Patent Application
20120165626
The present application relates generally to measuring or otherwise evaluating (e.g., estimating) the concentration of one or more analytes in a fluid sample. More specifically, the present application relates to devices, methods, and kits that may be used to collect sweat from a skin surface, and to measure the concentration of one or more analytes, such as glucose, in the collected sweat.
Many people around the world suffer from diabetes, and the number of affected people continues to increase. Diabetes is a leading cause of death and can result in broad complications, such as blindness, kidney disease, nerve disease, heart disease, amputation, or stroke.
Diabetes results from the inability of the body to produce or properly use insulin. In simple terms, insulin is a hormone that regulates the level of glucose in the blood and allows glucose to enter cells. In diabetics, glucose cannot enter the cells, so glucose builds up in the blood to toxic levels. Although the cause of diabetes is not completely understood, it is believed that genetics, environmental factors, and viral causes contribute to the incidence of diabetes in the world population.
There are two major types of diabetes: Type 1 and Type 2. Type 1 diabetes (also known as juvenile diabetes) is caused by an autoimmune process destroying the beta cells that secrete insulin in the pancreas. Type 1 diabetes most often occurs in young adults and children. People with Type 1 diabetes are typically required to self-administer insulin using, for example, a syringe or a pen with a needle and cartridge. Continuous subcutaneous insulin infusion via external or implanted pumps is also available. Type 2 diabetes, which is more common than Type 1 diabetes, is a metabolic disorder resulting from the body's inability to make enough insulin or to properly use insulin. People with Type 2 diabetes are typically treated with changes in diet and exercise, as well as with oral medications. Many Type 2 diabetics become insulin-dependent at later stages of the disease. Diabetics using insulin to help regulate their blood sugar levels are at an increased risk for medically-dangerous episodes of low blood sugar due to errors in insulin administration, and/or unanticipated changes in insulin absorption.
It is highly recommended by medical professionals that insulin-using patients practice self-monitoring of blood glucose (“SMBG”). Based upon the level of glucose in the blood, individuals may make insulin dosage adjustments before injection. Adjustments are generally necessary since blood glucose levels vary from day to day for a variety of reasons, such as exercise, stress, rates of food absorption, types of food, hormonal changes (pregnancy, puberty, etc.), and the like. Despite the importance of SMBG, several studies have found that the proportion of individuals who self-monitor at least once a day significantly declines with age. This decrease is likely the result of the most widely used method of SMBG involving obtaining blood from a capillary fingerstick, which can be painful, as discussed below.
The vast majority of equipment used to self-monitor blood glucose is invasive, requiring fingersticks (or lancing alternative sites, such as the forearm) and application of whole blood samples to test strips. Lancing the fingers can be particularly painful over time, and can therefore prevent many users from measuring their blood glucose as frequently as they should. Although non-invasive systems have been developed, some of them exhibit poor correlation to invasive blood glucose measurements, and/or high cost.
In view of the above, it would be desirable to provide additional devices, methods, and kits for measuring or otherwise evaluating the concentration of glucose, and/or other analytes, in a body fluid. It would also be desirable for such devices, methods, and kits to be non-invasive and easy to use. It would further be desirable to provide methods for measuring or otherwise evaluating the concentration of one or more analytes in a body fluid in a relatively short period of time.
Described here are devices, methods, and kits for measuring or otherwise evaluating (e.g., estimating) the concentration of one or more analytes in a body fluid. The devices, methods, and/or kits may be non-invasive, and thus may not require painful blood draws (e.g., fingersticks), or their resulting wounds. Moreover, the devices, methods, and/or kits may be used to measure the concentration of one or more analytes in a body fluid relatively efficiently (e.g., in a relatively short period of time).
While the devices, methods, and kits may be configured, as appropriate, to measure or otherwise evaluate the concentration of any analyte or analytes (e.g., glucose, proteins, enzymes, cholesterol, phenylalanine, ketones, etc.) in any body fluid sample (e.g., sweat, blood, serum, urine, saliva, amniotic fluid, etc.), for illustrative purposes, they will be described here with reference to measuring the concentration of glucose in sweat. It should be understood, however, that descriptions provided here with respect to evaluating sweat glucose concentration may also be applied to other suitable analytes and/or body fluid samples. For example, devices, methods, and/or kits described here may be used to test whole blood samples (e.g., relatively small volume samples) for the presence of one or more analytes (e.g., glucose).
Additionally, if so desired, the concentration of an analyte in one body fluid may be used to estimate the concentration of the analyte in another body fluid. For example, a sweat glucose concentration value may be used to estimate a blood glucose concentration value. As an example, a sweat glucose concentration measurement may be correlated to a blood glucose concentration value using one or more algorithms. Thus, a user may be able to determine critical blood glucose values, without having to endure the pain and difficulty that may be associated with obtaining a whole blood sample. Because users may not have to endure any pain associated with testing, it is expected that users will test more frequently than they might with other, more invasive, testing methods. This, in turn, may lead to better compliance with prescribed regimens and, therefore, better clinical outcomes. Moreover, in some cases, the devices described here may be manufactured relatively inexpensively (e.g., by using low-cost materials and/or methods). Accordingly, a user may pay a relatively low cost per test, thereby allowing for more frequent sweat and blood glucose concentration evaluation.
The devices described here typically include one or more membranes. In some variations, the devices may include one or more colorimetric membranes, such that a chemical reaction may occur between an analyte in the collected sweat and one or more chemicals contained in the colorimetric membrane to thereby produce an optically detectable reactant. While devices, methods, and kits are generally described here with respect to colorimetric membranes, it should be understood that devices, methods, and/or kits described here may alternatively or additionally comprise one or more other types of collection and/or analysis supports, such as one or more electrochemical chambers, as appropriate.
In some variations, a colorimetric membrane may be placed into contact with a skin surface and used to collect sweat from the skin surface (e.g., via capillary action or by diffusion or other fluid sequestering means). The concentration of glucose in the collected sweat may then be evaluated (e.g., by imaging the colorimetric membrane after it has collected and reacted with sweat). In certain variations, the devices described here may additionally comprise one or more wicking or collection portions (e.g., layers). The wicking or collection portions may, for example, be located between the colorimetric membrane and the skin surface during use, and may help to wick or collect sweat into the membrane.
In some variations, the devices described here may be in the form of a testing substrate, such as a test strip. While features and characteristics of test strips are described herein, it should be understood that these features and characteristics may also be applied to other types of testing substrates, as appropriate. Testing substrates may have any suitable configuration, including but not limited to circular, oval, square, and rectangular shapes, irregular shapes, uniform thicknesses, and non-uniform thicknesses. In some variations, a testing substrate may be in the form of a tape that may be stored and administered in a roll. The configuration of a testing substrate may depend, for example, on the particular analyte and/or fluid sample being evaluated, the anatomical characteristics of the site that contacts the testing substrate during use, and the methods (e.g., colorimetric or electrochemical) for determining the concentration of the analyte. Moreover, testing substrates may comprise any variety of different suitable materials.
In certain variations, the devices, methods, and/or kits described here may be used to collect a volume of sweat that is relatively small. For example, the volume of sweat may be less than about 10 microliters (e.g., about 5 microliters, about 3 microliters, about 1 microliter, about 0.8 microliter, about 0.5 microliter, about 0.3 microliter, about 0.1 microliter, or less). In some cases, the volume of the sweat may be less than about 1 nanoliter. The concentration of glucose in the sweat may be, for example, from about 0.1 mg/dL to about 10 mg/dL (e.g., from about 0.1 mg/dL to about 5 mg/dL). Glucose concentration may be measured at these levels or in certain variations, may be measured at levels of, for example, less than about 0.5 mg/dL.
Some variations of methods for measuring the concentration of an analyte in sweat of a subject may comprise placing a membrane (e.g., a colorimetric membrane or electrochemical strip) into contact with a skin surface of the subject so that the membrane or strip collects a volume of sweat from the skin surface, and analyzing the membrane or strip to determine the concentration of the analyte in the collected volume of sweat.
The membrane may be analyzed using any of a number of different methods. As an example, an optical system may be used to evaluate spectral emissions (e.g., when fluorescence is used), or the spectral absorption or reflection, of a colorimetric membrane. As another example, light from one or more light-emitting diodes may be applied to a colorimetric membrane, and/or one or more photodiodes may be used to detect light reflected from a colorimetric membrane. As an additional example, an optical system may be used to evaluate the intensity of spectral light reflected from a colorimetric membrane. As another example, an optical system may be used to evaluate the intensity of monochromatic light reflected from a colorimetric membrane. In certain variations, a densitometer may be used to analyze a colorimetric membrane. In some variations, light from a laser, and/or a wide spectrum light source, may be directed to a colorimetric membrane. In certain variations, a charge-coupled device (CCD), a CMOS-based detector, and/or a camera may be used to image a colorimetric membrane. Some methods may include scanning a colorimetric membrane to determine the optical density of at least one colored portion of the membrane. In certain variations, the optical transmission property of a colorimetric membrane may be evaluated.
In some variations, a colorimetric membrane may include one or more spots generated by a chemical reaction between the analyte and chemicals contained in the colorimetric membrane, where the chemical reaction occurs when the colorimetric membrane contacts the skin surface. The method may comprise discriminating the background color of the membrane from the spot(s). This may, for example, help to distinguish the target analyte(s) from contaminants. Alternatively or additionally, the appearance of spots on the colorimetric membrane may be used to estimate the sweat rate of the subject.
Contacting the membrane with the skin surface may comprise holding the membrane against the skin surface. The membrane may, for example, be in contact with the skin surface for at most about one hour (e.g., at most about 30 minutes, at most about 10 minutes, at most about 5 minutes, at most about 4 minutes, at most about 3 minutes, at most about 2 minutes, at most about 1 minute, at most about 30 seconds, at most about 20 seconds, at most about 10 seconds, at most about 5 seconds). Alternatively or additionally, the membrane may, for example, be in contact with the skin surface for at least about 1 second (e.g., at least about 5 seconds, at least about 10 seconds, at least about 20 seconds, at least about 30 seconds, at least about 1 minute, at least about 5 minutes, at least about 10 minutes, at least about 30 minutes).
In some variations, the collected volume of sweat may saturate the membrane. In certain variations, the collected volume of sweat may be collected by a portion of the membrane, and the method may comprise analyzing the portion of the membrane.
In some variations, the analyte may comprise glucose. The method may further comprise calculating or estimating the concentration of glucose in blood of the subject (e.g., using at least one algorithm that converts the concentration of glucose in sweat to the concentration of glucose in blood). In certain variations, a colorimetric membrane may comprise a first component (e.g., glucose oxidase) that converts glucose to hydrogen peroxide. The colorimetric membrane may further comprise a second component (e.g., a peroxidase, such as horseradish peroxidase) that reacts with the hydrogen peroxide. The colorimetric membrane may also comprise a third component comprising an indicator that changes color in the presence of hydrogen peroxide. The indicator may, for example, comprise an oxidizable dye or a dye couple, such as meta [3-methyl-2-benzothiazolinone]N-sulfonyl benzenesulfonate monosodium combined with 8-anilino-1-naphthalene sulfonic acid ammonium.
The method may further comprise inducing sweat prior to collecting the volume of sweat from the skin surface. Sweat may be induced, for example, by administering pilocarpine to the skin surface.
Devices, methods, and kits for sensing and/or measuring glucose in sweat are described. In general, sweat may be collected from a skin surface of a subject (e.g., a patient) using, for example, a testing substrate such as a test strip. The collected sweat may then be evaluated to determine its concentration of glucose. In some cases, the test strip may be a colorimetric test strip. For example, the test strip may comprise one or more colorimetric membranes. The membrane or membranes may contain one or more reagents that change color as a function of the concentration of glucose in the collected sweat. After sweat has been collected for a certain period of time (which may be relatively short), the color of the membrane may be measured (e.g., using optical techniques, as discussed further below). If so desired, the resulting measurement may then be correlated to a blood glucose concentration. The devices, methods, and kits will now be described below. While certain components and materials will be described, it should be understood that other appropriate components and materials may alternatively or additionally be used in some variations. For example, in certain variations, one or more components and/or materials described in U.S. patent application Ser. Nos. 11/159,587 (published as US 2006/0004271 A1) and/or 11/451,738 (published as US 2007/0027383 A1) may be used. Both of these references are incorporated herein by reference in their entirety.
Any suitable test strip or other testing substrate may be used to measure the concentration of glucose in sweat. It should be noted again that while the example of measuring the concentration of glucose in sweat and then correlating the sweat concentration to a blood concentration is discussed in detail here, the devices, methods, and kits described here may be used to measure or otherwise evaluate the concentration of any analyte in any fluid sample, as appropriate.
In certain variations, membrane (104) of test strip (100) may be a colorimetric membrane, such that the above-described measured property of the target analyte may be conveyed via color changes of the membrane. In some variations, a colorimetric membrane may comprise a substrate or matrix material and one or more reagents selected to react with or in the presence of one or more analytes. When a fluid sample comprising one or more of the specific analytes is applied to the colorimetric membrane, the color of the colorimetric membrane may change, thereby providing a visual indication of the presence of the analyte or analytes in the fluid sample. In some cases, the color change (e.g., the change in the optical absorption and/or reflection spectrum) may then be evaluated and/or measured (e.g., to determine the concentration of the analyte or analytes in the fluid sample). Examples of measurement devices that may be used to measure and/or evaluate such a change, as well as examples of colorimetric membranes, are described in further detail below.
Test strip (100) may also comprise a spreading layer. In some variations, the spreading layer may extend across a substantial portion of test strip (100), such as at least about 20% of the length of test strip (100). In certain variations, a spreading layer may extend over the entirety of a membrane (e.g., membrane (104)). In other variations, a spreading layer may only extend over one or more portions of a membrane. In variations in which a test strip comprises a membrane and a spreading layer, the membrane may be located anywhere along the length of the spreading layer. For example, the membrane may be generally centered relative to the spreading layer. The spreading layer may be used to help distribute a fluid sample on the test strip, so that the sample does not over-saturate a single location of a membrane of the test strip. Spreading layers are described in additional detail below.
Membrane (104) (and, e.g., a spreading layer) may be mounted on base (106). Base (106) may provide additional structural support and ease of handling. However, other variations of test strips may have different configurations that may or may not include a base. For example, in certain variations, instead of including a base, a test strip may comprise a spreading layer and a membrane in the form of a tape that is enclosed within a cartridge as a spool, and installed in a device requiring little or no manual handling.
Referring again to
As shown in
Referring again to
Test strips may comprise any appropriate number of layers. For example, a test strip may comprise the same number of layers as test strip (100), or may comprise fewer layers or more layers. Different exemplary variations of test strips comprising different layers, configurations, and compositions are described in further detail below.
A variation of a test region (200) of a test strip is depicted in
In some variations, a test strip may comprise one or more layers that separate a fluid sample source (e.g., a source of blood, or a skin surface) from a membrane of the test strip. For example, some variations of test strips may have two separating layers, such as a spreading layer and a porous layer (e.g., test region (240) of the test strip depicted in
The layers of a test strip may have the same thickness, or varying thicknesses throughout. For example, the test strip test region (220) shown in
The test region (240) of another variation of a test strip is shown in
The thickness of any layer in a test strip, such as one of the test strips described above, may be based on any of a number of factors. For example, the thickness of a layer may depend on the fluid characteristics of the sample to be tested, the porosity of the layer (and/or other layers), the quantity of the fluid sample required to provide an accurate detection, the sensitivity of the membrane to the target analyte, and any characteristics that may impact the fluid flow from the sample source (e.g., a skin surface). As an example, in certain variations, the thickness of the spreading layer may be selected based on the features of the fluid sample being tested, and/or based on the target analyte. In some variations, the spreading layer may have a thickness of about 5 microns to about 700 microns. The material composition of each layer may also be chosen based on optical, electrical, and/or capacitive characteristics, and/or one or more other characteristics.
As described previously, membranes that are used in the devices described here may have any appropriate size and shape (e.g., rectangular, circular, oval, etc.). In some variations, a membrane may have a thickness of about 5 microns to about 400 microns (e.g., about 5 microns to about 30 microns, about 25 microns to about 50 microns, about 50 microns to about 75 microns, about 75 microns to about 100 microns, about 100 microns to about 150 microns, about 150 microns to about 350 microns, about 200 microns to about 300 microns, about 225 microns to about 275 microns). For example, a membrane may have a thickness of about 5 microns, about 10 microns, about 25 microns, about 50 microns, about 75 microns, about 100 microns, about 115 microns, about 125 microns, about 140 microns, about 145 microns, about 150 microns, about 170 microns, about 178 microns, about 200 microns, about 250 microns, about 280 microns, about 305 microns, about 318 microns, about 330 microns, about 343 microns, or about 350 microns. In some cases, the thickness of a membrane may be selected based on the analyte that is being evaluated.
Wicking layer (254) may be composed of any appropriate absorbent material or materials, such as hydrophilic treated polycarbonate or polyester, or any other material or materials that may provide for relatively efficient fluid transfer from membrane (256) to sink layer (252). For example, wicking layer (254) may be composed of hydrophilic track etched polycarbonate, such as the polycarbonate track etch (PCTE) series of materials from Sterlitech, of Kent, Wash. Alternatively, wicking layer (254) may be composed of one or more hydrophilic monofilament open mesh fabrics, such as the PETEX® series of materials from Sefar Filtration, of Depew, N.Y. In some variations, sink layer (252) may be in the form of a chamber configured to contain excess fluid sample transferred via wicking layer (254). A sink layer (252) that acts as a chamber may be made of, for example, an injection molded thermoplastic, such as polycarbonate, acrylic, acrylonitrile butadiene styrene (ABS), or polystyrene. In some variations, sink layer (252) may comprise one or more porous materials that absorb a greater quantity of fluid than the wicking layer. An absorbent sink layer (252) may be composed of any appropriate highly absorbent material(s), such as Porex Fiber Media or Porex Sintered Porous Media from Porex Corporation of Fairburn, Ga.
Including an additional wicking layer (254) and sink layer (252) may, for example, enhance the precision and accuracy of analyte detection by membrane (256). As an example, the presence of the wicking layer and sink layer may prevent the membrane from becoming over-saturated with the fluid sample and providing an invalid measurement. For example, during use the volume of sweat produced by one sweat gland may over-saturate the reagent(s) in membrane (256). Such over-saturation may lead to an erroneous reading. However, by including a wicking layer (254) and a sink layer (252), excess sweat may be removed from membrane (256), thereby enhancing the accuracy of the sweat glucose concentration measurement. It should be understood, however, that these additional layers below the membrane are optional (e.g., depending on the saturation level of the reagent(s) and the desired detection precision).
The different layers of a test strip may be attached or otherwise coupled to each other in a variety of ways. In some variations, the individual layers may be bonded with one or more adhesives, such as pressure sensitive or heat activated acrylic adhesives, such as the ARcare® series from Adhesives Research of Glen Rock, Pa. The adhesive(s) may be transparent or opaque, as appropriate for the detection technique of the membrane. In some variations, test strips that are optically interrogated may be bonded with a transparent adhesive. In certain variations, the adhesive(s) may be applied throughout the test strip, except in the proximity of the test region. This may prevent any cross-contamination between the adhesive(s) and the sample. Additionally, in the case of methods in which a test strip is optically probed, using an opaque adhesive away from the test region may minimize optical interference. Test strip layers may also be attached to each other by electrostatic forces, welding, clip compression, hook-and-loop fasteners, and any other suitable mechanism that ensures secure and reliable fluid contact between layers.
As described above, in some variations of test strips, the fluid sample (here, sweat) initially contacts a spreading layer. Portions of different variations of spreading layers are depicted in
Some variations of spreading layers may be porous. The pores in a spreading layer may all be of substantially the same size, or at least some of the pores may differ in size. In certain variations, a pore may range in size from about 2 microns to about 350 microns (e.g., about 2 microns to about 20 microns, about 50 microns to about 250 microns, about 50 microns to about 150 microns, about 100 microns to about 150 microns). Alternatively or additionally, the pores in a spreading layer may have a mean size of about 100 microns.
As shown in
A spreading layer may comprise pores that are all of approximately the same size, or may comprise at least some pores having different sizes. Pores may be uniformly distributed throughout a spreading layer, or may be located in one or more specific regions of a spreading layer. In variations of spreading layers including pores of different sizes, the pores may be uniformly distributed, or may be distributed in a gradient, for example, such that the pores are grouped by size.
Depending on, for example, the fluid sample, the spreading layer may comprise any of a variety of different materials or combinations thereof. Examples of materials which may be suitable for use in a spreading layer include hydrophilic woven fabrics (e.g., Tetko mesh #7-280/44, from Sefar America Inc. (formerly Tetko Inc.)), sintered hydrophilic materials (e.g., from Porex Corporation, Fairburn, Ga.), and membranes (e.g., Nuclepore™ track-etched polycarbonate membranes from Whatman/GE Healthcare, such as Nuclepore #113516, 12 micron hydrophilic membrane, or the PCTE series of materials from Sterlitech, of Kent, Wash.). Membrane materials also are described, for example, in U.S. patent application Ser. Nos. 11/159,587 (published as US 2006/0004271 A1) and 11/451,738 (published as US 2007/0027383 A1), both of which were previously incorporated herein by reference in their entirety. In some variations, a spreading layer may comprise one or more heat-sintered plastics (e.g., polyethylene, polypropylene, etc.) that have been rendered hydrophilic by pre- or post-treatment with one or more surfactants. An example of such a material is a porous polyethylene treated with sodium methyl oleoyl taurate and available from Porex Corporation (Fairburn, Ga.). One advantage of this material is that it has relatively strong absorption, which can cause fluid to be drawn away from the surface, where it might otherwise transfer to objects or people it contacts. Other appropriate materials may alternatively or additionally be used.
As described above, some variations of devices described here may comprise one or more membranes. In some cases, a membrane may comprise a colorimetric membrane. For example, the membrane may be used to wick small volumes of sweat from a skin surface, to provide a matrix for one or more reagents that are to come into contact with the collected sweat, and/or to allow for optical measurement of color. Additionally or alternatively, as described above, a spreading layer or porous layer may be used to wick small volumes of sweat from a skin surface and transfer it through capillary action to the membrane.
A colorimetric membrane may comprise any of a variety of different materials. The selected materials may depend on a number of factors, such as the sample volume required for testing, color development, wicking action, optical properties, and desired shelf life. Examples of materials that may be appropriate include charged nylon membranes (e.g., from General Electric Company and Pall Corporation), polysulfone membranes (e.g., HT Tuffryn® Polysulfone Membrane Disc Filters from Pall Corporation), nitrocellulose membranes (e.g., from Sartorius AG), and the like.
In some variations, the material or materials that are used in a colorimetric membrane may be selected based on the reagent(s) that are used to detect the target analyte(s). Alternatively or additionally, the material(s) may be selected based on one or more indicator dyes that may be added to the colorimetric membrane. As an example, a membrane material may be selected based on its ability to retain certain reagent(s) and/or indicator dye(s). In some variations, a reagent may be fixedly cross-linked to the membrane material. For example, in some variations, an enzyme reagent may be immobilized using glutaraldehyde. Alternatively or additionally, a colorimetric membrane may comprise a reagent that is not fixedly cross-linked to the membrane, such that the reagent is mobile. In certain variations, membrane materials, as well as reagents and/or indicator dyes, may be selected based on their non-toxicity and safety for human contact.
As shown above, in some variations, a test strip membrane, and/or any other test strip components, may be porous. Porous membranes may comprise pores of a relatively uniform size, or may comprise pores of different sizes. In certain variations, a porous membrane may include pores having a size of about 0.2 micron to about 5 microns (e.g., about 0.45 micron to about 3 microns, about 0.65 micron to about 1.2 microns, 0.8 micron to about 1.2 microns). For example, a pore may have a size of about 0.2 micron, about 0.45 micron, about 0.65 micron, about 0.8 micron, about 1.2 microns, about 3 microns, or about 5 microns. In some variations, a porous membrane may have at least two different regions having different average pore sizes. For example, one side of a porous membrane may have an average pore size of about 0.2 micron, while an opposite side of the porous membrane may have an average pore size of about 20 microns.
A test strip may comprise one membrane or a combination of membranes, including, for example, any of the membranes described here. Any material having any suitable pore distribution (e.g., a pore distribution that promotes efficient unidirectional fluid flow) may be used in a test strip.
As discussed above, in some variations, a colorimetric membrane may comprise one or more reagents that are selected to react with one or more specific analytes to produce a certain color or colors. For example, in cases in which sweat glucose concentration is being evaluated, a colorimetric membrane may comprise one or more reagents that are selected to provide optimal performance in the range of expected sweat glucose concentrations. A colorimetric membrane may comprise, for example, any suitable combination of enzymes, dyes, and/or additives for detecting a target analyte or analytes.
As an example, some variations of colorimetric membranes for evaluating sweat glucose concentration (and blood glucose concentration therefrom) may comprise one or more reagents that react with glucose to cause a detectable color change. For example, a reagent may comprise a component (e.g., glucose oxidase) that converts glucose to hydrogen peroxide, as well as one or more components that detect the resulting hydrogen peroxide. An example of such a hydrogen peroxide-detecting component is a peroxidase (e.g., horseradish peroxidase) acting in conjunction with an indicator that changes color in the course of the reaction. The indicator may, for example, be an oxidizable dye or a dye couple. In some variations, the indicator may comprise meta [3-methyl-2-benzothiazolinone]N-sulfonyl benzenesulfonate monosodium combined with 8-anilino-1-naphthalene sulfonic acid ammonium (MBTHSB-ANS). The peroxidase may catalyze the oxidation of the indicator in the presence of hydrogen peroxide.
In certain variations in which a specific analyte is being detected, the reagent may be selected for optimal use with certain concentration ranges of that analyte. For example, in the case of glucose, the reagent may be optimized for measurement of sweat glucose concentrations in the range of 0.1 mg/dL to 10 mg/dL (e.g., 0.5 mg/dL to 10 mg/dL, 0.5 mg/dL to 4 mg/dL). Additionally, the shelf life of a reagent may, for example, be from about 6 months to about 2 years.
In certain variations, one or more reagents may be coated onto a colorimetric membrane. This may, for example, result in maximized color development while requiring application of only a minimal sample volume of sweat.
Test strips or other testing substrates may be made using any appropriate method. Typically, a test strip may be designed so that it is easy to use and/or manufacture. In certain variations, a test strip may comprise a colorimetric membrane mounted on a holder. A test strip may be designed both to position a colorimetric membrane close to a skin surface during use, and to register the colorimetric membrane with regard to a reading device (e.g., an optical device) when the color is read.
In some variations, the sample may be collected and tested using an array of wells or chambers. A top view of an example of a test well array (500) is shown in
Referring again to
There may be any number of posts (512) arranged in an array; for example, there may be 4, 9, 16, 25, 49, 64, or 100 posts.
Optionally, test well array (500) may also comprise a hydrophilic porous membrane to wick secreted sweat into well (510).
A testing device including the above-described structures and features may enable the measurement of glucose from the secretion of a single sweat gland anywhere on the skin. As a result, the testing device may allow for completion of a sweat glucose test within a few seconds. In one variation of the above described well array, a sweat bolus may be secreted onto the hydrophilic wicking layer, where the pores draw the sweat bolus into one of the chambers/wells. The sweat bolus may then react with the chemistry that was previously adsorbed into the chamber. In some variations, the chemistry may be any enzyme for glucose detection, and may be capable of changing color to indicate the quantity of glucose in the sample. In certain variations, the chemistry applied in the interior of the chamber may be a reagent used in an ELISA. Once the ELISA is completed in the chamber, an optical system may view each chamber in the array of chambers, and may detect any color changes in each of the chambers. The collected optical data may then be used to determine the quantity of glucose in the sweat bolus by downstream processing (e.g., using an external or embedded computing device), which may be recorded and/or reported to the subject.
Test well array (500) may be made using any suitable technique, for example, using photolithography methods, such as the method (620) shown in
In other variations, an array of chambers may be formed by crushing or micro-embossing crushed and uncrushed regions into a colorimetric membrane that is reactive to glucose in a sweat bolus. Other appropriate methods may also be used.
In a method that includes collecting sweat for glucose concentration analysis, once the glucose in the collected sweat has reacted with the reagent or reagents in the colorimetric membrane, any of a variety of different devices and methods may be used to measure the resulting color. In some variations, an optical system may be used to read the color of the membrane, and to correlate the reading to blood glucose concentration. The optical system may, for example, be relatively precise, easy to use, and/or inexpensive. The particular optical system that is employed may depend, for example, on the dye or dyes that are used, and/or on the pattern of color development in the membrane. In some variations, the optical system will measure one or more optical properties of the test strip, such as reflective, transmissive, absorptive, or emission properties of the membrane of the test strip. Each of these properties may require specific forms of optical illumination and detectors.
In certain variations, the optical system may comprise a light-tight chamber that is configured to retain the test strip. In some variations, the test strip may be manually placed in the chamber. In other variations, a test strip-dispensing mechanism may be integral with the optical system, thereby eliminating the need for any manual intervention. Within the light-tight chamber, the test strip may be positioned (e.g., manually, mechanically, or electrically) so that the region of interest (e.g., a test region containing the sample) is accessible for optical probing.
Optical data obtained from the test strip may be used in a number of ways. For example, optical data may be used to determine whether a sufficient quantity of fluid (e.g., sweat) is present for accurate testing, and/or may be used to analyze the quantity and/or concentration of a target analyte.
Reflectance and transmission readings at single or multiple wavelengths in both the visible and non-visible ranges may be employed. In some variations, fluorescent indicators may be used. In certain variations, relatively simple reflectance measurements may be made using any of a variety of light sources, such as single or multiple light-emitting diodes (LEDs), lasers, and/or laser diodes. Illumination may be at a specific wavelength or wavelengths, or may incorporate a broad range of wavelengths (e.g., depending on the indicator dye that is used in the colorimetric membrane). For example, certain light-emitting indicators (e.g., fluorescent indicators) may emit a stronger light signal if excited by light within a particular range of wavelengths. Some variations of optical systems may illuminate using monochromatic light, or may incorporate a filter that selects for the range(s) of wavelength light (e.g., bandpass, low pass, or high pass filters). The characteristics of the light that is used to illuminate the test strip (e.g., wavelength, intensity, exposure time) preferably are such that the dye provides reliable emissions, but does not bleach the dye indicator.
The light emitted or reflected by a dye indicator may be detected by one or more sensors configured to capture light of the emission or reflected wavelength. For example, the light emitted and/or reflected by the indicator may be detected by one or multiple photodiodes, where the photodiodes may be tuned to detect a narrow or broad band of wavelengths. Reflectance data (e.g., color data) may be obtained by at least one photodiode, as appropriate. In some variations, a wide spectrum light may be used to illuminate the membrane, and light emitted or reflected from the dye indicator may be detected by a charge-coupled device (CCD) or CMOS-based detector. For example, the emitted or reflected light may be detected by a CMOS-based camera or any digital camera which images the membrane on a pixel-by-pixel basis. Alternatively or additionally, the light may be captured on a photographic medium, such as light-sensitive film, or using a reflection densitometer. The image may be monochromatic, or may incorporate light of a range of wavelengths. In other variations, the light emitted and/or reflected from the colorimetric membrane may be recorded over a period of time, in preprogrammed intervals (e.g., using a video camera). The color of the test strip can be measured while the colorimetric membrane is reacting with the sample and changing color (on-meter dosing), or after the colorimetric membrane has completed the color change (off-meter dosing). Time-lapsed image recording may provide additional data that may be used to evaluate the fluid sample, for example, to estimate the sweat rate by monitoring the appearance of colored spots, and may be used to signal whether sufficient sample has been collected (e.g., to signal insufficient or excessive sample volume). Monitoring the appearance of the colored spots (e.g., timing and location) may be used as criteria to distinguish between sweat-derived glucose, and glucose from other sources that do not change rapidly with time.
The detector or detectors may acquire an image of a substantial portion of the test region, or may acquire an image of a small portion of the test region (e.g., a single pixel). When a focal light source is used to image the test strip, such as a laser or pin hole light source, the light beam may be scanned across the test region to generate a full image, or the test strip may be mechanically scanned through the light beam to generate a full image. The scanning procedure may be pre-programmed and/or automated, or may be manual, and subject to real-time adjustment by the user. The scan speed may be selected to achieve a certain resolution suitable for adequately precise analyte detection, and may be adjusted to reduce photo-bleaching and to acquire the image before substantial dye indicator migration. The image data acquired by the detector or detectors may be transmitted and/or stored for processing and analysis, or may be processed in real-time, as described below.
Various optical components may be included to focus light onto the test strip and/or detectors. For example, one or more lenses, mirrors, and/or filters may be employed to direct the path of illuminating and/or emitted light. The optical system and its constituent components may be configured for the illumination and detection of sub-millimeter features. For example, the optical system may be tuned to examine the concentration of an analyte (e.g., glucose) in a sample volume of less than one microliter, where the colored indicator may be on the order of tens or hundreds of microns. Focal light sources, such as lasers, may be suitable for the detection and measurement of sub-millimeter and sub-micron test strip features. The light source, optical components, and detectors may be calibrated as needed to ensure consistently precise measurements for both microliter and nanoliter sample sizes. In some optical systems, calibration may take place at programmed time intervals, or may be initiated by the user.
In certain variations of optical systems, the optical transmission property of the test region may be evaluated. For instance, the optical density of a test region may be measured using a variety of instruments, such as transmission densitometers, infrared transducers and receivers, where some instruments use a scanning optical arrangement and/or others use a fixed optical arrangement. In some optical systems, light emitted from each region of the test strip may be detected by a different detector, and the data may be combined in post-processing and analysis to form a complete image. To this end, the membrane may be scanned, in much the same way as electrophoresis gels are scanned, with the optical density of the colored portions analyzed and the transmission property correlated to glucose concentrations. The optical transmission data from the instrument may be transmitted and/or stored for processing and analysis, as described below.
Optical data collected from a test strip may be stored in a memory buffer, or in an external memory resource (e.g., flash drive, CD/DVD, magnetic tape, etc.) for post-processing. In some cases, the data may contain multiple wavelength lengths (e.g., dichromatic or trichromatic), or may be monochromatic. Monochromatic data may be analyzed for intensity, where the intensity may be denoted as an eight bit value (0 to 255, where 0 is absolute darkness and 255 is maximum brightness). Individual wavelengths of light may be extracted from wide spectrum light, and the intensity of each channel (e.g., red, green, and blue) may be analyzed similarly.
The optical data collected from a test strip may be mapped against a standardized curve or plot that correlates that optical property with the concentration of the analyte. Alternatively or additionally, the optical data collected may be compared with a calibration curve that is obtained prior to analyzing the test sample. For example, the glucose concentration in a sweat sample may be determined based on the optical density of a single wavelength channel extracted from a composite image. In some variations, the glucose concentration may be directly related to the image data. For example, the intensity value per pixel may be correlated to the analyte concentration in the fluid sample. As an example, the intensity value of a given pixel may be proportional to the concentration of glucose in a sweat sample. Alternatively, the intensity value of a given pixel may be proportional to the quantity of the glucose in a sweat sample. Experiments and examples of optical detection techniques used to detect the concentration of glucose in sweat are provided and described below.
Alternatively, sweat may be applied to the test strip before the test strip is inserted into the meter. In this variation, spot formation on the colorimetric membrane may be measured after the user's finger has been removed from the membrane. Of course, while the concentration of glucose in a sweat sample is discussed here, it should be understood that any of the devices, methods, and/or kits described here may be used to detect other analytes, and/or may be used to evaluate other types of fluid samples, as appropriate.
Some variations of a meter may also comprise an embedded optical system, configured to interface with a test strip inserted into the meter. In certain variations, the interface between the embedded optical system may include components that provide illumination of the test strip, and detect light emitted from the test strip. Examples of such components have been described above.
During use, a colorimetric test strip may be optically interrogated to determine the quantity (e.g., volume, concentration) of glucose in the sweat sample. This value may then be presented to the user on display (706). Display (706) may also prompt the user to take specific actions based on the glucose concentration in the sweat sample. For example, the user may be prompted to eat certain foods to increase blood glucose, or to take insulin to reduce blood glucose. After the glucose reading is completed, the test strip may be removed from the meter and disposed.
In some variations, an access port may be used, either as an alternative to, or in addition to, an optical window. The access port may allow for substantial contact of a fingertip to a colorimetric membrane contained in the meter. In such variations, the colorimetric membrane may be in the form of a spool that is turned as each test is conducted, where one spool accumulates used colorimetric membrane material, while another spool retains new colorimetric membrane materials. The access port would allow for unobstructed contact between a skin surface and the reactive layer.
As discussed above, in some variations, a meter or measurement device may include one or more algorithms to convert a sweat glucose concentration value to a blood glucose concentration value. For example, the meter or measurement device may comprise computer-executable code containing a calibration algorithm, which may be used to relate measured values of detected glucose to blood glucose values. In some variations, the algorithm may be a multi-point algorithm, which is typically valid for about 30 days or longer. The algorithm may necessitate multiple capillary blood glucose measurements (e.g., blood sticks) with simultaneous test strip measurements over about a one-hour to about a three-day period. This could be accomplished using a separate dedicated blood glucose meter provided with a glucose measurement device described herein, which comprises a wireless (or other suitable) link to the glucose measurement device. In this way, an automated data transfer procedure may be established, and user errors in data input may be minimized.
Once a statistically significant number of paired data points has been acquired having a sufficient range of values (e.g., covering changes in blood glucose of about 100 mg/dL), a calibration curve may be generated to relate the measured sweat glucose to blood glucose. Subjects (e.g., patients) may perform periodic calibrations checks with single blood glucose measurements, or total recalibrations as desirable or necessary.
Certain variations of glucose measurement devices may also comprise a memory for saving readings and the like. Additionally, glucose measurement devices may comprise a processor configured to access the memory and execute computer-executable code stored therein. It should be understood that glucose measurement devices may include other hardware such as an application specific integrated circuit (ASIC). In addition, glucose measurement devices may include a link (wireless, cable, or the like) to a computer. In this way, stored data may be transferred from a glucose measurement device to a computer for later analysis, etc. Alternatively or additionally, glucose measurement devices may include an interface that is compatible with a mobile device, such as a Blackberry™ or iPhone™ or iPod™ mobile device, where sweat glucose measurements may be recorded and optionally uploaded to a website or remote server in real-time. The sweat glucose data may be analyzed to determine trends in a subject's glucose levels, as well as develop predictive models to aid in glucose management. Trends and models of glucose levels as a function of any variable (i.e., time, disease progression, behavior, caloric intake, etc.) may be displayed on the website that is accessible to a medical professional monitoring the health of the subject and the subject. Glucose measurement devices may also comprise various buttons to control the various functions of the devices and to power the devices on and off when necessary.
As discussed above, test strips and related devices described here may be used to measure the concentration of glucose in sweat. A test strip comprising a porous membrane such as one of those described above may be used, for example, to collect sweat from the skin surface of a diabetic patient. The test strip may then be evaluated to estimate the blood glucose level of the diabetic patient using the collected sweat. During use, as the sweat enters the pores, one or more analytes in the sweat may react with one or more reagents in the membrane, thereby causing a color to form in the membrane. The color in the membrane may be measured and correlated to glucose concentration in the sweat. The sweat glucose concentration may then be correlated to glucose concentration in whole blood. Hence, methods described here may be used as a substitute for traditional blood glucose monitoring, where samples of blood are obtained by way of a fingerstick. One variation of a non-invasive method (820) is depicted in
As shown in
Next, the subject may hold the test strip against a skin surface (802). While it may not be necessary to do so, in some variations, the subject may attach the test strip to the skin surface. The test strip may be attached to a skin surface in any of a number of different ways. In some variations, the subject may remove a release liner from a bottom surface of the test strip to expose a pressure-sensitive adhesive that may adhere to the skin. Alternatively or additionally, other adhesives (e.g., heat-sensitive or soluble adhesives) may be used. In certain variations, the test strip may be positioned using an elastic band configured to hold the test strip in place. In some variations, the subject may tape the test strip to a skin surface (e.g., using medical tape), and/or may hold the test strip to a skin surface. In certain variations, the test strip may be held in place on the skin using a “watch-like” device. In other variations, the test strip may be retained within the meter, where the meter comprises an access port. The subject may contact a portion of skin (e.g., a finger tip) to the test strip by placing the finger through the access port and pressing against the test strip. Alternatively, the membrane portion of the test strip may protrude from the meter to ensure sufficient contact with a subject's skin.
The subject's skin surface may be engaged with the test strip for a period of time so that a sufficient quantity of sweat is collected (804). The meter may employ optical means (such as those described previously) to determine the volume of sweat collected. A program or algorithm may determine whether the collected volume is sufficient, and indicate an instruction to the subject to maintain contact with the test strip, or disengage from the test strip. In some variations, skin may be engaged with a test strip for a pre-determined amount of time that has been shown to be sufficiently long to collect a testable quantity of sweat. For example, the subject may contact his/her skin to the test strip for a period of about 2 seconds to about 30 seconds. In some variations, the subject may contact his/her skin to the test strip for about 1 minute to about 30 minutes. Alternatively or additionally, a colorimetric test strip may comprise a dye indicator that changes its optical qualities (e.g., changes color and/or opacity) to signal that a sufficient quantity of sweat sample has been collected. The optical change may be detected by an optical system, or by visual inspection.
Once the test strip has collected a sufficient volume of sweat, the subject may disengage from the test strip (806) and use a measurement device (e.g., a meter) to interrogate the test strip and quantitatively measure the sweat glucose concentration (808). In some variations, the test strip may be removed from the skin and inserted into, or otherwise contacted with, the measurement device (for example, as shown in
During interrogation (808), the sweat glucose concentration may be obtained, and if so desired, may then be used to derive a blood glucose concentration. The concentration of other analytes may also be determined, as enabled by the colorimetric membrane of the test strip. The concentration of the target analyte(s) may be output to the patient (810) using, for example, a display and/or sound speaker. Optionally, the measurement device may also issue instructions to the subject based on the concentration of the target analyte(s), where the instructions are pre-programmed by a physician or healthcare professional. The subject may respond to the test result (812). For example, based on the sweat glucose concentration and/or blood glucose concentration, the subject may be instructed to self-administer insulin. Once the testing is completed, the subject may remove the test strip from the measurement device and dispose of the test strip (814). In some variations where the test strip is retained by the measurement device, the device may then advance the used test strip and present an unused test strip for the next test.
It should be noted that in some variations, method (820) may be performed by someone other than the subject (e.g., a medical/healthcare professional) on the subject's behalf. Additionally, the above description is directed to employing test strips to obtain a sweat glucose concentration from skin surface sweat. It should be understood that method steps may be removed or added, and/or repeated as appropriate.
In some variations, the devices, methods, and kits described here may be configured for use with measuring an analyte in a specific concentration range in a fluid sample. For example, in certain variations in which sweat glucose concentration is being evaluated, the expected concentration range may be from about 0.1 mg/dL to about 10 mg/dL (e.g., about 0.5 mg/dL to about 4 mg/dL). Accordingly, the devices used to measure the sweat glucose concentration may be designed or otherwise configured to measure the concentration in that expected range. In some variations, devices, methods, and/or kits described here may be used to measure the concentration of an analyte in a fluid sample when the expected concentration is up to about 500 mg/dL (e.g., from about 0.1 mg/dL to about 500 mg/dL, from about 0.1 mg/dL to about 400 mg/dL, from about 0.1 mg/dL to about 300 mg/dL, from about 0.1 mg/dL to about 200 mg/dL, from about 0.1 mg/dL to about 100 mg/dL, from about 0.1 mg/dL to about 50 mg/dL, from about 0.1 mg/dL to about 10 mg/dL, from about 0.1 mg/dL to about 4 mg/dL, from about 0.5 mg/dL to about 500 mg/dL, from about 0.5 mg/dL to about 400 mg/dL, from about 0.5 mg/dL to about 300 mg/dL, from about 0.5 mg/dL to about 200 mg/dL, from about 0.5 mg/dL to about 100 mg/dL, from about 0.5 mg/dL to about 50 mg/dL, from about 0.5 mg/dL to about 10 mg/dL, from about 0.5 mg/dL to about 4 mg/dL, from about 50 mg/dL to about 500 mg/dL, from about 50 mg/dL to about 400 mg/dL, from about 50 mg/dL to about 300 mg/dL, from about 50 mg/dL to about 200 mg/dL, from about 50 mg/dL to about 100 mg/dL). The expected concentration range of an analyte will likely depend, for example, on the type of analyte and/or the type of fluid sample involved.
While both detection of an analyte in a fluid sample and measurement of the concentration of the analyte in the fluid sample have been described, some variations of methods may comprise detecting an analyte in a fluid sample without also measuring the concentration of the analyte in the fluid sample. Additionally, while measurement of the concentration of an analyte in a sweat sample and correlation of the sweat concentration measurement to a blood concentration measurement have been described, certain variations of methods may comprise measuring the concentration of an analyte in a first fluid sample (e.g., sweat) without later correlating the measurement to a concentration of the analyte in a second, different fluid sample (e.g., blood). For example, a diabetic may use a sweat glucose concentration measurement to determine whether to administer insulin, and therefore may not need to convert the sweat glucose concentration value to a blood glucose concentration value.
In certain variations, a relatively small sample of sweat may be collected and evaluated. This may be advantageous because, for example, it may result in a short procedure time. Moreover, it may allow relatively small test strips to be used. Such relatively small test strips may, for example, be easily transportable and/or inexpensive to produce.
In some variations, a test strip may be used to determine the concentration of glucose in a sample of sweat having a volume of about 220 picoliters to about 0.01 microliter (e.g., about 1 nanoliter to about 10 nanoliters, or about 0.001 microliter). The volume of sweat collected may be determined in part by the material composition and structure of the portion of the test strip that directly contacts the skin surface (e.g., the spreading layer, and/or the membrane). Some test strip membranes may have a structure and material composition configured to obtain the volume of one, and only one, sweat secretion of a given sweat gland. This may be achieved, for example, using an array of chambers where each chamber is capable of completing a measurement of the glucose in a sweat secretion and of retaining a given volume of a fluid sample (e.g., about 1 nanoliter of a sweat sample). The reactive dye indicator in each chamber may be capable of detecting the quantity of glucose in that given volume of sweat. The concentration of glucose may be determined by dividing the quantity of glucose measured by the volume of sample collected. This computation may be completed for a single chamber, or for multiple chambers in an array.
The following examples are intended to be illustrative and not to be limiting.
OneTouch® SureStep® test strips (from LifeScan, Inc.) were purchased from pharmacies and disassembled to obtain their colorimetric membranes. According to their package inserts, the colorimetric membranes included a reagent that reacts with glucose to cause a detectable color change.
Three different types of fluid samples were applied to the test regions of the colorimetric membranes removed from the test strips: (1) aqueous glucose solutions of known concentration, (2) contrived sweat (i.e., a solution of salt and glucose meant to simulate sweat), and (3) sweat from human subjects. The results of the glucose solution tests will be described in Example 1, and the results of the human sweat tests will be described in Example 2 below.
This experiment suggests that the glucose in the sucrose solution on the surface of the finger and thumb quickly migrated into the pores of colorimetric membrane (910), and that the colorimetric membrane may be suitable for measuring the glucose concentration of a thin film of liquid sample on the surface of skin.
A colorimetric membrane was obtained from a OneTouch® SureStep® test strip (from LifeScan, Inc.), and its ability to detect glucose in unstimulated sweat was evaluated.
First, a finger tip and thumb of a subject were washed with soap and water, and then wiped with ethanol.
Next, a portion of the colorimetric membrane was squeezed between the finger tip and thumb of a subject. The process was repeated for additional colorimetric membranes from OneTouch® SureStep® test strips, varying the amount of squeezing time. The time in which colorimetric membrane (1000) was squeezed was varied.
Colorimetric membrane (1010) was relatively lightly contacted with a skin surface, with only enough pressure to ensure physical contact.
As shown in
Referring to
By 60 seconds (
Membranes were removed from OneTouch® SureStep® test strips (from LifeScan, Inc.) as described in Example 1 above, and mounted on a base, so that they could be fed into an inkjet printer.
Inkjets and micropipettes were then used to dispense glucose solutions onto the membranes, and the color of the reacted membranes was measured.
As seen in
Color changes in a colorimetric membrane may be calibrated to a glucose concentration.
Six colorimetric membranes were obtained from a OneTouch® SureStep® test strip as described in Example 1.
A 5 microliter drop of glucose solution was applied to each test strip, where the glucose concentration was different for each strip (100, 50, 10, 5, 1, or 0 mg/dL of glucose).
After developing the colorimetric membranes for about 2 minutes, a camera module was used to capture an image of the colorimetric membranes. The camera module was IV-CCAM2, with a normal lens, backlight compensation OFF, manual shutter at a speed of 1/60 second, and white balance AWC calibrated against a white background. The colorimetric membranes were illuminated by a light source (Dolan-Jenner MI-150, quartz-halogen, 3200K, color temperature, intensity 80% of max, backlight compensation OFF), using a microscope (Optem). The light source was applied with a dual-arm fiber optic head without focusing lenses, where both fiber optic heads shine into stack of two inverted coffee filters with a hole punched in the center for optics.
The image for each of the six test strips was cropped in the center (100×100 pixel patch).
The six cropped images were analyzed with the ImagJ program (NIH) for optical density (pixel value of zero for total darkness, and 255 for maximum brightness). A profile with the six cropped images (from an image with red, green and blue channels) is shown in
The red, green, and blue channels may be extracted and analyzed separately. Thus,
The optical density for each component was plotted against glucose concentration, thereby calibrating an optical change in the colorimetric membrane with glucose concentration.
The plots from
A linear approximation was obtained for each channel, where the slope of the best-fit line indicates the sensitivity of that channel to glucose concentration. A larger slope indicates that for a given magnitude change in glucose concentration, a greater change in optical density occurs to signal that change. As shown, the red channel has the largest slope, while the blue channel has the smallest slope, which indicates that the red channel signals changes in glucose concentrations with greater sensitivity.
The sensitivity of each channel to glucose concentration is also shown in histograms depicted in
Also described here are kits. The kits may include one or more packaged test strips, either alone, or in combination with other test strips, one or more glucose measurement devices, and/or instructions. Typically the test strips may be individually packaged in sterile containers or wrappings, and may be configured for a single use. In some variations, multiple test strips may be individually sealed within one sterile container or wrapping. Additionally, some kits may comprise multiple test strips that test for the same analyte, and/or may comprise multiple test strips that test for different analytes.
While the devices, methods, and kits have been described in some detail here by way of illustration and example, such illustration and example is for purposes of clarity of understanding only. It will be readily apparent to those of ordinary skill in the art in light of the teachings herein that certain changes and modifications may be made thereto without departing from the spirit and scope of the described variations.
| Number | Date | Country | Kind |
|---|---|---|---|
| 61225153 | Jul 2009 | US | national |
| Filing Document | Filing Date | Country | Kind | 371c Date |
|---|---|---|---|---|
| PCT/US10/40845 | 7/1/2010 | WO | 00 | 1/12/2012 |
