Method for improved determination of analyte concentrations in body fluids - Patents.com

Abstract

The present invention relates to a computer-implemented analytical method for determining the concentration of an analyte in a bodily fluid by using a mobile device having at least one camera, comprising: i) receiving at least one image captured by the camera of the mobile device, the image including at least a portion of a reagent test area associated with an optical test element and / or associated with a color reference card, the reagent test area having an applied sample of the bodily fluid, the image further including at least a portion of at least one hydrochromic indicator field associated with the optical test element and / or associated with the color reference card, the hydrochromic indicator field indicating a relative humidity rH threshold(m) and ii) receiving at least one image showing at least one optically detectable color change at a predetermined threshold level of the hydrochromic indicator field; and ii) determining an estimate of the local relative humidity rH from the color of the hydrochromic indicator field in the image. estimate Derive the estimated value rH estimate Based on the relative humidity rH appl-range(n) and iii) selecting one of at least two predetermined applicable ranges of the relative humidity rH selected in step ii). appl-range(n) determining the concentration of the analyte from the color of the reagent test area in the image based on a color reaction in the reagent test area with the sample of bodily fluid applied, taking into account the applicability range of the reagent test area.

Description

[Technical Field]

[0001] The present invention relates to a method for determining the concentration of an analyte in a body fluid using at least one mobile device with a camera. Furthermore, the present invention relates to a mobile device with a camera for performing the method, a kit comprising a mobile device with a camera, a computer program, and a computer-readable storage medium. The method, mobile device, computer program, and storage medium may be used in medical diagnostics, in particular for qualitatively or quantitatively detecting one or more analytes in a body fluid, such as for detecting glucose in blood or interstitial fluid. [Background technology]

[0002] In the field of medical diagnostics, one or more analytes must often be detected in a sample of bodily fluid, such as blood, interstitial fluid, urine, saliva, or other types of bodily fluid. Examples of analytes to be detected are glucose, triglycerides, lactate, cholesterol, or other types of analytes typically present in these bodily fluids. Depending on the concentration and / or presence of the analytes, an appropriate treatment may be selected as needed.

[0003] Generally, devices and methods known to those skilled in the art utilize a test element containing one or more test chemicals that can perform one or more detectable, such as optically detectable, detection reactions in the presence of the analyte to be detected. For test chemicals contained in test elements, see, for example, J. Hoenes et al.: The Technology Behind Glucose Meters: Test Strips, Diabetes Technology & Therapeutics, Volume 10, Supplement 1, 2008, S-10 to S-26.

[0004] In analytical measurements, particularly those based on colorimetric reactions, one technical challenge lies in the evaluation of the color change resulting from the detection reaction. In addition to using dedicated analytical equipment such as portable blood glucose meters, the use of commonly available electronic devices such as smartphones, portable computers, or other mobile devices has become increasingly common in recent years.

[0005] In contrast to laboratory measurements and measurements performed using dedicated analytical measurement equipment, when using a mobile computing device such as a smartphone, various additional influences, such as lighting conditions and positioning aspects, need to be taken into account, which can be quite difficult to account for. Nevertheless, to improve the accuracy of analyte detection results in these cases, it is beneficial to properly consider any parameters known to be involved in the desired analyte detection or measurement.

[0006] In the case of analytical measurements based on test chemicals, one such parameter is usually the temperature at which the reaction between the analyte and the test chemical occurs; see, for example, J. Hoenes et al., supra, for such test chemicals contained in the test element. Yet another such parameter that can affect the test chemical is humidity, particularly the ambient humidity at the measurement location, which is often referred to in terms of relative humidity.

[0007] When using a mobile device, one approach to taking into account the temperature of the reaction on the test element is to provide a temperature sensor or temperature display area directly on the test strip itself; see, for example, U.S. Pat. No. 9,778,200 B2, which describes, among other things, a method for a portable computing device having an image sensor to read a reaction area on a test strip located in a peripheral device, where the test strip may include a temperature display area, and test strip characteristics can be corrected based on the captured temperature display area in the image. EP 3,018,470 A1 describes, among other things, a method for a terminal to measure biometric information, the method including receiving an image of a biosensor including a reagent pad on which a sample is collected, and the method may further include determining the temperature of the sample based on temperature information indicated by a temperature measuring device attached to the reagent pad in the received image. U.S. Patent Application Publication No. 2013 / 267032A1 and European Patent Application Publication No. 3575781A2 relate, inter alia, to analyte test strips for detecting a property of an analyte in an analyte sample, which may include a temperature indicating area configured to correct the measurement of the property of the analyte.

[0008] In contrast to the previous example, for analytical measurements involving the use of color-based test chemicals and involving the use of mobile computing devices such as smartphones, the goal may be to take into account the effects of temperature, and similar considerations have not been given to taking into account the effects of humidity in such scenarios.

[0009] An example of a humidity-sensitive scenario in the non-diagnostic field is described in U.S. Patent Application Publication No. 2021350689A1, which relates, inter alia, to a workstation monitoring system comprising a camera for receiving images, identifying surfaces and surface conditions (e.g., including clean, dirty, contaminated, attended, or unattended), tracking individual actions, object movements, and / or surface occurrences that cause changes in the surface condition, and generating a trigger event signal based on the change in the surface condition. Here, a unique identifier may be embedded in a sticker, for example, hidden under hydrochromic ink when the sticker is dry and only visible when the ink is wet, and therefore transparent, and said unique identifier may be read by a scanning mobile handheld device such as a mobile phone.

[0010] EP 2941630 relates to an analyte test strip for detecting a characteristic of an analyte in a sample, comprising a reaction zone and a color calibration zone, the test strip further comprising a path for the sample defined by a capillary extending from the capillary inlet to the reaction zone, a hole defined through the capillary between the capillary inlet and the reaction zone, an upper opening of the hole covered by a first transparent film, and a bottom opening of the hole covered by a second film. The test strip may further comprise a timer zone that receives the sample and changes color linearly in response to the sample, and the test strip may further comprise a timer zone that changes color in response to light or humidity.

[0011] U.S. Patent Application Publication No. 2022 / 381773A1 relates to an analytical method for determining the concentration of an analyte in a bodily fluid using a mobile device having a camera and a processor, where local temperature information at the mobile device's current location is used to determine a correction temperature and / or correction temperature function, which is taken into account when determining the analyte concentration from an image captured by the camera based on a color reaction in a reagent test area of ​​an optical test strip to which a sample of the bodily fluid has been applied. The described method may also take into account humidity information from various sources.

[0012] Despite the advantages associated with using mobile computing devices for the purposes of performing analytical measurements, one remaining technical challenge is properly considering the temperature of the reaction involving the analyte being detected and the test chemicals contained in the test element. Summary of the Invention [Problem to be solved by the invention]

[0013] It would therefore be desirable to provide devices and methods that at least partially address the above-mentioned challenges, particularly devices and methods that enable efficient, mobile-based determination of analyte concentrations in bodily fluids with reliable accuracy, but that require low setup and implementation effort and that specifically consider the effects of humidity. [Means for solving the problem]

[0014] This problem is addressed by a computer-implemented analytical method for determining the concentration of an analyte in a body fluid using at least one mobile device with a camera, further by a mobile device with a camera, by a kit comprising a mobile device and optical test strips and / or color reference cards, as well as by a computer program and a computer-readable storage medium having the features of the independent claims. Advantageous embodiments, which may be realized alone or in any combination, are set out in the dependent claims.

[0015] When used below, the terms "have", "comprise", or "include", or any grammatical variations thereof, are used in a non-exclusive manner. Thus, these terms may refer both to a situation in which, in addition to the features introduced by these terms, no further features are present in the entity described in this context, and to a situation in which one or more additional features are present. For example, the expressions "A has B", "A comprises B", and "A includes B" may both refer to a situation in which, apart from B, no other elements are present in A (i.e., a situation in which A consists solely and exclusively of B), and to a situation in which, apart from B, one or more further elements are present in the entity A, such as element C, elements C and D, as well as further elements.

[0016] Furthermore, it should be noted that the terms "at least one" or "one or more" or similar expressions, indicating that a feature or element may be present more than once, are typically used only once when introducing each feature or element. In the following, in most cases, when referring to each feature or element, the expressions "at least one" or "one or more" will not be repeated, despite the fact that each feature or element may be present more than once.

[0017] Furthermore, when used hereinafter, the terms "preferably," "more preferably," "particularly," "more particularly," "specifically," "more specifically," or similar terms may be used in conjunction with any feature without limiting its alternatives. Therefore, features introduced by these terms are optional features and are not intended to limit the scope of the claims in any way. The present invention may be implemented by using alternative features, as would be understood by a person skilled in the art. Similarly, features introduced by "in an embodiment of the invention" or similar expressions are intended to be optional features without any limitations regarding alternative embodiments of the invention, without any limitations regarding the scope of the invention, and without any limitations regarding the possibility of combining the feature introduced in this manner with other optional or non-optional features of the invention.

[0018] In a first aspect of the present invention, a computer-implemented, particularly in vitro analytical, method for determining the concentration of an analyte in a body fluid is disclosed, the method comprising using at least one camera, particularly a mobile device having a processor. The method includes, by way of example, the following steps, which may be performed in a given order. However, it should be noted that different orders are also possible. Furthermore, one or more of the method steps may be performed once or repeatedly. Furthermore, two or more method steps may be performed simultaneously or overlapping in time. The method may also include additional method steps not listed. In a first step i), the method includes, particularly by a processor of the mobile device, receiving at least one image captured by a camera of the mobile device. The image includes at least a portion of a reagent test area associated with an optical test element and / or a color reference card, the reagent test area having a sample of the body fluid applied thereto. Furthermore, the image includes at least a portion of at least one hydrochromic indicator field associated with the optical test element and / or a color reference card. The hydrochromic indicator field is configured to detect a predetermined threshold level of relative humidity rH. threshold(m) exhibits at least one optically detectable color change.

[0019] The method comprises: ii) Specifically, the mobile device processor derives an estimate of the local relative humidity rH from the color of the hydrochromic indicator field in the image. estimate This includes deriving

[0020] Step ii) is specifically performed by the processor of the mobile device to generate the estimated value rH estimate Based on the relative humidity rH appl-range(n) and selecting one of at least two, specifically one of at least three, of the predetermined applicability ranges.

[0021] The method comprises: iii) determining, specifically by a processor of the mobile device, the concentration of the analyte from the color of the reagent test area in the image based on a color reaction in the reagent test area having a sample of the bodily fluid applied thereto.

[0022] In step iii), determining the analyte concentration is performed at the relative humidity rH selected in step ii). appl-range(n) Taking into account the scope of applicability of

[0023] Without narrowing the scope, the present invention may be described with particular reference to blood glucose measurements, however, it should be noted that the present invention may also be used for other types of analytical measurements that use test elements.

[0024] As used herein, the term "determining the concentration of an analyte in a bodily fluid," also referred to as "analytical measurement," is a broad term and should be given its ordinary and customary meaning to those skilled in the art and should not be limited to any special or customized meaning. This term may specifically, but is not limited to, refer to the quantitative and / or qualitative determination of at least one analyte in any sample or aliquot of bodily fluid. For example, the bodily fluid may include one or more of blood, interstitial fluid, urine, saliva, or other types of bodily fluid, particularly blood. The result of the concentration determination may be, by way of example, the concentration of the analyte and / or the presence or absence of the determined analyte. Specifically, by way of example, the analytical measurement may be a blood glucose measurement, and thus the result of the analytical measurement may be, for example, a blood glucose concentration. In particular, the analytical measurement may determine an analytical measurement result value.

[0025] Thus, as used herein, the term "analyte concentration value," often also referred to as "analytical measurement result value," is a broad term and should be given its ordinary and customary meaning to one of ordinary skill in the art and should not be limited to any special or customized meaning. The term may particularly, but not exclusively, refer to a numerical representation of the analyte concentration in a sample.

[0026] By way of example, the at least one analyte may be or may include one or more specific chemical compounds and / or other parameters. By way of example, one or more analytes involved in metabolism, such as blood glucose, may be determined. Additionally or alternatively, other types of analytes or parameters, such as pH, may be determined.

[0027] The method outlined above involves using at least one mobile device having at least one camera. As used herein, the term "mobile device" is a broad term and should be given its common and ordinary meaning to those skilled in the art and should not be limited to a specific or special meaning. The term may particularly, but not exclusively, refer to mobile electronic devices, more specifically, mobile communication devices such as mobile phones or smartphones. Additionally or alternatively, a mobile device may also refer to a tablet computer or another type of portable computer having at least one camera and at least one processor.

[0028] As used herein, the term "camera" is a broad term and should be given its common and ordinary meaning to those skilled in the art and should not be limited to a specific or special meaning. The term may specifically, but not exclusively, refer to an apparatus having at least one imaging element configured to record or capture spatially resolved one-dimensional, two-dimensional, or even three-dimensional optical data or information. As an example, a camera may include at least one camera chip, such as at least one CCD chip and / or at least one CMOS chip, configured to record an image. As used herein, but not exclusively, the term "image" may specifically refer to data recorded using a camera, such as a plurality of electronic readings from an imaging device, such as pixels of a camera chip.

[0029] In addition to at least one camera chip or imaging chip, the camera may also include one or more optical elements, such as one or more lenses. As an example, the camera may be a fixed-focus camera with at least one lens that is fixedly adjusted relative to the camera. Alternatively, however, the camera may also include one or more variable lenses that can be adjusted automatically or manually. The present invention is particularly applicable to cameras typically used in mobile applications, such as notebook computers, tablets, or mobile phones, particularly smartphones. Thus, in particular, the camera may be part of a mobile device that, in addition to at least one camera, includes one or more data processing devices, such as one or more data processors. However, other cameras are also possible.

[0030] In the method, at least one image is received, the image including at least a portion of a reagent test area associated with one of the optical test element and / or the color reference card. Specifically, the optical test element and / or the color reference card may comprise a reagent test area. Furthermore, if the reagent test area is provided on the optical test element, the color reference card may be adapted to be associated with said optical test element having the reagent test area. The reagent test area is adapted for application of a sample of bodily fluid, and the reagent test area is adapted to at least partially undergo a color-developing reaction when the sample of bodily fluid is applied to the reagent test area. The reagent test area is sometimes referred to herein as a "test field." As used herein, the term "optical test element" is a broad term and should be given its ordinary and customary meaning to those skilled in the art and should not be limited to a special or customized meaning. This term may specifically refer to, but is not limited to, any element or device configured to perform a color change detection reaction. The optical test element may also be referred to as a test strip or a test element, and all three terms may refer to the same element. The optical test element and / or color reference card may have, among other things, a reagent test area containing at least one test chemical for detecting at least one analyte. By way of example, the optical test element may include at least one substrate, such as at least one carrier, to which at least one reagent test area is applied or incorporated. In particular, the optical test element may further include one or more reference areas, such as a white field and / or a black field. Additionally or alternatively, the substrate or carrier itself may be or include such reference areas. By way of example, at least one carrier may be strip-shaped, thereby making the test element a test strip. These test strips are commonly used and readily available. A test strip may have a single test field or multiple test fields with the same or different test chemicals contained therein.The color reference card may include similar features as described herein above for the optical test strip. In particular, the color reference card may be provided in credit card format, i.e., the size and shape of a conventional plastic credit card. Typically, such card-sized color reference cards exhibit multiple reference areas, such as white, black, and / or gray fields. Additionally or alternatively, the color reference card may exhibit multiple reference areas having different reference colors, the reference colors having colors other than white, black, or gray.

[0031] Further, as used herein, the term "reagent test region" (also referred to herein as "test field") is a broad term and should be given its ordinary and customary meaning to one of ordinary skill in the art and should not be limited to any special or customized meaning. This term particularly, but not exclusively, refers to a mass of test chemical, e.g., a circular, polygonal, or rectangular field having one or more layers of material, at least one layer of the test field having the test chemical contained therein. For example, regarding test chemicals contained in optical test strips, see J. Hoenes et al.: The Technology Behind Glucose Meters: Test Strips, Diabetes Technology & Therapeutics, Volume 10, Supplement 1, 2008, S-10 to S-26. Other types of test chemistries are possible and may be used to practice the present invention.

[0032] As outlined above, the method includes receiving at least one image of at least a portion of a reagent test area having a sample of bodily fluid applied thereto, captured by a camera of a mobile device. As used herein, the term "receiving at least one image" is a broad term and should be given its ordinary and customary meaning to those skilled in the art and should not be limited to any special or customized meaning. This term may specifically refer, without limitation, to one or more of imaging, image recording, image acquisition, and image capture. The term "receiving at least one image" may include capturing a single image and / or multiple images, such as a series of images. For example, receiving and / or capturing images may include continuously recording a series of images, such as a video or movie. Receiving and / or capturing the at least one image may be initiated by a user action or automatically, for example, upon automatic detection of the presence of at least one object within the camera's field of view and / or within a predetermined sector of the field of view. These automatic image capture techniques are known in the field of automated barcode readers, such as automated barcode reading apps. Receiving and / or capturing images may be done, by way of example, by a camera capturing a stream or "live streaming" of images, one or more of which are stored and used as at least one first image or at least one second image, respectively, either automatically or through user interaction such as pressing a button. Image capture may be supported by a processor of the mobile device, and image storage may occur within a data storage facility of the mobile device.

[0033] Receiving and / or capturing at least one image may include receiving and / or capturing at least one image with a sample of bodily fluid applied to the test strip, and optionally, receiving and / or capturing at least one image without applying a sample of bodily fluid to the test strip, for example, before capturing an image with the sample applied to the test strip. The latter image may be specifically used for comparison purposes and may be referred to as a "blank image" or a "dry image." Sample application may generally be performed, for example, directly or indirectly, for example, via at least one capillary element. The at least one image captured after sample application may typically be referred to as a "wet image," even if the sample may be dry when the image is actually captured. The wet image may typically be received and / or acquired after at least a predetermined waiting time, for example, 5 seconds or more, to allow a detection reaction to occur. Thus, by way of example, the method may include waiting at least a predetermined minimum time between receiving and / or acquiring at least one optional dry image and at least one wet image. This predetermined minimum time may specifically be sufficient for the detection reaction to occur within the test strip. As an example, the minimum amount of waiting time may be at least 5 seconds.

[0034] The method includes determining an analyte concentration, particularly an analyte concentration value, from the color development of the reagent test area. Thus, the method may be an analytical measurement involving a change in at least one optical property of an optical test element, such as an optical test strip, that can be visually measured or determined using a camera. Specifically, the analytical measurement may be or include a color formation reaction in the presence of at least one analyte to be determined. The term "color formation reaction," as used herein, is a broad term and should be given its ordinary and customary meaning to those skilled in the art and should not be limited to a specific or special meaning. The term may particularly refer, without limitation, to a chemical, biological, or physical reaction in which the color, particularly the reflectance, of at least one element involved in the reaction changes as the reaction progresses. The color development may be detected by a mobile device, such as by a processor in the mobile device, and may be quantitatively evaluated, such as by deriving from at least one image at least one parameter that quantifies or characterizes the color development of the test field due to the presence of the analyte in the bodily fluid. For this purpose, one or more specific color coordinates may be used. Thus, the mobile device, and in particular the processor of the mobile device, may be configured to determine the color change by determining a change in one or more color coordinates that occurs due to the detection response.

[0035] The analyte concentration, specifically the analyte concentration value, is determined from the color development of the test field. At least one image is used for this purpose. The analyte concentration value may be a numerical indicator of the result of the analytical measurement, such as, for example, indicating the concentration of at least one analyte in the sample, such as blood glucose concentration.

[0036] The image received in step i) further includes at least a portion of at least one hydrochromic indicator field associated with the optical test element and / or associated with the color reference card, specifically associated with the color reference card. For example, the at least one hydrochromic indicator field may be attached to the optical test element, or the at least one hydrochromic indicator field may be attached to the color reference card. Alternatively or additionally, the at least one hydrochromic indicator field may be provided separately from the optical test element and the color reference card, but may be used in conjunction with the optical test element and / or the color reference card. The hydrochromic indicator field may be associated with one or more predetermined threshold levels of relative humidity rH. threshold(m) and exhibits at least one optically detectable color change.

[0037] The relative humidity (rH) of an air-water mixture is defined as the ratio of the partial pressure of water vapor in the mixture to the equilibrium vapor pressure of water on a flat surface of pure water at a given temperature. In other words, relative humidity is the ratio of the amount of water vapor present in the air to the amount of water vapor that the air can potentially contain at a given temperature. Relative humidity is usually expressed as a percentage (also referred to herein as "%rH," i.e., percentage relative humidity), with higher percentages indicating more humid air-water mixtures. At 100% relative humidity, air is saturated and at its dew point. As those skilled in the art will recognize, commonly used instruments for measuring air humidity include psychrometers and hygrometers. A summary of such instruments can be found, for example, in Kohlrausch, F., Praktische Physik 1, Kose, V.; Wagner, S. (eds.), 24th Edition, Teubner: Stuttgart, (1996), p. 400. Any relative humidity value, also referred to herein as an "rH" value, as well as any threshold level of relative humidity used herein, e.g., rH threshold(m) , rH threshold(m1) , rH threshold(m2) , and rH estimateAny relative humidity level, including , is provided as a number having units of "%rH," i.e., a percentage of relative humidity. Typically, any rH value referred to herein may be associated with a given ambient temperature and / or a given ambient pressure. Generally, in the context of the present invention, the ambient temperature may be any temperature between 0°C and 65°C, such as 0, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, and 65°C, particularly 20 or 25°C. Furthermore, generally, in the context of the present invention, the ambient pressure may be any pressure between 900 hPa and 1080 hPa (mean sea level pressure, MSLP), such as 990, 1013, or 1040 hPa.

[0038] In step ii), the estimated local relative humidity rH estimate is derived from the color of the hydrochromic indicator field in the image. The term "local," as used in this context, refers to the relative humidity at the mobile device's current location, e.g., an indoor or outdoor location. Furthermore, as used herein, the term "local" may refer to any location or area that can be designated or defined to adequately represent or approximate the relative humidity conditions in or within the locally limited surroundings of the mobile device. For example, particularly when the mobile device's current location is outdoors, it may be appropriate to refer to the relative humidity conditions of a region (e.g., a city, part of a city, a neighborhood, a landscape or part thereof, a county, or federal state, etc.). In this regard, "local relative humidity" may relate to information about relative humidity provided by commonly available online weather services, so long as information about local relative humidity is provided. When the mobile device's current location is indoors, it may alternatively or additionally be appropriate to refer to the relative humidity conditions within a housing or room.

[0039] The method may further include displaying the analyte concentration values, such as on a display of the mobile device. Additionally or alternatively, the method may include storing the at least one analyte concentration value in at least one data storage device of the mobile device. Again additionally and alternatively, the method may further include transmitting the at least one analyte concentration value via the at least one interface and / or via at least one data transmission network to another computer or the like, for example, for further evaluation.

[0040] Thus, in a first aspect, the present invention relates in particular to a computer-implemented, and in particular an in vitro analytical method for determining the concentration of an analyte in a body fluid, by using a mobile device having at least one camera and in particular having at least one processor, i) specifically receiving, by a processor of the mobile device, at least one image captured by a camera of the mobile device, the image including at least a portion of a reagent test area associated with the optical test element and / or associated with a color reference card, the reagent test area having a sample of bodily fluid applied thereto, the image further including at least a portion of at least one hydrochromic indicator field associated with the optical test element and / or associated with the color reference card, the hydrochromic indicator field correlating at least one optically detectable color change with a predetermined threshold level of relative humidity rH; threshold(m) Specifically, two or more different predetermined threshold levels of relative humidity rH threshold(m) receiving at least one image, ii) Specifically, the mobile device processor derives an estimate of the local relative humidity rH from the color of the hydrochromic indicator field in the image. estimate Specifically, the processor of the mobile device calculates the estimated value rH estimate Based on at least two, specifically at least three, relative humidity rH appl-range(n)selecting one of the predetermined applicability ranges of iii) specifically by the processor of the mobile device, determining the relative humidity rH selected in step ii) based on a color reaction in the reagent test area where the sample of bodily fluid was applied. appl-range(n) determining the concentration of the analyte from the color of the reagent test area in the image, taking into account the coverage of rH threshold(m) and rH estimate determining the concentration of the analyte, each of which is an rH value provided in the form of "%rH", i.e., as a percentage of relative humidity; Includes:

[0041] The proposed method provides efficient mobile-based determination of analyte concentrations in body fluids by considering information about the relative humidity at the current location of the mobile device used to perform the method. Information about the local relative humidity is obtained from a cost-effective hydrochromic indicator field, which is available with low effort. Therefore, reliable accuracy of analyte measurements can be achieved efficiently, especially with low setup and implementation effort.

[0042] The image received in step i) includes at least a portion of at least one hydrochromic indicator field, the hydrochromic indicator field indicating one or more predetermined threshold levels rH of relative humidity, e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10. threshold(m) and exhibit at least one optically detectable color change, specifically at one or two, or more than two, e.g., two or three, or even more than three, e.g., three, four, five, six, or seven, different predetermined threshold levels of relative humidity rH threshold(m) In particular, the hydrochromic indicator field may include one or more distinct hydrochromic indicator fields, e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10. Each of said distinct hydrochromic indicator fields corresponds to a predetermined threshold level of relative humidity rH threshold(m)and the humidity sensor may exhibit at least one, and in particular one, optically detectable color change at said predetermined threshold level rH threshold(m) may be partially identical, i.e. there may be at least some redundant separate hydrochromic indicator fields, or the predetermined threshold level of relative humidity rH threshold(m) For example, the hydrochromic indicator field may include a particular number of distinct hydrochromic indicator fields, e.g., in the range of 1 to 10, e.g., 3, 4, 5, 6, or 7, each corresponding to a different predetermined threshold level of relative humidity rH threshold(m) Such a hydrochromic indicator field may therefore comprise seven distinct hydrochromic indicator fields, each of said distinct hydrochromic indicator fields indicating a different predetermined threshold level of relative humidity rH threshold(m) exhibits an optically detectable color change, and a predetermined threshold level of relative humidity, rH threshold(1) =20%rH, rH threshold(2) =30%rH, rH threshold(3) =40%rH, rH threshold(4) =50%rH, rH threshold(5) =60%rH, rH threshold(6) = 70% rH, and rH threshold(7)= 80% rH. Providing at least one hydrochromic indicator field in the form of a plurality of distinct hydrochromic indicator fields may significantly facilitate the detection of the local relative humidity in step ii) derived from the color of the hydrochromic indicator field in the image. Because the locations of the distinct hydrochromic indicator fields in the image may be known or predetermined, for example, by their known locations on an optical test element and / or a color reference card, color changes occurring at any of such known or predetermined locations may be more easily and therefore more accurately determined. Thus, from such a configuration of at least one hydrochromic indicator field, in step ii) an estimate of the local relative humidity rH estimate However, for the purposes of the present invention, one or more single hydrochromic indicator fields may be used to determine two or more different predetermined threshold levels of relative humidity, rH threshold(m) It may also be possible to show more than one color change.

[0043] The materials for the hydrochromic indicator field used herein may provide a reversible or irreversible color change, specifically a reversible color change. Suitable color-changing materials are commercially available and may include, for example, a compound selected from the list including cobalt dichloride, cobalt dibromide, and copper oxide. Such color-changing materials may be commercially obtained, for example, from Long Life for Art (Germany). See https: / / llfa.eu. Typically, such color-changing materials are provided in the form of test strips impregnated with a solution of the material.

[0044] It is particularly useful if each of the at least one optically detectable color change occurs essentially entirely within at least one narrow interval of rH values, each of said at least one narrow interval of rH values ​​being within a predetermined threshold level of relative humidity rH threshold(m)Specifically, each of the at least one narrow interval of rH values ​​may include rH values ​​spanning a range of 15% rH or less, more specifically a range of 10% rH or less, and even more specifically a range of 5% rH or less. In this context, the term "essentially completely" may refer to a degree of color change from a first color to a second color, the second color being visually distinguishable from the first color. Specifically, the color change from the first color to the second color occurs to an extent of at least 80%. More specifically, the degree of color change of at least 80% occurs between an extent of 10% and 90% color change, in each case relative to a complete color change from the first color to the second color, a complete color change representing an extent of 100%. Furthermore, in this context, the term "essentially centered around" refers to a degree of color change from a predetermined threshold level rH of relative humidity. threshold(m) represents a given rH value, e.g., 30% rH, and a narrow interval of rH values, e.g., a range of up to 10% rH values, represents a given threshold level of relative humidity, rH threshold(m) may refer to a configuration adapted to be at least approximately in the center of said narrow interval of rH values. Thus, in this example, a predetermined threshold level of relative humidity rH threshold(m) is 30% rH, said narrow interval of rH values ​​covering a range of up to 10% rH values ​​results in a range of rH values ​​of 25% rH to 35% rH, which is equal to 30% rH ± 5% rH.

[0045] In step i), a predetermined threshold level or levels of relative humidity rH threshold(m) may include one or more rH values ​​selected from 10, 15, 20, 25, 30, 45, 50, 55, 60, 65, 70, 75, and 80% rH. For example, the hydrochromic indicator field may exhibit an optically detectable color change at the following predetermined relative humidity threshold levels: rH threshold(1) =20%rH, rH threshold(2) =30%rH, rH threshold(3) =40%rH, rHthreshold(4) =50%rH, rH threshold(5) =60%rH, rH threshold(6) =70%rH, rH threshold(7) = 80% rH. As another example, the hydrochromic indicator field may exhibit an optically detectable color change at or below a predetermined threshold level of relative humidity, i.e., rH threshold(1) =30%rH, rH threshold(2) =40%rH, rH threshold(3) =50%rH.

[0046] Specifically, the at least one hydrochromic indicator field may include one or more separate hydrochromic indicator fields, each independently of the other, capable of detecting relative humidity rH threshold(m) and in each case exhibiting at least one optically detectable color change at specifically different predetermined threshold levels of relative humidity rH threshold(m) comprises one or more, specifically one, rH value selected from 10, 15, 20, 25, 30, 45, 50, 55, 60, 65, 70, 75 and 80% rH.

[0047] In step ii), the local relative humidity estimate rH estimate is derived from the color of the hydrochromic indicator field in the image, specifically by the processor of the mobile device. threshold(m) A certain predetermined threshold level of relative humidity, e.g., rH = 30% rH threshold(m) If the hydrochromic indicator field exhibits an optically detectable color change, an estimate of the local relative humidity rH can be derived from it. estimate is the specific predetermined threshold level of relative humidity rH threshold(m) may be at least essentially equal to rH estimate An estimate of local relative humidity of =30%rH may be obtained.

[0048] The at least one hydrochromic indicator field includes two or more distinct hydrochromic indicator fields, e.g., seven, each of which indicates a different predetermined threshold level of relative humidity rH threshold(m) , and local relative humidity estimates rH derived from optically detectable color changes at rH thresholds equal to, for example, 20, 30, 40, 50, 60, 70, and 80% rH. estimate is the predetermined threshold level of relative humidity rH that actually exhibits an optically detectable color change when the method is performed. threshold(m) In such a case, the relative humidity may be equal to the highest of all of the seven different predetermined threshold levels rH threshold(m) In the example, when the method is performed, five predetermined threshold levels of relative humidity rH threshold(1) =20%rH, rH threshold(2) =30%rH, rH threshold(3) =40%rH, rH threshold(4) = 50% rH, and rH threshold(5) = 60% rH, if it actually shows an optically detectable color change, rH estimate = 60% rH. The remaining two predetermined threshold levels of relative humidity, rH threshold(6) =70%rH and rH threshold(7) = 80% are their respective rH thresholds threshold(m) is higher than the actual local relative humidity and therefore does not actually exhibit such an optically detectable color change when the method is performed.

[0049] Alternatively, the color of the hydrochromic indicator field in the image can be used to estimate the local relative humidity, rH. estimate Other ways of deriving, particularly by a processor of a mobile device, may be contemplated herein.

[0050] In step ii), furthermore, one of at least two, in particular at least three, relative humidities rH appl-range(n) The mobile device may use one of the given applicability ranges to estimate the local relative humidity, rH estimateSpecifically, the relative humidity rH appl-range(n) One given range of application is that it gives an estimate of the local relative humidity rH estimate For example, if the estimate of local relative humidity is rH estimate = 70% rH, including rH values ​​> 60%, e.g., rH values ​​from > 60% to ≤ 90% appl-range(n) A predetermined applicability range of may be selected.

[0051] Specifically, in step ii), the relative humidity rH appl-range(n) At least two, particularly at least three, predetermined application ranges are different from one another and do not overlap with one another. Typically, at least two, particularly at least three, relative humidity rH appl-range(n) The predetermined applicability ranges of rH are defined such that they form a continuous range of rH values. Such a continuous range of rH values ​​may span a range of rH values ​​from 0% rH to 100% rH, e.g., 0% rH to 90% rH, or 10% rH to 80% rH. Specifically, the predetermined applicability range may have an upper threshold rH value, e.g., an rH value of <30% rH, and thus an rH threshold(k) rH, with an upper threshold of 30% rH appl-range(1)_low (a threshold rH value of 30% rH is excluded from said first rH value range) may itself have a lower threshold of another adjacent range of applicability of predetermined relative humidity, e.g., an rH value of ≥ 30% rH, and thus an rH threshold(k1) rH, with a lower threshold of 30% rH appl-range(2)_high (The threshold rH value of 30% rH may be included in the second rH value range).

[0052] Relative humidity rH appl-range(n) If there are two predetermined applicable ranges, the first range is the low relative humidity range, e.g., rH having <30% rH. appl-range(1) and the second range is a high relative humidity range, e.g., rH having >60% rH. appl-range(2) Generally, the relative humidity rH appl-range(n) At least two predetermined applicability ranges of <X1 rH <rHthreshold(k) rH value x1 rH Relative humidity rH appl-range(1)_low The first applicable range of rH threshold(k) ≦X2 rH rH value x2 rH Relative humidity rH appl-range(2)_high and a second applicability range of:

[0053] Alternatively, relative humidity rH appl-range(n) At least two predetermined applicability ranges of relative humidity rH appl-range(n) Specifically, the relative humidity rH appl-range(n) At least three predetermined applicability ranges of <X1 rH <rH threshold(k1) rH value x1 rH Relative humidity rH appl-range(1)_low At least a first applicable range of rH threshold(k1) ≦X2 rH ≦rH threshold(k2) rH value x2 rH Relative humidity rH appl-range(2)_medium The second applicable range of rH threshold(k2) <X3 rH rH value x3 rH Relative humidity rH appl-range(3)_high and a third applicability range of:

[0054] With respect to the exemplary rH ranges set forth above, in particular, rH threshold(k) , 15, 30, 45, 60, and 75% rH, or rH threshold(k1) may be an rH value selected from one of 15, 20, 25, 30, 35, and 40% rH, and rH threshold(k2) may be an rH value selected from one of 50, 55, 60, 65, 70, and 75% rH. threshold(k) may be an rH value selected from one of 30% rH and 60% rH. Alternatively, rH threshold(k1) may be an rH value selected from one of 25, 30, and 35% rH, and rHthreshold(k2) may be an rH value selected from one of 55, 60, and 65% rH.

[0055] where X1 rH , X2 rH , X3 rH , rH threshold(m) , rH threshold(k) , rH threshold(k1) , and rH threshold(k2) are rH values ​​provided in units of "% rH", specifically at a given ambient temperature and / or a given ambient pressure.

[0056] In step iii), the concentration of the analyte in the body fluid is determined, particularly by a processor of the mobile device, from the color of the reagent test area in the image based on a color reaction in the reagent test area having a sample of the body fluid applied thereto. Determining the concentration of the analyte is performed using the relative humidity rH selected in step ii). appl-range(n) Taking into account the scope of application.

[0057] Advantageously, determining the concentration of the analyte in step iii) is performed by the processor of the mobile device, in particular by determining the concentration of the analyte by means of at least one relative humidity correction rH corr and / or at least one relative humidity correction function rH corr-fct independently of each other, in each case the relative humidity rH selected in step ii) appl-range(n) The at least one relative humidity correction rH may be determined based on one of the ranges of applicability of corr and / or said at least one relative humidity correction function rH corr-fct may be taken into account in step iii) for determining the concentration of the analyte.

[0058] As used herein, "corrected relative humidity, rH" corr (relative humidity correction rH corrThe term "relative humidity corrected rH )" is a broad term and should be given its ordinary and customary meaning to one of ordinary skill in the art and should not be limited to any special or customized meaning. The term may specifically refer to, but is not limited to, one or more of a specified relative humidity value, an average relative humidity value, a representative relative humidity value, a reference relative humidity value, a range of relative humidity values, and a delta relative humidity value, particularly a delta relative humidity value from a reference relative humidity value. Additionally or alternatively, but not limited to, the term "relative humidity corrected rH )" may refer to, but is not limited to, a specified relative humidity value, an average relative humidity value, a representative relative humidity value, a reference relative humidity value, a range of relative humidity values, and a delta relative humidity value, particularly a delta relative humidity value from a reference relative humidity value. corr The term "relative humidity correction function rH" may refer to one or more of a delta analyte concentration value, an average delta analyte concentration value, a representative delta analyte concentration value, a reference delta analyte concentration value, a range of delta analyte concentration values, and specifically, a delta analyte concentration value. corr-fct (relative humidity correction function rH corr-fct ) may refer to a mathematical function, coefficient, formula, or algorithm, each of which may be applied to the determination of the analyte concentration in step iii). Specifically, the "relative humidity correction function rH corr-fct The term "relative humidity corrected rH" may include, but is not limited to, using one or more of a specified relative humidity value, an average relative humidity value, a representative relative humidity value, a reference relative humidity value, a range of relative humidity values, a delta relative humidity value, a delta analyte concentration value, an average delta analyte concentration value, a representative delta analyte concentration value, a reference delta analyte concentration value, and a range of delta analyte concentration values. For practical implementations, the term "relative humidity corrected rH" may be used. corr " and / or "Relative humidity correction function rH corr-fct " advantageously includes a delta analyte concentration value. An estimate of the local relative humidity rH estimate The relative humidity rH selected in step ii) is derived from appl-range(n) The predetermined applicability range of rH may be used as an input or a trigger for applying said function, coefficient, formula, or algorithm in determining the analyte concentration in step iii). corr " and "Relative humidity correction function rH corr-fct" may be useful to properly take into account the effect of relative humidity on the chemical reactions used herein in the reagent test area of ​​the optical test element. Such effects may, for example, be determined empirically by one skilled in the art for any particular type of chemical test reagent. In some cases, the determination of the analyte concentration in step iii) based on a color reaction in the reagent test area may be assumed to be performed at a typical relative humidity, such as, for example, an ambient relative humidity of about 45% rH. In such cases, any effect of relative humidity on the chemical reaction may not be explicitly represented by a coefficient, formula, or algorithm that uses the local relative humidity as an input. In these cases, the "relative humidity corrected rH" may be used. corr " may be determined to be set as the ambient relative humidity, such as 45% rH. Alternatively, in these cases, the "relative humidity correction function rH corr-fct " may be determined to be a multiplier equal to "1," i.e., does not affect the calculation of the analyte concentration.

[0059] Relative humidity rH appl-range(n) One or more of the applicable ranges of RH, optionally each with their own relative humidity correction rH corr and / or relative humidity correction function rH corr-fct Specifically, the relative humidity correction rH corr and / or relative humidity correction function rH corr-fct is the relative humidity rH appl-range(n) may be selected independently of each other for each scope of application.

[0060] In particular, the relative humidity rH appl-range(n) At least one of the ranges of applicability is relative humidity corrected rH corr and / or relative humidity correction function corr-fct and consequently the relative humidity rH appl-range(n) It may be contemplated that for said at least one of said applicability ranges, no relative humidity correction is taken into account for determining the concentration of the analyte. For example, a relative humidity correction rH corr and / or relative humidity correction function rH corr-fct For example, rH threshold(k) =30%rH or rHthreshold(k) = 60% rH, rH threshold(k) ≦X2 rH rH value x2 rH having rH appl-range(2)_high Relative humidity rH appl-range(n) may be related to the applicability range of, for example, rH threshold(k) =30%rH or rH threshold(k) = 60% rH, 0 <X1 rH <rH threshold(k) rH value x1 rH having rH appl-range(1)_low Another relative humidity rH has a low rH value such as appl-range(n) The applicable range of the relative humidity correction function rH corr and / or relative humidity correction function rH corr-fct Additionally or alternatively, relative humidity correction rH corr and / or relative humidity correction function rH corr-fct may be provided in the form of, for example, numbers, coefficients, parameters, and / or functions, such that the relative humidity rH appl-range(n) For the applicable range of corr and / or said relative humidity correction function corr-fct No correction for relative humidity is applied when is considered for determining the concentration of the analyte in step iii).

[0061] Specifically, in step iii), the at least one relative humidity correction rH corr and / or said at least one relative humidity correction function rH corr-fct Taking into account the relative humidity correction rH corr and / or the relative humidity correction function rH corr-fctThe method may further include associating one or more, particularly one, two or three, more particularly each, independently of one another, with a predefined concentration range of analyte concentrations. The predefined concentration ranges may be selected from at least two, particularly at least three, predefined analyte concentration ranges. Specifically, the predefined analyte concentration ranges are different from one another and do not overlap with one another.

[0062] In this regard, the relative humidity rH appl-range(n) As with the predetermined range of applicability of , typically at least two, and more particularly at least three, predefined analyte concentration ranges are defined such that they form a continuous range of analyte concentration values. Such a continuous range of analyte concentration values ​​may span the entire range of analyte concentration values ​​that can be obtained for any particular analyte in the body fluid. Specifically, the relative humidity rH appl-range(n) In a manner similar to that described herein above for a predetermined range of applicability, an upper threshold analyte concentration value of a predefined analyte concentration range (which predefined analyte concentration range may, for example, not include the threshold concentration value) may itself be a lower threshold analyte concentration value of another adjacent predefined analyte concentration range (which predefined analyte concentration range may, for example, include the threshold concentration value).

[0063] Specifically, at least one of the predefined concentration ranges of analyte concentrations is determined by a relative humidity correction function rH corr and / or relative humidity correction function rH corr-fct It may be contemplated that for said at least one of the predefined concentration ranges of analyte concentrations, a relative humidity correction rH is not taken into account for determining the concentration of the analyte in step iii). Additionally or alternatively, for at least one of the predefined concentration ranges of analyte concentrations, a relative humidity correction rH is not taken into account for determining the concentration of the analyte. corr and / or its associated relative humidity correction function rH corr-fctmay be provided, for example, in the form of a number, a coefficient, a parameter, and / or a function, such that for said at least one of the predefined concentration ranges of analyte concentrations, no correction for relative humidity is taken into account for determining the concentration of the analyte in step iii).

[0064] In certain aspects, the methods described herein above specifically involve the mobile device obtaining at least one additional estimate of local relative humidity rH from at least one of the following: add-estimate The method may further include receiving the a) Remote weather services via wireless connection to mobile devices b) An external electronic device with an ambient humidity sensor via a wireless connection to the mobile device c) an ambient humidity sensor located within the mobile device

[0065] Furthermore, step ii) may be implemented by a processor of the mobile device to generate an additional estimate rH add-estimate The local relative humidity estimate rH is calculated by taking into account at least one of the estimate This may include verifying or adjusting the

[0066] where rH estimate and rH add-estimate are rH values ​​provided in the form of "%rH" at a given ambient temperature and / or a given ambient pressure, respectively.

[0067] Specifically, the external electronic devices may be selected from one or more of wearables such as fitness trackers, smart watches, smart glasses, smart clothing, smart home components such as electronic heating systems, smart temperature measurement units, home weather stations, and body-worn sensors such as non-invasive analyte measurement sensors, provided that each external electronic device includes an ambient humidity sensor and the ability to wirelessly connect to a mobile device, e.g., via WiFi, Bluetooth, BLE, etc.

[0068] In another aspect, the present invention relates to a mobile device having at least one camera and at least one processor, the mobile device configured to determine a concentration of an analyte in a bodily fluid, the concentration of the at least one analyte being determined from a color reaction at a reagent test area; The mobile device is further configured to perform at least steps i) to iii) of the computer-implemented analytical methods, particularly the computer-implemented in vitro analytical methods, described herein.

[0069] In another aspect, the present invention relates to a kit comprising: a mobile device having at least one camera and at least one processor, the mobile device configured to determine concentrations of analytes in a body fluid, the concentration of at least one of the analytes being determined from a color reaction at a reagent test area, the mobile device further configured to perform at least steps i) to iii) of the computer-implemented analytical method, in particular the computer-implemented in vitro analytical method, described herein; - at least one of an optical test element and a color reference card, wherein the optical test element and / or the color reference card is associated with the reagent test area; and Includes:

[0070] In another aspect, the present invention relates to a computer program comprising instructions, the instructions causing the program to: when executed by a mobile device having at least one camera and at least one processor, the mobile device configured to determine concentrations of analytes in a bodily fluid, wherein the concentration of at least one of the analytes is determined from a color reaction at a reagent test area, the mobile device further configured to perform at least steps i) to iii) of the computer-implemented analytical method, particularly the computer-implemented in vitro analytical method, described herein; The mobile device is caused to perform at least steps i) to iii) of the computer-implemented analytical method, in particular steps i) to iii) of the computer-implemented in vitro analytical method described herein.

[0071] In another aspect, the present invention relates to a computer-readable storage medium containing instructions, the instructions comprising: - when executed by a mobile device having at least one camera and at least one processor, the mobile device configured to determine the concentration of an analyte in a bodily fluid, wherein the concentration of at least one of said analytes is determined from a color reaction at a reagent test area, the mobile device further configured to perform at least steps i) to iii) of the computer-implemented analytical method, in particular the computer-implemented in vitro analytical method, described herein; The mobile device is caused to perform at least steps i) to iii) of the computer-implemented analytical method, in particular steps i) to iii) of the computer-implemented in vitro analytical method described herein. [Brief explanation of the drawings]

[0072] [Figure 1] 1 illustrates the effect of humidity on blood glucose measurements.

[0073] [Figure 2] Some examples of relative humidity correction functions rHcorr-fct are shown below.

[0074] [Figure 3] 1 shows a perspective view of one embodiment of a kit and a mobile device for performing analytical measurements.

[0075] [Figure 4] 1 shows a flow chart of an exemplary embodiment for carrying out the method of the present invention. DETAILED DESCRIPTION OF THE INVENTION

[0076] As used herein, all rH values ​​referred to are expressed as "% rH", i.e., e.g., rH threshold(m) , rH threshold(k) , rH estimate It is provided in the form of a percentage of relative humidity, including

[0077] 1 shows the effect of humidity on blood glucose measurements in the range of analyte concentrations below 120 mg / dL without applying correction for relative humidity as measured by the Accu-Chek® SugarView® app from Roche Diabetes Care GmbH (Germany) using Accu-Chek® Active optical test strips from Roche Diabetes Care GmbH (Germany). At higher analyte concentrations of approximately 450 mg / dL (not shown), no significant dependence on relative humidity is observed.

[0078] In Figure 1, the deviation in measurements, which is the deviation due to the effect of relative humidity, is expressed as a delta concentration percentage relative to the average measurement at 45% rH. The lines shown represent the average deviation at 15% rH, 45% rH, and 85% rH, respectively.

[0079] Figure 2 shows the relative humidity rH appl-range(n) Several relative humidity correction functions rH, each associated with one of several applicability ranges of corr-fct In this example, each relative humidity correction function rH corr-fct is the relative humidity appl-range(n) Specifically, the first relative humidity correction function rH corr-fct(1) is 0 <X1 rH <rH threshold(k1) rH value x1 rH Relative humidity rH appl-range(1)_low associated with the first applicable range of rH threshold(k1) = 30% rH, and the second relative humidity correction function rH corr-fct(2) is rH threshold(k1) ≦X2 rH ≦rH threshold(k2) rH value x2 rHRelative humidity rH appl-range(2)_medium associated with the second applicability range of rH threshold(k1) = 30% rH, and rH threshold(k2) = 60% rH, and the third relative humidity correction function rH corr-fct(3) is rH threshold(k2) <X3 rH rH value x3 rH Relative humidity rH appl-range(3)_high Associated with the third applicable range of rH threshold(k2) =60%rH.

[0080] Furthermore, in Figure 2, three relative humidity correction functions rH corr-fct(1) , rH corr-fct(2) and rH corr-fct(3) Each of the predefined concentration ranges of analyte concentration is associated with three predefined concentration ranges of analyte concentration. Specifically, the first predefined concentration range of analyte concentration has concentration values ​​of 0 mg / dl to <120 mg / dl, the second predefined concentration range of analyte concentration has concentration values ​​of 120 mg / dl to 200 mg / dl, and the third predefined concentration range of analyte concentration has concentration values ​​>200 mg / dl. Thus, when a measurement is taken in the first analyte concentration range of less than 120 mg / dl, in step iii), each of the predefined concentration ranges is assigned its own relative humidity correction function rH corr-fct Relative humidity rH appl-range(n) For each of the three applicability ranges, a certain correction is applied to determine the analyte concentration. For the second analyte concentration range (120 mg / dL to 200 mg / dL), the relative humidity rH appl-range(n) For two of the three applicable ranges, the correction factor applied to the measurements decreases linearly until one correction factor occurs, so that correction for relative humidity is no longer considered. For the third analyte concentration range >200 mg / dl, the relative humidity rH appl-range(n) For each of the three applicability ranges, no correction for relative humidity is applied or considered.

[0081] FIG. 3 illustrates, in perspective view, an embodiment of a kit 148 and a mobile device for performing analytical measurements. The kit 148 includes at least one mobile device 112 and at least one optical test element 118, i.e., a test strip configured to perform a color change detection reaction. The mobile device 112 has a camera 114 and may further include a processor 149. The mobile device 112 may be configured to perform the methods described herein, particularly by using the processor 149. The optical test element 118 is an optical test strip. In particular, the optical test strip 118 may include at least one reagent test area 120, which includes at least one test chemical for detecting at least one analyte in a sample. The optical test strip 118 further includes a hydrochromic indicator field 121. The mobile device 112 may capture at least one image 124 of at least a portion of the reagent test area 120 associated with the optical test strip 118 by using the camera 114, as shown in FIG. 3.

[0082] FIG. 4 shows a flow chart of an exemplary embodiment for carrying out the method of the present invention using a kit such as that shown in FIG.

[0083] A computer-implemented in vitro analysis method for determining an analyte concentration in a bodily fluid by using a mobile device 112 having at least one camera 114 and at least one processor 149 includes, in a first step i) shown in FIG. 4 as 100, receiving, specifically by the processor 149 of the mobile device 112, at least one image 124 captured by the camera 114 of the mobile device 112. Herein, the image 124 includes at least a portion of a reagent test area 120 associated with an optical test element 118. Alternatively, the image 124 including at least a portion of the reagent test area 120 may be associated with a color reference card 118. The reagent test area 120 has a sample of the bodily fluid applied thereto.

[0084] Additionally, the image 124 includes at least a portion of at least one hydrochromic indicator field 121 associated with the optical test element 118. Alternatively, the hydrochromic indicator field 121 may be associated with the color reference card 118. The hydrochromic indicator field 121 may be associated with a predetermined threshold level of relative humidity rH threshold(m) For example, the hydrochromic indicator field 121 may exhibit at least one optically detectable color change at two or more different predetermined threshold levels of relative humidity rH threshold(m) Advantageously, the at least one hydrochromic indicator field 121 comprises a plurality of separate hydrochromic indicator fields, each of which indicates a different predetermined threshold level of relative humidity rH. threshold(m) It exhibits an optically detectable color change at a predetermined threshold level of relative humidity rH threshold(m) may include, in each case, i.e., in each case of a separate hydrochromic indicator field, an rH value selected from 10, 15, 20, 25, 30, 45, 50, 55, 60, 65, 70, 75 and 80% rH, for example, the following seven different rH values ​​are threshold(7) Predetermined threshold levels of relative humidity rH for: 20, 30, 40, 50, 60, 70, and 80% rH threshold(1) may be selected as

[0085] Generally, each of the at least one optically detectable color change occurs essentially entirely within a narrow interval of rH values, each of said narrow intervals of rH values ​​being essentially within a predetermined threshold level of relative humidity rH threshold(m) Advantageously, each of the narrow intervals of rH values ​​includes rH values ​​spanning a range of 15% rH or less.

[0086] An exemplary embodiment for carrying out the method shown in FIG. 4 includes, in a second step ii) indicated by reference numeral 200 in FIG. 4, specifically, a step in which the processor 149 of the mobile device 112 calculates an estimate of the local relative humidity rH from the color of the hydrochromic indicator field 121 in the image 124. estimate and deriving a predetermined threshold level rH, each of which is a different relative humidity. threshold(1) ~rH threshold(7) In the example of seven distinct hydrochromic indicator fields, which exhibit an optically detectable color change at one of the rH values ​​(having rH values ​​of 20, 30, 40, 50, 60, 70, and 80%, respectively), the estimated local relative humidity rH estimate is all the predetermined threshold levels of relative humidity rH that actually exhibit an optically detectable color change when the method is performed. threshold(m) or any other predetermined threshold level of relative humidity rH threshold(m) For humidity levels (having a rH threshold higher than the actual local humidity), no optically detectable color change is actually observed when the method is performed. Thus, in this example, when the method is performed, an optically detectable color change is observed above a predetermined threshold level of relative humidity rH. threshold(1) = 20% rH and rH threshold(2) If only two of the seven distinct hydrochromic indicator fields with rH = 30% are actually observed, then rH estimate An estimate of local relative humidity of =30%rH may be derived in step ii).

[0087] Step ii) (reference numeral 200) specifically involves the processor 149 of the mobile device 112 generating the estimate rH estimate Based on the relative humidity rH appl-range(n) For example, the method further includes selecting one of at least two predetermined applicable ranges of relative humidity rH appl-range(n) The relative humidity rH appl-range(1)_low The first applicable range (0 <X1 rH <rH threshold(k1)rH value x1 rH and rH threshold(k1) = 30% rH), relative humidity rH appl-range(2)_medium The second applicable range ((rH threshold(k1) ≦X2 rH ≦rH threshold(k2) rH value x2 rH and rH threshold(k1) = 30% rH, and rH threshold(k2) = 60% rH), relative humidity rH appl-range(3)_high The third applicable range (rH threshold(k2) <X3 rH rH value x3 rH and rH threshold(k2) = 60% rH). Therefore, the rH derived in the example above may be selected. estimate Based on an estimate of local relative humidity of =30% rH, the relative humidity appl-range(2)_medium The second applicable range (rH threshold(k1) ≦X2 rH ≦rH threshold(k2) rH value x2 rH and rH threshold(k1) = 30% rH, and rH threshold(k2) = 60% rH) is selected.

[0088] 4 , the exemplary embodiment for carrying out the method further includes, in a third step iii) indicated by reference numeral 300 in FIG. 4 , specifically by the processor 149 of the mobile device 112, determining the concentration of the analyte from the color of the reagent test area 120 in the image based on a color reaction in the reagent test area 120 to which the sample of bodily fluid has been applied. Here, the relative humidity rH selected in step ii) is used. appl-range(n) the applicable range of relative humidity rH appl-range(2)_medium As an example, a second range of applicability of relative humidity rH is considered, with rH values ​​between 30% rH and 60% rH. appl-range(2)_mediumThe second applicable range may be assumed to represent a range of moderate relative humidity values, i.e., a range that does not include particularly low rH values ​​(e.g., <30% rH) or particularly high rH values ​​(e.g., >60% rH), where such moderate relative humidity values ​​have a relatively limited effect on the measured analyte concentration in the bodily fluid. This is illustrated, for example, in FIG. 1, where the moderate range of rH values ​​(30 to 60% rH) represents a reference for both a range of fairly low rH values ​​(<30% rH) and a range of fairly high rH values ​​(>30% rH), and it is shown that for both the low and high rH ranges, significant deviations in the measured blood glucose concentration occur due to either a fairly low rH value (e.g., 15% rH) or a fairly high rH value (e.g., 85% rH), respectively. Therefore, when determining the analyte concentration from the color of the reagent test area 120 in the image in step iii), the relative humidity rH selected in step ii) can be used. appl-range(2)_medium Taking into account the applicability range of RH, it may be appropriate not to apply the correction for relative humidity. In Figure 2, this situation is shown as the relative humidity rH appl-range(2)_medium The dashed lines represent the applicable range of

[0089] On the other hand, if the measurement of blood glucose concentration is performed at a rather low rH value (such as 15% rH) or a rather high rH value (such as 85% rH), a correction for the influence of relative humidity may be appropriate. Deviations in the measured blood glucose concentration resulting from the influence of such low or high rH values ​​are indicated in Figure 1 by a cross ("x" for 15% rH) and a plus sign ("+" for 85% rH), respectively. Thus, as an example, the relative humidity rH shown in Figure 2 appl-range(n) If another one of the three predetermined application ranges is selected (i.e., other than the medium range), the accuracy of the blood glucose measurement obtained can be improved by taking humidity correction into account.

[0090] For this purpose, determining the concentration of the analyte in step iii) is performed at the relative humidity rH selected in step ii). appl-range(n) In each case, at least one relative humidity correction rH corrand / or at least one relative humidity correction function rH corr-fct and taking them into account for determining the concentration of the analyte in step iii). appl-range(n) The applicability range of each is independent of the other and can be calculated using their own relative humidity correction rH corr and / or relative humidity correction function rH corr-fct In Figure 2, three relative humidity ranges (0 <X1 rH <rH threshold(k1) rH value x1 rH and rH threshold(k1) = 30% rH, rH appl-range(1)_low and rH threshold(k1) ≦X2 rH ≦rH threshold(k2) rH value x2 rH and rH threshold(k1) =30% rH and rH threshold(k2) = 60% rH, rH appl-range(2)_medium and rH threshold(k2) <X3 rH rH value x3 rH and rH threshold(k2) = 60% rH, rH appl-range(3)_high ) is its own relative humidity correction function rH corr-fct However, it can alternatively be related to the relative humidity rH appl-range(n) Some of the applicability ranges of the relative humidity correction rH corr and / or relative humidity correction function corr-fct and consequently the relative humidity rH appl-range(n) For some of the applicability ranges of the relative humidity, correction for the relative humidity is not taken into account for determining the concentration of the analyte. The latter situation is, for example, appl-range(2)_medium A second scope of applicability can be considered, which is given as an example herein above.

[0091] Relative humidity correction rH in step iii) corr and / or relative humidity correction function rH corr-fct Considering rH corr and / rH corr-fctThe method may further include associating the relative humidity correction function rH with a predefined concentration range of analyte concentrations. The predefined concentration range is selected from at least two predefined analyte concentration ranges. By way of example, with reference to FIG. 2 , a first predefined concentration range of analyte concentrations has concentration values ​​from 0 mg / dL to <120 mg / dL, a second predefined concentration range has concentration values ​​from 120 mg / dL to 200 mg / dL, and a third predefined concentration range has concentration values ​​>200 mg / dL. In this example, the relative humidity correction function rH corr-fct Each of the three predefined concentration ranges of analyte concentration is associated with a different one of the three predefined concentration ranges of analyte concentration. In this scenario, according to FIG. 2, a different correction for relative humidity is considered for each of the three concentration ranges. However, alternatively, some of the predefined concentration ranges of analyte concentration may be considered for each of the three concentration ranges with a relative humidity correction function rH. corr-fct , so that for some of the predefined concentration ranges of analyte concentrations, no relative humidity correction is taken into account for determining the concentration of the analyte in step iii). The latter situation may be envisaged, for example, for the third predefined concentration range of analyte concentrations having analyte concentration values ​​above 200 mg / dL of analyte concentration, which was given as an example above.

[0092] As a specific example, rH estimate An estimate of the local relative humidity, rH = 20%, may be derived from the color of the hydrochromic indicator field in the image of step ii). estimate Based on the above estimate of local relative humidity of rH = 20% rH, the relative humidity rH appl-range(1)_low The first applicable range (0 <X1 rH <rH threshold(k1) rH value x1 rH and rH threshold(k1) = 30% rH) are the three relative humidity values ​​rH shown in Figure 2. appl-range(n) may be selected from a predetermined range of applicability.

[0093] Relative humidity rH appl-range(1)_lowThe first applicability range of the function is further associated with three predefined concentration ranges of analyte concentration shown in Figure 2, with concentration values ​​of 0 mg / dl to <120 mg / dl, 120 mg / dl to 200 mg / dl, and >200 mg / dl, respectively. In this example, the relative humidity correction function rH corr-fct is rH appl-range(1)_low Relative humidity, including rHappl-range(n) are associated with three predefined predetermined concentration ranges of analyte concentration, respectively, thereby allowing for a different correction of relative humidity for each of the three concentration ranges.

[0094] The relative humidity rH considered in this example appl-range(1)_low For the first predetermined applicability range, with reference to FIG. 2, if the measured blood glucose concentration value is less than 120 mg / dL, a fixed correction is applied to determine the analyte concentration in step iii). This fixed correction at least partially compensates for the positive deviation of the blood glucose measurement, which is observed at a relative humidity of 15% rH and averages more than 10% in terms of Δconcentration at analyte concentration values ​​<120 mg / dL. For measured analyte concentrations between 120 mg / dL and 200 mg / dL, a similar correction is applied to determine the analyte concentration in step iii), but in this case the correction decreases linearly from 120 mg / dL to 200 mg / dL. If the measured analyte concentration is greater than 200 mg / dL, the relative humidity correction is not applied or considered, respectively.

[0095] Similarly, the relative humidity correction function rH corr-fct The relative humidity rH associated with appl-range(3)_high The third predetermined applicable range (rH threshold(k2) <X3 rH rH value x3 rH and rH threshold(k2) = 60% rH) may be considered, which itself is further related to three predefined concentration ranges of analyte concentration shown in Figure 2. appl-range(3)_highSimilarly, with respect to FIG. 2, if the measured blood glucose concentration value is less than 120 mg / dl, a certain correction is applied to determine the concentration of the analyte in step iii). However, rH appl-range(3)_high A constant correction at least partially compensates for the negative deviation in blood glucose measurements observed at a relative humidity of 85% rH, which averages more than 5% for Δconcentration at analyte concentration values ​​<120 mg / dL. For measured analyte concentrations between 120 mg / dL and 200 mg / dL, a correction is similarly applied to determine the analyte concentration in step iii), with the correction decreasing linearly from 120 mg / dL to 200 mg / dL. If the measured analyte concentration is above 200 mg / dL, the relative humidity correction is not applied or considered, respectively. [Explanation of symbols]

[0096] 112 Mobile devices 114 Camera 118 Optical Test Elements (Optical Test Strips, Color Reference Cards) 120 Reagent Testing Area 121 Hydrochromic Indicator Field 124 images 148 kits 149 processors

Claims

1. 1. A computer-implemented analytical method for determining a concentration of an analyte in a bodily fluid by using a mobile device having at least one camera, comprising: i) receiving at least one image captured by the camera of the mobile device, the image including at least a portion of a reagent test area associated with an optical test element and / or associated with a color reference card, the reagent test area having a sample of the body fluid applied, the image further including at least a portion of at least one hydrochromic indicator field associated with the optical test element and / or associated with the color reference card, the hydrochromic indicator field indicating a relative humidity rH ｔｈｒｅｓｈｏｌｄ（ｍ） receiving at least one image exhibiting at least one optically detectable color change at a predetermined threshold level of ii) deriving an estimate of the local relative humidity rH from the color of the hydrochromic indicator field in the image; ｅｓｔｉｍａｔｅ and derive the estimated value rH ｅｓｔｉｍａｔｅ Based on the relative humidity rH ａｐｐｌ－ｒａｎｇｅ（ｎ） selecting one of at least two predetermined applicability ranges; iii) the relative humidity rH selected in step ii) ａｐｐｌ－ｒａｎｇｅ（ｎ） determining the concentration of the analyte from the color of the reagent test area in the image based on a color reaction in the reagent test area to which the sample of the bodily fluid was applied, taking into account the applicable range of Including, where rH ｔｈｒｅｓｈｏｌｄ（ｍ） and rH ｅｓｔｉｍａｔｅ each of which is an rH value provided in the format "% rH" Computer-implemented analysis methods.

2. Each of the at least one optically detectable color change occurs essentially entirely within at least one narrow interval of rH values, and each of the at least one narrow interval of rH values ​​is within a range of a relative humidity rH ｔｈｒｅｓｈｏｌｄ（ｍ） 2. The method of claim 1, wherein each of the at least one narrow interval of rH values ​​is essentially centered around at least one of the predetermined threshold levels, and specifically includes rH values ​​spanning a range of 15% rH or less.

3. The at least one hydrochromic indicator field includes one or more separate hydrochromic indicator fields, each independently of the other, capable of detecting a relative humidity rH ｔｈｒｅｓｈｏｌｄ（ｍ） and the relative humidity rH ｔｈｒｅｓｈｏｌｄ（ｍ） 3. The method according to claim 1, wherein the predetermined threshold level comprises in each case one or more, in particular one, rH value selected from 10, 15, 20, 25, 30, 45, 50, 55, 60, 65, 70, 75 and 80% rH.

4. Relative humidity rH ａｐｐｌ－ｒａｎｇｅ（ｎ） the at least two predetermined applicability ranges of: -0<X1 ｒＨ <rH ｔｈｒｅｓｈｏｌｄ（ｋ） rH value X1 ｒＨ Relative humidity rH ａｐｐｌ－ｒａｎｇｅ（１）＿ｌｏｗ The first applicability range of rH ｔｈｒｅｓｈｏｌｄ（ｋ） ≦X2 ｒＨ rH value x2 ｒＨ Relative humidity rH ａｐｐｌ－ｒａｎｇｅ（２）＿ｈｉｇｈ the second scope of applicability of - relative humidity rH ａｐｐｌ－ｒａｎｇｅ（ｎ） at least three predetermined applicable ranges of relative humidity rH ａｐｐｌ－ｒａｎｇｅ（ｎ） The at least three predetermined applicability ranges are at least: 0 < X1 ｒＨ <rH ｔｈｒｅｓｈｏｌｄ（ｋ１） rH value X1 ｒＨ Relative humidity rH ａｐｐｌ－ｒａｎｇｅ（１）＿ｌｏｗ The first applicability range of rH ｔｈｒｅｓｈｏｌｄ（ｋ１） ≦X2 ｒＨ ≦rH ｔｈｒｅｓｈｏｌｄ（ｋ２） rH value x2 ｒＨ Relative humidity rH ａｐｐｌ－ｒａｎｇｅ（２）＿ｍｅｄｉｕｍ The second applicability range of rH ｔｈｒｅｓｈｏｌｄ（ｋ２） <X3 ｒＨ rH value x3 ｒＨ Relative humidity rH ａｐｐｌ－ｒａｎｇｅ（３）＿ｈｉｇｈ Third scope of applicability Including, X1 ｒＨ , X2 ｒＨ , X3 ｒＨ , rH ｔｈｒｅｓｈｏｌｄ（ｋ） , rH ｔｈｒｅｓｈｏｌｄ（ｋ１） , and rH ｔｈｒｅｓｈｏｌｄ（ｋ２） each of which is an rH value provided in the format "% rH" 4. The method according to any one of claims 1 to 3.

5. rH ｔｈｒｅｓｈｏｌｄ（ｋ） is an rH value selected from one of 15, 30, 45, 60 and 75% rH, or ｔｈｒｅｓｈｏｌｄ（ｋ１） is an rH value selected from one of 15, 20, 25, 30, 35, and 40% rH, and ｔｈｒｅｓｈｏｌｄ（ｋ２） 5. The method of claim 1, wherein R is an rH value selected from one of 50, 55, 60, 65, 70, and 75% rH.

6. In step iii), determining the concentration of the analyte comprises determining the concentration of the analyte using at least one relative humidity corrected rH ｃｏｒｒ and / or at least one relative humidity correction function rH ｃｏｒｒ－ｆｃｔ independently of one another, in each case the relative humidity rH selected in step ii) ａｐｐｌ－ｒａｎｇｅ（ｎ） and determining the concentration of the analyte based on one of the applicability ranges of the at least one relative humidity corrected rH ｃｏｒｒ and / or said at least one relative humidity correction function rH ｃｏｒｒ－ｆｃｔ and considering:

7. Relative humidity rH ａｐｐｌ－ｒａｎｇｅ（ｎ） one or more of the applicability ranges of the relative humidity correction rH ｃｏｒｒ and / or relative humidity correction function rH ｃｏｒｒ－ｆｃｔ and the relative humidity correction rH ｃｏｒｒ and / or relative humidity correction function rH ｃｏｒｒ－ｆｃｔ is the relative humidity rH ａｐｐｌ－ｒａｎｇｅ（ｎ） may be selected independently of each other, and optionally, ａｐｐｌ－ｒａｎｇｅ（ｎ） At least one of the applicability ranges is the relative humidity correction rH ｃｏｒｒ , and / or the relative humidity correction function rH ｃｏｒｒ－ｆｃｔ and therefore the relative humidity rH ａｐｐｌ－ｒａｎｇｅ（ｎ） 7. The method of claim 6, wherein for at least one of the applicability ranges, relative humidity correction is not taken into account for the determining the concentration of the analyte.

8. In step iii), the at least one relative humidity correction rH ｃｏｒｒ and / or said at least one relative humidity correction function rH ｃｏｒｒ－ｆｃｔ The step iii) considers the relative humidity correction rH ｃｏｒｒ and / or the relative humidity correction function rH ｃｏｒｒ－ｆｃｔ 8. The method of claim 6, further comprising associating one or more of, independently of each other, a predefined concentration range of the analyte concentration, wherein the predefined concentration range is selected from at least two predefined analyte concentration ranges.

9. At least one of the predefined concentration ranges of the analyte concentration is a relative humidity corrected rH ｃｏｒｒ and / or relative humidity correction function rH ｃｏｒｒ－ｆｃｔ 9. The method of claim 8, wherein the predetermined concentration range of the analyte concentration is not associated with a relative humidity correction, such that for the at least one of the predefined concentration ranges of the analyte concentration, no relative humidity correction is taken into account for the determining the concentration of the analyte in step iii).

10. The method comprises: a) a remote weather service via a wireless connection to the mobile device; b) an external electronic device comprising an ambient humidity sensor via a wireless connection to the mobile device; c) an ambient humidity sensor located within the mobile device; at least one additional estimate of the local relative humidity rH ａｄｄ－ｅｓｔｉｍａｔｅ receiving the Step ii) is to determine the additional estimate rH ａｄｄ－ｅｓｔｉｍａｔｅ the estimate of the local relative humidity rH ｅｓｔｉｍａｔｅ including verifying or adjusting rH ｅｓｔｉｍａｔｅ and rH ａｄｄ－ｅｓｔｉｍａｔｅ each of which is an rH value provided in the format "% rH" 10. The method according to any one of claims 1 to 9.

11. a mobile device having at least one camera and at least one processor, the mobile device configured to determine concentrations of analytes in a bodily fluid, the concentration of at least one of the analytes being determined from a color reaction at a reagent test area; The mobile device is further configured to perform at least steps i) to iii) of the computer-implemented analysis method of any one of claims 1 to 10. Mobile devices.

12. A kit comprising the mobile device of claim 11 and at least one of an optical test element and a color reference card, wherein the optical test element and / or the color reference card is associated with the reagent test area.

13. 12. A computer program comprising instructions which, when executed by a mobile device according to claim 11, cause the mobile device to perform at least steps i) to iii) of the computer-implemented analysis method according to any one of claims 1 to 10.

14. A computer-readable storage medium comprising instructions that, when executed by a mobile device according to claim 11, cause the mobile device to perform at least steps i) to iii) of the computer-implemented analysis method according to any one of claims 1 to 10.

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