Patent Application
20150216471
The present invention relates to sensing of physiological conditions including hydration state (e.g., euhydration or dehydration) utilizing saliva of mammalian subjects.
Maintaining appropriate hydration level is critical for health and performance of humans and other mammals. Water lost through processes including perspiration and respiration must be replaced. Fluid losses of between 2-3% of body mass detrimentally affect cardiovascular function, thermal dissipation, and exercise performance. Overhydration can also detrimentally affect exercise performance (e.g., due to electrolyte imbalance) and stress a subject's kidneys. Relying upon thirst as a feedback mechanism to trigger demand for fluid intake may not be adequate to maintain an optimal hydration level, since a sensation of thirst sufficient to cause a subject to drink may not be triggered until after the subject is already dehydrated.
One method to assess hydration is to periodically weigh a subject under controlled conditions. For example, over a bout of exercise, a reduction in body weight measured nude before and after exercise will indicate a state of dehydration. While nude body weight changes may be used to assess acute changes in hydration status during a single exercise bout, over longer periods of time, body weight changes may be influenced by many factors other than change in hydration status, such as: food intake, bowel movements, and changes in body composition. As a result, measurement of body weight over a prolonged period is an inaccurate way of assessing whole body hydration status. But even in a single bout of exercise, it may be highly impractical to stop and subject for purposes of measuring nude body weight to assess hydration status.
Other known methods to assess hydration status involve use of testing of urine or blood. For example, urine specific gravity is a common standard among certain physicians. For patients that can be monitored over time, total urine output or urine specific gravity may be used as a metric. Hydration status can also be assessed using a blood sample, since an increase in plasma osmolality can often identify a state of dehydration, but such sensing requires invasive collection of a venous blood sample by a qualified phlebotomist. In numerous settings, use of urine or blood for assessment of hydration status can be highly impractical.
For many reasons, saliva is an ideal choice for development of a rapid, point-of-care diagnostic measurement for dehydration and/or stress. The sample is easily obtained with minimal invasiveness. No blood must be drawn. In many cases, it is difficult for an individual or health care provider to access urine in a patient (especially for the elderly or infants). Also, urine assessment could be indicative of a prior state of dehydration because the urine is maintained in the bladder and does not necessarily reflect a subject's current hydration state. It would be desirable to provide a convenient device and method for sensing hydration status without requiring use of conventional laboratory equipment and specially trained personnel.
Reduced saliva production or hypo-salivation may be caused by certain disease states (e.g., Sjögren's syndrome) or embody a side effect of certain medications. Dry mouth, also called xerostomia, is the medical term for the subjective complaint of dry mouth which is often associated with lack of saliva. Dry mouth can lead to problems with tooth decay, the ability to swallow, and the abilities to taste and digest food. When hypo-salivation is a side effect of one or more medications, such condition may improve with an adjusted dosage or a new prescription.
When saliva production is reduced to an extremely low level (e.g., around 10 microliters per minute or less), it can be difficult to obtain accurate measurements of salivary flow rate using conventional methods. One significant concern is that measured values may be on the same order of magnitude as the range of experimental error. Accordingly, it can be difficult to accurately and reproducibly measure salivary flow rate for subjects with extremely low salivary production. Measurement difficulties at extremely low salivary flow rates also render it very difficult to assess benefits or side effects of medications in relation to salivary function, since a doubling of salivary production rate from, say, 0.3 ml/min to 0.8 ml/min would be beneficial, but may be difficult to detect using conventional methods. It can also be difficult to determine abnormal function of one or more salivary gland relative to other salivary glands of the same mammalian subject, which might be indicative of physiologic abnormalities or disease state (e.g., inflammation, tumors, etc.).
Based on the foregoing, the art continues to seek diagnostic devices and methods for sensing hydration state and/or salivary flow rate of a mammalian subject that are adapted to overcome one or more of the foregoing limitations. It would be desirable to provide non-invasive point of care diagnostic devices and methods capable of sensing salivary flow rate and/or hydration state quickly, accurately, and with a high degree of reproducibility, even for subjects with very low saliva production rates.
Certain embodiments according to the present invention involve sampling of saliva within the mouth of a subject proximate to at least one salivary gland duct, to identify a state of euhydration, state of dehydration, or salivary secretion rate. Certain embodiments according to the present invention relate to use of a liquid collection element arranged for placement under the tongue of a subject, with positioning aided by a substrate including a notch or recess arranged to receive at least a portion of the sublingual frenulum of the subject. Certain embodiments include use of a substrate arranged to support a liquid collection element and multiple non-collinearly arranged saliva detection regions (including electrical contacts) arranged to detect a front of saliva absorbing and advancing simultaneously in multiple directions following migration of saliva through the liquid collection element. In certain embodiments, a liquid collection element may be placed into a sublingual area or buccal cavity of a mammalian subject following swabbing of the sublingual area or buccal cavity with an absorptive medium to remove ambient saliva. In certain embodiments, sensing of salivary flow rate may be further augmented by sensing presence and/or concentration of at least one analyte in saliva.
In one aspect, the invention relates to an apparatus for sensing a state of euhydration, state of dehydration, or salivary secretion rate of a mammalian subject, the apparatus comprising: a liquid collection element comprising a hydrophilic, porous medium or fibrous medium; and a substrate including a frontal portion arranged to support the liquid collection element and including a leading edge defining a notch or recess, wherein the notch or recess is arranged to receive at least a portion of a sublingual frenulum of a mammalian subject upon insertion of the frontal portion under a tongue of the mammalian subject. In certain embodiments, a plurality of electrical contacts may be supported by the frontal portion of the substrate, and arranged to detect presence of saliva following migration of saliva through portions of the liquid collection element.
In another aspect, the invention relates to an apparatus for sensing a state of euhydration, state of dehydration, or salivary secretion rate of a mammalian subject, the apparatus comprising: a liquid collection element comprising a hydrophilic, porous medium or fibrous medium arranged to contact oral mucosa of a mammalian subject; a plurality of saliva detection regions comprising a plurality of electrical contacts arranged to detect presence of saliva following migration of saliva through portions of the liquid collection element, wherein the plurality of saliva detection regions includes multiple non-collinearly arranged saliva detection regions arranged to detect a front of saliva advancing simultaneously in multiple directions; and a substrate arranged to support the plurality of electrical contacts and the liquid collection element.
Further aspects of the invention relate to methods utilizing the foregoing apparatuses for sensing a state of euhydration, state of dehydration, or salivary secretion rate of a mammalian subject.
A further aspect of the invention relates to method of sensing a state of euhydration, state of dehydration, or salivary secretion rate of a mammalian subject, the method comprising: swabbing a sublingual area of a mammalian subject with an absorptive medium to remove ambient sublingual saliva; and following said swabbing, inserting under the tongue of the mammalian subject a liquid collection element comprising a hydrophilic, porous medium or fibrous medium supported by a substrate comprising a frontal portion including a notch or recess, wherein said inserting includes positioning the frontal portion to receive at least a portion of a sublingual frenulum of the mammalian subject in the notch or recess.
A further aspect of the invention relates to method of sensing a state of euhydration, state of dehydration, or salivary secretion rate of a mammalian subject, the method comprising: swabbing a portion of an oral cavity between (a) teeth or gums and (b) at least one of a cheek and a lip of a mammalian subject with an absorptive medium to remove ambient saliva proximate to at least one salivary duct; and following said swabbing, inserting into said portion of the oral cavity, proximate to a salivary duct, a liquid collection element comprising a hydrophilic, porous medium or fibrous medium supported by at least a frontal portion of a flexible substrate.
Another aspect of the invention relates to an apparatus for sensing a state of euhydration, state of dehydration, or salivary secretion rate of a mammalian subject, the apparatus comprising: a substrate supporting a plurality of electrical contacts arranged to detect presence of saliva, wherein at least a portion of the substrate is arranged for insertion in the mouth of the mammalian subject; and an accelerometer associated with the substrate and arranged to detect tilt or position of the substrate.
Yet another aspect of the invention relates to an apparatus for sensing a state of euhydration, state of dehydration, or salivary secretion rate of a mammalian subject, the apparatus comprising: a substrate supporting a plurality of electrical contacts disposed in a multi-dimensional array and arranged to detect presence of saliva, wherein at least a portion of the substrate is arranged for insertion in the mouth of the mammalian subject; a processing element arranged to receive signals from the plurality of electrical contacts; and a transmitter or transceiver arranged to receive signals from the processing element and arranged to wirelessly transmit at least one signal indicative of at least one of the following to a terminal or remote communication device: (i) number of electrical contacts triggered within a predetermined time period by saliva in the mouth of the mammalian subject; (ii) rate of triggering of at least some electrical contacts of the plurality of electrical contacts by saliva in the mouth of the mammalian subject; (iii) time within which a predetermined number of electrical contacts of the plurality of electrical contacts are triggered by saliva in the mouth of the mammalian subject; and (iv) a time until changes detected by one or more sensors ceases.
Another aspect of the invention relates to an apparatus for sensing a state of euhydration, state of dehydration, or salivary secretion rate of a mammalian subject, the apparatus comprising: a flexible substrate supporting a plurality of electrical contacts disposed in a multi-dimensional array and arranged to detect presence of saliva; wherein a first portion of the substrate includes a first subset of the plurality of electrical contacts and is arranged for placement in a first location selected from: a sublingual cavity, a left buccal cavity, a right buccal cavity, and a cavity between lower lip and teeth/gums; wherein a second portion of the substrate includes a second subset of the plurality of electrical contacts and is arranged for placement in a second location selected from a sublingual cavity, a left buccal cavity, a right buccal cavity, and a cavity between lower lip and teeth/gums; and wherein the second location differs from the first location; a microprocessor in electrical communication with the plurality of electrical contacts and arranged to receive signals from the plurality of electrical contacts; and a memory arranged to store information derived from the plurality of electrical contacts.
Still another aspect of the invention relates to a method for sensing a state of euhydration, state of dehydration, or salivary secretion rate of a mammalian subject, the method comprising: inserting under the tongue of the mammalian subject a liquid collection element comprising a hydrophilic, porous medium or fibrous medium, a substrate, and a plurality of saliva detection regions including a plurality of electrical contacts arranged to detect presence of saliva following migration of saliva through portions of the liquid collection element, wherein the plurality of saliva detection regions includes multiple non-collinearly arranged saliva detection regions arranged to detect a front of saliva advancing simultaneously in multiple directions; utilizing at least one microprocessor in electrical communication with the plurality of electrical contacts to identify a state of euhydration, state of dehydration, or salivary secretion rate of the mammalian subject based at least in part on one of the following items (i) to (iv): (i) a count of a number of electrical contacts triggered within a predetermined time period by saliva following migration of saliva through portions of the liquid collection element; (ii) a rate of triggering of at least some electrical contacts of the plurality of electrical contacts; (iii) a time within which a predetermined number of electrical contacts of the plurality of electrical contacts are triggered; and generating an output signal indicative of state of euhydration, state of dehydration, or salivary secretion rate of the mammalian subject; and (iv) a time until changes detected by one or more sensors ceases.
Still another aspect of the invention relates to a method for sensing state of euhydration, sensing state of dehydration, sensing salivary secretion rate, or sensing salivary gland function of a mammalian subject, the method comprising: inserting into the mouth of a mammalian subject a flexible substrate supporting a plurality of electrical contacts disposed in a multi-dimensional array and arranged to detect presence of saliva; wherein a first portion of the substrate includes a first subset of the plurality of electrical contacts and is arranged for placement in a first location selected from: a sublingual cavity, a left buccal cavity, a right buccal cavity, and a cavity between lower lip and teeth/gums; wherein a second portion of the substrate includes a second subset of the plurality of electrical contacts and is arranged for placement in a second location selected from a sublingual cavity, a left buccal cavity, a right buccal cavity, and a cavity between lower lip and teeth/gums; and wherein the second location differs from the first location; receiving signals from the plurality of electrical contacts; and performing at least one of the following steps (i) and (ii): (i) mapping salivary secretion rates in the first location and the second location; and (ii) comparing salivary secretion rates in the first location and the second location.
Further aspects of the invention relate to use of the described devices and methods to diagnose a disease state of the mammalian subject, and/or to detect a side effect of an interaction of at least one drug with the mammalian subject. Still further aspects include performing an assay utilizing saliva collected with a liquid collection element to generate a quantitative or qualitative output signal based on concentration of at least one analyte in the saliva.
In a further aspect, any of the foregoing aspects or features and elements as disclosed herein may be combined for additional advantage.
Other aspects, features and embodiments of the invention will be more fully apparent from the ensuing disclosure and appended claims.
The present invention relates in various embodiments to sensing of salivary secretion rate (e.g., as may be measured by collecting of saliva in a liquid collection element inserted proximate to at least one salivary duct of a mammalian subject) as indicative of state of euhydration or dehydration. As noted previously, determination of state of euhydration or dehydration may be further aided by sensing of at least one analyte in saliva.
Sources of unstimulated saliva in humans have been determined to be approximately 60% submandibular gland, 7-8% sublingual gland, 25% parotid gland, and 7-8% through other glandular sources. (See Dawes, C., “Salivary flow patterns and the health of hard and soft oral tissues,” JADA 139:18-24, 2008.)
Certain aspects of the present invention benefit from recognition by the inventor that (i) placement of a saliva collection element in close proximity to a salivary duct (within the oral cavity of a mammalian subject) enables rapid, accurate, and reproducible saliva collection and saliva flow rate measurement even at very low flow rates, and (ii) multiple non-collinearly arranged saliva detection regions (e.g., including electrical contacts) may be arranged to detect a front of saliva advancing simultaneously in multiple directions following migration of saliva through the liquid collection element.
As opposed to the use of saliva detection regions that are linearly arranged (such as disclosed in U.S. Patent Application Publication No. 2012/0083711 to Goldstein, et al., which is hereby incorporated by reference in its entirety, for all purposes), using multiple non-collinearly arranged saliva detection regions (e.g., including electrical contacts) permits saliva flow rate to be determined rapidly from the multi-directional spread of saliva through a porous or fibrous liquid collection element preferably contained entirely within the oral cavity of a mammalian subject, thereby dispensing with any need for waiting for collected saliva to migrate to or be channeled to a detection region outside the oral cavity or distal to the saliva gland duct, and insuring saliva collection substantially instantaneously with saliva secretion. Various schemes that may be employed using multiple non-collinearly arranged saliva detection regions include (but are not limited to) the following: (i) counting a number of electrical contacts triggered within a predetermined time period by saliva following migration of saliva through portions of the liquid collection element; (ii) determining a rate of triggering of at least some electrical contacts; (iii) determining a time within which a predetermined number of electrical contacts of the plurality of electrical contacts are triggered, and/or (iv) sensing of time to a condition of stasis—i.e., a time to a stop in changes detected by one or more sensors. Although certain embodiments herein refer to the use of electrical contacts arranged to permit closure of circuits by conduction of current though saliva, saliva detection regions may additionally or alternatively use one or more types of sensing elements such as capacitive sensing elements, conductivity sensing elements, optical sensing elements, and the like.
Detection of saliva absorbed by a porous or fibrous liquid collection element as disclosed herein may be used to determine state of euhydration, state of dehydration, state of disease (e.g., where the disease state includes hyposalivation as a symptom thereof), and/or to detect a side effect of interaction of one or more drugs with the mammalian subject. For example, Sjögren's syndrome is a chronic autoimmune disease in which a person's immune system attacks moisture-producing glands, and such disease is characterized in part by hyposalivation. Detection of salivary secretion rate below a predetermined threshold (such as may be optionally validated by multiple runs of substantially the same type, or multiple tests of different types) utilizing devices and/or methods as disclosed herein may be used to diagnose Sjögren's syndrome or detect other disease states (such as may include hyposalivation as a symptom thereof). Similarly, certain drugs are characterized by hyposalivation as a side effect, and devices and/or methods as disclosed herein may be used to detect a side effect of interaction of one or more drugs with a user (e.g., by comparison of an output signal or an apparatus disclosed herein, or information derived from such signal, with at least one reference value or reference value range correlative of the side effect of drug interaction, or comparison to baseline salivary flow information previously established for the same mammalian subject). In certain embodiments, dosage and/or administration of a drug may be adjusted in response to the detection of a side effect (such as hyposalivation) of the drug interaction. In certain embodiments, an apparatus and/or method as disclosed herein may be used to determine suitability or readiness of a patient to undergo a medical or dental procedure that requires or is benefitted by maintenance of a particular saliva secretion rate range or threshold (whether low or high).
Various embodiments of the invention facilitate positioning of a liquid collection element proximate to a sublingual, parotid, or minor salivary duct. In certain embodiments, a liquid collection element including hydrophilic, porous medium or fibrous medium is supported by a substrate that includes a leading edge defining a notch or recess arranged to receive at least a portion of a sublingual frenulum of a mammalian subject, in order to reproducibly position at the frontal portion of a sensing apparatus (including a liquid collection element, preferably in conjunction with multiple non-collinearly arranged saliva detection regions including electrical contacts) under the tongue of a subject proximate to a sublingual salivary duct. In certain embodiments, the hydrophilic, porous medium or fibrous medium is also proteophobic. A frontal portion of such a substrate may be optionally supported by a convex lower surface to conform to the lower surface of the sublingual cavity and facilitate user comfort. Other surface shapes conforming to a sublingual cavity and/or buccal cavity may be employed. In certain embodiments, a liquid collection element including hydrophilic, porous medium or fibrous medium is supported by a flexible substrate (e.g., a thin film substrate), permitting at least a frontal portion of a sensing apparatus (including a liquid collection element, preferably in conjunction with multiple non-collinearly arranged saliva detection regions including electrical contacts) to be positioned in a buccal cavity of a mammalian subject (e.g., between maxillary second molar and cheek) proximate to a parotid salivary duct.
In certain embodiments, the hydrophilic, porous medium or fibrous medium is also proteophobic. In certain embodiments, one or more travel stops or tab portions arranged to be secured by a user by biting (clenching between teeth) may be employed to maintain a sensing apparatus with a liquid collection element in a buccal cavity proximate to a parotid salivary duct.
In certain embodiments, electrical contacts (saliva detection regions) and appurtenant electrical traces may be patterned on a substrate, such as a thin film substrate (e.g., a polymeric thin film), by printing, etching, and/or other conventional circuit patterning techniques. Contacts and/or associated traces may be patterned on one or multiple surfaces of a substrate. Electrically conductive wires or cables may alternatively (or additionally) be used. Multiple positive contacts may be dispersed on a substrate in an array or other pattern, accompanied by one or multiple ground or electrical neutral regions. In certain embodiments, a shared electrical ground region or shared electrically neutral region is arranged between each (e.g., positive) electrical contact of a plurality of electrical contacts. When an advancing front of conductive saliva closes a gap between a positive contact and a ground or neutral region, an electric circuit is closed (or electrical resistance or impedance is reduced). In certain embodiments, electrodes may be provided in complementary pairs, and arranged to form multiple non-collinearly arranged saliva detection regions. In certain embodiments, electrical conductivity of saliva may be enhanced by presence of one or more electrolytes (e.g., sodium chloride) in, on or against a liquid collection element arranged to contact saliva.
In certain embodiments, one or more contacts or electrodes are exposed (e.g., not covered by a liquid collection element) to sense a condition indicative of exposure of a portion of the liquid collection element to oral mucosa and/or salivary duct secretions of a mammalian subject. Such exposed contacts may be used to detect insertion of at least a frontal portion of a sensing device in the mouth of a subject, and automatically establish a starting time (initial time value) and/or automatically start a timer indicative of the start of a sampling period, with an initial time value, elapsed time values, and/or values derived therefrom preferably being stored in a memory associated with a sensing device. In certain embodiments, the exposed contacts may also be used to determine state of the apparatus prior to insertion in the mouth of the mammalian subject, such as by performing a control check for the absence of saliva (e.g., detectable as the absence of closed contacts) prior to initiation of testing/sample collection. One or more time value may be useful in with various saliva flow detection schemes that may be employed using multiple non-collinearly arranged saliva detection regions, such as (i) counting a number of electrical contacts triggered within a predetermined time period by saliva following migration of saliva through portions of the liquid collection element; (ii) determining a rate of triggering of at least some electrical contacts; and (iii) determining a time within which a predetermined number of electrical contacts of the plurality of electrical contacts are triggered. In certain embodiments, a scheme may include sensing of time to a condition of stasis—i.e., a time to a stop in changes detected by one or more sensors.
In certain embodiments, a liquid collection element comprises a porous medium or a fibrous medium arranged to absorb saliva (hydrophilic) and also resistant to adhesion of a protein adlayer (proteophobic). A liquid collection element may be formed of paper, fabric, nitrocellulose, or any other suitable material. In certain embodiments, a liquid collection element comprises a material having directionally uniform liquid wicking characteristics. Thickness, area, porosity, and other parameters of a liquid collection element may be selected to provide a liquid collection element with suitable capacity and absorption characteristics. A liquid collection element may be arranged to cover (and preferably arranged in contact with) multiple saliva detection regions, with the liquid collection element held in place with one or more adhesives or other retaining elements. In certain embodiments, a liquid collection element is retained along peripheral portions thereof via adhesive bonding to a substrate. In certain embodiments, a continuous bead or line of adhesive is provided along peripheral portions of a liquid collection element to prevent saliva from entering into the space between a liquid collection element and multiple saliva detection regions without passage through a face of a liquid collection element. In certain embodiments, at least one peripheral portion of a liquid collection element may be covered with a retaining element (e.g., arranged to compress peripheral portions of a liquid collection against a substrate) that leaves a central portion of the liquid collection element uncovered, with the retaining element resembling a window frame. Such a retaining element may be used to prevent saliva from entering into the space between a liquid collection element and multiple saliva detection regions without passage through a face of a liquid collection element. In certain embodiments, a retaining element is arranged for permanent retention of a liquid collection element; in other embodiment, a retaining element may be arranged to facilitate removal of a liquid collection element, such as by using removable closures and/or hinges.
In certain embodiments, a portion of a liquid collection element may be covered by a removable liquid-impermeable covering element, such as a removable adhesive tape or other covering element. Such a covering element may be arranged to cover a liquid collection element during transit and/or storage to prevent moisture from being absorbed by the liquid collection element, with the covering element subject to being removed prior to use.
In certain embodiments, a liquid collection element may be arranged in or on a sample collection portion of an apparatus for sensing state of euhydration or dehydration, with other components of the apparatus (e.g., timing element, processing element/comparator, input element(s) and/or signaling element(s), among others) being arranged within a monitoring portion. In certain embodiments, a sampling portion may be operatively connected to a monitoring portion via an electrical interface connector (optionally extended with an electrical communication cable), or via wireless communication, thereby permitting the sampling portion to be inserted into the mouth of a user while a monitoring portion is spatially separated therefrom. By providing a sampling portion separate from the monitoring portion, the monitoring portion may be sequentially reused with numerous sampling portions of disposable character. A monitoring portion may be arranged to sense salivary secretion rate alone, or may be arranged to further sense concentration of at least one analyte in saliva (e.g., using an optical reading element and/or any other suitable type of analyzer). A monitoring portion may include any suitable combination of various components such as (but not limited to) a battery, a timer, a processing and/or control element, a comparator, a memory, a display, one or more indicator lights, an audible output element, sensor traces or wires, an electrical interface plug, a sampling portion receiving cavity, an optical reading element (or other sample analyzing element), and a communication element arranged to communicate (whether in wired or wireless fashion) with one or more terminals or other remote communication devices.
In certain embodiments, an apparatus for sensing state of euhydration or dehydration is arranged to generate a user-perceptible output signal indicative of hydration status that is quantitative in character. A user perceptible output signal generated by such an apparatus may be visible, audible, and/or tactile in character. Examples of quantitative signals include salivary secretion rate (e.g., in μl/min or other suitable units, obtainable by dividing volumetric capacity of the liquid collection element over measured time to saturation), number of electrical contacts triggered in a predetermined time period, rate of triggering of at least some electrical contacts, time within which a predetermined number of electrical contacts have been triggered, analyte concentration level (e.g., in μg/ml or other suitable units, obtainable via use of an optical reading element or other analytical element) and the like. In certain embodiments, a sensing scheme may include sensing of time to a condition of stasis—i.e., a time to a stop in changes detected by one or more sensors.
In certain embodiments, a user-perceptible output signal generated by an apparatus for sensing state of euhydration or dehydration with an array of multiple non-collinearly arranged saliva detection regions includes a display arranged to actuate pixels (or groups of pixels) in an array that corresponds to the array of saliva detection regions, such that triggering of individual saliva detection regions (e.g., contacts) results in actuation of corresponding pixels of the display. In this manner, a front of saliva advancing simultaneously in multiple directions following migration of saliva through the liquid collection element may be visualized on a pixel-based display.
In certain embodiments, an apparatus for sensing state of euhydration or dehydration is arranged to generate a user-perceptible output signal indicative of hydration status that is qualitative in character. With respect to salivary secretion, one or more threshold values for salivary secretion rate indicative of euhydration or dehydration may be stored in memory of the apparatus, and sensed values may be compared to the one or more threshold values to provide a simple qualitative assessment as to whether a user is in a state of euhydration or dehydration. A qualitative signal may be selected from two, three, four, or more possible results. For example, in certain embodiments, a qualitative signal may be limited to two possible results of euhydration or dehydration. In other embodiments, a qualitative signal may be selected from three possible results of euhydration, dehydration, and severe dehydration. In other embodiments, a qualitative signal may be selected from four possible results of euhydration, slight dehydration, moderate dehydration, and severe dehydration. If one or more analytes in saliva are analyzed, then output of an optical reading element may be compared to one or more threshold signal level to provide a qualitative output. A processing element and/or comparator may be arranged to compare at least one test value against at least one predetermined threshold value, and/or to compare multiple test values against one another (or one or more values derived therefrom), and responsively trigger a signaling element to generate a user-perceptible qualitative signal indicative of state of euhydration, state of dehydration, or salivary secretion rate based at least in part on such comparison.
In certain embodiments, a hydration state sensing device may provide a quantitative output signal based on results of one salivary test method, and provide a qualitative output signal based on results of one salivary test method. For example, a device may provide a quantitative output signal indicative of salivary secretion rate, and provide a qualitative output signal indicative of analyte concentration (or vice-versa).
One or more user-perceptible output signals representing a quantitative and/or qualitative values may be generated by one or more signaling elements, such as (but not limited to) a LCD display, a LED array, an alphanumeric display, one or more lamps (e.g., LEDs), a sound generating device (e.g., a speaker), and/or a tactile signaling element such as a vibration generator. Multiple signaling elements may be provided. In certain embodiments, a sound generating device may provide an output signal in the form of a synthesized voice.
In certain embodiments, a system for sensing a state of euhydration, state of dehydration, or salivary secretion rate of a mammalian subject may include a sampling component, a monitoring/communication interface component connected via a wired interface to the sampling component, and a remote communication device such as a smartphone, tablet computer, laptop computer, or similar device arranged to communicate wirelessly with the monitoring/communication interface component. Wireless communication may be conducted by Bluetooth Low Energy (BLE) (also known as Bluetooth Smart), Zigbee, or any other suitable wireless communication protocol. At least a portion of a sampling component may be arranged for insertion into a mouth of a mammalian subject, whereas a monitoring/communication interface component may be arranged to be maintained outside the mouth of the mammalian subject. A remote communication device (e.g., smartphone, tablet computer, laptop computer, or similar device) may be loaded with a software application facilitating wireless communication with the monitoring/communication wireless interface component.
In certain embodiments, a monitoring/communication interface component may include a battery, a microprocessor, a wireless transceiver or transmitter, at least one input element arranged to receive a user input, and at least one output element. Examples of input signals that may be communicated via at least one user input element include activation, deactivation, reset, and mode selection. In certain embodiments, at least one output may provide a user-perceptible output signal such an audible signal, a visual signal (e.g., illumination of one or more indicator lights or a display element), and/or a touch-based (e.g., haptic or vibratory) signal. User-perceptible output signals may be used to signal initiation of a test or sampling run, to signal termination of a test or sampling run, to signal a valid or invalid test or sampling run, to signal correct placement or orientation of a sampling component, to signal a salivary secretion rate, and/or to signal a state of dehydration or euhydration.
At least a portion of a monitoring/communication interface component may include an electronic module such as the ConnectBlue OLP425 Bluetooth® Low Energy (BLE) Platform Module (e.g., such as may include BLE chipset, antenna, embedded processor, analog-to-digital converter, battery holder temperature sensor, accelerometers, and/or other sensors) (available from ConnectBlue AB, Malmo, Sweden). Various other types of modules could be used, such as the Bluegiga BLE 112 (Bluegiga Technologies Oy, Espoo, Finland), Blue Radios BR-LE4 0-S2A (Blue Radios, Inc., Englewood, Colo., U.S.A.), Panasonic PAN1720 (Panasonic Electronic Components, Seacaucus, N.J., U.S.A.), or Insight SiP ISP091201 (Insight SiP, Sophia-Antipolis, France). As an alternative to prepackaged modules, BLE chipsets such as the Texas Instruments TI CC2540 or Nordic nRF8001 may be used in conjunction with discrete components to form a monitoring/communication interface component.
In certain embodiments, a monitoring/communication interface component may include one or more sensors arranged to monitor ambient conditions. One or more sensors may be arranged to sense humidity, temperature, pressure, and/or altitude, which may affect a subject's hydration rate. In certain embodiments, output signals from one or more sensors associated with a monitoring/communication interface component may be logged in conjunction with data received or derived from a sampling component, and/or such output signals may be used to validate or assist in determination of a state of dehydration or euhydration of a mammalian subject.
In certain embodiments, a monitoring/communication interface component may include a multiplexing element, which may be embodied in one or more dedicated processors or may include instructions or a routine executed by a single (e.g., central) microprocessor of the monitoring/communication interface component. A multiplexing element may be used to send multiple signals or streams of information on a carrier at the same time in the form of a single, complex signal. In certain embodiments, a multiplexed signal may be transmitted wirelessly from a monitoring/communication interface component to a remote communication device such as a smartphone, tablet computer, laptop computer, or similar device. The remote communication device may be positioned within sufficient range of the monitoring/communication interface component to enable communication of a low power wireless radio frequency signal such as a BLE signal or the like.
In certain embodiments, a monitoring/communication interface component may include at least one timer, which may be embodied in a discrete element or may include instructions or one or more routines executed by a single (e.g., central) microprocessor of the monitoring/communication interface component. In certain embodiments, at least one timer may be used to indicate the start of a sampling period, to indicate elapsed time of a sampling period, to indicate time of closure of one or more electrical contacts, to indicate rate of closure of electrical contacts, and/or to indicate any other time-dependent values. In certain embodiments, a timer may be used to control (e.g., automatically terminate) operation of a wireless transceiver or transmitter associated with a monitoring/communication interface component, in order to conserve battery life by preventing the transceiver or transmitter from being activated more than a specified period (e.g., two to five minutes, or any desired period) after a sampling run has been initiated.
In certain embodiments, a sampling component may include multiple electrical contacts arranged to detect presence of liquid (e.g., saliva) supported by a substrate, wherein at least a portion of the substrate including the contacts may be arranged for placement in the mouth of a mammalian subject. The electrical contacts may be arranged in a multi-dimensional array. At least a portion of the substrate may be flexible. A liquid collection element (e.g., including a hydrophilic, porous medium or fibrous medium that may also be proteophobic in character) may be arranged to cover the electrical contacts, wherein the electrical contacts may be arranged to detect presence of saliva following migration of saliva through portions of the liquid collection element. In certain embodiments, the plurality of electrical contacts may be arranged in physical contact with portions of the liquid collection element. In certain embodiments, a mouth of a mammalian subject may be at least partially cleared of ambient saliva (e.g., by expectoration, swabbing with absorbent media, and/or other means) prior to initiation sample collection, so that presence of saliva detected by the electrical contacts preferably corresponds to saliva secreted contemporaneously with and/or after insertion of the liquid collection device into the subject's mouth. A state of dehydration, state of euhydration, or salivary secretion rate of the mammalian subject based at least in part on one of the following items: count of a number of electrical contacts triggered within a predetermined time period by saliva following migration of saliva through portions of the liquid collection element; a rate of triggering of at least some electrical contacts of the plurality of electrical contacts; a time within which a predetermined number of electrical contacts of the plurality of electrical contacts are triggered; or a time to a stop in changes detected by one or more sensors. At least one exposed electrical contact may be supported by the substrate (e.g., a frontal portion of the substrate) and arranged to detect a condition indicative of placement of the frontal portion into contact with at least one of oral mucosa and salivary duct secretions of the mammalian subject, such as may be useful to automatically initiate operation of a sampling run.
In certain embodiments, a sampling component may include one or more temperature sensors arranged for placement within a mouth of a mammalian subject (e.g., to sense temperature therein) or arranged for placement outside the mouth (e.g., to sense ambient temperature conditions). In certain embodiments, multiple temperature sensors may be arranged in a multi-dimensional array to permit detection of temperature at different locations within a mouth of a mammalian subject. In certain embodiments, multiple temperature sensors may be dispersed among multiple electrical contacts. In certain embodiments, one or more temperature sensors may be uncovered by a liquid collection element. In certain embodiments, one or more temperature sensors may be arranged along a surface of a substrate opposing a surface of the substrate bearing multiple electrical contacts covered by a liquid collection element.
In certain embodiments, a sampling component may include one or more humidity sensors arranged for placement within a mouth of a user (e.g., to sense humidity therein) or arranged for placement outside the mouth (e.g., to sense ambient humidity conditions). In certain embodiments, multiple humidity sensors may be arranged in a multi-dimensional array to permit detection of humidity at different locations within a mouth of a mammalian subject. In certain embodiments, multiple humidity sensors may be dispersed among multiple electrical contacts. In certain embodiments, one or more humidity sensors may be uncovered by a liquid collection element. In certain embodiments, one or more humidity sensors may be arranged along a surface of a substrate opposing a surface of the substrate bearing multiple electrical contacts covered by a liquid collection element.
In certain embodiments, a sampling component may include one or more accelerometers arranged to detect placement or orientation (e.g., tilt) of a substrate when at least a portion of the substrate is placed within a mouth of a mammalian subject. It is believed that salivary secretion rate and/or sample collection may be affected by placement or orientation (e.g., tilt) of a subject's head and/or orientation of at least the portion of a sampling component arranged within the subject's mouth. In certain embodiments, a user-perceptible and/or test administrator-perceptible feedback signal may be generated (e.g., by an output element associated with a monitoring/communication interface component to which the sampling component is connected via a wired interface) based on signals generated by one or more accelerometers based on positioning or orientation of a substrate as affected by positioning or orientation of a subject's head or mouth. In certain embodiments, one or more accelerometers may be associated with (e.g., contacting or otherwise supported by) a substrate, and either arranged for placement within or (more preferably) outside the mouth of a mammalian subject.
The remote communication device may optionally be arranged to communicate (e.g., via a network) with at least one other terminal or other remote device. Wired and/or wireless communication may be employed.
As noted previously, a system for sensing a state of euhydration, state of dehydration, or salivary secretion rate of a mammalian subject may include a sampling component, a monitoring/communication interface component connected via a wired interface to the sampling component, and a remote communication device such as a smartphone, tablet computer, laptop computer, or similar device arranged to communicate wirelessly with the monitoring/communication interface component. In certain embodiments, the remote communication device may provide primary or secondary data processing, primary or secondary data logging/storage, primary or secondary display, and/or primary or secondary condition diagnosis functions. A remote communication device may include a processor (e.g., microprocessor), a display, a memory, at least one input element, and (optionally) a camera or scanning device that may also provide barcode reading functionality. Such a remote communication device may optionally be arranged to communicate (e.g., via a network) with at least one other terminal or other remote device that may have still further data storage and/or data retrieval capability. Utilizing a remote communicate device in wireless communication with a monitoring/communication interface component as outlined above may provide various advantages, including: reduced processing requirements and reduced cost for the monitoring/communication interface component; reduced size/weight of the monitoring/communication interface component; enhanced comfort to the mammalian subject during sampling; enhanced flexibility to the user to store, share, and/or retrieve data; and enhanced access to distributed networks (e.g., the World Wide Web) to facilitate exchange with electronic medical record and/or patient health record systems—which may be aided in particular when a remote communication device includes barcode scanning capability (e.g., for automated merger and/or retrieval of data). Data input via a remote communication device may enable configuration options include steps in a procedure to be performed. A remote communication device may enable retrieval of saliva flow rate reference values. A remote communication device may enable communication with inventory/disposables management and/or support and troubleshooting. A remote communication device may further be used to enter weight of a liquid collection element following completion of a sampling run to compare the entered weight against test results for test validation.
In certain embodiments, a remote communication device may be utilized to capture and store one or more of the following parameters: (i) date/time of sampling run; (ii) patient ID; (iii) patient name; (iv) patient image; (v) sampling data; (vi) error logs; (vii) one or more scanned barcodes; (viii) geolocation via an integrated global positioning chip to identify location of sampling run; (ix) images or video of device placement and/or test administration, and/or (x) graphical representations of test results.
In certain embodiments, one or more control sensors may be provided to provide features such as start timing, timing customization, threshold cutoff on timing, and/or detection of used sampling components.
In certain embodiments, results obtained from a system for sensing a state of euhydration, state of dehydration, or salivary secretion rate of a mammalian subject may be integrated with patient heath records and/or electronic medical records.
In certain embodiments, a substrate of a sampling component may include a first portion arranged for insertion into a mouth of a mammalian subject and a second portion arranged to extend into an ambient environment to interface with a monitoring/communication interface component. In certain embodiments, the first portion includes a leading edge defining a notch or recess, wherein the notch or recess is arranged to receive at least a portion of a sublingual frenulum of a mammalian subject upon insertion of the frontal portion under a tongue of the mammalian subject. In certain embodiments, the second portion may include a flexible and/or curved electrical interface including at least one electrical cable or conductor arranged to permit signals to be conducted to a monitoring/communication interface component. In certain embodiments, part or all of a substrate may be flexible in character. In certain embodiments, a portion of a substrate may be flexible and another portion may be substantially rigid. In certain embodiments, one or more portions of a substrate and/or an electrical interface may be curved in shape and/or include a center of gravity arranged proximate to a chin (or between a chin and neck) of a mammalian subject to facilitate comfort of the subject when at least a portion of the substrate is arranged within a subject's mouth.
In certain embodiments, a liquid collection element may be arranged over a portion of a substrate to cover multiple electrical contacts, and may include a protruding tab or other feature facilitating removal of the liquid collection element (e.g. by peeling) to facilitate subsequent analysis of the liquid collection element (whether by weighing and/or utilization in an assay or another chemical test), to facilitate retention of the liquid collection element in a suitable container, or to permit disposal of the liquid collection element. In certain embodiments, a liquid collection element may include at least one registration feature (e.g., protrusion, hole, or recess) arranged to mate with a corresponding at least one registration feature associated with a substrate (e.g., recess, hole, or protrusion) to facilitate alignment and/or retention of the liquid collection element.
In certain embodiments, instantaneous and/or time-dependent state various contacts and/or sensors associated with a sampling component of a system for sensing a state of euhydration, state of dehydration, or salivary secretion rate may be represented visually using software and a display device. Such software interface and display device may be associated with a remote communication device and/or other terminal or remote device. In certain embodiments, a software user interface may be arranged to color or darken regions to represent closed contacts, and to vary color or vary (e.g., increase) darkness of regions based on increasing elapsed time since initiation of a sampling run. In certain embodiments, state of individual electrical contacts or groups of electrical contacts of a multi-dimensional array of electrical contacts covered with a liquid collection element may be visually represented. In certain embodiments, state of one or more exposed electrical contacts (e.g., for initiating a sampling run) may be visually represented. In certain embodiments, state of individual temperature sensors or groups of temperature sensors of a multi-dimensional array of temperature sensors may be visually represented. In certain embodiments, data obtained from one sampling run may be visually compared to reference data, such as one or more raw or processed (e.g., averaged) sets of data corresponding to previously-captured sampling runs of the same mammalian subject, or one or more sets of raw or processed sets of data corresponding to one or more other mammalian subjects or groups of subjects.
In certain embodiments, an apparatus for sensing a state of euhydration, state of dehydration, or salivary secretion rate of a mammalian subject may include a sampling component that includes a flexible substrate with multiple subsets of electrical contacts, wherein different portions of the substrate are arranged for simultaneous placement in multiple different locations of the mouth, such as two, three, or four of the following locations: a sublingual cavity, a left buccal cavity, a right buccal cavity, and a cavity between lower lip and teeth/gums. Providing multiple subsets of electrical contacts proximate to different salivary glands may permit function of different salivary glands of the same subject to be individually quantified and compared. In certain embodiments, the multiple subsets of electrical contacts may be covered with one or more liquid collection elements. In certain embodiments, at least a frontal portion of the sampling component may include a notch or recess arranged to receive at least a portion of the sublingual frenulum of the subject. In certain embodiments, one or more exposed electrical contacts may not be covered with a liquid collection element, and may be used to automatically signal initiation of a sampling run. In certain embodiments, such as substrate may include one or more additional sensors such as one or more temperature sensors (optionally arranged in a multi-dimensional array), humidity sensors (optionally arranged in a multi-dimensional array), and/or accelerometers as described herein. In certain embodiments, a multi-dimensional array of electrical contacts may overlap or be interspersed with at least one multi-dimensional array of one or more other type(s) of sensors to permit conditions in different portions of a subject's mouth to be separately sampled, monitored, and/or mapped with respect to one or more parameters. In certain embodiments, a heat map of regions of a subject's mouth may be developed using multiple temperature sensors. In certain embodiments, such a heat map may be used to indicate salivary function. In certain embodiments, a sampling component may be used in conjunction with a monitoring/communication interface component connected via a wired interface to the sampling component, and a remote communication device as described herein, and may further be used in conjunction with software (e.g., visualization and comparison software) as described herein.
In certain embodiments, various steps may be performed to prepare a mammalian subject and sensing apparatus for detecting state of euhydration, state of dehydration, or salivary secretion rate and/or perform sensing operations. In certain embodiments, a subject may be prompted to expectorate ambient saliva. The mouth of the subject may be swabbed. Optionally a salivary stimulating agent may be administered. Hardware and/or sensors may be initiated (e.g., including checking for closed/wetted contacts). A sampling component (e.g., including liquid collection element) may be placed in a mouth of the subject and positioned as appropriate for the sampling component (e.g., with portions in one, some, or all of the following locations: sublingual cavity, a left buccal cavity, a right buccal cavity, and a cavity between lower lip and teeth/gums). The subject's head or mouth position or orientation (e.g., tilt) may be sensed with one or more accelerometers. One or more feedback signals may be provided to confirm satisfaction or non-attainment of desired or necessary conditions. Error signals may be handled to display error information such as failure based on control sensors, failed insertion of sensing device, and/or loss of communications. Exposed contacts may be used to initiate data collection and/or initiate operation of a wireless transmitter or transceiver, and initiate operation of a timer used to automatically deactivate the wireless transmitter or transceiver after a conceivable sampling period to conserve battery life of a monitoring/communication interface component. Analysis, display, comparison, and/or trending may be performed utilizing data obtained in a sampling run, optionally in conjunction with data obtained from prior sampling runs. Patient treatment may be performed based on results obtained in a sampling run.
In certain embodiments, a method for sensing state of euhydration, sensing state of dehydration, sensing salivary secretion rate, or sensing salivary gland function of a mammalian subject, the method comprising: inserting into the mouth of a mammalian subject a flexible substrate supporting a plurality of electrical contacts disposed in a multi-dimensional array and arranged to detect presence of saliva; wherein a first portion of the substrate includes a first subset of the plurality of electrical contacts and is arranged for placement in a first location selected from: a sublingual cavity, a left buccal cavity, a right buccal cavity, and a cavity between lower lip and teeth/gums; wherein a second portion of the substrate includes a second subset of the plurality of electrical contacts and is arranged for placement in a second location selected from a sublingual cavity, a left buccal cavity, a right buccal cavity, and a cavity between lower lip and teeth/gums; and wherein the second location differs from the first location; receiving signals from the plurality of electrical contacts; and performing at least one of the following steps (i) and (ii): (i) mapping salivary secretion rates in the first location and the second location; and (ii) comparing salivary secretion rates in the first location and the second location. In certain embodiments, both (i) and (ii) may be performed. In certain embodiments, a substrate includes at least three or at least four portions arranged for placement in different portions of a subject's mouth, and salivary secretion rates are mapped and/or compared in at least three locations or at least four locations.
In certain embodiments, a salivary stimulating agent may be applied to a subject prior to or concurrent with placement of a liquid collection element (or portion thereof) in the subject's mouth, utilizing a device and method for sensing salivary secretion rate. In certain embodiments, a salivary stimulating agent may be coated on or otherwise administered to a user by a liquid collection element. A salivary stimulating agent may be arranged for gustatory and/or olfactory stimulation of saliva production. Examples of gustatory salivary stimulating agents include (but are not limited to) citric acid and sodium chloride. In one embodiment, a saliva stimulant coating may include citric acid (35-45%), sugarless sour candy (54%-64%) and sodium chloride (1%). Mechanical stimulation of saliva production (e.g., a mechanical salivary stimulating element) may also be used. In certain embodiments, a chewable article such as chewing gum is administered to a user prior to or concurrent with placement of a liquid collection element (or portion thereof) in a subject to mouth, in order to stimulate saliva production by chewing.
In certain embodiments, at least one method for sensing a state of euhydration or dehydration as described herein is applied to a user according to a first testing step, one or more output values yielded from the first testing step is stored in a memory, then at least one method for sensing a state of euhydration or dehydration as described herein is applied to the same user according to a second testing step, and one or more output value yielded from the first testing step are compared to one or more stored values. Such steps may be periodically repeated as necessary to assess change in hydration state of the user.
In certain embodiments, at least one of oral fluids, intravenous fluids, electrolytes, medication, and medical treatment may be administered to a user based on one or more output signals generated by hydration state sensing devices and methods as described herein. In certain embodiments, an output signal from an apparatus as described herein may be communicated (e.g., via wired or wireless communication) to an administering element to facilitate automated administration of at least one of oral fluids, intravenous fluids, electrolytes, medication, and medical treatment of fluids without human intervention.
In certain embodiments, operation of one or more sensing methods or processing of results thereof may be affected by one or more signals received from a user input element. In various embodiments, a user input element may be used to store one or more sensed values, to compare one or more currently sensed values to one or more stored values corresponding to previously sensed values, and/or to select a user population of which the user is a member. To the extent that user population status (e.g., age, sex, disease state, medication usage, activity level, or the like) may affect comparison values used to provide qualitative assessments, user input information may be used to adjust or select appropriate comparison values to as a basis for providing a qualitative output signal.
In various embodiments, a liquid collection element may be placed into a portion of an oral cavity between (a) teeth or gums and (b) at least one of a cheek and a lip of a mammalian subject with an absorptive medium to remove ambient saliva proximate to at least one salivary duct. In certain embodiments, the oral cavity portion may include a buccal cavity, and the at least one salivary duct may include at least one parotid duct. In certain embodiments, the oral cavity portion may include a cavity between (a) lower teeth or gums and (b) a lower lip of the mammalian subject, and the at least one salivary duct may include at least one minor salivary duct. In certain embodiments, the oral cavity portion may include a sublingual cavity, and the at least one salivary duct may include a sublingual salivary duct. Such swabbing may be useful to remove ambient saliva, thereby reducing a potential source of variability in determining saliva flow rate. In certain embodiments, an apparatus for sensing a state of euhydration, state of dehydration, or salivary secretion rate of a mammalian subject may be packaged together with at least one swab (to perform the foregoing swabbing function) and usage instructions in a kit. As an alternative to or in addition to (e.g., preceding) swabbing, a subject may be prompted to expectorate and/or swallow in order to remove ambient saliva from at least a portion of the oral cavity.
In certain embodiments, a liquid collection element, sampling portion, and/or an entire device (which may or may not include saliva detection regions and/or electrodes) as described herein may be weighed following collection of a saliva sample to determine an amount of collected saliva. For example, a liquid collection element, sampling portion, and/or an entire device may have a predetermined weight or may be weighed before (or contemporaneously with) administration to a user, and following placement of a liquid collection element and/or sampling portion into the mouth of a user (e.g., to position the liquid collection element sublingually or in a buccal cavity) for a specified time period, the liquid collection element, sampling portion, and/or entire device may be weighed (e.g., using a high precision digital scale), whereby the amount of weight gained represents absorbed saliva. Such determination of salivary flow rate may be used in conjunction with any of various devices as disclosed herein as an alternative to, or in addition to, one or more salivary flow rate measurement techniques described herein. In certain embodiments, saliva flow rate may be determined utilizing the difference in weight of the at least a portion of the salivary diagnostic device and utilizing a difference in time from (i) a time initiated by triggering of at least one saliva detection region to (ii) a time indicative of an end of saliva collection by the liquid collection element.
In certain embodiments, a liquid collection element utilized for sensing salivary secretion rate may embody, or may be provided in fluid communication with, an immunochromatographic lateral flow test strip including at least one indicator or test region arranged to interact with at least one analyte in saliva obtained from the mammalian subject, so that a salivary analyte concentration in sensing method may be performed following the sensing of salivary secretion rate utilizing the same saliva sample. A conjugate pad (e.g., including monoclonal antibodies conjugated to gold nanoparticles) employed by an immunochromatographic assay for sensing salivary analyte concentration may be arranged between a liquid collection element and an immunochromatographic test strip. One or more analytes in saliva may be correlated to hydration level. For example, research recently performed by Dr. Neil P. Walsh of the University of Wales (Bangor) School of Sport, Health and Exercise Sciences (as subsidized by the assignee of the present application, and published as Appl. Physiol. Nutr. Metab. 37:1-10 (June 2012)) has demonstrated that dehydration is accompanied by a reduction in salivary secretion rate, as well as increases in certain analyte contained in saliva, such as IgA and albumin. It has also been theorized that dehydration may be accompanied by an increase in salivary aldosterone concentration may be correlative of dehydration.
In certain embodiments, a liquid collection element and an immunochromatographic test strip may be arranged in or on a common substrate (with at least portions thereof optionally contained in a housing). Alternatively, an electrochemical immunoassay may be utilized. In other embodiments, a liquid collection element is associated with a first substrate, and an immunochromatographic test strip is associated with a second substrate or housing. Following completion of a salivary secretion rate sensing method, a liquid collection pad may be treated with a buffer solution (e.g., by dipping a liquid collection element in a container (e.g., vial) of buffer solution), and a buffered saliva composition may be supplied to an immunochromatographic test device. One potential benefit of such buffering is to mitigate variability in saliva samples (e.g., viscosity, tonicity, ionic strength, and/or pH) that may otherwise reduce reliability of an immunochromatographic assay.
In certain embodiments, an immunochromatographic lateral flow test strip may include a uniform layer of monoclonal antibodies adapted to bind a selected analyte in saliva. Examples of suitable analytes include (but are not limited to) IgA (e.g., secretory IgA, or SIgA), salivary albumin, secretory component, and salivary aldosterone, and while SIgA is mentioned hereafter, it is to be understood that any suitable analyte may be used. An immunochromatographic lateral flow test strip may be designed to bind a calibrated quantity of SIgA (e.g., using anti-SIgA) per millimeter of strip length. As saliva enters the strip, the SIgA may be colorized by passing through a conjugate pad containing anti-SIgA conjugated to nano-gold particles which binds to the SIgA, imparting a color (e.g., pink) to the analyte. When all of the colored SIgA is bound to the strip, the remaining length of the strip remains white. Marks may be delineated by a cover optionally containing multiple holes that reveal the strip at various points along its length, with each pointing represents a total amount of SIgA per ml of saliva. Calibration marks may be arranged proximate to openings in the cover to permit quantitative assessment of analyte concentration based upon presence (or absence) of color in an adjacent window.
In certain embodiments, an immunochromatographic lateral flow test strip may include a series of antibody (e.g., anti-SIgA) bands arranged as stripes aligned perpendicular to a long dimension of the strip. Each stripe line has a specific (though not necessarily the same) analyte absorptive capacity. Thus, substantially the same method as articulated in the preceding paragraph can be accomplished using a series of striped bands rather than a uniform layer of antibodies for the selected analyte over the entire strip.
In certain embodiments, an immunochromatographic lateral flow test strip and cover may be arranged to provide a positive control region (e.g., corresponding to a window defined in a cover over the strip) disposed downstream of a conjugate pad but upstream of one or more indicator windows providing quantitative or qualitative indication of hydration state. Colorization of such a positive control region (e.g., with pink color) will indicate that a liquid sample is present within the lateral flow test strip, that the conjugate pad is functional, and that the sample contains the analyte (or analytes) of interest. Presence of a colored signal in the positive control region may increase confidence in quantitative or qualitative signals generated in downstream test windows.
In certain embodiments, one or more immunochromatographic lateral flow test strips or portions thereof within the same apparatus may include different monoclonal antibodies arranged to bind different analytes. In certain embodiments, an immunochromatographic lateral flow test strip may include a first group of monoclonal antibodies arranged to interact with a first analyte selected from IgA, albumin, secretory component, and aldosterone, and a second group of different monoclonal antibodies arranged to interact with a second analyte selected from IgA, albumin, secretory component, and aldosterone, wherein the second analyte differs from the first analyte. Different antibodies arranged to interact with different analytes may be provided in one or more of same test or indicator regions located along a single immunochromatographic lateral flow test strip, may be provided in different test or indicator regions located along parallel flow paths in a single immunochromatographic lateral flow test strip, or may be provided in different test or indicator regions located in multiple immunochromatographic lateral flow test strips arranged in parallel within a single device or system. Different analytes may be colored differently (e.g., blue and yellow) via one or more conjugate pads. Signals based upon a combination of different analytes bound in the same region may be combined (e.g., blue and yellow combined to make a green color). lmmunochromatographic lateral flow test strips arranged to interact with multiple analytes may be arranged to perform different assay formats, such as a competitive binding assay format or a sandwich assay format.
Referring to the figures, a schematic diagram showing interconnection of various components of a system 100 for sensing a state of euhydration or dehydration of a subject via saliva of the subject is illustrated in
Although
In certain embodiments, separable sampling and monitoring portions of a hydration state sensing apparatus may be connected via an electrical cable and/or other wired or wireless interface. Referring to
Continuing to refer to
While the invention has been described herein in reference to specific aspects, features and illustrative embodiments of the invention, it will be appreciated that the utility of the invention is not thus limited, but rather extends to and encompasses numerous other variations, modifications and alternative embodiments, as will suggest themselves to those of ordinary skill in the field of the present invention, based on the disclosure herein. Correspondingly, the invention as hereinafter claimed is intended to be broadly construed and interpreted, as including all such variations, modifications and alternative embodiments, within its spirit and scope.
This application claims priority to U.S. Provisional Patent Application No. 61/683,637 filed on Aug. 15, 2012, and the contents of such application are hereby incorporated by reference herein for all purposes.
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/US13/55057 | 8/15/2013 | WO | 00 |
| Number | Date | Country | |
|---|---|---|---|
| 61683637 | Aug 2012 | US |
