Patent Application
20190314192
The present disclosure relates generally to respiratory monitoring. More particularly, aspects of this disclosure relate to using sensors attached to a body to measure indicators of the onset of sleep disorders.
Integrated circuits (ICs) are the cornerstone of the information age and the foundation of today's information technology industries. The integrated circuit, a.k.a. “chip” or “microchip,” is a set of interconnected electronic components, such as transistors, capacitors, and resistors, which are etched or imprinted onto a semiconducting material, such as silicon or germanium. Integrated circuits take on various forms including, as some non-limiting examples, microprocessors, amplifiers, Flash memories, application specific integrated circuits (ASICs), static random access memories (SRAMs), digital signal processors (DSPs), dynamic random access memories (DRAMs), erasable programmable read only memories (EPROMs), and programmable logic. Integrated circuits are used in innumerable products, including computers (e.g., personal, laptop and tablet computers), smartphones, flat-screen televisions, medical instruments, telecommunication and networking equipment, airplanes, watercraft and automobiles.
Advances in integrated circuit technology and microchip manufacturing have led to a steady decrease in chip size and an increase in circuit density and circuit performance. The scale of semiconductor integration has advanced to the point where a single semiconductor chip can hold tens of millions to over a billion devices in a space smaller than a U.S. penny. Moreover, the width of each conducting line in a modern microchip can be made as small as a fraction of a nanometer. The operating speed and overall performance of a semiconductor chip (e.g., clock speed and signal net switching speeds) has concomitantly increased with the level of integration. To keep pace with increases in on-chip circuit switching frequency and circuit density, semiconductor packages currently offer higher pin counts, greater power dissipation, more protection, and higher speeds than packages of just a few years ago.
The advances in integrated circuits have led to related advances within other fields. One such field is sensors. Advances in integrated circuits have allowed sensors to become smaller and more efficient, while simultaneously becoming more capable of performing complex operations. Other advances in the field of sensors and circuitry in general have led to wearable circuitry, a.k.a. “wearable devices” or “wearable systems.” Within the medical field, as an example, wearable devices have given rise to new methods of acquiring, analyzing, and diagnosing medical issues with patients, by having the patient wear a sensor that monitors specific characteristics. Related to the medical field, other wearable devices have been created within the sports and recreational fields for the purpose of monitoring physical activity and fitness. For example, a user may don a wearable device, such as a wearable running coach, to measure the distance traveled during an activity (e.g., running, walking, etc.), and measure the kinematics of the user's motion during the activity.
One example of a body function that is desirable to monitor is respiration during sleep to detect abnormalities such as sleep apnea. Sleep apnea is a condition that manifests itself by lack of breathing during sleep. Sleep apnea is caused by an obstruction in the airway pipe or by the inability of the body to relay the proper neural signals to induce the respiratory system. Sleep apnea inhibits a person's ability to adequately inspire oxygen while sleeping, causing the heart to work harder to oxygenate the body's vital organs. This condition may be caused by the most common form of sleep apnea, known as Obstructive Sleep Apnea (OSA). One symptom of this condition includes lack of breathing for long seconds or even minutes, caused by a narrowing of the airway that restricts the flow of air into the lungs.
If the duration and frequency of breathing absence were measurable by a sensor and coupled with ECG data from another sensor, inferences regarding the loading on the cardiovascular system may be drawn. Furthermore, if a motion-based sensor were coupled with this measurement to indicate posture and position during sleep, a determination may be made regarding whether the sleep apnea is caused by positional (PP) or non-positional (NPP) OSA. Unfortunately, currently there is no convenient mechanism to continuously monitor a person during sleep for measurements to indicate the occurrence of sleep apnea.
Thus, there is a need for an accurate system to characterize the occurrence of sleep apnea. There is yet another need for a system to provide non-invasive monitoring for the occurrence of sleep apnea. There is another need for a system that allows the detection of sleep apnea for activating an external correction mechanism.
One disclosed example is a sensor system for sensing a sleep abnormality in a user. The system includes an accelerometer sensor in contact with the skin of the user to measure a deflection of the body during respiration and generate a respiration waveform. A controller receives the respiration waveform from the accelerometer sensor to determine a sleep abnormality measurement as a function of the respiration waveform.
Another disclosed example is a method of detecting a sleep abnormality in a user. An accelerometer sensor is attached in contact with the skin of the user to measure a deflection of the body during respiration. A respiration waveform is generated from the accelerometer sensor. A respiration waveform from the accelerometer sensor is received by a controller. A sleep abnormality measurement is determined as a function of the respiration waveform by the controller.
The above summary is not intended to represent each embodiment or every aspect of the present disclosure. Rather, the foregoing summary merely provides an exemplification of some of the novel aspects and features set forth herein. The above features and advantages, and other features and advantages of the present disclosure, will be readily apparent from the following detailed description of representative embodiments and modes for carrying out the present invention when taken in connection with the accompanying drawings and the appended claims.
The disclosure will be better understood from the following description of exemplary embodiments together with reference to the accompanying drawings, in which:
The present disclosure is susceptible to various modifications and alternative forms, and some representative embodiments have been shown by way of example in the drawings and will be described in detail herein. It should be understood, however, that the invention is not intended to be limited to the particular forms disclosed. Rather, the disclosure is to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the invention as defined by the appended claims.
The present inventions can be embodied in many different forms. There are shown in the drawings, and will herein be described in detail, representative embodiments with the understanding that the present disclosure is to be considered as an exemplification or illustration of the principles of the present disclosure and is not intended to limit the broad aspects of the disclosure to the embodiments illustrated. To that extent, elements and limitations that are disclosed, for example, in the Abstract, Summary, and Detailed Description sections, but not explicitly set forth in the claims, should not be incorporated into the claims, singly or collectively, by implication, inference, or otherwise. For purposes of the present detailed description, unless specifically disclaimed: the singular includes the plural and vice versa; and the word “including” means “including without limitation.” Moreover, words of approximation, such as “about,” “almost,” “substantially,” “approximately,” and the like, can be used herein in the sense of “at, near, or nearly at,” or “within 3-5% of,” or “within acceptable manufacturing tolerances,” or any logical combination thereof, for example.
The wearable sensor device 110 is preferably positioned on the neck in close proximity to the carotid artery above the left clavicle. However, the sensor device 110 can be located in any area in proximity to the carotid artery such that it can sense the motion or vibration produced by the respiratory airway during respiration. As shown in
The wearable sensor device 110 and, optionally, wearable ECG sensor device 112 can be in communication with a smart device or hub such as a user device 130. The user device 130 can be a computing device such as a smart phone, a tablet, a laptop or desktop computer, a personal digital assistant or a network of computers (e.g., a cloud or a cluster). The user device 130 can used to control and/or program the wearable sensor device 110 and, optionally, control and/or program wearable ECG sensor 112. Although the wearable sensor devices 110 and 112, as described herein, are used for non-invasive respiratory and/or heart monitoring, each can have other measurement and sensing functions in relation to the user 100. In accordance with some embodiments, the ECG sensor 112 can include an implanted component (e.g., a pace maker).
The data from the wearable sensor device 110 representative of the respiration activity signals (e.g., waveform 116) and, optionally, the data from wearable ECG sensor device 112 representative of the heartbeat signal (e.g., waveform 114) can be uploaded to a cloud storage server 140 periodically (e.g., in time-stamped blocks) or continuously (e.g., streamed) and analyzed by applications running on one or more cloud application servers 142. The data can be processed in real time or using post-processing techniques. The user can access the data, the analysis applications or the output of the applications by accessing the cloud server 142, such as through a website.
As will be explained below, any of the sensors 110 and 112 may be used to sense and store data to determine sleep disorders. The user device 130 can include software that processes the sensed data in order to determine the occurrence and characterization of sleep apnea. Alternatively, on or more cloud applications executed on the cloud application server 160 can process the data received from the sensors 110 and 112 (e.g., via the user device 130) to the determination of the occurrence and characterization of sleep apnea based on the sensed data.
In accordance with some embodiments of the invention, the system shown in
In addition, the wearable ECG sensor 112 can measure the ECG waveform and can be used to detect irregular patterns in heart rate activity. These irregular heart beat patterns can be analyzed (with or without the respiration data) by one or more applications executed by the smart device 130 or one or more applications executed on the cloud server 142 to determine cardiovascular health issues. For example, changes in the ECG signal coincident with shallow or lack of breathing associated with sleep apnea can be used to determine an impact of the apneic events on the user's heart. More specifically, changes in the amplitude, for example, of the R wave or Q wave can be detected and used to determine a measure of strain on the user's heart.
This respiration and/or sound data can be analyzed in real time by the smart device 130 or cloud server 142 to determine whether the user 100 is suffering from a sleep apnea event (e.g., shallow breathing or lack of breathing associated with sleep apnea). Once this determination is made, the smart device 130 (or the cloud server 142) can sound an alarm or send a signal to an external device, such as an alarm or motor actuators on a mattress, to change the subject's environment and mitigate the apnea event while minimizing the disruption to the user's sleep. In one example, the user device 130 can be programmed to sound an audio alarm when an abnormal breathing pattern associated with sleep apnea is detected. The alarm can be selected such that it will jostle the user 100 promoting a body position change to promote respiration. The user device 130 can also send a signal to a mattress 150 that includes one or more mechanical actuators (e.g., vibration motors) to induce a change in the sleeping position of the user 100 (e.g., raise the user's head or feet). In this manner, the sleep apnea system in
Further, the system shown in
The wearable device 200 described herein can be formed as a patch. The patch can be flexible and stretchable, and can include stretchable and/or conformal electronics and/or conformal electrodes disposed in or on a flexible and/or stretchable substrate. Alternatively, the wearable device 200 can be rigid but otherwise attachable to a user. In accordance with some embodiments of the invention, the wearable device 200 can include portions that are stretchable and/or conformable and portions that are rigid. Thus, the wearable device 200 can be any device that is wearable on a user, such as coupled to the skin of the user, to provide measurement and/or analysis of physiological information of the user. For example, the wearable device can be adhered to the body by adhesive (e.g. a pressure sensitive adhesive), held in place against the body by tape or straps, or held in place against the body by clothing. The more conformal the sensing device is more likely to stay in position on the skin and produce more reliable and accurate sensor data.
In general, the wearable device 200 of
The processor 201 can be used as a controller that is configured to control the wearable device 200 and components thereof based on computer program code (e.g., one or more software modules). Thus, the processor 201 can control the wearable device 200 to receive and store sensor data from one or more of the sensors 205, 213, 217. The sensor data can be calibrated and used to determine measures indicative of temperature, motion and/or other physiological data (e.g., ECG, EMG, EEG signals and data), and/or analyze such data indicative of temperature, motion and/or other physiological data according to the principles described herein.
The memory storage module 203 can be configured to save the generated sensor data (e.g., the time when a pulse in blood flow is sensed, accelerometer 205 information, temperature sensor 213 information, or other physiological information, such as ECG, EMG, EEG signals and data) or information representative of acceleration and/or temperature and/or other physiological information derived from the sensor data. Further, according to some embodiments, the memory storage module 203 can be configured to store the computer program code that controls the processor 201. In some implementations, the memory storage module 203 can include volatile and/or non-volatile memory. For example, the memory storage module 203 can include flash memory, static memory, solid state memory, removable memory cards, or any combination thereof. In certain examples, one or more of the memory storage modules 203 can be removable from the wearable device 200. In some implementations, one or more of the memory storage modules 203 can be local to the wearable device 200, while in other examples one or more of the memory storage modules 203 can be remote from the wearable device 200. For example, one or more of the memory storage modules 203 can include the internal memory of a smartphone such as the user device 130 in
In some embodiments, the generated data, including the temperature information, the acceleration information, and/or the other physiological information (e.g., ECG, EMG, EEG etc.), can be stored in one or more of the memory storage modules 203 for processing at a later time. Thus, in some embodiments, the wearable device 200 can include more than one memory storage module 203, such as one volatile and one non-volatile memory storage module 203. In other examples, the memory storage module 203 can store the information indicative of motion (e.g., acceleration information), temperature information, physiological data, or analysis of such information indicative of motion, temperature, physiological data according to the principles described herein, such as storing historical acceleration information, historical temperature information, historical extracted features, and/or historical locations. The memory storage module 203 can also store time and/or date information about when the information was received from the sensor. For example, each data element or block of data elements can be associated with a date and/or time at which it was created.
Although described as the processor 201 being configured according to computer program code in the form of software and firmware, the functionality of the wearable device 200 can be implemented based on hardware, software, or firmware or a combination thereof. For example, the memory storage module 203 can include computer program code in the form of software or firmware that can be retrieved and executed by the processor 201. The processor 201 executes the computer program code that implements the functionality discussed below with respect to determining the on-body status of the wearable device 200, the location of the wearable device 200 on a user, and configuring functionality of the wearable device 200 (e.g., based on the on-body status and sensed location). Alternatively, one or more other components of the wearable device 200 can be hardwired to perform some or all of the functionality.
The power source 209 can be any type of rechargeable (or single use) power source for an electronic device, such as, but not limited to, one or more electrochemical cells or batteries, one or more photovoltaic cells, or a combination thereof. In the case of the photovoltaic cells, the cells can charge one or more electrochemical cells and/or batteries. In accordance with some embodiments, the power source 209 can be a small battery or capacitor that stores enough energy for the device to power up and execute a predefined program sequence before running out of energy, for example, an NFC based sensing device.
As discussed above, the wearable device 200 can include one or more sensors, such as the accelerometer 205, a temperature sensor 213, electrical contacts 215 (e.g., electrical contacts or electrodes), and/or an optical sensor 217. In accordance with some embodiments, one or more of the sensors, such as accelerometer 205, the optical sensor 217 and/or electrical contacts 215, can be separate components from the wearable device 200. That is, the wearable device 200 can be connected (by wire or wirelessly) to each sensor (e.g., accelerometer 205, temperature sensor 213, electrical contacts 215, and optical sensor 217). This enables the wearable device 200 to sense conditions at one or more locations that are remote from the wearable device 200. In accordance with some embodiments, the wearable device 200 can include one or more integral sensors in addition to one or more remote sensors.
The accelerometer 205 measures and/or generates acceleration information indicative of a motion and/or acceleration of the wearable device 200, including information indicative of a user wearing, and/or body parts of the user wearing, the wearable device 200. In accordance with one embodiment, the accelerometer 205 within the wearable device 200 can include a 3-axis accelerometer that generates acceleration information with respect to the x-axis, the y-axis, and the z-axis of the accelerometer based on the acceleration experienced by the wearable device 200. Alternatively, the wearable device 200 can include three independent accelerometers (not shown for illustrative convenience) that each generate acceleration information with respect to a single axis, such as the x-axis, the y-axis, or the z-axis of the wearable device 200. Alternatively, the wearable device 200 can include an inertial measurement unit (IMU) that measures the angular velocity, the orientation, and the acceleration using a combination of one or more accelerometers, gyroscopes, and magnetometers. Thus, although generally referred to herein as an accelerometer 205, the accelerometer 205 can be any motion sensing element or combination of elements that provides acceleration information.
In this example, the accelerometer 205 is an MPU-6500 manufactured by Invensense. According to some embodiments, the accelerometer 205 includes a detection range of ±2 times the force of gravity (Gs). However, the range can vary, such as being ±16 Gs or ±2 Gs. Further, the accelerometer 205 can have a sampling rate of 100 hertz (Hz) such that each second the accelerometer 205 generates 300 points of acceleration information, or 100 points within each axis. However, the sampling rate can vary, such as being 20 Hz to 100 Hz.
According to some embodiments, one or more sensors of the wearable device 200, such as the accelerometer 205, can include a built-in temperature sensor, such as the temperature sensor 211 within the accelerometer 205. For example, the temperature sensor 211 within the accelerometer 205 can be used to calibrate the accelerometer 205 over a wide temperature range and to measure the temperature of the area of the body that the accelerometer 205 is coupled to. Other temperature sensors included with other device components can also be used. Other than the accelerometer 205, and temperature sensor 211, other subcomponents or elements of the wearable device 200 can include one or more microelectromechanical system (MEMS) components within the wearable device 200 that is designed to measure motion or orientation (e.g., angular-rate gyroscope, etc.).
In accordance with some embodiments of the invention, an accelerometer (or an acoustic sensor) such as the accelerometer 205 of the wearable sensor device 200 shown in
Alternatively, or in addition, the wearable device 200 can include a discrete temperature sensor, such as the temperature sensor 213 which can be positioned in a different location from the wearable device 200. The wearable device 200 can use the temperature information detected by the temperature sensor 211 and/or the temperature sensor 213 according to various methods and processes. For purposes of convenience, reference is made below to the temperature sensor 211. However, such reference is not limited to apply only to the temperature sensor 211, but applies to any one or more temperature sensors within or connected to the wearable device 200.
The electrical contacts 215 can be formed of conductive material (e.g., copper, silver, gold, aluminum, a hydrogel, conductive polymer, etc.) and provide an interface between the wearable device 200 and the skin of the user 100, for receiving electrical signals (e.g., ECG, EMG, etc.) from the skin. The electrical contacts 215 can include one or more electrical contacts 215, such as two electrical contacts 215, electrically connecting the skin of the user 100 to an amplifier circuit that can be part of an analog front end circuit 216, to amplify and condition electrical signals (e.g., ECG, EMG, etc.). With two electrical contacts 215, one contact can be electrically configured as a positive contact and the other contact can be electrically configured as a negative contact. However, in some aspects, there may be more than two electrical contacts, such as four electrical contacts 215 (e.g., two positive and two negative electrical contacts), six electrical contacts 215, etc.
The optical sensor 217 can measure the photoplethysmography (PPG) signal when placed on the skin's surface, allowing for the monitoring of various biometrics including, but not limited to, heart rate, respiration, and blood oxygen measurements. The optical sensor 217 can include one or more light emitters that can emit red, green, infrared light or a combination thereof and one or more optical transducers (e.g., photodiode, CCD sensors). Using the one or more optical transducers, the optical sensor 217 can sense the wavelength of the reflected light. In this example, the optical sensor 217 illuminates the skin and the reflected light changes intensity based on the concentration of oxygen in a blood vessel such as an artery or a capillary bed. Thus, a pulse can be detected as a change in the amount of the reflected light due to a change in the concentration of oxygen in a blood vessel and thus the reflected light detected by the optical sensor 217. The system can contain an array of optical sensors in a one-dimensional or two-dimensional grid. In this configuration, the optical sensors can measure reflected light (pulse oxygenation and pulse waveforms) at multiple locations along the vasculature, enabling measurement of time of flight and pulse wave velocity over a given distance (e.g., the separation distance between individual optical sensors. Of course other sensors can be included on the wearable device 200 to detect the pulse such as the accelerometer 205, a pressure sensor, a strain gauge sensor or an acoustic sensor to measure the mechano-acoustic signatures of the pulse.
In addition to the above-described components, the wearable device 200 can include one or more additional components without departing from the spirit and scope of the present disclosure. Such components can include a display (e.g., one or more light-emitting diodes (LEDs), liquid crystal display (LCD), organic light-emitting diode (OLED)), a speaker, a microphone, a vibration motor, a barometer, a light sensor, a photoelectric sensor, or any other sensor for sensing, measuring, or otherwise quantifying parameters and/or characteristics of the body. In other embodiments of the invention, the wearable device 200 can include components for performing one or more additional sensor modalities, such as, but not limited to, hydration level measurements, conductance measurements, and/or pressure measurements. For example, the wearable device 200 can be configured to, or include one or more components that, perform any combination of these different types of sensor measurements, in addition to the accelerometer 205 and temperature sensor 211.
Referring back to the temperature sensor 211, according to some embodiments, the primary purpose of the temperature sensor 211 is for calibrating the accelerometer 205. Accordingly, the temperature sensor 211 does not rely on direct contact to an object to detect the temperature. By way of example, the temperature sensor 211 does not require direct contact to the skin of a user when coupled to the user to determine the skin temperature. For example, the skin temperature affects the temperature information generated by the wearable device 200 without direct contact between the temperature sensor 211 and the skin. Accordingly, the temperature sensor 211 can be fully encapsulated and, therefore, be waterproof for greater durability. The thermal conductivity of the encapsulating material can be selected to control the ability of the temperature sensor 211 to detect the temperature without direct contact.
The wearable device 200 can be constructed of a flexible and/or stretchable printed circuit (e.g., a flex printed circuit board) that can be encapsulated in an elastomer (e.g., silicone, poly urethane, PDMS) that enables the device to stretch and bend. In accordance with some embodiments of the invention, the wearable device 200 can be constructed to have modulus of elasticity (e.g., Young's modulus) similar to the skin of the user or subject. This construction enables the wearable device 200 to be tightly adhered to the skin using a pressure sensitive adhesive such that the sensors in the wearable device are able to detect the slightest motion of the skin as well as the muscles and organ under the skin in the area of the body where the wearable device 200 is attached. This tight coupling can be accomplished using a thin layer (e.g., less than 150 um) of pressure sensitive adhesive and a thin layer (e.g., less than 150 um) of encapsulating material (e.g., silicone). The adhesive and encapsulating materials can be selected to faithfully transmit to the sensors any vibrations or motions from the skin to which it is attached. In accordance with some embodiments of the invention, the sensors in wearable device 200 placed on the neck adjacent the carotid artery can detect the motion of the esophagus expanding and contracting during breathing as well as the vibrations caused by air flowing through the esophagus. In accordance with some embodiments of the invention, the sensors in wearable device 200 placed on the neck adjacent the carotid artery can detect the motion of the user's neck and chest during respiration. In accordance with some embodiments of the invention, the sensors in wearable device 200 placed on the neck adjacent the carotid artery can detect the motion and vibration of the carotid artery as the blood flows through it to detect the heart beat and the heart rate.
The form factor of the wearable device 200 allows positioning and repositioning of the sensor devices at different locations on the body of the user 100 in order to achieve the highest quality of data. In this example, the sensor device 120 placed on the chest of the user 100 in
The sleep apnea detection system in
In accordance with some embodiments of the invention, the user 100 can attach the sensor 110 on the neck near the left clavicle and the sensor 112 near the heart and left clavicle respectively before sleeping. The sensors 110 and 112 allow the user device 130 to monitor respiration for events related to sleep apnea throughout a sleep period. The sensor 110 measures the motion of the user 100 and detects breathing inactivity from the waveform such as that shown in
The smart device 130 collects data from the sensors 110 and 112 via a wireless communication channel such as a BlueTooth Low Energy signal. Based on the collected data, the user device 130 makes a determination if the event is due to apnea. For example, motion-based data can be used to detect and record the respiration movements of the user 100. An abrupt cessation of respiration, as identified by the motion data can be used to detect a sleep apnea event. This manifests itself by an absence of the waveform morphology found in the waveform 116 (i.e., the steady undulation of the waveform in the respiration frequency range indicates respiration). In addition to this data stream, data from the sensor 112 can be used to augment the analysis by providing ECG data. This can inform the algorithm that runs on the cloud server 142 or user device 130 whether the user's heart is loaded more heavily by the lack of respiration (i.e., the heart must pump more quickly to feed oxygen to the body, compensating for the lack of oxygen in the system). The user device 130 may provide activation of an external device such as an alarm or the actuators on the mattress 150 or a bed to mitigate the sleep apnea event.
In this example, the sensor device 112 can continuously (or periodically) send the output of the ECG signal received from the electrical contacts 215 in
The user device 130 receives the ECG output waveform signal from the sensor device 112 and the accelerometer output waveform signal from the sensor device 110 (408). The user device 130 determines whether there is an abnormal event such as an occurrence of an interruption in respiration indicating sleep apnea based on the analysis of the received data (410). If there is no abnormal event, the user device 130 returns to receiving the output signals (408). If an interruption is detected, the user device 130 stores the data from the waveform signals in memory (412). The device 130 then sends a corrective signal to an external device such as an alarm or an actuator (414). The user device 130 then returns to receiving data (408).
The process described in
Knowledge of the data relating to sleep abnormalities from the data collected from the sensors 110 and 112 may allow physicians to tailor treatment options for OSA patients. In addition, Central Sleep Apnea (CSA), where the brain fails to relay the appropriate signals to initiate breathing, is a condition that may be differentiated from OSA by data from other sensors on the body. These may include, but are not limited to, motion, ECG, and PPG based sensors. Based on the above background, the system 100 allows accurate and non-invasive characterization of sleep apnea using the sensors 110 and 112, providing a means to potentially predict the onset of sleep apnea and/or augment a user's environment to prevent its persistence throughout the night.
The system 100 may also function as a real time health monitor for at-risk patients and their caregivers. Examples of the former include, but are not limited to: infants at risk for Sudden Infant Death Syndrome (SIDS) and patients with severe forms of sleep apnea, etc. In other embodiments, the system can be used to gauge frequency and efficacy of blood flow through the carotid artery. This can be accomplished by using the data from the accelerometer 205 in
In some embodiments, the aforementioned methods include at least those steps enumerated above. It is also within the scope and spirit of the present disclosure to omit steps, include additional steps, and/or modify the order of steps presented herein. It should be further noted that each of the foregoing methods can be representative of a single sequence of related steps; however, it is expected that each of these methods will be practiced in a systematic and repetitive manner.
While particular embodiments and applications of the present disclosure have been illustrated and described, it is to be understood that the present disclosure is not limited to the precise construction and compositions disclosed herein and that various modifications, changes, and variations can be apparent from the foregoing descriptions without departing from the spirit and scope of the invention as defined in the appended claims.
The present application claims priority to U.S. Provisional Application No. 62/415,255, filed on Oct. 31, 2016. The entirety of that application is hereby incorporated by reference.
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/US17/59210 | 10/31/2017 | WO | 00 |
| Number | Date | Country | |
|---|---|---|---|
| 62415255 | Oct 2016 | US |
