Patent Application
20210311027
The present invention relates to an optical test strip as well as to a kit for measuring an analyte concentration in a sample of bodily fluid. The invention further relates to a method for measuring an analyte concentration in a sample of bodily fluid optical test strips, kits and methods according to the present invention may be used in medical diagnostics, in order to quantitatively or qualitatively detect and/or measure a concentration of one or more analytes in one or more bodily fluids. Other fields of application of the present invention are also feasible.
In the field of medical diagnostics, in many cases, concentrations of one or more analytes in samples of body fluids, such as blood, interstitial fluid, urine, saliva or other types of bodily fluids have to be detected and/or measured. Examples of analytes to be detected are glucose, triglycerides, lactate, cholesterol or other types of analytes typically present in these body fluids. According to the concentration and/or the presence of the analyte, an appropriate treatment may be chosen, if necessary.
US 2006/0051738 A1 describes diagnostic dry reagent tests capable of reacting with a single drop of whole blood and reporting both glucose and lightscattering analytes, such as chylomicrons. Such dry reagent tests may employ electrochemical detection methodologies, optical detection methodologies, or both methodologies. These tests alert diabetics to excessive levels of postprandial lipemia caused by meals with excessive amounts of fat, and thus can help reduce the risk of cardiovascular complications in diabetic patients.
US 2018/0172591 A1 describes an optical biosensor. The optical biosensor includes: a substrate; a photo-sensor disposed on the substrate and generating an electrical signal upon irradiation with light; and a bio-sample layer disposed on the photo-sensor and containing a target substance to be assayed and an induction material emitting light through fluorescence, extinction or luminescence upon irradiation with light, wherein the photo-sensor is irradiated with light emitted from the induction material through fluorescence, extinction or luminescence. The optical sensor detects a spectrum of a bio-sample changed by light through the photo-sensor upon irradiation with light and converts the changed spectrum into an electrical signal, thereby enabling assay of the bio-sample without using a separate detector.
US 2005/0109951 A1 describes a device, system and method for portable fluorescence detection. The portable device of the present invention features a low power light, in which a wavelength range is defined as at least one wavelength of light. The light source is preferably highly energy efficient, such that a majority of the electrical power which is consumed is then converted into transmitted light. The emitted light from the excited fluorophore is then preferably detected with any low cost and low power photodetector. Although optionally a highly sensitive optical detector may be used, preferably fluorescence is detected with any light sensing device, such as a regular photodiode or a CCD (charge-coupled device) sensor for example.
WO 2013/158505 A1 describes enzyme-based diagnostic testing systems for detecting and quantifying at least one of the activity level or the concentration of an enzyme or a biochemical analyte in a biological sample. Such enzyme-based diagnostic testing systems can provide rapid, accurate, affordable laboratory-quality testing at the point of care. An enzyme-based diagnostic testing system may include a lateral-flow chromatographic assay cassette that is configured for assaying an amount or activity of an enzyme in a sample or for enzymatically determining the concentration of an enzyme substrate in a sample. Additionally, the enzyme-based diagnostic testing systems may include testing devices (e.g., a smartphone or a similar remote computing device) having data collection and data analysis capabilities. Such testing devices may also include automated data reporting and decision support.
Generally, devices and methods known to the skilled person make use of test elements comprising one or more test chemistries, which, in presence of the analyte to be detected, are capable of performing one or more detectable detection reactions, such as optically detectable detection reactions.
Typically, one or more optically detectable changes in the test chemistry are monitored, in order to derive the concentration of the at least one analyte to be detected from these changes. For detecting the at least one change of optical properties of the test chemistry, various types of detectors are known in the art. In recent developments, consumer-electronics such as mobile phones, laptops, smartphones and other portable devices have become popular to be used as detectors for detecting the changes in the test chemistry. Besides using consumer-electronics for detecting the changes of optical properties of the test chemistry in common test strips, acquiring information from specially designed test modules by using consumer-electronics, e.g. a camera of a portable device, are also known from the art. Thus, US 2017/0343480 A1 discloses a method for measuring blood glucose levels by a portable terminal using a strip module. The strip module includes a dye pad having a color that changes in response to a sample applied to the dye pad. The strip module also includes a transparent strip having a first side and a second side. The first side is opposite the second side. The dye pad is mounted on the first side of the transparent strip, and the transparent strip reflects light provided from a light source of a portable terminal located adjacent to the second side and transmits the light to the dye pad.
However, despite the advantages involved in using consumer-electronics for the purpose of measuring an analyte concentration in samples of bodily fluid, several technical challenges remain. Specifically, ambient light may contribute significantly to the light detected by a camera of the mobile device, such as a smartphone camera. Thus, the impact of ambient light on the determined analyte concentration generally needs to be considered which, so far, requires complex combinations of lighting arrangements, additional coupling means and specially designed test strips, such as for example known from US 2017/0343480 A1. In particular, the common approach of considering impact of ambient light by using additional hardware, generally leads to significant inconvenience for the user and an increase of the economic burden.
It is therefore desirable to provide devices and methods which address the above mentioned technical challenges of analytical measurements. Specifically, an optical test strip, a kit and a method shall be provided which lessen the impact of ambient light when determining or measuring an analyte concentration in a sample of bodily fluid, without requiring additional hardware.
This problem is addressed by an optical test strip, a kit and method for measuring an analyte concentration in a sample of bodily fluid with the features of the independent claims. Advantageous embodiments which might be realized in an isolated fashion or in any arbitrary combinations are listed in the dependent claims.
As used in the following, the terms “have”, “comprise” or “include” or any arbitrary grammatical variations thereof are used in a non-exclusive way. Thus, these terms may both refer to a situation in which, besides the feature 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 further features are present. As an example, the expressions “A has B”, “A comprises B” and “A includes B” may both refer to a situation in which, besides B, no other element is present in A (i.e. a situation in which A solely and exclusively consists of B) and to a situation in which, besides B, one or more further elements are present in entity A, such as element C, elements C and D or even further elements.
Further, it shall be noted that the terms “at least one”, “one or more” or similar expressions indicating that a feature or element may be present once or more than once typically will be used only once when introducing the respective feature or element. In the following, in most cases, when referring to the respective feature or element, the expressions “at least one” or “one or more” will not be repeated, non-withstanding the fact that the respective feature or element may be present once or more than once.
Further, as used in the following, the terms “preferably”, “more preferably”, “particularly”, “more particularly”, “specifically”, “more specifically” or similar terms are used in conjunction with optional features, without restricting alternative possibilities. Thus, features introduced by these terms are optional features and are not intended to restrict the scope of the claims in any way. The invention may, as the skilled person will recognize, be performed by using alternative features. Similarly, features introduced by “in an embodiment of the invention” or similar expressions are intended to be optional features, without any restriction regarding alternative embodiments of the invention, without any restrictions regarding the scope of the invention and without any restriction regarding the possibility of combining the features introduced in such way with other optional or non-optional features of the invention.
In a first aspect, an optical test strip for measuring an analyte concentration in a sample of bodily fluid is disclosed. The optical test strip comprises a test strip carrier having at least one transparent area and a test field. The test field comprises at least one carrier foil, at least one test chemical applied to the carrier foil and at least one porous material.
As used herein, the term “optical test strip” is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may, without limitation, refer to an arbitrary element configured for measuring an analyte concentration in a sample of bodily fluid. The optical test strip may particularly be configured for performing a color-change detection reaction and thereby providing optically detectable information on the analyte concentration. As an example, the optical test strip may particularly be strip shaped, thus, the test strip may have a long and narrow shape.
The term “analyte” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to one or more specific chemical compounds and/or other parameters to be detected and/or measured. As an example, the at least one analyte may be a chemical compound which takes part in metabolism, such as one or more of glucose, cholesterol or triglycerides. Additionally or alternatively, other types of analytes or parameters may be determined, e.g. a pH value.
The term “measuring an analyte concentration in a sample” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a quantitatively and/or qualitatively determination of at least one analyte in an arbitrary sample. For example, the sample may comprise a body fluid, such as blood, interstitial fluid, urine, saliva or other types of body fluids. The result of the measurement, as an example, may be a concentration of the analyte and/or the presence or absence of the analyte to be measured. Specifically, as an example, the measurement may be a blood glucose measurement, thus the result of the measurement may for example be a blood glucose concentration.
The term “test strip carrier” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to an arbitrary substrate configured to provide stabilizing means to the optical test strip, specifically to the test field. The test strip carrier specifically may have a strip-shape, e.g. a shape of a rectangular strip. The test strip carrier, as an example, may be flexible and/or deformable. The test strip carrier, as an example, may have a width, e.g. a lateral extension perpendicular to a longitudinal axis of the test strip, of 1 mm to 20 mm, e.g. 2 mm to 5 mm. The test strip carrier further may have a length, e.g. a longitudinal extension of 10 mm to 70 mm, e.g. 15 mm to 50 mm. The length may exceed the width by e.g. a factor of at least 1.5. The test strip carrier further may have a thickness of 100 micrometers to 2 mm, e.g. 500 micrometers to 1 mm. The test strip carrier may fully or partially be made of at least one material such as one or more of a plastic material, a ceramic material or a paper. Specifically, the test strip carrier may fully or partially be made of at least one plastic foil. The test strip carrier may be made of a single layer or of a plurality of layers. The test strip carrier specifically may be opaque, such as by comprising at least one material which is fully or partially intransparent for visible light.
The test strip carrier has at least one transparent area, such as for example an area fully or partially made of a translucent material or an area having at least one opening, breakthrough or hole in the test strip carrier. The transparent area, as an example, may have a round, oval or polygonal shape. The transparent area, as an example, may fully or partially be surrounded by intransparent or opaque material of the test strip carrier. The transparent area, as an example, may form at least one window, specifically a window opening, in the test strip carrier. The window or window opening specifically, as will be outlined in further detail below, may fully or partially be covered by the test field, which, as an example, may be applied to the test strip carrier in the region of the at least one transparent area, thereby, e.g., covering at least the window. However, the transparent area may for example expand over the whole test strip, such as cover the test strip completely. Thus, in particular, the test strip carrier itself may for example be fully made of a transparent material and may therefore, for example, itself be the transparent area.
The term “test field” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to an arbitrary element having at least one amount of a test chemical for detecting at least one analyte. The test field, as an example, may comprise at least one layer comprising the test chemical. As an example, the test field may comprise an arbitrary layered element, having a layered structure, with the test chemical being comprised by at least one layer of the layered structure. Particularly, the term may refer to a coherent amount of the test chemical, such as to a field, e.g. a field of round, polygonal or rectangular shape, having one or more layers of material, with at least one layer of the test field, such as the carrier foil, having the test chemical applied thereto. Other layers may be present providing spreading properties for spreading the sample or providing separation properties such as for separating of particulate components of the sample, such as cellular components, for example by comprising the at least one porous material.
In particular, the test field comprises the at least one porous material, for example material being fully or partially porous, for at least partially filtering out solid components contained in the sample. The porous material in particular may be configured for separating particulate or solid components of the sample. Thus, the porous material may specifically be or may comprise a filter material, such as for example titanium dioxide (TiO2). In particular, the porous material may for example filter out cellular components comprised in the sample of bodily fluid.
Further, the test field comprises the at least one carrier foil. The at least one carrier foil of the test field is applied to the test strip carrier and covers the transparent area of the test strip carrier. Thus, the carrier foil may for example cover or overlap the transparent area, for example an opening or hole, of the test strip carrier. Specifically, the carrier foil may be or may comprise a material having an inherent rigidity so as to be suitable for covering the transparent area, such as the opening or hole, of the test strip carrier.
The term “carrier foil” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to an arbitrary film like material. Specifically, the carrier foil may have a foil shape wherein the carrier foil in a first extension direction may be at least ten times smaller than an extension of the carrier foil in another direction, extending orthogonally to the first direction. The carrier foil specifically may be made of at least one flexible or deformable material, such as at least one flexible or deformable plastic foil. The plastic foil, as an example, may have a thickness of 10 micrometers to 500 micrometers. The carrier foil, specifically, may comprise at least one transparent matrix material, such as at least one transparent plastic material being translucent in the visible spectral range. Examples will be given in further detail below.
In particular, the carrier foil may comprise a complex structure, for example a layered structure having one or more layers of material. Thus, the carrier foil may specifically comprise the at least one layer of transparent matrix material. Other layers may be present, for example adhesive layers, such as glue layers, adhesive tape layers, or other layers for bonding.
The carrier foil further has at least one wavelength filter component which is adapted to essentially block light having wavelengths λblc of λblc≤WLlow, with 550 nm≤WLlow≤650 nm. In particular, WLlow refers to a wavelength characterizing the at least one wavelength filter component. The term “light” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to an electromagnetic radiation having wavelengths within an electromagnetic spectrum. Specifically, the term light as referred to hereinafter, may specifically be or may comprise electromagnetic radiation having wavelengths λe at least in the range of 10 nm≤λe≤1200 nm, particularly 100 nm≤λe≤1200 nm, more particularly 250 nm≤λe≤1200 nm, even more particularly 400 nm≤λe≤1200 nm.
In particular, the wavelength filter component may for example be introduced into or mixed within a matrix material of the carrier foil, e.g. a transparent matrix material, of the carrier foil, specifically within at least one layer of the carrier foil. Additionally or alternatively, the wavelength filter component may be implemented into the matrix material by being one or more of dispersed in the matrix material or chemically bound to the matrix material, e.g. by covalent bond, chemical complexing or ion bonding. Additionally or alternatively, the wavelength filter component may also form at least one filter layer, e.g. at least one layer disposed on one or both sides of at least one layer of the matrix material.
The term “essentially block” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a process of a majority of electromagnetic radiation being stopped or blocked from passing through matter. In particular, the wavelength filter component having the characterizing wavelength WLlow and configured for essentially blocking light having wavelengths λblc, may specifically be configured for one or both of absorbing or reflecting ≥80% of the intensity of electromagnetic radiation having wavelengths λblc≤WLlow, from transmitting or passing through the carrier foil. Thus, the wavelength filter component having the characterizing wavelength WLlow and configured for essentially blocking light having wavelengths λblc, may specifically be configured for transmitting less than 20%, in particular less than 10%, more particular less than 5%, of light having wavelengths λblc≤WLlow through the carrier foil. The transmission may specifically be defined as a quotient of an intensity of light, e.g. electromagnetic radiation, transmitted by the filter, divided by the starting intensity of the light incident on the filter, multiplied by 100%.
The blocking effect of the at least one wavelength filter component may be based on various physical principles. Thus, as an example, the wavelength filter component may comprise at least one filter material being suited for absorbing the light, specifically in a wavelength-selective fashion, such as at least one dye, e.g. at least one organic or inorganic dye. The filter material, e.g. the at least one dye, as an example, may be introduced in at least one matrix material, e.g. as outlined above. Additionally or alternatively, the filter material may also be comprised by at least one filter layer, e.g. at least one layer of the filter material being directly or indirectly applied onto one or both sides of the carrier foil. Further, in addition or as an alternative to an absorption, the blocking effect may be also achieved by a reflection, e.g. in a wavelength-selective fashion. Thus, as an example and as will be outlined in further detail below, the wavelength filter component may comprise at least one multi-layer setup comprising a plurality of layers having differing optical refractive indices. Thus, as an example, the wavelength filter component may comprise at least one interference filter, e.g. at least one interference filter having a plurality of layers of at least one organic or inorganic material, the layers having a varying refractive index, e.g. a periodically varying refractive index. The layer setup, as an example, may directly or indirectly be applied to the carrier foil on one or both sides. Additionally or alternatively, the carrier foil itself may be part of the wavelength-selective element. Combinations of the named possibilities are feasible.
The test field further comprises at least one test chemical directly or indirectly applied to the carrier foil. The test chemical is configured for performing an optically detectable detection reaction with the analyte. The term “test chemical” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a chemical compound or a plurality of chemical compounds such as a mixture of chemical compounds suited for performing a detection reaction in the presence of the analyte, wherein the detection reaction is detectable by specific means, such as optically. The detection reaction specifically may be analyte-specific. The test chemical, in the present case, specifically may be an optical test chemical, such as a color-change test chemical which changes in color in the presence of the analyte. The color change specifically may depend on the amount of analyte present in the sample. The test chemical, as an example, may comprise at least one enzyme, such as glucose oxidase and/or glucose dehydrogenase. Additionally, other components may be present, such as one or more dyes, mediators and the like. Test chemicals are generally known to the skilled person and reference may be made to J. 20 Hönes et al.: Diabetes Technology and Therapeutics, Vol. 10, Supplement 1, 2008, pp. 10-26. Other test chemicals, however, are feasible, too.
The test chemical is further configured for at least partially, for example fully or partially, absorbing light having at least one absorption wavelength λabs in the range 650 nm<λabs≤1100 nm. In particular, light having the at least one absorption wavelength λabs may in particular be fully or partially absorbed by the test chemical. The term “absorb” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a process of energy being taken up by matter, such as the electrons of an atom. Thus, in particular, electromagnetic energy of light having the at least one absorption wavelength λabs may be at least partially taken up by the test chemical and thereby for example be transformed into internal energy of the test chemical. Thus, as an example, the test chemical may specifically have an extinction or attenuation coefficient α>0.
As an example, for the blocking wavelength λblc of the wavelength filter component adapted to essentially block light having wavelengths λblc, may specifically apply 10 nm≤λblc≤WLlow, e.g. 100 nm≤λblc≤WLlow, 250 nm≤λblc≤WLlow, or 400 nm≤λblc≤WLlow. Thus, in particular, the wavelength filter component may be adapted to essentially block all light from an ultraviolet range to WLlow. Specifically, the wavelength filter component may, for example, be configured to essentially block ultraviolet (UV) light, such as electromagnetic radiation in the UV range, as well as visible light, specifically electromagnetic radiation visible for human eyes, below or equal to WLlow.
The wavelength filter component, in particular, may be located within the carrier foil. Specifically, the wavelength filter component may, for example, be dispersed within the carrier foil, such as mixed within the material of the carrier foil.
As an example, the wavelength filter component may be selected from the group consisting of a longpass filter component and a bandpass filter component. Specifically, the wavelength filter component may specifically be or may comprise a longpass filter, such as for example the wavelength filter component may be configured for essentially block light having wavelengths λblc≤WLIow. Alternatively, the wavelength filter component may be or may comprise a bandpass filter. The bandpass filter may specifically be or may comprise a combination of a longpass filter and a shortpass filter and may thus only transmit light within a predefined wavelength range, for example only within a wavelength band. Thus, in particular, the wavelength filter component may additionally be configured to block light having wavelengths λblc≥WLhigh. Specifically, WLhigh may refer to an additional wavelength further characterizing the at least one wavelength filter component. As an example, the wavelength filter component may be configured to essentially block light for example having a wavelength of WLhigh and higher, as well as light having wavelengths WLlow and lower.
In particular, the wavelength filter component may specifically be or may comprise at least one longpass filter. The longpass filter may particularly have a transmission edge rising with the wavelength of the light. Thus, the longpass filter may specifically show a higher transmission of light, the higher the wavelength. In particular, the transmission of light through the longpass filter may rise with rising wavelength. Further, the longpass filter may have a characterizing wavelength λLP. Thus, WLlow may equal . In particular, a transmission TLP of the longpass filter at λLP may be 50% of a maximum transmission λLPmax of the longpass filter. Thus, the characterizing wavelength λLP may be defined such that a transmission TLP of the longpass filter at λLP may be 50% of the maximum transmission TLPmax of the longpass filter. In particular, as an example, if the longpass filter, for example in its transmission range, has a maximum transmission of 85%, the characteristic wavelength λLP for this case is defined as that wavelength at which the longpass filter attains a transmission of 0.5×85%=42.5%, for example when viewing the transmission spectrum with rising wavelengths. In particular, the maximum transmission of the longpass filter may for example be at least 75%, specifically at least 80%, more specifically at least 85% or even at least 90% or at least 95%.
Further, the longpass filter may have a steepness SLP of the rising transmission edge. In particular, it may be preferred when the longpass filter has a steep transmission edge in order to block or absorb a maximum part of light having wavelengths below kly and a maximum part of light having wavelengths over or above kly. The steepness of the longpass filter may generally be reported in the unit electron volts (eV) and may be defined as
S
LP
=h·c·[(1/λblc)−(1/λtrans)]. (1)
In Equation (1), λblc may specifically be that wavelength at and below which the longpass filter essentially blocks light. Thus, at wavelength λblc the Transmission TLP of the longpass filter may specifically be smaller than 20%, in particular smaller than 10%, more particular smaller than 5%. Further, λtrans may be defined as being that wavelength at and above which the longpass filter attains a value of 95% of the maximum transmission TLPmax of the longpass filter. Thus, at wavelengths smaller than λtrans the transmission TLP of the longpass filter may be <95% of the maximum transmission TLPmax of the longpass filter and at wavelengths equal or greater than λtrans the transmission TLP may be ≥95% of TLPmax, for example 95% to 100% of TLPmax. If, for example, the longpass filter, more particularly in a transmission region, has a maximum transmission of 85%, λtrans may be defined as that wavelength at which, for example with rising wavelength, the transmission attains a value of 0.95×85%=80.75%. In addition, the above mentioned formula for the steepness of the longpass filter, the parameter h denotes Planck's constant (h≈6.626·10−34 Js) and c the speed of light in a vacuum (c·3.0·108 m/s). With steepness defined in such a way, specifically, the steepness SLP may for example be 0 eV<SLP<1.2 eV, specifically 0.1 eV≤SLP≤1.1 eV, more specifically 0.2 eV≤SLP≤0.9 eV.
In particular, the characterizing wavelength WLlow characterizing the at least one wavelength filter component, may for example be in the range of 550 nm≤WLlow≤650 nm, specifically in the range of 600 nm≤WLlow≤650 nm, more specifically in the range of 625 nm≤WLlow≤650 nm.
The test field of the optical test strip may particularly have a shape selected from the group consisting of: a rectangular shape; a square shape; a round shape; a circular shape. Further, the test field may comprise at least one spreading layer. In particular, the spreading layer may be configured to equally spread or distribute the sample of bodily fluid over a surface of the test field on which the sample may be applied.
The wavelength filter may for example comprise an interference filter, specifically a high-pass interference filter. The term “interference filter” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to an optical filter that reflects one or more spectral bands or lines and transmits others, while maintaining a nearly zero coefficient of absorption for all wavelengths of interest. As an example, the interference filter may comprise multiple layers of dielectric material having different refractive indices. In particular, the interference filter comprises wavelength selective properties. Thus, as an example, the high-pass interference filter having a characteristic wavelength XHpF also referred to as cut-off frequency, may selectively block or attenuate all light having wavelengths below λHPF, wherein the high-pass interference filter may transmit all light having wavelengths higher than λHPF.
The interference filter may specifically be located on at least one surface of the carrier foil. As an example, the interference filter may be directly or indirectly applied to an upper surface of the carrier foil, for example as a separate layer. Additionally or alternatively, the interference filter may be directly or indirectly applied to a lower surface of the carrier foil. Thus, the interference filter may for example be located on both the upper and the lower surface of the carrier foil.
Further, the optical test strip, specifically the carrier foil, may comprise at least one further filter component. In particular, the at least one further filter component may comprise a shortpass filter. Specifically, the shortpass filter may have a transmission edge falling with the wavelength of the light. Thus, the shortpass filter may specifically show an increasing transmission of light for decreasing wavelengths. In particular, the transmission of light through the shortpass filter may fall with rising wavelength. Further, the shortpass filter may have a characteristic wavelength λSP, wherein λSP may equal WLhigh. In particular, a transmission TSP of the shortpass filter at λSP may be 50% of a maximum transmission TSPmax of the shortpass filter. For example, the characteristic wavelength λSP of the shortpass filter may be in the range of 630 nm≤λSP≤800 nm, specifically in the range of 640 nm≤λSP≤680 nm.
As an example, the further filter component, specifically the shortpass filter, may be or may comprise a short-pass interference filter. Specifically, the short-pass interference filter may for example be an interference filter as defined above. In particular, the short-pass interference filter may comprise multiple layers of dielectric material having different refractive indices. In particular, the short-pass interference filter may also comprise wavelength selective properties. Thus, as an example, the short-pass interference filter may have a characteristic wavelength λSPF and may selectively block or attenuate all light having wavelengths higher than λSPF, wherein the short-pass interference filter may transmit all light having wavelengths lower than λSPF.
The optical test strip, specifically the carrier foil, may for example comprise a combination of filter components. As an example, the optical test strip may comprise a combination of a longpass filter and a shortpass filter, e.g. a high-pass interference filter and a short-pass interference filter. However, other combinations of filters are feasible.
In particular, the further filter component may be configured for essentially blocking transmission of light having wavelengths λ≥WLhigh, with WLhigh>WLlow, specifically WLhigh≥WLlow+20 nm, more specifically WLhigh≥WLlow +30 nm, e.g. WLlow+20 nm≤WLhigh+60 nm, e.g. WLlow+30 nm≤WLhigh+50 nm.
In particular, the carrier foil may for example comprise at least one material selected from the group consisting of: a thermoplastic material; a Polyethylene terephthalate (PET); a polyethylene glycol (PEG); a polycarbonate (PC), specifically Pokalon®; a polypropylene (PP), a polystyrene (PS). Further, as an example, the test strip carrier may comprise at least one material selected from the group consisting of: a plastic material; a thermoplastic material; a polycarbonate, specifically Makrolon® or Lexan®.
The optical test strip, for example, may further comprise at least one reference color field. The term “reference color field” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to an arbitrary two-dimensional area which has a predetermined color of known properties. In particular, the reference color field may for example comprise at least one white field, such as a field having a white color. Further, the reference color field may have a shape which is selected from the group consisting of: a rectangular shape; a square shape; a round shape; a circular shape.
In particular, the reference color field may for example be used as a reference. Specifically, when determining the analyte concentration within the sample applied to the test field, the color of the reference color field may be used as a reference to be compared to the optically detectable detection reaction of the test chemical with the analyte.
In a further aspect of the invention, a method for measuring an analyte concentration in a sample of bodily fluid applied to a test field of an optical test strip by using a mobile device is disclosed. The method comprises the following method steps, which may be performed in the given order. However, a different order may also be possible. Further, one, more than one or even all of the method steps may be performed once or repeatedly. Further, the method steps may be performed successively or, alternatively, two or more method steps may be performed in a timely overlapping fashion or even in parallel. The method may further comprise additional method steps which are not listed.
The method comprises the following steps:
The term “mobile device” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a mobile electronics device, more specifically to a mobile communication device such as a cell phone or smart phone. Additionally or alternatively, the mobile device may also refer to a tablet computer or another type of portable computer having at least one camera.
The term “camera” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a device having at least one imaging element configured for recording or capturing spatially resolved one-dimensional, a two-dimensional or even three-dimensional optical information. As an example, the camera may comprise at least one camera chip, such as at least one CCD chip and/or at least one CMOS chip configured for recording images. As used herein, without limitation, the term “image” specifically may relate to data recorded by using a camera, such as a plurality of electronic readings from the imaging device, such as the pixels of the camera chip. The image itself, thus, may comprise pixels, the pixels of the image correlating to pixels of the camera chip.
The camera specifically may be a color camera. Thus, e.g. for each pixel, color information may be provided or generated, such as color values for three colors R, G, B. A larger number of color values is also feasible, such as four colors for each pixel. Color cameras are generally known to the skilled person. Thus, as an example, each pixel of the camera chip may have three or more different color sensors, such as color recording pixels like one pixel for red (R), one pixel for yellow (G) and one pixel for blue (B). For each of the pixels, such as for R, G, B, values may be recorded by the pixels, such as digital values in the range of 0 to 255, depending on the intensity of the respective color. Instead of using color triples such as R, G, B, as an example, quadruples may be used, such as C, M, Y, K. These techniques are generally known to the skilled person.
The wavelength filter of the mobile device may be integrated into the camera chip, for example into at least one CMOS chip. Thus, specifically when taking images using the camera of the mobile device, light having wavelengths λ of 1200 nm≥λ≥WLhigh may be essentially blocked. Thus, in particular, when recording images using the mobile device, the wavelength filter with the characterizing wavelength WLhigh may essentially block light having wavelengths λ from being recorded.
For further possible definitions of terms and possible embodiments, reference may be made to the description of the optical test strip given above or as further described below.
The mobile device may further comprise at least one illumination source. The illumination source may specifically be configured for emitting light for the purpose of illuminating an object when taking an image thereof using the mobile device. In particular, the method step iv) may further comprise illuminating the optical test strip, specifically the test field, in particular by using the illumination source of the mobile device.
The optical test strip may, for example, comprises at least one reference color field. In particular, the method may further comprise step vi) of capturing at least one image of the reference color field by using the mobile device, e.g. the camera of the mobile device. Further, the method step vi) may comprise illuminating the optical test strip, specifically the reference color field.
The wavelength filter of the mobile device, in particular, may comprise at least one shortpass filter. As an example, the shortpass filter may specifically have a transmission edge falling with the wavelength of the light. Thus, the shortpass filter may specifically show a rising transmission of light, the lower the wavelength. In particular, the transmission of light through the shortpass filter may fall with rising wavelength. Further, the shortpass filter may have a characteristic wavelength λSP. Thus, WLhigh may equal λSP. In particular, as an example, the transmission TSP of the shortpass filter at λSP may be 50% of a maximum transmission TSPmax of the shortpass filter.
In particular, the characterizing wavelength WLhigh characterizing the at least one wavelength filter of the mobile device, may for example be in the range of 800 nm≤WLhigh≤1000 nm, specifically in the range of 800 nm≤WLhigh≤950 nm, more specifically 800 nm≤WLhigh≤900 nm.
Specifically, the optical test strip may as an example be or may comprise the optical test strip as disclosed above or as further described below.
In a further aspect of the present invention, a kit for measuring an analyte concentration in a sample of bodily fluid is disclosed. The kit comprises an optical test strip according to any one of the embodiments as described above or as described in further detail below and a mobile device comprising at least one camera. The mobile device further comprises at least one wavelength filter, wherein the wavelength filter is configured for essentially blocking transmission of light having wavelengths λ of 1200 nm≥λ≥WLhigh, with 800 nm≤WLhigh≤1000 nm.
In particular, the mobile device may further comprise at least one illumination source. Specifically, the at least one illumination source of the mobile device may be configured for illuminating an object, such as the optical test strip, when taking an image of the object, e.g. the optical test strip, using the mobile device.
Further, the mobile device may comprise at least one processor. The processor, as an example, may be configured for performing method steps ii) to v) of the method for measuring an analyte concentration in a sample of bodily fluid applied to a test field of an optical test strip by using a mobile device, as described above or as further described below. In addition the processor may also be configured for performing method step vi) of the method.
The devices and methods according to the present invention may provide a large number of advantages over known methods and devices for measuring an analyte concentration in a sample of bodily fluid. Thus, specifically the present invention may be more independent from ambient lighting conditions than common devices and methods. In particular, as an example the optically detectable detection reaction of the test chemical, specifically the color reaction itself, may vary with spectral range, e.g. may change for different spectral ranges. Thus the optically detectable detection reaction may be dependent on ambient lighting conditions. However, the present invention may provide devices and methods for lessening the impact of ambient light on the optically detectable detection reaction without for example, making use of an additional color filter as hardware element, such as additional filters for a camera. In particular, as an example, when analyzing or evaluating calorimetric color strips, such as for example optical test strips, e.g. for detecting blood glucose, by using a mobile device, e.g. a smartphone camera, in particular, different ambient lighting conditions may need to be compensated and additionally various camera specific properties or characteristics may need to be taken into account. Even, as an example, an illumination source of the mobile device itself may vary for different types and models of mobile devices, e.g. smartphones. Further, as an example, color filters used in RGB channels, such as in camera chips, e.g. in CCD chips or CMOS chips, may differ greatly for various cameras. The present invention may allow an evaluation of the analyte concentration by tracking the intensity change of the test chemical in only a narrowed frequency range. For example, as a result, the evaluation of the analyte concentration may be less dependent on ambient lighting condition, e.g. the lighting situation, and may therefore be more clearly attributed to the observed color reaction, than in known methods and devices.
Summarizing and without excluding further possible embodiments, the following embodiments may be envisaged:
Embodiment 1: An optical test strip for measuring an analyte concentration in a sample of bodily fluid, comprising:
Embodiment 2: The optical test strip according to the preceding embodiment, wherein the wavelength filter component is adapted to essentially block light having wavelengths λblc (146) of 10 nm≤λblc≤WLlow, specifically 100 nm≤λblc≤WLlow, more specifically 250 nm≤λblc≤WLlow, and even more specifically 400 nm≤λblc≤WLlow
Embodiment 3: The optical test strip according to any one of the preceding embodiments, wherein the wavelength filter component is located within the carrier foil, specifically the wavelength filter component is dispersed within the carrier foil.
Embodiment 4: The optical test strip (110) according to any one of the preceding embodiments, wherein the wavelength filter component (121) is selected from the group consisting of a longpass filter component and a bandpass filter component.
Embodiment 5: The optical test strip according to any one of the preceding embodiments, wherein the wavelength filter component comprises at least one longpass filter, wherein the longpass filter has a transmission edge rising with the wavelength of the light, wherein the longpass filter further has a characteristic wavelength X4_,P, wherein a transmission of the longpass filter at λLP is 50% of a maximum transmission of the longpass filter and wherein WLlow=λLP.
Embodiment 6: The optical test strip according to the preceding embodiment, wherein the longpass filter has a steepness SLP of the rising transmission edge, wherein 0 eV<SLP≤1.2 eV, specifically 0.1 eV≤SLP≤1.1 eV, more specifically 0.2 eV≤SLP≤0.9 eV, wherein SLP=h·c·[(1/λblc)−(1/λtrans)], wherein at wavelength λtrans the Transmission TLP of the longpass filter is equal to or smaller than 5%, wherein at wavelength λtrans the Transmission TLP of the longpass filter is equal to or greater than 95% of TLPmax.
Embodiment 7: The optical test strip according to any one of the preceding embodiments, wherein 600 nm≤WLlow≤650 nm, specifically 625 nm≤WLlow <650 nm.
Embodiment 8: The optical test strip according to any one of the preceding embodiments, wherein the test field has a shape which is selected from the group consisting of: a rectangular shape; a square shape; a round shape; a circular shape.
Embodiment 9: The optical test strip according to any one of the preceding embodiments, wherein the test field further comprises at least one spreading layer, wherein the spreading layer is configured to equally spread or distribute the sample of bodily fluid over a surface of the test field on which the sample is applied.
Embodiment 10: The optical test strip according to any one of the preceding embodiments, wherein the wavelength filter component comprises an interference filter, wherein the interference filter has a characteristic wavelength λHPF, wherein WLlow=λHPF.
Embodiment 11: The optical test strip according to the preceding embodiment, wherein the interference filter is located on at least one surface of the carrier foil, specifically on an upper surface of the carrier foil, on a lower surface of the carrier foil or on both an upper and a lower surface of the carrier foil.
Embodiment 12: The optical test strip (110) according to any one of the preceding embodiments, wherein the optical test strip (110), specifically the carrier foil (120), comprises at least one further filter component, wherein the at least one further filter component comprises a shortpass filter.
Embodiment 13: The optical test strip (110) according to the preceding claim, wherein the further filter component is configured for essentially blocking transmission of light having wavelengths λ≥WLhigh, with WLhigh>WLIow, specifically WLhigh≥WLIow+20 nm, more specifically WLhigh≥WLlow+30 nm, e.g. WLlow+20 nm≤WLhigh≤WLlow+60 nm, e.g. WLlow+30 nm≤WLhigh≤WLlow+50 nm.
Embodiment 14: The optical test strip according to any one of the preceding embodiments, wherein the carrier foil comprises at least one material selected from the group consisting of: a thermoplastic material; a Polyethylene terephthalate (PET); a polyethylene glycol (PEG); a polycarbonate (PC), specifically Pokalon®; a polypropylene (PP), a polystyrene (PS).
Embodiment 15: The optical test strip according to any one of the preceding embodiments, wherein the test strip carrier comprises at least one material selected from the group consisting of: a plastic material; a thermoplastic material; a polycarbonate, specifically Makrolon® or Lexan®.
Embodiment 16: The optical test strip according to any one of the preceding embodiments, wherein the optical test strip further comprises at least one reference color field.
Embodiment 17: The optical test strip according to the preceding embodiment, wherein the reference color field contains at least one white field.
Embodiment 18: The optical test strip according to any one of the two preceding embodiments, wherein the reference color field has a shape which is selected from the group consisting of: a rectangular shape; a square shape; a round shape; a circular shape.
Embodiment 19: A method for measuring an analyte concentration in a sample of bodily fluid applied to a test field of an optical test strip by using a mobile device, comprising:
Embodiment 20: The method according to the preceding embodiment, wherein the wavelength filter (134) is configured for essentially blocking transmission of light having wavelengths λ of 1200 nm≥λ≥WLhigh
Embodiment 21: The method according to any one of the preceding embodiments referring to a method, wherein the mobile device further comprises at least one illumination source, wherein method step iv) further comprises illuminating the optical test strip, specifically by using the illumination source of the mobile device.
Embodiment 22: The method according to any one of the preceding embodiments referring to a method, wherein the optical test strip further comprises at least one reference color field and wherein the method further comprises step vi) of capturing at least one image of the reference color field by using the mobile device.
Embodiment 23: The method according to the preceding embodiment, wherein method step vi) further comprises illuminating the optical test strip, specifically by using the illumination source of the mobile device.
Embodiment 24: The method according to any one of the preceding embodiments referring to a method, wherein the wavelength filter comprises at least one shortpass filter wherein the shortpass filter has a transmission edge falling with the wavelength of the light, wherein the shortpass filter further has a characteristic wavelength ksp, wherein a transmission of the shortpass filter at λSP is 50% of a maximum transmission of the shortpass filter and wherein WLhigh=λSP.
Embodiment 25: The method according to any one of the preceding embodiments referring to a method, wherein 800 nm≤WLhigh≤950 nm, specifically 800 nm≤WLhigh≤900 nm.
Embodiment 26: The method according to any one of the preceding embodiments referring to a method, wherein the optical test strip comprises an optical test strip according to any one of the preceding embodiments referring to an optical test strip.
Embodiment 27: A kit for measuring an analyte concentration in a sample of bodily fluid, the kit comprising an optical test strip according to any one of the preceding embodiments referring to an optical test strip and the kit further comprising a mobile device, wherein the mobile device comprises at least one camera, wherein the mobile device further comprises at least one wavelength filter, wherein the wavelength filter is configured for essentially blocking transmission of light having wavelengths λ of λ≥WLhigh, with 800 nm≤WLhigh≤1000 nm.
Embodiment 28: The kit (128) according to the preceding embodiment, wherein the wavelength filter (134) is configured for essentially blocking transmission of light having wavelengths λ of 1200 nm≥λ≥WLhigh.
Embodiment 29: The kit according to any one of the preceding embodiments referring to a kit, wherein the mobile device further comprises at least one illumination source.
Embodiment 30: The kit according to any one of the preceding embodiments referring to a kit, wherein the mobile device further comprises at least one control unit, specifically at least one processor.
Embodiment 31: The kit according to the preceding embodiment, wherein the at least one processor is configured for performing method steps iii) to v) of the method according to any one of the preceding embodiments referring to a method.
Further optional features and embodiments will be disclosed in more detail in the subsequent description of embodiments, preferably in conjunction with the dependent claims. Therein, the respective optional features may be realized in an isolated fashion as well as in any arbitrary feasible combination, as the skilled person will realize. The scope of the invention is not restricted by the preferred embodiments. The embodiments are schematically depicted in the Figures. Therein, identical reference numbers in these Figures refer to identical or functionally comparable elements.
In the Figures:
In
In
As illustrated in
The carrier foil 120 further has the at least one wavelength filter component 121 which is adapted to essentially block light having λblc of λblc≤WLlow, with 550 nm≤WLlow≤650 nm. In particular, the wavelength filter component 121 may for example be located within the carrier foil 120, specifically the wavelength filter component 121 may be dispersed within the carrier foil 120, as for example illustrated in
Further, the interference filter 152 may have a characteristic wavelength λHPF 176, wherein, as illustrated by the second transmission spectrum 156 in
As an example, the wavelength filter component 121 may specifically allow an intensity based evaluation of the optical test strip 110, specifically of the optically detectable detection reaction of the test chemical 122, as an example, independently from ambient light and characteristics of the mobile device 130, specifically characteristics of the camera 132.
As illustrated, the different blood glucose concentrations may be separated clearly and may show linear courses for wavelengths λ≥550 nm, specifically for λ≥600 nm. Thus, determining an analyte concentration such as the blood glucose concentration, of a sample 112 applied to the test field 118 of an optical test strip 110 according to the present invention, may particularly improve a measurement accuracy of the analyte concentration. Specifically, since, as illustrated, a determination of an analyte concentration may be difficult in a wavelength-range, for example for wavelengths λ<550 nm, in which the analyte concentration, e.g. blood glucose concentration, significantly varies for very small changes of lighting conditions.
In
| Number | Date | Country | Kind |
|---|---|---|---|
| 18187931.3 | Aug 2018 | EP | regional |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/EP2019/071064 | 8/6/2019 | WO | 00 |
