 7.2-7.4 at temperature 40-45°C during 25-30 min. The culture fluid containing Escherichia cell culture and phosphate-carbamide buffer are taken in mass ratio 1:0.4-0.6 respectively. After extraction the supernatant is heated up at 65-68°C within 25-30 min.

EFFECT: method allows for high-quality end product due to improved sensitivity and specificity.

3 ex

FIELD: veterinary science.

SUBSTANCE: invention refers to veterinary microbiology and biotechnology can be used for development of specific diagnostic aids. According to the invention the method covers producing antigen erythrocytic pasteurellosis diagnosticum by extracting pasteurellosis capsular antigen from Pasteurella cultures with sodium chloride brine, with centrifuging the extract and separating the supernatant exposed to sterilisation filtration and used for sensitisation of formalinised anionised animal erythrocytes. Pasteurellosis capsular antigen is extracted with 2.0-2.5% sodium chloride brine at 40-42°C during 30-40 min. Prior to sterilisation filtration, the supernatant is heated up at 65-70°C within 15-30 minutes.

EFFECT: application of the method allows for high-quality end product due to improved sensitivity and specificity.

3 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to medical diagnostics. Offered is method of specific macromolecules record in biological sample by means of the device equipped with optical disk (laser CD) used as sensitive element with applied macromolecular probes specific to disease associated macromolecular markers. Detected macromolecules and their complexes are recorded on CD surface using laser CD reader.

EFFECT: simplification of record process, as well as in higher sensitivity of test system.

4 cl, 3 dwg

FIELD: biology.

SUBSTANCE: invention concerns molecular biology and physics and can be applied in detection of analysed object in a medium. Photosensitive layer is formed on a substrate reflecting or diffusing light. This sensitive material is specific to the object to be detected, and can bind it. When the sensitive material covering the substrate is irradiated in the presence of a stencil, a biosensor with a pattern of active and inactive sensitive material areas is obtained.

EFFECT: evokes visible diffraction at the contact and light irradiation of a medium containing the analysed object.

23 cl, 5 dwg, 1 ex

FIELD: medicine, immunology, allergology.

SUBSTANCE: method involves determination of the level of allergen-specific antibodies - immunoglobulins of subclasses IgG1 and IgG4 in serum blood using the specific allergen Coefficient of specific allergizing (SAC) is calculated by the following formula:

SAC = (parent (IgG4 + IgG1) - control sample (G4C + G1C))/(parent (IgG4 + IgG1) - sample with allergen (G4A + G1A)) wherein IgG1 and IgG4 are the level of the parent indices of corresponding subclasses of immunoglobulins G; G1A and G4A are the levels of corresponding subclasses of immunoglobulins G in addition of allergen; GrC + G1C are the level of corresponding subclasses of immunoglobulins G without addition of allergen. The presence of IgG-dependent sensitizing to a specific industrial allergen is provide at SAC value less 2.5. Method provides enhancing diagnosis for the presence of sensitizing to allergen and to reduce time of analysis. Invention can be used for diagnosis of professional diseases.

EFFECT: improved method of diagnosis.

2 ex

FIELD: medicine.

SUBSTANCE: invention refers to medical equipment, namely to a cell for fluid sampling and presentation of a sample for analysis. The cell for fluid sampling and presentation of a sample for analysis comprises an input cavity for receiving a sample of fluid to be analysed, a centrifugating receiving cavity and a receiving cavity for the analysed sample. The centrifugating receiving cavity is communicating with the input cavity so that to prevent spontaneous current from the input cavity to the centrifugating receiving cavity and so that to make it possible to discharge the fluid from the input cavity into the centrifugating receiving cavity by applying centrifugation force to the cell. The receiving cavity for the analysed sample is capillary connected with at least a part of the centrifugating receiving cavity to maintain the sample transportation ensured by capillary effect from the centrifugating receiving cavity into the receiving cavity for the analysed sample test. The input cavity, centrifugating receiving cavity and receiving cavity for the analysed sample are apertured through an external wall of the cell which pass full-width of these cavities respectively. The method for making said consists that it provides the basic material used to mould the cell. It is moulded with using at least one moulding instrument that is arranged so that it passes in said basic material for cell moulding with the input cavity, the centrifugating receiving cavity and the receiving cavity for analysed sample. The moulding instrument is removed through lateral wall of the cell. The moulding instrument for cell moulding is inserted in the basic material to form the cavities therein, and removed from the basic material once the cavities are formed. The moulding instrument comprises the first flange shaped as reciprocating to the input cavity the cells. The second flange is shaped as reciprocating to the centrifugating receiving cavity of the cell, and the third flange is shaped as reciprocating to the receiving cavity for the analysed sample. The second flange forms the centrifugating receiving cavity adjoining the receiving cavity, and has the thickness that prevents capillary fluid transportation from the input cavity into the centrifugating receiving cavity. The third flange forms the receiving cavity for the analysed sample adjoining the centrifugating receiving cavity, and has the thickness that provides capillary fluid transportation from the centrifugating receiving cavity into receiving cavity for the analysed sample.

EFFECT: invention provides for appropriate separation of the sample, as well as reliable and simple manufacturing of the cell.

29 cl, 4 dwg

FIELD: technological processes.

SUBSTANCE: group of inventions is related to sampling and delivery of controlled liquid volumes. Method for control of required liquid volume in pipette designed for operation with liquid, by means of correction depending on current physical parametre of pipette, includes selection of required volume in pipette containing drive mechanism of piston arranged with the possibility of contact with piston unit to provide for displacement of piston stem of mentioned unit in cap holder to therefore provide for control of liquid amount in cap holder, at that required volume represents amount of controlled liquid; calculation of correction volume with application of volume characteristic that characterises difference of liquid amount controlled in cap holder as function of required volume, at that volume characteristic is defined with application of calibration process; and display of correction volume for pipette user. It is also presented a device for control of required volume of liquid in pipette by means of correction depending on current physical parametre in pipette.

EFFECT: accurate control of required liquid volume is achieved in pipette, as well as pipette manufacture simplification.

26 cl, 16 dwg

FIELD: engines and pumps.

SUBSTANCE: liquid proportioner comprises a casing, a cylindrical part arranged inside aforesaid casing, a piston reciprocating in the aforesaid cylindrical part and piston drive. It incorporates also a secondary appliance to accelerate the piston on emptying the proportioner as compared to the piston motion on suction. The said secondary appliance incorporates the means to generate power required for acceleration, appliance to block the said power generation source and the appliance to start up the latter. The invention also covers the method of proportioning using the aforesaid proportioner.

EFFECT: simple and accurate proportioning.

14 cl, 3 dwg

FIELD: physics, measurements.

SUBSTANCE: invention relates to proportioning appliances designed to feed proportioned medium in present amounts and can be used in various technical equipment, medicine, chemistry, etc. The proposed proportioner comprises the case with an outlet arranged in or on the said case, the proportioning unit communicating with the said outlet. Note that the device has also the vessel for medium located in or on the aforesaid case and communicating with the proportioning unit. In compliance with this invention, a proportioning shaft is fitted inside the said case. Note that some sections of the said shaft are enveloped by a transfer shaft with a transportation duct for the control element to penetrate into the case through slot.

EFFECT: batching minimum quantities of liquid or pastelike media, containing medium fillers or chemically active media, limited time of processing, exact batching in range varying from 0,01 to 200 mcl.

16 cl, 8 dwg

FIELD: physics.

SUBSTANCE: in an electronic pipette there is provision for controlling suction and distribution of liquids. The electronic pipette contains a computing device. The computing device consists of a control module and a main communication interface. The control module determines the operation carried out in the pipette. The main communication interface transmits electrical signal to the pipette, which determine the operation to be carried out in the pipette. The pipette consists of a sample pipe, piston unit, piston driving mechanism, second communication interface and a microprocessor. The piston unit is fixed to the sample pipe and has a piston plunger, which is inserted into the sample pipe. The piston driving mechanism has an actuating shaft, whose surface is in contact with the piston unit. The piston driving mechanism moves the piston plunger of the piston unit in the sample pipe, in a way that enables regulation of liquid in the sample pipe. The second communication interface receives electrical signals from the computing device. The microprocessor controls the piston driving mechanism and executes operations determined by the electrical signals.

EFFECT: simplification of choosing operational parameters; cutting time for changing settings in the device and provision for controlling using one hand.

28 cl, 20 dwg

FIELD: mechanics.

SUBSTANCE: method of jointing corking device (9) with open end (6) of vessel (5) to make receiving device (1) for biological fluids, fabric particles or cultures includes arranging threaded device (40) with turns (42, 43) between cap (20) incorporating a sealing device and receiving vessel (5), relative positioning of the aforesaid parts (5, 20) by revolving them about common lengthwise axis (14), applying a force (F) of 10 to 50 N to one of them along the aforesaid axis. Note here that interacting turns are arranged so that the aforesaid force gets transformed into a relative rotary motion between the aforesaid cap and the receiving vessel and the said turns (42, 43) of the threaded device (40) are engaged along their entire length till a complete screwing on. The invention proposes also the receiving device for biological fluids, fabric particles or cultures.

EFFECT: simpler cap-to-vessel joint.

72 cl, 24 dwg

Gate // 2329101

FIELD: engines and pumps.

SUBSTANCE: invention relates to devices for regulation of feeding a liquid or gas in the pipeline and can be used in labware, for example, in burets. The shut-off device incorporates a coaxial pair of pipes wherein the clearance of an inner pipe is stopped by a partition. On one or both sides of the said partition, the inner pipe wall has, respectively, one or two holes. Here, the outer pipe is arranged to rotate about the inner pipe. A recess of variable depth, its section shape approximating to that of a comma, is made on a limited length of the said outer tube inner surface at the level of the aforesaid hole (or holes).

EFFECT: higher reliability and better performances.

4 dwg

FIELD: medical equipment.

SUBSTANCE: invention refers to laboratory equipment and concerns lock unit for container end wall, specifically for test-tubes with blood sample used for following analysis. Lock unit contains cover, cover rotating mechanism, agitator of analysed agent fixed on lower end side of cover and plate-shaped in cross-section. Destruction of blood corpuscle is minimised within blood sample agitation that provides increased accuracy of analysis results and state diagnostics, and more adequate therapy.

EFFECT: provided easy and effective agitation of analysed object.

20 cl, 8 dwg

FIELD: creation of bio-polymeric fields for enhancing quality of bio-polymeric matrixes prepared for analysis purposes.

SUBSTANCE: method for detecting application of sample substance on surface of carrier at creating bio-polymeric fields comprises steps of placing tip of applicator with applied bio-polymer as liquid sample near surface of carrier coated with electrically conducting material and creating between them voltage equal almost to 5V; applying liquid sample onto surface of carrier; detecting presence and controlling quality of liquid contact between tip of applicator and electrically conducting surface material according to feed of electric current signal between applicator and electrically conducting material on surface of carrier. Apparatus for detecting application of liquid sample of bio-polymer onto surface of carrier is also offered.

EFFECT: improved quality of created bio-polymeric matrixes at process of producing them.

15 cl, 1 dwg

Test-tube // 2300364

FIELD: medicine; manufacture of medical ware.

SUBSTANCE: test-tube has case. Cross-lateral section of test-tube has one line of external boundary of section and one line of internal boundary of section. Line of section external boundary of all the possible pairs of points has two pints being mostly distant one from other. Line of internal boundary of section of all possible pairs of points has two points being most distant one from other. Straight line drawn onto plane of section through points being most distant one from other and which are disposed onto line of external boundary of section, is disposed at angle of 0,017 radian to 3,123 radian to straight line drawn onto plane of section. Thickness of test-tube along external border of section varies. Moreover one part of line of external section in rectangular coordinate system has onto plane is descried by equation of (X/A)2-(Y/B)2 -1=0, where X and Y are coordinate axes, A and B are rational numbers different from zero. One part of line of internal boundary of cross-section in rectangular coordinate system is described by equation of (X/C)2-(Y/D)2-1=0, where X and Y are coordinates, C and D are rational numbers different from zero.

EFFECT: improved efficiency of heat transfer.

10 cl, 14 dwg

FIELD: analytical methods in veterinary.

SUBSTANCE: invention provides device for testing animal body fluid for presence of disease in tested animal, which device comprises container, measuring rod, and luminometer. End of measuring rod is made such that it can be immersed into fluid sample in a manner to fix a specified amount of fluid to the rod for taking part in chemical reaction (within container) generating light emission. The latter comes into luminometer to be converted into bacterial level indicative of the presence of a disease.

EFFECT: enabled fast and accurate reveal of mastitis in cows.

13 cl, 3 dwg

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