Patent Application
20170303815
All publications and patent applications mentioned in this specification are herein incorporated by reference in their entirety to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference.
Apparatuses, including devices and systems, as well as methods for determining lung wetness are described herein. In particular, described herein are non-invasive methods and systems for determining lung wetness using a patch sensor (patch) including an array of electrodes having a fixed predetermined configuration are configured to conform to a subject's body to electrical properties that indicate lung wetness.
The reference in this specification to any prior publication (or information derived from it), or to any matter which is known, is not, and should not be taken as an acknowledgment or admission or any form of suggestion that the prior publication (or information derived from it) or known matter forms part of the common general knowledge in the field of endeavour to which this specification relates.
Tissue water content is an important and informative diagnostic parameter. Dehydration decreases cognitive and physical work capabilities, while the excessive hydration (swelling, edema) is a common symptom of cardiac, hepatic or renal pathology, malnutrition and many other pathologies and diseases. Edema causes muscle aches and pains and may affect the brain, causing headaches and irritability. Edema is a major symptom for deep venous thrombosis. It may be caused by allergies or more serious disorders of the kidney, bladder, heart, and liver, as well as food intolerance, poor diet (high sugar & salt intake), pregnancy, abuse of laxatives, diuretics, drugs, the use of contraceptive pills, hormone replacement therapy, phlebitis, etc.
For example, muscle water content (MWC) is a clinically useful measure of health. Monitoring of muscle water content can serve as an important indicator of body hydration status in athletes during the training as well as in soldiers during deployment. It is generally known that body hypohydration causes severe complications, health and performance problems, and that increasing body water weight loss causes increasing problems: water weight loss of up to 1% causes thirst, 2% may cause vague discomfort and oppression, 4% may cause increased effort for physical work, 5% may cause difficulty concentrating, 6% may cause impairment in exercise temperature regulation, increases in pulse and respiratory rate; 10% may cause spastic muscles; and 15% may cause death. Soldiers commonly dehydrate 2% -5% of body weight due to high rate of water loss from environmental exposure and performing stressful physical work. Dehydration by modest amounts (2%) decreases cognitive and physical work capabilities, while larger water losses have devastating effects on performance and health. Numerous pathologic signs and symptoms due to body dehydration include digestion problems, high blood pressure, muscle cramps, etc. MWC monitoring by an objective instrument may help prevent hazard thresholds. This is important because subjective indicators like thirst can be inadequate.
Control of MWC in athletes and soldiers could help in monitoring total body hydration during long-term endurance exercise or performance in hot weather conditions. In addition, tissue wetness may be particularly helpful in assessing lung wetness, which may be an important metric for treating cardiac disorders such as congestive heart failure.
Congestive heart failure (CHF) causes difficulty breathing because oxygen exchange in the lung is impeded by pulmonary congestion. The vast majority of CHF hospital admissions are because of difficulty breathing. Further, the high rate of CHF readmission (by some estimates approximately 24% within 30 days) is due to re-accumulation or inadequate removal of pulmonary congestion resulting in difficulty breathing. Currently, there is no quantifiable method or metric to identify pulmonary congestion and better prevent difficulty breathing and hospital admission. This problem is growing. In 2010, there was an estimated of 5.8 million CHF cases in the U.S., with over 670,000 new cases each year.
A subject suffering from CHF may be diagnosed using a physical exam and various imaging techniques to image the subject's chest. Treatment typically includes the use of vasodilators (e.g., ACEI/ARB), beta blockers, and diuretic therapy (e.g., Lasix). Management of treatment often proves difficult and unsuccessful. In particular, diuretic therapy is difficult for subjects and physicians to optimally manage. For example, changes in diet may require frequent changes in the diuretic therapy. Overuse (an underuse) of diuretic therapy may negatively impact clinical outcomes.
Pulmonary congestion is typically the result of high pulmonary blood pressures that drive fluid into the extravascular “spongy” interstitial lung tissue. High pulmonary blood pressures are present in subjects with elevated intravascular filling pressures as a result of heart failure. This high pulmonary blood pressure may also lead to increased amounts of fluid entering the extravascular space. Congestion within the extravascular interstitial lung tissue may prevent gas exchange ultimately, leading to a difficulty breathing that may require hospitalization. Hospital therapies are typically directed at reducing the pulmonary blood pressure by removing intravascular fluid with diuretic therapy. Although subject symptoms may improve, significant extravascular interstitial fluid may still be present. Subjects may feel well enough for discharge, but only a small change in pulmonary blood pressures will cause fluid to quickly re-accumulate, requiring readmission. Thus, subject symptoms do not reflect adequate treatment for the extent of the disease. Therefore, there is a need to detect and monitor extravascular interstitial fluid (e.g., lung wetness) and to provide an index or measure of the level extravascular interstitial fluid both instantaneously, and over time.
There are several methods for assessing total body water, as the most prominent indicator of hydration status, including methods based on bioelectrical impedance and conductance. For example, U.S. Pat. No. 4,008,712 to Nyboer discloses method and apparatus for performing electrical measurement of body electrical impedances to determine changes in total body water in normal and deranged states of the body, U.S. Pat. No. 5,615,689 to Kotler discloses a method of predicting body cell mass using impedance analysis, U.S. Pat. No. 6,280,396 to Clark discloses an apparatus and method for measuring subject's total body water content by measuring the impedance of the body, and U.S. Pat. No. 6,459,930 to Takehara et al. discloses a dehydration condition judging apparatus by measuring bioelectric impedance. However, these methods and systems have proven unreliable and difficult to implement. The aqueous tissues of the body, due to their dissolved electrolytes, are the major conductors of an electrical current, whereas body fat and bone have relatively poor conductance properties. Significant technical problems have hampered many such electrical methods for in vivo body composition analyses; impedance spectroscopy is an attempt to refine bioimpedance measurements, which measures resistance and reactance over a wide range of frequencies. A technique based on this approach is described in U.S. Pat. No. 6,125,297 to Siconolfi which describes a method and apparatus for determining volumes of body fluids in a subject using bioelectrical response spectroscopy.
Although various systems for using electrical energy have been proposed and developed, many of these systems are complex and difficult and expensive to implement. For example, systems such as electrical impedance imaging/tomography (EII/EIT) and applied potential tomography have been described elsewhere. For example, a system such as the one described in U.S. 2007/0246046 to Teschner et al. (and others owned by the Draeger corporation) uses an electrical impedance tomography (EIT) method for reconstituting impedance distributions. In such systems, a plurality of electrodes may be arranged for this purpose on the conductive surface of the body being examined, and a control unit, usually a digital signal processor, typically ensures that a pair of (preferably) adjacent electrodes are each supplied consecutively with an electric alternating current (for example, 5 mA at 50 kHz), and the electric voltages are detected at the remaining electrodes acting as measuring electrodes and are sent to the control unit. Typically, a ring-shaped, equidistant arrangement of 16 electrodes is used, and these electrodes can be placed around the body of a subject, for example, with a belt. Alternating currents may be fed into two adjacent electrodes each, and the voltages are measured between the remaining currentless electrode pairs acting as measuring electrodes and recorded by the control unit.
Other described EIT systems, such as those illustrated in U.S. Pat. No. 7,660,617, U.S. 2010/0228143, and WO 91/019454, do not show evidence that measurements would not vary with subject habitus, e.g., body shape or geometry.
Unfortunately, electrical impedance methods have proven difficult to reliably and accurately implement for determining tissue wetness, and particularly lung wetness. Often, additional anthropometric terms (i.e., weight, age, gender, race, shoulder width, girth, waist-to-hip ratio, and body mass index) must be included in these previous prediction models to reduce the error of the estimate within acceptable boundaries. In addition, the reliability and reproducibility of the wetness estimates may vary depending on the geometry and placement of the electrodes. Thus, current methods and systems for assessing water content based on the bioimpedance of tissues may result in low accuracy, significant dependence of testing results on the anthropometrical features of the subject and on electrolyte balance.
There is therefore a need for a simple and highly accurate method and device for monitoring tissue hydration status that can be used in a broad range of field conditions.
Described herein are method and apparatuses (devices and systems) for determining tissue wetness, and particularly lung wetness. In particular, described herein are apparatuses including patch sensors having a plurality of electrodes on a substrate that includes alignment tabs for aiding in alignment. Also described herein are patch sensors having one or more substrate modifications to enhance local flexibility of the patch. Finally, described herein are apparatuses for determining lung wetness that determine the contour of the body region onto which the patch is applied, e.g., using a diagnostic tool to measure or otherwise assess body contour.
For example, described herein are systems, devices and methods that may provide an objective measure of tissue wetness. In some specific variations, the systems, devices and methods may be configured to measure pulmonary congestion (e.g., extravascular interstitial fluid) in in-subject and/or out-subject settings, including home use. For example, the systems described herein may provide non-invasive, accurate, and reproducible measures of pulmonary congestion. These systems may be referred to as lung fluid assessment monitors. Any of the systems described herein and may include executable logic to detect tissue wetness utilizing relative percent differences of apparent resistivities from the skin into the tissue derived from applying currents and measuring voltages in a specified geometric pattern of electrodes applied to the skin. The systems described herein may therefore be non-invasive, rapid, and do not use ionizing radiation.
Some variations of the systems described herein may be referred to as lung fluid assessment monitors, and may have executable logic configured to detect extravascular interstitial lung fluid utilizing determining relative spatial change in subsurface resistivities across frequencies from the skin to the lung region derived from applying currents and measuring voltages in a specified geometric pattern of electrodes applied to the skin. As mentioned, these systems may also provide an objective absolute measurement of pulmonary fluid status, such as an extravascular lung water (EVLW) index. The systems, devices and methods described herein may address many of the problems identified above, and may offer reliable and effective techniques for determining tissue wetness by determining a distribution of relative percent differences of the tissue regions beneath the electrodes to derive a value or distribution of values that are independent of the subject's body geometry. The resulting information may provide a map indicating the relative percent differences of spatial distributions of resistivities within the body across multiple frequencies. Also described herein are methods of interpreting the relative percent difference map to determine tissue wetness and, in particular, to monitor changes in tissue wetness.
For example, an array of electrodes having a predetermined configuration for detecting lung wetness may be referred to as a patch, sensor patch or patch sensor. The sensor patches described herein may hold the plurality of electrodes in a predetermined arrangement, yet may be sufficiently flexible or conformable so that they can be self-adherent to the subject's body (e.g., back) to hold each of the electrodes in the plurality of electrodes on the patch (where a patch may be greater than 1 inch (2.5 cm) wide and 6 inches (15 cm) in length in some variations) while maintaining continuous electrical contact with the patient's body. Thus, any of the patches described may include local regions that enhance flexibility of the overall patch without compromising the fixed spatial relationship between the electrodes. The local regions that enhance flexibility may be referred as a substrate modification (or flexibility-enhancing substrate modifications). A substrate modification may be a cut-out region, a cut (e.g., slit), or generally a local region in the substrate of the patch that has a greater flexibility than the rest of the patch. In general, the substrate modifications enhance conformance of the patch sensor (electrodes) against the three-dimensional contour of a patient's body, and particularly the patient's back. The local regions of the substrate that include substrate modifications enhancing flexibility of the overall patch may reduce the lifting force resulting from the relatively rigid electrodes and other patch substrate regions when the patch sensor is applied against the subject's body, e.g., preventing the patch from lifting away from the skin when force is applied by the electrodes contacting the skin.
Any of the patch sensors (patches) including electrodes described herein may also include one or more alignment tabs for assisting a user in applying the patch on a subject in a predetermined location. For example, a patch may include one or more alignment tabs and/or alignment or positioning markings/features that may be used to aid in positioning a patch on a subject, including in particular on a subject's back.
Also described herein are diagnostic tools that may be used to determine the contour of the subject's back. These tools may be integrated into a patch or used with a patch (or independent of the patch). For example, a diagnostic tool may be configured to measure contours of the subject's body, including contours of the subject's back. Measurements taken with the diagnostic tools may be used with the system to help determine lung wetness, and/or to help align and/or position a sensor patch properly on the subject's body. For example, measurement data can be used by any of the systems described herein to determine tissue wetness.
In general, systems for measuring electrical properties (e.g., relative changes in resistivities) are described. For example, a system may include an apparatus for applying and recording electrical signals. Exemplary embodiments of these systems, including patch sensors, are provided herein including dimensions, signal parameters, etc. Also described herein are modifications or variations of the apparatus. For example, an apparatus may include a strap cradle that attaches a portion of the device (e.g., an acquisition module) to a subject, and/or a garment worn by the subject, such as a strap. The strap cradle may limit or restrict access ports when the acquisition module is worn by a patient, which may prevent incorrect use/operation of the device, and/or undesired communication.
Also described herein are other variations of patch sensors, including patches that have a visible protective layer. The protective layer may be used (e.g., in manufacturing) to protect exposed electrode surfaces.
In one broad form the present invention seeks to provide a non-invasive lung wetness patch sensor, the patch sensor comprising a substrate; a plurality of electrodes on the substrate, wherein the substrate maintains a predetermined spacing between the electrodes; and at least one substrate modification to enhance local flexibility of the substrate so that the patch sensor may conform to a contour of a subject's body, wherein the plurality of electrodes are configured to form a plurality of pairs of current-injecting electrodes and a plurality of pairs of voltage detection electrodes.
Typically the substrate modifications to enhance local flexibility of the substrate comprise at least one of cut-out regions through the substrate, slits cut through the substrate and regions of material within the substrate having a greater flexibility than the substrate.
Typically the substrate is flexible and relatively inelastic, so that the spacing between each of the electrodes remains relatively fixed as the sensor is manipulated.
The patch sensor can further comprise an adhesive hydrogel.
Typically the substrate is less than about 5 mils (0.127 mm) thick.
Typically the substrate comprises at least one of a polyester material and a polyester material and an anti-bacterial titanium oxide material.
Typically the width of the substrate is between about 0.5 inches (1.3 cm) and about 2.5 inches (6.4 cm).
Typically the plurality of electrodes comprise more than 6 elongate electrodes each having a length of between about 1.5 (3.8 cm) and about 2.5 inches (6.4 cm) and a width of between about 0.1 inches (0.3 cm) and about 0.5 inches (1.3 cm), wherein the electrodes are arranged with their lengths perpendicular to a proximal to distal axis on a subject-contacting surface of the substrate so that the electrodes extend in a line parallel to the proximal to distal axis of the substrate to form an active region that extends between about 6 inches (15 cm) and about 14 inches (36 cm) along the proximal to distal axis.
Typically the plurality of electrodes comprise more than at least one of 10 electrodes and more than 25 electrodes.
Typically the electrodes have a rectangular shape on the substrate.
Typically the electrodes comprise silver/silver chloride electrodes.
Typically the electrodes are separated by a fixed distance of between about 0.2 inches (0.5 cm) and about 0.5 inches (1.3 cm) on center down a proximal to distal length of the substrate.
In one broad form the present invention seeks to provide a non-invasive lung wetness patch sensor, the patch sensor comprising a substrate; a plurality of electrodes on the substrate, wherein the substrate maintains a predetermined spacing between the electrodes; and a plurality of alignment tabs extending from a lateral side of the substrate wherein the alignment tabs are between about 0.2 inches (0.5 cm) and about 2 inches (5 cm) long and greater than about 0.1 inches (0.3 cm) wide, wherein the plurality of electrodes are configured to form a plurality of pairs of current-injecting electrodes and a plurality of pairs of voltage detection electrodes.
Typically the alignment tabs are between about 0.1 inches (0.3 cm) and about 3 inches (7.6 cm) wide.
Typically the alignment tabs comprise an upper alignment tab and a lower alignment tab.
Typically the substrate is flexible and relatively inelastic, so that the spacing between each of the electrodes remains relatively fixed as the sensor is manipulated.
Typically the patch sensor further comprises an adhesive hydrogel.
Typically the substrate is less than about 5 mils (0.127 mm) thick.
Typically the substrate comprises at least one of a polyester material and a polyester material and an anti-bacterial titanium oxide material.
Typically the width of the substrate is between about 0.5 inches (1.3 cm) and about 2.5 inches (6.4 cm).
Typically the plurality of electrodes comprise more than 6 elongate electrodes each having a length of between about 1.5 (3.8 cm) and about 2.5 inches (6.4 cm) and a width of between about 0.1 inches (0.3 cm) and about 0.5 inches (1.3 cm), wherein the electrodes are arranged with their lengths perpendicular to a proximal to distal axis on a subject-contacting surface of the substrate so that the electrodes extend in a line parallel to the proximal to distal axis of the substrate to form an active region that extends between about 6 inches (15 cm) and about 14 inches (36 cm) along the proximal to distal axis.
Typically the plurality of electrodes comprise more than at least one of 10 electrodes and more than 25 electrodes.
Typically the electrodes have a rectangular shape on the substrate.
Typically the electrodes comprise silver/silver chloride electrodes.
Typically the electrodes are separated by a fixed distance of between about 0.2 inches (0.5 cm) and about 0.5 inches (1.3 cm) on center down a proximal to distal length of the substrate.
In one broad form the present invention seeks to provide a diagnostic tool device for measuring the surface contour of a region of a patient's body, the diagnostic tool comprising a body extending in an arch from a first contact region to a second contact region, wherein a straight line extending between the first and second contact regions forms a neutral line; and a plurality of distance measuring elements coupled to the body and configured to measure the distance from a surface beneath the arch of the body and the neutral line.
The device can further comprise a flexible member extending between the first contact region and second contact region.
The device can further comprise a handle opposite the arch.
The device can further comprise a first alignment mark on the first contact region and a second alignment mark on the second contact region.
Typically the distance measuring elements comprise sliders configured to be pushed by the surface beneath the arch of the body.
Typically the distance measuring elements comprise sliders coupled to a flexible member extending between the first contact region and second contact region.
The device can further comprise a plurality of guides on the body configured to provide an estimate of distance based on the deflection of the distance measuring elements.
The device can further comprise an electronic reader configured to read measurements from the distance measuring elements.
Typically the distance measuring elements comprise non-contact, optical distance measuring elements.
In one broad form the present invention seeks to provide a method of determining tissue wetness, the method comprising attaching a patch sensor comprising a plurality of drive electrodes and sensing electrodes to a skin surface of a subject's body; measuring a curvature of the skin surface of the subject's body; applying drive currents at a plurality of different frequencies to the drive electrodes and measuring voltages at a plurality of different sensing electrodes; determining an estimate of electrical properties for a plurality of regions beneath the patch sensor using the applied drive currents and measured voltages; and determining an estimate of tissue wetness from a frequency response of the determined electrical properties.
It will be appreciated that the broad forms of the invention and their respective features can be used in conjunction and/or independently, and reference to separate broad forms in not intended to be limiting.
The novel features of the invention are set forth with particularity in the claims that follow. A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings of which:
This information can then be used to derive an indicator, indicative of the wetness. This could be in the form of an absolute wetness, or relative wetness, for example compared to a baseline or other reference wetness. The indicator could additionally or alternatively, be indicative of a medical condition associated with the wetness, such as a likelihood of the subject having a condition, or a degree of a condition.
In
In general, many features of the patch 101 are similar to those described in U.S. Patent Application Publication No. 2013/0165761 (application Ser. No. 13/715,788) and U.S. patent application Ser. No. 14/171,499, each herein incorporated by reference in its entirety. For example, the patch 101 may include a plurality of elongate current injecting electrode pairs (simulation electrodes) and a plurality of elongate voltage sensing electrode pairs (sensing electrode pairs) which may be used sequentially or simultaneously to apply current/voltage and to sense a resulting current/voltage from which electrical properties (e.g., regional electrical properties) for one or more volumes of tissue beneath the patch may be determined. A patch 101 such as the one shown as an example in
The current injecting pairs and voltage recording pairs in the example shown in
In general, the substrate may be a flexible material that supports the electrodes, as well as adhesive, traces, connector(s), and other elements (including circuitry) on the patch. For example, the substrate may include a flexible material supporting electrodes, traces, connectors, etc. In some variations, the substrate is a polyester or other non-conductive, flexible material. The substrate may have any appropriate dimensions. For example, the substrate may be approximately 0.003 inch (0.01 cm) thick, and may be relatively long and wide (e.g., between about 0.8 inches (2 cm) and about 5 inches (13 cm) wide, between about 0.8 inches (2 cm) and about 3 inches (8 cm) wide, between about 4 inches (10 cm) and about 16 inches (40 cm) long, between about 4 inches (10 cm) and about 14 inches (35 cm) long, between about 5 inches (13 cm) and about 13 inches (33 cm) long, etc., greater than 0.8 inches (2 cm) wide, greater than 4 inches (10 cm) long, etc.).
The patch can be relatively large (e.g., greater than 4 inches long by 1 inch wide), and can allow each (or at least a majority) of the individual electrode contacts (e.g., voltage sensing pairs, and current injecting pairs) to make good electrical contact with the body (e.g., back) of a patient in order to take accurate, reliable and reproducible readings. However, it is also important that the spacing between individual electrodes in the array have a relatively fixed predetermined relationship relative to each other (e.g., the distance between the electrodes and between the sensing and driving electrode pairs). Although a rigid substrate would best preserve the predetermined spacing relationship between the electrodes, e.g., preventing buckling, bending, or the like, the more rigid the substrates are less likely to conform to the outer surface of the patient's body in a region where readings are to be taken. Thus, there is a tradeoff between how rigid (e.g., stiff) to make the substrate and how flexible (bendable) to make the substrate.
Accordingly, in one example, the patch includes a substrate and a plurality of electrodes on the substrate which are configured to form a plurality of pairs of current-injecting electrodes and a plurality of pairs of voltage detection electrodes, with the substrate maintaining a predetermined spacing between the electrodes. Additionally the patch includes at least one substrate modification to enhance local flexibility of the substrate so that the patch sensor may conform to a contour of a subject's body.
In this regard, this arrangement allows the patch to conform to the subject's body, thereby ensuring good electrical contact with the body, whilst substantially maintaining a physical spacing between the electrodes, which in turn allows for improved measurement accuracy.
In
The flexible portions are shown as slits cut or formed into the substrate. In
The system, and particularly the patch 101, shown in
As mentioned, in
In general, the individual electrodes 102 on the patch 101 may each have a surface area that is sized (e.g., is sufficiently large) to sufficiently reduce impedance encountered at electrode/patient interface. For example, electrodes 102 configured to inject current (stimulating electrodes) can comprise a skin-contacting surface large enough to avoid damage to skin and/or require high voltage drive signal. Alternatively or additionally, electrodes 102 configured for voltage or other signal sensing (sensing electrodes) can comprise a skin-contacting surface large enough to accurately record the desired signal, for example, as described briefly above, in some variations the sensor includes electrodes that are approximately 2 inches (5 cm) long, although they may be 1.5 inches (3.8 cm) long or smaller, and may be one or more order of magnitude narrower (e.g., less than about 0.2 inches (0.5 cm) wide, such as approximately about 0.160 inches (0.4 cm) wide). As mentioned, in general, the individual electrodes may be any appropriate conductive material, and may have a contact impedance of between about 10-10 kOhms, such as between 10-1000 Ohms As mentioned above, in some variations, the stimulation electrodes and the sensing electrodes may have different surface areas. For example, the stimulation electrode surface area maybe greater than the sensing electrode surface area. For example the ratio of stimulation electrode surface area to sensing electrode surface area may be greater than 5:1, 10:1, 50:1; 100:1; 1000:1, etc. The contacting surface of the electrodes (e.g., the portion of the electrode that contacts the subject's skin) could have any appropriate shape, including a shape such as rectangular (e.g. square), elliptical (e.g. circular), polygonal, etc.
In general, any of these sensors (e.g., electrodes 102) could be configured as self-adhesive electrodes and may also include one or more agents to enhance electrical contact with the subject's skin. For example, the electrodes 102 may be hydrogel electrodes. In some variations the electrodes 102 include AG603 sensing gel with a thickness of about 0.025″ (0.064 cm). In some variations, the volume resistivity of each electrode 102 is about 1000 ohm-cm maximum.
Any of the patch sensors 101 (patches) described herein may be adapted for connecting to a particular region of a patient's body, and in particular, a patient's back. Any of these patches may include one or more alignment elements, such as alignment tabs, to help align and couple the patch with a predetermined region of the subject's body.
Accordingly, in one example a non-invasive lung wetness patch sensor is provided that includes a substrate and a plurality of electrodes on the substrate configured to form a plurality of pairs of current-injecting electrodes and a plurality of pairs of voltage detection electrodes, with the substrate maintaining a predetermined spacing between the electrodes. A plurality of alignment tabs are provided extending from a lateral side of the substrate wherein the alignment tabs are between about 0.2 inches (0.5 cm) and about 2 inches (5 cm) long and greater than about 0.1 inches (0.3 cm) wide.
The use of alignment tabs allows the patch to be aligned relative to features of the subject's anatomy, such as the subject's spine. This can be used to assist in ensuring accurate and/or consistent placement of the patch on the subject. For example, this ensures the patch is positioned over the lung whose wetness is being measured, whilst ensuring that measurements are taken at the same location in the event that longitudinal monitoring is being performed.
In
As mentioned above, the patch 101 may also include one or more connecting tabs. For example, a patch 101 may include connecting tabs 103 that include traces and a connector for connection to the acquisition module 117. The connecting tabs 103 may include a flex portion/region 104 that allows the connection to move slightly (e.g. allows the acquisition module to move relative to patch 101) without disturbing the patch 101 (e.g., moving it off of the subject's body). In addition, the connecting tabs 103 may include a stiffener 111 that assists in connection with the connecting cable(s) 113. The connecting tabs 103 may include insulated traces connecting to each electrode 102 in the patch 101. In
Although the patch 101 show in
As shown in
In general, the applied current may be a constant current source. In some variations, the drive signal may be multiple sinusoids delivered sequentially and/or simultaneously by the patch. For example, the acquisition module 117 may be configured to deliver 2-5 simultaneously delivered different frequency sinusoids. In some variations, the apparatus may be adapted to include a common ground, e.g. a large electrode placed on patient. This may allow “monopolar” stimulation and/or “monopolar” sensing from a single electrode 102 in the patch 101. In
An acquisition module 117 may also include a user interface 119, such as one or more of a display (including a display, touchscreen, etc.), light such as an LED, audible transducer, tactile transducer, and combinations thereof. The acquisition module may also include a control (e.g., knob, button, dial, etc.). For example, the user interface 119 may be a graphical user interface (GUI). The user interface for the acquisition module 117 may display information about the status of the acquisition module 117 or other component of system 100, and may include one or more controls for controlling activity of the acquisition module 117 or other component of system 100 (e.g., start/stop, pause/resume, inputs for user information such as height, weight, age, gender, etc.).
In general, the acquisition module 117 includes an electrode recording module (e.g., electrode recording circuitry) that allows the acquisition module 117 to record energy from the subject's skin in response to the applied energy. For example, the acquisition module 117 may record voltages from one or more pairs of the electrodes 102, including at least 1 pair, 3 pairs, 5 pairs, 10 pairs, etc. of electrodes 102.
In addition to receiving the voltage information from the patch 101, the acquisition module 117 may also correlate the received voltage with the applied energy (e.g., current), including which drive electrodes (of electrodes 102) were driven and which sensing electrodes (of electrodes 102) were used to record. The acquisition module 117 may store, transmit, process (e.g., filter, amplify, etc.) this information, and/or it may pass it directly on to a data analysis unit 161, which may be connected to the acquisition module 117 (including within the same housing) or it may be remote from the acquisition module 117.
In addition, as mentioned above, the acquisition module 117 may include an interface (e.g., interface 119) that receives subject-specific information about and/or from the subject. For example, the acquisition module 117 may include one or more inputs (e.g., buttons such as: keyboard; mouse; touchscreen; and combinations of these), and/or may receive inputs from additional measuring tools such as the diagnostic tool 151, as shown in
In
As mentioned and described in greater detail below, the acquisition module 117 may be integrated partially or entirely with the data analysis unit 161.
In some variations, the acquisition module 117 may include an interface or connector to one or more additional modules/devices. For example, an acquisition module 117 may include a USB Port or other data acquisition port for attachment to an external device. As mentioned, in some variations, system 100 (including the acquisition module 117) may include a wireless communication module, for wireless data transfer.
In one example, the acquisition module includes an electronic processing device, such as a microprocessor, microchip processor, logic gate configuration, firmware optionally associated with implementing logic such as an FPGA (Field Programmable Gate Array), or any other electronic device, system or arrangement, that operates to control the current source and voltage sensor. This arrangement typically includes digital to analogue converters (DACs) for coupling the processing device to amplifier for generating the required drive currents, and voltage buffer circuits coupled via analogue to digital converters (ADCs) to the electronic processing device, for returning a voltage signal.
As shown in
In general, the apparatuses described herein include a data analysis unit 161 that may receive and/or analyze the sensed electrical energy (e.g., voltage) evoked by the applied energy (e.g., current). The data analysis unit 161 typically receives information (data) from the acquisition module 117. For example, the data analysis unit 161 may upload or otherwise access information from the acquisition module 117. For example, recorded voltage data, applied drive signal data, error data and/or timing data may be received by the data analysis unit 161 from the acquisition module 117. Additionally and/or alternatively, the acquisition module could perform at least some processing of the information, for example to calculate impedance values, such as magnitudes and/or phase angle values, with the impedance values being provided to the data analysis unit.
A data analysis unit 161 may include hardware, software, firmware, or the like that is configured to operate on the received data to estimate tissue wetness, e.g., lung wetness. For example, the data analysis unit 161 may be adapted to operate on the received data and perform a tissue wetness assessment based on voltages measured from pairs of electrodes (e.g. two or more of electrodes 102) in response to multiple-frequency drive of other pairs of electrodes (e.g. two or more of electrodes 102). U.S. 2013/0165761, previously incorporated by reference, describes and illustrates one variation of a method of determining/estimating tissue wetness based on multiple frequency information. In essence, the system may determine regional electrical characteristics (such as conductivity/resistivity) for sub-regions of tissue beneath the patch at different frequencies to determine a frequency response for different regions beneath the patch. This frequency response may be compared to the frequency response for water (e.g., saline or other liquids that include water), and this comparison may be used to estimate tissue wetness. In some variations, the comparison of the frequency response may be made independently of body geometry. For example, the relative change in resistivities, which may look at the percent change in resistivities, dividing resistivity (e.g. a measured resistivity at a first location at a first frequency) by resistivity (e.g. a measured Resistivity at the first location at a second, different frequency) resulting in a “unit less” measure that may be independent of body geometry. Alternatively, in some variations the estimate of the frequency response may use body geometry or other patient diagnostic information to determine and/or compare the frequency response. For example, a correction factor based on body geometry may be used. Alternatively or additionally, body geometry may inform system 100 as to which portion of determined signal to use or the like. As discussed herein, body geometry may be entered manually or automatically, and may be determined in part from one or more tools, such as the diagnostic tools 151 discussed in more detail below.
In general, the data analysis unit 161 may receive voltage information related to multiple frequency drive signal, along with the drive signals; drive signals may comprise sequential or simultaneous delivery of 2 or more frequencies. For example, for simultaneously driven signals, the recorded voltages can be split into frequency-correlated components (“bins”) and then analyzed by comparing magnitude/phase of the data in the various frequency “bins”. For example, a 256 pt FFT with 1K bin widths that are centered at the two or more application frequencies may be used. The use of simultaneously driven frequencies may greatly reduce the time to apply/record over all of the electrode/electrode pairs used to calculate the signal and estimate wetness.
Any of the data analysis units 161 described herein may also include a user interface 163. For example, a data analysis unit 161 may include a user output component (e.g. screen) to “report” tissue wetness assessment. Alternatively, the output may be stored, and/or transmitted, e.g. including transmission back to the acquisition module 117 and/or to a separate component such as a third-party database (either with or without concurrent display).
In any of the variations described herein, the output may be an indicator of tissue (e.g., lung) wetness. For example, the apparatus may determine and present a quantitative assessment of lung wetness. The assessment may be a relative indicator, such as a numeric (e.g., 1-10) or qualitative assessment of lung wetness (e.g., dry, somewhat wet, wet, etc.). The assessment may be made for a partial portion of a lung, or an assessment of multiple discrete portions of a lung, or may be generalized to the entire lung, or for one lobe of the lung (or one side of the lung).
As mentioned above, the data analysis unit 161 may also include user interface (e.g., GUI) similar to the user interface described above for the acquisition module 117.
It will be appreciated from the above that the data analysis unit 161 could be of any appropriate form and could include a processing system, such as a suitably programmed PC, Internet terminal, lap-top, or hand-held PC, computer server, or the like. In one example the data analysis unit 161 is a tablet, smart phone, or other portable processing device, that is optionally connected to one or more computer servers, which could be distributed over a number of geographically separate locations, for example as part of a cloud based environment. In this example, the functionality provided by the data analysis unit could be distributed between multiple processing systems and/or devices, depending on the preferred implementation.
In variations including one or more connecting cables, as shown in
Any of the apparatuses described herein may include one or more wearable holders that may be used to hold some of the components of the apparatus. For example, a patient strap 141 may be used, as shown in
In some variations the system does not include a strap. For example, the acquisition module, battery, etc. may be directly (e.g., adhesively) connected to the body, or may be placed near the subject's body, e.g., on a surface such as a bed, table, etc.
As mentioned above, any of the variations described herein may include a diagnostic tool 151, as will be described in greater detail below. For example, a diagnostic tool may generally be a device to gather patient information. This patient information may be used by the systems (e.g., the data analysis unit 161) to assess tissue wetness. Examples of diagnostic tools include devices to gather back contour information, as illustrated in
In some variations the apparatus may include control logic that, when executed on a processor causes the device to process the camera image to determine back curvature information. This information may be used to help position the patch and/or correct for patch position when calculating lung wetness. In some variations, the apparatus may include control logic to assist in taking an image (e.g., to guide to user to take an image by providing an orthogonally check, alignment (with patch) check, proper distance from the patient, etc.).
Any of the apparatuses described herein may also include one or more self-diagnostic and/or self-correcting capabilities. For example, U.S. Patent Application Publication No. 2013/0165761 (previously incorporated by reference in its entirety) described a system and method of determining which electrodes 102 to keep/reject when applying stimulation and/or recording signals for determining lung wetness. Such self-diagnostic capability can be incorporated into any of the elements of the apparatus, including the data analysis unit 161 and/or the acquisition module 117 and/or the patch 101.
Diagnostic capabilities may include: applicable patch tests, patch type testing, individual electrode testing (e.g. to determine one or more electrodes 102 “not to be used”, as described above). For example, a voltage may be supplied between an electrode 102 pair (similar to normal operation), and the current measured. If the measured current is within expected range then the electrodes can be determined to be making good contact. If the measured current falls below expected range then it implies the impedance between electrodes is too high, thus poor or no contact. The test may be performed across different combination of pairs of electrodes 102 covering the whole patch. In some instances, a patch 101 with “bad” connections can be used (e.g., if below a maximum) by avoiding using those particular (i.e. identified as bad) electrodes 102 for stimulating and/or sensing.
Although the variations described above include a substrate for the electrodes 102 that is generally less stretchable than other regions that modify the substrate to enhance flexibility, in some variations the substrate is instead relatively highly flexible, but is treated to provide regions of enhanced stiffness, particularly around the electrodes, to maintain the predetermined relationship (e.g., spacing) between the electrodes. For example, the patch could include a flexible but relatively inelastic spine running substantially along a length of the patch, so that the spacing between electrodes is maintained, whilst allowing the patch to flex and conform to the tissue surface of the subject, for example by allowing the patch to bend along its length or width and/or to allow the patch to twist.
In general, any of the patch 102 variations described herein may also include multiplexing circuitry, for example, to reduce the number of connections to the electrodes.
Another variation of a sensor patch 601 including an array of electrodes is shown in
In the exemplary patch shown in
In some variations one or more components, such as the acquisition module 703, power supply 707, data analysis unit, etc. may be held by an intermediary structure such as a cradle or the like.
In some variations the apparatus may include additional or alternative attachments to secure components to each other and/or to the wearable holding member. For example, the various components may be magnetically secured to a wearable holding member. A magnetic or other sensor in cradle 731 and/or acquisition module 703 can be configured as a safety interlock, such as to require attachment between the two to allow an apparatus to operate (e.g., drive current). In some embodiments, cradle 731 comprises a sensor 743 and/or acquisition module 703 comprises a sensor 745, each as shown in
In some variations of a cradle such as the one shown in
In one example, the diagnostic tool device includes body extending in an arch from a first contact region to a second contact region, wherein a straight line extending between the first and second contact regions forms a neutral line and a plurality of distance measuring elements coupled to the body and configured to measure the distance from a surface beneath the arch of the body and the neutral line. Thus, this allows the diagnostic tool to be positioned in contact with the subject, and a degree of curvature for the subject's body surface measured. This in turn allows a relative physical geometry of the electrodes to be determined, in turn allowing an accurate electrode separation to be calculated, which can in turn be used when analyzing the measured impedances to determine the wetness.
For example, in
In some variations, the tool 801 may include one or more registration mark(s) 809, 810 or other alignment marks/features, e.g. at the ends, that may be used to characteristically position/align the tool 801 relative to the patient and/or the patch 833. For example, an alignment mark on a tool 801 may be aligned with registration marks or features of a patch 833, e.g. aligned with most superior electrode 831 and most inferior electrode 837, and/or other registration mark of a patch 833. In operation, these alignment features may help the tool measure consistent information over time.
In the curvature measuring tool 801 shown in
In the examples shown in
where
for i=1, 2 and x is an element of the set [0, 11]. Using this polynomial, each electrode's elevation can be evaluated; thus, the subject's topography may be approximated based on the two slide measurements taken. The tool may contact just the patch, thereby avoiding touching the patient's back, which may enhance cleanliness/sterility of the procedure, although in some variations the tool may touch the patient's back. The tool may be sterilizable.
In any of the tool variations described herein, the tool may include a display for indicating the measurements or providing feedback to the user (e.g., ready to use, measuring, etc.).
As mentioned above, the data captured by the tool may be manually captured (e.g., visually read and recorded) or it may be automatically or semi-automatically captured. The data may be transmitted to the data analysis unit, where it may be used in determining lung wetness, and/or stored for future reference, and/or transmitted. In some variations, the information recorded by the tool may be sent via a wired or wireless communication to the data analysis unit. In some variations, the apparatus may include a control or input, such as a button, knob, trigger, etc., to initiate capture of the measurement and/or storage or transmission of the values measured. For example a button or other control may be located on the handle 805.
In some variations, the tool may include translating slides that pass through an electronic measurement element, as illustrated in
This variation of a non-contacting image analyzer may therefore work with markings on the patch to determine curvature of back. As mentioned, in
Another variation of a tool for measuring the surface (e.g. curvature) onto which the patch is connected may be illustrated in
As illustrated in
Once the area is prepared, the wearable holding element (e.g., strap) may be placed on (worn by) the subject in step 1320. The acquisition module may be attached to the holding element (e.g., within a cradle) or it may be attached later. For example, a strap may be laid over the subjects shoulder (e.g., the left shoulder). As mentioned above, a power supply may be positioned on the front side of the strap, and the acquisition module may be attached to the back. In variations in which the battery is integrated with the acquisition module, nothing (or a dummy weight) may be attached to the front.
The more precise location for placement of the patch may then be determined. For example, when measuring lung wetness, the spine location that may be used to guide positioning of the patch over the lung may be determined in step 1330. For example, the back of the patient may be palpated to find the specific vertebral location (e.g., T2), which can be identified, for example, by having the patient lower their head (chin to chest). The subject can then be asked to look up/down, left/right—to confirm proper identification at T2 (no motion should be present). A mark may be made (e.g., with a non-toxic, washable marker) and used to orient the patch. The patch may then be positioned in step 1340, such as by positioning a superior end and/or a superior alignment tab of the patch relative to T2. Thereafter, the patch may be applied in step 1360. For example, the patch may be positioned with the superior alignment tab at the upper spine location and the other tabs oriented with the other alignment tabs. At least a portion (or all) of a protective covering of electrodes (backing) can be removed, and the patch applied directly to the skin while maintaining the location of the superior alignment tab. In some variations the inferior alignment tab may aligned with the spine in the proper location in step 1350 before adhering the patch to the skin in step 1360. For example, the top-left portion of patch may be adhered at location identified in step 1330, so that a superior-inferior location as well as a medial-lateral location of the patch are properly located on the patient's back.
When adhering the patch in step 1360, the patch may be slowly laid down, electrode by electrode, being careful to maintain the alignment (e.g., vertical alignment), while avoiding tugging of the patch in a way that may cause one or more electrodes (gel) to shift. Gentle pressure may be applied to each electrode, though large forces that may flatten the electrode (gel) should be avoided. Buckling of the patch should also be avoided, so that the orientation of the electrodes on the patch relative to each other may be maintained. In some variations, the patch may be removed and repositioned to remove or otherwise avoid buckling, misalignment, etc. For patients with kyphosis (e.g., curvature toward slouching or hunchback), the patch may be placed farther laterally (e.g., farther to the right) to compensate for the tendency for diagonal placement in such patients. For patients with scoliosis (e.g., sideways curvature of the spine), the patch may be positioned to best align with the underlying lung while avoiding placement over the spine and scapula. For patients with excessive fat deposits or skin folds, the patch may be placed by following the curve of the skin fold and apply extra pressure during adhesion (making sure to prepare all of the skin, including the skin in skin fold(s)). In placing the patch on patients with skin folds, the user may avoid placing the patch in regions with folds that are too large or to deep.
Once the patch has been placed, in some variations a diagnostic assessment of the patch placement may be performed in step 1365. For example, as described above, information about the patient may be collected, including but not limited to the body contour information. For example, a tool as described above may be used to perform patient diagnostics to collect information. This step may be repeated to collect additional data, or to refine the data collected. As mentioned above, in any of the variations described herein, the patient's body contour information may be collected before applying the patch (e.g., up to a day or more before applying the patch) or after collecting electrical properties data in step 1380.
Once the patch is attached to the patient, it may be connected to the acquisition module in step 1370. In some variations, the patch may be collected to the acquisition module before the patch is attached to the patient's skin. More often, the patch is attached to the acquisition module after it has been attached to the skin. In the variation shown in
Once the patch is attached, data may be collected by driving power through the electrodes and sensing the resulting response of the tissue in step 1380. For example, voltage data between two or more pairs of electrodes may be collected while driving current from other pairs of electrodes (e.g., at one or more frequencies as described above). Thus, multiple currents may be driven at different frequencies simultaneously or sequentially. Data may be collected as described in U.S. 2013/0165761 from multiple pairs of sensing electrodes. This data may be gathered, processed (e.g., filtered, averaged, etc.) and transmitted, stored and/or analyzed, for example, by a data analysis unit in step 1390 to determine tissue wetness.
For example, the process may be performed to determine a lung wetness assessment that is qualitative and/or quantitative and may provide output either directly (e.g., on a display on the apparatus) and/or indirectly, e.g., by transmitting to a physician, patient medical record, or the like. In some variations, the wetness assessment may be performed without using body geometry information. Alternatively, in some variations, the wetness assessment may be performed using body geometry information.
In one example, wetness assessment is performed to determine a wetness indicator, which could be a numerical value or graphical representation of an absolute wetness, or wetness relative to a baseline or other reference. For example, wetness measurements could be obtained for individuals in a reference population, with comparison to the wetness measurements being used to determine the wetness indicator, indicating whether the wetness is greater or less than desirable/expected which could in turn be indicative of a medical condition associated with the wetness, or the like.
Thus, in one example, a method of determining tissue wetness includes attaching a patch sensor comprising a plurality of drive electrodes and sensing electrodes to a skin surface of a subject's body, measuring a curvature of the skin surface of the subject's body, applying drive currents at a plurality of different frequencies to the drive electrodes and measuring voltages at a plurality of different sensing electrodes, determining an estimate of electrical properties for a plurality of regions beneath the patch sensor using the applied drive currents and measured voltages and determining an estimate of tissue wetness from a frequency response of the determined electrical properties.
When a feature or element is herein referred to as being “on” another feature or element, it can be directly on the other feature or element or intervening features and/or elements may also be present. In contrast, when a feature or element is referred to as being “directly on” another feature or element, there are no intervening features or elements present. It will also be understood that, when a feature or element is referred to as being “connected”, “attached” or “coupled” to another feature or element, it can be directly connected, attached or coupled to the other feature or element or intervening features or elements may be present. In contrast, when a feature or element is referred to as being “directly connected”, “directly attached” or “directly coupled” to another feature or element, there are no intervening features or elements present. Although described or shown with respect to one embodiment, the features and elements so described or shown can apply to other embodiments. It will also be appreciated by those of skill in the art that references to a structure or feature that is disposed “adjacent” another feature may have portions that overlap or underlie the adjacent feature.
Terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. For example, as used herein, the singular forms “a”, “an” and “the” are intended to include the plural forms as well, unless the context clearly indicates otherwise. It will be further understood that the terms “comprises” and/or “comprising,” when used in this specification, specify the presence of stated features, steps, operations, elements, and/or components, but do not preclude the presence or addition of one or more other features, steps, operations, elements, components, and/or groups thereof. As used herein, the term “and/or” includes any and all combinations of one or more of the associated listed items and may be abbreviated as “/”.
Spatially relative terms, such as “under”, “below”, “lower”, “over”, “upper” and the like, may be used herein for ease of description to describe one element or feature's relationship to another element(s) or feature(s) as illustrated in the figures. It will be understood that the spatially relative terms are intended to encompass different orientations of the device in use or operation in addition to the orientation depicted in the figures. For example, if a device in the figures is inverted, elements described as “under” or “beneath” other elements or features would then be oriented “over” the other elements or features. Thus, the exemplary term “under” can encompass both an orientation of over and under. The device may be otherwise oriented (rotated 90 degrees or at other orientations) and the spatially relative descriptors used herein interpreted accordingly. Similarly, the terms “upwardly”, “downwardly”, “vertical”, “horizontal” and the like are used herein for the purpose of explanation only unless specifically indicated otherwise.
Although the terms “first” and “second” may be used herein to describe various features/elements, these features/elements should not be limited by these terms, unless the context indicates otherwise. These terms may be used to distinguish one feature/element from another feature/element. Thus, a first feature/element discussed below could be termed a second feature/element, and similarly, a second feature/element discussed below could be termed a first feature/element without departing from the teachings of the present invention.
As used herein in the specification and claims, including as used in the examples and unless otherwise expressly specified, all numbers may be read as if prefaced by the word “about” or “approximately,” even if the term does not expressly appear. The phrase “about” or “approximately” may be used when describing magnitude and/or position to indicate that the value and/or position described is within a reasonable expected range of values and/or positions. For example, a numeric value may have a value that is +/−0.1% of the stated value (or range of values), +/−1% of the stated value (or range of values), +/−2% of the stated value (or range of values), +/−5% of the stated value (or range of values), +/−10% of the stated value (or range of values), etc. Any numerical range recited herein is intended to include all sub-ranges subsumed therein.
Although various illustrative embodiments are described above, any of a number of changes may be made to various embodiments without departing from the scope of the invention as described by the claims. For example, the order in which various described method steps are performed may often be changed in alternative embodiments, and in other alternative embodiments one or more method steps may be skipped altogether. Optional features of various device and system embodiments may be included in some embodiments and not in others. Therefore, the foregoing description is provided primarily for exemplary purposes and should not be interpreted to limit the scope of the invention as it is set forth in the claims.
The examples and illustrations included herein show, by way of illustration and not of limitation, specific embodiments in which the subject matter may be practiced. As mentioned, other embodiments may be utilized and derived there from, such that structural and logical substitutions and changes may be made without departing from the scope of this disclosure. Such embodiments of the inventive subject matter may be referred to herein individually or collectively by the term “invention” merely for convenience and without intending to voluntarily limit the scope of this application to any single invention or inventive concept, if more than one is, in fact, disclosed. Thus, although specific embodiments have been illustrated and described herein, any arrangement calculated to achieve the same purpose may be substituted for the specific embodiments shown. This disclosure is intended to cover any and all adaptations or variations of various embodiments. Combinations of the above embodiments, and other embodiments not specifically described herein, will be apparent to those of skill in the art upon reviewing the above description.
Throughout this specification and claims which follow, unless the context requires otherwise, the word “comprise”, and variations such as “comprises” or “comprising”, will be understood to imply the inclusion of a stated integer or group of integers or steps but not the exclusion of any other integer or group of integers.
This material may related to the following patents and patent applications, herein incorporated by reference in their entirety: U.S. Provisional Patent Application No. 62/073,790, filed on Oct. 31, 2014 (titled “APPARATUSES AND METHODS FOR DETERMINING LUNG WETNESS”); U.S. patent application Ser. No. 13/715,788, filed on Dec. 14, 2012 (titled “METHODS FOR DETERMINING THE RELATIVE SPATIAL CHANGE IN SUBSURFACE RESISTIVITIES ACROSS FREQUENCIES IN TISSUE”); U.S. patent application Ser. No. 14/171,499, filed Feb. 3, 2014 (titled “DEVICES FOR DETERMINING THE RELATIVE SPATIAL CHANGE IN SUBSURFACE RESISTIVITIES ACROSS FREQUENCIES IN TISSUE”); and U.S. Pat. No. 8,068,906, issued Nov. 29, 2011 (titled “CARDIAC MONITORING SYSTEM”).
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/AU2015/050686 | 10/30/2015 | WO | 00 |
| Number | Date | Country | |
|---|---|---|---|
| 62073790 | Oct 2014 | US |
