Patent Publication Number: US-2020282180-A1

Title: System, Method, and Apparatus for Detecting Tube Misplacement in a Patient&#39;s Airway

Description:
FIELD 
     The present subject matter relates generally to a system, method, and apparatus for administering fluids to body cavities and, more particularly, to such systems, methods, and apparatus utilizing a carbon dioxide sensor to detect whether a tube is incorrectly inserted into a patient&#39;s airway. 
     BACKGROUND 
     Physicians and other health care providers frequently use catheters, which include tubes inserted into the human body, to treat patients. A nasogastric (NG) tube is one type of tube that is placed in the gastrointestinal tract for patients experiencing a variety of ailments. NG tubes are placed through the nasal cavity and are intended to traverse through the esophagus down into the stomach and into the small bowel, if desired. As the tube travels through the oropharynx and hypopharynx, the anatomy splits into the trachea and the esophagus. Tubes commonly are misplaced into the trachea, which can result in pneumonia, pneumothoraces, or even death. As such, there is a critical need for a way to determine when the tube has taken the path of the trachea as opposed to the desired path of the esophagus. 
     In some cases, health care providers use X-ray machines to gather information about the location of the catheters within the body. There are several disadvantages in using X-ray machines. For instance, X-rays from these machines are a known carcinogen, if received in sufficient doses. Also, X-ray machines are relatively large and heavy, consume a relatively large amount of energy, and may expose the patient to a relatively high degree of radiation. Moreover, these machines are typically not readily accessible for use because, due to their size, they are usually installed in a special X-ray room. This room can be relatively far away from the patient&#39;s room. Therefore, health care providers may find it inconvenient to use these machines for their catheter procedures. Further, it can be inconvenient to transport these machines to a patient&#39;s home for home care catheter procedures. As such, X-ray confirmation of the tube tip position may be performed only when the position is uncertain, and the enteral tube position more commonly is checked by assessing the pH of tube aspirate. However, it can be difficult to determine a practical pH cutoff level for reliable confirmation of NG tube placement, particularly for pediatric patients. 
     In other cases, electromagnetism is used to monitor the location or position of the enteral tube tip. For example, an electromagnetic stylet inserted into the patient&#39;s body with the enteral tube may provide real-time location information on the tube tip placement within a patient&#39;s anatomy. A receiver unit outside the body detects an electromagnetic field transmitted by the stylet and provides on-screen visualization and, thereby, immediate feedback on tube placement. Nevertheless, due to, e.g., variation in placement of the receiver unit and user misinterpretations of the feedback from the electromagnetic stylet, a health care provider can fail to recognize a misplacement of the enteral tube tip within the patient&#39;s airway. 
     Thus, recognition of the airway when placing an enteral tube is an important way to prevent harm to a patient, and the art is continuously seeking new and improved systems, apparatus, and methods for determining a location of a tip of a catheter, such as an NG tube, being inserted into a patient. For instance, an improved enteral tube, such as an NG tube, incorporating means for detecting carbon dioxide to determine whether the enteral tube is being improperly inserted in a patient&#39;s airway would be useful. More particularly, embedding one or more CO 2  sensors in an enteral tube, such as an NG tube, for detecting the CO 2  concentration along the path of the tube would be desirable. Further, incorporating a micro-electro-mechanical system (MEMS) that detects CO 2  in a range of the CO2 concentration in a person&#39;s exhaled breath into, e.g., the tip of the enteral tube would be useful. Additionally, systems for conveying feedback from such carbon dioxide sensors to a health care provider would be beneficial. Moreover, methods for detecting a tube misplacement in a patient&#39;s airway utilizing such carbon dioxide sensors would be advantageous. 
     SUMMARY 
     Objects and advantages of the invention will be set forth in part in the following description, or may be obvious from the description, or may be learned through practice of the invention. 
     In one aspect, the present subject matter is directed to a tube tip detection system that comprises an enteral tube having a tip, a first sensing component disposed at the tip, and a feedback display. Feedback from the first sensing component is displayed on the feedback display to indicate to a user of the tube tip detection system whether the tip is misplaced in a patient&#39;s airway. It should also be understood that the system may further include any of the additional features as described herein. 
     In another aspect, the present disclosure is directed to an enteral tube that comprises a tip, a length, and a sensing component. The sensing component is a micro-electro-mechanical system (MEMS) infrared carbon dioxide sensor. It should also be appreciated that the enteral tube may further include any of the additional features as described herein. 
     In yet another aspect, the present disclosure is directed to a method for detecting a tube misplacement in a patient&#39;s airway. The method comprises embedding a carbon dioxide sensing component into an enteral tube, inserting the enteral tube into the patient through the patient&#39;s nose or mouth, and monitoring feedback from the carbon dioxide sensing component to determine if the enteral tube is traveling into the patient&#39;s airway. It should also be understood that the method may further include any of the additional features as described herein. 
     These and other features, aspects and advantages of the present subject matter will become better understood with reference to the following description and appended claims. The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate embodiments of the invention and, together with the description, serve to explain the principles of the invention. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       A full and enabling disclosure of the present subject matter, including the best mode thereof, directed to one of ordinary skill in the art, is set forth in the specification, which makes reference to the appended figures, in which: 
         FIG. 1A  provides a schematic view of a tube tip detection system having an enteral tube, a sensing component embedded in the enteral tube, and a feedback display, according to an exemplary embodiment of the present subject matter. 
         FIG. 1B  illustrates the tube tip detection system of  FIG. 1A  and provides an enlarged view of a tip of the enteral tube. 
         FIG. 2  illustrates a tube tip detection system according to another exemplary embodiment of the present subject matter, the system having an enteral tube and more than one sensing component embedded in the enteral tube. 
         FIG. 3  provides a side perspective view of a portion of an enteral tube having a plurality of sensing components disposed in a channel formed in a wall of the enteral tube. 
         FIG. 4  provides a schematic view of a human patient with a tip of an enteral tube entering the patient&#39;s airway and a sensing component disposed at or near the tip to detect that the tip is entering the patient&#39;s airway. 
         FIG. 5  provides a flow diagram illustrating a method for detecting a tube misplacement in a patient&#39;s airway. 
     
    
    
     DETAILED DESCRIPTION 
     Reference will now be made in detail to one or more embodiments of the invention, examples of the invention, examples of which are illustrated in the drawings. Each example and embodiment is provided by way of explanation of the invention, and is not meant as a limitation of the invention. For example, features illustrated or described as part of one embodiment may be used with another embodiment to yield still a further embodiment. It is intended that the invention include these and other modifications and variations as coming within the scope and spirit of the invention. 
     Before explaining at least one embodiment of the invention in detail, it is to be understood that the invention is not limited in its application to the details of construction and the arrangement of the components set forth in the following description or illustrated in the drawings. The invention is capable of other embodiments or of being practiced or carried out in various ways. Also, it is to be understood that the phraseology and terminology employed herein is for the purpose of description and should not be regarded as limiting. 
     Generally, the present subject matter provides catheters for intubating patients having one or more sensing components for sensing carbon dioxide to determine, using the carbon dioxide concentration sensed by the sensing component(s), whether the catheter is being inserted into the patient&#39;s airway. Certain catheters are inserted into through the patient&#39;s nose or mouth and extend into the patient&#39;s gastrointestinal tract and, thus, also may be referred to as enteral catheters or enteral tubes. More particularly, enteral tubes inserted through the patient&#39;s nose are called nasogastric (NG) tubes, which typically are feeding tubes. The feeding tube tip, through which a fluid flows into the patient, is disposed in the stomach or intestines, and a feeding source delivers liquid nutrient, liquid medicine, or a combination of the two to the patient. Because erroneous placement of the tube tip may injure or harm the patient, particularly if the tube is misplaced into the patient&#39;s airway, it is important to place the tip of the tube at the proper location within the patient&#39;s body. Thus, the present subject matter provides enteral tubes having one or more carbon dioxide sensors, which continuously sense carbon dioxide as the enteral tube is inserted into a patient such that a user (such as a health care provider) can determine whether the enteral tube is being misplaced into the patient&#39;s airway, where the carbon dioxide concentration is increased compared to the carbon dioxide concentration in the correct placement area, the patient&#39;s esophagus and gastrointestinal tract. Further, the present subject matter provides systems and methods for detecting a tube misplacement in a patient&#39;s airway. 
     Referring now to the drawings,  FIGS. 1A and 1B  illustrates a tube tip detection system  100  having an enteral tube  102  that includes a proximal end or head  104  and a distal end or tip  106 . The enteral tube  102  has a length L between the proximal end  104  and the tip  106 . Further, the enteral tube  102  should have an appropriate diameter and be sufficiently flexible for insertion through, e.g., a patient&#39;s nose or mouth and into the patient&#39;s gastrointestinal tract. For instance, the enteral tube  102  should have a size within a range of five to seven French (5 Fr to 7 Fr) for pediatric patients and within a range of ten to twelve French (8 Fr to 12 Fr) for adult patients. 
     In exemplary embodiments the enteral tube  102  is a nasogastric (NG) tube, which, through a process called nasogastric intubation, is inserted through a patient&#39;s nose into the patient&#39;s stomach. In other exemplary embodiments, the enteral tube  102  is an orogastric (OG) tube inserted during orogastric intubation through the patient&#39;s mouth into the stomach. Alternatively, the tube tip  106  may extend into the patient&#39;s intestines rather than the stomach. Whether the tip  106  is disposed in the stomach or intestines may depend on, e.g., the specific needs of the patient. For typical nasogastric intubations or orogastric intubations, the tube tip  106  should be in a sub-diaphragmatic position in the stomach, e.g., at least ten (10) centimeters (cm) beyond the gastro-esophageal junction (GOJ), also known as the oesophagogastric junction, which is the part of the gastrointestinal tract where the esophagus and stomach are joined. 
     As discussed herein, misplacement of the tip  106  in the patient&#39;s airway, e.g., the bronchi or the lungs, rather than in the patient&#39;s gastrointestinal tract is a complication of nasogastric or orogastric intubation. To avoid such misplacement, the present subject matter provides enteral tubes  102  with sensing components to detect whether the tube tip  106  is being misplaced in the patient&#39;s airway. In the depicted embodiment, a first sensing component  108  is disposed at the tip  106 , and a feedback display  110  is disposed at the head  104 . In exemplary embodiments, the first sensing component  108  is a micro-electro-mechanical system (MEMS) component, which provides a miniaturized sensor having appropriate dimensions to be embedded in a wall  112  of enteral tube  102  at its tip  106 . More specifically, silicon-based MEMS sensors can be fabricated in small sizes, such as in micrometer (μm) to millimeter (mm) sizes, in clean rooms and then embedded in enteral tubes  102 . Feedback from the first sensing component  108  is displayed on the feedback display  110  to indicate to a user of the tube tip detection system  100  whether the tip  104  is misplaced in a patient&#39;s airway or is properly placed in the patient&#39;s esophagus or gastrointestinal tract. The user may be a health care provider, such as a physician, clinician, nurse, etc. 
     The MEMS component  108  includes one or more MEMS active and passive components that form a non-dispersive infrared (IR) sensor. Carbon dioxide (CO2) strongly absorbs infrared radiation at a wavelength of 4.3 μm. Further, the CO 2  concentration at the end of a person&#39;s exhaled breath is approximately 5% to 6% of the exhaled air, which corresponds to about 35 mmHg to about 45 mmHg. Therefore, the MEMS infrared sensor is configured to detect CO 2  to determine whether the enteral tube is being misplaced in the patient&#39;s airway and may be referred to as a MEMS infrared carbon dioxide sensor  108 . More particularly, the MEMS component  108  includes an IR emitter  108   a  and an IR receiver  108   b , which form the MEMS infrared carbon dioxide sensor  108 . The IR emitter  108   a  emits infrared radiation, and the IR receiver  108   b  receives any reflected radiation. An IR path length between the IR emitter  108   a  and the IR receiver  108   b  dictates the CO 2  concentration the IR carbon dioxide sensor  108  can detect. Thus, the MEMS component  108 , particularly the IR emitter  108   a  and IR receiver  108   b , should be constructed such that the sensor  108  can detect a CO 2  concentration of at least 30 mmHg to 50 mmHg and, in particular embodiments, of at least 35 mmHg to 45 mmHg. 
     Based on the reflected IR radiation, the tube tip detection system  100  determines how much IR radiation was absorbed by the air surrounding the enteral tube  102  and thereby determines the CO 2  concentration of the air within a pathway  114  ( FIG. 4 ) being traversed by the tube  102 . In some embodiments, if the CO 2  concentration is at least 30 mmHg, the tube tip detection system  100  may determine that the tip  106  of the enteral tube  102  is being misplaced in the patient&#39;s airway. In other embodiments, the tube tip detection system  100  may determine that the tip  106  of the enteral tube  102  is being misplaced in the patient&#39;s airway if the CO 2  concentration is at least 35 mmHg. That is, the first sensing component  108 , or MEMS infrared carbon dioxide sensor  108 , embedded in the enteral tube  102  near its tip  106  is configured to sense a CO 2  concentration of at least 30 mmHg, or in other embodiments, of at least 35 mmHg, which corresponds to the low end of the typical range of CO 2  concentration in a person&#39;s exhaled breath. When the sensing component  108  senses such a CO 2  concentration, the sensing component  108  provides feedback of the CO 2  concentration to the user via the feedback display  110 . In some embodiments, the feedback from the sensing component  108  indicates the tip  106  is entering the airway when the CO 2  concentration sensed by the sensing component  108  is 30 mmHg or 35 mmHg. In other embodiments, if the CO 2  concentration continues to rise past 30-35 mmHg as the enteral tube  102  is advanced into the patient, as shown on the feedback display  110 , the user may determine that the enteral tube  102  is being incorrectly placed in the patient&#39;s airway because the rising CO 2  concentration likely corresponds to the patient&#39;s respirations conveyed through the patient&#39;s airway. Stated differently, using the CO 2  level or concentration that is detected by the first sensing component  108 , the user can determine whether the enteral tube tip  106  resides in the patient&#39;s airway. 
       FIGS. 2 and 3  illustrate other exemplary embodiments of the tube tip detection system  100 . As shown, in some embodiments, the enteral tube  102  includes a plurality of sensing components that are spaced apart from one another along the length L of the tube  102 . As described above, each sensing component of the plurality of sensing components is a carbon dioxide sensor for detecting the CO 2  concentration in the air along the pathway traversed by the enteral tube  102  through the patient. More particularly, the embodiment illustrated in  FIG. 2  comprises the first sensing component  108  disposed at the tube tip  106  and a second sensing component  116  disposed along the length L at a position spaced apart from the tip  106 . For example, the second sensing component  116  may be disposed at a midpoint of the tube length L, i.e., halfway between the proximal end  104  and the tip  106 . In other embodiments, such as depicted in  FIG. 3 , a third sensing component  118  also is disposed along the tube length L at a position spaced apart from the tip  106 . 
     As shown in  FIG. 3 , to embed the sensing components  108 ,  116 , and/or  118  in the enteral tube  102 , in some embodiments a channel  122  is defined in the tube  102  during fabrication of the tube  102 . Then, the first sensing component  108 , the second sensing component  116 , and/or the third sensing component  118  is disposed within the channel  122 . Next, a filler material (not shown) is disposed within the channel  122  around the first, second, and/or third sensing components  108 ,  116 ,  118  such that the sensing component(s)  108 ,  116 ,  118  are embedded within the enteral tube  102 . The sensing components  108 ,  116 ,  118  may be embedded within the tube  102  in other ways as well. 
     In some embodiments, like the exemplary embodiment of  FIG. 3 , the first sensing component  108 , the second sensing component  116 , and the third sensing component  118  are unequally spaced apart from one another. That is, the distance, or portion of the tube length L, between the first and second sensing components  108 ,  116  is different from the distance between the second and third sensing components  116 ,  118 . In other embodiments, the first sensing component  108 , the second sensing component  116 , and the third sensing component  118  are equidistant from one another, i.e., the distance between the first and second sensing components  108 ,  116  is the same as the distance between the second and third sensing components  116 ,  118 . Also as illustrated in  FIG. 3 , in some embodiments the first sensing component  108  may not be disposed at the tip  106  of the enteral tube  102  but may be disposed along the tube length L such that the first sensing component  108  is spaced apart from the tip  106 . In such embodiments, no sensing component may be disposed at the tip  106 ; that is, in some embodiments of the tube tip detection system  100 , one or more sensing components are disposed on the tube  102  at a distance from the tube tip  106 , with no sensing component disposed right at the tip  106 . Thus, a variety of placements or positions for the one or more sensing components may be used in various embodiments of the tube tip detection system  100 . 
     Further, in exemplary embodiments, each of the first, second, and third sensing components  108 ,  116 ,  118  is a MEMS infrared carbon dioxide sensor. The miniaturized sensors located on the tip  106  and/or other locations of the enteral tube  102  detect a CO 2  pattern in the air within the passage traversed by the tube  102 . Because the enteral tube  102  has a known length L, the CO 2  pattern (a waveform, as the CO 2  concentration rises and falls with the patient&#39;s respirations, typically three (3) to four (4) respirations per minute) determines if the tube  102  has deviated to the patient&#39;s airway. Stated differently, the amount or length of the enteral tube  102  that has been inserted into the patient together with the CO 2  concentration detected by the sensor(s)  108 ,  116 ,  118  convey to a user of the tube tip detection system  100  whether the tube tip  106  is near the patient&#39;s airway and is possibly entering the patient&#39;s airway rather than continuing down the pathway toward the patient&#39;s stomach or intestines, the intended destination of the tube tip  106 . For example, it is known that bifurcation of the pathway  114  into the esophagus and the trachea, as illustrated in  FIG. 4 , occurs at a certain distance from the entrance to the nostril in a patient, with the certain distance varying between pediatric and adult patients. Knowing this distance for a given patient, as well as the length L of the enteral tube  102 , the user can determine how much (or what length) of the tube  102  has been inserted into the patient and, thus, know whether the tube tip  106  is at or near the point where the trachea branches off from the pathway  114 , from which the tube  102  could be misplaced into the patient&#39;s airway. 
     As an example, bifurcation typically occurs around 18-20 cm from the entrance to the nostril in adults; the area where bifurcation occurs may be referred to as a bifurcation zone  120 , which is depicted in  FIG. 4 . Thus, for nasogastric intubation of an adult patient, if the CO 2  concentration begins to increase when approximately 18 cm of the length L of the enteral tube  102  has been inserted into the patient, the user of the system  100  can conclude that the tube tip  106  is at or near the bifurcation zone  120 . If the CO 2  concentration continues to increase as the tube  102  is further inserted, the user may determine that the tube tip  106  is or has entered the patient&#39;s airway and can correct the tube&#39;s position within the patient before continuing to insert the tube  102 . If, however, the CO 2  concentration does not continue to increase past the bifurcation zone  120 , the user may determine that the tube tip  106  is continuing on the correct pathway  114  (i.e., the tube  106  is within the esophagus rather than the trachea) to the patient&#39;s stomach or bowel. 
     Accordingly, the one or more sensing components  108 ,  116 ,  118  likely would register, and display on the feedback display  110 , an elevated CO 2  concentration as the tip  106  of the enteral tube  102  nears the bifurcation zone  120 . Thus, the user should monitor the CO 2  pattern to distinguish between an appropriately placed tube tip  106  and a misplaced tube tip  106 . The CO 2  concentration for an appropriately placed tip  106  should decrease upon further insertion of the tube past the bifurcation zone  120 , but the CO 2  concentration for a misplaced tip  106  should increase as a greater length of the tube  102  (greater than the length of tube  102  to reach the bifurcation zone  120 ) is inserted into the patient. 
     In some embodiments, e.g., as shown in  FIG. 1B , the feedback display  110  is attached to the enteral tube  102 , but in other embodiments, e.g., as shown in  FIG. 1A , the feedback display  110  is separate from and not attached to the enteral tube  102 . The feedback display  110  displays the actual CO 2  concentration detected by the one or more sensing components  108 ,  116 ,  118 . Additionally or alternatively, the feedback display  110  displays a non-numerical visual indicator of the CO 2  concentration, such as one or more colors, symbols, or words. As an example, the visual indicator may comprise a plurality of light emitting diodes (LEDs), such as green, yellow, and red LEDs. In such embodiments, the feedback display  110  illuminates the green LED(s) if the sensed CO 2  concentration is below a typical low value of the CO 2  concentration of a person&#39;s exhaled breath (e.g., if the CO 2  concentration is below 30 mmHg), illuminates the yellow LED(s) if the CO 2  concentration is within a typical low range of the CO 2  concentration of a person&#39;s exhaled breath (e.g., if the CO 2  concentration is at or between 30 mmHg to 40 mmHg), and illuminates the red LED(s) if the CO 2  concentration increases beyond an initial reading at the low end of typical CO 2  concentration in a person&#39;s exhaled breath. As another example, the feedback display  110  may illuminate a series of colored or non-colored LEDs or display words or symbols to indicate various states of the sensed CO 2  concentration (e.g., below low end, at low end, or increasing beyond low end of typical CO 2  concentration of a person&#39;s exhaled breath). In still other embodiments, the feedback display  110  may utilize audible feedback, such as one or more beeping or other sounds, in addition to or in lieu of visual feedback to convey to the user of the system  100  CO 2  concentration sensed by the one or more sensing components  108 ,  116 ,  118  disposed on the enteral tube  102 . 
     The present subject matter also provides methods for detecting a tube misplacement in a patient&#39;s airway. Referring now to  FIG. 5 , an exemplary method  200  is illustrated. The method  200  comprises embedding a carbon dioxide sensing component  108  into an enteral tube  102 , as shown at  202  in  FIG. 5 . The enteral tube  102  is configured as described herein, having a proximal end  104  and a tip  106  separated by a length L of tubing. Moreover, the sensing component  108  may be a MEMS-based infrared carbon dioxide sensor as described above. As shown at  204  in  FIG. 5 , the method  200  also includes inserting the enteral tube  102  into the patient through the patient&#39;s nose or mouth. Thus, the enteral tube  102  may be a nasogastric or orogastric tube as described herein. Further, as shown at  206  and  208  in  FIG. 5 , the method  200  includes monitoring feedback from the carbon dioxide sensing component  108  to determine if the enteral tube  102  is traveling into the patient&#39;s airway and, if so, then adjusting the location of the tube tip  106  such that it is no longer in the patient&#39;s airway. The feedback may be displayed on a feedback display  110  as described herein. 
     It will be appreciated that, in other embodiments, the method  200  may accommodate other configurations of the tube tip detection system  100  as described in greater detail herein. For example, step  202  of the method  200  may comprise embedding a plurality of sensing components into the enteral tube  102 , e.g., a first and second sensing component  108 ,  116  as illustrated in  FIG. 2  or a first, second, and third sensing component  108 ,  116 ,  118  as illustrated in  FIG. 3 . Of course, the method  200  may vary to include other configurations of the apparatus and system described herein. 
     Accordingly, the present subject matter provides a system and apparatus for detecting a tip of an enteral tube as it is inserted into a patient. In exemplary embodiments, the system uses MEMS sensor(s) on the tube to detect elevated levels of CO 2  if the tube is inserted into the airway instead of traveling past the bifurcation of the patient&#39;s trachea from the patient&#39;s esophagus toward the gastrointestinal tract. The system may utilize a single MEMS-based infrared carbon dioxide sensor disposed on the tip of the tube to sense the CO 2  concentration within the pathway being traversed by the tube. In other embodiments, the system utilizes a plurality of MEMS-based infrared carbon dioxide sensors disposed along the length of the tube to sense the CO 2  concentration within the pathway being traversed by the tube. The system provides feedback to the user of the system, e.g., a physician, clinician, nurse, or other caregiver, via a feedback display or other device for receiving feedback from the one or more sensing components such that the user can determine whether the tube tip is appropriately placed or is misplaced. Methods for detecting whether the tube tip is misplaced also are provided. Such methods, systems, and apparatus can help reduce the occurrence of misplaced enteral tubes, such as nasogastric or orogastric feeding tubes, thereby reducing complications from administering fluid to a patient through a misplaced tube. Further, the methods, systems, and apparatus described herein reduce such misplacements in a cost-efficient and time-efficient manner. More particularly, the carbon dioxide sensors described herein are a relatively low-cost solution and are easily embedded in enteral tubes during the manufacture of the tubes. Moreover, the system described herein allows real-time, bedside verification of the tube placement, which can save time and money, e.g., compared to existing systems that require tube placement to be verified by x-ray or the like. Other benefits and advantages of the present subject matter also may be recognized by those of ordinary skill in the art. 
     It should also be appreciated that these procedures may involve treatment of humans by physicians, physician assistants, nurses, or other health care providers. In addition, these procedures may involve treatment of other mammals and animals by veterinarians, researchers, and others. 
     It is appreciated that certain features of the invention, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the invention, which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable sub combination. 
     Although the present subject matter has been described in conjunction with specific embodiments thereof, it is evident that many alternatives, modifications and variations will be apparent to those skilled in the art. Accordingly, it is intended to embrace all such alternatives, modifications and variations that fall within the spirit and broad scope of the appended claims. 
     This written description uses examples to disclose the invention, including the best mode, and also to enable any person skilled in the art to practice the invention, including making and using any devices or systems and performing any incorporated methods. The patentable scope of the invention is defined by the claims, and may include other examples that occur to those skilled in the art. Such other examples are intended to be within the scope of the claims if they include structural elements that do not differ from the literal language of the claims or if they include equivalent structural elements with insubstantial differences from the literal language of the claims.