Automated precision device for detecting, monitoring and removing dental plaque

Abstract

Automated devices for detecting and removing dental biofilms are described herein. In some embodiments, the disclosed subject matter includes devices for administering a suspension containing iron oxide nanoparticles to teeth to chemically treat and mechanically remove dental biofilms. In some embodiments, the disclosed subject matter includes devices for administering a suspension containing iron oxide nanoparticles and hydrogen peroxide to teeth to kill bacteria within the biofilm matrix, disintegrate the biofilm matrix, and assemble the iron oxide nanoparticles into autonomous magnetic bristles or antibacterial robots to mechanically remove the biofilm. Devices and methods for real-time detection of dental plaque and monitoring of plaque removal are also disclosed herein.

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Patent Application No. 62 / 927,414, filed October 29, 2019, the contents of which are incorporated herein by reference in their entirety. [Background technology]

[0002] Regular self-administered oral care, such as brushing, flossing, and antibacterial mouthwash, is necessary to maintain healthy teeth and gums. The American Dental Association recommends brushing twice a day for both adults and children. However, brushing is often performed below the recommended standard, e.g., less than the recommended number of times per day or less than the recommended time intervals. Reasons for not brushing to the recommended standard can include, for example, the time and effort required to adequately clean all teeth on the upper and lower jaws, boredom of the user during movement, manual dexterity, and lack of interest in performing chore-like activities. Furthermore, optimal plaque removal requires multiple steps, such as flossing (between the teeth) and mouth rinsing to chemically kill bacteria.

[0003] Poor dental care can result in the formation of biofilms. Biofilms are structured communities of bacterial cells surrounded by a matrix of extracellular polymeric substances such as exopolysaccharides (EPS), which can act as a barrier providing protection against antimicrobial agents, mechanical stability for cohesion into biofilm structures, and firm adhesion to surfaces. Biofilms formed on teeth are associated with dental caries (tooth decay), gingivitis, and periodontal disease.

[0004] Specific techniques to combat biofilms on teeth are largely inadequate and cumbersome because they cannot kill and physically remove bacteria and require dexterity for manual biofilm removal, such as brushing and flossing. Certain antibacterial agents, such as oral disinfectants and mouthwashes, cannot disrupt the biofilm matrix and have limited killing effect on bacteria embedded inside the protected biofilm structure, and biofilms retain biofilm debris and the ability to rapidly recolonize if bacteria are not removed. Specific devices and methods are available for mechanically removing plaque both at the dental clinic (scraping) and at home (toothbrushes, dental floss and power brushes), but they require manual dexterity.

[0005] The above-mentioned technologies pose challenges to both consumers, who are at risk of plaque buildup and oral disease due to lack of compliance, and elderly and physically and cognitively impaired patients, who may have poor manual dexterity.

[0006] These challenges are exacerbated by the lack of available technologies for real-time detection and monitoring of plaque accumulation or plaque-biofilm-related oral health conditions.

[0007] Therefore, there is a need for a device that can simultaneously accomplish plaque detection, monitoring, and removal in an automated manner with high accuracy. Summary of the Invention

[0008] DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Devices and methods are presented herein for removing dental biofilms from teeth and eradicating bacteria within such dental biofilms. Although overlapping with other descriptions, various aspects of the present invention are as follows. However, the present invention is not limited to the following. [1] 1. An oral care device comprising: a flexible mouthpiece having an upper channel configured to fit the user's upper teeth and a lower channel configured to fit the user's lower teeth; The mouthpiece, one or more magnetic elements; Vibration motor Further comprising: Oral care devices. [2] The oral care device described in [1], wherein the one or more magnetic elements include a permanent magnet or an electromagnet adapted to apply a magnetic field to the biofilm to activate the iron oxide nanoparticles and assemble them into an antibacterial robot or autonomous magnetic bristles or robots. [3] The device described in [1], further comprising a photodetector or an RGB sensor. [4] The device of [3], wherein the photodetector is coupled to a light emitting diode. [5] the mouthpiece comprises a suspension comprising iron oxide nanoparticles; The device of [1], wherein the mouthpiece is configured to provide contact between the suspension and surfaces of the user's upper teeth, lower teeth, and gums, including between the teeth. [6] 5. The device of claim 4, wherein the suspension further comprises an ingredient selected from the group consisting of hydrogen peroxide, carbamide peroxide, one or more enzymes, one or more antimicrobial compounds, one or more surfactants, one or more cleaning agents, one or more fluoride ion sources, one or more abrasive compounds, glycerol, one or more flavonoids, terpenoids, polyphenols, proanthocyanidins, tannins, coumarin, rose bengal, perborate, metaperiodate, sorbitol, xylitol, 1-deoxynojirimycin, and combinations thereof. [7] The device described in [6], wherein the suspension contains hydrogen peroxide. [8] The device described in [6], wherein the suspension contains one or more enzymes. [9] The device described in [8], wherein the one or more enzymes are mutanase, dextranase, DNase, protease, lipase, amyloglucosidase, glucose oxidase, or a combination thereof.

[10] The device described in [7], wherein the suspension further contains a peroxidase-sensitive dye.

[11] 1. A method for removing dental biofilm, the method comprising: Inserting the device according to [1] into the mouth of the user; administering a suspension containing iron oxide nanoparticles into an upper channel and a lower channel of the mouthpiece; actuating said iron oxide nanoparticles with one or more magnetic elements for assembly into an antibacterial robot or autonomous magnetic bristles or robots suitable for removing dental biofilms; applying a magnetic field to move the antibacterial robot or autonomous magnetic bristles or robot along the surfaces of the user's upper teeth, lower teeth, and gums, including between the teeth, to mechanically remove dental biofilm; A method comprising:

[12] 11. The method of claim 10, wherein the suspension further comprises an ingredient selected from the group consisting of hydrogen peroxide, carbamide peroxide, one or more enzymes, one or more antimicrobial compounds, one or more fluoride ion sources, one or more abrasive compounds, glycerol, surfactants, detergents, flavonoids, terpenoids, polyphenols, proanthocyanidins, tannins, coumarins, rose bengal, perborate, metaperiodate, sorbitol, xylitol, 1-deoxynojirimycin, and combinations thereof.

[13] the suspension comprises hydrogen peroxide;

[12] The method according to claim 12, wherein the iron oxide nanoparticles activate hydrogen peroxide to generate radicals capable of degrading dental biofilms and eradicating bacteria within the dental biofilms.

[14] 11. The method of claim 10, wherein the suspension comprises 2000 micrograms of iron oxide nanoparticles per milliliter of 50% glycerol or aqueous buffer.

[15] 12. The method of claim 11, wherein the suspension comprises one or more enzymes selected from the group consisting of mutanase, dextranase, and combinations thereof.

[16] The suspension is dissolved in 1% H 2 O 2 and 1.75U / 8.75U mutanase / dextranase.

[17] 1. A method for detecting and removing dental biofilm, the method comprising: [3] Inserting the device according to the present invention into the mouth of the user; administering a suspension comprising iron oxide nanoparticles and hydrogen peroxide into the upper and lower channels of the mouthpiece, wherein a portion of the iron oxide nanoparticles bind to the dental biofilm and a remainder of the iron oxide nanoparticles remain unbound; administering 3,3',5,5'-tetramethylbenzidine into the upper and lower channels of the mouthpiece to stain the bound iron oxide nanoparticles blue; Locating the dental biofilm by detecting the bound iron oxide nanoparticles with a photodetector; and actuating said unbound iron oxide nanoparticles with one or more magnetic elements to assemble into an antibacterial robot or an autonomous magnetic bristles or robots suitable for removing dental biofilms; applying a magnetic field to move the antibacterial robot or autonomous magnetic bristles or robot along surfaces of the user's upper teeth, lower teeth, and gums, including between the teeth, to mechanically remove dental biofilm; A method comprising:

[18] The method of claim 17, further comprising detecting the amount of biofilm removed from the tooth.

[19] 17. The method of claim 15, further comprising monitoring the level of plaque accumulation and the level of plaque removal, the method comprising: collecting, at a server, data relating to a location and amount of dental biofilm, said data being obtained from detecting bound iron oxide nanoparticles; converting the data by a processor into a numerical value indicative of the level of plaque accumulation and the level of plaque removal; displaying a representation of the level of plaque accumulation and the level of plaque removal on a user interface of a terminal device or a web-based application; A method comprising:

[20] The method of claim 19, wherein the representation of the level of plaque accumulation and the level of plaque removal is one or more of a numerical, graphical or color / visual output.

[0009] In certain embodiments, the present disclosure provides an oral care device. An exemplary device includes a flexible mouthpiece having an upper channel adapted to fit the upper teeth of a user and a lower channel adapted to fit the lower teeth. In certain embodiments, the mouthpiece includes one or more magnetic elements and a vibration motor. In certain embodiments, the one or more magnetic elements include permanent magnets and / or electromagnets adapted to apply a magnetic field to the biofilm to activate the iron oxide nanoparticles and assemble into an antibacterial robot or an autonomous magnetic bristles or robots.

[0010] In certain embodiments, the oral care device of the present disclosure further comprises a photodetector or an RGB sensor, hi certain embodiments, the photodetector is coupled to a light emitting diode.

[0011] In certain embodiments, the upper and lower channels of the mouthpiece of the present disclosure contain a suspension including iron oxide nanoparticles, and the upper and lower channels of the mouthpiece are configured to provide contact between the suspension and the surfaces of the user's upper teeth, lower teeth, interdental, and gums.

[0012] In certain embodiments, the upper and lower channels of the mouthpiece contain a suspension comprising iron oxide nanoparticles and a component selected from the group consisting of hydrogen peroxide, carbamide peroxide, enzymes, antimicrobial compounds, fluoride ion sources, abrasive compounds, flavonoids, terpenoids, polyphenols, proanthocyanidins, tannins, coumarins, surfactants, detergents, glycerol, rose bengal, perborate, metaperiodate, sorbitol, xylitol, 1-deoxynojirimycin, and combinations thereof. In certain embodiments, the suspension comprises hydrogen peroxide. In certain embodiments, the suspension comprises one or more enzymes. In certain embodiments, the one or more enzymes are mutanase, dextranase, or combinations thereof.

[0013] In certain embodiments, the suspension comprises hydrogen peroxide and a peroxidase-sensitive dye. In certain embodiments, the peroxidase-sensitive dye is 3,3',5,5'-tetramethylbenzidine (TMB). Other dyes include 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS), o-phenylenediamine (OPD), 3,3'-diaminobenzidine (DAB), pyrogallol, 4-amino-2,3-dimethyl-1-phenyl-3-pyrazolinone (4-aminoantipyrine), 5-aminosalicylic acid (5-AS), 3-methyl-2-benzothiazolinone (MBTH), as well as 10-acetyl-3,7-dihydroxyphenoxazine, terephthalic acid, phosphatidylcholine ... Examples of fluorescent dyes include movanilic acid, 2-[6-(4-aminophenoxy)-3-oxo-3H-xanthen-9-yl]benzoic acid, (2-[6-(4'-hydroxy)phenoxy-3H-xanthen-3-one-9-yl]benzoic acid, 2',7'-dichlorofluorescein diacetate, 2,7-dichlorodihydrofluorescein diacetate, coumarin boronic acid, coumarin boronic acid pinacolate ester, dihydrorhodamine 123, lucigenin, and dihydroethidium.

[0014] In certain embodiments, the present disclosure provides a method for removing dental biofilm. An exemplary method includes inserting the oral care device of the present disclosure into a user's mouth, administering a suspension containing iron oxide nanoparticles into the upper and lower channels of the mouthpiece, activating the iron oxide nanoparticles with one or more magnetic elements to assemble into an antibacterial robot or autonomous magnetic bristles or robot suitable for removing dental biofilm, applying a magnetic field to move the antibacterial robot or autonomous magnetic bristles or robot along the surfaces of the upper teeth, lower teeth, and gums of the user, including between the teeth, to mechanically remove dental biofilm.

[0015] In certain embodiments, the suspension further comprises an ingredient selected from hydrogen peroxide, carbamide peroxide, enzymes, antimicrobial compounds, surfactants, detergents, fluoride ion sources, abrasive compounds, glycerol, flavonoids, terpenoids, polyphenols, proanthocyanidins, tannins, coumarins, rose bengal, perborate, metaperiodate, sorbitol, xylitol, 1-deoxynojirimycin, and combinations thereof.

[0016] In certain embodiments, a method for removing dental biofilm includes inserting an oral care device of the present disclosure into a user's mouth and administering a suspension comprising iron oxide nanoparticles and hydrogen peroxide into the upper and lower channels. In certain embodiments, the suspension comprises from about 0.1% w / w to about 10% w / w, from about 0.5% w / w to about 7.5% w / w, or from about 1% w / w to about 5% w / w of hydrogen peroxide based on the total weight of the suspension. In certain embodiments, the suspension may comprise at least about 0.1% w / w, at least about 0.5% w / w, at least about 1.0% w / w, at least about 2.0% w / w, at least about 3.0% w / w, at least about 4.0% w / w, at least about 5.0% w / w, at least about 6.0% w / w, at least about 7.0% w / w, at least about 8.0% w / w, at least about 9.0% w / w, or at least about 10% w / w, based on the total weight of the suspension. In certain embodiments, the suspension may comprise less than about 0.5% w / w, less than about 1.0% w / w, less than about 2.0% w / w, less than about 3.0% w / w, less than about 4.0% w / w, less than about 5.0% w / w, less than about 6.0% w / w, less than about 7.0% w / w, less than about 8.0% w / w, less than about 9.0% w / w, or less than about 10% w / w based on the total weight of the suspension. The iron oxide nanoparticles activate hydrogen peroxide to generate bioactive radicals that can degrade dental biofilms and eradicate bacteria within the dental biofilm. The method further comprises actuating the iron oxide nanoparticles with one or more magnetic elements to assemble into an antibacterial robot or autonomous magnetic bristles or robot suitable for removing dental biofilms, applying a magnetic field to move the antibacterial robot or autonomous magnetic bristles or robot along the surfaces of the user's upper teeth, lower teeth, interdental spaces, and gingiva to mechanically remove dental biofilms.In certain embodiments, the suspension contains about 500 micrograms to about 5000 micrograms, about 750 micrograms to about 4750 micrograms, about 1000 micrograms to about 4500 micrograms, about 1250 micrograms to about 4250 micrograms, about 1500 micrograms to about 4000 micrograms, about 1750 micrograms to about 3750 micrograms, or about 2000 micrograms to about 3500 micrograms of iron oxide nanoparticles per milliliter of 50% glycerol in water, or water, or aqueous buffer. In certain embodiments, the suspension contains less than 5000 micrograms, less than 4500 micrograms, less than 4000 micrograms, less than 3500 micrograms, less than 3000 micrograms, less than 2500 micrograms, less than 2000 micrograms, less than 1500 micrograms, or less than 1000 micrograms of iron oxide nanoparticles per milliliter of 50% glycerol in water, or water. In certain embodiments, the suspension comprises at least 500 micrograms, at least 1000 micrograms, at least 1500 micrograms, at least 2000 micrograms, at least 2500 micrograms, at least 3000 micrograms, at least 3500 micrograms, at least 4000 micrograms, or at least 4500 micrograms of iron oxide nanoparticles per milliliter of 50% glycerol in water, or water, or aqueous buffer. In one embodiment, the suspension comprises 2000 micrograms of iron oxide nanoparticles per milliliter of 50% glycerol. In certain embodiments, the suspension comprises one or more enzymes selected from the group consisting of mutanase, dextranase, and combinations thereof. In certain embodiments, the suspension comprises 1% hydrogen peroxide and 1.75U / 8.75U of mutanase / dextranase.

[0017] In certain embodiments, the present disclosure provides a method for detecting and removing dental biofilm, the method comprising inserting an oral care device of the present disclosure into a user's mouth, administering a suspension comprising iron oxide nanoparticles and hydrogen peroxide into the upper and lower channels. Some of the iron oxide nanoparticles bind to the dental biofilm, and another portion of the iron oxide nanoparticles remain unbound. The method further comprises administering 3,3',5,5'-tetramethylbenzidine into the upper and lower channels to stain the iron oxide nanoparticles bound to the biofilm blue, locating the dental biofilm by detecting the bound iron oxide nanoparticles with a photodetector, actuating the unbound iron oxide nanoparticles with one or more magnetic elements to assemble into an antibacterial robot or autonomous magnetic bristles or robot suitable for removing dental biofilm, and mechanically removing the dental biofilm by applying a magnetic field to move the antibacterial robot or autonomous magnetic bristles or robot along the surface having the bound iron oxide nanoparticles. In certain embodiments, the method further comprises detecting the amount of dental biofilm removed.

[0018] In certain embodiments, the method of the present disclosure further includes monitoring the level of plaque accumulation and the level of plaque removal, the method including collecting, at a server, data related to the location and amount of dental biofilm, the data being obtained from detecting the bound iron oxide nanoparticles with a photodetector, converting the data by a processor into a numerical value indicative of the level of plaque accumulation and the level of plaque removal, and displaying the representation of the level of plaque accumulation and the level of plaque removal on a user interface of a terminal device or web-based application. In certain embodiments, the representation of the level of plaque accumulation and the level of plaque removal is one or more of a numerical, graphical, or color / visual output.

[0019] The accompanying drawings, which are incorporated in and constitute a part of this disclosure, illustrate preferred embodiments of the invention and serve to explain the principles of the invention. [Brief description of the drawings]

[0020] [Figure 1A] FIG. 1 illustrates the dual catalytic-magnetic functionality of iron oxide nanoparticles. [Figure 1B] FIG. 1 shows biofilm resistance to antimicrobial agents and mechanical removal by EPS matrices. [Figure 1C] FIG. 1 shows detection and disruption of biofilm. [Figure 1D] FIG. 1 illustrates magnetic actuation and removal of biofilm. [Figure 2A] The device is made of a flexible material that conforms to the dental arch, and the close-up shows the device has multiple functions for dental biofilm removal as well as biofilm detection and monitoring. [Figure 2B] FIG. 1 shows a device wirelessly linked to an app / mobile for monitoring oral health and hygiene (dental biofilm build-up and removal). [Figure 3A] FIG. 1 shows that iron oxide nanoparticles do not bind to human gingival epithelial cells. [Figure 3B] FIG. 1 shows that iron oxide nanoparticles bind to biofilms. [Figure 3C] FIG. 1 shows the efficacy of iron oxide nanoparticles in eradicating biofilm bacteria. [Figure 4A] Figure 4 shows the catalytic activity of iron oxide nanoparticles in biofilms as a function of iron oxide nanoparticle concentration. The inset in Figure 4A further shows the color change (to blue) of the biofilms after treatment with iron oxide nanoparticles, TMB and hydrogen peroxide. [Figure 4B] Figure 4A shows the color change (to blue) of biofilm on real teeth using a mouse model after treatment with iron oxide nanoparticles, TMB and hydrogen peroxide. Figure 4B further shows that TMB and hydrogen peroxide stain only the biofilm and not the tooth. [Figure 4C] FIG. 1 shows a magnified view of a tooth stained for biofilm without staining the tooth surface. [Figure 5A]FIG. 1 shows a plaque detection circuit used to detect blue color. [Figure 5B] FIG. 13 illustrates that an indicator LED of the plaque detection circuit is illuminated when blue is detected. [Figure 5C] FIG. 13 illustrates that the indicator LED of the plaque detection circuit is turned off when no blue color is detected. [Figure 5D] FIG. 1 shows the relationship between the amount of various biofilms removed and the blue indicator used for biofilm (plaque) detection. [Figure 6A] FIG. 1 shows iron oxide nanoparticles being manipulated back and forth by a magnetic element. [Figure 6B] FIG. 1 shows iron oxide nanoparticles being manipulated back and forth by a magnetic element. [Figure 6C] FIG. 1 shows iron oxide nanoparticles being manipulated back and forth by a magnetic element. [Figure 6D] FIG. 1 shows iron oxide nanoparticles being manipulated back and forth by a magnetic element. [Figure 6E] FIG. 1 shows iron oxide nanoparticles being manipulated back and forth by a magnetic element. [Figure 6F] FIG. 1 shows iron oxide nanoparticles being manipulated back and forth by a magnetic element. [Figure 7A] FIG. 1 shows the bristle-like structures that iron oxide nanoparticles exhibit on the tooth surface in a magnetic field. [Figure 7B] FIG. 1 shows the bristle-like structures that iron oxide nanoparticles exhibit on the tooth surface in a magnetic field. [Figure 7C] FIG. 1 shows the bristle-like structures that iron oxide nanoparticles exhibit on the tooth surface in a magnetic field. [Figure 7D] 7A and 7B show the bristle-like structures that iron oxide nanoparticles assume on the tooth surface in a magnetic field: the left panel of Fig. 7B shows the magnetic field off, and the center and right panels of Fig. 7B show just after the magnetic field is turned on, showing the assembly of bristle-like structures. [Figure 8A]FIG. 1 shows removal of plaque biofilm from enamel surfaces by magnetically controlled movement of bristle-like iron oxide nanoparticle robotic structures. [Figure 8B] FIG. 1 shows removal of plaque biofilm from enamel surfaces by magnetically controlled movement of bristle-like iron oxide nanoparticle robotic structures. [Figure 8C] FIG. 1 shows removal of plaque biofilm from enamel surfaces by magnetically controlled movement of bristle-like iron oxide nanoparticle robotic structures. [Figure 8D] FIG. 1 shows removal of plaque biofilm from enamel surfaces by magnetically controlled movement of bristle-like iron oxide nanoparticle robotic structures. [Figure 9A] FIG. 1 shows the removal of biofilm plaque from the narrow interproximal region. [Figure 9B] FIG. 1 shows the removal of biofilm plaque from the narrow interproximal region. [Figure 9C] FIG. 1 shows the removal of biofilm plaque from the narrow interproximal region. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0021] The subject matter of the present disclosure provides an oral care device capable of eradicating bacteria and degrading the biofilm matrix of dental plaque with a suspension containing iron oxide nanoparticles. In certain embodiments, the device of the present disclosure can also detect and monitor dental plaque. The device of the present disclosure can further include sensors such as Bluetooth and microprocessing features to allow real-time monitoring of the amount and removal of dental plaque. The present disclosure also provides a method of eradicating bacteria and degrading the biofilm matrix of dental plaque with a suspension containing iron oxide nanoparticles forming an antibacterial robot or an autonomous magnetic bristles or robot.

[0022] For purposes of clarity, and not limitation, this detailed description is divided into the following subsections. -definition, - iron nanoparticle suspensions, -Oral care devices, -How to remove dental biofilm.

[0023] definition The terms used herein generally have their ordinary meaning in the art, within the context of this subject matter and within the specific context in which each term is used. To provide further guidance in describing the compositions and methods of the disclosed subject matter and how to make and use them, certain terms are defined below.

[0024] As used in this specification and the appended claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to a "compound" includes a mixture of compounds.

[0025] In the detailed description of this specification, references to "embodiment", "an embodiment", "one embodiment", "in various embodiments", etc. indicate that the described embodiment may include a particular feature, structure, or characteristic, but not all embodiments necessarily include the particular feature, structure, or characteristic. Moreover, such phrases do not necessarily refer to the same embodiment. Moreover, when a particular feature, structure, or characteristic is described in relation to an embodiment, it is believed to be within the knowledge of a person skilled in the art to affect such feature, structure, or characteristic in relation to other embodiments, whether or not explicitly stated. After reading the description, it will be apparent to a person skilled in the art how to implement the present disclosure in alternative embodiments.

[0026] The term "coupled" as used herein with respect to a photodetector and a light emitting diode refers to an electrical or wireless connection between the two components, and the light emitting diode is capable of generating a visual indicator of the information detected by the photodetector.

[0027] The terms "dental biofilm" and "dental plaque" are used interchangeably herein and refer to a biofilm or mass of bacteria that grows on surfaces in the mouth.

[0028] As used herein, the term "user" includes a mammal, such as an animal or a human. In a preferred embodiment, the subject is a human. In certain non-limiting embodiments, a "user" can be any individual using or interacting with a terminal device that can use or interact with a user interface.

[0029] The term "terminal device" refers to, for example, but not limited to, a personal computer, a laptop computer, a workstation, a mobile device, a terminal device, or any other user equipment. In some non-limiting examples, the terminal device may include a graphical user interface used to display a graphical representation of plaque detection, plaque removal, and oral hygiene status to a user of the terminal device. In certain embodiments, a web-based application may be installed on the user's terminal device. The user may use the web-based application to monitor the progress of plaque removal.

[0030] As used herein, "high frequency" refers to frequencies above 10 Hz.

[0031] Iron nanoparticle suspension In certain embodiments, iron oxide nanoparticles according to the disclosed subject matter can mechanically remove dental plaque. FIG. 6A shows that iron oxide nanoparticles can form clusters in a magnetic field, which are pulled along the surface to generate a controlled pivoting motion. FIGS. 7A-7D show different mechanisms by which bristle-like structures are formed on tooth surfaces in a magnetic field. As shown in FIGS. 7A and 7B, by controlling the direction and gradient of the magnetic field, bristle-like structures of iron oxide nanoparticles are formed from the solution and extend to the enamel surface. FIG. 7C further shows that the bristles of iron oxide nanoparticles can extend to a biofilm-covered surface and are actuated laterally to sweep and remove the biofilm. Notably, as shown in FIG. 7D, the bristles of iron oxide nanoparticles conform to the changing surface contours while degrading and removing the biofilm.

[0032] In alternative embodiments, permanent magnets or electromagnets can be used while rotating, translating and vibrating within the device.

[0033] In certain embodiments, the suspensions of the present disclosure include hydrogen peroxide in addition to iron oxide nanoparticles. The iron oxide nanoparticles activate the hydrogen peroxide to generate bioactive radicals that can degrade dental biofilms and eradicate bacteria within the dental biofilms. In particular, the iron oxide nanoparticles catalyze the decomposition of hydrogen peroxide to produce HO. · and HO2 ·1A and 1B show the dual catalytic-magnetic functionality of iron oxide nanoparticles according to an embodiment of the disclosed subject matter. The iron oxide nanoparticles can catalyze hydrogen peroxide (H2O2) to substantially eradicate bacteria and degrade the biofilm matrix. Degradation of the biofilm matrix is ​​important to disrupt the structural framework while also facilitating penetration and eradication of bacteria. When the biofilm matrix is ​​degraded, the bacterial eradication effect is substantially enhanced. The biofilm matrix is ​​degraded when it is sufficiently disrupted to allow substantial bacterial eradication (>99.999% kill). The iron oxide nanoparticles can be magnetically activated to actuate the iron oxide nanoparticles for assembly into an antibacterial robot or autonomous magnetic bristles or robot, and the antibacterial robot or autonomous magnetic bristles or robot can be moved to remove biofilm debris.

[0034] Figure 1C and Figure 1D show the conceptual framework of a plaque removal and detection system using catalytic antibacterial robots. In Figure 1C, iron oxide nanoparticles bind and penetrate biofilms and catalyze H2O2 in situ to disrupt the biofilm matrix and kill bacteria. At the same time, the nanoparticles react with TMB during catalysis (see claim 11) to produce a blue color that serves as an indicator of plaque (biofilm), and thus can serve as a detector of biofilm accumulation. When the nanoparticles are activated by a magnetic field (Figure 1D left panel), they aggregate and assemble into bristle-like structures that remove and scrape off the biofilm (Figure 1D right panel), and importantly, these nanoparticles do not bind to teeth or mucosal surfaces. As these biofilms can also be labeled with blue (see above), the amount of plaque removal can also be measured, thereby serving as a plaque removal detection.

[0035] In certain embodiments, the suspensions of the present disclosure include a peroxidase-sensitive dye in addition to iron oxide nanoparticles and hydrogen peroxide. In certain embodiments, the peroxidase-sensitive dye is 3,3',5,5'-tetramethylbenzidine. Other dyes include 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS), o-phenylenediamine (OPD), 3,3'-diaminobenzidine (DAB), pyrogallol, 4-amino-2,3-dimethyl-1-phenyl-3-pyrazolinone (4-aminoantipyrine), 5-aminosalicylic acid (5-AS), 3-methyl-2-benzothiazolinone (MBTH), as well as 10-acetyl-3,7-dihydroxyphenoxazine, terephthalic acid, homovanillic acid, 2-[6-(4-aminophenoxy)-3-oxo-3H-xanthene-9- Fluorescent dyes such as (2-[6-(4'-hydroxy)phenoxy-3H-xanthen-3-one-9-yl]benzoic acid, (2-[6-(4'-hydroxy)phenoxy-3H-xanthen-3-one-9-yl]benzoic acid, 2',7'-dichlorofluorescein diacetate, 2,7-dichlorodihydrofluorescein diacetate, coumarin boronic acid, coumarin boronic acid pinacolate ester, dihydrorhodamine 123, lucigenin, and dihydroethidium. Iron oxide nanoparticles can bind to dental biofilms and, in the presence of hydrogen peroxide and peroxidase-sensitive dyes, produce a color that can be used to detect dental plaque.

[0036] The suspension containing iron oxide particles may further include one or more enzymes, such as mutanase or dextranase, to further aid in the degradation of the biofilm matrix. In certain embodiments, the suspension may be formulated with 1% hydrogen peroxide and 1.75U / 8.75U mutanase / dextranase to substantially eradicate bacteria and degrade the biofilm matrix. Figure 3C shows the biofilm eradication efficacy of a suspension containing iron oxide nanoparticles, hydrogen peroxide, and mutanase / dextranase.

[0037] In certain embodiments, the suspension containing iron oxide nanoparticles comprises glycerol and / or water, or an aqueous buffer solution. In certain embodiments, the suspension comprises about 500 micrograms to about 5000 micrograms, about 750 micrograms to about 4750 micrograms, about 1000 micrograms to about 4500 micrograms, about 1250 micrograms to about 4250 micrograms, about 1500 micrograms to about 4000 micrograms, about 1750 micrograms to about 3750 micrograms, or about 2000 micrograms to about 3500 micrograms of iron oxide nanoparticles per milliliter of 50% glycerol in water, water, or aqueous buffer solution. In certain embodiments, the suspension comprises less than 5000 micrograms, less than 4500 micrograms, less than 4000 micrograms, less than 3500 micrograms, less than 3000 micrograms, less than 2500 micrograms, less than 2000 micrograms, less than 1500 micrograms, or less than 1000 micrograms of iron oxide nanoparticles per milliliter of 50% glycerol in water or water. In certain embodiments, the suspension comprises at least 500 micrograms, at least 1000 micrograms, at least 1500 micrograms, at least 2000 micrograms, at least 2500 micrograms, at least 3000 micrograms, at least 3500 micrograms, at least 4000 micrograms, or at least 4500 micrograms of iron oxide nanoparticles per milliliter of 50% glycerol in water or water. In one embodiment, the suspension comprises 2000 micrograms of iron oxide nanoparticles per milliliter of 50% glycerol in water.

[0038] In certain embodiments, the suspension containing iron oxide nanoparticles may contain additional ingredients commonly used in oral care compositions, such as, but not limited to, carbamide peroxide, antimicrobial compounds, fluoride ion sources, abrasive compounds, surfactants, detergents, enzymes, and combinations thereof. Non-limiting examples of antimicrobial compounds include triclosan, essential oils, terpenoids, flavonoids, polyphenols, proanthocyanidins, tannins, coumarins, chlorhexidine, antimicrobial peptides, arginine. Non-limiting examples of enzymes include dextranase, mutanase, lipase, DNAse, amyloglucosidase, glucose oxidase. Non-limiting examples of fluoride ion sources include alkali metal fluorides such as sodium fluoride, alkali metal monofluorophosphates, stannous fluoride, and the like. Non-limiting examples of abrasive compounds include silica dental abrasives, calcium carbonate, dicalcium phosphate dihydrate, beta-calcium pyrophosphate, insoluble alkali metal metaphosphates, plastic dental abrasives, and combinations thereof.

[0039] Oral Care Devices The disclosed device is configured to contact the user's teeth and gum surfaces with a suspension including iron oxide nanoparticles. In certain embodiments, the disclosed oral care device includes a flexible mouthpiece including an upper channel configured to fit the user's upper teeth and a lower channel configured to fit the user's lower teeth. The mouthpiece can be sized to fit a range typical of humans, from children to adults. Adult mouth openings range from 30-70 mm, and adult total arch lengths range from 35-45 mm. In certain embodiments, the size of the mouthpiece is adjustable. Figures 2A and 2B provide non-limiting examples of mouthpieces. Specifically, Figure 2A shows an exemplary flexible mouthpiece, which includes upper and lower channels that are adjustable to the dental arch. A close-up view shows the device housing magnetically controlled bristles that remove plaque, as well as a means for monitoring plaque in real time and a means for providing a vibratory motion.

[0040] FIG. 2B shows the device wirelessly linked to an app / mobile for monitoring oral health and hygiene (dental biofilm buildup and removal).

[0041] In certain embodiments, the mouthpiece of the present disclosure includes one or more magnetic elements for generating a magnetic field. Non-limiting examples of magnetic elements include electromagnets that include a magnetic core that can concentrate and amplify pulling forces. In certain embodiments, the magnetic gradient generated by these magnets may range from about 0.01 mT / millimeter to about 200 mT / millimeter, about 1 mT / millimeter to about 180 mT / millimeter, about 25 mT / millimeter to about 150 mT / millimeter, or about 50 mT / millimeter to about 100 mT / millimeter. In certain embodiments, the magnetic gradient generated by these magnets is at least 1 mT / millimeter, at least 10 mT / millimeter, at least 25 mT / millimeter, at least 50 mT / millimeter, at least 75 mT / millimeter, at least 100 mT / millimeter, at least 125 mT / millimeter, at least 150 mT / millimeter, or at least 175 mT / millimeter. In certain embodiments, the maximum gradient does not exceed 200 mT / millimeter. The switching of the magnetic field can occur over a frequency range including, but not limited to, values ​​of about 0.2 Hz to about 100 Hz, about 5 Hz to about 75 Hz, about 20 Hz to about 60 Hz, about 30 Hz to about 50 Hz, In certain embodiments, the magnetic field is generated by a permanent magnet, such as, but not limited to, iron, iron nickel alloy, neodymium iron boron, and samarium cobalt.

[0042] In certain embodiments, the oral care device includes one or more tactile actuators (e.g., vibration actuators). In certain embodiments, actuators as used herein are small vibrating devices (motors or piezoelectric materials) that can generate and sense (tactile) vibrations and further resuspend nanoparticles and / or aid in biofilm removal. Non-limiting examples of vibration actuators include rotary motors with unbalanced masses that can be actuated and altered in terms of frequency and amplitude of vibration. In certain embodiments, the one or more vibration actuators are vibration motors. Non-limiting commercially available embodiments of vibration actuators include Z7AL2B1690002 by Jinlong Machinery&Electronics. In certain embodiments, the frequency of vibration varies from about 10 Hz to about 20,000 Hz. In certain non-limiting embodiments, the vibration motion is induced by high frequency magnetic motion, and electromagnets and / or piezoelectric actuators transport iron oxide nanoparticles via high frequency vibrations of about 10 Hz to about 20,000 Hz. In certain embodiments, the electromagnet responsible for moving the iron oxide nanoparticles can also generate mechanical vibrations.

[0043] In certain embodiments, the oral care device of the present disclosure further includes a photodetector or RGB sensor. In certain embodiments, the photodetector or RGB sensor is coupled to a light emitting diode to provide a visual indicator of color or fluorescence detection. A non-limiting example of such a configuration is shown in FIG. 5A. FIG. 5A shows an electrical circuit 500 for detecting blue color in a tray 502. The circuit 500 includes a light emitting diode 504 and a photodetector 506. FIGS. 5B and 5C show that the indicator light emitting diode 504 turns on when blue light is detected in the tray 502 by the photodetector 506 and remains off when blue light is not detected.

[0044] The oral care devices of the present disclosure are sized to accommodate batteries and power electronics, hi certain embodiments, the oral care devices further include microprocessing capabilities.

[0045] In certain embodiments, the oral care device can be wirelessly connected to another device for real-time monitoring of dental biofilm removal.

[0046] Method for detecting and removing dental plaque The present disclosure further relates to a method for removing plaque using the oral care device described herein. In certain embodiments, a user can remove plaque by administering the suspension disclosed herein containing iron oxide nanoparticles into the upper and lower channels of a mouthpiece and fitting the mouthpiece to the upper and lower teeth. When the device is turned on, the iron oxide nanoparticles move by magnetic fields and / or vibrational motion to form antibacterial robots or autonomous magnetic bristles or robots, thereby mechanically removing plaque.

[0047] In certain embodiments, plaque can be removed by administering a suspension containing iron oxide nanoparticles and hydrogen peroxide into the upper and lower channels of a mouthpiece and fitting the mouthpiece to the upper and lower teeth. The iron oxide nanoparticles catalyze the decomposition of hydrogen peroxide to form HO. · and HO2 · It generates radicals that eradicate the bacteria in the biofilm and break down the biofilm.Furthermore, when the device is turned on, the iron oxide nanoparticles are moved by the magnetic field and / or vibration motion, thereby mechanically removing the plaque.

[0048] In a particular embodiment, plaque can be detected and removed by administering a suspension containing iron oxide nanoparticles, hydrogen peroxide and a peroxidase-sensitive dye into the upper and lower channels of the mouthpiece and fitting the mouthpiece to the upper and lower teeth. A portion of the iron oxide nanoparticles bind to the plaque. The suspension further stains the plaque blue with the bound iron oxide particles without staining the teeth, as shown in Figures 4A-4C, thereby serving as a plaque detection. A visual indicator can further be used to identify the location of the plaque, and subsequently, the unbound iron oxide nanoparticles can be guided towards the stained plaque, which can then be mechanically removed. Also, since the biofilm is stained blue, the amount of plaque removal can also be measured, serving as a plaque (biofilm) removal detection.

[0049] Figures 8A-8D further illustrate the ability of the antibacterial robot or autonomous magnetic bristles or robot to remove plaque from teeth: Figures 8A and 8C show "before" images of a pink stained biofilm formed on a tooth block, while Figures 8B and 8D provide "after" images showing the same tooth block after undergoing automatic cleaning by the autonomous magnetic bristles or robot, showing that the biofilm has been completely removed.

[0050] 9A-9C further illustrate the ability of the antibacterial robot or autonomous magnetic bristles or robot to remove plaque from narrow areas, such as the area between teeth. Such cleaning is performed by driving iron oxide nanoparticle aggregates in a reciprocating motion through the interproximal space. FIG. 9B provides a "before" image showing plaque in a narrow area between two "model teeth," and FIG. 9C provides an "after" image showing that plaque in the interproximal area has been removed, with a close-up showing that biofilm has been completely removed in the narrow space between the teeth.

[0051] In certain embodiments, the level of plaque accumulation and the level of plaque removal can be monitored and / or visualized on a terminal device or a web-based application within the terminal device. Once the photodetector or RGB sensor acquires data regarding plaque and its amount, the data can be transmitted to a memory device located external to the sensor for real-time monitoring and storage. A given sensor can transmit the obtained data to a server, which can then collect data regarding the amount of plaque and its location, as well as plaque removal. In certain non-limiting embodiments, a centralized server can collect all of the data, while in other non-limiting embodiments, the collection of data can be distributed across multiple servers. Each server can include one or more databases that store the collected information. Once the centralized server collects all of the data, the data can be persisted in one database or multiple databases. The databases can include tags or identifiers that describe characteristics of the collected data, such as the type of data collected. In certain embodiments, the data can be converted by a processor into a numerical value that indicates the level of plaque accumulation and the level of plaque removal. In certain embodiments, the results can be visualized using a range of colors. In certain embodiments, the collected data can be used to monitor oral hygiene and oral health over time, hi certain embodiments, a web-based application or terminal device can be used to monitor real-time removal of plaque and real-time monitoring of the amount of plaque accumulation on the teeth.

[0052] The foregoing merely illustrates the principles of the disclosed subject matter. Various modifications and alterations to the described embodiments will be apparent to those skilled in the art in light of the teachings herein. It will thus be appreciated that those skilled in the art will be able to devise numerous techniques, not explicitly described herein, which embody the principles of the disclosed subject matter and are therefore within its spirit and scope.

Claims

1. 1. An oral care device comprising: a flexible mouthpiece having an upper channel configured to fit the user's upper teeth and a lower channel configured to fit the user's lower teeth; the mouthpiece comprises a suspension comprising iron oxide nanoparticles; one or more magnetic elements; and A vibration motor for resuspending the iron oxide nanoparticles Further comprising: Oral care devices.

2. The oral care device of claim 1, wherein the one or more magnetic elements include a permanent magnet or an electromagnet adapted to apply a magnetic field to the biofilm to activate the iron oxide nanoparticles and assemble into an antibacterial robot or autonomous magnetic bristles or robots.

3. The device of claim 1 , further comprising a photodetector or an RGB sensor.

4. The device of claim 3 , wherein the photodetector is coupled to a light emitting diode.

5. The device of claim 1, wherein the mouthpiece is configured to provide contact between the suspension and surfaces of the user's upper teeth, lower teeth, and gums, including between the teeth.

6. 6. The device of claim 5, wherein the suspension further comprises an ingredient selected from the group consisting of hydrogen peroxide, carbamide peroxide, one or more enzymes, one or more antimicrobial compounds, one or more surfactants, one or more detergents, one or more sources of fluoride ions, one or more abrasive compounds, glycerol, one or more flavonoids, terpenoids, polyphenols, proanthocyanidins, tannins, coumarins, rose bengal, perborate, metaperiodate, sorbitol, xylitol, 1-deoxynojirimycin, and combinations thereof.

7. The device of claim 6 , wherein the suspension comprises hydrogen peroxide.

8. The device of claim 6 , wherein the suspension comprises one or more enzymes.

9. 9. The device of claim 8, wherein the one or more enzymes are mutanase, dextranase, DNase, protease, lipase, amyloglucosidase, glucose oxidase, or combinations thereof.

10. The device of claim 7 , wherein the suspension further comprises a peroxidase-sensitive dye.

Images