Patent Application
20180141039
Embodiments of the disclosed subject matter include analyte detection devices. More specifically, embodiments of the disclosure are directed to portable, single use cards for quantifiable analyte detection in a sampling fluid.
Water quality and safety are major concerns for communities. Contaminated water can be global contributors to human disease, disability, and mortality. Waterways are not only used for drinking water, but also for recreation. The safety of waterways, such as rivers, lakes, oceans, and reservoirs, is of importance to water professionals and citizens alike. Spills and contamination of water can include introducing cadmium, lead, iron, zinc, arsenic, copper, and more, all of which are toxic to humans, wildlife, and plants. Damage from spills can be ongoing. Highly chlorinated and therefore corrosive water can cause lead to leach out of pipes and into publicly accessible water sources at unsafe levels. Lead exposure is correlated with severe mental and physical developmental issues, and at very high levels, lead poisoning can result in fatality.
Dissolved aquatic metals are presently measured in two distinct ways: using in-field or laboratory methods. Common laboratory methods include atomic absorption spectroscopy (AAS) and inductively coupled plasma (ICP) coupled with either emissions spectroscopy (OES) or mass spectrometry (MS). These methods are sensitive and selective but require large complicated instruments that limit the total number of samples that can be analyzed and delay the time between sample and results. As a result, in-field assays that are not as sensitive or selective are frequently used.
The in-field analysis technologies can be broken down into three categories: non-instrumented analysis (i.e., dipstick style tests), portable instrument supported analysis, and indirect analysis ‘point and shoot’. Non-instrumented tests include basic visual comparative colorimetric products such as the Hach Colorwheel™, available from Hach of Loveland, Colo.; Millipore Mquant™ and MColortest™, available from Merck KGaA; and CHEMetrics Colorimetrics and Titrimetrics, available from CHEMetrics, Inc. of Midland, Va. These solution chemistry kits require up to 19 steps of adding and mixing reactants which can introduce human error, can have a narrow dynamic range, and are inherently subjective since the result is based on human observation of visual color comparison. The subjectivity can be reduced by adding electronic ‘reading’ of the colorimetric reaction with a fluorimeter or spectrophotometer but these add anywhere from $400 to $3,000. The CHEMetrics Instrumental Colorimeter and Hach SL1000 Portable Parallel Analyzer can streamline analysis by removing the sample preparation and interference blocking steps via disposable Vacu-Vial® and Chemkey® consumables, respectively, but require a relatively high upfront investment.
Point and shoot methods, such as handheld X-Ray Fluorescence (XRF) instruments, are an alternative for solution-phase measurements. XRF instruments are often mentioned synonymously with aquatic testing, but can actually only analyze solids/soil for total elemental components and cannot differentiate between dissolved contaminants (mobile or leachable) and sequestered immobile ones. As many firms now remediate metals via chemical sequestration (i.e., converting the metals to an immobile state and leaving them in the ground), there is a need to differentiate between mobile and immobile metals, which the XRF method does not do. XRF can also be performed off-site, but this requires additional time and cost. Analysis may consume, in some cases, as much as approximately 10% of a project budget, which may amount to significant cost burdens that ultimately create backlogs and costly wait times between sampling and results. The relatively low sample throughput from third-party analyses limits on-site decision making, slows the time-to-completion, and increases overall project costs. A relatively quick, user-friendly, and inexpensive technique to analyze fluids at any location for contaminants such as dissolved metals with on-site, quantifiable results available.
Embodiments include a simple, inexpensive, user-friendly, fast, and accurate environmental, chemical, and/or bio-chemical testing device for fluid analysis.
In an Example 1, an analyte detection device, comprises: a fluid impermeable layer having a first thickness and comprising at least one inlet port having a diameter, the at least one inlet port defining a fluid pathway through the first thickness; and a reagent-hosting layer having a second thickness and comprising at least one of a chemical reagent and a bio-chemical reagent, the reagent-hosting layer configured to radially receive a sampling fluid via the fluid pathway, the sampling fluid configured to interact with the at least one of a chemical reagent and a bio-chemical reagent in the porous layer to indicate a characteristic associated with an analyte in the sampling fluid.
In an Example 2, the analyte detection device of Example 1, wherein the characteristic is at least one chosen from a chemical species, a biochemical species, a polarity, a refractive index, an oxidation-reduction potential, a redox activity, a turbidity, a pH, and combinations thereof.
In an Example 3, the analyte detection device of Example 1, wherein the characteristic is the presence or absence of the analyte in the sampling fluid.
In an Example 4, the analyte detection device of any of Examples 1-3, wherein the diameter is greater than or equal to approximately 0.5 mm and less than or equal to approximately 10 mm.
In an Example 5, the analyte detection device of any of Examples 1-4, wherein the second thickness is greater than or equal to approximately 0.05 mm and less than or equal to approximately 2.0 mm.
In an Example 6, the analyte detection device of any of Examples 1-5, wherein the sum of the first thickness and the second thickness is less than or equal to approximately 3.5 mm.
In an Example 7, the analyte detection device of any of Examples 1-6, the porous layer further comprising a detection zone, the detection zone having an additional diameter from greater than or equal to approximately 1 mm and less than or equal to approximately 500 mm.
In an Example 8, the analyte detection device of Example 7, the detection zone indicating the characteristic of the analyte via a color change.
In an Example 9, the analyte detection device of either of Examples 7 or 8, further comprising a central axis wherein the inlet port and the detection zone are concentric about the central axis.
In an Example 10, the analyte detection device of any of Examples 7-9, further comprising a barrier along a circumference of the detection zone, wherein the barrier is continuous or non-continuous.
In an Example 11, the analyte detection device of Example 10, wherein the barrier comprises at least one of a polymer, a glass, a ceramic, a wax, a paint, a cured resin, a plastic, a rubber, a thin film, a metal, a plurality of microparticles, and a plurality of nanoparticles.
In an Example 12, the analyte detection device of any of Examples 1-11, further comprising at least one additional layer, the additional layer having a third thickness, wherein the reagent-hosting layer is disposed between the fluid impermeable layer and the at least one additional layer.
In an Example 13, the analyte detection device of any of Examples 1-12, wherein the reagent-hosting layer comprises at least one of a porous medium and a fibrous medium.
In an Example 14, the analyte detection device of Example 13, wherein the reagent-hosting layer comprises at least one of a paper, a filter paper, a nitrocellulose, a glass fiber mesh, a metal screen, a metal wool, a polymer coated fiber mesh, a polymer filter media, a woven graphite, a non-woven graphite, a carbon fiber mesh, a natural textile, a synthetic textile, a cotton, a wool, and a polyester.
In an Example 15, the analyte detection device of any of Examples 1-14, wherein the fluid impermeable layer is at least partially transparent.
In an Example 16, the analyte detection device of Example 15, wherein the fluid impermeable layer comprises at least one of a polymer, a glass, a ceramic, a wax, a paint, a cured resin, a plastic encasement, a thin film, and a metal coating.
In an Example 17, the analyte detection device of any of Examples 1-16, wherein the at least one of a chemical reagent and a bio-chemical reagent in the porous layer is a material chosen from a redox dye, a solvent polarity dye, a Polypyridyl species, a plurality of nanoparticulates, a thiocarbazone, a glyoxime, a complexometric dye, a pH indicator dye, an Azo dye, and combinations thereof.
In an Example 18, an analyte detection laminate comprises: a central axis; a first layer perpendicular to the central axis and having an inlet aperture, the inlet aperture disposed about the central axis and defining a fluid pathway through the first layer; a second layer, adjacent to the first layer and in fluid communication with the fluid pathway, the second layer comprising: a reagent-hosting medium; at least one of a chemical reagent and a bio-chemical reagent disposed in or on the host medium and configured to interact with a sampling fluid received via the fluid pathway to provide an indicator of a characteristic of an analyte in the sampling fluid; a detection zone, extending radially from the central axis, for quantifying the indicator; and a third layer adjacent to the second layer, wherein the second layer is porous relative to the first and third layers.
In an Example 19, a method of making an analyte detection device comprises: forming a fluid impermeable layer having at least one inlet port defining a fluid pathway therethrough, the at least one inlet port configured to receive a sampling fluid; laminating a reagent-hosting layer to the fluid impermeable layer, the porous layer in fluid communication with the at least one inlet port, the porous layer further comprising a detection zone; and impregnating the detection zone with at least one of a chemical reagent and a bio-chemical reagent, wherein the at least one of a chemical reagent and a bio-chemical reagent is configured to interact with the sampling fluid received at the inlet port and flowing radially in the detection zone to provide an indicator of a characteristic of an analyte in the sampling fluid.
In an Example 20, the method of Example 19, further comprising quantifying the indicator.
While multiple embodiments are disclosed, still other embodiments of the presently disclosed subject matter will become apparent to those skilled in the art from the following detailed description, which shows and describes illustrative embodiments of the disclosed subject matter. Accordingly, the drawings and detailed description are to be regarded as illustrative in nature and not restrictive.
While the disclosed subject matter is amenable to various modifications and alternative forms, specific embodiments have been shown by way of example in the drawings and are described in detail below. The intention, however, is not to limit the disclosure to the particular embodiments described. On the contrary, the disclosure is intended to cover all modifications, equivalents, and alternatives falling within the scope of the disclosure as defined by the appended claims.
As the terms are used herein with respect to measurements (e.g., dimensions, characteristics, attributes, components, etc.), and ranges thereof, of tangible things (e.g., products, inventory, etc.) and/or intangible things (e.g., data, electronic representations of currency, accounts, information, portions of things (e.g., percentages, fractions), calculations, data models, dynamic system models, algorithms, parameters, etc.), “about” and “approximately” may be used, interchangeably, to refer to a measurement that includes the stated measurement and that also includes any measurements that are reasonably close to the stated measurement, but that may differ by a reasonably small amount such as will be understood, and readily ascertained, by individuals having ordinary skill in the relevant arts to be attributable to measurement error; differences in measurement and/or manufacturing equipment calibration; human error in reading and/or setting measurements; adjustments made to optimize performance and/or structural parameters in view of other measurements (e.g., measurements associated with other things); particular implementation scenarios; imprecise adjustment and/or manipulation of things, settings, and/or measurements by a person, a computing device, and/or a machine; system tolerances; control loops; machine-learning; foreseeable variations (e.g., statistically insignificant variations, chaotic variations, system and/or model instabilities, etc.); preferences; and/or the like.
Although the term “block” may be used herein to connote different elements illustratively employed, the term should not be interpreted as implying any requirement of, or particular order among or between, various blocks disclosed herein. Similarly, although illustrative methods may be represented by one or more drawings (e.g., flow diagrams, communication flows, etc.), the drawings should not be interpreted as implying any requirement of, or particular order among or between, various steps disclosed herein. However, certain embodiments may require certain steps and/or certain orders between certain steps, as may be explicitly described herein and/or as may be understood from the nature of the steps themselves (e.g., the performance of some steps may depend on the outcome of a previous step). Additionally, a “set,” “subset,” or “group” of items (e.g., inputs, algorithms, data values, etc.) may include one or more items, and, similarly, a subset or subgroup of items may include one or more items. A “plurality” means more than one.
As used herein, the term “based on” is not meant to be restrictive, but rather indicates that a determination, identification, prediction, calculation, and/or the like, is performed by using, at least, the term following “based on” as an input. For example, predicting an outcome based on a particular piece of information may additionally, or alternatively, base the same determination on another piece of information.
The terms “up,” “upper,” and “upward,” and variations thereof, are used throughout this disclosure for the sole purpose of clarity of description and are only intended to refer to a relative direction (i.e., a certain direction that is to be distinguished from another direction), and are not meant to be interpreted to mean an absolute direction. Similarly, the terms “down,” “lower,” and “downward,” and variations thereof, are used throughout this disclosure for the sole purpose of clarity of description and are only intended to refer to a relative direction that is at least approximately opposite a direction referred to by one or more of the terms “up,” “upper,” and “upward,” and variations thereof.
Embodiments of the disclosed subject matter include analyte detection systems. Embodiments of an analyte detection system may include an analyte detection device having media hosting a reagent. A sampling fluid may be introduced to the analyte detection device, which facilitates a radial dispersion of the sampling fluid. As the analyte in the sampling fluid encounters the reagent, a color change is produced in a detection zone. The user may determine one or more characteristics of the analyte (and/or the sampling fluid) by measuring a diameter, area, and/or the like, of the color change. In embodiments, the system may also may include, e.g., a ruler, a mobile phone, a computer, a communications network, and/or any number of other devices, users, and/or the like for fluid analysis to provide quantifiable results. Embodiments of the systems and devices disclosed herein may be configured to provide users with quantifiable results within minutes, thus providing information that may, in embodiments, facilitate keeping people and communities safer. Embodiments of the device permit detection and/or characterization of various analytes from various fluid sources on-site and in real time. Fluid samples collected using embodiments of the device can be subsequently processed (e.g., by image analysis) and/or used to generate data regarding fluid quality (e.g., water) and characteristics (e.g., contaminants), which may be used, for example, to establish whether water is safe for drinking, farming, bathing, and/or the like.
Embodiments of the present disclosure take advantage of recent advances in consumer electronics and opensource software platforms. In accordance with these embodiments, the present disclosure provides an analyte detection device that is economical, compact, lightweight, and disposable as compared with conventional devices. Data can be collected manually and/or by using a mobile device application such as, for example, the “Water Chemistry” app (available in the Apple App Store or Google Play), and provided by Access Sensor Technologies, of Fort Collins, Colo., USA.
Throughout this disclosure, the term “radial” and/or “radially” can mean extending along a radius, or extending outwardly from a center point to an arc or segment of a circle (or approximate circle), and/or the like. While this disclosure discusses using the analyte detection device to analyze the presence (and/or absence) of analytes in a sampling fluid such as water, embodiments of the analyte detection device may also, or alternatively, be used to characterize particles in other fluid media including, but not limited to, a liquid, a plasma, and/or the like.
According to embodiments, the analyte detection device includes a fluid impermeable layer having at least one inlet port defined therethrough. The inlet port may be, for example, an aperture through the thickness of the fluid impermeable layer. The inlet port defines a fluid pathway, through the thickness of the fluid impermeable layer to allow a sampling fluid to enter the device. In embodiments, the device further includes a reagent-hosting layer (e.g., a porous layer) adjacent to the fluid impermeable layer. The layers may be placed next to one another directly or otherwise associated with each other via attachment by lamination and/or adhesion. The reagent-hosting layer, which may be a fibrous or non-fibrous (e.g., cellular, etc.) medium, hosts at least one of a chemical reagent and a bio-chemical reagent.
One or more reagents may be loaded onto (and/or into) the reagent-hosting layer. Loading the reagent-hosting layer may include embedding, impregnating, coating, and/or otherwise depositing the reagent-hosting layer with the reagent or reagents. The reagents may be dispersed evenly through the host medium or may be anisotropically distributed. An example of anisotropic distribution may be reagents materially coating the upper and/or lower surface layer of a porous medium.
In operation, a sampling fluid enters the reagent-hosting layer via the inlet port. The reagent-hosting layer receives the sampling fluid via the fluid pathway and the fluid is radially distributed in a detection zone. The sampling fluid interacts with the at least one of a chemical reagent and a bio-chemical reagent in the reagent-hosting layer to indicate a characteristic (e.g., presence or absence, concentration, etc.) of an analyte in the sampling fluid. The indicator may be a visual change such as a color change or other change detectable by the eye or by image analysis techniques known in the art. The concentration of the indicator present, as determined in parts per million (ppm) for example, may be quantified by measuring the diameter (or radius) of the visual indicator in the detection zone. In embodiments, the visual indicator may be measured manually and/or via image analysis for example using a hand held device such as a smart phone equipped with a suitable application.
In embodiments, the top layer 12 may be a fluid impermeable layer. The fluid impermeable layer may be formed of any suitable material and the examples herein are non-limiting. In embodiments, for example, the top layer 12 may include at least one material chosen from a polymer, a glass, a ceramic, a wax, a paint, a cured resin, a metal, or combinations thereof. In embodiments, the top layer 12 is at least partially transparent, which means that the fluid impermeable layer 12 may be sufficiently transparent to facilitate optical detection, through the top layer 12 (e.g., by eyesight, camera, etc.) of an indicator of a characteristic of an analyte and/or sampling fluid. In embodiments, the top layer 12 may be or include a colored film or layer to improve optical contrast. Alternatively or additionally, the top layer 12 may include markings on the surface or through the thickness thereby partially obscuring the transparency of the impermeable layer.
The inlet port 14, having diameter d1, also includes a thickness t1, which, in the case of the inlet port 14, refers to the depth of the port (corresponding to the thickness of the top layer 12). In embodiments, diameter d1 is greater than or equal to approximately 0.5 mm and less than or equal to approximately 10 mm. In embodiments, diameter d1 is approximately 0.5 mm, or approximately 1 mm, or approximately 1.5 mm, or approximately 2 mm, or approximately 2.5 mm, or approximately 3 mm, or approximately 4 mm, or approximately 5 mm, or approximately 6 mm, or approximately 7 mm, or approximately 8 mm, or approximately 9 mm, or approximately 10 mm. In embodiments, diameter d1 is approximately 2 mm. The inlet port 14 allows fluid to enter the device 10 in a controlled manner.
In embodiments, the inlet port 14 may vary in shape, location, and relative size with respect to the rest of device 10. Shapes and sizes of the inlet port may be varied to influence the direction, flow rate, and/or the two-dimensional or three-dimensional flow pattern of fluid that is delivered to the reagent-hosting layer 16. A multitude of inlet ports may be used rather than a single inlet port. Embodiments of the device 10 include additional inlet ports. In embodiments, the device 10 includes at least one inlet port. In embodiments, the device 10 may include at least two inlet ports, at least three inlet ports, at least four inlet ports, or more. In embodiments, the device 10 may include at least two layers, at least three layers, at least four layers, or more. In embodiments, for example, the device 10 may include at most ten layers.
Disposed adjacent to a lower surface 12b of the top layer 12 is a reagent-hosting layer 16. In embodiments, the reagent-hosting layer 16 may be, include, or be included in a porous medium that allows for radial fluid transport away from the inlet port 14. According to embodiments, the reagent-hosting layer 16 may be porous, fibrous, and/or the like. The reagent-hosting layer 16 includes a thickness t2 and a detection zone 20. In embodiments, the thickness t2 is greater than or equal to approximately 0.05 mm and less than or equal to approximately 2.0 mm. In embodiments, thickness t2 is approximately 0.05 mm, or approximately 0.10 mm, or approximately 0.12, or approximately 0.14 mm, or approximately 0.16 mm, or approximately 0.18 mm, or approximately 0.2 mm, or approximately 0.3 mm, or approximately 0.4 mm, or approximately 0.5 mm, or approximately 1 mm, or approximately 1.5 mm, or approximately 2.0 mm. In embodiments, thickness t2 is approximately 0.18 mm.
In embodiments, the detection zone 20 is an area and/or volume of the reagent-hosting layer 16 that includes at least one reagent disposed thereon and/or therein. The detection zone 20 may be configured to be analyzed via image analysis to identify characteristics of a sampling fluid and/or one or more analytes therein. The detection zone 20 may include a diameter and/or an area. In embodiments, the detection zone 20 may include at least a portion of the area of the reagent-hosting layer 16. In embodiments, the detection zone 20 may be disposed concentrically about a central axis and may include a diameter d2. In embodiments, diameter d2 is greater than or equal to approximately 1 mm and less than or equal to approximately 500 mm. In embodiments, diameter d2 is greater than or equal to approximately 10 mm and less than or equal to approximately 100 mm. In embodiments, diameter d2 is greater than or equal to approximately 20 mm and less than or equal to approximately 60 mm. In embodiments, diameter d2 is approximately 5 mm, or approximately 10 mm, or approximately 20 mm, or approximately 40 mm, or approximately 60 mm, or approximately 80 mm, or approximately 100 mm, or approximately 200 mm, or approximately 300 mm, or approximately 400 mm, or approximately 500. In embodiments, diameter d2 is approximately 40 mm.
In embodiments, for example, the detection zone 20 may facilitate detecting the presence of an analyte (if any) in the sampling fluid. In embodiments, a characteristic of the analyte (e.g., the presence or absence of the analyte, the concentration of the analyte, etc.) is detected via a color change. Color change is just one example of a visual indicator. The visual indicator may be quantified by manual measurement (e.g., by measuring a radial distance or diameter by ruler or micrometer) and/or via image analysis. According to embodiments, image analysis may be performed using any number of different types of computing devices such as, for example, a laptop, a workstation, a mobile device, and/or the like. In embodiments, for example, an application may be instantiated on a smartphone that utilizes the integrated smartphone camera. Upon opening the application, the user may be prompted, for example, to select an analyte to measure (e.g., via a menu of analytes), a fluid property to measure, and/or the like. In response to selecting an analyte, the application may present a user interface that includes a virtual detection zone overlaying a dynamic image provided by the camera. The user may adjust the smartphone and/or camera such that the detection zone of the device 10 (e.g., as delineated by a visible barrier, a different color, etc.) is completely covered by the virtual detection zone. Upon achieving this positioning, the user may provide an input to the smartphone that causes the smartphone to take a picture, capturing an image of the detection zone of the device 10.
The application (or a related application or application component) may be configured to analyze the image to determine an area of the detection zone that has undergone a color change as a result of an analyte reacting with a reagent. In embodiments, this determination may be made by analyzing the image to identify a region (e.g., an area) of the detection zone that has a different color than the remaining portion of the detection zone. Upon determining the area of color change, the application may be configured to calculate (e.g., based on a determined radius, area, etc.) a characteristic of the analyte and/or sampling fluid. In embodiments, the application may be configured, for example, to measure the area of the color change inside the detection zone and to determine, based on the measured area, the concentration (and/or other characteristic) of the analyte. The application may, for example, present the calculated characteristic to the user such as, for example, by displaying the concentration as parts per million.
In embodiments, this image analysis may be performed using any number of different digital image analysis techniques known to those having skill in the relevant arts. Such techniques may include, for example, edge detection techniques, foreground detection techniques, image segmentation techniques, classifiers, and/or the like. In embodiments, machine learning may be utilized to enhance the accuracy of the image analysis over time. Further, in embodiments, the device 10 may be formed having one or more position indicators (e.g., a dot in the middle of the detection zone, markings disposed around the periphery of the detection zone, etc.) that can be aligned, via the user interface of the application, with corresponding virtual position indicators to ensure proper alignment of the detection zone with the virtual detection zone. In embodiments, image analysis applications may be instantiated on devices separate from the imaging device.
Chemical and/or bio-chemical reagents 22 may be supported by a porous medium of the reagent-hosting layer 16 and may be immobilized or partially immobilized. In embodiments, chemical and/or biochemical reagents 22 may be immobilized using any number of different methods. In embodiments, for example, immobilization may be achieved by selecting reagents largely insoluble in the fluid to be analyzed. For aqueous fluid analysis, reagents may be immobilized by ion-pairing water soluble ionic reagents with water insoluble counter ions. Examples of ion-pairing useful for the invention are combinations of anionic colorimetric reagents such as Zincon (2-Carboxy-2′-hydroxy-5′-sulfoformazyl-benzene monosodium salt), Bromothymol Blue sodium salt (3′,3″-dibromothymolsulfonephthalein sodium salt), Bathophenanthrolinedisulfonic acid disodium salt in combination with hydrophobic cations such as tetrabutylammonium, tetrahexylammonium, tetraoctylamonium ions. These examples are not a complete list of ion-pairing combinations.
Alternatively, ion pairing may be achieved using a hydrophobic (or lipophilic) anion that substantially immobilizes the reagents or the reagent-analyte complex. One non-limiting example of this approach is the use of hexafluorophosphate anions to precipitate the colored divalent iron tris 1,10-phenanthroline complex. This method produces, upon reaction of the reagent with analytes (if present) in the sampling fluid, an example of a visual indicator to provide quantifiable results. Other indicators include any detectable change, such as but not limited to, at least one of a visual change in color or visual indicator, a fluorescence yield, an electrochemical property, an electromagnetic absorbance, an electromagnetic reflectance, an electromagnetic scattering, an electrical conductivity, an acoustic or vibrational impedance, or combinations thereof. As the analytes encounter and react with the reagents loaded in the porous medium they may be largely removed from the fluid. Indicators may represent detected changes in at least one of chemical species, polarity, refractive index, oxidation-reduction potential or redox activity, turbidity, pH, and biochemical species (e.g. enzyme). Reagents deposited on the porous medium may be dispersed evenly throughout or may be anisotropically distributed. An example of anisotropic distribution may be reagents materially coating the upper or lower surface of the porous medium. Reagent distribution may be varied to control the response of the test such that reagents are loaded on the porous medium that vary over the area of the device. A number of reagents may be used in order to detect more than one analyte present in the fluid. These reagents may be combined over the same area (or volumes) or kept separate such that isolated analytes are detected in unique locations on the device.
Reagents useful according to embodiments include reagents to detect changes in at least one of chemical species, polarity, refractive index, oxidation-reduction potential or redox activity, turbidity, pH, and biochemical species (e.g. enzyme). Examples of redox indicator dyes include: 2,6-Dichlorophenolindophenol for vitamin K or vitamin C detection, 3,3′-Dimethylnaphthidine for bromate detection. Examples of solvent polarity dyes include azomerocyanine betaines such as 2,6-Diphenyl-4-(2,4,6-triphenyl-1-pyridinio)phenolate (Reichardt's Dye). Examples of element and species specific colorimetric indicators include: polypyridyl species (e.g. bipyridine, terpyridine and phenanthroline and chemically modified derivatives of those) for the determination of metal ions. Nanoparticulates are useful according to embodiments as direct indicators for refractive index changes. Nanoparticulates with chemically modified surfaces are useful according to embodiments as chemical and biochemical reagents, for example, nanoparticles of gold (Au) and silver (Ag). Examples of reagents suitable for the detection of lead (Pb), zinc (Zn), and cadmium (Cd) include thiocarbazones such as diphenylthiocarbazone. Examples of reagents suitable for the detection of nickel include glyoximes such as dimethylglyoxime. Examples of reagents suitable for the detection of metals include complexometric dyes such as xylenol organge. Examples of reagents suitable for the detection of pH include indicator dyes such as: bromocresol green, phenol red, methyl red. Examples of reagents suitable for the determination of β-glucuronidase enzyme include biochemical enzyme substrates such as 5-Bromo-4-Chloro-3-Indolyl β-D-Glucoronide for the determination of β-glucuronidase enzyme. Examples of reagents suitable for the determination of zinc (Zn) or copper (Cu) include azo dyes such as 2,5-Diphenyl-3-(1-naphthyl) tetrazolium chloride (Tetrazolium Violet) as metabolic indicator, 2-Carboxy-2′-hydroxy-5′-sulfoformazylbenzene monosodium salt (Zincon). Examples of reagents suitable for the detection of organic and metal ion include molecules of a combination of chemical classes such as: 1-(2-Pyridylazo)-2-naphthol and 4-(2-Pyridylazo)resorcinol) as non-selective metal indicators, 2,4,6-Tri(2-pyridyl)-s-triazine for the determination of iron (Fe), 8-Hydroxyquinoline for the determination of aluminum (Al); 1-(4-Nitrophenyl)-3-(4-phenylazophenyl)triazene (Cadion) for determination of cadmium (Cd) and nickel (Ni).
In embodiments, the detection zone 20 may include the entire reagent-hosting layer 16 or a portion of the reagent-hosting layer 16. The detection zone may include any number of different shapes such as, for example, a circular shape, an oval shape, a rectangular shape, and/or the like. In embodiments, the reagent-hosting layer 16 allows for fluid transport through capillary action or by means of an applied force such as elevated pressure at the inlet or a reduced pressure located radially from the inlet 14. The reagent-hosting layer 16 further includes one or more reagents 22 (e.g., chemical reagents and/or bio-chemical reagents) shown schematically throughout thickness t2 and the detection zone 20 of layer 16. Reagents 22 react with analytes present in a sampling fluid introduced into the reagent-hosting layer 16 via the inlet port 14.
According to embodiments, the reagent-hosting layer 16 may be a porous and/or fibrous medium that is associated with, or otherwise affixed to, the top layer 12. The reagent-hosting layer 16 may be formed of any suitable material and the examples herein are non-limiting. In embodiments, the reagent-hosting layer 16 may include at least one material chosen from a filter paper, a nitrocellulose, a glass fiber mesh, a metal screen, a metal wool, a polymer coated fiber mesh, a polymer filter media, a woven or non-woven graphite, a woven or non-woven carbon fiber mesh, a natural and/or synthetic textile materials such as a cotton, a wool or a polyester, or combinations thereof.
As shown in
According to embodiments, each layer 12, 16, and 18 includes opposite surfaces referred to herein as upper and lower surfaces, though these terms, as explained above, are used only for clarity of description and are not meant to impart any particular required or desired orientation of the device 10 or its components. In embodiments, one or more of the surfaces of the layers may be at least approximately planar, while, in embodiments, one or more of the surfaces of the layers may be non-planar (e.g., concave, convex, etc.). As shown, the top layer 12 includes an upper surface 12a and a lower surface 12b; the reagent-hosting layer 16 includes an upper surface 16a and a lower surface 16b; and the support layer 18 includes an upper surface 18a and a lower surface 18b.
In embodiments, at least two layers are used to form a laminate. That is, in other words, at least two layers form a laminated structure or material made of layers fixed together to form a detection device. For example, the device 10, also referred to interchangeably herein as a laminate 10 or a card 10, includes at least layer 12 and layer 16. In embodiments, the layers may be fixed together using adhesives applied to at least one of the surfaces 12b, 16a, 16b, 18a, or by other such manner as known to those of skill in the art. In embodiments, for example, the top layer 12 may be affixed to the reagent-hosting layer 16 through permanent (e.g. glue, resin bonding), semi-permanent (e.g. electrostatic cohesion), or temporary means (e.g. external pressure applied to the device to maintain contact). Similarly, the support layer 18 may be affixed to the reagent-hosting layer 16 through permanent (e.g. glue, resin bonding), semi-permanent (e.g. electrostatic cohesion), or temporary means (e.g. external pressure applied to the device to maintain contact).
According to embodiments, a detection device 10 constructed in accordance with embodiments described herein to be a laminate (e.g., card) may be flexible (e.g., much like a laminated piece of paper). In other embodiments, the detection device 10 may be at least partially inflexible, formed using at least one of a rigid top layer 12 and a rigid support layer 18, in which case the layers 12 and 18 form an encasement of the reagent-hosting layer 16. In embodiments, the layers 12 and 18 may be configured to be removably coupled to one another to encase the reagent-hosting layer 16 so that, for example, the encasement can be reused, such as by replacing the reagent-hosting layer 16 with a new and/or different reagent-hosting layer 16 after use.
According to embodiments, the device 10 has dimensions advantageously suited for portability and ease of use. In some embodiments, the device 10 is approximately the same size as (or smaller than) a credit card. In embodiments, the device 10 has a total thickness, tT, which is the sum of the at least two layers adjacently disposed. In embodiments, the total thickness tT is greater than or equal to approximately 0.2 mm and less than or equal to approximately 5.0 mm. In embodiments, the total thickness tT is less than or equal to approximately 3.5 mm, or less than or equal to approximately 4.0, or less than or equal to approximately 4.5 mm, or less than or equal to approximately 5 mm. In embodiments, the device 10 has a shape characterized by a generally flat or planar area, the planar area chosen from at least one of a polygon, a rectangle, a square, a circle, an oval, an ellipse, or a triangle.
The illustrative analyte detection device 10 shown in
As shown, the top layer 32 includes an inlet port 40, disposed about axis A and having a diameter d1, in fluid communication with reagent-hosting layer 34, in accordance with embodiments of the subject matter disclosed herein. In operation, sampling fluid 42 is introduced to the inlet port 40, as illustrated by arrow 44. In embodiments, the fluid 42 is introduced by a pipette or vial (not shown), which may be of the small or miniature, plastic and disposable variety. In embodiments, the pipette or vial has a capacity of about 100 although sampling size may vary according to reagent/analyte combinations and design of analyte detection device. In embodiments, the vial includes a cap or cover. In embodiments, the vial is capped in order to homogenize the sampling fluid by shaking or other means. Alternatively in embodiments, the inlet port 40 may be exposed to the sampling fluid 42 by dipping the device 30 into a sampling fluid 42. In embodiments, for example, the device 30 may be dipped into the sampling fluid for a pre-determined time (e.g., a few seconds) or until a detection zone 46 of the reagent-hosting layer 34 absorbs as much of the sampling fluid 42 that it can. When using dipping as a method of exposure to sampling fluid, a third impermeable support layer (e.g., the support layer 18 depicted in
As shown in
The illustrative analyte detection device 30 shown in
In embodiments, the barrier 52 may be configured to impede fluid transport in the device, particularly in the reagent-hosting layer 50, containing a volume of sampling fluid within the detection zone 54. One or more barriers may provide a complete impediment to fluid flow or, in embodiments, may reduce the flow rate of sampling fluid flowing radially through the reagent-hosting layer 50. In embodiments, the barrier 52 may serve as a physical and/or chemical barrier that may inhibit flow of sampling fluid outwardly beyond the barrier 52 and/or beyond the detection zone 54. In embodiments, the barrier 52 may serve as a physical and/or chemical barrier that may inhibit impregnation (or otherwise) of one or more reagents 56 beyond the detection zone 54. As shown in
In embodiments, one or more of the barriers 52 and 62 may be disposed along a circumference of the detection zone, where the barrier is continuous or non-continuous. The barrier geometry may take the form of any advantageous shape that benefits device performance. The barrier may only partially bind the lateral flow of fluid. The barrier may be semi-permeable, which may reduce the rate of fluid flow but not completely cease it. Examples of barrier materials used in the porous medium include at least one material chosen from a polymer, a glass, a ceramic, a wax, a paint, a cured resin, a plastic, a rubber, a thin film, a metal, metal oxide materials, solder or solder paste, a plurality of microparticles, a plurality of nanoparticles, and combinations thereof. Using particles as a non-continuous barrier includes the particles filling pores in the reagent-hosting layer 16 to create a barrier to flow. Alternatively, another means of creating a barrier to flow is to remove or partially remove the porous medium of layer 16 itself in order to restrict flow.
In embodiments, the barrier 52, for example, serves as an optical or visual tool for identifying the detection zone and may aid in image analysis. For example, in embodiments, an image analysis application such as embodiments discussed above may be configured to provide, via a user interface, a virtual barrier, which represents an outer border of a detection zone, and which may be aligned, using a camera, with an actual barrier on a device 10 so as to facilitate image analysis.
The illustrative reagent-hosting layers 50 and 60 shown in
According to embodiments, the top layer 112 may be impermeable, and the reagent-hosting layer 116 may be porous and impregnated, or otherwise loaded, with chemical and/or bio-chemical reagents. The device 100 includes detection zones 120a and 120b; and the reagents disposed within the detection zone 120a may be the same as, or different than, the reagents disposed within the detection zone 120b. The device 100 may optionally include at least one additional layer, e.g., a support layer (e.g., the support layer 18 depicted in
The illustrative analyte detection device card 100 shown in
According to embodiments, the device 200 includes at least two layers, including a top layer 212 having at least one inlet port and a reagent-hosting layer 216 disposed adjacent to the top layer 212. The inlet ports 214a and 214b may be concentrically disposed about individual axes (e.g., the axis A depicted in
According to embodiments, devices described herein may facilitate determination of analytes in sampling fluid. Non-limiting examples of analytes include at least one analyte chosen from a proton concentration (i.e. pH value), a metal concentration (e.g. Calcium, Magnesium, Aluminum, Iron, Lead, Zinc, Copper, Cadmium, Manganese, Chromium, Nickel), a non-metallic inorganic species (e.g. Chloride, Chlorite, Hypochlorite, Nitrate, Nitrite, Ammonia), an organic species (e.g. Ethanol, Glucose, Acetic Acid, Pesticides, Hormones), and a biochemical compounds (e.g. enzymes, enzyme substrates). While the preceding analytes are presented as illustrative examples, the listing is not all-encompassing of the species or properties that may be detected using embodiments of the device or method of the present disclosure.
The device may include an inlet port that restricts the flow of fluid into the device. Fluid may be driven through the porous medium by capillary action and/or by using a positive or negative pressure to actively drive fluid through the medium. Fluid may be delivered to the device using a vial or pipette. Alternatively, fluid may be delivered without restricting the fluid volume by dropping fluid on to the top of the inlet. Methods of using a timer also may be used to create a consistent fluid volume delivered to the porous medium by removing excess fluid once a set time has expired. Alternatively or in addition to, a barrier within layer 16 allows fluid delivery of a fixed volume to the device.
As fluid enters the device, the analytes present in the fluid encounter the reagents supported by the reagent-hosting layer to provide an indicator. The analytes react with the reagents yielding a detectable change and/or visual indicator as detailed above. As the analytes encounter and react with the reagents loaded in the reagent-hosting layer, they may be largely removed from the fluid. Once the analyte has been largely removed from the fluid, the fluid may continue to propagate radially from the inlet disposed about axis A but without a detectable change as described above. The termination of the detectable change serves as an endpoint of the reaction between the reagent(s) and analyte(s). The termination of the detectable change is measurable (e.g., radial distance or diameter).
To quantify the analyte(s) present in the fluid the geometric properties of the detectable change may be measured. In embodiments where a circular inlet guides fluid to a porous medium with a colorimetric indicator reagent that is unbounded in the plane of the porous medium, a largely circular pattern develops. Once the fluid has ceased to flow, the area (or diameter or radius or geometric derivations of those parameters) of the color formed may be related to the concentration of the analyte in the fluid. Typically, a calibration curve is constructed by delivering fluids with known concentration of analytes to individual devices. The geometric properties of the area where analyte has reacted with reagents can be quantified a number of different ways. A ruler, or other geometric measurement tool, may be used to measure the geometric dimensions. Additionally, images of the device may be analyzed using analysis algorithms based on the detectable changes. The algorithms may be executed by computers (e.g., smartphones, tablets, workstations, laptops, etc.) or conducted by users.
According to embodiments, the top layer 306 may be impermeable, and the reagent-hosting layer 310 may be porous and impregnated, or otherwise loaded, with chemical and/or bio-chemical reagents. That is, for example, embodiments of the reagent-hosting layer 310 may be loaded with a chemical reagent configured to react with iron in a sampling fluid, thereby indicating a characteristic (e.g., a presence and/or concentration) of iron in the sampling fluid. The card 300 may optionally include at least one additional layer, e.g., a support layer (e.g., the support layer 18 depicted in
In the illustrated embodiments of
According to embodiments, the diameter 318 may refer to a single diameter measurement, multiple diameter measurements, an aggregation of multiple diameter measurements (e.g., an average diameter measurement, a normalized diameter measurement), and/or the like (any or all of which may be referred to simply as “a diameter” or “diameter measurement” or similar, in various embodiments). In embodiments, the concentration of iron may be determined by comparing the diameter to the response of known standards, which may be embodied, for example, in a table, a graph, a curve, a chart, and/or the like. For example,
In operation, for example, a user may introduce a sampling fluid to the inlet port 308 of the card 300, which may result in a reaction that creates the region 316 of color change. In embodiments, the user may measure a diameter 318 of the region 316 using a ruler or other manual instrument. In embodiments, the user may instantiate an application on a computing device (e.g., a mobile device such as a smartphone) and use the device to acquire an image of the QR code 314. The application may be configured to receive the image of the QR code 314 from the imaging device and to determine, based on the image of the QR code 314, that the card 300 is configured to facilitate determining a concentration of iron in a sampling fluid. The application may be configured to, in response to determining the analyte associated with the card 300 (and/or the type of characteristic to be determined), access a calibration curve associated with iron. The application may, via any number of different image analysis techniques, determine a diameter of the region 316 of color change, and to compare the diameter to the calibration curve to determine the concentration of iron in the sampling fluid. In response to making this determination, in embodiments, the application may be configured to provide a representation of the concentration to a user such as, for example, by displaying the concentration on a graphical user interface (GUI). In embodiments, the application may be configured to store the determined concentration, use the determined concentration to determine some other characteristic of the iron and/or sampling fluid, transmit the determined concentration (and/or information associated therewith) to another device (e.g., another mobile device, a server, etc.), and/or the like.
The illustrative analyte detection device card 300 and graph 400 shown in
The system 500 may further include a computing device 504 configured to obtain an image of a detection zone of the analyte detection device 502, determine a diameter of a region of a color change within the detection zone, and determine, based on the diameter, one or more characteristics of the analyte and/or the sampling fluid, as described in association with embodiments described herein. The computing device 504 may include any type of computing device suitable for implementing aspects of embodiments of the disclosed subject matter. Examples of computing devices include specialized computing devices or general-purpose computing devices such “workstations,” “servers,” “laptops,” “desktops,” “tablet computers,” “hand-held devices,” “smartphones,” “general-purpose graphics processing units (GPGPUs),” and the like, all of which are contemplated within the scope of
In embodiments, the computing device 504 includes a bus 506 that, directly and/or indirectly, couples the following devices: a processor 508, a memory 510, an input/output (I/O) port 512, an I/O component 514, and a power supply 516. Any number of additional components, different components, and/or combinations of components may also be included in the computing device 504. The I/O component 514 may include a presentation component configured to present information to a user such as, for example, a display device, a speaker, a printing device, and/or the like, and/or an input component such as, for example, a microphone, a joystick, a satellite dish, a scanner, a printer, a wireless device, a keyboard, a pen, a voice input device, a touch input device, a touch-screen device, an interactive display device, a mouse, and/or the like.
The bus 506 represents what may be one or more busses (such as, for example, an address bus, data bus, or combination thereof). Similarly, in embodiments, the computing device 504 may include a number of processors 508, a number of memory components 510, a number of I/O ports 512, a number of I/O components 514, and/or a number of power supplies 516. Additionally any number of these components, or combinations thereof, may be distributed and/or duplicated across a number of computing devices.
In embodiments, the memory 510 includes computer-readable media in the form of volatile and/or nonvolatile memory and may be removable, nonremovable, or a combination thereof. Media examples include Random Access Memory (RAM); Read Only Memory (ROM); Electronically Erasable Programmable Read Only Memory (EEPROM); flash memory; optical or holographic media; magnetic cassettes, magnetic tape, magnetic disk storage or other magnetic storage devices; data transmissions; and/or any other medium that can be used to store information and can be accessed by a computing device such as, for example, quantum state memory, and/or the like. In embodiments, the memory 510 stores computer-executable instructions 518 for causing the processor 508 to implement aspects of embodiments of system components discussed herein and/or to perform aspects of embodiments of methods and procedures discussed herein.
The computer-executable instructions 518 may include, for example, computer code, machine-useable instructions, and the like such as, for example, program components capable of being executed by one or more processors 508 associated with the computing device 504. For example, in embodiments, the computer-executable instructions 518 may be configured to cause the one or more processors 508 to instantiate an application (e.g., “mobile app”) configured to facilitate any number of different aspects of analyte detection and/or analysis, as discussed throughout this document. Program components may be programmed using any number of different programming environments, including various languages, development kits, frameworks, and/or the like. Some or all of the functionality contemplated herein may also, or alternatively, be implemented in hardware and/or firmware.
The illustrative system 500 shown in
Various modifications and additions can be made to the exemplary embodiments discussed without departing from the scope of the presently disclosed subject matter. For example, while the embodiments described above refer to particular features, the scope of this disclosure also includes embodiments having different combinations of features and embodiments that do not include all of the described features. Accordingly, the scope of the subject matter disclosed herein is intended to embrace all such alternatives, modifications, and variations as fall within the scope of the claims, together with all equivalents thereof.
This application claims priority to U.S. Provisional Application No. 62/426,062 filed Nov. 23, 2016, entitled “DETECTION DEVICE FOR ANALYSIS OF FLUID PROPERTIES AND METHODS OF USE;” which is hereby incorporated by reference in its entirety for all purposes.
This invention was made with government support under grant No. 1534786 awarded by the National Science Foundation. The government has certain rights in the invention.
| Number | Date | Country | |
|---|---|---|---|
| 62426062 | Nov 2016 | US |
