BRISTLES AND MECHANICAL MOTION

Field of the Invention

[0001] The present disclosure is directed generally to devices for use in cleaning the surface of the tongue utilizing a synergistic combination of optimized bristles and mechanical motion.

Background

[0002] Halitosis, also known as bad breath, is a common complaint among the adult population, affecting as much as 20-30% or more of adults. The vast majority of halitosis cases, greater than 90%, are caused by malodorous compounds and gases that are emitted from a dense bacteria biofilm coating that forms on the surface of the tongue. This surface of the tongue, especially the posterior portion, is generally difficult to clean and coated with debris, dead cells, and postnasal drip. Accordingly, the tongue is a hospitable location for a wide variety of bacterial species to colonize and form a thick, nearly impenetrable biofilm. This biofilm generates a variety of compounds, such as skatoles and volatile sulfur, which contribute to halitosis.

[0003] Treatment of halitosis typically consists of cleaning the tongue surface using a tongue scraper and/or mouthwash. The tongue scraper is utilized in an attempt to physically scrape the bacteria off the surface, although this method is largely unsuccessful. Too much pressure during scraping can cause damage to the tongue microstructure. Typically the bacteria, especially in biofilm form, remain firmly entrenched in the spaces between neighboring papillae (the protrusions on the surface of the tongue) despite the application of force during scraping. Instead of removing the biofilm, tongue scrapers often flatten the papillae and trap the biofilm in the spaces, which can then quickly regrow. Accordingly, tongue scrapers typically only reduce halitosis conditions for very short period of time, ranging from minutes to at most several hours.

[0004] Another method of treatment for halitosis consists of using mouthwash to dislodge bacteria or, in the case of antibacterial mouthwashes, kill the bacteria inhabiting the surface of the tongue. Although gargling with mouthwash can temporarily cover the symptoms of halitosis by introducing a strong odorant, mouthwash is ineffective against halitosis after any significant period of time. The biofilms found on the surface of the tongue have a coating that is largely impervious to the chemicals or antibacterial agents found within the mouthwash, even if the use of mouthwash is combined with physical scraping.

[0005] Accordingly, there is a need in the art for methods and apparatus for the treatment of halitosis caused by bacterial biofilms coating the tongue.

Summary of the Invention

[0006] The present disclosure is directed to inventive methods and devices for removing the bacterial biofilm coating the surface of the tongue using a synergistic combination of optimized bristles and mechanical motion. Various embodiments and implementations herein are directed to a tongue cleaning method and device in which a tongue cleaner mechanically vibrates tongue- cleaning bristles which are optimized to attack the bacterial biofilm, alone or in combination with appropriate mouth cleaning chemistry and/or antibacterial agents.

[0007] Using the various embodiments and implementations herein, effective cleaning of the tongue can be achieved using bristles that are soft enough and of the right material and size to avoid damaging the tongue surface but are pointed and spaced to efficiently reach the spaces between the papillae of the tongue where bacteria normally hide.

[0008] For example, in some embodiments, the device is a mechanical tongue cleaner capable of generating vibrations and transmitting those vibrations to a plurality of optimized bristles that engage the surface of the tongue. In these embodiments, the optimized bristles are composed of a soft elastomeric polymer, and are both pointed and intentionally spaced at a predetermined density to deliver the pointed ends of the optimized bristles to the spaces between the papillae of the tongue surface. The mechanical vibrations generated by the tongue cleaner allow the pointed ends of the bristles to attack and break apart the bacterial biofilm located between the papillae.

[0009] In some embodiments, the mechanical tongue cleaner combines the vibration of optimized bristles with chemistry to introduce an antibacterial agent and/or cleaning agent to the bacterial biofilm. While the pointed bristles are attacking and dislodging the bacteria located between neighboring papillae the antibacterial agent and/or cleaning agent can be delivered, thereby introducing the agent deeper into the biofilm than is possible using existing methods. [0010] Generally in one aspect, a tongue cleaning device is provided. The tongue cleaning device includes a body portion having a vibration generator; an elongated head extending from the body portion, the head comprising a bristle face proximate its distal end, where the head is configured to vibrate relative to the body portion; a plurality of bristles connected at one end to the bristle face, and each having a pointed end extending along an axis perpendicular to the head's axis of elongation, the plurality of soft bristles arranged in a density configured to engage the surface of the tongue; wherein the vibration generator generates vibrations and transmits the vibrations to the head such that the pointed ends of the plurality of bristles vibrate.

[0011] According to an embodiment, each of the bristles is cone-shaped with an aspect ratio of 1 : 1.

[0012] According to an embodiment, each of the plurality of bristles has a durometer hardness measurement of between approximately 40 and 70 on the Shore A scale.

[0013] According to an embodiment, each of the plurality of bristles are approximately 250 to 3000 microns in length, and more particularly, approximately 500 - 1500 microns in length, and optimally approximately 1000 microns in length.

[0014] Generally, in one aspect, a method for cleaning the surface of the tongue includes the steps of: providing a tongue cleaning device having: (i) a body portion with a vibration generator; (ii) an elongated head extending from the body portion and having a bristle face proximate its distal end, where the head is configured to vibrate relative to the body portion; and (iii) a plurality of bristles each connected at one end to the bristle face and each having a pointed end extending along an axis perpendicular to the head's axis of elongation; vibrating, using the vibration generator, the pointed ends of the plurality of bristles; and cleaning the surface of the tongue with the vibrating plurality of bristles.

[0015] According to an embodiment, each of the bristles is cone-shaped with an aspect ratio of 1 : 1.

[0016] According to an embodiment, each of the plurality of bristles has a durometer of between approximately 40 and 70 on the Shore A scale.

[0017] According to an embodiment, the method also includes the step of introducing an additive to the surface, such as ingesting the agent just prior to cleaning, or spraying on the surface of the tongue just prior to cleaning. According to an embodiment, the additive is a cleaning agent and/or an antibacterial agent.

[0018] According to an embodiment, the bristles are vibrated at approximately 75 Hz or greater.

[0019] According to an embodiment, each of the plurality of bristles are approximately 250 to 3000 microns in length.

[0020] It should be appreciated that all combinations of the foregoing concepts and additional concepts discussed in greater detail below (provided such concepts are not mutually inconsistent) are contemplated as being part of the inventive subject matter disclosed herein. In particular, all combinations of claimed subject matter appearing at the end of this disclosure are contemplated as being part of the inventive subject matter disclosed herein.

[0021] These and other aspects of the invention with be apparent from and elucidated with reference to the embodiment(s) described hereinafter.

Brief Description of the Drawings

[0022] In the drawings, like reference characters generally refer to the same parts throughout the different views. Also, the drawings are not necessarily to scale, emphasis instead generally being placed upon illustrating the principles of the invention.

[0023] FIG. 1 is a schematic representation of a tongue cleaning device in accordance with an embodiment.

[0024] FIG. 2 is a schematic representation of the head member of a tongue cleaning device in accordance with an embodiment.

[0025] FIGS. 3 and 4 are schematic representations of optimized tongue cleaning bristles in accordance with an embodiment.

[0026] FIG. 5 is a graph of biofilm removal by bristles of different lengths and hardness in accordance with an embodiment.

[0027] FIG. 6 is a graph of volatile sulfur compound production following treatment with a traditional tongue scraper and additive versus treatment with a tongue cleaning device and additive in accordance with an embodiment.

[0028] FIG. 7 is a flow chart of a method for cleaning the tongue using a mechanical tongue cleaning device with optimized bristles in accordance with an embodiment.

[0029] FIG. 8 is a graph of organoleptic scores following treatment with water versus the mechanical tongue cleaning device with optimized bristles, with and without additive, in accordance with an embodiment.

Detailed Description of Embodiments

[0030] The present disclosure describes various embodiments of devices, systems, and methods that use mechanical motion to attack the bacterial biofilm coating the surface of the tongue. More generally, Applicants have recognized and appreciated that it would be beneficial to treat halitosis caused by bacterial biofilms coating the surface of the tongue. It was discovered that there is an unexpected synergistic effect resulting from the combination of mechanical motion and bristles having optimized shape and density. For example, effective cleaning of the tongue is substantially improved by a device and method in which a mechanical tongue cleaner generates vibrations and transmits those vibrations to a plurality of optimized bristles that engage the surface of the tongue.

[0031] In view of the foregoing, various embodiments and implementations are directed to devices and methods in which a mechanical tongue cleaner generates vibrations and transmits those vibrations to a plurality of optimized bristles composed of a soft polymer. The optimized bristles are pointed and intentionally spaced at a predetermined density to deliver the pointed ends of the optimized bristles to the spaces between the papillae of the tongue surface. The mechanical vibrations generated by the tongue cleaner allow the pointed ends of the bristles to attack and break apart the bacterial biofilm located between the papillae. In some embodiments, the device combines the vibration of optimized bristles with a mouthwash, antibacterial agent, and/or cleaning agent that is introduced deep into the biofilm by the vibrating bristles.

[0032] Referring to FIG. 1 , in one embodiment, a tongue cleaning device 10 is provided that includes a body portion 12 and a head member 14 mounted on the body portion. Head member 14 includes at its end remote from the body portion a brush head 16. Brush head 16 includes a bristle face 18 proximate the distal end 40 of the head member, and the bristle face provides a plurality of bristles 20. According to an embodiment, the bristles extend along an axis substantially perpendicular to the head's axis of elongation.

[0033] Head member 14, brush head 16, and/or bristle face 18 are mounted so as to be able to vibrate relative to the body portion 12. The vibrations can be any of a variety of different vibrations, including up and down, side to side, and in a circle, among others. According to an embodiment, head member 14 is mounted to the body so as to be able to vibrate relative to body portion 12, or, as another example, brush head 16 is mounted to head member 14 so as to be able to vibrate relative to body portion 12. For example, in accordance with an embodiment, the bristles are vibrated at a first frequency 38 that is equal to or greater than approximately 75 Hz, but many other frequencies, patterns, and vibrations are possible. The head member 14 can be fixedly mounted onto body portion 12, or it may alternatively be detachably mounted so that head member 14 can be replaced with a new one when the bristles 20 or another component of the device are worn out and require replacement.

[0034] Body portion 12 includes a vibration generator 22 for generating vibrations and a transmission component 24 for transmitting the generated vibrations to head member 14. For example, vibration generator 22 can comprise a motor or electromagnet(s) that generate vibrations of the transmission component 24, which are subsequently transmitted to the head member 14. Vibration generator 22 may alternatively comprise any other known type of vibration mechanism capable of generating high frequency vibrations. The vibration generator 22 can include vibration electronics such as a power supply, an oscillator, and one or more electromagnets, among other components. In this embodiment the power supply comprises one or more rechargeable batteries, not shown in FIG. 1 , which can be electrically charged in a charging holder in which tongue cleaning device 10 is placed when not in use. In this embodiment, body portion 12 is further provided with an on/off button 26 to activate and deactivate vibration generator 22. It is anticipated that head member 14 can be affixed to and used with a body portion 12 of a powered oral care device, such as a power toothbrush, varieties of which are commonly known in the industry.

[0035] Referring to FIG. 2, in one embodiment, a head member 14 is provided, separate from body portion 12. The head member includes at its distal end 40 remote from the body portion a brush head 16 with a bristle face 18 having multiple bristles 20. The length of head member 14 is configured to be suitable for cleaning both the anterior and posterior surfaces of a human tongue.

[0036] According to an embodiment, bristles 20 are optimized to a density (42) that maximizes the effect of the pointed tips 30 of the bristles on the spaces between papillae on the human tongue. For example, in FIG. 3, the density (42) of the optimized bristles varies and can include density 42a, density 42b, density 42c, and density 42d, for example, which depend at least in part on the shape and size of the bristles. Referring to FIGS. 3 and 4, in one embodiment, a variety of bristles 20 are provided. In this embodiment, bristles 20 are cone-shaped with a pointed tip 30. The cone-shaped bristles have a height H and a base width of W. Width W decreases continuously along height H, ranging from a maximum value W to a minimum value at pointed tip 30. Since the bases of neighboring cone-shaped bristles cannot overlap, width W also defines a maximum density (42) of these bristles. As a result, the density of the plurality of bristles 20 on the bristle face 18 can be varied by spacing apart the bristles, or by increasing or decreasing the value of width W of the base of the cone-shaped bristles. According to an embodiment, each of cone-shaped bristles 20 have an aspect ratio of 1 : 1 , meaning that the values of width W and height H are approximately equal. According to an embodiment, bristles 20 are approximately 250 to 3000 microns in length. In an embodiment with cone-shaped bristles having a height H of approximately 250 microns and an aspect ratio of 1 :1 , width W will similarly be approximately 250 microns. In a preferred embodiment, the bristles 20 are cone- shaped bristles of approximately 1000 microns in length, where height H and width W (at the cone base, for example) are approximately 1000 microns. In an embodiment where the base of each of the cone-shaped bristles has a diameter of approximately 1000 microns, the cone-shaped bristles can be manufactured or arranged in a density of approximately 100 bristles per cm .

[0037] Bristles 20 may alternatively comprise another shape optimized to reach between the papillae on the human tongue without damaging or flattening the microstructure of the tongue. It is also anticipated that an arrangement of a brush head 16 having varying bristles of differing sizes and densities can exist.

[0038] Bristles 20 are preferably composed of a material suitable for attacking a biofilm or other bacterial coating on the surface of the tongue without significantly damaging the microstructure of the tongue. For example, bristles 20 can be composed of a polymer such as polydimethylsiloxane (PDMS), Evoprene ^® , or similar thermoplastic or cast elastomers, other silicones, or any other known type of polymer suitable for the mouth. Similarly, the durometer, or measure of hardness, of the polymer can vary depending on a variety of factors. For example, according to an embodiment, a harder bristle may be more efficient at removing bacteria from the surface of the tongue. Referring to FIG. 5 is a graph of the effectiveness of bristles having different hardness (or "shore") values. In a set of in vitro experiments using a biofilm model, bristles having durometer or shore hardness measurements of 5, 40, and 70 on the Shore A scale were used in conjunction with sonic vibrations at 250 Hz to determine the ability of the bristles to remove a biofilm compared to a control of no treatment at all. Bristles of each durometer were used at varying lengths of 500 microns, 1000 microns, and 2000 microns. While some ability change in the cleaning was seen at different bristle lengths, a durometer measurement of greater than 5, particularly between 40 and 70, had an unexpected effect on the removal of the biofilm.

[0039] In accordance with an embodiment, an additive 36 known or otherwise configured to attack bacteria such as a biofilm on the surface of the tongue can be used in conjunction with a tongue cleaning device 10. For example, additive 36 can be a commercially-available mouthwash, and can optionally include an antibacterial agent. For example, zinc ions, chlorhexidine (CHX), and cetylpyridinium (CPC) inhibit production of volatile sulfur compounds, which are created by the bacterial biofilm lining the surface of the tongue and contribute to halitosis. Alternatively, the additive can be or include alcohol, fluoride, hydrogen peroxide, phenol, sanguinarine, sodium bicarbonate, sodium chloride, sodium lauryl sulfate, tetracycline, and/or triclosan, among other additives. One example of a mouthwash with an antibacterial agent suitable to serve as additive 36 is BreathRX. It is anticipated that a tongue cleaning device 10 can be provided that includes further includes a fluid container which can deliver additive contained therein directly through the brush head 16, such as the oral care assembly device disclosed in U.S. Provisional Patent Application Number 62/056,662, filed contemporaneously herewith on September 29, 2014.

[0040] Although mouthwashes are highly effective at killing bacteria, many fail to provide breath odor protection for more than a few hours. The biofilm on the surface of the tongue forms a dense, liquid-repellent layer and is therefore resistant to antibacterial attack. For example, although biofilm on the tongue may be as much as 500 micrometers thick, mouthwashes are typically only able to penetrate up to 20 micrometers. Although a mouthwash may temporarily inhibit production of volatile sulfur compounds, the biofilm is not significantly damaged by the mouthwash and quickly grows back to normal levels. Experiments showed that even if combined with traditional cleaners that scrape the surface of the tongue, mouthwash does not exhibit an increased ability to inhibit biofilm growth and production of volatile sulfur compounds.

[0041] However, as shown in FIG. 6, use of an additive 36 with a tongue cleaning device 10 having a plurality of optimized vibrating bristles 20 in accordance with an embodiment displays an unexpected synergistic effect on biofilm re-growth and the production of volatile sulfur compounds. Volatile sulfur compounds, a symptom of biofilm, recover quickly following treatment with a traditional tongue scraper and additive, returning to 80% of the baseline within 3 hours of treatment. In contrast, after using an additive 36 together with tongue cleaning device 10 having a plurality of optimized vibrating bristles 20 in accordance with an embodiment, it takes almost 7 hours for volatile sulfur compound production to return to 80% of the baseline. Thus, it is hypothesized that when tongue cleaning device 10 generates vibrations of the optimized bristles 20, it delivers the additive 36 significantly deeper into the bio film by acting between the papillae, in addition to removal of the biofilm. Indeed, the optimized density, shape, and/or hardness of the plurality of bristles likely plays a role in the unexpected synergistic effect demonstrated in FIGS. 5, 6, and similar experiments.

[0042] Similarly, referring to FIG. 8, a graph of organoleptic scores following treatment with water versus the mechanical tongue cleaning device with optimized bristles, with and without additive, is provided. Use of an additive 36 with a tongue cleaning device 10 having a plurality of optimized vibrating bristles 20 in accordance with an embodiment displays an unexpected synergistic effect on biofilm re-growth and the production of volatile sulfur compounds. The graph in FIG. 8 represents experimental data in which subjects performed four different treatments: (i) water alone; (ii) additive (such as BreathRx antibacterial mouthwash spray); (iii) tongue cleaning device 10 with water; or (iv) tongue cleaning device 10 with additive, in which . the users used the device for three rounds of 20 seconds each, using three sprays of additive (approximately 1.8 mL). The bristles in these experiments were 1000 microns in length, and had a durometer measurement of approximately 40 on Shore scale A. Measurement of odor was performed by an organoleptic judge on a scale of 0-5 (with "0" being no odor, "1" being barely detectable odor, "2" being slight malodour, "3" being definitely detected maldour, "4" being strong malodour, and "5" being very strong malodour). Measurements were taken prior to cleaning, and at 1, 3, and 6 hours after cleaning. As shown in the graph in FIG. 8, there is a significant, prolonged decrease in malodour levels that results from use of the mechanical tongue cleaning device with optimized bristles. Indeed, use of an anti-bacterial additive with the tongue cleaning device 10 displayed a striking and unexpected synergistic effect on the production of odor, with the device plus additive treatment being a full point lower than the next best treatment at both 3 and 6 hours post-treatment.

[0043] Referring to FIG. 7, a flow chart illustrating a method 700 for cleaning the surface of the tongue in accordance with an embodiment of the invention is disclosed. In step 710, a tongue cleaning device 10 is provided. Tongue cleaning device 10 may be any of the embodiments described herein or otherwise envisioned, and can include any of the components of the units described in conjunction with FIGS. 1-4. For example, tongue cleaning device 10 can include a body portion 12 and a head member 14 mounted on the body portion with a brush head 16, bristle face 18, and plurality of bristles 20.

[0044] In optional step 720, an additive 36 is introduced to the surface of the tongue during cleaning. The additive may be any of the additives disclosed or otherwise envisioned herein, and may include a cleaning agent and/or an antibacterial agent. The additive may be added at any point in the method. For example, the user can ingest into the mouth (but not swallow) the additive, such as a mouthwash, just prior to activating and using the tongue cleaning device. The additive will then be present in the mouth as the tongue cleaning device is used to clean the tongue. Alternatively, the additive may be introduced during the cleaning cycle.

[0045] In step 730, the vibration generator of tongue cleaning device 10 is activated and the vibrations are transmitted to head member 14 and the plurality of bristles 20, causing each of the plurality of bristles to vibrate. The vibrations can be up and down, side to side, and/or rotating, among other variations. For example, in accordance with an embodiment, the bristles are vibrated at or greater than approximately 75 Hz, but many other frequencies, patterns, and vibrations are possible. The vibration generator of tongue cleaning device 10 can be activated for example, by the on/off button 26 on body portion 12, or any other known method or mechanism for activating or deactivating vibration generator 22.

[0046] In step 740, the vibrating plurality of bristles is used to clean the surface of the tongue. For example, the user can move tongue cleaning device 10 around, thereby causing the handle and bristles to move while vibrating, or the user can keep the tongue cleaning device 10 substantially still and let the vibrating bristles penetrate the biofilm by vibrations alone.

[0047] According to one embodiment, a specific cleaning cycle shows an unexpected improvement in cleaning the tongue and inhibiting the recovery of volatile sulfur compounds. Cleaning the surface of the tongue three times in a row significantly improves the inhibition of volatile sulfur compounds compared to other cycles such as twice in a row. For example, cleaning three times each for approximately 10 to 20 seconds is more effective than cleaning twice in a row, even if the cleaning sessions are longer (20 seconds, 30 seconds, or longer). Thus, it is repetition rather than length of time cleaning affecting the effectiveness of cleaning. There may be multiple explanations for this unexpected phenomenon including the breakup of the biofilm during the brief interludes, among other explanations. To effectuate multiple cleaning repetitions in a cleaning session, tongue cleaning device 10 can include a timer or other mechanism that assists the user in counting the number of repetitions and the length of time of each repetition. According to an embodiment, tongue cleaning device 10 includes a counter to count up to three repetitions, and a timer to count down at least 10 to 20 seconds. Alternatively, tongue cleaning device 10 can come with instructions or other directions to induce the user to clean the surface of the tongue at least three times in a row, each for approximately 10 to 20 seconds.

[0048] All definitions, as defined and used herein, should be understood to control over dictionary definitions, definitions in documents incorporated by reference, and/or ordinary meanings of the defined terms.

[0049] The indefinite articles "a" and "an," as used herein in the specification and in the claims, unless clearly indicated to the contrary, should be understood to mean "at least one."

[0050] The phrase "and/or," as used herein in the specification and in the claims, should be understood to mean "either or both" of the elements so conjoined, i.e., elements that are conjunctively present in some cases and disjunctively present in other cases. Multiple elements listed with "and/or" should be construed in the same fashion, i.e., "one or more" of the elements so conjoined. Other elements may optionally be present other than the elements specifically identified by the "and/or" clause, whether related or unrelated to those elements specifically identified.

[0051] As used herein in the specification and in the claims, "or" should be understood to have the same meaning as "and/or" as defined above. For example, when separating items in a list, "or" or "and/or" shall be interpreted as being inclusive, i.e., the inclusion of at least one, but also including more than one, of a number or list of elements, and, optionally, additional unlisted items. Only terms clearly indicated to the contrary, such as "only one of or "exactly one of," or, when used in the claims, "consisting of," will refer to the inclusion of exactly one element of a number or list of elements. In general, the term "or" as used herein shall only be interpreted as indicating exclusive alternatives (i.e. "one or the other but not both") when preceded by terms of exclusivity, such as "either," "one of," "only one of," or "exactly one of."

[0052] As used herein in the specification and in the claims, the phrase "at least one," in reference to a list of one or more elements, should be understood to mean at least one element selected from any one or more of the elements in the list of elements, but not necessarily including at least one of each and every element specifically listed within the list of elements and not excluding any combinations of elements in the list of elements. This definition also allows that elements may optionally be present other than the elements specifically identified within the list of elements to which the phrase "at least one" refers, whether related or unrelated to those elements specifically identified.

[0053] It should also be understood that, unless clearly indicated to the contrary, in any methods claimed herein that include more than one step or act, the order of the steps or acts of the method is not necessarily limited to the order in which the steps or acts of the method are recited.

[0054] In the claims, as well as in the specification above, all transitional phrases such as "comprising," "including," "carrying," "having," "containing," "involving," "holding," "composed of," and the like are to be understood to be open-ended, i.e., to mean including but not limited to. Only the transitional phrases "consisting of and "consisting essentially of shall be closed or semi-closed transitional phrases, respectively, as set forth in the United States Patent Office Manual of Patent Examining Procedures, Section 2111.03.

[0055] While several inventive embodiments have been described and illustrated herein, those of ordinary skill in the art will readily envision a variety of other means and/or structures for performing the function and/or obtaining the results and/or one or more of the advantages described herein, and each of such variations and/or modifications is deemed to be within the scope of the inventive embodiments described herein. More generally, those skilled in the art will readily appreciate that all parameters, dimensions, materials, and configurations described herein are meant to be exemplary and that the actual parameters, dimensions, materials, and/or configurations will depend upon the specific application or applications for which the inventive teachings is/are used. Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific inventive embodiments described herein. It is, therefore, to be understood that the foregoing embodiments are presented by way of example only and that, within the scope of the appended claims and equivalents thereto, inventive embodiments may be practiced otherwise than as specifically described and claimed. Inventive embodiments of the present disclosure are directed to each individual feature, system, article, material, kit, and/or method described herein. In addition, any combination of two or more such features, systems, articles, materials, kits, and/or methods, if such features, systems, articles, materials, kits, and/or methods are not mutually inconsistent, is included within the inventive scope of the present disclosure.